Science Study Scraper Report

Abstract:
Forest bathing is a traditional practice characterized by visiting a forest and breathing its air. This review aims to investigate the effects of forest bathing on levels of salivary or serum cortisol as a stress biomarker in order to understand whether forest bathing can reduce stress. Medline/PubMed, Embase, Scopus, Web of Science, Cochrane Library, and Google Scholar were systematically searched for relevant articles. The quality of included trials was assessed following the criteria of the NIH dedicated tools. Afterwards, a qualitative and quantitative synthesis of retrieved evidence was performed. A total of 971 articles were screened; 22 of them were included in the systematic review and 8 in the meta-analysis. In all but two included studies, cortisol levels were significantly lower after intervention in forest groups if compared with control/comparison groups, or a significant pre-post reduction of cortisol levels was reported in the forest groups. The main results of the meta-analysis showed that salivary cortisol levels were significantly lower in the forest groups compared with the urban groups both before (MD = - 0.08 μg/dl [95% CI - 0.11 to - 0.05 μg/dl]; p < 0.01; I2 = 46%) and after intervention (MD = - 0.05 μg/dl [95% CI - 0.06 to - 0.04 μg/dl]; p < 0.01; I2 = 88%). Overall, forest bathing can significantly influence cortisol levels on a short term in such a way as to reduce stress, and anticipated placebo effects can play an important role in it. Further research is advised because of the limited available data.

Abstract:
Background: Current literature supports the comprehensive health benefits of exposure to nature and green environments on human systems. The aim of this state-of-the-art review is to elucidate empirical research conducted on the physiological and psychological effects of Shinrin-Yoku (or Forest Bathing) in transcontinental Japan and China. Furthermore, we aim to encourage healthcare professionals to conduct longitudinal research in Western cultures regarding the clinically therapeutic effects of Shinrin-Yoku and, for healthcare providers/students to consider practicing Shinrin-Yoku to decrease undue stress and potential burnout. Methods: A thorough review was conducted to identify research published with an initial open date range and then narrowing the collection to include papers published from 2007 to 2017. Electronic databases (PubMed, PubMed Central, CINAHL, PsycINFO and Scopus) and snowball references were used to cull papers that evaluated the use of Shinrin-Yoku for various populations in diverse settings. Results: From the 127 papers initially culled using the Boolean phrases: "Shinrin-yoku" AND/OR "forest bathing" AND/OR "nature therapy", 64 studies met the inclusion criteria and were included in this summary review and then divided into "physiological," "psychological," "sensory metrics" and "frameworks" sub-groups. Conclusions: Human health benefits associated with the immersion in nature continue to be currently researched. Longitudinal research, conducted worldwide, is needed to produce new evidence of the relationships associated with Shinrin-Yoku and clinical therapeutic effects. Nature therapy as a health-promotion method and potential universal health model is implicated for the reduction of reported modern-day "stress-state" and "technostress.".

Abstract:
The aim of this systematic review of systematic reviews was to identify, summarise, and synthesise the available evidence of systematic reviews (SRs) and meta-analyses (MAs) on the preventative and therapeutic psychological and physical effects of forest-based interventions. Methods: Both bibliographic databases and grey literature sources were searched for SRs and MAs published until May 2020. Eight databases were searched for relevant articles: MEDLINE, Embase, Web of Science, Cochrane Library, PsycInfo, CiNii, EBSCO, and Scopus. Grey literature was sourced from Google Scholar and other web-based search tools. SRs and MAs that included randomised controlled (RCT), non-randomised controlled (NRCT), and non-controlled trials (NCT) on health-related effects of forest-based interventions were eligible if they had searched at least two databases. The methodological quality of eligible reviews was assessed by AMSTAR-2. Results: We evaluated 11 systematic reviews covering 131 different primary intervention studies, mostly from Asian countries, three of which included supplementary meta-analyses. The quality assessment resulted in moderate confidence in the results of two reviews, low confidence in six, and critically low confidence in three. The results of the eight moderate and low-rated reviews indicated that forest-based interventions are beneficial to the cardiovascular system, immune system, and mental health (in the areas of stress, depression, anxiety, and negative emotions). Evidence for the effectiveness of forest-based interventions on metabolic parameters in adults, the severity of atopic dermatitis in children and adolescents, and social skills and sociality in healthy primary school children was weak. Discussion/Conclusions: Evidence suggests beneficial therapeutic effects of forest-based interventions on hypertension, stress, and mental-health disorders, such as depression and anxiety. Changes in immunological and inflammatory parameters after forest therapy should be verified in bio-geographically native forests. In the future, more attention should be paid to careful planning, implementation, and reporting of primary studies and to systematic reviews on the effects of forest-based interventions.

Abstract:
Humans have enjoyed forest environments for ages because of the quiet atmosphere, beautiful scenery, mild climate, pleasant aromas, and fresh, clean air. In Japan, since 2004, serial studies have been conducted to investigate the effects of forest environments (Forest bathing/Shinrin-yoku) on human health. My research team has established a new medical science called Forest Medicine. The Forest Medicine is a new interdisciplinary science, belonging to the categories of alternative medicine, environmental medicine and preventive medicine, which studies the effects of forest environments (Forest bathing/Shinrin-yoku) on human health. It has been reported that Forest bathing/Shinrin-yoku has the following beneficial effects on human health:1 Shinrin-yoku increases human natural killer (NK) activity, the number of NK cells, and the intracellular levels of anti-cancer proteins, suggesting a preventive effect on cancers. 2 Shinrin-yoku reduces blood pressure and heart rate showing preventive effect on hypertension and heart diseases. 3 Shinrin-yoku reduces stress hormones, such as urinary adrenaline and noradrenaline and salivary/serum cortisol contributing to stress management. 4 Shinrin-yoku increases the activity of parasympathetic nerves and reduces the activity of sympathetic nerves to stabilize the balance of autonomic nervous system. 5 Shinrin-yoku improve sleep. 6 Shinrin-yoku increases the levels of serum adiponectin and dehydroepiandrosterone sulfate. 7 In the Profile of Mood States (POMS) test, Shinrin-yoku reduces the scores for anxiety, depression, anger, fatigue, and confusion, and increases the score for vigor, showing preventive effects on depression. 8 Shinrin-yoku may apply to rehabilitation medicine 9 Shinrin-yoku in city parks also has benefits on human health. 10 Shinrin-yoku may have preventive effect on COVID-19 by boosting immune function and by reducing mental stress.Taken together, these findings suggest that Shinrin-yoku may have potential preventive effects on non-communicable diseases.

Abstract:
Background: Shinrin-yoku (experiencing the forest atmosphere or forest bathing) has received increasing attention from the perspective of preventive medicine in recent years. Some studies have reported that the forest environment decreases blood pressure. However, little is known about the possibility of anti-hypertensive applications of Shinrin-yoku. This study aimed to evaluate preventive or therapeutic effects of the forest environment on blood pressure. Methods: We systematically reviewed the medical literature and performed a meta-analysis.Four electronic databases were systematically searched for the period before May 2016 with language restriction of English and Japanese. The review considered all published, randomized, controlled trials, cohort studies, and comparative studies that evaluated the effects of the forest environment on changes in systolic blood pressure. A subsequent meta-analysis was performed. Results: Twenty trials involving 732 participants were reviewed. Systolic blood pressure of the forest environment was significantly lower than that of the non-forest environment. Additionally, diastolic blood pressure of the forest environment was significantly lower than that of the non-forest environment. Conclusions: This systematic review shows a significant effect of Shinrin-yoku on reduction of blood pressure.

Abstract:
Mindfulness and Shinrin-yoku (SY) translated as forest bathing, is potentially effective to alleviate mental health issues related to the COVID-19 pandemic and beyond. The purpose of this article is to provide a translational and pragmatic approach to understanding mindfulness in the context of SY and psychological wellbeing through a rapid review of the literature. The background of mindfulness and SY practice are discussed and the emotional, neuroendocrine, and neurobiological responses are examined. Next, a rapid review of the literature examined six studies, published between 2010 and 2020 to determine what is known regarding the relationship between SY, mindfulness, and psychological wellbeing. The studies included 21-360 participants with a mean age of 20-55 years. The results demonstrated a significant positive correlation between nature, mindfulness, and measures of psychological wellbeing. During uncertain events, including COVID-19, weaving mindfulness with SY may be specifically important to at-risk groups, those experiencing depression, loneliness, and social isolation, and at-risk populations such as college students, veterans, and professionals with high levels of stress. The goal of this review is to provide a thorough background and support of this cost-effective modality to promote overall psychological wellbeing as a preventative measure to those at risk or experiencing psychological illnesses.

Abstract:
Aims: This study focused on the newest evidence of the relationship between forest environmental exposure and human health and assessed the health efficacy of forest bathing on the human body as well as the methodological quality of a single study, aiming to provide scientific guidance for interdisciplinary integration of forestry and medicine. Method: Through PubMed, Embase, and Cochrane Library, 210 papers from January 1, 2015, to April 1, 2019, were retrieved, and the final 28 papers meeting the inclusion criteria were included in the study. Result: The methodological quality of papers included in the study was assessed quantitatively with the Downs and Black checklist. The methodological quality of papers using randomized controlled trials is significantly higher than that of papers using non-randomized controlled trials (p < 0.05). Papers included in the study were analyzed qualitatively. The results demonstrated that forest bathing activities might have the following merits: remarkably improving cardiovascular function, hemodynamic indexes, neuroendocrine indexes, metabolic indexes, immunity and inflammatory indexes, antioxidant indexes, and electrophysiological indexes; significantly enhancing people's emotional state, attitude, and feelings towards things, physical and psychological recovery, and adaptive behaviors; and obvious alleviation of anxiety and depression. Conclusion: Forest bathing activities may significantly improve people's physical and psychological health. In the future, medical empirical studies of forest bathing should reinforce basic studies and interdisciplinary exchange to enhance the methodological quality of papers while decreasing the risk of bias, thereby raising the grade of paper evidence.

Abstract:
The aim of this review was to outline the most relevant benefits of forest bathing for well-being promotion. This study was designed as an umbrella literature review. Medline (via PubMed), EMBASE, Web of Science, Cochrane Library, Google Scholar, Scopus, PsycINFO, CINAHL and the DOAJ were systematically searched for relevant reviews up to February 2021. After article selection, 16 systematic reviews met inclusion criteria. Overall, the best available evidence supports the use of forest bathing as a complementary practice for the promotion of psychophysical well-being, whereas evidence for its use as a therapeutic practice for the improvement of organic diseases needs to grow before clear and specific clinical indications can be formulated. The positive impact of forest bathing on individual quality of life, along with its favorable cost-effectiveness profile, may justify its possible adoption for public health strategies of well-being promotion. Further investigations on the topic are advised.

Abstract:
There is growing interest in the idea of integrating Nature Therapies into the multidisciplinary management of complex conditions such as depression. Shinrin-Yoku (Forest Bathing), a practice involving spending time in a forested environment while paying attention to multi-sensory stimuli has been proposed as one such modality. The objectives of this review were to critically analyse the current evidence base on the efficacy of Shinrin-Yoku for the treatment of depression, and to examine how the findings may reflect and/or inform osteopathic principles and clinical practice. An integrative review of the evidence for Shinrin-Yoku in the management of depression published between 2009 and 2019 was conducted resulting in n = 13 peer-reviewed studies meeting inclusion criteria. Two themes emerged from the literature, the positive effect of Shinrin-Yoku on self-reported mood scores, and physiological changes arising from forest exposure. However, the methodological quality of the evidence is poor and experiments may not be generalisable. Suggestions were made for improving the research base via mixed-method studies in a biopsychosocial framework, and aspects of the research which may be applicable to evidence-based osteopathy were noted.

Abstract:
In Japan, forest-air bathing and walking (shinrin-yoku) has been proposed as a health-facilitating activity in which people spend a short period of time in a forest environment. Initially, we examined the usefulness of salivary amylase activity as an indicator of an individual's stress levels in a forest environment. The circadian rhythm of salivary amylase activity was measured in healthy young male subjects under stress-free conditions. The salivary amylase activity remained relatively constant throughout the day. Salivary amylase activity was then measured before and after walking in both urban and forest environments using a hand-held monitor. Our results indicated that (i) the circadian rhythm fluctuations in salivary amylase activity were much smaller than the stressor-induced variations; (ii) salivary amylase activity was an excellent indicator of the changes in sympathetic nervous activity; and (iii) the forest was a good environment in which people could experience much less environment-derived stress.

Abstract:
Shinrin-yoku, forest bathing, may provide relief from chronic and breakthrough pain in patients with axial spondyloarthritis and improve immune function through increasing NK cell numbers and activity and their downstream effectors, perforin and granulysin, after chemo- or radiation therapy in breast and prostate cancer patients. The aim of this paper is to describe the study protocol for a simulated forest immersion therapy using virtual reality and atomized phytoncides, volatile organic compounds found in forested areas designed to effect positive change for these two patient populations. The setting, including the room set up and samples with inclusion/exclusion specific to this type of intervention, is outlined. Measures and calibration procedures pertinent to determining the feasibility of simulated forest immersion therapy are presented and include: ambient and surface room temperatures and relative humidity in real time, ambient ultrafine particulate matter, ambient droplet measurement that coincides with volatile organic compounds, specific phytoncides, and virtual reality and atomization of phytoncide set up. Particular lessons learned while training and setting up the equipment are presented. Simulated forest immersion therapy is possible with attention to detail during this early phase when development of methods, equipment testing, and feasibility in deploying the intervention become operational. The expected outcome of the development of the methods for this study is the creation of a standardized approach to simulating forest therapy in a controlled laboratory space.

Abstract:
Humans have enjoyed forest environments for ages because of the quiet atmosphere, beautiful scenery, mild climate, pleasant aromas, and fresh, clean air. In Japan, since 2004, serial studies have been conducted to investigate the effects of forest environments on human health. We have established a new medical science called Forest Medicine. The Forest Medicine is a new interdisciplinary science, belonging to the categories of alternative medicine, environmental medicine and preventive medicine, which encompasses the effects of forest environments on human health. It has been reported that forest environments have the following beneficial effects on human health:1. Increase human natural killer (NK) activity, the number of NK cells, and the intracellular levels of anti-cancer proteins, suggesting a preventive effect on cancers.2. Reduce blood pressure, heart rate, and stress hormones, such as urinary adrenaline and noradrenaline and salivary cortisol.3. Increase the activity of parasympathetic nerves and reduce the activity of sympathetic nerves.4. Increase the levels of serum adiponectin and dehydroepiandrosterone sulfate.5. In the Profile of Mood States (POMS) test, reduce the scores for anxiety, depression, anger, fatigue, and confusion, and increase the score for vigor, showing psychological effects as well.These findings suggest that forest environments may have preventive effects on lifestyle-related diseases.

Abstract:
In 1980, Jonas Salk (1914-1995) encouraged professionals in anthropology and related disciplines to consider the interconnections between "planetary health," sociocultural changes associated with technological advances, and the biology of human health. The concept of planetary health emphasizes that human health is intricately connected to the health of natural systems within the Earth's biosphere; experts in physiological anthropology have illuminated some of the mechanisms by which experiences in natural environments (or the built environment) can promote or detract from health. For example, shinrin-yoku and related research (which first emerged from Japan in the 1990s) helped set in motion international studies that have since examined physiological responses to time spent in natural and/or urban environments. However, in order to advance such findings into planetary health discourse, it will be necessary to further understand how these biological responses (inflammation and the collective of allostatic load) are connected to psychological constructs such as nature relatedness, and pro-social/environmental attitudes and behaviors. The exposome refers to total environmental exposures-detrimental and beneficial-that can help predict biological responses of the organism to environment over time. Advances in "omics" techniques-metagenomics, proteomics, metabolomics-and systems biology are allowing researchers to gain unprecedented insight into the physiological ramifications of human behavior. Objective markers of stress physiology and microbiome research may help illuminate the personal, public, and planetary health consequences of "extinction of experience." At the same time, planetary health as an emerging multidisciplinary concept will be strengthened by input from the perspectives of physiological anthropology.

Abstract:
This study investigated the physiological and psychological therapeutic effects of a digital Shinrin-yoku environment constructed indoors in an urban facility as well as the characteristics of the environment that contribute to restorativeness (restorative traits). We measured the fluctuations in the physical and mental states of 25 subjects by obtaining both before-after measurements and continuous measurements while exposed to a digital Shinrin-yoku environment that reproduced visual, auditory, and olfactory elements. The results demonstrated that the parasympathetic nerve activity was significantly increased and that the heart rate was significantly decreased during the exposure compared with that during the resting state. As for mood, five of the six Profile of Mood States (POMS) scales ("Tension-Anxiety," "Depression," "Anger-Hostility," "Fatigue," and "Confusion") were significantly decreased after the experience. In addition, psychological restorative effects were also confirmed, with a significant decrease in "negative affect" (measured using the Positive and Negative Affect Schedule (PANAS)) and a significant increase in the sense of restorativeness (Restorative Outcome Scale (ROS)) after the experience. In contrast, comparing the digital Shinrin-yoku environment with the actual forest environment and the urban environment using POMS, PANAS, ROS, and Perceived Restorativeness Scale (PRS), the psychological effects and environmental traits of the digital Shinrin-yoku were found to be considerably similar to those of the actual forest environment.

Abstract:
Background: Numerous studies have reported that spending time in nature is associated with the improvement of various health outcomes and well-being. This review evaluated the physical and psychological benefits of a specific type of exposure to nature, forest therapy. Method: A literature search was carried out using MEDLINE, PubMed, ScienceDirect, EMBASE, and ProQuest databases and manual searches from inception up to December 2016. Key words: "Forest" or "Shinrin -Yoku" or "Forest bath" AND "Health" or "Wellbeing". The methodological quality of each randomized controlled trials (RCTs) was assessed according to the Cochrane risk of bias (ROB) tool. Results: Six RCTs met the inclusion criteria. Participants' ages ranged from 20 to 79 years. Sample size ranged from 18 to 99. Populations studied varied from young healthy university students to elderly people with chronic disease. Studies reported the positive impact of forest therapy on hypertension (n = 2), cardiac and pulmonary function (n = 1), immune function (n = 2), inflammation (n = 3), oxidative stress (n = 1), stress (n = 1), stress hormone (n = 1), anxiety (n = 1), depression (n = 2), and emotional response (n = 3). The quality of all studies included in this review had a high ROB. Conclusion: Forest therapy may play an important role in health promotion and disease prevention. However, the lack of high-quality studies limits the strength of results, rendering the evidence insufficient to establish clinical practice guidelines for its use. More robust RCTs are warranted.

Abstract:
Professional healthcare worker burnout is a crisis in the United States healthcare system. This crisis can be viewed at any level, from the national to local communities, but ultimately, must be understood at the level of the individual who is caring for patients. Thus, interventions to reduce burnout symptoms must prioritize the mental health of these individuals by alleviating some of the symptoms of depression, grief, and anxiety that accompany burnout. The practice of Shinrin-Yoku (Forest Bathing) is a specific evidence-based practice which research has shown can improve an individual's mental health and, when performed in a group, can support a sense of social connection. We investigated the impact of a three-hour, guided Shinrin-Yoku (Forest Bathing) nature-based intervention on burnout symptoms among physicians and other healthcare workers by using a randomized, controlled trial. The Oldenburg Burnout Inventory (OLBI) and Mini-Z assessments were used to collect baseline burnout scores and participants were randomized into the intervention group, which completed the assessment again after the Shinrin-Yoku walk, or into a control group, which completed the assessments again after a day off from any clinical duties. A total of 34 participants were enrolled in the intervention group and a total of 22 participants were enrolled in the control group. Ultimately, no statistically significant differences were detected between the pre-test and post-test scores for the intervention group or between the post-test scores of the intervention group compared to the control group. However, the subjective responses collected from participants after participating in the Shinrin-Yoku walk overwhelmingly reported decreased feelings of stress and increased mental wellbeing. This raises important questions about the difference between symptoms of burnout and other aspects of mental health, as well as the limitations of a one-time nature-based intervention on levels of chronic burnout symptoms. Thus, further research on the effects of engaging healthcare providers in an ongoing practice of Shinrin-Yoku is warranted.

Abstract:
Background: We previously found that a forest bathing (shinrin-yoku) program significantly reduced the scores for depression, anxiety, anger, fatigue, and confusion and increased the score for vigor in the profile of mood states (POMS) test and showed a potential preventive effect on the depressive status in both males and females. In the present study, we investigated the effects of a forest bathing program on the level of serotonin in serum, depressive symptoms and subjective sleep quality in middle-aged males. Methods: Twenty healthy male subjects aged 57.3 ± 8.4 years were selected after obtaining informed consent. These subjects took day trips to a forest park, the birthplace of forest bathing in Japan named Akasawa Shizen Kyuyourin, Agematsu, Nagano Prefecture (situated in central Japan), and to an urban area of Nagano Prefecture as a control in June 2019. On both trips, they walked 2.5 km for 2 hours each in the morning and afternoon on Saturday and Sunday, respectively. Blood was sampled in the afternoon before and after each trip. Concentrations of serotonin and lactic acid in serum were measured. The POMS test and a questionnaire for subjective sleep quality were conducted before and after the trips. Ambient temperature and humidity were monitoring during the trips. The Ethics Committees of the Nippon Medical School and Nagano Prefectural Kiso Hospital approved this study. Results: The forest bathing program significantly increased level of serotonin in serum, and significantly increased the score for vigor and decreased the score for fatigue in the POMS test. The forest bathing program also improved the sleepiness on rising and feeling refreshed (recovery from fatigue) in the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA). Conclusions: Taken together, the present study suggests that forest bathing may have potential preventive effects on depression (depressive status).

Abstract:
Since a single forest walk (Shinrin-yoku or forest bathing) session is reported to improve sleep temporarily, occasional forest walks may have a positive effect on daily sleep. Therefore, this study aimed to examine whether more frequent forest walking is associated with better daily sleep conditions. Data from the second survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Daiko Study conducted among residents of Nagoya City, Japan, were used. The study design was a cross-sectional study. In total, 2044 participants (529 men and 1515 women; age, mean ± standard deviation: 58.8 ± 9.9 years) were included in the analysis. Frequent forest walks were associated with a low percentage of insomnia symptoms (Insomnia Severity Index ≥10) in women, but not in men. The adjusted odds ratio for the group that rarely took forest walks with reference to the group that engaged in the activity once a month or more often was 2.04 (95% confidence interval: 1.29-3.23) in women. Forest walk frequency was not significantly associated with sleep duration or sleep efficiency as measured by actigraphy in either men or women. In conclusion, the results suggested that increasing the frequency of forest walks or Shinrin-yoku may be effective in preventing insomnia in women.

Abstract:
The potential of forests as a source of health has been addressed by the scientific community and is now being considered in national forest strategies, management plans and policies. Studies identifying the mechanisms by which forest characteristics may induce these effects on human health are nevertheless scarce. This systematic review of literature on forests and human health with real-life human exposure was conducted to assess the extent to which forests have been studied and described in detail and the extent to which relationships between forest variables and health effects have been reported. The analysis underlines the lack of forest descriptions in 19.35% of the 62 studies selected for review as well as the high heterogeneity of forest variables' description. Patterns among the articles could not be identified correlating the broader forest variable (forest type) and the most studied health variables identified (blood pressure, pulse rate or/and cortisol levels). These findings, together with previous ex situ researches, suggest the need to ameliorate and incorporate more accurate descriptions of forest variables within human health studies to provide data for forest management and the potential use of these habitats for preventive medicine and clinical practice guidelines.

Abstract:
The influence of "shinrin-yoku" (forest-air bathing and walking) on blood glucose levels in diabetic patients was examined. Eighty-seven (29 male and 58 female) non-insulin-dependent diabetic patients [61 (SEM 1) years old] participated in the present study. Shinrin-yoku was performed nine times over a period of 6 years. The patients were divided into two parties. They then walked in the forest for 3 km or 6 km according to their physical ability and/or the existence of diabetic complications. The mean blood glucose level after forest walking changed from 179 (SEM 4) mg.100 ml-1 to 108 (SEM 2) mg.100 ml-1 (P < 0.0001). The level of glycated haemoglobin A1c also decreased from 6.9 (SEM 0.2)% (before the first shinrin-yoku) to 6.5 (SEM 0.1)% (after the last shinrin-yoku; P < 0.05). Blood glucose values declined by 74 (SEM 9) mg.100 ml-1 and 70 (SEM 4) mg.100 ml-1 after short- and long-distance walking respectively. There was no significant difference between these values. Since the forest environment causes changes in hormonal secretion and autonomic nervous functions, it is presumed that, in addition to the increased calorie consumption and improved insulin sensitivity, walking in a forest environment has other beneficial effects in decreasing blood glucose levels.

Abstract:
The aim in this literature review was (1) to explore the physiologically and psychologically therapeutic benefits of forest bathing on adults suffering from pre-hypertension or hypertension, and (2) to identify the type, duration, and frequency of an effective forest bathing intervention in the management of pre-hypertension and hypertension, so as to provide directions for future interventions or research. The electronic databases PubMed, Cochrane Library, CINAHL, PsyINFO, and the China Academic Journals (CAJ) offered through the Full-text Database (CNKI) were searched for relevant studies published from the inception of the databases to April 2019. Of the 364 articles that were identified, 14 met the criteria for inclusion in this review. The synthesis of the findings in the included studies revealed that forest bathing interventions were effective at reducing blood pressure, lowering pulse rate, increasing the power of heart rate variability (HRV), improving cardiac-pulmonary parameters, and metabolic function, inducing a positive mood, reducing anxiety levels, and improving the quality of life of pre-hypertensive or hypertensive participants. Forest walking and forest therapy programs were the two most effective forest bathing interventions. Studies reported that practicing a single forest walking or forest therapy program can produce short-term physiological and psychological benefits. It is concluded that forest bathing, particularly forest walking and therapy, has physiologically and psychologically relaxing effects on middle-aged and elderly people with pre-hypertension and hypertension.

Abstract:
The purpose of this study is to examine the physiological effects of Shinrin-yoku (taking in the atmosphere of the forest). The subjects were 12 male students (22.8+/-1.4 yr). On the first day of the experiments, one group of 6 subjects was sent to a forest area, and the other group of 6 subjects was sent to a city area. On the second day, each group was sent to the opposite area for a cross check. In the forenoon, the subjects were asked to walk around their given area for 20 minutes. In the afternoon, they were asked to sit on chairs and watch the landscapes of their given area for 20 minutes. Cerebral activity in the prefrontal area and salivary cortisol were measured as physiological indices in the morning at the place of accommodation, before and after walking in the forest or city areas during the forenoon, and before and after watching the landscapes in the afternoon in the forest and city areas, and in the evening at the place of accommodation. The results indicated that cerebral activity in the prefrontal area of the forest area group was significantly lower than that of the group in the city area after walking; the concentration of salivary cortisol in the forest area group was significantly lower than that of the group in the city area before and after watching each landscape. The results of the physiological measurements show that Shinrin-yoku can effectively relax both people's body and spirit.

Abstract:
Recent advances in research concerning the public health value of natural environments have been remarkable. The growing interest in this topic (often housed under terms such as green and/or blue space) has been occurring in parallel with the microbiome revolution and an increased use of remote sensing technology in public health. In the context of biodiversity loss, rapid urbanization, and alarming rates of global non-communicable diseases (many associated with chronic, low-grade inflammation), discussions of natural vis-a-vis built environments are not merely fodder for intellectual curiosity. Here, we argue for increased interdisciplinary collaboration with the aim of better understanding the mechanisms-including aerobiological and epigenetic-that might help explain some of the noted positive health outcomes. It is our contention that some of these mechanisms are related to ecodiversity (i.e., the sum of biodiversity and geodiversity, including biotic and abiotic constituents). We also encourage researchers to more closely examine individual nature relatedness and how it might influence many outcomes that are at the interface of lifestyle habits and contact with ecodiversity.

Abstract:
Objective: Gambling disorder (GD) has been associated with economic, social, mental, and physical problems. Alternative leisure activities or stress-relieving activities have been adopted as part of GD treatment. Moreover, it has been proven that activities utilizing the natural environment, such as shinrin-yoku, have a relaxing effect on healthy people. In this study, we examined the physiological and psychological responses of patients with GD to determine whether nature therapy could reduce their stress responses. Design: This study included 22 Japanese male participants who were found to be pathological gamblers, with a South Oaks Gambling Screen score of ≤5. We exposed the participants to the digital nature sounds of insects and city sounds of a scramble intersection. The nature and city sounds were presented in a counterbalanced order. Outcome measures: A two-channel near-infrared spectroscopy system was used to measure the changes in oxyhemoglobin (oxy-Hb) concentrations in the bilateral prefrontal cortex. The heart rate variability was measured to evaluate the autonomic nervous activity. Subjective evaluation was performed using the modified version of the semantic differential method and the Profiles of Mood States, Second Edition (POMS2). Results: The oxy-Hb level in the bilateral prefrontal cortex significantly decreased. No significant difference in the high-frequency (HF) and low-frequency/HF ratio was observed. The subjective evaluation indicated that the participants experienced increased comfort and relaxation and had more natural feelings. Nature sounds significantly decreased the POMS2 negative emotion subscale and total mood disturbance scores and increased the positive emotion subscale scores. Nature-based stimulus exposure induces physiological relaxation and other positive effects among individuals even with GD. Conclusion: Exposure to nature-based sounds induces physiological relaxation and other positive responses among individuals with GD. In patients with GD, nature sounds produce the same relaxation response as in healthy individuals. (Umin.ac.jp under registration number: UMIN000042368).

Abstract:
Background: In recent years, many of Japanese workers have complained of fatigue and stress, considering them as risk factors for depression. Studies have found that "forest bathing" (Shinrin-yoku) has positive physiological effects, such as blood pressure reduction, improvement of autonomic and immune functions, as well as psychological effects of alleviating depression and improving mental health. In this study, we investigate the physiological and psychological effects of "forest bathing" on people of a working age with and without depressive tendencies. Methods: We conducted physiological measurements and psychological surveys before and after forest bathing with subjects who participated in day-long sessions of forest bathing, at a forest therapy base located in Hiroshima Prefecture. After excluding severely depressed individuals, the participants were classified into two groups: those with depressive tendencies (5 ≤ K6 ≤ 12) and those without depressive tendencies (K6 < 5) for comparative study. The evaluation indices measured were systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate (PR), autonomic functions, and profile of mood states (POMS). Results: Of the 155 participants, 37% had depressive tendencies, without any differences observed between males and females. All participants showed significant decrease in SBP, DBP, and in negative POMS items after a forest bathing session. Before the session, those with depressive tendencies scored significantly higher on the POMS negative items than those without depressive tendencies. After forest bathing, those with depressive tendencies demonstrated significantly greater improvement in many of POMS items than those without depressive tendencies, and many of them no longer differed between those with and without depressive tendencies. Conclusions: Examining the physiological and psychological effects of a day-long session of forest bathing on a working age group demonstrated significant positive effects on mental health, especially in those with depressive tendencies. Not applicable; this is not a report of intervention trial.

Abstract:
The physiological effects of "Shinrin-yoku" (taking in the atmosphere of the forest) were examined by investigating blood pressure, pulse rate, heart rate variability (HRV), salivary cortisol concentration, and immunoglobulin A concentration in saliva. Subjective feelings of being "comfortable", "calm", and "refreshed" were also assessed by questionnaire. The subjects were 12 male university students aged from 21 to 23 (mean+/-SD: 22.0+/-1.0). The physiological measurements were conducted six times, i.e., in the morning and evening before meals at the place of accommodation, before and after the subjects walked a predetermined course in the forest and city areas for 15 minutes, and before and after they sat still on a chair watching the scenery in the respective areas for 15 minutes. The findings were as follows. In the forest area compared to the city area, 1) blood pressure and pulse rate were significantly lower, and 2) the power of the HF component of the HRV tended to be higher and LF/(LF+HF) tended to be lower. Also, 3) salivary cortisol concentration was significantly lower in the forest area. These physiological responses suggest that sympathetic nervous activity was suppressed and parasympathetic nervous activity was enhanced in the forest area, and that "Shinrin-yoku" reduced stress levels. In the subjective evaluation, 4) "comfortable", "calm", and "refreshed" feelings were significantly higher in the forest area. The present study has, by conducting physiological investigations with subjective evaluations as supporting evidence, demonstrated the relaxing and stress-relieving effects of "Shinrin-yoku".

Abstract:
There is a growing awareness that spending time in nature is associated with improvement of well-being; nevertheless, the prescription of forest bathing is still limited. The aim of this systematic review was to explore the physiological and psychological benefits of different forest therapies on healthy and pathological elderly populations (>60 years) to identify the most-effective type, duration, and frequency of these interventions. A search for literature was carried out in December 2021 using PubMed, EMBASE, ResearchGate, Google Scholar and Web of Science. Grey literature was searched as well. After removal of the duplicates, within the 214 articles identified, ten met the inclusion criteria. The methodological quality of the selected studies was rated. Forest walking, alone and in combination with other activities is the most effective intervention. The selected studies reported a positive impact on physical components, including reduction in blood pressure and heart rate and improvements in cardiopulmonary and neurochemical parameters. Favorable modifications have also been noted in the psychological field, with improvements in depression, stress levels and in quality of life perception. In conclusion, forest walking may play an important role in promoting physical and mental health in healthy and pathological elderly populations. However, the lack of high-quality studies limits the strength of the results, calling for more trials.

Abstract:
This study was aimed to clarify the physiological effects of visual stimulation using forest imagery on activity of the brain and autonomic nervous system. Seventeen female university students (mean age, 21.1 ± 1.0 years) participated in the study. As an indicator of brain activity, oxyhemoglobin (oxy-Hb) concentrations were measured in the left and right prefrontal cortex using near-infrared time-resolved spectroscopy. Heart rate variability (HRV) was used as an indicator of autonomic nervous activity. The high-frequency (HF) component of HRV, which reflected parasympathetic nervous activity, and the ratio of low-frequency (LF) and high-frequency components (LF/HF), which reflected sympathetic nervous activity, were measured. Forest and city (control) images were used as visual stimuli using a large plasma display window. After sitting at rest viewing a gray background for 60 s, participants viewed two images for 90 s. During rest and visual stimulation, HRV and oxy-Hb concentration in the prefrontal cortex were continuously measured. Immediately thereafter, subjective evaluation of feelings was performed using a modified semantic differential (SD) method. The results showed that visual stimulation with forest imagery induced (1) a significant decrease in oxy-Hb concentrations in the right prefrontal cortex and (2) a significant increase in perceptions of feeling "comfortable," "relaxed," and "natural."

Abstract:
Background: Forest therapy demonstrates positive effects on mood, immune system, stress levels, and general well-being. Studies on depression, stress-related illnesses, sleep disorders, and arterial hypertension have provided evidence-based proof of this. Summary: The aim of this review was to examine the possible effects of forest therapy with regard to its evidence in the treatment of chronic neurological diseases such as stroke in the rehabilitation phase, Parkinson's disease, dementia, and multiple sclerosis. Therefore, the electronic databases Medline, Scopus, and Cochrane were searched for such clinical trials for the years 1970 to mid-2023 without language restriction. The literature search revealed only few studies with positive indications but too few cases to be able to make generalizable evidence-based statements. In terms of improvement in the Hamilton Depression Scale analysis of two studies in stroke patients showed slight benefits in the forest therapy group (standard mean difference -0.43; 95% CI: -0.76 to -0.10; p < 0.01). One observational study revealed a higher rate of stroke survival in patients living in marked greenness. Few nature-based interventions in dementia patients showed certain benefits in particular details. Key messages: There are no evidence-based results on the benefit of forest therapy for chronic neurological diseases. However, there are hints that forest therapy could have a positive benefit. Therefore, a proposal for forest therapy as a component of multimodal neurological rehabilitation is presented. Die Waldtherapie zeigt positive Auswirkungen auf die Stimmung, das Immunsystem, das Stressniveau und das allgemeine Wohlbefinden. Studien zu Depressionen, stressbedingten Erkrankungen, Schlafstörungen und arteriellem Bluthochdruck haben dies evidenzbasiert belegt.Ziel dieser Übersichtsarbeit war es, die möglichen Wirkungen der Waldtherapie im Hinblick auf ihre Evidenz bei der Behandlung chronischer neurologischer Erkrankungen wie Schlaganfall in der Rehabilitationsphase, Morbus Parkinson, Demenz und Multiple Sklerose zu untersuchen. Dazu wurden die elektronischen Datenbanken Medline, Scopus und Cochrane für die Jahre 1970 bis Mitte 2023 ohne sprachliche Einschränkung nach solchen klinischen Studien durchsucht. Die Literaturrecherche ergab nur wenige Studien mit positiven Indikationen, aber zu wenigen Fällen, um verallgemeinerbare evidenzbasierte Aussagen machen zu können. Im Hinblick auf Verbesserung in der Hamilton Depressionsskala zeigte die Analyse von 2 Studien bei Schlaganfallpatienten leichte Vorteile der Waldtherapiegruppen (Standard Mean Difference −0.43; 95% CI: -0.76- -0,10; p < 0.01). Eine Beobachtungsstudie ergab eine höhere Schlaganfall-Überlebensrate bei Patienten, die in ausgeprägtem Grün leben. Einige naturbasierte Interventionen bei Demenzpatienten zeigten in einzelnen Parametern gewisse Vorteile.Es gibt bis dato keine verallgemeinerbaren evidenzbasierten Ergebnisse zum Nutzen der Waldtherapie bei chronischen neurologischen Erkrankungen. Es gibt jedoch Hinweise, dass die Waldtherapie einen positiven Nutzen haben könnte. Es wird daher ein Vorschlag für eine Waldtherapie als Bestandteil einer multimodalen neurologischen Rehabilitation vorgestellt.

Abstract:
A recent study (FIBROWALK has supported the effectiveness of a multicomponent treatment based on pain neuroscience education (PNE), exercise therapy (TE), cognitive behavioral therapy (CBT), and mindfulness in patients with fibromyalgia. The aim of the present RCT was: (a) to analyze the effectiveness of a 12-week multicomponent treatment (nature activity therapy for fibromyalgia, NAT-FM) based on the same therapeutic components described above plus nature exposure to maximize improvements in functional impairment (primary outcome), as well as pain, fatigue, anxiety-depression, physical functioning, positive and negative affect, self-esteem, and perceived stress (secondary outcomes), and kinesiophobia, pain catastrophizing thoughts, personal perceived competence, and cognitive emotion regulation (process variables) compared with treatment as usual (TAU); (b) to preliminarily assess the effects of the nature-based activities included (yoga, Nordic walking, nature photography, and Shinrin Yoku); and (c) to examine whether the positive effects of TAU + NAT-FM on primary and secondary outcomes at post-treatment were mediated through baseline to six-week changes in process variables. A total of 169 FM patients were randomized into two study arms: TAU + NAT-FM vs. TAU alone. Data were collected at baseline, at six-week of treatment, at post-treatment, and throughout treatment by ecological momentary assessment (EMA). Using an intention to treat (ITT) approach, linear mixed-effects models and mediational models through path analyses were computed. Overall, TAU + NAT-FM was significantly more effective than TAU at posttreatment for the primary and secondary outcomes evaluated, as well as for the process variables. Moderate-to-large effect sizes were achieved at six-weeks for functional impairment, anxiety, kinesiophobia, perceived competence, and positive reappraisal. The number needed to treat (NNT) was 3 (95%CI = 1.6-3.2). The nature activities yielded an improvement in affective valence, arousal, dominance, fatigue, pain, stress, and self-efficacy. Kinesiophobia and perceived competence were the mediators that could explain a significant part of the improvements obtained with TAU + NAT-FM treatment. TAU + NAT-FM is an effective co-adjuvant multicomponent treatment for improving FM-related symptoms.

Abstract:
Objectives: Shinrin-yoku (walking and/or staying in forests in order to promote health) is a major form of relaxation in Japan; however, its effects have yet to be completely clarified. The aims of this study were: (1) to evaluate the psychological effects of shinrin-yoku in a large number of participants; and (2) to identify the factors related to these effects. Methods: Four hundred and ninety-eight healthy volunteers took part in the study. Surveys were conducted twice in a forest on the same day (forest day) and twice on a control day. Outcome measures were evaluated using the Multiple Mood Scale-Short Form (hostility, depression, boredom, friendliness, wellbeing and liveliness) and the State-Trait Anxiety Inventory A-State Scale. Statistical analyses were conducted using analysis of variance and multiple regression analyses. Results: Hostility (P<0.001) and depression (P<0.001) scores decreased significantly, and liveliness (P=0.001) scores increased significantly on the forest day compared with the control day. The main effect of environment was also observed with all outcomes except for hostility, and the forest environment was advantageous. Stress levels were shown to be related to the magnitude of the shinrin-yoku effect; the higher the stress level, the greater the effect. Conclusions: This study revealed that forest environments are advantageous with respect to acute emotions, especially among those experiencing chronic stress. Accordingly, shinrin-yoku may be employed as a stress reduction method, and forest environments can be viewed as therapeutic landscapes. Therefore, customary shinrin-yoku may help to decrease the risk of psychosocial stress-related diseases, and evaluation of the long-term effects of shinrin-yoku is warranted.

Abstract:
Background. In Japan, "Shinrin-yoku" or forest bathing (spending time in forests) is a major practice used for relaxation. However, its effects on promoting human mental health are still under consideration. The objective of this study was to investigate the physiological and psychological relaxation effects of forest walking on adults. Sixty participants (50% males; 50% females) were trained to walk 15-minute predetermined courses in a bamboo forest and a city area (control). The length of the courses was the same to allow comparison of the effects of both environments. Blood pressure and EEG results were measured to assess the physiological responses and the semantic differential method (SDM) and STAI were used to study the psychological responses. Blood pressure was significantly decreased and variation in brain activity was observed in both environments. The results of the two questionnaires indicated that walking in the bamboo forest improves mood and reduces anxiety. Moreover, the mean meditation and attention scores were significantly increased after walking in a bamboo forest. The results of the physiological and psychological measurements indicate the relaxing effects of walking in a bamboo forest on adults.

Abstract:
This study aimed to clarify the psychological benefits of brief walks through forest areas. In addition, we aimed to examine the associations between psychological responses and trait anxiety levels. Five-hundred-and-eighty-five participants (mean age, 21.7 ± 1.6 years) were instructed to walk predetermined courses through forest (test) and city (control) areas for 15 min. The Profile of Mood State (POMS) questionnaire and State-Trait Anxiety Inventory were used to assess participants' psychological responses and trait anxiety levels, respectively. The results revealed that walking through forest areas decreased the negative moods of "depression-dejection", "tension-anxiety", "anger-hostility", "fatigue", and "confusion" and improved the participants' positive mood of "vigor" compared with walking through city areas. Furthermore, a significant correlation was found between participants' trait anxiety levels and their changes in the subscale of "depression-dejection" of POMS after walking through forest areas. A more effective reduction in the feeling of "depression-dejection" after walking through forest areas was observed for participants with high trait anxiety levels than for those with normal and low trait anxiety levels. This study showed the psychological benefits of walking through forest areas and identified a significant correlation between psychological responses to walking through forests and trait anxiety levels.

Abstract:
Research suggests that stays in a forest promote relaxation and reduce stress compared to spending time in a city. The aim of this study was to compare stays in a forest with another natural environment, a cultivated field. Healthy, highly sensitive persons (HSP, SV12 score > 18) aged between 18 and 70 years spent one hour in the forest and in the field at intervals of one week. The primary outcome was measured using the Change in Subjective Self-Perception (CSP-14) questionnaire. Secondary outcomes were measured using the Profile Of Mood States (POMS) questionnaire and by analyzing salivary cortisol. We randomized 43 participants. Thirty-nine were allocated and included in the intention-to-treat analysis (90% female, mean age 45 years). CSP-14 in part showed significant differences-total score (p = 0.054, Cohen's d = 0.319), item "integration" (p = 0.028, Cohen's d = 0.365)-favoring the effects of the forest. These effects were more pronounced in summer (August). In October, during rainfall, we detected no relevant differences. POMS only showed a significant difference in the subcategory "depression/anxiety" in favor of the field. The amount of cortisol in saliva was not different between the groups. A short-term stay in a forest in summer caused a greater improvement in mood and well-being in HSP than in a field. This effect was not detectable during bad weather in the fall.

Abstract:
Objective: To study the non-temporary effects of successive walks in forested areas (shinrin-yoku) on hypertension prevalence and blood pressure levels. Methods: Data for the analysis were derived from the baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study in the Shizuoka area. Eligible participants were individuals aged 35-69 years who attended a health check-up center during 2006 and 2007. Of the 5,040 individuals who participated in the J-MICC study, Shizuoka, 4,666 were included in this analysis [3,174 men and 1,492 women; age (mean ± standard deviation) 52.1 ± 8.7 years]. The frequency of forest walking was estimated by a self-administrated questionnaire. Hypertension was defined as a systolic blood pressure ≥ 140 mmHg, a diastolic blood pressure ≥ 90 mmHg or, based on information provided in the questionnaire, the use of medication for hypertension. Results: After adjusting for age, body mass index (BMI), smoking status, alcohol consumption, and habitual exercise, the odds ratios of hypertension associated with forest walking once a week or more frequently, relative to less than once a month were 0.98 in men [95% confidence interval (CI) 0.68-1.42] and 1.48 (95% CI 0.80-2.71) in women. There was no significant trend between adjusted blood pressure levels and the frequency of forest walking. Conclusion: The results of our cross-sectional study in a Japanese population show no association between either blood pressure levels or the prevalence of hypertension and the frequency of forest walking.

Abstract:
Forest bathing practices benefit individuals' physical and mental health. A growing number of published studies provide evidence of such effects in diverse populations and contexts. However, no literature has been found that evaluates the effects of forest bathing on people with intellectual disabilities. In this paper, we present a quasi-experimental pre-post protocol for assessing the preliminary efficacy and feasibility of a forest bathing intervention in a group of adults with intellectual disability. An 11-weekly session program will be applied in the forests of the Ollo Valley, Navarre (Spain). The preliminary efficacy outcomes will be blood pressure, psycho-physiological coherence parameters and quality of life. The feasibility of the intervention will be assessed through data on barriers and facilitators of the implementation process and indicators of environmental comfort (physiological equivalent temperature and thermic perception). This study offers an opportunity for people with intellectual disabilities to benefit from a forest bathing intervention and explore its effects not only on their quality of life, but also on the improvement in their physiological and psychological state. This feasibility study is an essential step to explore crucial aspects for a future full-scale trial.

Abstract:
The effects of forest activities on health promotion have received increasing attention. The aim of this study was to evaluate the physiological and psychological effects of brief walks in forests on young women. The experiments were conducted in 6 forests (test) and 6 city areas (control). Overall, 12 participants in each area (60 participants in total, mean age: 21.0 ± 1.3 years) were instructed to walk in a forest and a city area for approximately 15 min; simultaneously, their heart rate variability, heart rate, blood pressure, and pulse rate were measured to quantify their physiological responses to walking. The modified semantic differential method, Profile of Mood States (POMS), and the State⁻Trait Anxiety Inventory (STAI) were used to determine their psychological responses. Walking in a forest was associated with significantly higher parasympathetic nervous activity and lower sympathetic nervous activity and heart rate. In addition, scores for the comfortable, relaxed, and natural parameters and vigor subscale of POMS were significantly higher, whereas scores for negative feelings, such as tension⁻anxiety, depression⁻dejection, anger⁻hostility, fatigue, and confusion, were significantly lower, as were the total mood disturbance of POMS and the anxiety dimension of the STAI. The subjective evaluations were generally in accordance with the physiological responses. A brief walk in a forest resulted in physiological and psychological relaxation effects in young women.

Abstract:
Numerous medical studies have shown the positive effects of forests on different aspects of human health. This study deals with the content of major terpenes in dominant coniferous species in Tara National Park, Serbia, in order to explore the potential for the development of a novel health tourism programme based on forest therapy. Main terpenes were analysed using a headspace-sampling technique coupled with gas-chromatography-mass spectrometry (Head-space-GC/MS). Needles of fir and spruce growing in the vicinity of hiking trails were investigated for possibilities to perform such therapy. Major detected terpenes were α-cadinol and spathulenol previously described as antiviral, antitumor, antimicrobial and immunomodulatory agents. The results of the study were favourable and worked well with the existing walking infrastructure in the observed area of the Tara Mountain, as they act as invaluable resources for designing the structured forest bathing walks. The study not only adds to the knowledge in the environmental and public health realm but also to tourism and sustainability studies.

Abstract:
Forest walking or Shinrin-yoku is a health promotion activity in Japan. Although some studies have reported the acute effects of walking a few hours in forested areas in reducing blood pressure level compared to other environments, studies investigating whether successive walking has long-term effects in lowering blood pressure levels or lowering prevalence of hypertension are rare. This study aimed to reconfirm the presence or absence of an association between the frequency of forest walking and prevalence of hypertension in a Japanese population. This J-MICC Daiko Study was conducted targeting residents in Nagoya City. A total of 5,109 participants (1,452 men and 3,657 women; age, mean ± standard deviation: 52.5 ± 10.3 years) were included in the analysis. Age-adjusted blood pressure level by frequency of forest walking was not significant. After adjusting for age and lifestyle, the adjusted odds ratios (aORs) of the most frequent group (n=88, 1.7%; once a week or more group) relative to the less than once a month group (n=4,558, 89.2%) for prevalence of hypertension were not also significant [0.80 (95% CI: 0.40-1.62) for men and 1.48 (95% CI: 0.73-3.00) for women]. This study reconfirmed that either lowering blood pressure level or lowering the prevalence of hypertension is not associated with frequency of forest walking, similar to the results of our previous J-MICC Shizuoka Study. Given that these two studies were cross-sectional studies, cohort studies investigating the causal relationship are required to evaluate the effect of frequent forest walking on the prevention of hypertension.

Abstract:
Nature-based solutions inherently require a multifaceted perspective that encompasses diverse fields. The aim of this project is to develop more effective nature-based solutions, climate action and environmental awareness by breaking down boundaries between disciplines and fostering a co-creative process. Concepts of ecology and urban forestry were combined with the research on political ecology, environmental humanities, land art, regenerative art, performing art, participatory art, and more-than-human art. This process resulted in the creation of Aula Verde Aniene. It is located in an urban park in Rome and consists of a stand of trees arranged in circles with a specific design to give the perception of being in an outdoor vegetated room. The project activities involved community participation through art performances and citizen science initiatives. Regulating and cultural ecosystem services of Aula Verde were assessed using i-Tree Eco software and citizens' surveys. Beyond numerical descriptions of ecosystem services, the manuscript introduces shinrin-yoku as a practice to raise awareness of nature. The distinctive approach here described contributed to convey a sense of belonging to the ecosystem to citizens. The project framework and study findings have been developed to formulate policy recommendations and disseminate a format that can be adapted to diverse locations.

Abstract:
Previous research has mainly dealt with the physiological and psychological restorative effects of the forest environment. However, comparatively few studies have focused on how the traits and attributes of individuals (individual traits) affect the restorative effects of the forest environment. In this study, we examined the relationships between the psychological restorative effects offered by perceived restorativeness of outdoor settings and the individual traits. Then, we investigated the relationships between the restorative indicators that are useful in examining the restorative properties (i.e., the Perceived Restorativeness Scale (PRS); seven indicators in total), the psychological restorative effect (Profile of Mood States (POMS), Restorative Outcome Scale (ROS), positive and negative affect schedule (PANAS), and Subjective Vitality Scale (SVS); 10 indicators in total), and the individual trait indicators that could be used to investigate individual traits (Development of Health and Life Habit Inventory for lifestyle, Lazarus-type Stress Coping Inventory for stress coping, World Health Organization Quality of Life Assessment 26 for quality of life (QOL), and Sukemune-Hiew Resilience test for resilience; 28 indicators in total) in forest and urban settings. Respondents consisted of 46 male students in their twenties. A short-term experiment was conducted using the same method in both environmental settings. We then analyzed the intrinsic restorative properties and the restorative effects of the settings and referred to prior research to determine the restorative effects. Furthermore, we analyzed the relationship between the restorative indicators and the individual trait indicators by correlation analysis and multiple regression (step-wise) analysis. These new findings were obtained: (1) the forest setting was a restorative environment with a higher restorative effect than the urban setting; (2) although the forest setting had a higher restorative effect than the urban setting, and the influence of individual traits was small; (3) in the forest setting, the relationship between the restorative indicators and individual traits indicators were arranged; (4) distancing (Stress coping), psychological health (QOL), and satisfaction with living environment (QOL) were likely important indicators that are related to the restorative effects in the forest setting.

Abstract:
Aim: Globally, awareness of the vital link between health and the natural environment is growing. This pilot study, based on the idea of "forest bathing," or shinrin-yoku, the mindful use of all five senses to engage with nature in a natural environment, was initiated in order to determine whether stimulation by viewing an individual's preferred video of sea or forest had an effect on relaxation. Methods: The participants were 12 healthy men in their twenties and they were divided into two groups based on their preference for sea or forest scenery by using the Visual Analogue Scale. The participants watched 90 min DVDs of sea with natural sounds and forest with natural sounds while their heart rate variability and Bispectral Index System value were measured by using MemCalc/Tawara and a Bispectral Index System monitor. Results: The participants were divided into two groups of six based on their preference for sea or forest scenery and each indicator was compared between them. Significant differences in a decrease in heart rate, increase in high frequency, and sustained arousal level were observed while viewing the preferred video. These results indicated that the viewing individual's preferred video of sea or forest had a relaxation effect. Conclusion: This study suggests that individual preferences should be taken into consideration for video relaxation therapy.

Abstract:
We investigated the influence of forest management on landscape appreciation and psychological restoration in on-site settings by exposing respondents to an unmanaged, dense coniferous (crowding) forest and a managed (thinned) coniferous forest; we set the two experimental settings in the forests of the Fuji Iyashinomoroi Woodland Study Center. The respondents were individually exposed to both settings while sitting for 15 min and were required to answer three questionnaires to analyze the psychological restorative effects before and after the experiment (feeling (the Profile of Mood States), affect (the Positive and Negative Affect Schedule), and subjective restorativeness (the Restorative Outcome Scale). To compare landscape appreciation, they were required to answer another two questionnaires only after the experiment, for scene appreciation (the semantic differential scale) and for the restorative properties of each environment (the Perceived Restorativeness Scale). Finally, we obtained these findings: (1) the respondents evaluated each forest environment highly differently and evaluated the thinned forest setting more positively; (2) the respondents' impressions of the two physical environments did not appear to be accurately reflected in their evaluations; (3) forest environments have potential restorative effects whether or not they are managed, but these effects can be partially enhanced by managing the forests.

Abstract:
The positive effect of forest bathing on the mental health and wellbeing of those suffering from post-traumatic stress disorder or experiencing stress has been proven. It is not known, however, how 'forest therapy' affects the mental health of people who are treated in a psychiatric hospital for affective or psychotic disorders. Potentially, forest therapy could bring many benefits to these people. To test the potential effectiveness of this therapy, a quasi-experiment was carried out in a psychiatric hospital in Olsztyn (north Poland). In the summer and autumn of 2018, the patients of the psychiatric hospital in Olsztyn participated in forest therapy interventions. The proposed forest therapy consisted of participating in one hour and forty-five minutes walks under the supervision of a therapist. Subjects filled out the Profile of Mood States Questionnaire (POMS) and the State Trait Anxiety Inventory (STAI-S) before and after the study. In the case of a group of patients with affective disorders, forest therapy had a positive effect on nearly all POMS scale subscales, with the exception of the 'anger-hostility' subscale, which did not change its values significantly after the intervention. In these patients, the greatest impacts were noted in the subscales 'confusion' and 'depression-dejection'; the level of anxiety measured with the STAI-S scale also significantly decreased. In the case of patients with psychotic disorders, the values of the 'confusion' and 'vigour' subscales and the STAI-S scale exhibited the greatest changes. These changes were positive for the health of patients. Regarding the 'fatigue' subscale, no significant changes were observed in patients with psychotic disorders. The observed changes in psychological indicators in psychiatric hospital patients with both kinds of disorders indicate that the intervention of forest therapy can positively affect their mental health. The changes observed in psychological indicators were related to the characteristics of the given disorder.

Abstract:
Objectives: In the present study, we aimed to clarify the psychological effects of shinrin-yoku (taking in the atmosphere of the forest) by conducting field experiments. Methods: The experiments were conducted in 19 forested and urban areas in Japan during the 2007-2010 period. Twelve male students participated at each of the 19 areas (a total of 228 persons). Subjective ratings of "comfortable-uncomfortable", "soothing-stimulating", and "natural-artificial" feelings were conducted after each of the participants had viewed the scenery for 15 min in the forested and urban areas. A postviewing questionnaire on "stressed-refreshed" feelings was also administered and the Profile of Mood State (POMS) questionnaire was employed to assess six aspects of mood before and after viewing the sceneries. Results: The forest environments were perceived as significantly more "comfortable", "soothing", and "natural" than the urban environments after viewing the sceneries. The score for "refreshed feeling" was also significantly higher in the forested areas. The score for the "vigor" subscale of POMS was significantly higher after viewing the scenery in the forested areas, whereas the scores for negative feelings such as "tension-anxiety", "depression-dejection", "anger-hostility", "fatigue", and "confusion" significantly decreased. Conclusion: Collectively, these results suggest that the forest environments have significant beneficial and relaxing effects on human's moods compared with the urban environments.

Abstract:
In the troubled times in which we currently live, the tourism industry has called into question a need for more responsible social practices and more mindful utilisation of natural environments. The Japanese practice of shinrin-yoku, or forest bathing, has not only become a new wellness trend, but also a great potential for deeply immersive tourist experiences. While there is a wealth of studies examining the positive effects of forest bathing focussing principally on its medical benefits, this qualitative study extends these debates through documenting lived experiences of forest bathers. In so doing forest bathing suggests its latent potential to offer a profoundly mindful experience, and aims to situate this practice more prominently within the tourism discourse.

Abstract:

Abstract

Background

Sleep disturbance is a major health issue in Japan. This before-after study aimed to evaluate the immediate effects of forest walking in a community-based population with sleep complaints.

Methods

Participants were 71 healthy volunteers (43 men and 28 women). Two-hour forest-walking sessions were conducted on 8 different weekend days from September through December 2005. Sleep conditions were compared between the nights before and after walking in a forest by self-administered questionnaire and actigraphy data.

Results

Two hours of forest walking improved sleep characteristics; impacting actual sleep time, immobile minutes, self-rated depth of sleep, and sleep quality. Mean actual sleep time estimated by actigraphy on the night after forest walking was 419.8 ± 128.7 (S.D.) minutes whereas that the night before was 365.9 ± 89.4 minutes (n = 42). Forest walking in the afternoon improved actual sleep time and immobile minutes compared with forest walking in the forenoon. Mean actual sleep times did not increase after forenoon walks (n = 26) (the night before and after forenoon walks, 380.0 ± 99.6 and 385.6 ± 101.7 minutes, respectively), whereas afternoon walks (n = 16) increased mean actual sleep times from 342.9 ± 66.2 to 475.4 ± 150.5 minutes. The trend of mean immobile minutes was similar to the abovementioned trend of mean actual sleep times.

Conclusions

Forest walking improved nocturnal sleep conditions for individuals with sleep complaints, possibly as a result of exercise and emotional improvement. Furthermore, extension of sleep duration was greater after an afternoon walk compared to a forenoon walk. Further study of a forest-walking program in a randomized controlled trial is warranted to clarify its effect on people with insomnia.

Abstract:
Background: We previously found that a forest bathing (shinrin-yoku) program significantly reduced the scores for depression, anxiety, anger, fatigue, and confusion and increased the score for vigor in the profile of mood states (POMS) test and showed a potential preventive effect on the depressive status in both males and females. In the present study, we investigated the effects of a forest bathing program on the level of serotonin in serum, depressive symptoms and subjective sleep quality in middle-aged males. Methods: Twenty healthy male subjects aged 57.3 ± 8.4 years were selected after obtaining informed consent. These subjects took day trips to a forest park, the birthplace of forest bathing in Japan named Akasawa Shizen Kyuyourin, Agematsu, Nagano Prefecture (situated in central Japan), and to an urban area of Nagano Prefecture as a control in June 2019. On both trips, they walked 2.5 km for 2 hours each in the morning and afternoon on Saturday and Sunday, respectively. Blood was sampled in the afternoon before and after each trip. Concentrations of serotonin and lactic acid in serum were measured. The POMS test and a questionnaire for subjective sleep quality were conducted before and after the trips. Ambient temperature and humidity were monitoring during the trips. The Ethics Committees of the Nippon Medical School and Nagano Prefectural Kiso Hospital approved this study. Results: The forest bathing program significantly increased level of serotonin in serum, and significantly increased the score for vigor and decreased the score for fatigue in the POMS test. The forest bathing program also improved the sleepiness on rising and feeling refreshed (recovery from fatigue) in the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA). Conclusions: Taken together, the present study suggests that forest bathing may have potential preventive effects on depression (depressive status).

Abstract:
Environmental health research has recently started to study the health effects of well-being-promoting practices based on forest exposure. This narrative review aims to understand whether forest exposure can directly improve respiratory function. PubMed, Cochrane Library and Google Scholar were screened, up until April 2021, for clinical studies about changes of respiratory function induced by forest exposure, preferably measured with spirometry. Relevant evidence was summarized and critically discussed. Five studies were included in this review (three trials, an observational study and a case report). Globally, forest exposure seems to be associated with improved forced expiratory volume (FEV), peak expiratory flow (PEF) and forced vital capacity (FVC). In most included studies, exposure time was at least 1 h, and sessions were repeated over time. Study participants were either healthy subjects or patients with respiratory diseases. The benefits were reported, even in terms of inflammatory markers, and were detected in children, adults and elderly individuals of both genders. The number of participants per study ranged from 1 to 65. Forest exposure coupled with light physical activity may result in short-term improvements of some respiratory function parameters (FEV1, FEV6, PEF, FVC). Autonomic responses to environmental stimuli and the inhalation of some volatile compounds detectable in the forest air seem to directly contribute to the overall effect, which may be enhanced around waterfalls and creeks due to water nebulization. However, current scientific evidence is limited, and high atmospheric levels of some plant-derived compounds, especially when reacting with air pollutants, may even worsen certain respiratory conditions. Further studies on the topic are recommended to better quantify the effect size of forest-based interventions, assess long-term benefits, ascertain potential health risks and identify any moderator variables or confounding factors.

Abstract:
Abstract Nature-based solutions inherently require a multifaceted perspective that encompasses diverse fields. The aim of this project is to develop more effective nature-based solutions, climate action and environmental awareness by breaking down boundaries between disciplines and fostering a co-creative process. Concepts of ecology and urban forestry were combined with the research on political ecology, environmental humanities, land art, regenerative art, performing art, participatory art, and more-than-human art. This process resulted in the creation of Aula Verde Aniene. It is located in an urban park in Rome and consists of a stand of trees arranged in circles with a specific design to give the perception of being in an outdoor vegetated room. The project activities involved community participation through art performances and citizen science initiatives. Regulating and cultural ecosystem services of Aula Verde were assessed using i-Tree Eco software and citizens’ surveys. Beyond numerical descriptions of ecosystem services, the manuscript introduces shinrin-yoku as a practice to raise awareness of nature. The distinctive approach here described contributed to convey a sense of belonging to the ecosystem to citizens. The project framework and study findings have been developed to formulate policy recommendations and disseminate a format that can be adapted to diverse locations.

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Since 2017, France has seen some extensive literature, books, woodland sites, professionals tackle the issue of forest bathing or “shinrin yoku”. This social phenomenon reflects a present-day concern, an activity which takes the form of taking a tour, following an itinerary or wandering, roaming a woodland environment (i.e. some mountain here) to come and meet the trees and their forest environment. The goal is to immerse oneself in the community of forests and trees. This analysis questions our relationships with our natural surroundings, to get a better understanding of how individuals consider themselves and act within the environment they are in. By structuring space and time in an orderly universe, mythical narratives give meaning to this roaming practice.These social experiments are analysed from a roaming anthropology standpoint, an approach which combines spatial, cultural, body, emotional and spiritual dimensions. The various forms of roaming the forest are said to enhance the capacitive body.

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Abstract Background In recent years, many of Japanese workers have complained of fatigue and stress, considering them as risk factors for depression. Studies have found that “forest bathing” (Shinrin-yoku) has positive physiological effects, such as blood pressure reduction, improvement of autonomic and immune functions, as well as psychological effects of alleviating depression and improving mental health. In this study, we investigate the physiological and psychological effects of “forest bathing” on people of a working age with and without depressive tendencies. Methods We conducted physiological measurements and psychological surveys before and after forest bathing with subjects who participated in day-long sessions of forest bathing, at a forest therapy base located in Hiroshima Prefecture. After excluding severely depressed individuals, the participants were classified into two groups: those with depressive tendencies (5 ≤ K6 ≤ 12) and those without depressive tendencies (K6 < 5) for comparative study. The evaluation indices measured were systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate (PR), autonomic functions, and profile of mood states (POMS). Results Of the 155 participants, 37% had depressive tendencies, without any differences observed between males and females. All participants showed significant decrease in SBP, DBP, and in negative POMS items after a forest bathing session. Before the session, those with depressive tendencies scored significantly higher on the POMS negative items than those without depressive tendencies. After forest bathing, those with depressive tendencies demonstrated significantly greater improvement in many of POMS items than those without depressive tendencies, and many of them no longer differed between those with and without depressive tendencies. Conclusions Examining the physiological and psychological effects of a day-long session of forest bathing on a working age group demonstrated significant positive effects on mental health, especially in those with depressive tendencies. Not applicable; this is not a report of intervention trial.

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AimThis study aims to explore the physiological effect of forest bathing on stress management.MethodsA total of 29 volunteers participated in this pre-post design, which lacked a control group. Several physiological parameters were recorded, including heart rate (HR), heart rate variability (HRV), electrodermal activity (EDA), blood pressure (BP), immunoglobulin A (IGA), and salivary cortisol (sCort). Additionally, the Perceived Stress Scale (PSS-10) was administered before forest exposure. Measurements were taken before and after participants spent 2 days fully immersed in a forest environment. To further assess stress management, participants completed a Mental Arithmetic Task (MAT) before and after forest immersion, during which EDA, HRV, and HR were monitored using an Empatica E4 wristband. Measurements were taken at baseline, during MAT, and afterward (recovery).ResultsParticipants exhibited moderate perceived stress levels before forest immersion (mean PSS-10 = 21.22, SD = 3.78). Post-forest exposure, there was a significant decrease in sCort (p < 0.05) and EDA (p < 0.001), while HRV increased (p < 0.001), and diastolic blood pressure rose (p < 0.05). ANOVA results from the MAT showed a significant increase in parasympathetic activity across all conditions post-immersion (p < 0.05), except during recovery, while EDA decreased in all conditions post-forest exposure (p < 0.05).ConclusionShinrin-yoku significantly improved stress management at a physiological level and could be a valuable intervention for individuals experiencing stress. However, longitudinal studies with a control group are necessary to determine whether these effects are sustained over time. Nonetheless, this study highlights the potential benefits of forest immersion for stress reduction by enhancing sympathovagal balance and the adaptability of the stress response system.

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Przedmiotem naszego namysłu jest shinrin-yoku, praktykowane w ramach zaliczenia przedmiotu z arteterapii przez studentów Wydziału Nauk o Wychowaniu UŁ. Przeprowadzane przez nas działania dydaktyczne i analizy materiału empirycznego (dzienniki spacerów) wpisują się w nurt badań opartych na sztuce. Park rozumiemy jako świadomie kształtowany krajobraz, a ten uznajemy za empiryczny przykład środowiska w rozumieniu Radlińskiej. Poprzez swoje atmosfery parki przenoszą znaczenia i wartości kształtowane także przez minione pokolenia, a w relacje z nimi wchodzą sprawcze podmioty, które w przestrzeni parków uczestniczą. Odnosząc się do dzienników spacerów przygotowanych przez studentów i powiązanych z nimi prac plastycznych, wyróżniamy cztery wyidealizowane typy uczestniczenia w parku (krajobrazie, środowisku): antropocentryczny zamknięty, antropocentryczny otwarty, równoległy, nieantropocentryczny/autoteliczny. Wyróżniamy także trzy etapy edukacji związanej z nabywaniem kompetencji do uczestniczenia w środowisku: utylitarny, pośredni, nieantropocentryczny/dialogiczny.

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Background: The most common type of pollinosis in Japan is Japanese cedar pollinosis (JCP). While forest walking is a common form of recreation for Japanese people, it has been unclear whether forest walkers with JCP still choose to visit forested areas during the pollen season or whether they avoid those areas, and as such, the aim of this study was to investigate this question. Methods: The study participants were all healthy men and women volunteers aged 20 years or over who visited the Tokyo University Forest in Chiba during 4 different days. The survey was conducted using self-administered questionnaires. Results: The number of available responses was 498. Of these, 112 participants who experienced JCP were included in the analysis. Seventy-three participants (65.2%) responded that they visit forests even during the pollen season. The association between forest walking choices during the pollen season and self-rated levels of pollinosis symptoms was not statistically significant (Cramer’s V = 0.13, p = 0.47). As many as 60% of the participants who reported serious symptom levels responded that they visit forested areas even during the pollen season. Conclusions: These results revealed that two thirds of forest walkers who had experienced JCP visited forests even during the pollen season. This indicates the further need for public service announcements informing people with JCP that the risk of pollen exposure and subsequent JCP reaction is increased by visiting forested areas during the pollen season.

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Abstract Background Shinrin-yoku (experiencing the forest atmosphere or forest bathing) has received increasing attention from the perspective of preventive medicine in recent years. Some studies have reported that the forest environment decreases blood pressure. However, little is known about the possibility of anti-hypertensive applications of Shinrin-yoku. This study aimed to evaluate preventive or therapeutic effects of the forest environment on blood pressure. Methods We systematically reviewed the medical literature and performed a meta-analysis.Four electronic databases were systematically searched for the period before May 2016 with language restriction of English and Japanese. The review considered all published, randomized, controlled trials, cohort studies, and comparative studies that evaluated the effects of the forest environment on changes in systolic blood pressure. A subsequent meta-analysis was performed. Results Twenty trials involving 732 participants were reviewed. Systolic blood pressure of the forest environment was significantly lower than that of the non-forest environment. Additionally, diastolic blood pressure of the forest environment was significantly lower than that of the non-forest environment. Conclusions This systematic review shows a significant effect of Shinrin-yoku on reduction of blood pressure.

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Many studies have explored the physiological and psychological benefits of the Japanese nature therapy practice of “shinrin-yoku,” known in the West as forest bathing. This review article has narrowed its focus to include the most recent literature about the beneficial effects of forest bathing on heart rate variability, expressed as an increase in InHF, indicating activation of the parasympathetic nervous system and also its effect on reducing anxiety.

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Abstract Aims This study focused on the newest evidence of the relationship between forest environmental exposure and human health and assessed the health efficacy of forest bathing on the human body as well as the methodological quality of a single study, aiming to provide scientific guidance for interdisciplinary integration of forestry and medicine. Method Through PubMed, Embase, and Cochrane Library, 210 papers from January 1, 2015, to April 1, 2019, were retrieved, and the final 28 papers meeting the inclusion criteria were included in the study. Result The methodological quality of papers included in the study was assessed quantitatively with the Downs and Black checklist. The methodological quality of papers using randomized controlled trials is significantly higher than that of papers using non-randomized controlled trials (p < 0.05). Papers included in the study were analyzed qualitatively. The results demonstrated that forest bathing activities might have the following merits: remarkably improving cardiovascular function, hemodynamic indexes, neuroendocrine indexes, metabolic indexes, immunity and inflammatory indexes, antioxidant indexes, and electrophysiological indexes; significantly enhancing people’s emotional state, attitude, and feelings towards things, physical and psychological recovery, and adaptive behaviors; and obvious alleviation of anxiety and depression. Conclusion Forest bathing activities may significantly improve people’s physical and psychological health. In the future, medical empirical studies of forest bathing should reinforce basic studies and interdisciplinary exchange to enhance the methodological quality of papers while decreasing the risk of bias, thereby raising the grade of paper evidence.

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Shinrin-Yoku, also known as forest-bathing, has become the focus of much psychological and neuroscientific research in recent years. In this realm, it has been shown that spending time in the forest, with a focus on the forest environment, has positive effects on both cognition and emotion. Interestingly, an individual differences perspective from personality psychology is largely lacking in shedding light on the characteristics of persons reporting higher Shinrin-Yoku tendencies than others. Therefore, this study presents the psychometric properties of a new Shinrin-Yoku scale (with a focus on the recreational aspects of visiting the forest including finding peace) to assess individual differences in enjoying forest bathing tendencies. A final sample of 896 participants was analyzed not only regarding their Shinrin-Yoku tendencies, but also with respect to the Big Five of Personality traits, life satisfaction, and perceived life stress. This study shows that higher openness to experience is robustly linked to higher Shinrin-Yoku tendencies, and higher Shinrin-Yoku tendencies are also associated with higher life satisfaction. A mediation model showed that the association between openness and life satisfaction was partially mediated by Shinrin-Yoku tendencies. No significant association was observed between perceived life stress and the Shinrin-Yoku scores. This work should be just seen as the start of beginning to construct scales assessing individual differences in Shinrin-Yoku tendencies: As one will see from the items included in the here presented final brief Shinrin-Yoku scale, many facets of Shinrin-Yoku - such as mindfulness activities in the forest – need further investigation. More research is needed to grasp the broad concept of Shinrin-Yoku including its nuances.

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Humans have enjoyed forest environments for ages because of the quiet atmosphere, beautiful scenery, mild climate, pleasant aromas, and fresh, clean air. In Japan, since 2004, serial studies have been conducted to investigate the effects of forest environments (Forest bathing/Shinrin-yoku) on human health. My research team has established a new medical science called Forest Medicine. The Forest Medicine is a new interdisciplinary science, belonging to the categories of alternative medicine, environmental medicine and preventive medicine, which studies the effects of forest environments (Forest bathing/Shinrin-yoku) on human health. It has been reported that Forest bathing/Shinrin-yoku has the following beneficial effects on human health: 1 Shinrin-yoku increases human natural killer (NK) activity, the number of NK cells, and the intracellular levels of anti-cancer proteins, suggesting a preventive effect on cancers. 2 Shinrin-yoku reduces blood pressure and heart rate showing preventive effect on hypertension and heart diseases. 3 Shinrin-yoku reduces stress hormones, such as urinary adrenaline and noradrenaline and salivary/serum cortisol contributing to stress management. 4 Shinrin-yoku increases the activity of parasympathetic nerves and reduces the activity of sympathetic nerves to stabilize the balance of autonomic nervous system. 5 Shinrin-yoku improve sleep. 6 Shinrin-yoku increases the levels of serum adiponectin and dehydroepiandrosterone sulfate. 7 In the Profile of Mood States (POMS) test, Shinrin-yoku reduces the scores for anxiety, depression, anger, fatigue, and confusion, and increases the score for vigor, showing preventive effects on depression. 8 Shinrin-yoku may apply to rehabilitation medicine 9 Shinrin-yoku in city parks also has benefits on human health. 10 Shinrin-yoku may have preventive effect on COVID-19 by boosting immune function and by reducing mental stress. Taken together, these findings suggest that Shinrin-yoku may have potential preventive effects on non-communicable diseases.

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Forest is one of the natural sources of capital in tourism but not exploited enough for tourist purposes in the sense of taking advantage of the potential of its non-wood forest products (NWFP) and social and cultural values (SCV) in general. An exploitation of NWFP and SCV indicators can realize a well-being tourist experience. It has been proven that forest has stimulating effects on human health and the general welfare. This article deals with the issue of insufficient recognition of SCVs indicators and their potential for the development of well­being tourism in the world. This paper presents an overview and findings in the existing scientific literature regarding insufficient recognition of SCVs indicators and their potential for the development of well-being tourism in the world. Beneficial effects of forests on human wellbeing are presented as well as an example of good antistress practice of forest well-being tourist product named shinrin-yoku, which was carried out in Obedska bara, Serbia.

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We investigated the effects of walking in a forest environment on salivary cortisol concentrations. Seventy-four young male participants walked for 15 min in forested and urban environments, and saliva was collected before and after walking. Our previous study reported salivary cortisol concentrations after walking only. This study was aimed at clarifying the combined effects of walking and environment by comparing post-walking data with pre-walking data. Walking in a forest environment decreased mean cortisol concentration from 9.70 to 8.37 nmol/L, whereas walking in an urban environment barely changed mean cortisol concentration, from 10.28 to 10.01 nmol/L. Two-way repeated analysis of variance revealed a significant interaction effect between the environment and walking (p < 0.001) in addition to the main effects of each (p < 0.001 and p = 0.001, for walking and environment, respectively). For further analysis, the proportion of participants who exhibited decreased cortisol after forest-walking was compared with the previously reported proportion of participants who exhibited decreased cortisol after viewing forest landscapes. Although the proportion of positive responders was slightly higher after walking (69%) than it was after viewing (60%), this difference was not statistically significant (p = 0.093). The present study revealed a significant combined effect of walking and the environment on cortisol concentrations.

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Abstract In 1980, Jonas Salk (1914–1995) encouraged professionals in anthropology and related disciplines to consider the interconnections between “planetary health,” sociocultural changes associated with technological advances, and the biology of human health. The concept of planetary health emphasizes that human health is intricately connected to the health of natural systems within the Earth’s biosphere; experts in physiological anthropology have illuminated some of the mechanisms by which experiences in natural environments (or the built environment) can promote or detract from health. For example, shinrin-yoku and related research (which first emerged from Japan in the 1990s) helped set in motion international studies that have since examined physiological responses to time spent in natural and/or urban environments. However, in order to advance such findings into planetary health discourse, it will be necessary to further understand how these biological responses (inflammation and the collective of allostatic load) are connected to psychological constructs such as nature relatedness, and pro-social/environmental attitudes and behaviors. The exposome refers to total environmental exposures—detrimental and beneficial—that can help predict biological responses of the organism to environment over time. Advances in “omics” techniques—metagenomics, proteomics, metabolomics—and systems biology are allowing researchers to gain unprecedented insight into the physiological ramifications of human behavior. Objective markers of stress physiology and microbiome research may help illuminate the personal, public, and planetary health consequences of “extinction of experience.” At the same time, planetary health as an emerging multidisciplinary concept will be strengthened by input from the perspectives of physiological anthropology.

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Abstract The aim in this literature review was (1) to explore the physiologically and psychologically therapeutic benefits of forest bathing on adults suffering from pre-hypertension or hypertension, and (2) to identify the type, duration, and frequency of an effective forest bathing intervention in the management of pre-hypertension and hypertension, so as to provide directions for future interventions or research. The electronic databases PubMed, Cochrane Library, CINAHL, PsyINFO, and the China Academic Journals (CAJ) offered through the Full-text Database (CNKI) were searched for relevant studies published from the inception of the databases to April 2019. Of the 364 articles that were identified, 14 met the criteria for inclusion in this review. The synthesis of the findings in the included studies revealed that forest bathing interventions were effective at reducing blood pressure, lowering pulse rate, increasing the power of heart rate variability (HRV), improving cardiac-pulmonary parameters, and metabolic function, inducing a positive mood, reducing anxiety levels, and improving the quality of life of pre-hypertensive or hypertensive participants. Forest walking and forest therapy programs were the two most effective forest bathing interventions. Studies reported that practicing a single forest walking or forest therapy program can produce short-term physiological and psychological benefits. It is concluded that forest bathing, particularly forest walking and therapy, has physiologically and psychologically relaxing effects on middle-aged and elderly people with pre-hypertension and hypertension.

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Humanistyka i nauki społeczne długo były niewrażliwe na rośliny, nie dostrzegając ich znaczenia i wartości w naszym życiu, co bywa określane mianem ślepoty na rośliny. W związku z tym, iż subtelne życie roślin rozgrywa się poza ludzką percepcją, zwykle pozostaje ono niedostrzegalne i tym samym nieobecne w naszej świadomości. Postrzeganie roślin jako pozbawionych ruchu lokuje je na najniższych poziomach bytów. Swoją widzialność zyskują one dopiero wtedy, gdy w świecie człowieka pojawiają się jako źródło pokarmu, lek, materiał budowlany, czy dekoracja. Celem artykułu było zwrócenie uwagi na praktyki kulturowe związane z roślinami, nasze relacjami z nimi, aby dostrzec międzygatunkową zależność oraz co nie mniej istotne, konieczność rozwijania studiów nad roślinami. Wychodząc naprzeciw temu wyzwaniu, tekst ten stara się zrehabilitować długoterminową nieobecność roślin w dyskursie humanistycznym, uwalniając je od antropocentrycznej izolacji. Artykuł stanowi rozprawę o charakterze metateoretycznym i metadyscyplinarnym, i czerpie z dorobku plant studies w obrębie kulturoznawstwa, socjologii oraz filozofii. Tekst wprowadza w problematykę plant studies, próbując ustalić ich zakres i cel, ale także zwraca uwagę na wielowymiarowość nurtu plant studies, który funkcjonuje jako obszar badań humanistycznych oraz praktyka społeczna, redefiniująca rozumienie tego, co ludzkie i pozaludzkie. Artykuł postuluje budowanie relacji z roślinami w ontologii myśli słabej, z pełnym poszanowaniem niewyraźności i niejednoznaczności roślinnego życia.

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Objective: This study aimed to evaluate the potential role of Shinrin-yoku (forest bathing) in the therapy of hypertension.     Methods and materials: A literature search was conducted in the PubMed MEADLINE database of medical publications using the following keywords: Shinrin-yoku, forest bathing, hypertension, phytoncides   Results: Hypertension is a serious problem in the Polish population. The data from the National Health Fund show that in 2020 almost 10 million adult Poles were affected by this disease, and over 14% of the entire pharmacy reimbursement budget was used to reimburse drugs for hypertension. Primary arterial hypertension is caused by a mixture of environmental and genetic factors, including obesity, mental stress, low physical activity, and excessive sodium intake. Although hypertension is usually asymptomatic, it contributes to serious complications such as left ventricular hypertrophy, impaired renal function, changes in the vessels of the retina, and finally to stroke or aortic dissection. The Shinrin-yoku (forest bathing) is becoming a worldwide recognized method used in preventative medicine and can play a substantial role in decreasing the number of patients suffering from hypertension.   Conclusion: Shinrin-yoku (forest bathing) lowers blood pressure, heart rate, and the level of stress hormones, and therefore can be a prophylactic element in preventing the development of hypertension or an element of non-pharmacological therapy for this disease entity. Additionally, it has a positive effect on the immune system.

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Abstract Background Numerous studies have reported that spending time in nature is associated with the improvement of various health outcomes and well-being. This review evaluated the physical and psychological benefits of a specific type of exposure to nature, forest therapy. Method A literature search was carried out using MEDLINE, PubMed, ScienceDirect, EMBASE, and ProQuest databases and manual searches from inception up to December 2016. Key words: “Forest” or “Shinrin -Yoku” or “Forest bath” AND “Health” or “Wellbeing”. The methodological quality of each randomized controlled trials (RCTs) was assessed according to the Cochrane risk of bias (ROB) tool. Results Six RCTs met the inclusion criteria. Participants’ ages ranged from 20 to 79 years. Sample size ranged from 18 to 99. Populations studied varied from young healthy university students to elderly people with chronic disease. Studies reported the positive impact of forest therapy on hypertension (n = 2), cardiac and pulmonary function (n = 1), immune function (n = 2), inflammation (n = 3), oxidative stress (n = 1), stress (n = 1), stress hormone (n = 1), anxiety (n = 1), depression (n = 2), and emotional response (n = 3). The quality of all studies included in this review had a high ROB. Conclusion Forest therapy may play an important role in health promotion and disease prevention. However, the lack of high-quality studies limits the strength of results, rendering the evidence insufficient to establish clinical practice guidelines for its use. More robust RCTs are warranted.

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Depuis 2017, en France, nous assistons à une prolifération d’articles, d’ouvrages, de sites forestiers, de professionnels qui mobilisent la thématique de la sylvothérapie ou shinrin yoku. Ce fait social révèle donc une préoccupation contemporaine. Cette activité consiste au travers d’un tour, d’un parcours ou d’un cheminement, à fréquenter un espace forestier, ici montagnard, pour venir à la rencontre des arbres et de leur univers sylvestre. Il s’agit d’une immersion au sein de la communauté des montagnes et des arbres. Le propos de l’analyse présentée ici consiste donc à questionner les relations à l’espace naturel, afin de saisir la façon dont les individus se considèrent et agissent dans l’environnement fréquenté. Le récit mythique, en structurant l’espace et le temps en un univers ordonné, donne du sens à cette pratique itinérante.Nous explorons ces faits sociaux à partir de l’anthropologie de l’égarement, approche qui mêle des dimensions spatiale, culturelle, corporelle, émotionnelle et spirituelle. Les formes d’itinérances sylvestres développeraient le corps capacitaire.

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Forest bathing is an approach that uses the healing effects of forests to improve people's health and prevent disease through forest walks. Although the terms forest therapy and forest bath are used in the same sense, they are different applications. While the forest therapy application is carried out in the company of a professional trained in this subject, the therapist in the forest bath is the forest itself. Considering the positive effects of forest bathing on the cardiovascular system, nervous system, endocrine system, immune system and mental health, it is thought that it can be used as an approach to protect and improve women's health. In this context, the aim of the study is to examine the physiological and psychological effects of forest bathing and forest therapy on women's health. In this study, which was revealed by literature review, the results of national and international studies on the subject were compiled. Many positive effects of forest bathing and forest therapy on the protection of human health have been reported in the literature. There are limited studies on the effects of forest therapy and forest bathing on human health, and no scientific research has been found in the field of health in our country. It is thought that these practices can be used in our country, which is rich in forests, and that scientific studies on this subject can provide benefits for women's health.

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Depuis longtemps, les êtres humains apprécient les milieux forestiers grâce à l’atmosphère tranquille qui y règne, la beauté des paysages, le climat clément, les odeurs agréables et l’air frais et pur. Depuis 2004, des études en séries ont été menées au Japon afin d’étudier les effets des milieux forestiers sur la santé humaine. Nous avons établi une nouvelle science interdisciplinaire qui appartient aux catégories des médecines douces, de la médecine environnementale et de la médecine préventive. Elle recouvre les effets des milieux forestiers sur la santé humaine. Les effets bénéfiques suivants sur la santé humaine ont été recensés : augmentation de l’activité humaine des cellules tueuses naturelles (NK, natural killer), du nombre de cellules NK et du taux intracellulaire des protéines anticancéreuses, suggérant un effet préventif contre les cancers ; baisse de la pression artérielle, de la fréquence cardiaque et de certaines hormones de stress telles que l’adrénaline et la noradrénaline urinaires et le cortisol salivaire ; augmentation de l’activité du nerf parasympathique et réduction de celle du nerf sympathique ; augmentation des taux sériques d’adiponectine et du sulfate de déhydroépiandrostérone ; dans le test dit du profil des états d’humeur (PDEH), réduction des scores pour l’anxiété, la dépression, la colère, la fatigue et la confusion, et augmentation du score pour la vigueur, attestant également d’effets psychologiques. Ces résultats indiquent que les bains de forêt pourraient avoir des effets préventifs contre les maladies liées au mode de vie.

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Forest environments have been proven beneficial for physiological well-being, supporting relaxation and meditative processes. Unfortunately, some groups, predominantly those with reduced mobility, are prevented from forest visitation. Presenting such environments in virtual reality could provide a viable substitute. However, as forest structure and composition are important aspects of its restorative power, to accurately compare the efficacy of virtual forests to that of real natural spaces, the virtual environment should match the real location as closely as possible. Furthermore, if participants achieve similar benefits in both settings, virtual copies (digital twins) of forests could be a viable option for studying forest bathing in a controlled environment. We collected LiDAR scans of a forest location near Prague, took spatial audio recordings of the forest ambiance, and built the forest’s digital twin in Unreal Engine. To compare the therapeutic efficacy of the virtual forest with its real counterpart, groups of volunteers spent half an hour in either the real forest, the virtual forest, or both. We collected participants’ demographic and psychometric data, assessing their relaxation, emotional state, and cybersickness before and after the session. Our data show an increase in relaxation with no significant differences between the environments, although participants’ emotional states did not improve in either condition. We found that participants’ experiences were comparable between the environments, but cybersickness limited the potential efficacy of virtual forest bathing. The limitations of the virtual forests as a platform for research into forest bathing are discussed.

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Background: Among the several therapeutic options assessed for the treatment of coronavirus disease 2019 (COVID-19), tocilizumab (TCZ), an antagonist of the interleukine-6 receptor, has emerged as a promising therapeutic choice, especially for the severe form of the disease. Proper synthesis of the available randomized clinical trials (RCTs) is needed to inform clinical practice. Methods: A systematic review with a meta-analysis of RCTs investigating the efficacy of TCZ in COVID-19 patients was conducted. PubMed, EMBASE, and the Cochrane COVID-19 Study Register were searched up until 30 April 2021. Results: The database search yielded 2885 records; 11 studies were considered eligible for full-text review, and nine met the inclusion criteria. Overall, 3358 patients composed the TCZ arm, and 3131 the comparator group. The main outcome was all-cause mortality at 28–30 days. Subgroup analyses according to trials’ and patients’ features were performed. A trial sequential analysis (TSA) was also carried out to minimize type I and type II errors. According to the fixed-effect model approach, TCZ was associated with a better survival odds ratio (OR) (0.84; 95% confidence interval (CI): 0.75–0.94; I2: 24% (low heterogeneity)). The result was consistent in the subgroup of severe disease (OR: 0.83; 95% CI: 0.74–0.93; I2: 53% (moderate heterogeneity)). However, the TSA illustrated that the required information size was not met unless the study that was the major source of heterogeneity was omitted. Conclusions: TCZ may represent an important weapon against severe COVID-19. Further studies are needed to consolidate this finding.

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This systematic review and meta-analysis of randomized controlled trials (RCTs) compared body compositional changes, including fat mass (FM), body fat percentage (BF%), and fat-free mass (FFM), between different types of high-intensity interval training (HIIT) (cycling vs. overground running vs. treadmill running) as well as to a control (i.e., no exercise) condition. Meta-analyses were carried out using a random-effects model. The I2 index was used to assess the heterogeneity of RCTs. Thirty-six RCTs lasting between 3 to 15 weeks were included in the current systematic review and meta-analysis. RCTs that examined the effect of HIIT type on FM, BF%, and FFM were sourced from online databases including PubMed, Scopus, Web of Science, and Google Scholar up to 21 June 2022. HIIT (all modalities combined) induced a significant reduction in FM (weighted mean difference [WMD]: −1.86 kg, 95% CI: −2.55 to −1.18, p = 0.001) despite a medium between-study heterogeneity (I2 = 63.3, p = 0.001). Subgroup analyses revealed cycling and overground running reduced FM (WMD: −1.72 kg, 95% CI: −2.41 to −1.30, p = 0.001 and WMD: −4.25 kg, 95% CI: −5.90 to −2.61, p = 0.001, respectively); however, there was no change with treadmill running (WMD: −1.10 kg, 95% CI: −2.82 to 0.62, p = 0.210). There was a significant reduction in BF% with HIIT (all modalities combined) compared to control (WMD: −1.53%, 95% CI: −2.13, −0.92, p = 0.001). All forms of HIIT also decreased BF%; however, overground running induced the largest overall effect (WMD: −2.80%, 95% CI: −3.89 to −1.71, p = 0.001). All types of HIIT combined also induced an overall significant improvement in FFM (WMD: 0.51 kg, 95% CI: 0.06 to 0.95, p = 0.025); however, only cycling interventions resulted in a significant increase in FFM compared to other exercise modalities (WMD: 0.63 kg, 95% CI: 0.17 to 1.09, p = 0.007). Additional subgroup analyses suggest that training for more than 8 weeks, at least 3 sessions per week, with work intervals less than 60 s duration and separated by ≤90 s active recovery are more effective for eliciting favorable body composition changes. Results from this meta-analysis demonstrate favorable body composition outcomes following HIIT (all modalities combined) with overall reductions in BF% and FM and improved FFM observed. Overall, cycling-based HIIT may confer the greatest effects on body composition due to its ability to reduce BF% and FM while increasing FFM.

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INTRODUCTION This systematic review provides supporting evidence for a clinical practice guideline for the management of rapid eye movement (REM) sleep behavior disorder in adults and children. METHODS The American Academy of Sleep Medicine commissioned a task force (TF) of 7 experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials (RCT) and observational studies that addressed interventions for the management of REM sleep behavior disorder (RBD) in adults and children. Statistical analyses were performed to determine the clinical significance of critical and important outcomes. Finally, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence for making recommendations. RESULTS The literature search identified 4,690 studies; 148 studies provided data suitable for statistical analyses; evidence for 45 interventions is presented. The TF provided a detailed summary of the evidence assessing the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations.

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Animal and human studies have indicated anti‐diabetic effect of Asteraceae. The present study aimed to systematically review and analyse randomized controlled trials assessing the effect of Artemisia extract on glycemic status in patients with impaired glycemic control.

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This systematic review and meta-analysis aimed to consolidate evidence on dietary interventions for atopic eczema/dermatitis (AD) skin symptoms in children without food allergies, following PRISMA 2020 guidelines. Systematic review updates were conducted in May 2022 and June 2023, focusing on randomized placebo-controlled trials (RCTs) involving children with AD but without food allergies. Specific diets or supplements, such as vitamins, minerals, probiotics, prebiotics, symbiotics, or postbiotics, were explored in these trials. Exclusions comprised descriptive studies, systematic reviews, meta-analyses, letters, case reports, studies involving elimination diets, and those reporting on food allergens in children and adolescents. Additionally, studies assessing exacerbation of AD due to food allergy/sensitization and those evaluating elimination diets' effects on AD were excluded. Nutritional supplementation studies were eligible regardless of sensitization profile. Evaluation of their impact on AD clinical expression was performed using SCORAD scores, and a meta-analysis of SCORAD outcomes was conducted using random-effect models (CRD42022328702). The review encompassed 27 RCTs examining prebiotics, Vitamin D, evening primrose oil, and substituting cow's milk formula with partially hydrolyzed whey milk formula. A meta-analysis of 20 RCTs assessing probiotics, alone or combined with prebiotics, revealed a significant reduction in SCORAD scores, suggesting a consistent trend in alleviating AD symptoms in children without food allergies. Nonetheless, evidence for other dietary interventions remains limited, underscoring the necessity for well-designed intervention studies targeting multiple factors to understand etiological interactions and propose reliable manipulation strategies.

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Background The current studies explore the effect of omega-3 polyunsaturated fatty acids (PUFAs) on appetite. Objective To examine the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on appetite using a systematic review and meta-analysis of controlled clinical trials (CTs). Patients and methods Online databases including PubMed, Scopus, ISI Web of Science, and Google Scholar were searched up to January 2022. A random-effects model was used to compare the overall standardized mean difference in appetite scores between n-3 PUFAs supplemented and control individuals. Results Fifteen eligible CTs with 1504 participants (872 for n-3 PUFA supplementation and 632 for placebo groups) were included in our systematic review. The meta-analysis showed no significant difference in overall appetite score between n-3 PUFAs supplemented and control groups (standardized mean difference [SMD] = 0.458, 95% confidence interval [CI] − 0.327, 1.242, P value = 0.25). However, the n-3 PUFA supplementation significantly increased the desire to eat (SMD = 1.07, 95% CI 0.116, 2.029, P  = 0.02) compared to control. Conclusion Although we found no effect of omega-3 supplementation on overall appetite score, it modestly increases the desire to eat. Further CTs evaluating the effect of PUFAs on appetite are still needed to confirm these findings.

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Abstract Background Studies have examined the benefit of having keratinized peri‐implant mucosa width with mixed results. Purpose This study examines whether the lack of a prespecified (2 mm) amount of keratinized mucosa width (KMW) is a risk factor for peri‐implant diseases. Methods A systematic electronic and manual search of randomized or nonrandomized controlled or noncontrolled clinical trials was conducted. Qualitative review, quantitative meta‐analysis, and trial sequence analysis (TSA) of implants inserted at sites with <2 mm or ≥2 mm of KMW were analyzed to compare all the predetermined outcome variables. The level of evidence concerning the role of KMW in peri‐implant health was evaluated via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system guide. Results Nine studies were included in the qualitative analysis and four in the meta‐analysis and TSA. No significant inter‐group difference (p > 0.05) and a low power of evidence were found for probing depth, soft‐tissue recession, and marginal bone loss. A significant difference favoring ≥2 mm KMW had a lower mean plaque index (MD = 0.37, 95% CI: [0.16, 0.58], p = 0.002) (3 studies, 430 implants, low‐quality evidence). GRADE system showed very low and low quality of evidence for all other outcome measures. Conclusion Based on the available studies, the impact of amount of KMW (either <2 mm or ≥ 2 mm) as a risk factor for developing peri‐implant disease remains low. Future control studies with proper sample size and longer follow‐up are needed to further validate current findings.

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Nitazoxanide, a US Food and Drug Administration-approved antiparasitic agent, was reported to be effective in treating coronavirus disease 2019 (COVID-19). The lack of effective and precise treatments for COVID-19 infection earlier in the pandemic forced us to depend on symptomatic, empirical, and supportive therapy, which overburdened intensive care units and exhausted hospital resources. Therefore, the aim of this systematic review and meta-analysis was to assess the efficacy and safety of nitazoxanide for COVID-19 treatment. A systematic review and meta-analysis synthesizing relevant randomized controlled trials from six databases (MedRxiv, WOS, SCOPUS, EMBASE, PubMed, and CENTRAL) until 17 May 2022 was conducted. Risk ratio (RR) for dichotomous outcomes was used and data with a 95% confidence interval (CI) are presented. The protocol was registered in PROSPERO with ID: CRD42022334658. Six randomized controlled trials with 1412 patients were included in the analysis. Nitazoxanide was effective in accelerating viral clearance compared with placebo (RR: 1.30 with 95% CI 1.08, 1.56, p = 0.006) and reducing oxygen requirements (RR: 0.48 with 95% CI 0.39, 0.59, p = 0.00001), but we found no difference between nitazoxanide and placebo in improving clinical resolution (RR: 1.01 with 95% CI 0.94, 1.08, p = 0.88), reducing the mortality rate (RR: 0.88 with 95% CI 0.4, 1.91, p = 0.74), and intensive care unit admission (RR: 0.69 with 95% CI 0.43, 1.13, p = 0.14). Moreover, nitazoxanide was as safe as placebo (RR: 0.9 with 95% CI 0.72, 1.12, p = 0.34). Compared with placebo, nitazoxanide was effective in expediting viral clearance and decreasing oxygen requirements. However, there was no difference between nitazoxanide and placebo regarding clinical response, all-cause mortality, and intensive care unit admission. Therefore, more large-scale studies are still needed to ascertain the clinical applicability of nitazoxanide in COVID-19.

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INTRODUCTION: Artificial intelligence (AI) could minimize the operator-dependent variation in colonoscopy quality. Computer-aided detection (CADe) has improved adenoma detection rate (ADR) and adenomas per colonoscopy (APC) in randomized controlled trials. There is a need to assess the impact of CADe in real-world settings. METHODS: We searched MEDLINE, EMBASE, and Web of Science for nonrandomized real-world studies of CADe in colonoscopy. Random-effects meta-analyses were performed to examine the effect of CADe on ADR and APC. The study is registered under PROSPERO (CRD42023424037). There was no funding for this study. RESULTS: Twelve of 1,314 studies met inclusion criteria. Overall, ADR was statistically significantly higher with vs without CADe (36.3% vs 35.8%, risk ratio [RR] 1.13, 95% confidence interval [CI] 1.01–1.28). This difference remained significant in subgroup analyses evaluating 6 prospective (37.3% vs 35.2%, RR 1.15, 95% CI 1.01–1.32) but not 6 retrospective (35.7% vs 36.2%, RR 1.12, 95% CI 0.92–1.36) studies. Among 6 studies with APC data, APC rate ratio with vs without CADe was 1.12 (95% CI 0.95–1.33). In 4 studies with GI Genius (Medtronic), there was no difference in ADR with vs without CADe (RR 0.96, 95% CI 0.85–1.07). DISCUSSION: ADR, but not APC, was slightly higher with vs without CADe among all available real-world studies. This difference was attributed to the results of prospective but not retrospective studies. The discrepancies between these findings and those of randomized controlled trials call for future research on the true impact of current AI technology on colonoscopy quality and the subtleties of human-AI interactions.

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INTRODUCTION The purpose of this systematic review is to provide supporting evidence for a clinical practice guideline on the use of behavioral and psychological treatments for chronic insomnia disorder in adult populations. METHODS The American Academy of Sleep Medicine commissioned a task force of nine experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials that addressed behavioral and psychological interventions for the treatment of chronic insomnia disorder in adults. Statistical analyses were performed to determine if the treatments produced clinically significant improvements in a range of critical and important outcomes. Finally, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to evaluate the evidence for making specific treatment recommendations. RESULTS The literature search identified 1274 studies; 124 studies met the inclusion criteria; 89 studies provided data suitable for statistical analyses. Evidence for the following interventions are presented in this review: Cognitive Behavioral Therapy for Insomnia (CBT-I), Brief Therapies for Insomnia (BTIs), stimulus control, sleep restriction therapy, relaxation training, sleep hygiene, biofeedback, paradoxical intention, intensive sleep retraining and mindfulness. This review provides a detailed summary of the evidence along with the quality of evidence, the balance of benefits versus harms, patient values and preferences, and resource use considerations.

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Abstract STUDY QUESTION Is exposure to dydrogesterone a risk factor for congenital anomalies when given in the first trimester for recurrent/threatened pregnancy loss or as luteal support in assisted reproductive technology (ART)? SUMMARY ANSWER Dydrogesterone, when given in the first trimester for recurrent/threatened pregnancy loss or as luteal support in ART, is not a relevant additional risk factor for congenital anomalies. WHAT IS KNOWN ALREADY Despite large clinical trials and meta-analyses that show no association between dydrogesterone and congenital anomalies, some recently retracted publications have postulated an association with teratogenicity. Dydrogesterone is also often rated as less safe than bioidentical progestins. STUDY DESIGN, SIZE, DURATION A systematic review was conducted according to a pre-specified protocol with searches on Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinicaltrials.gov. The search was limited to human studies, with no restrictions on language, geographical region, or date. The search algorithm used a PICO (Population, Intervention, Comparison, Outcome)-style approach combining both simple search terms and medical subject heading terms. As congenital anomalies are mostly reported as secondary outcomes, the search term ‘safety’ was added. PARTICIPANTS/MATERIALS, SETTING, METHODS Interventional study and observational study (OS) designs were eligible for inclusion. Inclusion criteria were: women >17 years old treated for threatened miscarriage, recurrent pregnancy loss, and/or ART; the use of dydrogesterone in the first trimester compared with placebo, no treatment or other interventions; and reporting of congenital anomalies in newborns or infants ≤12 months old (primary outcome). Two authors (A.K., M.R.N.) independently extracted the following data: general study information, study population details, intervention and comparator(s), and frequencies of congenital anomalies (classification, time of determination, and type). Risk of bias focused on the reporting of congenital malformations and was assessed using the Cochrane Risk of Bias Tool Version 2 or the ROBINS-I tool. The GRADEproGDT platform was used to generate the GRADE summary of findings table. MAIN RESULTS AND THE ROLE OF CHANCE Of the 897 records retrieved during the literature search, 47 were assessed for eligibility. Nine studies were included in the final analysis: six randomized controlled trials (RCTs) and three OSs. Among the RCTs, three had a low risk and three a high risk of bias. Two of the OSs were considered to have a serious risk of bias and one with critical risk of bias and was excluded for the evidence syntheses. The eight remaining studies included a total of 5070 participants and 2680 live births from 16 countries. In the meta-analysis of RCTs only, the overall risk ratio (RR) was 0.92 [95% CI 0.55; 1.55] with low certainty. When the two OSs were included, the overall RR was 1.11 [95% CI 0.73; 1.68] with low certainty. LIMITATIONS, REASONS FOR CAUTION The studies included in the analysis do not report congenital anomalies as the primary outcome; reporting of congenital anomalies was often not standardized. WIDER IMPLICATIONS OF THE FINDINGS This systematic literature review and meta-analysis provide clear reassurance to both clinicians and patients that dydrogesterone is not associated with congenital anomalies above the rate that might be expected due to environmental and genetic factors. The results of this work represent the highest current level of evidence for the question of congenital anomalies, which removes the existing uncertainty caused by poor quality and retracted studies. STUDY FUNDING/COMPETING INTEREST(S) Editorial support was provided by Highfield Communication Consultancy, Oxford, UK, sponsored by Abbott Products Operations AG, Allschwil, Switzerland. A.K., J.A.G.-V., L.P.S., J.N.v.d.A., and J.F.S. received honoraria from Abbott for preparation and participation in an advisory board. J.A.G.-V. received grants and lecture fees from Merck, Organon, Ferring, Gedeon Richter, and Theramex. M.R.N. has no conflicts of interest. J.N.v.d.A. and J.A.G.-V. have no other conflicts of interest. A.K. received payment from Abbott for a talk at the IVF Worldwide congress on 22 September 2023. J.F.S. has received grants from the National Institutes of Health, royalties/licences from Elsevier and Prescient Medicine (SOLVD Health), consulting fees from Burroughs Wellcome Fund (BWF) and Bayer, honoraria from Magee Women's Research Institute, Wisconsin National Primate Research Centre, University of Kansas and Oakridge National Research Laboratory, Agile, Daiichi Sankyo/American Regent, and Bayer, and travel support to attend meetings for the International Academy of Human Reproduction (IAHR). J.F.S. has patents related to diagnosis and treatment of PCOS and prediction of preterm birth. J.F.S. participates on advisory boards for SOLVD Health, Wisconsin National Primate Research Centre, and FHI360, was the past President board member of the Society for Reproductive Investigation, has a leadership role for the following organizations: Scientific Advisory Board, SOLVD Health, EAB Chair for contraceptive technology initiative, FHI360, EAB member, Wisconsin National Primate Research Centre, Advisory Board for MWRI Summit, Chair of BWF NextGen Pregnancy Research Panel, Medical Executive Committee at the Howard, and Georgeanna Jones Foundation, and is Vice President, IAHR. L.P.S. has received consulting fees from Shield Pharmaceuticals, Scynexis, Organon, Natera, Celula China, AiVF, Agile, Daiichi Sankyo, American Regent, and Medicem, honoraria from Agile, Daiichi Sankyo/American Regent, and Bayer, and travel support from BD Diagnostics. L.P.S. participates on the data safety monitoring board for Astellas and is a Chair of DSMB for fezolinetant. Abbott played no role in the funding of the study or in study design, data collection, data analysis, data interpretation, or writing of the report. TRIAL REGISTRATION NUMBER PROSPERO 2022 CRD42022356977.

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In pre-hospital settings, efficient cardiopulmonary resuscitation (CPR) is challenging; therefore, the application of mechanical CPR devices continues to increase. However, the evidence of the benefits of using mechanical CPR devices in pre-hospital settings for adult out-of-hospital cardiac arrest (OHCA) is controversial. This meta-analysis compared the effects of mechanical and manual CPR applied in the pre-hospital stage on clinical outcomes after OHCA. Cochrane Library, PubMed, Embase, and ClinicalTrials.gov were searched from inception until October 2021. Studies comparing mechanical and manual CPR applied in the pre-hospital stage for survival outcomes of adult OHCA were eligible. Data abstraction, quality assessment, meta-analysis, trial sequential analysis (TSA), and grading of recommendations, assessment, development, and evaluation were conducted. Seven randomized controlled and 15 observational studies were included. Compared to manual CPR, pre-hospital use of mechanical CPR showed a positive effect in achieving return of spontaneous circulation (ROSC) and survival to admission. No difference was found in survival to discharge and discharge with favorable neurological status, with inconclusive results in TSA. In conclusion, pre-hospital use of mechanical CPR devices may benefit adult OHCA in achieving ROSC and survival to admission. With low certainty of evidence, more well-designed large-scale randomized controlled trials are needed to validate these findings.

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INTRODUCTION This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central disorders of hypersomnolence in adults and children. The review focuses on prescription medications with U.S. Food & Drug Administration approval and nonpharmacologic interventions studied for the treatment of symptoms caused by central disorders of hypersomnolence. METHODS The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to perform a systematic review. Randomized controlled trials and observational studies addressing pharmacological and nonpharmacological interventions for central disorders of hypersomnolence were identified. Statistical analyses were performed to determine the clinical significance of all outcomes. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for the purpose of making specific treatment recommendations. RESULTS The literature search identified 678 studies; 144 met the inclusion criteria and 108 provided data suitable for statistical analyses. Evidence for the following interventions is presented: armodafinil, clarithromycin, clomipramine, dextroamphetamine, flumazenil, intravenous immune globulin (IVIG), light therapy, lithium, l-carnitine, liraglutide, methylphenidate, methylprednisolone, modafinil, naps, pitolisant, selegiline, sodium oxybate, solriamfetol, and triazolam. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. CITATION Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(9):1895-1945.

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Actinic keratosis (AK) is a chronic skin condition that may progress to cutaneous squamous cell carcinoma. We conducted a systematic review of efficacy and safety for key treatments for AK of the face and scalp, including the novel 5-day tirbanibulin 1% ointment. MEDLINE, PubMed, Embase, Cochrane Library, clinical trial registries and regulatory body websites were searched. The review included 46 studies, of which 35 studies included interventions commonly used in Europe and were sufficiently homogenous to inform a Bayesian network meta-analysis of complete clearance against topical placebo or vehicle. The network meta-analysis revealed the following odds ratios and 95% credible intervals: cryosurgery 13.4 (6.2–30.3); diclofenac 3% 2.9 (1.9–4.3); fluorouracil 0.5% + salicylic acid 7.6 (4.6–13.5); fluorouracil 4% 30.3 (9.1–144.7); fluorouracil 5% 35.0 (10.2–164.4); imiquimod 3.75% 8.5 (3.5–22.4); imiquimod 5% 17.9 (9.1–36.6); ingenol mebutate 0.015% 12.5 (8.1–19.9); photodynamic therapy with aminolevulinic acid 24.1 (10.9–52.8); photodynamic therapy with methyl aminolevulinate 11.7 (6.0–21.9); tirbanibulin 1% 11.1 (6.2–20.9). Four sensitivity analyses, from studies assessing efficacy after one treatment cycle only, for ≤25 cm2 treatment area, after 8 weeks post-treatment, and with single placebo/vehicle node confirmed the findings from the base case. Safety outcomes were assessed qualitatively. These results suggest that tirbanibulin 1% offers a novel treatment for AK, with a single short treatment period, favourable safety profile and efficacy, in line with existing topical treatments available in Europe.

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STUDY OBJECTIVE Previous randomized controlled trials (RCTs) suggest that auricular stimulation (AS) is safe and effective in treatment of preoperative anxiety; however, a systematic evaluation is lacking. The aim was to summarize the evidence on efficacy and safety of AS for preoperative anxiety, as well as for other outcomes. DESIGN We conducted a systematic review of RCTs including patients from all available populations. The search was done through MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science and Scopus Database from inception to June 2020. Study selection and data extraction were performed in by 2 independent reviewers with ability to resolve disagreements by a third author. Meta-analyses as well as the risk of bias and evidence quality assessments were performed according to the Cochrane 6.2, 2021 handbook recommendations. INTERVENTIONS We compared AS with pharmacological and non-pharmacological interventions for different outcomes. MEASUREMENTS We assessed the repercussion of the evaluated interventions over anxiety scores and their safety, physiological parameters, perioperative medications requirement and intensity of postoperative pain. MAIN RESULTS We have included 15 studies with 1603 patients. AS has presented reduced anxiety scores as compared to the sham control (Standardized Mean Difference (SMD) -0.72, 95% confidence interval (CI) -1.09 to -0.36, p < 0.0001; 8 trials; 701 patients; heterogeneity: I2 80%; GRADE: moderate certainty) and to no intervention (SMD -1.01, 95% CI -1.58 to -0.45, p = 0.0004; 4 trials; 420 patients; heterogeneity: I2 84%; GRADE: very low certainty). There was no difference between AS and benzodiazepines (SMD -0.03; 95% CI: -0.34 to 0.28; p = 0.84; 3 trials; 158 patients; heterogeneity: I2 0%; GRADE: very low certainty). No trials reported serious adverse effects of AS. CONCLUSIONS AS may be useful in treatment of preoperative anxiety. Due to heterogenous certainty in effect estimates, further research is needed to clarify the actual efficacy of AS for preoperative anxiety.

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BACKGROUND Preclinical evidence suggests that modulation of the gut microbiome could represent a new therapeutic target in nonalcoholic fatty liver disease (NAFLD). OBJECTIVES The aim of this study was to evaluate the most current evidence for liver-specific and metabolic effects of microbiome-targeted therapies (MTTs) in persons with NAFLD. METHODS We searched multiple electronic databases for randomized controlled trials (RCTs) published from January 1, 2005 to December 1, 2018 that enrolled persons with NAFLD who received MTT rather than placebo or usual care. MTT was defined as antibiotics, probiotics, synbiotics, or fecal microbiota transplantation (FMT). Clinical outcomes were pooled with the use of random-effects models and heterogeneity was assessed with the I2 statistic. A random-effects meta-regression was performed to determine sources of heterogeneity in prevalence estimates between studies. RESULTS Twenty-one RCTs (1252 participants) were included; 9 evaluated probiotics and 12 evaluated synbiotics, with treatment duration ranging from 8 to 28 wk. No RCTs examined the efficacy of antibiotics or FMT. Probiotics/synbiotics were associated with a significant reduction in alanine aminotransferase activity [ALT, weighted mean difference (WMD): -11.23 IU/L; 95% CI: -15.02, -7.44 IU/L] and liver stiffness measurement (LSM) by elastography (reflecting inflammation and fibrosis) (WMD: -0.70 kPa; 95% CI: -1.00, -0.40 kPa), although analyses showed heterogeneity (I2 = 90.6% and I2 = 93.4%, respectively). Probiotics/synbiotics were also associated with increased odds of improvement in hepatic steatosis, as graded by ultrasound (OR: 2.40; 95% CI: 1.50, 3.84; I2 = 22.4%). No RCTs examined sequential liver biopsy findings. Probiotics (WMD: -1.84; 95% CI: -3.30, -0.38; I2 = 23.6%), but not synbiotics (WMD: -0.85; 95% CI: -2.17, 0.47; I2 = 96.6%), were associated with a significant reduction in body mass index. CONCLUSIONS The use of probiotics/synbiotics was associated with improvement in liver-specific markers of hepatic inflammation, LSM, and steatosis in persons with NAFLD. Although promising, given the heterogeneity in pooled analyses, additional well-designed RCTs are needed to define the efficacy of probiotics/synbiotics for treatment of NAFLD. This study was registered with PROSPERO as CRD42018091455.

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The use of anti-vascular endothelial growth factor (VEGF) agents has profoundly changed the prognosis of neovascular age-related macular degeneration (nAMD). As clinical experiences have accumulated, it has become mandatory to summarize data to give information that can be useful in everyday practice. We conducted a systematic review to identify randomized controlled trials (RCTs) and observational studies that reported 12-month changes in best-corrected visual acuity (BCVA) in patients with nAMD on anti-VEGF monotherapy. Data were analyzed in a random-effects meta-analysis with BCVA change as the primary outcome. Meta-regression was conducted to evaluate the impact of multiple covariates. Four hundred and twelve heterogeneous study populations (109,666 eyes) were included. Anti-VEGFs induced an overall improvement of +5.37 ETDRS letters at 12 months. Meta-regression showed that mean BCVA change was statistically greater for RCTs (p = 0.0032) in comparison with observational studies. Populations following a proactive regimen had better outcomes than those following a reactive treatment regimen. Mean BCVA change was greater in younger populations, with lower baseline BCVA and treated with a higher number of injections (p < 0.001). Our results confirm that anti-VEGFs may produce a significant functional improvement at 12 months in patients with nAMD.

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ABSTRACT Objectives Severe-to-critical COVID-19 has been associated with exaggerated immune responses, and anti-inflammatory agents including corticosteroid and interleukin-6 antagonist have been repurposed as the treatment modality against severe SARS-CoV-2 infections. However, the clinical efficacy and safety of intravenous immunoglobulin (IVIG) in the treatment of patients with COVID-19 was controversial. Methods This meta-analysis of randomized controlled trials (RCTs) investigated the effectiveness of IVIG in patients with COVID-19. Electronic databases were searched for RCTs that compared the clinical efficacy of IVIG with standard of care or placebo in the hospitalized patients with COVID-19 were included. Results Six RCTs involving 472 patients were included. Patients who received IVIG had a similar mortality rate to the controls (25.3% vs 27.0%, odds ratio [OR], 0.60; 95% confidence interval [CI], 0.27–1.31). Compared with the control group, the study group demonstrated a similar incidence of receiving mechanical ventilation (OR, 0.70; 95% CI, 0.45–1.11), intensive care unit (ICU) admission (OR, 0.58; 95% CI, 0.22–1.53), length of hospital stay (mean difference [MD], −1.81 days; 95% CI, −8.42 to 4.81) and ICU stay (MD, −0.61 days; 95% CI, −2.80 to 1.58). Conclusions The administration of IVIG in hospitalized patients with COVID-19 does not improve clinical outcomes.

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Abstract Background Systemic inflammation is implicated in the onset and progression of several chronic diseases. Periodontitis is a potential trigger of systemic inflammation. Purpose To comprehensively appraise all the evidence on the effects of the treatment of periodontitis on systemic inflammation assessed by serum C‐reactive protein (CRP) levels. Data Sources Six electronic databases were searched up to 10 February 2022 to identify and select articles in English language only. Study Selection Twenty‐six randomized controlled clinical trials reporting changes amongst 2579 participants about CRP levels at 6 months or more after treatment. Data Extraction Two reviewers independently extracted data and rated the quality of studies. Meta‐analyses were performed using random and fixed effect models. Risk of Bias Risk of bias (RoB 2.0 tool) and quality of evidence (GRADEpro GDT tool) analyses were completed. Data Synthesis Treatment of periodontitis reduced CRP levels by 0.69 mg/L (95% confidence interval: −0.97 to −0.40) after 6 months, but limited evidence was retrieved from studies with longer follow‐ups. Similar findings were observed in participants with other co‐morbidities in addition to periodontitis. Greatest reductions were observed in participants with concentrations of CRP >3 mg/L at baseline. Limitations High level of heterogeneity. Conclusions Treatment of periodontitis reduces serum CRP levels (up to 6 months follow‐up) to a degree equivalent to that observed after traditional lifestyle or drug interventions. This evidence supports a causal association between periodontitis and systemic inflammation.

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BackgroundShinrin-yoku (experiencing the forest atmosphere or forest bathing) has received increasing attention from the perspective of preventive medicine in recent years. Some studies have reported that the forest environment decreases blood pressure. However, little is known about the possibility of anti-hypertensive applications of Shinrin-yoku. This study aimed to evaluate preventive or therapeutic effects of the forest environment on blood pressure.MethodsWe systematically reviewed the medical literature and performed a meta-analysis.Four electronic databases were systematically searched for the period before May 2016 with language restriction of English and Japanese. The review considered all published, randomized, controlled trials, cohort studies, and comparative studies that evaluated the effects of the forest environment on changes in systolic blood pressure. A subsequent meta-analysis was performed.ResultsTwenty trials involving 732 participants were reviewed. Systolic blood pressure of the forest environment was significantly lower than that of the non-forest environment. Additionally, diastolic blood pressure of the forest environment was significantly lower than that of the non-forest environment.ConclusionsThis systematic review shows a significant effect of Shinrin-yoku on reduction of blood pressure.

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Background Biological agents used to treat moderate-to-severe plaque psoriasis have been associated with Candida infection and other serious infections. It is, however, necessary to verify whether biologic agents increase the risk of Candida infection and serious infections and whether these risks vary among biologics. Methods PubMed, EMBASE, and Cochrane Library were searched for eligible randomized controlled trials (RCTs) from their inception to December 2021. Results from individual RCT were pooled using Peto's method with a fixed-effects model, and I2 was calculated to assess the heterogeneity. A Cochrane collaboration tool was used to examine bias risk, and Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) were used to assess the quality of evidence. Results This study included 48 published articles with data from 52 RCTs involving 27297 participants. The anti-interleukin (IL)-17 agents (95% confidence interval (CI) = 1.54–3.45, P < 0.0001) and anti-IL-12/23 agents (95% CI = 1.69–3.83, P < 0.0001) were associated with an increased risk of Candida infection compared with placebos, but there was no difference in Candida infection risk between anti-IL-17 agents and tumor necrosis factor inhibitors (TNFi) (95% CI = 0.92–3.07, P=0.09). There was no evidence that the biological agents increased the risk of serious infections in adult psoriasis (95% CI = 0.93–2.06, P=0.11) or that the biologics differed in the risk of serious infections. Conclusions Our results indicated that anti-IL-17 agents, especially secukinumab, were associated with the increased risk of Candida infection. The clinically used biological agents did not increase the risk of serious infections.

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Background: Chronic wounds place a heavy burden on the healthcare system due to the prolonged, continuous need for human resources for wound management. Our aim was to investigate the therapeutic effects of platelet-rich plasma on the treatment of chronic wounds. Methods: The systematic literature search was performed in four databases. Randomized clinical trials reporting on patients with chronic wounds treated with platelet-rich plasma (PRP) were included, comparing PRP with conventional ulcer therapy. We pooled the data using the random effects model. Our primary outcome was the change in wound size. Results: Our systematic search provided 2688 articles, and we identified 48 eligible studies after the selection and citation search. Thirty-three study groups of 29 RCTs with a total of 2198 wounds showed that the odds for complete closure were significantly higher in the PRP group than in the control group (OR = 5.32; CI: 3.37; 8.40; I2 = 58%). Conclusions: PRP is a safe and effective modality to enhance wound healing. By implementing it in clinical practice, platelet-rich plasma could become a widely used, valuable tool as it could not only improve patients’ quality of life but also decrease the healthcare burden of wound management.

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OBJECTIVE To evaluate the efficacy of different approaches to personalization in psychological therapy. METHOD This was a systematic review and meta-analysis of randomized controlled trials that compared the mental health outcomes of personalized treatment with standardized treatment and other control groups. Eligible studies were identified through three databases (Scopus, APA PsycInfo, and Web of Science). We conducted a narrative synthesis and random effects meta-analysis of available outcomes date, including subgroup analyses to investigate sources of effect size heterogeneity. The review protocol was preregistered in the Open Science Framework. RESULTS Seventeen studies (N = 7,617) met inclusion criteria for the review, nine of which (N = 5,134) provided sufficient data for inclusion in meta-analysis. Eight studies were classed as having high risk of bias, eight had moderate risk, and one had low risk. There was no significant evidence of publication bias. A statistically significant effect size was found in favor of personalized treatment relative to standardized treatment (d = 0.22, 95% CI [0.05, 0.39], p = .011). When studies with a high risk of bias were removed, this effect size was smaller but remained statistically significant (d = 0.14, 95% CI [0.08, 0.20], p < .001). CONCLUSION Current evidence indicates that personalization is an effective strategy to improve outcomes from psychological therapy, and the seemingly small effect size advantage of personalization could have an important impact at a clinical population level. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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Objective To determine acupuncture-related treatments’ effects and duration on improving cognitive function, physical function, and quality of life in patients with Alzheimer's disease. Data sources Eight electronic databases were searched for eligible randomized controlled trials from database inception to January 2021, including Medline, PubMed, EBSCO, Embase, Cochrane, Airiti Library, China National Knowledge Infrastructure, and China Journal Full-text Database. Review methods A systematic review and meta-analysis were conducted on acupuncture types, cognitive function, activity of daily life, muscle strength and quality of life. Results Sixty-six studies in total with 4191 participants, the overall risk of bias was classified 60% as low and 24% as high. Acupuncture-related treatments for cognitive function and self-care ability revealed a moderate effect size, with a significant difference in noninvasive and invasive remedies (p < 0.001). Cognitive function showed significant differences in 6, 8, 12, and 24 weeks while self-care ability in the latter two weeks (p < 0.001). Meta-regression analysis showed cognitive function increased by 0.05 points (p = 0.002) and self-care ability decreased by 0.02 points (p = 0.04) after weekly treatment. There was a significant difference in muscle strength (p = 0.0003). Conclusion Acupuncture-related treatments effectively improved cognitive function with the treatment lasted 6 weeks at least, but self-care ability started showing effects after 12 weeks of treatment. The improvement of muscle strength was also confirmed. Acupuncture-related treatments, particularly noninvasive ones, have few complications and high safety, perhaps providing patients and caregivers diversified choices and clinical care guidelines for reference.

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BACKGROUND Physical exercise is effective in managing Parkinson's disease (PD), but the relative benefit of different exercise types remains unclear. OBJECTIVES To compare the effects of different types of physical exercise in adults with PD on the severity of motor signs, quality of life (QoL), and the occurrence of adverse events, and to generate a clinically meaningful treatment ranking using network meta-analyses (NMAs). SEARCH METHODS An experienced information specialist performed a systematic search for relevant articles in CENTRAL, MEDLINE, Embase, and five other databases to 17 May 2021. We also searched trial registries, conference proceedings, and reference lists of identified studies up to this date. SELECTION CRITERIA We included randomized controlled trials (RCTs) comparing one type of physical exercise for adults with PD to another type of exercise, a control group, or both. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data. A third author was involved in case of disagreements.  We categorized the interventions and analyzed their effects on the severity of motor signs, QoL, freezing of gait, and functional mobility and balance up to six weeks after the intervention using NMAs. Two review authors independently assessed the risk of bias using the risk of bias 2 (RoB 2) tool and rated the confidence in the evidence using the CINeMA approach for results on the severity of motor signs and QoL. We consulted a third review author to resolve any disagreements. Due to heterogeneous reporting of adverse events, we summarized safety data narratively and rated our confidence in the evidence using the GRADE approach. MAIN RESULTS We included 156 RCTs with a total of 7939 participants with mostly mild to moderate disease and no major cognitive impairment. The number of participants per study was small (mean 51, range from 10 to 474). The NMAs on the severity of motor signs and QoL included data from 71 (3196 participants), and 55 (3283 participants) trials, respectively. Eighty-five studies (5192 participants) provided safety data. Here, we present the main results. We observed evidence of beneficial effects for most types of physical exercise included in our review compared to a passive control group. The effects on the severity of motor signs and QoL are expressed as scores on the motor scale of the Unified Parkinson Disease Rating Scale (UPDRS-M) and the Parkinson's Disease Questionnaire 39 (PDQ-39), respectively. For both scales, higher scores denote higher symptom burden. Therefore, negative estimates reflect improvement (minimum clinically important difference: -2.5 for UPDRS-M and -4.72 for PDQ-39). Severity of motor signs The evidence from the NMA (71 studies; 3196 participants) suggests that dance has a moderate beneficial effect on the severity of motor signs (mean difference (MD) -10.32, 95% confidence interval (CI) -15.54 to -4.96; high confidence), and aqua-based, gait/balance/functional, and multi-domain training might have a moderate beneficial effect on the severity of motor signs (aqua-based: MD -7.77, 95% CI -13.27 to -2.28; gait/balance/functional: MD -7.37, 95% CI -11.39 to -3.35; multi-domain: MD -6.97, 95% CI -10.32 to -3.62; low confidence). The evidence also suggests that mind-body training and endurance training might have a small beneficial effect on the severity of motor signs (mind-body: MD -6.57, 95% CI -10.18 to -2.81; endurance: MD -6.43, 95% CI -10.72 to -2.28; low confidence). Flexibility training might have a trivial or no effect on the severity of motor signs (MD 2.01, 95% CI -4.82 to 8.98; low confidence). The evidence is very uncertain about the effects of strength/resistance training and "Lee Silverman Voice training BIG" (LSVT BIG) on the severity of motor signs (strength/resistance: MD -6.97, 95% CI -11.93 to -2.01; LSVT BIG: MD -5.49, 95% CI -14.74 to 3.62; very low confidence). Quality of life The evidence from the NMA (55 studies; 3283 participants) suggests that aqua-based training probably has a large beneficial effect on QoL (MD -14.98, 95% CI -23.26 to -6.52; moderate confidence). The evidence also suggests that endurance training might have a moderate beneficial effect, and that gait/balance/functional and multi-domain training might have a small beneficial effect on QoL (endurance: MD -9.16, 95% CI -15.68 to -2.82; gait/balance/functional: MD -5.64, 95% CI -10.04 to -1.23; multi-domain: MD -5.29, 95% CI -9.34 to -1.06; low confidence). The evidence is very uncertain about the effects of mind-body training, gaming, strength/resistance training, dance, LSVT BIG, and flexibility training on QoL (mind-body: MD -8.81, 95% CI -14.62 to -3.00; gaming: MD -7.05, 95% CI -18.50 to 4.41; strength/resistance: MD -6.34, 95% CI -12.33 to -0.35; dance: MD -4.05, 95% CI -11.28 to 3.00; LSVT BIG: MD 2.29, 95% CI -16.03 to 20.44; flexibility: MD 1.23, 95% CI -11.45 to 13.92; very low confidence). Adverse events Only 85 studies (5192 participants) provided some kind of safety data, mostly only for the intervention groups. No adverse events (AEs) occurred in 40 studies and no serious AEs occurred in four studies. AEs occurred in 28 studies. The most frequently reported events were falls (18 studies) and pain (10 studies). The evidence is very uncertain about the effect of physical exercise on the risk of adverse events (very low confidence). Across outcomes, we observed little evidence of differences between exercise types. AUTHORS' CONCLUSIONS We found evidence of beneficial effects on the severity of motor signs and QoL for most types of physical exercise for people with PD included in this review, but little evidence of differences between these interventions. Thus, our review highlights the importance of physical exercise regarding our primary outcomes severity of motor signs and QoL, while the exact exercise type might be secondary. Notably, this conclusion is consistent with the possibility that specific motor symptoms may be treated most effectively by PD-specific programs. Although the evidence is very uncertain about the effect of exercise on the risk of adverse events, the interventions included in our review were described as relatively safe. Larger, well-conducted studies are needed to increase confidence in the evidence. Additional studies recruiting people with advanced disease severity and cognitive impairment might help extend the generalizability of our findings to a broader range of people with PD.

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Background A limited number of studies have directly examined the effect of whole eggs on body weight and composition in adults, and they have led to inconsistent results. This study aimed to summarize the evidence on the effect of whole egg consumption on body weight and body composition in adults from clinical trials. Methods Online databases were searched from inception to April 2023 for clinical trials that directly or indirectly assessed the effect of whole eggs consumption on anthropometric measures including body weight, body mass index (BMI), waist circumference (WC), and fat-free mass (FFM) in adults. A random effects model was used for meta-analysis. Results In total, 32 controlled clinical trials were included in the systematic review. The analyses revealed that whole egg consumption has no significant effect on body weight ( n  = 22), BMI ( n  = 13), WC ( n  = 10), and FFM ( n  = 4, P  > 0.05). The subgroup analyses showed that whole egg consumption has an increasing effect on body weight and BMI in studies that lasted more than 12 weeks and in unhealthy participants ( P  < 0.05). A significant increasing effect on BMI was found in studies that the control group did not receive any egg ( P  < 0.05). Moreover, in studies that there was no significant difference in energy intake between the intervention and control groups, weight, and WC were significantly increased ( P  < 0.05). Additionally, in studies that participants in the control group received another food or supplement, studies with calorie restriction, and studies on healthy subjects, whole egg intake significantly decreased BMI ( P  < 0.05). Conclusions Although whole egg consumption had no adverse effect on body composition and body weight, in overall, it might increase body weight in long term. Egg consumption beneficially affects BMI in healthy people and during weight loss diet. Systematic review registration This systematic review and meta-analysis is registered in the International Prospective Register of Systematic Reviews (PROSPERO, Registration number: CRD42022308045).

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Background Autonomy-supporting interventions, such as self-determination theory and guided self-determination interventions, may improve self-management and clinical and psychosocial outcomes in people with diabetes. Such interventions have never been systematically reviewed assessing both benefits and harms and concurrently controlling the risks of random errors using trial sequential analysis methodology. This systematic review investigates the benefits and harms of self-determination theory-based interventions compared to usual care in people with diabetes. Methods We used the Cochrane methodology. Randomized clinical trials assessing interventions theoretically based on guided self-determination or self-determination theory in any setting were eligible. A comprehensive search (latest search April 2022) was undertaken in CENTRAL, MEDLINE, Embase, LILACS, PsycINFO, SCI-EXPANDED, CINAHL, SSCI, CPCI-S, and CPCI-SSH to identify relevant trials. Two authors independently screened, extracted data, and performed risk-of-bias assessment of included trials using the Cochrane risk-of-bias tool 1.0. Our primary outcomes were quality of life, all-cause mortality, and serious adverse events. Our secondary outcomes were diabetes distress, depressive symptoms, and nonserious adverse events not considered serious. Exploratory outcomes were glycated hemoglobin and motivation (autonomy, controlled, amotivation). Outcomes were assessed at the end of the intervention (primary time point) and at maximum follow-up. The analyses were conducted using Review Manager 5.4 and Trial Sequential Analysis 0.9.5.10. Certainty of the evidence was assessed by GRADE. Results Our search identified 5578 potentially eligible studies of which 11 randomized trials (6059 participants) were included. All trials were assessed at overall high risk of bias. We found no effect of self-determination theory-based interventions compared with usual care on quality of life (mean difference 0.00 points, 95% CI −4.85, 4.86, I ^2 = 0%; 225 participants, 3 trials, TSA-adjusted CI −11.83, 11.83), all-cause mortality, serious adverse events, diabetes distress, depressive symptoms, adverse events, glycated hemoglobulin A1c, or motivation (controlled). The certainty of the evidence was low to very low for all outcomes. We found beneficial effect on motivation (autonomous and amotivation; low certainty evidence). Conclusions We found no effect of self-determination-based interventions on our primary or secondary outcomes. The evidence was of very low certainty. Systematic review registration PROSPERO CRD42020181144

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Abstract Background Systematic reviews have established the short‐term improvements of periodontal regenerative/reconstructive procedures compared to conventional surgical treatment in intrabony defects. However, a hierarchy of periodontal regenerative/reconstructive procedures regarding the medium‐ to long‐term results of treatment does not exist. Aim To systematically assess the literature to answer the focused question “In periodontitis patients with intrabony defects, what are the medium‐ and long‐term benefits of periodontal regenerative/reconstructive procedures compared with open flap debridement (OFD), in terms of clinical and/or radiographic outcome parameters and tooth retention?”. Material & Methods Randomized controlled clinical trials (RCTs), reporting on clinical and/or radiographic outcome parameters of periodontal regenerative/reconstructive procedures ≥3 years post‐operatively, were systematically assessed. Clinical [residual probing pocket depth (PD) and clinical attachment level (CAL) gain, tooth loss] and radiographic [residual defect depth (RDD), bone gain (RBL)] outcome parameters were assessed. Descriptive statistics were calculated, and Bayesian random‐effects network meta‐analyses (NMA) were performed where possible. Results Thirty RCTs, presenting data 3 to 20 years after treatment with grafting, GTR, EMD, as monotherapies, combinations thereof, and/or adjunctive use of blood‐derived growth factor constructs or with OFD only, were included. NMA based on 21 RCTs showed that OFD was clearly the least efficacious treatment; regenerative/reconstructive treatments resulted in significantly shallower residual PD in 4 out 8 comparisons [range of mean differences (MD): −2.37 to −0.60 mm] and larger CAL gain in 6 out 8 comparisons (range of MD: 1.26 to 2.66 mm), and combination approaches appeared as the most efficacious. Tooth loss after regenerative/reconstructive treatment was less frequent (0.4%) compared to OFD (2.8%), but the evidence was sparse. There were only sparse radiographic data not allowing any relevant comparisons. Conclusion Periodontal regenerative/reconstructive therapy in intrabony defects results, in general, in shallower residual PD and larger CAL gain compared with OFD, translating in high rates of tooth survival, on a medium (3–5 years) to long‐term basis (5–20 years). Combination approaches appear, in general, more efficacious compared to monotherapy in terms of shallower residual PD and larger CAL gain. A clear hierarchy could, however, not be established due to limited evidence.

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BACKGROUND A normal chromosomal constitution defined through PGT-A assessing all chromosomes on trophectoderm (TE) biopsies represents the strongest predictor of embryo implantation. Yet, its positive predictive value is not higher than 50-60%. This gap of knowledge on the causes of euploid blastocysts' reproductive failure is known as 'the black box of implantation'. OBJECTIVE AND RATIONALE Several embryonic, maternal, paternal, clinical, and IVF laboratory features were scrutinized for their putative association with reproductive success or implantation failure of euploid blastocysts. SEARCH METHODS A systematic bibliographical search was conducted without temporal limits up to August 2021. The keywords were '(blastocyst OR day5 embryo OR day6 embryo OR day7 embryo) AND (euploid OR chromosomally normal OR preimplantation genetic testing) AND (implantation OR implantation failure OR miscarriage OR abortion OR live birth OR biochemical pregnancy OR recurrent implantation failure)'. Overall, 1608 items were identified and screened. We included all prospective or retrospective clinical studies and randomized-controlled-trials (RCTs) that assessed any feature associated with live-birth rates (LBR) and/or miscarriage rates (MR) among non-mosaic euploid blastocyst transfer after TE biopsy and PGT-A. In total, 41 reviews and 372 papers were selected, clustered according to a common focus, and thoroughly reviewed. The PRISMA guideline was followed, the PICO model was adopted, and ROBINS-I and ROB 2.0 scoring were used to assess putative bias. Bias across studies regarding the LBR was also assessed using visual inspection of funnel plots and the trim and fill method. Categorical data were combined with a pooled-OR. The random-effect model was used to conduct the meta-analysis. Between-study heterogeneity was addressed using I2. Whenever not suitable for the meta-analysis, the included studies were simply described for their results. The study protocol was registered at http://www.crd.york.ac.uk/PROSPERO/ (registration number CRD42021275329). OUTCOMES We included 372 original papers (335 retrospective studies, 30 prospective studies and 7 RCTs) and 41 reviews. However, most of the studies were retrospective, or characterized by small sample sizes, thus prone to bias, which reduces the quality of the evidence to low or very low. Reduced inner cell mass (7 studies, OR: 0.37, 95% CI: 0.27-0.52, I2 = 53%), or TE quality (9 studies, OR: 0.53, 95% CI: 0.43-0.67, I2 = 70%), overall blastocyst quality worse than Gardner's BB-grade (8 studies, OR: 0.40, 95% CI: 0.24-0.67, I2 = 83%), developmental delay (18 studies, OR: 0.56, 95% CI: 0.49-0.63, I2 = 47%), and (by qualitative analysis) some morphodynamic abnormalities pinpointed through time-lapse microscopy (abnormal cleavage patterns, spontaneous blastocyst collapse, longer time of morula formation I, time of blastulation (tB), and duration of blastulation) were all associated with poorer reproductive outcomes. Slightly lower LBR, even in the context of PGT-A, was reported among women ≥38 years (7 studies, OR: 0.87, 95% CI: 0.75-1.00, I2 = 31%), while obesity was associated with both lower LBR (2 studies, OR: 0.66, 95% CI: 0.55-0.79, I2 = 0%) and higher MR (2 studies, OR: 1.8, 95% CI: 1.08-2.99, I2 = 52%). The experience of previous repeated implantation failures (RIF) was also associated with lower LBR (3 studies, OR: 0.72, 95% CI: 0.55-0.93, I2 = 0%). By qualitative analysis, among hormonal assessments, only abnormal progesterone levels prior to transfer were associated with LBR and MR after PGT-A. Among the clinical protocols used, vitrified-warmed embryo transfer was more effective than fresh transfer (2 studies, OR: 1.56, 95% CI: 1.05-2.33, I2 = 23%) after PGT-A. Lastly, multiple vitrification-warming cycles (2 studies, OR: 0.41, 95% CI: 0.22-0.77, I2 = 50%) or (by qualitative analysis) a high number of cells biopsied may slightly reduce the LBR, while simultaneous zona-pellucida opening and TE biopsy allowed better results than the Day 3 hatching-based protocol (3 studies, OR: 1.41, 95% CI: 1.18-1.69, I2 = 0%). WIDER IMPLICATIONS Embryo selection aims at shortening the time-to-pregnancy, while minimizing the reproductive risks. Knowing which features are associated with the reproductive competence of euploid blastocysts is therefore critical to define, implement, and validate safer and more efficient clinical workflows. Future research should be directed towards: (i) systematic investigations of the mechanisms involved in reproductive aging beyond de novo chromosomal abnormalities, and how lifestyle and nutrition may accelerate or exacerbate their consequences; (ii) improved evaluation of the uterine and blastocyst-endometrial dialogue, both of which represent black boxes themselves; (iii) standardization/automation of embryo assessment and IVF protocols; (iv) additional invasive or preferably non-invasive tools for embryo selection. Only by filling these gaps we may finally crack the riddle behind 'the black box of implantation'.

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At a time of significant global unrest and uncertainty surrounding how the delivery of clinical training will unfold over the coming years, we offer a systematic review, meta-analysis, and bibliometric analysis of global studies showing the crucial role simulation will play in training. Our aim was to determine the types of simulators in use, their effectiveness in improving clinical skills, and whether we have reached a point of global acceptance. A PRISMA-guided global systematic review of the neurosurgical simulators available, a meta-analysis of their effectiveness, and an extended analysis of their progressive scholarly acceptance on studies meeting our inclusion criteria of simulation in neurosurgical education were performed. Improvement in procedural knowledge and technical skills was evaluated. Of the identified 7405 studies, 56 studies met the inclusion criteria, collectively reporting 50 simulator types ranging from cadaveric, low-fidelity, and part-task to virtual reality (VR) simulators. In all, 32 studies were included in the meta-analysis, including 7 randomised controlled trials. A random effects, ratio of means effects measure quantified statistically significant improvement in procedural knowledge by 50.2% (ES 0.502; CI 0.355; 0.649, p < 0.001), technical skill including accuracy by 32.5% (ES 0.325; CI − 0.482; − 0.167, p < 0.001), and speed by 25% (ES − 0.25, CI − 0.399; − 0.107, p < 0.001). The initial number of VR studies (n = 91) was approximately double the number of refining studies (n = 45) indicating it is yet to reach progressive scholarly acceptance. There is strong evidence for a beneficial impact of adopting simulation in the improvement of procedural knowledge and technical skill. We show a growing trend towards the adoption of neurosurgical simulators, although we have not fully gained progressive scholarly acceptance for VR-based simulation technologies in neurosurgical education.

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Background Prevention and timely treatment of gestational diabetes mellitus (GDM) are important to the prognosis of pregnant women and neonates. We aimed to conduct a meta-analysis to evaluate the effects and safety of vitamin D supplementation on GDM patients and neonates, to provide insights into clinical GDM treatment. Methods Two authors searched the Medline, PubMed, Cochrane Library, Web of Science, Embase, CNKI, and Wanfang databases for randomized controlled trials (RCTs) on the effects and safety of vitamin D supplementation in GDM patients. The quality of the included RCTs was evaluated according to Cochrane handbook. RevMan 5.3 software was used for statistical analysis. Results A total of 20 RCTs involving 1682 GDM patients were finally included, of whom 837 received vitamin D supplementation. Vitamin D supplementation in GDM patients increased the serum 25(OH)D level (SMD = 4.07, 95% CI: (2.73, 5.41)) and HDL level (SMD = 0.41, 95% CI: (0.23, 0.58)) and reduced serum LDL (SMD = −0.49, 95% CI: (−0.68, −0.29)), TG (SMD = −0.59, 95% CI: (−1.01, −0.17)), and TC (SMD = −0.67, 95% CI: (−1.19, −0.14)) levels in GDM patients (all P < 0.05). Besides, vitamin D supplementation reduced the risk of premature birth (OR = 0.37, 95% CI: (0.22, 0.62)), hyperbilirubinemia (OR = 0.38, 95% CI: (0.25, 0.58)), and neonatal hospitalization (OR = 0.38, 95% CI: (0.25, 0.58)) of neonates (all P < 0.05). No significant publication bias in synthesized results was found (all P > 0.05). Conclusions Vitamin D supplementation improves the blood lipid level in GDM patients and reduces adverse neonatal outcomes. The dose and duration of vitamin D supplementation for safety need to be further investigated in future high-quality studies.

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AIM To the best of our knowledge, no study has tried to quantitatively summarize the published evidence regarding the effect of hesperidin supplementation on blood glucose control. The present systematic review and meta-analysis of randomized controlled trials aimed to determine the effectiveness of hesperidin supplementation in improving blood glucose control in adults. MATERIALS AND METHODS Electronic databases including PubMed, ISI Web of Science, Scopus, and Google Scholar were searched up to February 2019. The risk of bias in individual studies was assessed using the Cochrane collaboration's tool. The overall estimates and their 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS Six trials with 318 participants were reviewed in the present systematic review. The results showed that hesperidin had no significant effect on serum fasting blood glucose (WMD = -1.10 mg/dL, 95% CI: -3.79, 1.57), plasma insulin (WMD = -0.01 μU/mL, 95% CI: -1.20, 1.19), glycated hemoglobin A1c (WMD = -0.04%, 95% CI: -0.14, 0.04), homeostasis model assessment for insulin resistance (HOMA-IR) (WMD = 0.117, 95% CI: -0.06, 0.29) and quantitative insulin sensitivity check index (QUICKI) (WMD = 0.135; 95% CI: -0.13, 0.39), with no significant between-study heterogeneity. Subgroup analyses also indicated that the effects were not different based on the studies' design andduration, or the health status of the participants. CONCLUSION Although several animal studies have proposed that hesperidin supplementation might improve blood glucose control, the present study could not confirm this benefit in humans.

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Objective To determine the effects of different therapeutic interventions that have ever been evaluated in randomized controlled trials on pain due to plantar fasciitis. Methods We searched different electronic databases until September 2022. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated. The Grading of Recommendations Assessment, Development and Evaluation was used to evaluate the overall certainty evidence. Results A total of 236 studies met the study criteria, including 15,401 patients. Botulinum toxin MD −2.14 (CI: −4.15, −0.14), micronized dehydrated human amnion/chorion membrane injection MD −3.31 (CI: −5.54, −1.08), dry needling MD −2.34 (CI: −4.64, −0.04), low-dye taping MD −3.60 (CI: −4.16, −3.03), low-level laser therapy MD −2.09 (CI: −2.28, −1.90), myofascial releases MD −1.79 (CI: −2.63, −0.94), platelet-rich plasma MD −2.40 (CI: −4.16, −0.63), radiofrequency MD −2.47 (CI: −4.65, −0.29), and stretching MD −1.14 (CI: −2.02, −0.26) resulted in being effective treatments for pain when compared to the control in the short term. In the medium and long term, only extracorporeal shock wave therapy MD −0.97 (CI: −1.13, −0.81)/MD −2.49 (CI: −3.17, −1.82) was effective for improving pain when compared to the control. Conclusions Considering the available studies, this systematic review and meta-analysis showed that different therapeutic interventions seem to be useful strategies for improving pain in patients with plantar fasciitis. In the medium and long term, only extracorporeal shock wave therapy was effective in improving pain when compared to the control.

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Objective To assess the benefits and harms of the human papillomavirus (HPV) vaccines. Data sources Clinical study reports obtained from the European Medicines Agency and GlaxoSmithKline from 2014 to 2017. Eligibility criteria Randomised trials that compared an HPV vaccine with a placebo or active comparator in healthy participants of all ages. Appraisal and synthesis Two researchers extracted data and judged risk of bias with the Cochrane tool (version 2011). Risk ratio (RR) estimates were pooled using random-effects meta-analysis. Outcomes Clinically relevant outcomes in intention to treat populations—including HPV-related cancer precursors irrespective of involved HPV types, treatment procedures and serious and general harms. Results Twenty-four of 50 eligible clinical study reports were obtained with 58,412 pages of 22 trials and 2 follow-up studies including 95,670 participants: 79,102 females and 16,568 males age 8–72; 393,194 person-years; and 49 months mean weighted follow-up. We judged all 24 studies to be at high risk of bias. Serious harms were incompletely reported for 72% of participants (68,610/95,670). Nearly all control participants received active comparators (48,289/48,595, 99%). No clinical study report included complete case report forms. At 4 years follow-up, the HPV vaccines reduced HPV-related carcinoma in situ (367 in the HPV vaccine group vs. 490 in the comparator group, RR 0.73 [95% confidence interval, CI, 0.53 to 1.00], number needed to vaccinate [NNV] 387, P  = 0.05, I 2  = 67%) and HPV-related treatment procedures (1018 vs. 1416, RR 0.71 [95% CI 0.63 to 0.80], NNV 75, P  < 0.00001, I 2  = 45%). The HPV vaccines increased serious nervous system disorders (exploratory analysis: 72 vs. 46, RR 1.49 [1.02 to 2.16], number needed to harm [NNH] 1325, P  = 0.040, I 2  = 0%) and general harms (13,248 vs. 12,394, RR 1.07 [95% CI 1.03 to 1.11], NNH 51, P  = 0.0002, I 2  = 77%) but did not significantly increase fatal harms (45 vs. 38, RR 1.19 [95% CI 0.65 to 2.19], P  = 0.58, I 2  = 30%) or serious harms (1404 vs. 1357, RR 1.01 [95% CI 0.94 to 1.08], P  = 0.79, I 2  = 0%). Conclusion At 4 years follow-up, the HPV vaccines decreased HPV-related cancer precursors and treatment procedures but increased serious nervous system disorders (exploratory analysis) and general harms. As the included trials were primarily designed to assess benefits and were not adequately designed to assess harms, the extent to which the HPV vaccines’ benefits outweigh their harms is unclear. Limited access to clinical study reports and trial data with case report forms prevented a thorough assessment. Systematic review registration CRD42017056093. Our systematic review protocol was registered on PROSPERO in January 2017: https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20170030.pdf . Two protocol amendments were registered on PROSPERO on November 2017: https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20171116.pdf . Our index of the HPV vaccine studies was published in Systematic Reviews in January 2018: https://doi.org/10.1186/s13643-018-0675-z . A description of the challenges obtaining the data was published in September 2018: https://doi.org/10.1136/bmj.k3694 .

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Background: The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a peripherally inserted central catheter (PICC). Objectives: This systematic review and meta-analysis aimed to identify the association between the levels of potential biomarkers that reflect the activation of the blood system, long-term vascular complications, inflammatory system, and the occurrence of PICC-related DVT. Methods: Seven electronic databases (Embase, Web of Science, Medline, Scopus, Cinahl, Cochrane Central Register of Controlled Trials, and ERIC) were searched to identify literature published until December 2022. Studies were required to report: (I) adult and pediatric patients, outpatient or admitted to clinical, surgical, or ICU with PICC; (II) patients with PICC-related DVT and patients without PICC-related DVT as a comparator; and (III) at least one biomarker available. The Newcastle–Ottawa Scale was used to evaluate the quality of the studies. Study precision was evaluated by using a funnel plot for platelets level. We provided a narrative synthesis and meta-analysis of the findings on the biomarkers’ outcomes of the studies. We pooled the results using random effects meta-analysis. The meta-analysis was conducted using Review Manager software v5.4. This systematic review is registered in PROSPERO (CRD42018108871). Results: Of the 3564 studies identified (after duplication removal), 28 were included. PICC-related DVT was associated with higher D-dimers (0.37 μg/mL, 95% CI 0.02, 0.72; p = 0.04, I2 = 92%; p for heterogeneity < 0.00001) and with higher platelets (8.76 × 109/L, 95% CI 1.62, 15.91; p = 0.02, I2 = 41%; p for heterogeneity = 0.06). Conclusions: High levels of D-dimer and platelet were associated with DVT in patients with PICC. However, biomarkers such as APTT, fibrinogen, FDP, glucose, hemoglobin, glycated hemoglobin, INR, prothrombin time, prothrombin fragment 1.2, the thrombin–antithrombin complex, and WBC were not related to the development of DVT associated with PICC.

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Category: Sports; Trauma Introduction/Purpose: Uncertainty exists regarding the best treatment for acute Achilles tendon ruptures. Simultaneous comparison of the multiple treatment options using traditional study designs is problematic; multiarm clinical trials often are logistically constrained to small sample sizes, and traditional meta-analyses are limited to comparisons of only two treatments that have been compared in head-to-head trials. Network meta-analyses allow for simultaneous comparison of all existing treatments utilizing both direct and indirect evidence. We performed a network meta-analysis of randomized controlled trials to answer the following questions: Considering open repair, minimally invasive surgery repair, functional rehabilitation, or primary immobilization for acute Achilles tendon ruptures, (1) which intervention is associated with the lowest risk of rerupture? (2) Which intervention is associated with the lowest risk of complications resulting in surgery? Methods: Five databases and grey literature sources were searched from inception to September 30, 2019. Included studies were RCTs comparing treatment of acute Achilles tendon ruptures using two or more of the following interventions: primary immobilization, functional rehabilitation, open surgical repair, or MIS repair. We excluded studies enrolling patients with chronic ruptures, reruptures, and preexisting Achilles tendinopathy as well as studies with more than 20% loss to follow-up or less than 6 months of follow-up. Nineteen RCTs (1316 patients) were included in the final analysis. The mean number of patients per study treatment arm was 35 +- 16, mean age was 41 +- 5 years, mean sex composition was 80% +- 10% males, and mean follow-up was 22 +- 12 months. The four treatment groups were compared for the main outcomes of rerupture and complications resulting in operation. The analysis was conducted using random-effects Bayesian network meta-analysis with vague priors. Results: Treatment with primary immobilization had a greater risk of rerupture than open surgery (odds ratio 4.06 [95% credible interval {CrI} 1.47 to 11.88]; p < 0.05). There were no other differences between treatments for risk of rerupture. Minimally invasive surgery was ranked first for fewest complications resulting in surgery and was associated with a lower risk of complications resulting in surgery than functional rehabilitation (OR 0.16 [95% CrI 0.02 to 0.90]; p < 0.05), open surgery (OR 0.22 [95% CrI 0.04 to 0.93]; p < 0.05), and primary immobilization (OR < 0.01 [95% CrI < 0.01 to 0.01]; p < 0.05). Risk of complications resulting in surgery was no different between primary immobilization and open surgery (OR 1.46 [95% CrI 0.35 to 5.36]). Data for patient-reported outcome scores and return to activity were inappropriate for pooling secondary to considerable clinical heterogeneity and imprecision associated with small sample sizes. Conclusion: Faced with acute Achilles tendon rupture, patients should be counseled that the risk of rerupture likely is no different across contemporary treatments. Considering the possibly lower risk of complications resulting in surgery associated with MIS repair, patients and surgeons must balance any benefit with the potential risks of MIS techniques. As treatments continue to evolve, consistent reporting of validated patient-reported outcome measures is critically important to facilitate analysis with existing RCT evidence. Infrequent but serious complications such as rerupture and deep infection should be further explored to determine whether meaningful differences exist in specific patient populations.

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Immaturity in digestive-tract motor function and altered intestinal microbiome may play roles in pathogenesis of infantile colic. We assessed the impact of probiotic therapy on crying duration day, in newborns experiencing colic attacks. The PubMed, Embase, Cinnahl, Web of Science databases, and a clinical trials registry (ClinicalTrials.gov) were searched from inception until 12/02/2020. Random-effects meta-analyses were used to derive standardized mean differences/differences in means and risk ratios. We included 16 studies, which involved 1319 newborns aged up to 6 months. Lactobacillus reuteri strain DSM17938 was administered predominantly (n = 10). Probiotic intervention reduced the duration of crying (standardized mean difference = −2.012, 95% confidence interval: −2.763 to −1.261, z = −5.25, p < 0.0001). The probability of at least a 50% reduction in crying duration was at least 1.98 times higher in the intervention group than in controls (Z = 4.80, p < 0.0001). The effects of the intervention were not significantly affected by the risk of bias assessment, percentage of breastfed infants, and duration of the study. In 11 studies, data concerning gut microbiota composition and function and/or immunological markers were given. Probiotics significantly shortened the crying duration, but a causal relationship between the modulatory effect of probiotics on microbiota and the immune system has not been confirmed.

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Background Repetitive transcranial magnetic stimulation (rTMS) applied to the mylohyoid cortical region has positive clinical effects on post-stroke. Therefore, we conducted a meta-analysis to investigate the efficacy of rTMS for patients with post-stroke dysphagia. Methods According to PRISMA guidelines, we searched the databases of MEDLINE (PubMed), Cochrane Library, Embase, Web of Science, CNKI, Wangfang. We searched for studies of randomized controlled trials (RCTs) of rTMS to treat dysphagia after stroke and screened by inclusion and exclusion criteria. Features of RCTs were extracted. The heterogeneity of the trials was measured by I2 statistic. Results In total, 11 RCTs with 463 dysphagia patients fulfilled our inclusion criteria. In our analysis, rTMS demonstrated a great beneficial effect for post-stroke dysphagia when combined with traditional swallowing exercises. Moreover, a greatly significant difference (P = 0.008) was noted based on stimulation frequency (high frequency vs. low frequency). Additionally, no significant difference (P = 0.53) was observed based on stimulation site (affected vs. unaffected hemisphere). Conclusions Overall, rTMS can effectively accelerate the improvement of swallowing function in patients with post-stroke swallowing disorders.

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Objective: To determine the effects of behavioural interventions in people with oropharyngeal dysphagia. Methods: Systematic literature searches were conducted to retrieve randomized controlled trials in four different databases (CINAHL, Embase, PsycINFO, and PubMed). The methodological quality of eligible articles was assessed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2), after which meta-analyses were performed using a random-effects model. Results: A total of 37 studies were included. Overall, a significant, large pre-post interventions effect size was found. To compare different types of interventions, all behavioural interventions and conventional dysphagia treatment comparison groups were categorised into compensatory, rehabilitative, and combined compensatory and rehabilitative interventions. Overall, significant treatment effects were identified favouring behavioural interventions. In particular, large effect sizes were found when comparing rehabilitative interventions with no dysphagia treatment, and combined interventions with compensatory conventional dysphagia treatment. When comparing selected interventions versus conventional dysphagia treatment, significant, large effect sizes were found in favour of Shaker exercise, chin tuck against resistance exercise, and expiratory muscle strength training. Conclusions: Behavioural interventions show promising effects in people with oropharyngeal dysphagia. However, due to high heterogeneity between studies, generalisations of meta-analyses need to be interpreted with care.

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AIMS To synthesise and evaluate the effectiveness of virtual reality interventions in preoperative children. BACKGROUND Children consider operations as a predictable threat and stressful event. Children's anxiety before an operation increases as the time draws closer. Children could understand the operating room environment and process before the operation using virtual reality, which may reduce their anxiety before an operation. DESIGN A systematic review and meta-analysis of randomised controlled trials following the Cochrane method were conducted. METHOD CINAHL, Cochrane Library, Embase, Joanna Briggs Institute, MEDLINE and PubMed databases were searched for randomised controlled trials published before February 2021. A random-effects model meta-analysis to calculate pooled prevalence and 95% confidence intervals was performed. Conduction of the review adheres to the PRISMA checklist. RESULTS Of 257 articles screened, six interventions involving 529 participants aged 4-12 years were included in the analysis. All study evidence levels were B2/Level 2, the quality was medium to high on the modified Jadad scale, with a low risk of bias. The results revealed that virtual reality significantly reduced preoperative anxiety in children (SMD: -0.91, 95% CI: -1.43 to -0.39, p = .0006). Furthermore, virtual reality significantly improved children's compliance with anaesthesia (SMD: 3.49, 95% CI: 1.32 to 9.21, p = .01). CONCLUSION Children who used virtual reality before an operation felt more familiar with the operating room environment and understood the preoperative preparation procedures. Virtual reality effectively reduced children's anxiety and improved their compliance with anaesthesia. RELEVANCE TO CLINICAL PRACTICE This systematic review and meta-analysis investigated the effect of virtual reality on preoperative anxiety in children and the findings supported its positive effects. The results could provide a reference for incorporating virtual reality into preoperative preparation guidelines.

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Abstract Background Hallux valgus is the most common foot deformity and affects 23% to 35% of the general population. More than 150 different techniques have been described for surgical correction. Recently, there has been increasing interest in the use of minimally invasive surgery to correct hallux valgus deformities. A variety of studies have been published with differing outcomes regarding minimally invasive surgery. However, most studies lack sufficient power and are small, making it difficult to draw adequate conclusions. A meta-analysis can therefore be helpful to evaluate and compare minimally invasive and open surgery. Questions/purposes We performed a systematic review and meta-analysis of randomized controlled trials and prospective controlled studies to answer the following question: Compared with open surgery, does minimally invasive surgery for hallux valgus result in (1) improved American Orthopaedic Foot and Ankle Society (AOFAS) scores and VAS scores for pain, (2) improved radiologic outcomes, (3) fewer complications, or (4) a shorter duration of surgery? Methods The systematic review and meta-analysis was conducted according to the guidelines of the Cochrane Handbook for Systematic Reviews of Intervention and the Preferred Reporting Items for Systematic Reviews and Meta-analyses. A search was performed in the PubMed, Embase, Scopus, CINAHL, and CENTRAL databases on May 3, 2022. Studies were eligible if they were randomized controlled or prospective controlled studies that compared minimally invasive surgery and open surgery to treat patients with hallux valgus. We defined minimally invasive surgery as surgery performed through the smallest incision required to perform the procedure accurately, with an incision length of approximately 2 cm at maximum. Open surgery, on the other hand, involves a larger incision and direct visualization of deeper structures. Seven studies (395 feet), consisting of six randomized controlled studies and one prospective comparative study, were included in the qualitative and quantitative data synthesis. There were no differences between the minimally invasive and open surgery groups regarding age, gender, or severity of hallux valgus deformity. Each included study was assessed for the risk of bias using the second version of the Cochrane tool for assessing the risk of bias in randomized trials or by using the Newcastle-Ottawa Scale for comparative studies. Most of the included studies had intermediate quality regarding the risk of bias. We excluded one study from our analysis because of its high risk of bias to avoid serious distortions in the meta-analysis. We performed a sensitivity analysis to confirm that our meta-analysis was robust by including only studies with a low risk of bias. The analyzed endpoints included the AOFAS score (range 0 to 100), where higher scores represent less pain and better function; the minimum clinically important difference on this scale was 29 points. In addition, the VAS score was analyzed, which is based on a pain rating scale (range 0 to 10), with higher scores representing greater pain. Radiologic outcomes included the hallux valgus angle, intermetatarsal angle, and distal metatarsal articular angle. Complications were qualitatively assessed and evaluated for differences. A random-effects model was used if substantial heterogeneity (I2 > 50%) was found; otherwise, a fixed-effects model was used. Results We found no clinically important difference between minimally invasive and open surgery in terms of the AOFAS score (88 ± 7 versus 85 ± 8, respectively; mean difference 4 points [95% CI 1 to 6]; p < 0.01). There were no differences between the minimally invasive and open surgery groups in terms of VAS scores (0 ± 0 versus 0 ± 1, respectively; standardized mean difference 0 points [95% CI -1 to 0]; p = 0.08). There were no differences between the minimally invasive and open surgery groups in terms of the hallux valgus angle (12° ± 4° versus 12° ± 4°; mean difference 0 points [95% CI -2 to 2]; p = 0.76). Radiographic measurements of the intermetatarsal angle did not differ between the minimally invasive and open surgery groups (7° ± 2° versus 7° ± 2°; mean difference 0 points [95% CI -1 to 1]; p = 0.69). In addition, there were no differences between the minimally invasive and open surgery groups in terms of the distal metatarsal articular angle (7° ± 4° versus 8° ± 4°; mean difference -1 point [95% CI -4 to 2]; p = 0.28). The qualitative analysis revealed no difference in the frequency or severity of complications between the minimally invasive and the open surgery groups. The minimally invasive and open surgery groups did not differ in terms of the duration of surgery (28 ± 8 minutes versus 40 ± 10 minutes; mean difference -12 minutes [95% CI -25 to 1]; p = 0.06). Conclusion This meta-analysis found that hallux valgus treated with minimally invasive surgery did not result in improved clinical or radiologic outcomes compared with open surgery. Methodologic shortcomings of the source studies in this meta-analysis likely inflated the apparent benefits of minimally invasive surgery, such that in reality it may be inferior to the traditional approach. Given the associated learning curves—during which patients may be harmed by surgeons who are gaining familiarity with a new technique—we are unable to recommend the minimally invasive approach over traditional approaches, in light of the absence of any clinically important benefits identified in this meta-analysis. Future research should ensure studies are methodologically robust using validated clinical and radiologic parameters, as well as patient-reported outcome measures, to assess the long-term outcomes of minimally invasive surgery.

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Cancer-related anorexia/cachexia is known to be associated with worsened quality of life and survival; however, limited treatment options exist. Although megestrol acetate (MA) is often used off-label to stimulate appetite and improve anorexia/cachexia in patients with advanced cancers, the benefits are controversial. The present meta-analysis aimed to better elucidate the clinical benefits of MA in patients with cancer-related anorexia/cachexia. A systematic search of PubMed, EMBASE, OVID Medline, Clinicaltrials.gov, and Google Scholar databases found 23 clinical trials examining the use of MA in cancer-related anorexia. The available randomized, controlled trials were appraised using Version 2 of the Cochrane risk-of-bias tool (RoB 2) and they had moderate-to-high risk of bias. A total of eight studies provided sufficient data on weight change for meta-analysis. The studies were divided into high-dose treatment (>320 mg/day) and low-dose treatment (≤320 mg/day). The overall pooled mean change in weight among cancer patients treated with MA, regardless of dosage was 0.75 kg (95% CI = −1.64 to 3.15, τ2 = 9.35, I2 = 96%). Patients who received high-dose MA tended to have weight loss rather than weight gain. There were insufficient studies to perform a meta-analysis for the change in tricep skinfold, midarm circumference, or quality of life measures. MA was generally well-tolerated, except for a clear thromboembolic risk, especially with higher doses. On balance, MA did not appear to be effective in providing the symptomatic improvement of anorexia/cachexia in patients with advanced cancer.

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Background. A number of recent randomized controlled trials reported the efficacy of brain–computer interface (BCI) for upper-limb stroke rehabilitation compared with other therapies. Despite the encouraging results reported, there is a significant variance in the reported outcomes. This paper aims to investigate the effectiveness of different BCI designs on poststroke upper-limb rehabilitation. Methods. The effect sizes of pooled and individual studies were assessed by computing Hedge’s g values with a 95% confidence interval. Subgroup analyses were also performed to examine the impact of different BCI designs on the treatment effect. Results. The study included 12 clinical trials involving 298 patients. The analysis showed that the BCI yielded significant superior short-term and long-term efficacy in improving the upper-limb motor function compared to the control therapies (Hedge’s g = 0.73 and 0.33, respectively). Based on our subgroup analyses, the BCI studies that used the intention of movement had a higher effect size compared to those used motor imagery (Hedge’s g = 1.21 and 0.55, respectively). The BCI studies using band power features had a significantly higher effect size than those using filter bank common spatial patterns features (Hedge’s g = 1.25 and − 0.23, respectively). Finally, the studies that used functional electrical stimulation as the BCI feedback had the highest effect size compared to other devices (Hedge’s g = 1.2). Conclusion. This meta-analysis confirmed the effectiveness of BCI for upper-limb rehabilitation. Our findings support the use of band power features, the intention of movement, and the functional electrical stimulation in future BCI designs for poststroke upper-limb rehabilitation.

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BACKGROUND AND OBJECTIVES Animal experiments showed that resistant starch (RS) had an antioxidant and antiinflammatory effect. However, clinical studies showed both insignificant and significant effects of RS on inflammation and oxidative stress. The purpose of this work is to conduct a systematic review and meta-analysis of previous randomized controlled trials (RCTs) to investigate these effects. METHODS AND STUDY DESIGN A systematic literature search was conducted on Web of Science, Scopus, PubMed and Cochrane electronic databases, which included studies from the earliest date of the database to September 2021. Key inclusion criteria were: RCTs; reporting at least one inflammatory or oxidative stress biomarker as endpoint; more than seven day intervention. Key exclusion criteria were: using a mixture of RS and other functional food ingredients as intervention substance; inappropriate controls. RESULTS A total of 16 RCTs including 706 subjects were included. RS supplementation significantly improved total antioxidant capacity [standard mean difference (SMD) (95% CI): 2.64 (0.34, 4.94), p=0.03], and significantly reduced blood malondialdehyde concentration [SMD (95% CI): -0.55 (- 0.94, -0.17), p=0.01]. RS supplementation significantly reduced blood C-reactive protein concentration in type 2 diabetes mellitus (T2DM) patients [SMD (95% CI): -0.35 (-0.65, -0.05), p=0.02]. RS consumption significantly reduced blood interlukin-6 and tumor necrosis factor- concentration if removing one distinct trial. CONCLUSIONS RS supplementation may significantly reduce a few oxidative-stress and inflammation biomarkers such as malondialdehyde and C-reactive protein, particularly in T2DM patients. Future work should investigate the optimal dosage of RS supplementation for modulating oxidative stress and inflammation biomarkers related to T2DM.

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AIM The aim of the present study was to evaluate the efficacy of probiotics as an adjunct to scaling and root planning (SRP) in the treatment of chronic periodontitis (CP). METHODS The focused question of the study was: Does adjunctive use of probiotics yield better clinical periodontal outcomes compared to placebo/no treatment group in the treatment of CP? Electronic and manual literature searches were conducted up to December 2017 using the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register. Forest plots were computed reporting weighted mean difference (WMD) of outcomes and 95% confidence intervals (CI). RESULTS Seven clinical studies were included. Four studies showed additional benefits in reducing periodontal probing depth (PPD) and gaining clinical attachment level (CAL), whereas, three studies showed comparable clinical periodontal outcomes between probiotics and SRP/placebo. Significant heterogeneity was observed for PPD reduction and CAL gain. The overall mean difference for CAL gain between probiotics and placebo/SRP was significant (WMD = 1.41, 95% CI = 0.15-2.67, P = .028) at follow up. CONCLUSION Adjunctive probiotics could result in additional benefits in CAL gain in CP. Nevertheless, further high-quality randomized clinical trials with microbiological outcomes are warranted to obtain strong conclusions in this regard.

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STUDY OBJECTIVES Robotic pets or companion robots have demonstrated positive effects on several emotional and physiological factors in humans. Robots could constitute a complementary or alternative method to treat sleep problems, but individual studies on robots' effectiveness regarding sleep show mixed results. The aim of the current study was to compare the effects of robots, plush toys, and treatment as usual on sleep in adults. METHODS The current study is a systematic review and frequentist network meta-analysis of all randomized and cluster randomized controlled trials comparing the effects of robots, plush toys, and treatment as usual on total sleep time in adults. RESULTS Four studies were included in the analysis. Three studies were considered to have a high risk of bias, whereas one was rated with some concerns. The studies comprised 381 participants. These subjects were older adults, with or without dementia, living in nursing homes. The total sleep time was the only common sleep measure included in all four studies. The network meta-analysis showed no statistically significant differences between the three experimental groups. CONCLUSIONS The robot interventions were not found to have positive effects on total sleep time in older adults compared with plush toys or treatment as usual. Future studies should use robots especially made to target sleep, include a thorough screening of the participants, and exclude people with adequate sleep, select appropriate sleep measures, and report the results appropriately for future meta-analyses.

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The review systematically explored in vivo or in situ studies investigating the efficacy of nano-hydroxyapatite (nHA) to reduce initiation of or to remineralize initial caries lesions. Prospective controlled (non-)randomized clinical trials investigating the efficacy of a nHA compared to any other (placebo) treatment or untreated/standard control. Three electronic databases (Central Cochrane, PubMed-MEDLINE, Ovid EMBASE) were screened. Outcomes were, e.g., ICDAS score, laser fluorescence, enamel remineralization rate, mineral loss, and lesion depth. No language or time restrictions were applied. Risk of bias and level of evidence were graded using the Risk of Bias 2.0 tool and GRADE profiler. Five in vivo (and 5 in situ) studies with at least 633 teeth (1031 specimens) being assessed in more than 420 (95) patients were included. No meta-analysis could be performed for in vivo studies due to the high heterogeneity of the study designs and the variety of outcomes. In situ studies indicate that under demineralization conditions, NaF was able to hinder demineralization, whereas nHA did not; simultaneously, nHA did not differ from the fluoride-free control. In contrast, under remineralizing conditions, nHA and NaF show the same remineralizing potential. However, the level of evidence was very low. Furthermore, six studies showed a high risk of bias, and six studies were funded/published by the manufacturers of the tested products. The low number of clinical studies, the relatively short follow-up periods, the high risks of bias, and the limiting grade of evidence do not allow for conclusive evidence on the efficacy of nHA. No conclusive evidence on the efficacy of nHA could be obtained based on the low number of clinical studies, the relatively short follow-up periods, the high risks of bias, the limiting grade of evidence, and study conditions that do not reflect the everyday conditions.

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This systematic review and meta-analysis examined the effects of electronic cigarettes on periodontal health compared to conventional cigarette smoke and a non-smoking population. MEDLINE, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov were screened for literature. Eligibility criteria included clinical studies published between 2006 and 2022 that compare e-cigarettes and conventional cigarettes on periodontal health (bleeding on probing (BoP), plaque index (PI), probing depth (PD), attachment loss (AL), marginal bone loss (MBL), tooth loss, molecular inflammation markers, salivary flow rate). Meta-regression analysis was used to examine the influence of moderator variables. Sixteen studies were found to be eligible for qualitative synthesis. Individual analyses showed that cigarette smokers had significantly higher PI, PD, AL, and MBL and increased concentrations of proinflammatory mediators than e-cigarette users and non-smokers. Meta-analysis revealed a 0.33-fold lower chance for BoP in e-cigarette users compared to smokers (p = 0.03), whereby meta-regression failed to detect any effects regarding the age of users and frequency of smoking. A 0.01-fold decreased chance for positive BoP in e-cigarette users compared with non-smokers was seen (p < 0.01). The current findings suggest that that e-cigarette use might be considered a healthier alternative to cigarette smoking concerning periodontal health. Even so, harmful effects of electronic nicotine delivery system (ENDS) usage on periodontal health were seen as well. However, a definitive decision on this research question remains elusive due to the absence of randomized controlled trials. Electronic cigarettes, marketed as a safer alternative to traditional cigarettes, are becoming increasingly popular. Evidence on the use of electronic cigarettes as a cessation aid and its beneficial impact compared to cigarette smoke remains inconclusive, so the analysis conducted in this review addresses a recent question of high clinical relevance.

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BACKGROUND It has been suggested that low-energy sweeteners (LES) may be associated with an increased risk of metabolic diseases, possibly due to stimulation of glucose-responsive mechanisms. OBJECTIVE We conducted a systematic review and meta-analysis of human intervention studies examining the acute effect of LES intake on postprandial glucose (PPG) and postprandial insulin (PPI) responses, in order to comprehensively and objectively quantify these relations. METHODS We systematically searched the Medline, OVID FSTA, and SCOPUS databases until January 2020. Randomized controlled trials comparing acute postprandial effects on PPG and/or PPI after exposure to LES, either alone, with a meal, or with other nutrient-containing preloads to the same intervention without LES were eligible for inclusion. PPG and PPI responses were calculated as mean incremental area under the curve divided by time. Meta-analyses were performed using random effects models with inverse variance weighing. RESULTS Twenty-six papers (34 PPG trials and 29 PPI trials) were included. There were no reports of statistically significant differences in the effects of LES on PPG and PPI responses compared with control interventions. Pooled effects of LES intake on the mean change difference in PPG and PPI were -0.02 mmol/L (95% CI: -0.09, 0.05) and -2.39 pmol/L (95% CI: -11.83, 7.05), respectively. The results did not appreciably differ by the type or dose of LES consumed, cointervention type, or fasting glucose and insulin levels. Among patients with type 2 diabetes, the mean change difference indicated a smaller PPG response after exposure to LES compared with the control (-0.3 mmol/L; 95% CI: -0.53, -0.07). CONCLUSIONS Ingestion of LES, administered alone or in combination with a nutrient-containing preload, has no acute effects on the mean change in postprandial glycemic or insulinemic responses compared with a control intervention. Apart from a small beneficial effect on PPG (-0.3 mmol/L) in studies enrolling patients with type 2 diabetes, the effects did not differ by type or dose of LES, or fasting glucose or insulin levels. This review and meta-analysis was registered at PROSPERO as CRD42018099608.

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OBJECTIVE To assess the accuracy of dynamic computer-assisted implant surgery. MATERIALS AND METHODS An electronic search up to March 2020 was conducted using PubMed, Embase, and the Cochrane Central Register of Controlled Trial to identify studies using dynamic navigation in implant surgery, and additional manual search was performed as well. Clinical trials and model studies were selected. The primary outcome was accuracy. A single-arm meta-analysis of continuous data was conducted. Meta-regression was utilized for comparison on study design, guidance method, jaw and systems. RESULTS Ten studies, four randomized controlled trials (RCT) and six prospective studies, met the inclusion criteria. A total of 1298 drillings and implants were evaluated. The meta-analysis of the accuracy (five clinical trials and five model studies) revealed average global platform deviation, global apex deviation and angular deviation were 1.02 mm, CI: 95% [0.83, 1.21], 1.33 mm, CI: 95% [0.98, 1.67], and 3.59°, CI: 95% [2.09, 5.09]. Meta-regression shown no difference between model studies and clinical trials (p=0.295, 0.336, 0.185), drilling holes and implant (p =0.36, 0.279, 0.695), maxilla and mandible (p =0.875, 0.632, 0.281) and five different systems (p =0.762, 0.342, 0.336). CONCLUSION Accuracy of dynamic computer-aided implant surgery reaches a clinically acceptable range and has potential in clinical usage, but more patient-centered outcomes and socio-economic benefits should be reported.

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Parent stress and mental health problems negatively impact early child development. This study aimed to systematically review and meta-analyze the effect of eHealth interventions on parent stress and mental health outcomes, and identify family- and program-level factors that may moderate treatment effects. A search of PsycINFO, Medline, CINAHL, Cochrane and Embase databases was conducted from their inception dates to July 2020. English-language controlled and open trials were included if they reported: (a) administration of an eHealth intervention, and (b) stress or mental health outcomes such as self-report or clinical diagnosis of anxiety and depression, among (c) parents of children who were aged 1–5 years old. Non-human studies, case reports, reviews, editorials, letters, dissertations, and books were excluded. Risk of bias was assessed using the National Institutes of Health (NIH) Study Quality Assessment Tools. Random-effects meta-analyses of standardized mean differences (SMD) were conducted and meta-regressions tested potential moderators. 38 studies were included ( N  = 4360 parents), from 13 countries (47.4% USA). Meta-analyses indicated eHealth interventions were associated with better self-reported mental health among parents (overall SMD = .368, 95% CI 0.228, 0.509), regardless of study design ( k  = 30 controlled, k  = 8 pre-post) and across most outcomes ( k  = 17 anxiety, k  = 19 depression, k  = 12 parenting stress), with small to medium effect sizes. No significant family- or program-level moderators emerged. Despite different types and targets, eHealth interventions offer a promising and accessible option to promote mental health among parents of young children. Further research is needed on moderators and the long-term outcomes of eHealth interventions. Prospero Registration: CRD42020190719.

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Objective There is no medical treatment proven to limit abdominal aortic aneurysm (AAA) progression. This systematic review aimed to summarise available trial evidence on the efficacy of pharmacotherapy in limiting AAA growth and AAA-related events. Methods A systematic literature search was performed to examine the efficacy of pharmacotherapy in reducing AAA growth and AAA-related events. Pubmed, Embase (Excerpta Medica Database), and the Cochrane library were searched from March, 1999 to March 29, 2022. AAA growth (mm/year) in the intervention and control groups was expressed as mean and standard deviation (SD). The results of AAA growth were expressed as mean difference (MD) and its 95% confidence interval (95% CI). Odds ratios (ORs) were calculated for the AAA-related events.Heterogeneity was quantified using the I2 statistic. Forest plots were created to show the pooled results of each outcome. Outcomes A total of 1373 articles were found in different databases according to the search strategy, and 10 articles were identified by hand searching. A total of 26 articles were included in our systematic review after the screening. For the studies of metformin, the meta-analysis demonstrated that metformin use was associated with a lower AAA growth rate (MD: −0.81 mm/y, 95% CI: −1.19 to −0.42, P < 0.0001, I2 = 87%), Metformin use also was related to the lower rates of AAA-related events (OR: 0.53, 95% CI: 0.36 to 0.76, P = 0.0007, I2 = 60%). The hypotensive drugs of the studies mainly included angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type 1 receptor blockers (ARB), and propranolol. The overall meta-analysis of blood pressure-lowering drugs reported no significant effect in limiting the AAA growth (MD: 0.31mm/year, 95%CI: −0.03 to 0.65, P = 0.07, I2 = 66%) and AAA-related events (OR: 1.33, 95%CI: 0.76 to 2.32, P = 0.32, I2 = 98%), In the subgroup analysis of the hypotensive drugs, the ACEI/ARB and propranolol also showed no significant in reducing the AAA growth and AAA-related events. The meta-analysis of the antibiotics demonstrated that the antibiotics were not associated with a lower AAA growth rate (MD: −0.27 mm/y, 95% CI: −0.88 to 0.34, P = 0.39, I2 = 77%) and AAA-related events (OR: 0.94, 95%CI: 0.65 to 1.35, P = 0.72, I2 = 0%). The results of statins also showed no significant effect in limiting AAA growth (MD: −1.11mm/year, 95%CI: −2.38 to 0.16, P = 0.09, I2 = 96%) and AAA-related events (OR: 0.53, 95%CI: 0.26 to 1.06, P = 0.07, I2 = 92%). Conclusion In conclusion, effective pharmacotherapy for AAA was still lacking. Although the meta-analysis showed that metformin use was associated with lower AAA growth and AAA-related events, all of the included studies about metformin were cohort studies or case-control studies. More randomized controlled trials (RCTs) are needed for further verification.

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Background Stroke is the second leading cause of death worldwide, and 53.4% of stroke survivors suffer from post-stroke cognitive impairment. Post-stroke cognitive impairment can increase hospitalization rate and cost of care and decrease the quality of life of stroke patients. To date, multiple cognitive rehabilitation interventions have been tested in stroke populations with post-stroke cognitive impairment. However, the most efficacious intervention has not been established. This systematic review aims to compare the efficacy of cognitive rehabilitation interventions for patients with post-stroke cognitive impairment. Methods We will search MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, PubMed, and clinical trial registries to identify eligible randomized clinical trials with no restrictions in the date of publication and language. Studies conducted with patients aged 18 or over, with the presence of cognitive impairment after being diagnosed with stroke will be included. Studies will be restricted to randomized controlled trials comparing a cognitive rehabilitation intervention with another intervention. The primary outcome is any clinical changes in the general or specific cognitive domain (e.g., executive function, attention, memory, or perception). The secondary outcomes that will be collected include adverse effects (e.g., stroke, disability, or mortality) and quality of life. Two independent reviewers will assess articles to identify trials eligible for inclusion. Data extraction and risk of bias assessment of the included studies will also be done independently. Any discrepancies will be solved by discussion, or a third reviewer will be consulted if necessary. A meta-analysis will be carried out if appropriate. Discussion This systematic review for patients with post-stroke cognitive impairment will assess the efficacy of cognitive rehabilitation interventions. And our results will help clinical decision-making and support the development of clinical practice guidelines. Trial registration Systematic review registration: PROSPERO CRD42020173988

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Objective To analyse clinical outcomes with new oral anticoagulants for prophylaxis against venous thromboembolism after total hip or knee replacement. Design Systematic review, meta-analysis, and indirect treatment comparisons. Data sources Medline and CENTRAL (up to April 2011), clinical trials registers, conference proceedings, and websites of regulatory agencies. Study selection Randomised controlled trials of rivaroxaban, dabigatran, or apixaban compared with enoxaparin for prophylaxis against venous thromboembolism after total hip or knee replacement. Two investigators independently extracted data. Relative risks of symptomatic venous thromboembolism, clinically relevant bleeding, deaths, and a net clinical endpoint (composite of symptomatic venous thromboembolism, major bleeding, and death) were estimated using a random effect meta-analysis. RevMan and ITC software were used for direct and indirect comparisons, respectively. Results 16 trials in 38 747 patients were included. Compared with enoxaparin, the risk of symptomatic venous thromboembolism was lower with rivaroxaban (relative risk 0.48, 95% confidence interval 0.31 to 0.75) and similar with dabigatran (0.71, 0.23 to 2.12) and apixaban (0.82, 0.41 to 1.64). Compared with enoxaparin, the relative risk of clinically relevant bleeding was higher with rivaroxaban (1.25, 1.05 to 1.49), similar with dabigatran (1.12, 0.94 to 1.35), and lower with apixaban (0.82, 0.69 to 0.98). The treatments did not differ on the net clinical endpoint in direct or indirect comparisons. Conclusions A higher efficacy of new anticoagulants was generally associated with a higher bleeding tendency. The new anticoagulants did not differ significantly for efficacy and safety.

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BACKGROUND Depression and anxiety are highly prevalent among individuals struggling with infertility. Thus, numerous psychological interventions have been adapted to infertility, with the aim of relieving distress as well as increasing pregnancy rates. OBJECTIVE AND RATIONALE This systematic review and meta-analysis aimed to identify all randomized controlled trials (RCTs) evaluating the effect of psychological interventions on infertility-related distress and pregnancy rates among individuals and/or couples with infertility and to analyse their overall effect. It also sought to examine potential treatment moderators, including intervention length, format and therapeutic approach. SEARCH METHODS An electronic search of 11 databases, including MEDLINE, EMBASE, PsycINFO and Cochrane Central Register of Controlled Trials, was performed for studies published until January 2022. The inclusion criteria were RCTs conducted on humans and published in English. Psychological outcomes of interest included anxiety, depression, infertility-related distress, wellbeing and marital satisfaction. The Cochrane Risk of Bias tool was used to assess study quality, and the Grading of Recommendations Assessment, Development and Evaluation was used to assess the overall quality of the research evidence. OUTCOMES There were 58 RCTs in total, including 54 which included psychological outcomes and 21 which assessed pregnancy rates. Studies originated from all regions of the world, but nearly half of the studies were from the Middle East. Although a beneficial effect on combined psychological outcomes was found (Hedge's g = 0.82, P < 0.0001), it was moderated by region (P < 0.00001) such that studies from the Middle East exhibited large effects (g = 1.40, P < 0.0001), while the effects were small among studies conducted elsewhere (g = 0.23, P < 0.0001). Statistically adjusting for study region in a meta-regression, neither intervention length, therapeutic approach, therapy format, nor participant gender (P > 0.05) moderated the effect of treatment. A beneficial treatment effect on pregnancy (RR (95% CI) = 1.25 (1.07-1.47), P = 0.005) was not moderated by region, treatment length, approach or format (P > 0.05). Largely due to the lack of high quality RCTs, the quality of the available evidence was rated as low to moderate. WIDER IMPLICATIONS This is the first meta-analysis of RCTs testing the effect of psychological interventions on infertility-related distress and pregnancy rates. These findings suggest that in most regions of the world, psychological interventions are associated with small reductions in distress and modest effects on conception, suggesting the need for more effective interventions. These findings must be considered in light of the fact that the majority of the included RCTs were deemed to be at high risk of bias. Rigorously conducted trials are needed.

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OBJECTIVES To assess the effect of grafting the gap (SG) between the implant surface and alveolar socket on hard and soft tissue changes following single immediate implant placement (IIP). MATERIALS AND METHODS Two independent reviewers conducted an electronic literature search in Pubmed, Web of Science, Embase and Cochrane databases as well as a manual search to identify eligible clinical studies up to August 2021. Randomized controlled trials (RCTs) comparing IIP with and without SG were included for a qualitative analysis. Meta-analyses were performed when possible. RESULTS Out of 3627 records, 15 RCTs were selected and reported on 577 patients who received 604 single immediate implants (IIP + SG: 298 implants in 292 patients; IIP: 306 implants in 285 patients) with a mean follow-up ranging from 4 to 36 months. Two RCTs showed low risk of bias. Meta-analysis revealed 0.59 mm (95% CI [0.41; 0.78], p < 0.001) or 54% less horizontal buccal bone resorption following IIP + SG when compared to IIP alone. In addition, 0.58 mm (95% CI [0.28; 0.88], p < 0.001) less apical migration of the midfacial soft tissue level was found when immediate implants were installed with SG. A trend towards less distal papillary recession was found (MD 0.60 mm, 95% CI [-0.08; 1.28], p = 0.080) when SG was performed, while mesial papillae appeared not significantly affected by SG. Vertical buccal bone changes were also not significantly affected by SG. Insufficient data were available for meta-analyses on horizontal midfacial soft tissue changes, pink esthetic score, marginal bone level changes, probing depth and bleeding on probing. Based on GRADE guidelines, a moderate recommendation for SG following IIP can be made. CONCLUSION SG may contribute to horizontal bone preservation and soft tissue stability at the midfacial aspect of immediate implants. Therefore, SG should be considered as an adjunct to IIP in clinical practice.

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BACKGROUND Displaced mid-third clavicle fractures are common, and their management remains unclear. Although several meta-analyses have compared specific operative techniques with nonoperative management, it is not possible to compare different operative constructs with one another using a standard meta-analysis. Conversely, a network meta-analysis allows comparisons among more than two treatment arms, using both direct and indirect comparisons between interventions across many trials. To our knowledge, no network meta-analysis has been performed to compare the multiple treatment options for displaced clavicle fractures. QUESTIONS/PURPOSES We performed a network meta-analysis of randomized, controlled trials (RCTs) to determine from among the approaches used to treat displaced midshaft clavicle fractures: (1) the intervention with the highest chance of union at 1 year, (2) the intervention with the lowest risk of revision surgery, and (3) the intervention with the highest functional outcome scores. Secondarily, we also (4) compared the surgical subtypes in the available RCTs on the same above endpoints. METHODS MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were reviewed for relevant randomized controlled trials published up to July 25, 2018. Two hundred and eighty four papers were reviewed, with 22 meeting inclusion criteria of RCTs with appropriate randomization techniques, adult population, minimum of 1 year follow-up and including at least one operative treatment arm. In total, 1002 patients were treated with a plate construct, 378 with an intramedullary device, and 585 patients were managed nonoperatively. Treatment subtypes included locked intramedullary devices (56), unlocked intramedullary devices (322), anterior plating (89), anterosuperior plating (150), superior plating (449) or plating not otherwise specified (314). We performed a network meta-analysis to compare and rank the treatments for displaced clavicle fractures. We considered the following outcomes: union achievement, revision surgery risk and functional outcomes (DASH and Constant Scores). The minimal clinically important difference (MCID) was considered for both Constant and DASH scores to be at 8 points, representing the average of MCID scores reported for both DASH and Constant in the evidence, respectively. RESULTS Union achievement was lower in patients treated nonoperatively (88.9%), and higher in patients treated operatively (96.7%, relative risk [RR] 1.128 [95% CI 1.1 to 1.17]; p < 0.001), Number needed to treat (NNT) = 10). Union achievement increased with any plate construct (97.8%, RR 1.13 [95% CI 1.1 to 1.7]; p < 0.0001, NNT = 9) and with anterior or anterosuperior plates (99.3%, RR 1.14 [95% CI 1.1 to 1.8]; p < 0.0001, NNT = 8). Risk of reoperation, when considering planned removal of hardware, was similar across all treatment arms. Lastly, operative treatment outperformed nonoperative treatment with minor improvements in DASH and Constant scores, though not approaching the MCID. At the subtype level, anterosuperior plating ranked highest in DASH and Constant functional scores with mean differences reaching 10-point improvement for Constant scores (95% CI 4.4 to 2.5) and 7.6 point improvement for DASH (95% CI 5.2 to 20). CONCLUSIONS We found that surgical treatment led to a greater likelihood of union at 1 year of follow-up among adult patients with displaced mid-third clavicle fractures. In aggregate, surgical treatment did not increase functional scores by amounts that patients were likely to consider clinically important. Use of specific subtypes of plating (anterior, anterosuperior) resulted in improvements in the Constant score that were slightly above the MCID but did not reach the MCID for the DASH score, suggesting that any outcomes-score benefits favoring surgery were likely to be imperceptible or small. In light of these findings, we believe patients can be informed that surgery for this injury can increase the likelihood of union incrementally (about 10 patients would need to undergo surgery to avoid one nonunion), but they should not expect better function than they would achieve without surgery; most patients can avoid surgery altogether with little absolute risk of nonunion. Patients who opt for surgery must be told that the decision should be weighed against complications and the possibility of undergoing a second procedure for hardware removal. Patients opting not to have surgery for acute midshaft clavicle fractures can be told that nonunion occurs in slightly more than 10% of patients, and that these can be more difficult to manage than acute fractures. LEVEL OF EVIDENCE Level I, therapeutic study.

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INTRODUCTION The aim of this systematic review was to analyse current evidence regarding differences in early and late implant failure as well as in marginal bone level (MBL) changes between submerged and non-submerged healed dental implants. METHODS PUBMED, SCOPUS, EMBASE and Web of Science databases were searched for prospective randomized and non-randomized controlled studies addressing direct comparison between submerged and non-submerged implant healing, without performing immediate loading. Early and late implant failure (before or after 6 months from implant placement, respectively) together with MBL were the investigated outcomes. Risk of bias assessment was performed using the Cochrane Collaboration Tool for Randomized clinical trials. Meta-analysis was performed and the power of the meta-analytic findings determined by trial sequential analysis (TSA). RESULTS Eleven studies met the inclusion criteria and were included in the review. Results of this systematic review revealed a small higher rate (2%) of early implant failure when a non-submerged healing approach is performed. Late implant failure appears not to be different in submerged or non-submerged healing, but the power of evidence, as determined by TSA, is not high. If we consider MBL changes at 1 year from implant load, it seems that non-submerged healing may better preserve marginal bone, although with a small effect size (0.13 mm). CONCLUSIONS Implants placed with a non-submerged technique have a higher risk (2%) of early failure. The power of the evidence about the effects on MBL is low, but present results seem to favour non-submerged healing, although with a very small effect size.

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Objective: To evaluate the effectiveness of extracorporeal shockwave therapy compared with other interventions on pain, grip strength and disability in patients with lateral elbow tendinopathy. Data Sources: MEDLINE, PubMed, CINAHL, EMBASE, PEDro, ScienceDirect, Cochrane Library and clinical trial registries. Review methods: We included randomized controlled trials assessing the effectiveness of extracorporeal shockwave therapy alone or as an additive intervention compared with sham or other interventions. Pain intensity, grip strength and elbow disability were used as primary outcome measures. We assessed methodological quality with the PEDro score and quality of evidence with the GRADE approach. Results: Twenty-seven studies with 1871 patients were finally included. Extracorporeal shockwave therapy reduced pain intensity at mid-term follow-up (standardized mean difference: −1.21, 95% confidence interval:−1.53, −0.89, P < 0.001) and improved grip strength at very short- (mean difference:3.92, 95% confidence interval: 0.91, 6.94, P = 0.01) and short-term follow-up (mean difference:4.87, 95% confidence interval:2.24, 7.50, P < 0.001) compared with sham treatment. However, no clinically significant results were found between comparators in all outcomes and follow-up times. Extracorporeal shockwave therapy presented clinically better compared to Laser in grip strength at short-term (mean difference:3.50, 95% confidence interval:2.40, 4.60, P < 0.001) and ultrasound in pain intensity at very-short-term follow-up (standardized mean difference: −1.54, 95% confidence interval: −2.60, −0.48, P = 0.005). Conclusion: Low to moderate certainty of evidence suggests that there are no clinical benefits of extracorporeal shockwave therapy compared to sham interventions or corticosteroid injections. Based on very-low and moderate certainty of evidence, extracorporeal shockwave therapy outperforms against Laser and ultrasound, respectively. Level of Evidence: Therapy, level 1a.

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Objective Colchicine, an approved treatment for gout, has been trialed in many diseases including osteoarthritis (OA) due to its anti-inflammatory effects. However, its efficacy and safety remain unclear in OA. This systematic review and meta-analysis evaluated the efficacy and safety of colchicine for the treatment of OA. Methods PubMed, Web of Science, Scopus, and Cochrane Central were searched from inception through September 2022. Two reviewers independently screened for randomized controlled trials (RCTs) comparing colchicine with placebo or other active comparators for the treatment of OA (knee, hand, or hip OA), extracted data, and performed Cochrane risk of bias assessments. Result Nine RCTs for the knee OA and one for the hand OA were identified, consisting of 847 patients (429 in colchicine arms, 409 in control arms). The studies were conducted between 2002 and 2021 with follow-up periods ranging from 2 to 12 months, in India, Iran, Turkey, Australia, Singapore, and Iraq. Moderate-quality evidence showed no clinically important pain reduction with colchicine compared to control (standardized mean difference [SMD], 0.17; 95% confidence interval [CI], − 0.55, 0.22). Moderate-quality evidence showed no improvement in function with colchicine compared to control in knee OA patients (SMD, − 0.37; 95% CI, − 0.87, 0.13). Colchicine showed an acceptable safety profile with AEs/SAEs comparable to control. Conclusion Current evidence does not suggest a benefit of colchicine in reducing pain and improving physical function in the overall cohort of hand/knee OA patients. Future trials should focus on the subgroups of OA patients with local or systemic inflammation and/or mineralization who might benefit from colchicine. Graphical abstract

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Studies investigating the effects of spirulina on inflammation and oxidative stress status are controversial. Therefore, the current systematic review and meta‐analysis aimed to evaluate the impacts of spirulina supplementation on oxidative stress indicators and inflammatory markers. PubMed‐Medline, SCOPUS, Web of Science, Embase databases and Google Scholar were searched up to 1 October 2020. Random‐effect analysis was applied to perform meta‐analysis. Subgroup analyses and multivariate meta‐regression were performed to find heterogeneity sources. Quality assessment was conducted using Cochrane Collaboration’s tool. A total of 11 studies that enrolled 465 subjects were included in our meta‐analysis. Pooled results demonstrated a significant increase in interleukin‐2 (IL‐2) concentrations [Standardized mean difference (SMD = 2.69 pg/mL; 95% CI: 0.26, 5.11; P = .03)]; however this result changed to insignificant (SMD = 0.54 pg/mL; 95% CI: −1.29, 2.27; P > .05) when sensitivity analysis performed. A marginal decreasing effect were also found on interleukin‐6 (IL‐6) (SMD = −0.72 mg/dL; 95% CI: −1.50, 0.07; P = .073) and thiobarbituric acid reactive substances (TBARS) levels (SMD = −0.65; 95% CI: −1.37, 0.08; P = .08). In addition, results of subgroup analysis revealed a significant reduction in IL‐6 and TBARS concentrations when the baseline body mass index (BMI) of participants was lower than 25 kg/m2. Moreover, spirulina had no significant effect on tumour necrosis factor‐α (TNF‐α) (SMD = −0.07 mg/dL; 95% CI: −0.33, 0.18; P = .56) and malondialdehyde (MDA) concentrations (SMD = −0.42; 95% CI: −0.98, 0.14; P = .14). Spirulina consumption contributed to a significant increase in IL‐2 concentrations changing to insignificant after sensitivity analysis and marginal decreasing effects on IL‐6 and TBARS levels. No considerable impacts were observed on TNF‐α and MDA concentrations.

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OBJECTIVE To investigate the effect of mobile phone applications (apps) on glycemic control (HbA1c) in the self-management of diabetes. RESEARCH DESIGN AND METHODS Relevant studies that were published between 1 January 1996 and 1 June 2015 were searched from five databases: Medline, CINAHL, Cochrane Library, Web of Science, and Embase. Randomized controlled trials that evaluated diabetes apps were included. We conducted a systematic review with meta-analysis and GRADE (Grading of Recommendations Assessment, Development and Evaluation) of the evidence. RESULTS Participants from 14 studies (n = 1,360) were included and quality assessed. Although there may have been clinical diversity, all type 2 diabetes studies reported a reduction in HbA1c. The mean reduction in participants using an app compared with control was 0.49% (95% Cl 0.30, 0.68; I2 = 10%), with a moderate GRADE of evidence. Subgroup analyses indicated that younger patients were more likely to benefit from the use of diabetes apps, and the effect size was enhanced with health care professional feedback. There was inadequate data to describe the effectiveness of apps for type 1 diabetes. CONCLUSIONS Apps may be an effective component to help control HbA1c and could be considered as an adjuvant intervention to the standard self-management for patients with type 2 diabetes. Given the reported clinical effect, access, and nominal cost of this technology, it is likely to be effective at the population level. The functionality and use of this technology need to be standardized, but policy and guidance are anticipated to improve diabetes self-management care.

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Aim: We aimed to investigate the effectiveness of traction therapy in reducing pain by performing a systematic review with meta-analysis. We also explore the best modality for administering traction to patients with cervical radicular syndrome (CRS). Methods: We searched the Medline, Physiotherapy Evidence Database (PEDro), Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) electronic databases. Two reviewers independently selected randomized controlled trials (RCTs) that compared traction in addition to other treatments versus the effectiveness of other treatments alone for pain outcome. We calculated the mean differences (MDs) and 95% confidence intervals (CIs). We used Cochrane’s tool to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to evaluate the quality of evidence and summarize the study conclusions. Results: A total of seven studies (589 patients), one with low risk of bias, were evaluated. An overall estimate of treatment modalities showed low evidence that adding traction to other treatments is statistically significant (MD −5.93 [95% CI, −11.81 to −0.04] P = 0.05 and I2 = 57%) compared to other treatments alone. The subgroup analyses were still statistically significant only for mechanical and continuous modalities. Conclusions: Overall analysis showed that, compared to controls, reduction in pain intensity after traction therapy was achieved in patients with cervical radiculopathy. However, the quality of evidence was generally low and none of these effects were clinically meaningful.

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Background: Insufficient milk production is among the most cited reasons by mothers for discontinuing breastfeeding. Medications that can increase milk production, such as domperidone, an off-label galactagogue, are often prescribed. Domperidone is controversial as it is not approved for any purpose in the United States and is approved only for gastrokinetic purposes in Canada and other countries. Research aim: The aim was to update the existing literature on the efficacy of domperidone as a galactagogue compared to placebo when given to mothers with insufficient human milk production. The primary outcome is the change in expressed human milk volume per day from baseline. Methods: The authors independently searched the literature from inception to May 2018. The search included any randomized controlled trials examining the efficacy of domperidone increasing mothers’ expressed human milk, measured via a human milk pump. Both authors independently assessed quality and risk of bias and extracted relevant data. Meta-analysis on expressed human milk volume per day was performed. Results: Seven studies met the inclusion criteria for review; two were excluded from the meta-analysis due to quality grading and insufficient reporting of the outcome of interest. Five studies (N = 239) were combined in the meta-analysis. The effect size showed an increase in the mean difference of expressed human milk volume in mothers given domperidone, 93.97 mL per day (95% CI [71.12, 116.83 mL]; random effect, T2 0.00, I2 0%). Conclusion: This meta-analysis reports a significant improvement in expressed human milk volume per day with the use of domperidone in mothers experiencing insufficient human milk production.

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Dentists have a wide variety of techniques available to them such as tell -show-do, relaxation, distraction, systematic desensitisation, modelling, audio analgesia, hypnosis, and behaviour rehearsal. There is no concrete research as systematic review and meta-analysis indicating which explains the most effective distraction technique. AIM To summarize effectiveness of audio and audio-visual (AV) distraction aids for management of pain and anxiety in children undergoing dental treatment. STUDY DESIGN Literature search: PubMed/MEDLINE, DOAJ, Science Direct from June - July 2020 with randomized control clinical trials conducted on children with audio and AV distraction aids as intervention and those which had anxiety and pain as outcomes were searched. Fifty articles were identified and relevance was determined. 14 studies were included for qualitative synthesis and 05 were eligible for meta-analysis. Cochrane handbook used to assess the risk of bias. The meta analysis conducted using review manager 5.3 software. RESULTS Meta-analysis, cumulative mean difference for audio and AV distraction techniques was calculated with main outcomes as pulse rate, O2 level, Vehman's picture and clinical test. These findings showed significant difference favoring the intervention (audio and AV) group when compared with control but indicating more effectiveness of AV distractions. CONCLUSION Different audio-visual aids assist in reducing pain and anxiety in children but using audio distraction aids when audio-visual aids are not available could be acceptable way for distracting and treating children.

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Patients receiving thiazide diuretics have a higher risk of impaired glucose tolerance or even incident diabetes, but the change of blood glucose level varies across different trials. The aim of this study was to investigate the glycemic changes in hypertensive patients with thiazide‐type diuretics. Twenty‐six randomized trials involving 16,162 participants were included. Thiazide‐type diuretics were found to increase fasting plasma glucose (FPG) compared with nonthiazide agents or placebo or nontreatment (mean difference [MD], 0.27 mmol/L [4.86 mg/dL]; 95% confidence interval [CI], 0.15–0.39). Patients receiving lower doses of thiazides (hydrochlorothiazide or chlorthalidone ≤25 mg daily) had less change in FPG (MD, 0.15 mmol/L [2.7 mg/dL]; 95% CI, 0.03–0.27) than those receiving higher doses (MD, 0.60 mmol/L [10.8 mg/dL]; 95% CI, 0.39–0.82), revealed by the subgroup analysis of thiazides vs calcium channel blockers. Thiazide‐type diuretics are associated with significant but small adverse glycemic effects in hypertensive patients. Treatment with a lower dose might reduce or avoid glycemic changes.

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One of the latest approved therapies for spinal muscular atrophy (SMA) is onasemnogene abeparvovec, which transduces motor neurons with the survival of motor neuron gene. The aim of this meta-analysis was to estimate the effect of onasemnogene abeparvovec on motor function in participants with type 1 SMA. Medline, Web of Science, Scopus and Cochrane Library were searched for studies published from inception to August 2022. Pre-post clinical trials and observational studies determining the effect of onasemnogene abeparvovec on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score or motor milestones (i.e., head control, sit unassisted, feed orally, not use permanent ventilatory support, crawl, stand alone and walk alone) in participants with type 1 SMA were included. Continuous outcomes (i.e., CHOP-INTEND score) were expressed as pre-post mean difference and 95% confidence interval (CI), while the proportion of participants who achieved >40, >50, and >58/60 points on the CHOP-INTEND and the achievement of the motor milestones were expressed as proportions and 95% CI. A random effects meta-analysis was conducted on each outcome, and the baseline CHOP-INTEND score was considered a covariate. Eleven studies were included in the systematic review, and four were included in the meta-analyses. Onasemnogene abeparvovec improved CHOP-INTEND scores by 11.06 (9.47, 12.65) and 14.14 (12.42, 15.86) points at 3 and 6 months postinfusion, respectively. Moreover, 87%, 51%, and 12% achieved CHOP-INTEND scores of >40, >50, and >58/60 points, respectively. However, this proportion increased to 100% in presymptomatic participants with greater baseline CHOP-INTEND. Motor milestones were also improved, especially in presymptomatic participants. Our systematic review not only showed a marked improvement in motor function in type 1 SMA but also showed that treatment in the presymptomatic stage improves the development of these children towards an evolution close to normal for their age.

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AimsThis study focused on the newest evidence of the relationship between forest environmental exposure and human health and assessed the health efficacy of forest bathing on the human body as well as the methodological quality of a single study, aiming to provide scientific guidance for interdisciplinary integration of forestry and medicine.MethodThrough PubMed, Embase, and Cochrane Library, 210 papers from January 1, 2015, to April 1, 2019, were retrieved, and the final 28 papers meeting the inclusion criteria were included in the study.ResultThe methodological quality of papers included in the study was assessed quantitatively with the Downs and Black checklist. The methodological quality of papers using randomized controlled trials is significantly higher than that of papers using non-randomized controlled trials (p < 0.05). Papers included in the study were analyzed qualitatively. The results demonstrated that forest bathing activities might have the following merits: remarkably improving cardiovascular function, hemodynamic indexes, neuroendocrine indexes, metabolic indexes, immunity and inflammatory indexes, antioxidant indexes, and electrophysiological indexes; significantly enhancing people’s emotional state, attitude, and feelings towards things, physical and psychological recovery, and adaptive behaviors; and obvious alleviation of anxiety and depression.ConclusionForest bathing activities may significantly improve people’s physical and psychological health. In the future, medical empirical studies of forest bathing should reinforce basic studies and interdisciplinary exchange to enhance the methodological quality of papers while decreasing the risk of bias, thereby raising the grade of paper evidence.

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Background A potential link between toxoplasmosis with schizophrenia (SCZ) has been extensively studied over the past 2 decades. Our study was aimed to determine whether, beyond an association, the field is primed for randomized clinical trials of anti‐Toxoplasma prophylaxis in Toxoplasma seropositive patients with SCZ. Methods We performed a methodological appraisal of toxoplasmosis‐SCZ association studies, a meta‐analysis, and a compilation of claims and pathophysiologic hypotheses. Results We analyzed 66 studies with 11,540 patients with SCZ and 69,491 controls. For patients with SCZ, 54 studies targeted Toxoplasma‐IgG seropositivity, 18 targeted Toxoplasma‐IgG serointensity, and 17 targeted Toxoplasma‐IgM seropositivity. For SCZ‐phenotypes, 26 targeted Toxoplasma‐IgG seropositivity, six targeted Toxoplasma‐IgG serointensity, and three targeted Toxoplasma‐IgM seropositivity. Two‐thirds of these studies reported a positive association. Statistically significant associations with SCZ were reported in 31/54 studies, 11/18 studies, and 3/17 studies. Significant associations with SCZ‐phenotypes were reported in 20/26 studies, 2/6 studies, and 0/3 studies, respectively. Toxoplasma‐IgG seropositivity increased the odds of SCZ (OR = 1.91; 95% CI: 1.61–2.27). Heterogeneity across studies was large (I 2 = 80.03%). Adjusted analyses for at least age and socioeconomic status/place of residence were done in 17 studies; temporality was addressed only in 4. Conclusion A large number of observational studies revealed a modest to large association between toxoplasmosis and SCZ. Although important methodological biases were identified, further association studies are unlikely to change this association and are not justified. It is time to test this association in randomized double‐blind placebo‐controlled clinical trials of first line anti‐Toxoplasma prophylaxis in Toxoplasma seropositive patients with SCZ.

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Abstract Background A growing body of research shows the promise and efficacy of technology‐based or digital interventions in improving the health and well‐being of survivors of intimate partner violence (IPV). In addition, mental health comorbidities such as anxiety, post‐traumatic stress disorder (PTSD), and depression occur three to five times more frequently in survivors of IPV than non‐survivors, making these comorbidities prominent targets of technology‐based interventions. Still, research on the long‐term effectiveness of these interventions in reducing IPV victimization and adverse mental health effects is emergent. The significant increase in the number of trials studying technology‐based therapies on IPV‐related outcomes has allowed us to quantify the effectiveness of such interventions for mental health and victimization outcomes in survivors. This meta‐analysis and systematic review provide critical insight from several randomized controlled trials (RCTs) on the overall short and long‐term impact of technology‐based interventions on the health and well‐being of female IPV survivors. Objectives To synthesize current evidence on the effects of technology‐based or digital interventions on mental health outcomes (depression, anxiety, and PTSD) and victimization outcomes (physical, psychological, and sexual abuse) among IPV survivors. Search Methods We examined multiple traditional and grey databases for studies published from 2007 to 2021. Traditional databases (such as PubMed Central, Web of Science, CINAHL Plus, and PsychINFO) and grey databases were searched between April 2019 and February 2021. In addition, we searched clinical trial registries, government repositories, and reference lists. Authors were contacted where additional data was needed. We identified 3210 studies in traditional databases and 1257 from grey literature. Over 2198 studies were determined to be duplicates and eliminated, leaving 64 studies after screening titles and abstracts. Finally, 17 RCTs were retained for meta‐analysis. A pre‐registered protocol was developed and published before conducting this meta‐analysis. Selection Criteria We included RCTs targeting depression, anxiety, PTSD outcomes, and victimization outcomes (physical, sexual, and psychological violence) among IPV survivors using a technology‐based intervention. Eligible RCTs featured a well‐defined control group. There were no study restrictions based on participant gender, study setting, or follow‐up duration. Included studies additionally supplied outcome data for calculating effect sizes for our desired outcome. Studies were available in full text and published between 2007 and 2021 in English. Data Collection and Analysis We extracted relevant data and coded eligible studies. Using Cochrane's RevMan software, summary effect sizes (Outcome by Time) were assessed using an independent fixed‐effects model. Standardized mean difference (SMD) effect sizes (or Cohen's d) were evaluated using a Type I error rate and an alpha of 0.05. The overall intervention effects were analyzed using the Z‐statistic with a p‐value of 0.05. Cochran's Q test and Higgins' I 2 statistics were utilized to evaluate and confirm the heterogeneity of each cumulative effect size. The Cochrane risk of bias assessment for randomized trials (RoB 2) was used to assess the quality of the studies. Campbell Systematic Reviews registered and published this study's protocol in January 2021. No exploratory moderator analysis was conducted; however, we report our findings with and without outlier studies in each meta‐analysis. Main Results Pooled results from 17 RCTs yielded 18 individual effect size comparisons among 4590 survivors (all females). Survivors included college students, married couples, substance‐using women in community prisons, pregnant women, and non‐English speakers, and sample sizes ranged from 15 to 672. Survivors' ages ranged from 19 to 41.5 years. Twelve RCTs were conducted in the United States and one in Canada, New Zealand, China (People's Republic of), Kenya, and Australia. The results of this meta‐analysis found that technology‐based interventions significantly reduced depression among female IPV survivors at 0–3 months only (SMD = −0.08, 95% confidence interval [CI] = −0.17 to −0.00), anxiety among IPV survivors at 0–3 months (SMD = −0.27, 95% CI = −0.42 to −0.13, p = 0.00, I 2 = 25%), and physical violence victimization among IPV survivors at 0–6 months (SMD = −0.22, 95% CI = −0.38 to −0.05). We found significant reductions in psychological violence victimization at 0–6 months (SMD = −0.34, 95% CI = −0.47 to −0.20) and at >6 months (SMD = −0.29, 95% CI = −0.39 to −0.18); however, at both time points, there were outlier studies. At no time point did digital interventions significantly reduce PTSD (SMD = −0.04, 95% CI = −0.14 to 0.06, p = .46, I 2 = 0%), or sexual violence victimization (SMD = −0.02, 95% CI = −0.14 to 0.11, I 2 = 21%) among female IPV survivors for all. With outlier studies removed from our analysis, all summary effect sizes were small, and this small number of comparisons prevented moderator analyses. Authors' Conclusions The results of this meta‐analysis are promising. Our findings highlight the effectiveness of IPV‐mitigating digital intervention as an add‐on (not a replacement) to traditional modalities using a coordinated response strategy. Our findings contribute to the current understanding of “what works” to promote survivors' mental health, safety, and well‐being. Future research could advance the science by identifying active intervention ingredients, mapping out intervention principles/mechanisms of action, best modes of delivery, adequate dosage levels using the treatment intensity matching process, and guidelines to increase feasibility and acceptability.

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BACKGROUND Although many studies have shown that low zinc status is associated with diabetes, the putative effects of zinc supplementation on glycemic control are inconclusive. OBJECTIVES The aim of this meta-analysis of randomized controlled trials was to assess the effects of zinc supplementation in preventing and managing diabetes. METHODS PubMed, Embase, and the Cochrane Library were searched for articles that were published through February 10, 2019 and contained estimates for the outcomes of interest. The pooled results were then analyzed with the use of a random-effects model. RESULTS Thirty-two placebo-controlled interventions were extracted from 36 publications, involving a total of 1700 participants in 14 countries. Overall, compared with their respective control groups, the subjects in the zinc-supplementation group had a statistically significant reduction in fasting glucose [FG, weighted mean difference (WMD): -14.15 mg/dL; 95% CI: -17.36, -10.93 mg/dL], 2-h postprandial glucose (WMD: -36.85 mg/dL; 95% CI: -62.05, -11.65 mg/dL), fasting insulin (WMD: -1.82 mU/L; 95% CI: -3.10, -0.54 mU/L), homeostasis model assessment for insulin resistance (WMD: -0.73; 95% CI: -1.22, -0.24), glycated hemoglobin (WMD: -0.55%; 95% CI: -0.84, -0.27%), and high-sensitivity C-reactive protein (WMD: -1.31 mg/L; 95% CI: -2.05, -0.56 mg/L) concentrations. Moreover, subgroup analyses revealed that the effects of zinc supplementation on FG are significantly influenced by diabetic status and the formulation of the zinc supplement. CONCLUSIONS Our analysis revealed that several key glycemic indicators are significantly reduced by zinc supplementation, particularly the FG in subjects with diabetes and in subjects who received an inorganic zinc supplement. Together, these findings support the notion that zinc supplementation may have clinical potential as an adjunct therapy for preventing or managing diabetes. This trial was registered at PROSPERO as CRD42018111838.

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The pharmacotherapy of Takayasu arteritis (TAK) with disease-modifying anti-rheumatic drugs (DMARDs) is an evolving area. A systematic review of Scopus, Web of Science, Pubmed Central, clinical trial databases and recent international rheumatology conferences for interventional and observational studies reporting the effectiveness of DMARDs in TAK identified four randomized controlled trials (RCTs, with another longer-term follow-up of one RCT) and 63 observational studies. The identified trials had some concern or high risk of bias. Most observational studies were downgraded on the Newcastle-Ottawa scale due to lack of appropriate comparator groups. Studies used heterogenous outcomes of clinical responses, angiographic stabilization, normalization of inflammatory markers, reduction in vascular uptake on positron emission tomography, reduction in prednisolone doses and relapses. Tocilizumab showed benefit in a RCT compared to placebo in a secondary per-protocol analysis but not the primary intention-to-treat analysis. Abatacept failed to demonstrate benefit compared to placebo for preventing relapses in another RCT. Pooled data from uncontrolled observational studies demonstrated beneficial clinical responses and angiographic stabilization in nearly 80% patients treated with tumour necrosis factor alpha inhibitors, tocilizumab or leflunomide. Certainty of evidence for outcomes from RCTs ranged from moderate to very low and was low to very low for all observational studies. There is a paucity of high-quality evidence to guide the pharmacotherapy of TAK. Future observational studies should attempt to include appropriate comparator arms. Multicentric, adequately powered RCTs assessing both clinical and angiographic responses are necessary in TAK.

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Objective: We assessed the efficacy of colchicine in COVID-19 patients through a systematic review. Methods: Six databases were searched until March 2022 for studies assessing colchicine versus control in hospitalized patients with COVID-19. The primary outcome was mortality, and secondary outcome was length of hospitalization. Inverse variance and random effect meta-analyses were performed. The strength of evidence was assessed using GRADE. Results: Nine studies (five randomized clinical trials (RCTs) and four non-randomized studies of intervention (NRSI); n = 13,478). Colchicine did not reduce mortality in comparison with the standard of care in RCTs (RR 0.99; 95%CI 0.90 to 1.10; p = 0.90); however, it did reduce mortality in NRSI studies (RR 0.45; 95%CI 0.26 to 0.77; p = 0.02). In the analysis of RCTs, colchicine did not reduce the length of hospitalization in comparison with the standard of care (MD: −2.25 days; 95%CI: −9.34 to 4.84; p = 0.15). Most studies were scored as having a high risk of bias. Quality of evidence was very low for primary and secondary outcomes. Conclusion: Colchicine did not reduce the mortality and length of hospitalization in comparison with the standard of care in hospitalized patients with COVID-19. The published evidence is insufficient and of very low quality to recommend treatment in patients with COVID-19.

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Despite the availability of a numerous antihypertensive agents, hypertension treatment and control rates remain low in many countries. The role of the sympathetic nervous system has long been recognized, but recent sham control renal denervation studies demonstrated conflicting results. In this reviewe paper, the authors performed a systematic review and meta‐analysis to examine outcomes of sham‐controlled studies utilizing new technologies and procedures. Six published randomized, sham‐controlled studies were included in this meta‐analysis. Of those, three trials used the first‐generation radiofrequency renal denervation device and technique and the other three used second‐generation devices and techniques. In total, 981 patients with hypertension were randomized in all 6 trials to undergo renal denervation (n = 585) or sham procedure (n = 396). Overall, renal denervation resulted in a decrease of 24‐hours systolic ambulatory blood pressure (ABP) by 3.62 mm Hg (95% CI: −5.28‐−1.96; I2 = 0%), compared to sham procedure (GRADE: low). Renal denervation also reduced daytime systolic ABP by 5.51 mm Hg (95% CI: −7.79‐−3.23; I2 = 0%), compared to sham procedure but not nighttime systolic ABP. Office systolic blood pressure was reduced by 5.47 mm Hg (95% CI −8.10‐−2.84; I2 = 0%), compared to sham control. Further analysis demonstrated that second‐generation devices were effective in reducing blood pressure, whereas the first‐generation devices were not. These results indicate that effective renal denervation can result in significant and clinically meaningful blood pressure reduction. The second‐generation devices provide better renal nerve ablation.

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BackgroundRates of cannabis use are highest during emerging adulthood (age 18–25), with the prevalence of near daily and daily increasing among this age group. Emerging adults are clinically challenging in terms of harmful cannabis use due to perceptions of high rates of peer use, social acceptance, and low risk of harm. Brief interventions to increase awareness and promote motivation to change are therefore particularly important for this age group. There is existing evidence on the effectiveness of brief interventions for alcohol in emerging adults, but it is not clear if comparable evidence is present for cannabis. The objective of this systematic review is to summarize and critically appraise the existing literature of brief interventions for cannabis use both narratively, to describe the content and delivery of existing interventions, and meta-analytically, to determine the aggregated efficacy of these interventions on cannabis use and other outcomes (e.g., other substance use, mental health, help-seeking behaviors, and academic and occupational outcomes).MethodsA systematic search of randomized controlled trials, quasi-experimental trials, and pre-post designs will be conducted in the following electronic databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO. Ongoing trials will be identified using the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and Current Controlled Trials. Unpublished trials will be identified using Proquest Dissertations, OpenGrey, Google Scholar, and brief interventions on the Substance Abuse and Mental Health Services Administration webpage. Two authors will independently screen and extract data from articles using a predetermined screening and extraction forms (which will include risk of bias assessments). Calibration exercises will be performed prior to full screening and extraction. Disagreements will be resolved through discussion or consultation with a third reviewer. All studies will be reported narratively, and if appropriate, we will perform random effects meta-analyses with subgroup analyses and meta-regression.DiscussionResults of this review are expected to provide guidance on the content, delivery methods, and effectiveness of brief interventions for cannabis use to assist post-secondary institutions in identifying brief intervention strategies to implement prior to or in response to legalization.Systematic review registrationCRD42018085412

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Insomnia is a prevalent disorder and it leads to relevant impairment in health-related quality of life. Recent clinical guidelines pointed out that Cognitive-Behavior Therapy for Insomnia (CBT-I) should be considered as first-line intervention. Nevertheless, many other interventions are commonly used by patients or have been proposed as effective for insomnia. These include melatonin, light exposure, exercise, and complementary and alternative medicine. Evaluation of comparable effectiveness of these interventions with first-line intervention for insomnia is however still lacking. We conducted a systematic review and network meta-analysis on the effects of these interventions. PubMed, PsycInfo, PsycArticles, MEDLINE, and CINAHL were systematically searched and 40 studies were included in the systematic review, while 36 were entered into the meta-analysis. Eight network meta-analyses were conducted. Findings support effectiveness of melatonin in improving sleep-onset difficulties and of meditative movement therapies for self-report sleep efficiency and severity of the insomnia disorder. Some support was observed for exercise, hypnotherapy, and transcranial magnetic resonance, but the number of studies for these interventions is still too small. None of the considered interventions received superior evidence to CBT-I, which should be more widely disseminated in primary care.

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Background Observational evidence suggests higher nut consumption is associated with better glycemic control; however, it is unclear if this association is causal. Objectives We aimed to conduct a systematic review and meta-analysis of randomized controlled trials to examine the effect of tree nuts and peanuts on markers of glycemic control in adults. Methods A systematic review and meta-analysis of randomized controlled trials was conducted. A total of 1063 potentially eligible articles were screened in duplicate. From these articles, 40 were eligible for inclusion and data from these articles were extracted in duplicate. The weighted mean difference (WMD) between the nut intervention and control arms was determined for fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR) using the DerSimonian and Laird random-effects method. For outcomes where a limited number of studies were published, a qualitative synthesis was presented. Results A total of 40 randomized controlled trials including 2832 unique participants, with a median duration of 3 mo (range: 1-12 mo), were included. Overall consumption of tree nuts or peanuts had a favorable effect on HOMA-IR (WMD: -0.23; 95% CI: -0.40, -0.06; I2 = 51.7%) and fasting insulin (WMD: -0.40 μIU/mL; 95% CI: -0.73, -0.07 μIU/mL; I2 = 49.4%). There was no significant effect of nut consumption on fasting blood glucose (WMD: -0.52 mg/dL; 95% CI: -1.43, 0.38 mg/dL; I2 = 53.4%) or HbA1c (WMD: 0.02%; 95% CI: -0.01%, 0.04%; I2 = 51.0%). Conclusions Consumption of peanuts or tree nuts significantly decreased HOMA-IR and fasting insulin; there was no effect of nut consumption on HbA1c or fasting glucose. The results suggest that nut consumption may improve insulin sensitivity. In the future, well-designed clinical trials are required to elucidate the mechanisms that account for these observed effects.

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Abstract Objective To systematically review the evidence from randomized controlled trials comparing the effects of goal‐oriented care against standard care for multimorbid adults. Data Sources/Study Setting The literature presenting the results of randomized trials assessing the outcomes of goal‐oriented care compared with usual care for adults with multimorbidity. Study Design Systematic review and meta‐analysis. Data Collection/Extraction Methods We searched the Cochrane Database of Systematic Reviews (CENTRAL), EMBASE, MEDLINE, CINHAL, trial registries such as ClinicalTrial.gov and World Health Organization International Clinical Trials Registry Platform (ICTRP), and the references of eligible trials and relevant reviews. Goal‐oriented care was defined as an approach that engages patients, establishes personal goals, and sets targets for patients and clinicians to plan a course of action and measure outcome. We reviewed 228 trials, and 12 were included. We extracted outcome data on quality of life, hospital admission, patients' satisfaction, patient and caregiver burden. Risk of bias was assessed and certainty of evidence was evaluated using GRADE. Principal Findings No study was fully free of bias. No effect was found on quality of life (standardized mean difference [SMD]: 0.05; 95% CI: −0.05 to 0.16) and hospital admission (risk ratio [RR]: 0.87; 95% CI: 0.65 to 1.17). There was a very small effect for patients' satisfaction (SMD: 0.15; 95% CI: 0.00 to 0.29) and caregiver burden (SMD: −0.13; 95% CI: −0.26 to 0.00). Certainty of evidence was low for all outcomes. Conclusions No firm conclusions can be reached about the effects of goal‐oriented care for multimorbid adults. Future research should overcome the shortcomings of trials assessed in this meta‐analysis. Sound application of the indications for research of complex healthcare interventions is warranted.

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Objective To investigate the effectiveness of exercise interventions to improve gait and balance in individuals with lower limb amputations. Methods A systematic search was conducted on the PubMed, Scopus, Web of Science, SPORTDiscuss, and CINAHL databases until January 2022. Only randomized control trials that evaluated adults (>18 years old) with lower limb amputations and compared any exercise intervention with a traditional prosthetic training were included in the study. Two independent researchers screened articles for inclusion, extracted data, and evaluated the methodological quality of the trials. Findings were summarized and meta-analysis was conducted. Results Fifteen randomized clinical trials with 594 participants were included in the study and 12 in quantitative synthesis. Meta-analysis indicates that exercise interventions significantly improved walking distance measured with the 2-Minute Walking Test compared to traditional training (mean difference-MD: 8.38, 95% CI: 2.54−14.23; P < 0.01). Gait speed performance also significantly improved after exercise interventions compared to traditional training (MD: 0.10, 95% CI, 0.03−0.16, P <0.01). Meta-analysis of exercise interventions compared to traditional training on the Locomotor Capabilities Index, Timed Up and Go, and Activities-specific Balance Confidence did not show a statistically significant difference (P > 0.05). However, the qualitative analysis demonstrated significant improvement in balance performance after different exercise interventions and traditional training. The studies demonstrated overall good methodological quality. Conclusion Specific exercise interventions are more effective than traditional prosthetic training to improve walking speed and walking distance among people with lower limb amputation. Findings on balance outcomes are inconsistent and deserve further exploration.

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Context The efficacy and safety of testosterone replacement therapy (TRT) in hypogonadal men remain incompletely understood. Objective To conduct a systematic review and meta-analysis of randomized clinical trials (RCT) to determine the effects of TRT on patient-important outcomes and adverse events in hypogonadal men. Data Sources We searched Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, and Scopus from inception to March 2th, 2017. Study selection RCTs that assessed the efficacy and adverse events of TRT of at least 12 weeks compared with placebo in adult men with hypogonadism, defined by morning testosterone ≤300 ng/dL and at least one symptom or sign of hypogonadism. Data extraction Reviewers working independently and in duplicate assessed the quality of the trials and collected data on patient characteristics, interventions, and outcomes. Data synthesis We found 11 publications, reporting on 4 eligible trials (including 1,779 patients) at low risk of bias. Compared to placebo, TRT was associated with a small but significant increase in sexual desire or libido [standardized mean difference (SMD): 0.17, 95% CI 0.01, 0.34] (n=1383), erectile function [SMD: 0.16, 95% CI 0.06, 0.27] (n=1344), and sexual satisfaction [SMD: 0.16, 95% CI 0.01, 0.31] (n=676), but had no effect on energy or mood. TRT was associated with an increased risk of developing erythrocytosis [relative risk: 8.14, 95% CI: 1.87, 35.40] (n=1579) compared to placebo, but had no significant effect on lower urinary tract symptoms (LUTS). Conclusion In hypogonadal men TRT improves sexual desire, erectile function, and sexual satisfaction, however it increases the risk of erythrocytosis.

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BACKGROUND Although several studies have assessed the effects of nut consumption (tree nuts, peanuts, and soy nuts) on blood pressure (BP), the results are conflicting. OBJECTIVE The aim was to conduct a systematic review and meta-analysis of published randomized controlled trials (RCTs) to estimate the effect of nut consumption on BP. DESIGN The databases MEDLINE, SCOPUS, ISI Web of Science, and Google Scholar were searched for RCTs carried out between 1958 and October 2013 that reported the effect of consuming single or mixed nuts (including walnuts, almonds, pistachios, cashews, hazelnuts, macadamia nuts, pecans, peanuts, and soy nuts) on systolic BP (SBP) or diastolic BP (DBP) as primary or secondary outcomes in adult populations aged ≥18 y. Relevant articles were identified by screening the abstracts and titles and the full text. Studies that evaluated the effects for <2 wk or in which the control group ingested different healthy oils were excluded. Mean ± SD changes in SBP and DBP in each treatment group were recorded for meta-analysis. RESULTS Twenty-one RCTs met the inclusion criteria. Our findings suggest that nut consumption leads to a significant reduction in SBP in participants without type 2 diabetes [mean difference (MD): -1.29; 95% CI: -2.35, -0.22; P = 0.02] but not in the total population. Subgroup analyses of different nut types suggest that pistachios, but not other nuts, significantly reduce SBP (MD: -1.82; 95% CI: -2.97, -0.67; P = 0.002). Our study suggests that pistachios (MD: -0.80; 95% CI: -1.43, -0.17; P = 0.01) and mixed nuts (MD: -1.19; 95% CI: -2.35, -0.03; P = 0.04) have a significant reducing effect on DBP. We found no significant changes in DBP after the consumption of other nuts. CONCLUSIONS Total nut consumption lowered SBP in participants without type 2 diabetes. Pistachios seemed to have the strongest effect on reducing SBP and DBP. Mixed nuts also reduced DBP.

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Background Preoperative anemia is a common comorbidity that often necessitates allogeneic blood transfusion (ABT). As there is a risk associated with blood transfusions, preoperative intravenous iron (IV) has been proposed to increase the hemoglobin to reduce perioperative transfusion; however, randomized controlled trials (RCT) investigating this efficacy for IV iron are small, limited, and inconclusive. Consequently, a meta-analysis that pools these studies may provide new and clinically useful information. Methods/design Databases of MEDLINE, EMBASE, EBM Reviews; Cochrane-controlled trial registry; Scopus; registries of health technology assessment and clinical trials; Web of Science; ProQuest Dissertations and Theses; Clinicaltrials.gov; and Conference Proceedings Citation Index-Science (CPCI-S) were searched. Also, we screened all the retrieved reference lists. Selection criteria Titles and abstracts were screened for relevance (i.e., relevant, irrelevant, or potentially relevant). Then, we screened full texts of those citations identified as potentially applicable. Results Our search found 3195 citations and ten RCTs (1039 participants) that met our inclusion criteria. Preoperative IV iron supplementation significantly decreases ABT by 16% (risk ratio (RR): 0.84, 95% confidence interval [CI]: 0.71, 0.99, p = 0.04). In addition, preoperatively, hemoglobin levels increased after receiving IV iron (mean difference [MD] between the study groups: 7.15 g/L, 95% CI: 2.26, 12.04 g/L, p = 0.004) and at follow-up >  4 weeks postoperatively (MD: 6.46 g/L, 95% CI: 3.10, 9.81, p = 0.0002). Iron injection was not associated with increased incidence of non-serious or serious adverse effects across groups (RR: 1.13, 95% CI: 0.78, 1.65, p = 0.52) and (RR: 0.96, 95% CI: 0.44, 2.10, p = 0.92) respectively. Conclusions With moderate certainty, due to the high risk of bias in some studies in one or two domains, we found intravenous iron supplementation is associated with a significant decrease in the blood transfusions rate, and modest hemoglobin concentrations rise when injected pre-surgery compared with placebo or oral iron supplementation. However, further full-scale randomized controlled trials with robust methodology are required. In particular, the safety, quality of life, and cost-effectiveness of different intravenous iron preparations require further evaluation.

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Prenatal anxiety is extremely common and may result in adverse effects on both the mother and the baby. Music interventions have been used to reduce anxiety in various medical patients and in pregnant women during childbirth. This study aims to assess the clinical efficacy of music interventions in women during pregnancy rather than during labor. Seven databases were searched from inception to September 2019 without language restrictions. We included only randomized controlled trials that compared music intervention and control groups for anxiety reduction in pregnant women. We used the revised Cochrane risk-of-bias tool (RoB 2.0) for quality assessment. Finally, 11 studies with 1482 participants were included. The pooled meta-analysis results showed that music interventions significantly decreased anxiety levels (standardized mean difference (SMD), −0.42; 95% confidence interval (CI), −0.83 to −0.02; I2 = 91%). Moreover, subgroup analysis showed that listening to music at home had significant anxiolytic benefits (SMD, −0.28; 95% CI, −0.47 to −0.08; I2 = 0%). However, meta-regression revealed a nonsignificant trend for increase in the anxiety-reducing effects of music interventions with increasing maternal age. In conclusion, music interventions may be beneficial in reducing anxiety and may be applied in pregnant women.

Abstract:
Safinamide is a novel anti-parkinsonian drug with possible anti-dyskinetic properties. Parkinson's disease (PD) is a complex disease. The objective of this systematic review and meta-analysis is to evaluate the efficacy and safety of safinamide administration compared to placebo in PD patients on multiple outcomes. PubMed, EMBASE, Cochrane CENTRAL, LILACS, and trial databases were searched up to 23 December 2020 for randomized controlled studies (RCTs) comparing safinamide to placebo, alone or as add-on therapy in PD. Data were extracted from literature and regulatory agencies. Primary outcomes were ON-time without troublesome dyskinesia, OFF-time, and Unified Parkinson’s Disease Rating Scale (UPDRS) section III (UPDRS-III). Secondary outcomes included any dyskinesia rating scale (DRS), ON-time with troublesome dyskinesia, UPDRS-II, and Parkinson’s Disease Questionnaire 39 (PDQ-39). In order to estimate mean difference (MD) and odds ratios with 95% confidence intervals (CI), generic inverse variance and Mantel–Haenszel methods were used for continuous and dichotomous variables, respectively. Analyses were performed grouping by PD with (PDwMF) or without (PDwoMF) motor fluctuations, safinamide dose, and concomitant dopaminergic treatment. Summary of findings with GRADE were performed. Six studies with a total of 2792 participants were identified. In PDwMF patients, safinamide 100 mg as add-on to levodopa (l-dopa) significantly increased ON-time without troublesome dyskinesia (MD = 0.95 h; 95% CI from 0.41 to 1.49), reduced OFF-time (MD = − 1.06 h; 95% CI from − 1.60 to − 0.51), and improved UPDRS-III (MD = − 2.77; 95% CI from − 4.27 to − 1.28) with moderate quality of evidence. Similar results were observed for the 50 mg dose. However, the quality of evidence was moderate only for ON-time without troublesome dyskinesia, whereas for OFF-time and UPDRS-III was low. In PDwoMF patients taking a single dopamine agonist, safinamide 100 mg resulted in little to no clinically significant improvement in UPDRS-III (MD = − 1.84; 95% CI from − 3.19 to − 0.49), with moderate quality of evidence. Conversely, in PDwoMF patients, the 200 mg and 50 mg doses showed nonsignificant improvement in UPDRS-III, with very low and moderate quality of evidence, respectively. In PDwMF patients taking safinamide 100 mg or 50 mg, nonsignificant differences were observed for ON-time with troublesome dyskinesia and DRS, with high and low quality of evidence, respectively. In the same patients, UPDRS-II was significantly improved at the 100 mg and 50 mg dose, with high and moderate quality of evidence. In PDwoMF, UPDRS-II showed a little yet significant difference only at 100 mg, with low quality of evidence. PDQ-39 resulted significantly improved only with the 100 mg dose in PDwMF, with low quality of evidence. Overall, safinamide is effective in PDwMF patients taking l-dopa both at 100 and 50 mg daily. Evidence for efficacy in early PD is limited. Further trials are needed to better evaluate the anti-dyskinetic properties of safinamide.