scholarly journals The effect of short-term exposure to the natural environment on depressive mood: A systematic review and meta-analysis

2019 ◽  
Author(s):  
Hannah Roberts ◽  
Caspar J. Van Lissa
Keyword(s):  
Systematic Review ◽  
Effect Size ◽  
Natural Environment ◽  
Meta Analysis ◽  
Depressive Mood ◽  
Risk Of Bias ◽  
Short Term ◽  
Quality Of Evidence ◽  
Short Term Exposure

Background: Research suggests that exposure to the natural environment can improve mood, however, current reviews are limited in scope and there is little understanding of moderators.Objective: To conduct a comprehensive systematic review and meta-analysis of the evidence for the effect of short-term exposure to the natural environment on depressive mood.Methods: Five databases were systematically searched for relevant studies published up to March 2018. Risk of bias was evaluated using the Cochrane Risk of Bias (ROB) tool 1.0 and the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool where appropriate. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence overall. A random-effects meta-analysis was performed. 20 potential moderators of the effect size were coded and the machine learning-based MetaForest algorithm was used to identify relevant moderators. These were then entered into a meta-regression.Results: 33 studies met the inclusion criteria. Effect sizes ranged from −2.30 to 0.84, with a pooled effect size of γ = -0.30 95% CI [-0.50 to -0.10]. However, there was significant residual heterogeneity between studies and risk of bias was high. Type of natural environment, type of built environment, gender mix of the sample, and region of study origin, among others, were identified as relevant moderators but were not significant when entered in a meta-regression. The quality of evidence was rated very low to low. An assessment of publication bias was inconclusive.Conclusions: A small effect was found for reduction in depressive mood following exposure to the natural environment. However, the high risk of bias and low quality of studies limits confidence in the results. The variation in effect size also remains largely unexplained. It is recommended that future studies make use of reporting guidelines and aim to reduce the potential for bias where possible.

scholarly journals The effect of short-term exposure to the natural environment on depressive mood: A systematic review and meta-analysis

2019 ◽  
Vol 177 ◽  
pp. 108606 ◽  
Author(s):  
Hannah Roberts ◽  
Caspar van Lissa ◽  
Paulien Hagedoorn ◽  
Ian Kellar ◽  
Marco Helbich
Keyword(s):  
Systematic Review ◽  
Natural Environment ◽  
Meta Analysis ◽  
Depressive Mood ◽  
Short Term ◽  
Short Term Exposure

scholarly journals Weight loss for overweight and obese individuals with gout: a systematic review of longitudinal studies

2017 ◽  
Vol 76 (11) ◽  
pp. 1870-1882 ◽  
Author(s):  
Sabrina M Nielsen ◽  
Else M Bartels ◽  
Marius Henriksen ◽  
Eva E Wæhrens ◽  
Henrik Gudbergsen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Longitudinal Studies ◽  
Randomised Trial ◽  
Risk Of Bias ◽  
Current Evidence ◽  
Short Term ◽  
Quality Of Evidence

ObjectivesWeight loss is commonly recommended for gout, but the magnitude of the effect has not been evaluated in a systematic review. The aim of this systematic review was to determine benefits and harms associated with weight loss in overweight and obese patients with gout.MethodsWe searched six databases for longitudinal studies, reporting the effect of weight loss in overweight/obese gout patients. Risk of bias was assessed using the tool Risk of Bias in Non-Randomised Studies of Interventions. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation.ResultsFrom 3991 potentially eligible studies, 10 were included (including one randomised trial). Interventions included diet with/without physical activity, bariatric surgery, diuretics, metformin or no intervention. Mean weight losses ranged from 3 kg to 34 kg. Clinical heterogeneity in study characteristics precluded meta-analysis. The effect on serum uric acid (sUA) ranged from −168 to 30 μmol/L, and 0%–60% patients achieving sUA target (<360 μmol/L). Six out of eight studies (75%) showed beneficial effects on gout attacks. Two studies indicated dose–response relationship for sUA, achieving sUA target and gout attacks. At short term, temporary increased sUA and gout attacks tended to occur after bariatric surgery.ConclusionsThe available evidence is in favour of weight loss for overweight/obese gout patients, with low, moderate and low quality of evidence for effects on sUA, achieving sUA target and gout attacks, respectively. At short term, unfavourable effects may occur. Since the current evidence consists of a few studies (mostly observational) of low methodological quality, there is an urgent need to initiate rigorous prospective studies (preferably randomised controlled trials).Systematic review registrationPROSPERO, CRD42016037937.

scholarly journals Occupational risk factors for meniscal lesions: a systematic review and meta-analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Carolin Bahns ◽  
Ulrich Bolm-Audorff ◽  
Andreas Seidler ◽  
Karla Romero Starke ◽  
Elke Ochsmann
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Occupational Risk ◽  
Hard Coal ◽  
Occupational Risk Factors ◽  
Quality Of Evidence ◽  
Meniscal Lesions

Abstract Background Meniscal lesions are common and are associated with the development of knee osteoarthritis. Knee-straining activities at work such as kneeling or squatting cause high biomechanical stresses on the knee joints that can lead to acute or chronic injuries. The objective of this systematic review is to update the evidence on the potential relationship between occupational risk factors and meniscal lesions. Methods We searched the Medline, Embase and Web of Science databases until August 2021 to identify epidemiological observational studies on the association between occupational risk factors and meniscal lesions. Study selection, data extraction and risk of bias assessment were performed independently by two reviewers. Effect measures were extracted from individual studies and pooled with random effects meta-analysis. Heterogeneity analyses were conducted. We used GRADE (Grades of Recommendations, Assessment, Development and Evaluation) to assess the overall quality of evidence. Results The database search resulted in 11,006 references, and 46 additional studies were identified through hand search. Twenty-two studies (represented in 25 publications) met the predefined eligibility criteria and nine records were included in the meta-analysis. There was only one study with an overall low risk of bias. Significant associations between occupational risk factors and the development of meniscal lesions were found for kneeling (effect size (ES) 2.15, 95% CI 1.67–2.76), squatting (ES 2.01, 95% CI 1.34–3.03), climbing stairs (ES 2.28, 95% CI 1.58–3.30), lifting and carrying weights ≥ 10 kg (ES 1.63, 95% CI 1.35–1.96), lifting and carrying weights ≥ 25 kg (ES 1.56, 95% CI 1.08–2.24), playing football on a professional level (ES 5.22, 95% CI 3.24–8.41), working as a hard coal miner (ES 5.23, 95% CI 2.16–12.69) and floor layers (ES 1.99, 95% CI 1.43–2.78). The overall quality of evidence according GRADE was moderate to low. Conclusion We found consistent evidence of an increased risk of meniscal lesions by occupational knee-straining exposures. Our findings are important for the development of preventive strategies to reduce work-related knee disorders and work absence. Trial registration PROSPERO (registration no. CRD42020196279).

scholarly journals Does Ketorolac reduce the intensity of postoperative pain after impacted third molars surgery in adults compared to the use of tramadol? A systematic review and meta-analysis

2021 ◽  
Vol 10 (3) ◽  
pp. e19410313137
Author(s):  
Luciana Dorochenko Martins ◽  
Márcia Rezende ◽  
Ana Cláudia Chibinski ◽  
Alessandro Dourado Loguercio ◽  
Marcelo Carlos Bortoluzzi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Postoperative Pain ◽  
Adverse Effects ◽  
Qualitative Analysis ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Low Risk ◽  
Third Molars ◽  
Quality Of Evidence

This systematic review and meta-analysis evaluated if ketorolac reduces the intensity of postoperative pain after impacted third molars surgery in adults compared to the use of tramadol. A comprehensive search was performed in the MEDLINE/PubMed, Scopus, Web of Science, LILACS, BBO, EMBASE, Cochrane Library, SIGLE and grey literature, in accordance with the PRISMA guidelines. The quality of the evidence was evaluated using the GRADE approach. Meta-analysis was performed on studies considered at low risk of bias. After duplicates removal, 4526 articles were identified, but only nine studies were included for qualitative analysis. After updating in 2021, four studies were added, totaling 13 studies included for qualitative analysis. Only two studies, classified at “low” risk of bias, were included in the meta-analysis of the primary outcome. The difference in means for pain intensity (moderate quality of evidence due to imprecision) was – 0.27 (95% CI = – 0.82 to 0.28; p = 0.34). Data from adverse effects (low quality of evidence due to very serious issues in imprecision) was just reported in one study at “low” risk of bias. Data was not heterogeneous (Chi2 test p = 0.14; I2 = 55%). It was not possible to evaluate any secondary outcomes (time to first rescue analgesic drug in h, total amount of analgesics consumed and adverse effects) due to low number of studies included. There is a lack of strong evidence to assure the superiority of ketorolac or tramadol in reducing the postoperative pain after extraction of impacted third molars.

scholarly journals Subclinical thyroid dysfunction and incident atrial fibrillation - a systematic review and meta-analysis

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
H Singh ◽  
MZ Shahid ◽  
SL Harrison ◽  
DA Lane ◽  
GYH Lip ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Subgroup Analysis ◽  
Subclinical Hypothyroidism ◽  
Thyroid Dysfunction ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Subclinical Hyperthyroidism ◽  
Quality Of Evidence

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): This project was supported by the MRes programme in the Institute of Life Course and Medical Sciences at The University of Liverpool. Thyroid hormones can act directly and indirectly on the cardiovascular system and studies have demonstrated associations between overt and subclinical thyroid dysfunction and adverse cardiovascular outcomes including heart failure, myocardial infarction, and coronary heart disease. The aim of this study was to assess the association between subclinical thyroid dysfunction and atrial fibrillation (AF).  The protocol was registered on PROSPERO (CRD42020221565). MEDLINE and Scopus were searched from inception to 13th November 2020 for studies investigating subclinical thyroid dysfunction and incident AF. Risk of bias was assessed using the Risk of Bias Assessment Tool (RoBANS). The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Subgroup analysis was performed for post-operative and non-post-operative AF. 5413 records were identified. Nine cohort studies were suitable for inclusion in the systematic review, of which seven studies were included in the meta-analysis. The meta-analysis comprised 595,058 patients. Subclinical hyperthyroidism was associated with a 99% increase in the risk of incident AF (Risk ratio (RR): 1.99; 95% confidence intervals (CI); 1.43 to 2.77; p &lt; 0.0001; I² = 67%). Subclinical hypothyroidism was also associated with a greater risk of AF (RR: 1.24; 95% CI; 1.05 to 1.47; p = 0.01; I² = 65%). Subgroup analysis demonstrated a 76% increase in the risk of post-operative AF in patients with subclinical hypothyroidism compared to euthyroid post-operative patients (RR: 1.76; 95% CI; 1.36 to 2.28; p &lt; 0.0001; I² = 0%). Six studies were rated as low risk of bias and three as medium risk of bias according to the RoBANS tool. The quality of evidence for AF in subclinical hyper- and hypothyroid patients was low. Subclinical hyperthyroidism and subclinical hypothyroidism were associated with a higher risk of incident AF and post-operative AF, respectively. The quality of the current evidence is low and ideally a randomised controlled trial should be conducted to confirm these associations and assess impacts of treatments. Abstract Figure.

scholarly journals Efficacy and safety of Sihogayonggolmoryeo-tang (Saikokaryukotsuboreito, Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) for post-stroke depression: A systematic review and meta-analysis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chan-Young Kwon ◽  
Boram Lee ◽  
Sun-Yong Chung ◽  
Jong Woo Kim ◽  
Aesook Shin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Efficacy And Safety ◽  
Quality Of Evidence ◽  
Post Stroke Depression ◽  
Grade Approach

Abstract This systematic review and meta-analysis aimed to analyze the efficacy and safety of Sihogayonggolmoryeo-tang (SGYMT), a classical herbal medicine consisting of 11 herbs, for treatment of post-stroke depression (PSD). Thirteen databases were comprehensively searched from their inception dates until July 2019. Only randomized controlled trials (RCTs) using SGYMT as a monotherapy or adjunctive therapy for PSD patients were included. Where appropriate data were available, meta-analysis was performed and presented as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). We assessed the quality of RCTs using the Cochrane risk of bias tool and the Jadad scale. The quality of evidence for each main outcome was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Twenty-one RCTs with 1,644 participants were included. In the comparison between the SGYMT and antidepressants groups, the SGYMT group scored significantly lower on both the Hamilton Depression Scale (HAMD) (8 studies; MD −2.08, 95% CI −2.62 to −1.53, I2 = 34%) and the National Institutes of Health Stroke Scale (NIHSS) (2 studies; MD −0.84, 95% CI −1.40 to −0.29, I2 = 19%), and significantly higher on the Barthel index (3 studies; MD 4.30, 95% CI 2.04 to 6.57, I2 = 66%). Moreover, the SGYMT group was associated with significantly fewer adverse events (6 studies; RR 0.13, 95% CI 0.05 to 0.37, I2 = 0%) than the antidepressants group. In the subgroup analysis, SGYMT treatment consistently reduced HAMD scores within the first 8 weeks of treatment, but thereafter this difference between groups disappeared. Comparisons between SGYMT combined with antidepressants, and antidepressants alone, showed significantly lower scores in the combination group for both HAMD (7 studies; MD = −6.72, 95% CI = −11.42 to −2.01, I2 = 98%) and NIHSS scores (4 studies; MD −3.03, 95% CI −3.60 to −2.45, I2 = 87%). In the subgroup analysis, the reductions of HAMD scores in the SGYMT combined with antidepressants group were consistent within 4 weeks of treatment, but disappeared thereafter. The quality of RCTs was generally low and the quality of evidence evaluated by the GRADE approach was rated mostly “Very low” to “Moderate.” The main causes of low quality ratings were the high risk of bias and imprecision of results. Current evidence suggests that SGYMT, used either as a monotherapy or an adjuvant therapy to antidepressants, might have potential benefits for the treatment of PSD, including short-term reduction of depressive symptoms, improvement of neurological symptoms, and few adverse events. However, since the methodological quality of the included studies was generally low and there were no large placebo trials to ensure reliability, it remains difficult to draw definitive conclusions on this topic. Further well-designed RCTs addressing these shortcomings are needed to confirm our results.

scholarly journals 100 Prevalence of Cognitive Impairment in Vascular Surgery Patients: Preliminary Results of A Systematic Review and Meta-Analysis

2020 ◽  
Vol 49 (Supplement_1) ◽  
pp. i34-i36
Author(s):  
J Houghton ◽  
A Nickinson ◽  
S Nduwayo ◽  
B Bridgwood ◽  
C Pepper ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cognitive Impairment ◽  
Vascular Surgery ◽  
Cognitive Assessment ◽  
Assessment Tool ◽  
Carotid Artery Disease ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Quality Of Evidence

Abstract Introduction Single-centre studies have shown a high prevalence of undiagnosed cognitive impairment in patients undergoing vascular surgery. The aim of this meta-analysis was to estimate the pooled prevalence of cognitive impairment in vascular surgery patients. Methods A systematic review and meta-analysis was performed of studies reporting cognitive impairment in vascular surgery patients (PROSPERO registration: CRD42019134684). Databases searched included: Medline, Embase, Emcare, CINAHL, PsychINFO and Scopus. Studies were excluded if they: did not use a validated cognitive assessment tool, included patients with asymptomatic or sub-threshold (for treatment) disease, or excluded patients with cognitive impairment. Quality of included studies was assessed using Newcastle-Ottawa scores (NOS), risk of bias was assessed using the ROBINS-E tool, and quality of evidence assessed using GRADE criteria. A pooled estimate of prevalence was calculated using the inverse-variance method separately for carotid artery disease (CAD), lower extremity arterial disease (LEAD), and studies including patients with multiple vascular surgery presentations. Data were pooled using random effects models and estimated prevalence presented with 95% confidence intervals (95%CI). Subgroup analyses were performed by cognitive assessment tool used. Authors of 24 studies meeting inclusion criteria that did not report numbers of cognitively impaired patients were contacted to enable inclusion: responses are awaited. Results After de-duplication of search results, 7,169 records were screened and 11 studies (911 patients) included in the meta-analysis. Nine studies were deemed high quality (NOS ≥7) however 8 studies had a serious risk of bias. Only one study explicitly stated provision for recruiting patients without capacity. Six different tools were used to assess cognitive function (MoCA, MMSE, ACE-R, HDS-R, Mini-Cog and a global cognitive score). Two studies found an association of cognitive impairment with post-op delirium whilst one did not, and a further study showed an association with increased length of stay. Pooled estimate of prevalence of cognitive impairment in CAD patients was 38% (95%CI 17%, 62%; 7 studies), and in “vascular surgery patients” was 61% (95%CI 47%, 74%, 3 studies). Only one study reported prevalence of cognitive impairment in LEAD patients alone of 19% (95%CI 14%, 24%). Quality of evidence was moderate to very low. Conclusions Cognitive impairment is highly prevalent in vascular surgery patients highlighting the need for close collaboration between vascular surgeons and geriatricians.

scholarly journals Antibiotic therapy for pelvic inflammatory disease: an abridged version of a Cochrane systematic review and meta-analysis of randomised controlled trials

2018 ◽  
Vol 95 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Ricardo F Savaris ◽  
Daniele G Fuhrich ◽  
Rui V Duarte ◽  
Sebastian Franik ◽  
Jonathan D C Ross
Keyword(s):  
Systematic Review ◽  
Pelvic Inflammatory Disease ◽  
Inflammatory Disease ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Quality Of Evidence ◽  
Randomised Controlled

ObjectiveTo assess the effectiveness and safety of antibiotic regimens used to treat pelvic inflammatory disease (PID).DesignThis is a systematic review and meta-analysis of randomised controlled trials (RCTs). Risk of bias was assessed using the criteria outlined in the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation.Data sourcesEight electronic databases were searched from date of inception up to July 2016. Database searches were complemented by screening of reference lists of relevant studies, trial registers, conference proceeding abstracts and grey literature.Eligibility criteriaRCTs comparing the use of antibiotics with placebo or other antibiotics for the treatment of PID in women of reproductive age, either as inpatient or outpatient treatment.ResultsWe included 37 RCTs (6348 women). The quality of evidence ranged from very low to high, the main limitations being serious risk of bias (due to poor reporting of study methods and lack of blinding), serious inconsistency and serious imprecision. There was no clear evidence of a difference in the rates of cure for mild-moderate or for severe PID for the comparisons of azithromycin versus doxycycline, quinolone versus cephalosporin, nitroimidazole versus no use of nitroimidazole, clindamycin plus aminoglycoside versus quinolone, or clindamycin plus aminoglycoside versus cephalosporin. No clear evidence of a difference between regimens in antibiotic-related adverse events leading to discontinuation of therapy was observed.ConclusionsWe found no conclusive evidence that one regimen of antibiotics was safer or more effective than any other for the treatment of PID, and there was no clear evidence for the use of nitroimidazoles (metronidazole) compared with the use of other drugs with activity against anaerobes. More evidence is needed to assess treatments for women with PID, particularly comparing regimens with or without the addition of nitroimidazoles and the efficacy of azithromycin compared with doxycycline.

scholarly journals The effectiveness of digital technology interventions to reduce loneliness in adult people: A protocol for a systematic review and meta-analysis

2019 ◽  
Author(s):  
Syed Ghulam Sarwar Shah ◽  
David Nogueras ◽  
Hugo Cornelis van Woerden ◽  
Vasiliki Kiparoglou
Keyword(s):  
Public Health ◽  
Systematic Review ◽  
Digital Technology ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
List Type ◽  
Quality Of Evidence ◽  
Randomized Studies ◽  
Health And Social Care

ABSTRACTIntroductionLoneliness is an emerging public health problem, which is associated with social, emotional, mental and physical health issues. The application of digital technology (DT) interventions to reduce loneliness has increased in recent years. The effectiveness of DT interventions needs to be assessed systematically.Methods and analysisAimTo undertake a systematic review and meta-analysis on the effectiveness of digital technology interventions to reduce loneliness among adult people.Designsystematic review and meta-analysis.Data sourcesFive leading online bibliographic databases: PubMed, Medline, CINAHL, EMBASE, and Web of Science.Publication period1 January 2010 to 30 April 2019.Inclusion criteriaPrimary studies involving the application of digital technology interventions to reduce loneliness, involving adult participants (aged 18 years and more) and published in the English language.Search strategyLiterature searches using a priory list of keywords, involvement of two independent researchers in article screening, short listing and data extraction using a predefined template based on the population, intervention(s), comparator(s) and outcome(s) (PICO) framework.Synthesis and meta-analysisA narrative summary of the characteristics of included studies, findings by the type of DT intervention, and the age, gender and ethnicity of participants. A meta-analysis by the type of DT intervention and determination of effect sizes.Quality of evidence and biasQuality of evidence assessed the RoB 2.0 (revised tool for Risk of Bias in randomized trials) and ROBINS-I (Risk Of Bias in Non-randomized Studies - of Interventions) tools for randomized control trials and non-randomized studies respectively. Heterogeneity between studies determined by the I2 and Cochran’s Q statistics and publication bias checked with funnel plots and the Egger’s test.Patients and public involvementNoneEthics and disseminationEthics approval was not required for writing this protocol. The findings will be disseminated through the publication of research articles and conference presentations.PROSPERO Registration NumberCRD42019131524.Article SummaryStrengths and limitations of this studyThe main strength of this study includes a systematic assessment of evidence on the effectiveness of digital technology interventions to reduce loneliness, which is imperative from the health and social care and public health perspectives.Another strength of the study is the involvement of two independent researchers (and a third researcher as an arbitrator) involved in the identification, screening, inclusion and extraction of on a predefined template using the PICO framework.Limitations may include missing identification of additional relevant studies due to the application of selection filters such as the publication years and English as the publication language.

scholarly journals PL03: Prophylactic administration of diphenhydramine to reduce neuroleptic side-effects in the acute care setting: a systematic review and meta-analysis

CJEM ◽  
2018 ◽  
Vol 20 (S1) ◽  
pp. S5-S6
Author(s):  
A. Mokhtari ◽  
O. Yip ◽  
J. Alain ◽  
A. Turgeon ◽  
S. Berthelot
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Acute Care ◽  
Care Setting ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Acute Care Setting ◽  
Quality Of Evidence ◽  
Prophylactic Administration

Introduction: Neuroleptics are commonly used drugs to treat different conditions (e.g. psychosis, migraines) in the acute care setting and the emergency department. Their side effects can be disabling or, worse, fatal. The use of diphenhydramine to prevent those side-effects is widespread, but remains controversial. We performed a systematic review to determine if prophylactic administration of diphenhydramine (PAD) reduces the incidence of neuroleptic side-effects. Methods: Data sources: Medline, Embase, Cochrane Library, PsycInfo and Web of Science were searched. References from reviews that were identified in the search and from included studied were also reviewed for inclusion. Study selection: Randomized controlled trials evaluating any neuroleptic with PAD versus the same neuroleptic alone or with any inactive agent. Primary outcome was incidence of any extra-pyramidal side-effect. Secondary outcomes were akathisia, usage of rescue medication, subjective restlessness, neuroleptic malignant syndrome, sedation and sedation intensity. Data extraction: Independent reviewers scanned identified citations, extracted data and assessed for risk of bias. Data analysis: Meta-analysis was performed using random effect models. Heterogeneity and quality of evidence were assessed using, respectively, I2 and the GRADE approach. Results: Results: Of 1566 identified citations, nine studies (n=1436) met all eligibility criteria. Four studies were specifically designed to assess for neuroleptic side-effects. Four studies were at high risk of bias. In primary analysis, PAD had no effect on the incidence of extra-pyramidal symptoms (7 studies, n=1393 patients, RR 0.70 [0.40-1.22]), akathisia (5 studies, n=1094 patients, RR 0.81 [0.36-1.82]) and sedation (5 studies; n=1079, RR 1,48 [0.90-2.42]). Higher dosage of diphenhydramine was not associated with a greater reduction of extra-pyramidal side-effects. In a sensitivity analysis excluding an outlier study (n=120, RR 6.63 [1.55-28,35]), PAD was associated with a significant decrease in extra-pyramidal side-effects (6 studies, n=1273, RR 0.56 [0,38-0.82]), but not with any of the secondary outcome measures. Conclusion: Conclusion: When excluding an outlier study, PAD was associated with a significant reduction of extra-pyramidal side-effects. However, PAD did not significantly influence the incidence of akathisia. Overall quality of evidence is low. Further studies are warranted. PAD represents an interesting treatment option against neuroleptic side-effects, but its widespread usage whitout strong evidence to support it raises concerns.

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