scholarly journals Optimal Pharmacological Management and Prevention of Glucocorticoid-Induced Osteoporosis (GIOP): Protocol for a Systematic Review and Network Meta-Analysis

2019 ◽  
Author(s):  
Jiawen Deng ◽  
Emma Huang ◽  
Zachary Silver ◽  
Elena Zheng ◽  
Kyra Kavanaugh ◽  
...  

ABSTRACTIntroductionGlucocorticoid (GC) administration is an effective therapy commonly used in the treatment of autoimmune and inflammatory diseases. However, the use of GC can give rise to serious complications. The main detrimental side effect of GC therapy is significant bone loss, resulting in glucocorticoid-induced osteoporosis (GIOP).There are a variety of treatments available for preventing and managing GIOP; however, without clearly defined guidelines, it can be very difficult for physicians to choose the optimal therapy for their patients. Previous network meta-analyses (NMAs) and meta-analyses did not include all available RCT trials, or only performed pairwise comparisons. We present a protocol for a NMA that incorporates all available RCT patient data to provide the most comprehensive ranking of all available GIOP treatments in terms of their ability to increase bone mineral density (BMD) and decrease fracture incidences among adult patients undergoing GC treatments.Methods and AnalysisWe will search MEDLINE, EMBASE, PubMed, Web of Science, CINAHL, CENTRAL and Chinese literature sources (CNKI, CQVIP, Wanfang Data, Wanfang Med Online) for randomized controlled trials (RCTs) which fit our criteria. RCTs that evaluate different antiresorptive regimens taken by adult patients undergoing GC therapy during the study or had taken GC for at least 3 months in the year prior to study commencement with lumbar spine BMD, femoral neck BMD, total hip BMD, vertebral fracture incidences and/or non-vertebral fracture incidences as outcomes will be selected.We will perform title/abstract and full-text screening as well as data extraction in duplicate. Risk of bias (ROB) will be evaluated in duplicate for each study, and the quality of evidence will be examined using CINeMA in accordance to the GRADE framework. We will use R and gemtc to perform the NMA. We will report BMD results as weighted mean differences (WMDs) and standardized mean differences (SMDs), and we will report fracture incidences as odds ratios. We will use the surface under the cumulative ranking curve (SUCRA) scores to provide numerical estimations of the rankings of interventions.Ethics and DisseminationThe study will not require ethical approval. The findings of the NMA will be disseminated in a peer-reviewed journal and presented at conferences. We aim to produce the most comprehensive quantitative analysis regarding the management of GIOP. Our analysis should be able to provide physicians and patients with an up-to-date recommendation for pharmacotherapies in reducing incidences of bone loss and fractures associated with GIOP.Systematic Review RegistrationInternational Prospective Register for Systematic Reviews (PROSPERO) — CRD42019127073ARTICLE SUMMARYStrengths and limitations of this studyLiterature search in Chinese databases will likely yield huge amounts of new RCT evidence regarding GIOPReporting change in BMD outcomes as standardized mean differences allow the pooling of absolute and percentage change data, increasing the number of RCT trials includedOnly RCTs will be included, quality of trials and networks will be evaluated using Risk of Bias and GRADEOlder trials may report inaccurate results due to outdated procedures and hardwareChinese clinicians may not use the same procedures and practices as Western clinicians

2021 ◽  
pp. ASN.2021040554
Author(s):  
Nicole Lioufas ◽  
Elaine Pascoe ◽  
Carmel Hawley ◽  
Grahame Elder ◽  
Sunil Badve ◽  
...  

Background: Benefits of phosphate-lowering interventions on clinical outcomes in patients with chronic kidney disease (CKD) are unclear; systematic reviews have predominantly involved dialysis patients. This study aimed to summarize evidence from randomized controlled trials (RCTs) concerning benefits and risks of non-calcium-based phosphate-lowering treatment in non-dialysis CKD. Methods: We conducted a systematic review and meta-analyses of RCTs involving noncalcium-based phosphate-lowering therapy compared to placebo, calcium-based binders, or no study medication, in adults with CKD not on dialysis or post-transplant. RCTs had ≥3 months follow up and outcomes included biomarkers of mineral metabolism, cardiovascular parameters, and adverse events. Outcomes were meta-analyzed using the Sidik-Jonkman method for random effects. Unstandardized mean differences were used as effect sizes for continuous outcomes, with common measurement units and Hedge's g standardized mean differences (SMD) otherwise. Odds ratios were used for binary outcomes. Cochrane risk of bias and GRADE assessment determined the certainty of evidence. Results: Twenty trials involving 2,498 participants (median sample size 120, median follow up 9 months) were eligible for inclusion. Overall, risk of bias was low. Compared with placebo, non calcium-based phosphate binders reduced serum phosphate (12 trials, weighted mean difference -0.37, 95% CI -0.58,-0.15 mg/dL, low certainty evidence) and urinary phosphate excretion (8 trials, SMD -0.61, 95% CI -0.90,-0.31, low certainty evidence), but resulted in increased constipation (9 trials, log odds ratio [OR] 0.93, 95% CI 0.02, 1.83, low certainty evidence) and greater vascular calcification score (3 trials, SMD 0.47, 95% CI 0.17, 0.77, very low certainty evidence). Data for effects of phosphate-lowering therapy on cardiovascular events (log OR 0.51 [95% CI -0.51, 1.17]) and death were scant. Conclusions: Non-calcium-based phosphate-lowering therapy reduced serum phosphate and urinary phosphate excretion, but there was an unclear effect on clinical outcomes and intermediate cardiovascular end-points. Adequately powered RCTs are required to evaluate benefits and risks of phosphate-lowering therapy on patient-centered outcomes.


2017 ◽  
Vol 96 (3) ◽  
pp. 261-269 ◽  
Author(s):  
D.C. Penoni ◽  
T.K.S. Fidalgo ◽  
S.R. Torres ◽  
V.M. Varela ◽  
D. Masterson ◽  
...  

Osteoporosis is a systemic skeletal disease characterized by low bone mineral density (BMD) and has been considered a risk factor for periodontal disease. The aim of this systematic review and meta-analysis was to verify the scientific evidence for the association of periodontal attachment loss with low BMD in postmenopausal women. A systematic search of the literature was performed in databases until August 2016, in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Eligibility criteria included studies that compared clinical attachment loss (CAL) between postmenopausal women with low and normal BMD. Studies using similar methodology, with lower and higher risk of bias, were pooled into 3 different meta-analyses to compare CAL among women with normal BMD, osteoporosis, and osteopenia. In the first meta-analysis, mean CAL was compared among groups. In the other 2 meta-analyses, the mean percentages of sites with CAL ≥4 mm and ≥6 mm were respectively compared among groups. From 792 unique citations, 26 articles were selected for the qualitative synthesis. Eleven of the studies were appraised as presenting low risk of bias, and the association between low BMD and CAL was observed in 10 of these studies. Thirteen cross-sectional articles were included in the meta-analysis for osteoporosis and 9 in the osteopenia analysis. Women with low BMD presented greater mean CAL than those with normal BMD (osteoporosis = 0.34 mm [95% confidence interval (CI), 0.20–0.49], P < 0.001; osteopenia = 0.07 mm [95% CI, 0.01–0.13], P = 0.02). Only studies with lower risk of bias were available for the analysis of CAL severity. Women with low BMD presented more severe attachment loss, represented as mean percentage of sites with CAL ≥4 mm (osteoporosis = 3.04 [95% CI, 1.23–4.85], P = 0.001; osteopenia = 1.74 [95% CI, 0.36–3.12], P = 0.01) and CAL ≥6 mm (osteoporosis = 5.07 [95% CI, 2.74–7.40], P < 0.001). This systematic review and meta-analysis indicates that postmenopausal women with osteoporosis or osteopenia may exhibit greater CAL compared with women with normal BMD.


2021 ◽  
Author(s):  
Marianna Rosso ◽  
Robin Wirz ◽  
Ariane Vera Loretan ◽  
Nicole Alessandra Sutter ◽  
Charlène Tatiana Pereira da Cunha ◽  
...  

Animal research on anxiety and anxiety disorders relies on valid animal models of anxiety. However, the validity of widely used rodent behavioural tests of anxiety has repeatedly been questioned, as they often fail to produce consistent results across independent replicate studies using different study populations or different anxiolytic compounds. In this study, we assessed the sensitivity of behavioural tests of anxiety in mice to detect anxiolytic effects of drugs prescribed to treat anxiety in humans. To this end, we conducted a pre-registered systematic review of studies reporting tests of anxiolytic compounds against a control treatment using common behavioural tests of anxiety in mice. PubMed and EMBASE were searched on August 21 st 2019 for studies published in English and 814 papers were identified for inclusion. Risk of bias was assessed based on Syrcle’s risk of bias tool and the Camarades study quality checklist on a randomly selected subsample of 180 papers. Meta-analyses on effect sizes of treatments using standardized mean differences (Hedges’ g) showed that only two of 17 test measures reliably detected effects of anxiolytic compounds other than diazepam. Further, we report considerable variation in both direction and size of effects of most anxiolytics on most outcome variables, indicating poor replicability of test results. This was corroborated by high heterogeneity in most test measures. Finally, we found an overall high risk of bias. Our findings indicate a general lack of sensitivity of common behavioural tests of anxiety in mice to anxiolytic compounds and cast serious doubt on both construct and predictive validity of most of those tests. The use of animals to model human conditions can be justified only if the expected results are informative, reproducible, and translatable. In view of scientifically valid and ethically responsible research, we call for a revision of behavioural tests of anxiety in mice and the development of more predictive tests .


2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii51-ii52
Author(s):  
A M George ◽  
S Gupta ◽  
S M Keshwara ◽  
M A Mustafa ◽  
C S Gillespie ◽  
...  

Abstract BACKGROUND Systematic reviews and meta-analyses constitute the highest level of research evidence and for a disease with limited clinical trial activity, are often relied upon to help inform clinical practice. This review of reviews evaluates both the reporting & methodological quality of meningioma evidence syntheses. MATERIAL AND METHODS Potentially eligible meningioma reviews published between 1st January 1990 and 31st December 2020 were identified from eight electronic databases. Inclusion required the study to meet the Cochrane guideline definition of a systematic review or meta-analysis. Reviews concerning neurofibromatosis type 2, spinal and pediatric meningiomas were excluded. The reporting and methodological quality of articles were assessed against the following modified guidelines: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), A MeaSurement Tool to Assess Systematic Reviews (AMSTAR2) and the Risk of Bias in Systematic Reviews (ROBIS) guidelines. RESULTS 117 systematic reviews were identified, 57 of which included meta-analysis (48.7%). The number of meningioma systematic reviews published each year has increased with 63 studies (53.9%) published between 01/2018 and 12/2020. A median of 17 studies (IQR 9–29) were included per review. Impact factor of journals publishing a systematic review with or without a meta-analysis was similar (median 2.3 vs 1.8, P=0.397). The mean PRISMA scores for systematic reviews with a meta-analysis was 21.11 (SD 4.1, 78% adherence) and without was 13.89 (SD 3.4, 63% adherence). Twenty-nine systematic reviews with meta-analysis (51%) and 11 without meta-analysis (18%) achieved greater than 80% adherence to PRISMA recommendations. Methodological quality assessment using AMSTAR2 revealed one study (0.9%) as high quality whilst 111 (94.8%) studies were graded as critically low. One hundred and two articles (87.2%) did not utilize a comprehensive search strategy as defined by the AMSTAR2 tool. Ninety-nine studies (84.6%) obtained a high level of concern for potential bias as per the ROBIS assessment. One hundred and eight articles (92.3%) failed to present information that a protocol had been established prior to study commencement and 76 articles (65.0%) did not conduct a risk of bias assessment. Across the three tools, domains relating to the establishment of a protocol prior to review commencement and conducting appropriate risk of bias assessments were frequently low scoring. CONCLUSION Overall reporting and methodological quality of meningioma systematic reviews was sub-optimal. Established critical appraisal tools and reporting guidelines should be utilized a priori to assist in producing high-quality systematic reviews.


2021 ◽  
Author(s):  
Alaa Abd-alrazaq ◽  
Mohannad Alajlani ◽  
Dari Alhuwail ◽  
Jens Schneider ◽  
Laila Akhu-Zaheya ◽  
...  

BACKGROUND Anxiety is one of the mental disorders characterized by apprehension, tension, uneasiness, and other related behavioral disturbances. One of the non-pharmacological treatments used for reducing anxiety is serious games, which are games that have a purpose other than entertainment. The effectiveness of serious games in alleviating anxiety was investigated by several systematic reviews, however, they are limited by design and methodological weaknesses. OBJECTIVE This study aims to assess the effectiveness of serious games in alleviating anxiety through summarizing the results of previous studies and providing an up-to-date review. METHODS We carried out a systematic review of randomized controlled trials (RCTs). We searched 7 databases: MEDLINE, CINAHL, PsycINFO, ACM Digital Library IEEE Xplore, Scopus, and Google Scholar. We also conducted backward and forward reference list checking of the included studies and relevant reviews. Two reviewers independently carried out the study selection, data extraction, risk of bias assessment, and quality of evidence appraisal. We used a narrative and statistical approach, as appropriate, to synthesize results of the included studies. RESULTS Out of 935 citations retrieved, 33 studies were included in this review. Of those, 22 RCTs were eventually included in meta-analyses. Very low quality evidence from 9 RCTs and 5 RCTs showed no statistically significant effect of exergames (games entailing physical exercises) on the anxiety level as compared to conventional exercises (P=0.70) and no intervention (P=0.27), respectively. While 6 RCTs demonstrated a statistically and clinically significant effect of computerized cognitive behavioral therapy (CBT) games on the anxiety level when compared with no intervention (P=0.01), the quality of the evidence reported was low. Likewise, low quality evidence from 3 RCTs showed a statistically and clinically significant effect of biofeedback games on the anxiety level when compared with conventional video games (P=0.03). CONCLUSIONS This review shows that serious games have the potential in alleviating anxiety levels. However, our findings remain inconclusive mainly due to the high risk of bias in the individual studies included, the low quality of meta-analyzed evidence, few studies included in some meta-analyses, patients without anxiety recruited in most studies, and using purpose-shifted serious games in most studies. Therefore, serious games should be deemed as complementary to existing interventions. To have adequate and robust evidence, researchers should use serious games that are designed specifically to alleviate depression and deliver other therapeutic modalities, recruit a diverse population of patients with anxiety, and minimize the risk of bias by following the recommended guidelines for conducting and reporting RCTs.


2019 ◽  
Author(s):  
Jiawen Deng ◽  
Umaima Abbas ◽  
Oswin Chang ◽  
Sayan Dhivagaran ◽  
Stephanie Sanger ◽  
...  

ABSTRACTIntroductionPatients with type 2 diabetes mellitus (T2DM) are at risk for a variety of severe debilitating effects. One of the most serious complications experienced by T2DM patients are skeletal diseases caused by changes in the bone microenvironment. As a result, T2DM patients are at risk for higher prevalence of fragility fractures.There are a variety of treatments available for counteracting this effect. Some anti-diabetic medications, such as metformin, have been shown to have a positive effect on bone health without the addition of additional drugs into patients’ treatment plans. Chinese randomized controlled trial (RCT) studies have also proposed antiresorptive pharmacotherapies as a viable alternative treatment strategy. Previous network meta-analyses (NMAs) and meta-analyses regarding this topic did not include all available RCT trials, or only performed pairwise comparisons. We present a protocol for a two-part NMA that incorporates all available RCT data to provide the most comprehensive ranking of anti-diabetics (Part I) and antiresorptive (Part II) pharmacotherapies in terms of their ability to decrease fracture incidences, increase bone mineral density (BMD), improve indications of bone turnover markers (BTMs), and decrease pain in adult T2DM patients.Methods and AnalysisWe will search MEDLINE, EMBASE, PubMed, Web of Science, CINAHL, CENTRAL and Chinese literature sources (CNKI, CQVIP, Wanfang Data, Wanfang Med Online) for randomized controlled trials (RCTs) which fit our criteria. We will include adult T2DM patients who have taken anti-diabetics (Part I) or antiresorptive (Part II) therapies with relevant outcome measures in our study.We will perform title/abstract and full-text screening as well as data extraction in duplicate. Risk of bias (RoB) will be evaluated in duplicate for each study, and the quality of evidence will be examined using CINeMA in accordance to the GRADE framework. We will use R and gemtc to perform the NMA. We will report changes in BMD, BTM and pain scores in either weighted or standardized mean difference, and we will report fracture incidences as odds ratios. We will use the surface under the cumulative ranking curve (SUCRA) scores to provide numerical estimates of the rankings of interventions.Ethics and DisseminationThe study will not require ethics approval. The findings of the two-part NMA will be disseminated in peer-reviewed journals and presented at conferences. We aim to produce the most comprehensive quantitative analysis regarding the management of T2DM bone disease. Our analysis should be able to provide physicians and patients with up-to-date recommendations for anti-diabetic medications and antiresorptive pharmacotherapies for maintaining bone health in T2DM patients.Systematic Review RegistrationInternational Prospective Register for Systematic Reviews (PROSPERO) — CRD42019139320ARTICLE SUMMARYStrengths and limitations of this studyLiterature search in Chinese databases will yield new RCT evidence regarding the efficacy of anti-diabetics in treating T2DM bone diseaseUsing network meta-analytical techniques to analyze the relative efficacy of antiresorptive therapies will allow us to include new treatment arms, such as zoledronic acid and risedronate.Only RCTs will be included and the quality of trials and networks will be evaluated using Risk of Bias, GRADE and comparison-adjusted funnel plots.Chinese clinicians may not use the same procedures and practices as Western clinicians, therefore the outcomes from Chinese RCTs may not apply to the Western healthcare systems.The study design does not allow the comparison of anti-diabetics with antiresorptive therapies or combinations of the two.


2019 ◽  
Author(s):  
Syed Ghulam Sarwar Shah ◽  
David Nogueras ◽  
Hugo Cornelis van Woerden ◽  
Vasiliki Kiparoglou

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.


2020 ◽  
Vol 1;24 (1;1) ◽  
pp. 61-72

BACKGROUND: Psychological comorbidities in chronic pain (CP) are common and contribute to adverse health outcomes and poor quality of life. Evidence-based guidance for the management of depressive symptoms in CP is limited, particularly for mind-body interventions. OBJECTIVES: To investigate the effectiveness of mind-body interventions for the management of depressive symptoms in people with CP. STUDY DESIGN: Systematic review (SR) of SRs. SETTING: SRs with meta-analyses of clinical interventions for the management of depressive symptoms in people with CP. METHODS: This SR was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic searches were performed for MEDLINE, EMBASE, PsycINFO, CINAHL, AMED, the Cochrane Database of Systematic Reviews, and the Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports from inception to March 14, 2019. Reference lists and overviews were also hand-searched. SRs of mind-body interventions for CP were included if they conducted a meta-analysis of depression outcomes in people with any CP type not including headache. Two independent reviewers screened, extracted, and evaluated the quality of articles found. Quality was assessed using the AMSTAR 2 criteria and data were summarized narratively with standardized mean differences and 95% confidence intervals of the depression outcome. RESULTS: Eleven SRs with 20 distinct meta-analyses demonstrated a small to moderate beneficial effect for mind-body interventions (effect sizes: -0.05 to -0.63). LIMITATIONS: Depressive symptomatology was a subordinate concern compared with other outcomes. The primary literature base was reasonably broad with 33 primary studies, but small when compared with the number of meta-analyses. CONCLUSIONS: Mind-body interventions show consistent small to moderate effects in reducing depressive symptoms in CP. The literature in this area demonstrates understudy and oversynthesis. There is a need for more clinical trials focusing on people with axial pain, people with comorbid major depressive disorder, and with depression as the primary outcome of interest. Full SR registered on PROSPERO: CRD42019131871. KEY WORDS: Mind-body, meditation, yoga, depression, chronic pain, umbrella review


2021 ◽  
Vol 9 ◽  
Author(s):  
Mads Andersen ◽  
Mette Vestergård Pedersen ◽  
Ted Carl Kejlberg Andelius ◽  
Kasper Jacobsen Kyng ◽  
Tine Brink Henriksen

Background: Studies have suggested that neurological outcome may differ in newborns with encephalopathy with and without perinatal infection. We aimed to systematically review this association.Methods: We conducted this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies were obtained from four databases including Pubmed, Embase, Web of Science, and The Cochrane Database. Newborns with encephalopathy with and without markers of perinatal infection were compared with regard to neurodevelopmental assessments, neurological disorders, and early biomarkers of brain damage. Risk of bias and quality of evidence were assessed by the Newcastle-Ottawa scale and Grading of Recommendations Assessment, Development and Evaluation (GRADE).Results: We screened 4,284 studies of which eight cohort studies and one case-control study met inclusion criteria. A narrative synthesis was composed due to heterogeneity between studies. Six studies were classified as having low risk of bias, while three studies were classified as having high risk of bias. Across all outcomes, the quality of evidence was very low. The neurological outcome was similar in newborns with encephalopathy with and without markers of perinatal infection.Conclusions: Further studies of higher quality are needed to clarify whether perinatal infection may affect neurological outcome following newborn encephalopathy.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42020185717.


2021 ◽  
Author(s):  
Alaa Abd-Alrazaq ◽  
Eiman Al-Jafar ◽  
Mohannad Alajlani ◽  
Carla Toro ◽  
Dari Alhuwail ◽  
...  

BACKGROUND Depression is a common mental disorder characterized by disturbances in mood, thoughts, and/or behaviors. Serious games, which are games that have a purpose other than entertainment, have been used as a non-pharmacological therapeutic intervention for depression. Previous systematic reviews have summarized evidence of effectiveness of serious games in reducing depression symptoms, however, they are limited by design and methodological shortcomings. OBJECTIVE This study aims to assess the effectiveness of serious games in alleviating depression through summarizing and pooling the results of previous studies. METHODS A systematic review of randomized controlled trials (RCTs) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search sources included 6 bibliographic databases (e.g., MEDLINE, PsycINFO, IEEE Xplore), the search engine “Google Scholar,” and backward and forward reference list checking of the included studies and relevant reviews. Two reviewers independently carried out the study selection, data extraction, risk of bias assessment, and quality of evidence appraisal. Results of the included studies were synthesized narratively and statistically, as appropriate, according to the type of serious games (i.e., exergames or computerized cognitive behavioral therapy (CBT) games). RESULTS From an initial 966 citations retrieved, 27 studies met the eligibility criteria. Fifteen were eventually included in meta-analyses. Very low quality evidence from 7 RCTs and 5 RCTs showed no statistically significant effect of exergames on the severity of depressive symptoms as compared to conventional exercises (P=0.12) and no intervention level (P=0.30), respectively. Very low quality evidence from 9 RCTs showed a statistically and clinically significant effect of computerized CBT games on the severity of depressive symptoms in comparison with no intervention (P=0.003). CONCLUSIONS Serious games have the potential to alleviate depression as other active interventions do. However, we could not draw definitive conclusions regarding the effectiveness of serious games due to the high risk of bias in the individual studies examined and the low quality of meta-analyzed evidence. Therefore, we recommend that health care providers consider offering serious games as an adjunct to existing interventions until further, more robust, evidence is available. Future studies should assess the effectiveness of serious games that are designed specifically to alleviate depression and deliver other therapeutic modalities, recruit participants with depression, and avoid biases through following recommended guidelines for conducting and reporting RCTs.


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