Variation of effect estimates in the analysis of mortality and length of hospital stay in patients with infections caused by bacteria-producing extended-spectrum beta-lactamases: a systematic review and meta-analysis

ObjectiveTo assess the variation of effect estimates in the analysis of mortality and length of stay (LOS) in patients with infections caused by extended-spectrum beta-lactamase (ESBL)-producingEnterobacteriaceae.DesignSystematic review and meta-analysisMethodsLiterature search for clinical studies from 1 January 1960 to 1 October 2018 was conducted in PubMed. Primary outcomes were risk ratios (RRs) of all-cause and attributable mortality and weighted mean differences (WMDs) in LOS in patients with bloodstream infections (BSIs) and non-invasive infections. Any change in the effect estimates was assessed by grouping studies according to design, setting, economy-based country classification, reporting period, microbiological aetiology, infection type and adjustment for appropriateness of empirical treatment. The impact of ESBL production was calculated using random-effect meta-analysis and heterogeneity was evaluated by I2statistics and metaregression.ResultsEighty-four studies including 22 030 patients and 149 outcome measures were included in the meta-analysis. Most studies were retrospective cohorts from high-income countries, providing unadjusted estimates. ESBL production in patients with BSIs (56 studies) increased the RR for all-cause mortality by a factor of 1.70 (95% CI 1.52 to 1.90; p<0.001), attributable mortality (16 studies) by 1.75 (95% CI 1.448 to 2.108; p<0.001) and WMD in the intensive care unit by 3.07 days (95% CI 1.61 to 4.54; p<0.001). WMD in hospital LOS was significantly higher in BSIs (4.41 days; 95% CI 3.37 to 5.46; p<0.001) and non-invasive (2.19 days; 95% CI 1.56 to 2.81; p<0.001). Subgroup analyses showed variation of estimates by study design, population, strain and assessment of appropriateness of empiric treatment. High heterogeneity was observed in all analyses.ConclusionsCurrent evidence of the clinical burden of infections caused by ESBL-producing bacteria is highly heterogeneous and based mainly on unadjusted estimates derived from retrospective studies. Despite these limitations, ESBL production in strains causing BSIs seems associated with higher all-cause and attributable mortality and longer hospitalisation.

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Effect of garlic intake on inflammatory mediators: a systematic review and meta-analysis of randomised controlled trials

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2019-137267 ◽

2020 ◽

pp. postgradmedj-2019-137267

Author(s):

Mehdi Koushki ◽

Nasrin Amiri-Dashatan ◽

Yasin Pourfarjam ◽

Amir Hossein Doustimotlagh

Keyword(s):

Systematic Review ◽

Inflammatory Mediators ◽

Metabolic Diseases ◽

Meta Analysis ◽

Random Effect ◽

Sensitivity Analyses ◽

Current Evidence ◽

Cochrane Library ◽

Tnf Α ◽

The Impact

BackgroundGarlic is a species in the onion genus, Allium. Data have shown that garlic has anti-inflammatory activity; however, the findings are inconclusive and inconsistent. We aimed to evaluate the impact of garlic intake on inflammatory mediators through systematic review and meta-analysis of existing data.MethodsElectronic databases were completely investigated using databases of ISI Web of Science, Medline, Scopus, Cochrane Library and EMBASE until October 2019. A random effects model and the generic reverse variance procedure were used for quantitative data production. Sensitivity analyses and prespecified subgroup were done to evaluate potential heterogeneity. Random effect meta-regression was conducted to investigate the effects of possible confounders on the assessed effect size.ResultsTen trials with one observational study, including 530 participants, met the eligibility criteria. The findings showed reduction in the tumour necrosis factor alpha (TNF-α) (−0.31 pg/mL, 95% CI −1.07 to 0.46) and C reactive protein (CRP) levels (−0.20 mg/L, 95% CI −1.4 to 1.05) following supplementation with garlic, although it had no marked impact on the interleukin 6 (IL-6) level (0.37 pg/mL, 95% CI −0.58 to 1.33). In the subgroup analysis, we found that garlic supplementation significantly decreased TNF-α, highly sensitive CRP and IL-6 levels in subgroups of >8, >6 and ≥4 weeks of intervention duration, respectively, and dose of garlic consumption between 2 and 2.4 g/day.ConclusionThese findings suggested that current evidence may support garlic as an adjunct to pharmacological management of metabolic diseases.PROSPERO registration numberCRD42018108816.

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The Atrial Fibrillation Better Care (ABC) pathway in atrial fibrillation: a systematic review and meta-analysis of 285,000 patients

EP Europace ◽

10.1093/europace/euab116.290 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

GF Romiti ◽

D Pastori ◽

JM Rivera-Caravaca ◽

WY Ding ◽

YX Gue ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Clinical Outcomes ◽

Major Bleeding ◽

Meta Analysis ◽

Random Effect ◽

Significant Proportion ◽

Cardiovascular Death ◽

Current Evidence ◽

Meta Regression

Abstract Funding Acknowledgements Type of funding sources: None. Background The ‘Atrial Fibrillation Better Care’ (ABC) pathway has been recently proposed as a holistic approach for the comprehensive management of patients with Atrial Fibrillation (AF), standing on three main pillars: ‘A’ Avoid stroke (with Anticoagulants); ‘B’ Better symptom management; ‘C’ Cardiovascular and Comorbidity management. The ABC pathway is now recommended in several clinical guidelines, including the recent European Society of Cardiology (ESC) AF management guidelines. We performed a systematic review of the current evidence for use of the ABC pathway on clinical outcomes. Methods We performed a systematic review and meta-analysis according to PRISMA Guidelines. Pubmed and EMBASE were searched for studies reporting the prevalence of ABC pathway adherent management in AF patients, and its impact on clinical outcomes (all-cause death, cardiovascular death, stroke, and major bleeding). Metanalysis of odds ratio (OR) was performed with random-effect models; subgroup analysis and meta-regression were performed to account for heterogeneity; a CHA2DS2-VASc-stratified sensitivity analysis was also performed. Results Among 2862 records retrieved from the literature search, 8 studies were included. The pooled prevalence of ABC adherent management was 21% (95% confidence intervals (CI), 13-34%), with a high grade of heterogeneity; in a multivariable meta-regression model, adherence to each criteria of the ABC pathway explained most part of the heterogeneity (R2 = 98.9%). Patients treated according to the ABC pathway showed a lower risk of all-cause death (OR:0.42, 95%CI 0.31-0.56), cardiovascular death (OR:0.37, 95%CI 0.23-0.58), stroke (OR:0.55, 95%CI 0.37-0.82) and major bleeding (OR:0.69, 95%CI 0.51-0.94), with moderate heterogeneity. Meta-regressions showed that the increasing prevalence of diabetes mellitus, coronary artery disease, chronic heart failure and history of stroke were associated with a reduced effectiveness of the ABC pathway for all-cause and cardiovascular death; each comorbidity was able to explain a significant proportion of heterogeneity at univariate meta-regression. Conversely, longer follow-up time was associated with more effectiveness of the ABC pathway for all outcomes. Adherence to ABC pathway was associated with a progressively greater reduction of the all-cause death risk amongst patients with higher CHA2DS2-VASc scores; no difference in ABC pathway effectiveness was found across CHA2DS2-VASc strata for CV death and stroke occurrence. Conclusions Adherence to the ABC pathway was suboptimal, being adopted in 1 in every 5 patients. Adherence to the ABC pathway was associated with a reduction in the risk of major adverse outcomes. Our data supports extensive application of the ABC pathway for the management of AF. Abstract Figure.

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The Effect of Anakinra in Hospitalized Patients with COVID-19: An Updated Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10194462 ◽

2021 ◽

Vol 10 (19) ◽

pp. 4462

Author(s):

Konstantinos G. Kyriakoulis ◽

Anastasios Kollias ◽

Garyphallia Poulakou ◽

Ioannis G. Kyriakoulis ◽

Ioannis P. Trontzas ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Interleukin 1 ◽

Severe Pneumonia ◽

Hospitalized Patients ◽

Current Evidence ◽

Adjusted Risk ◽

Risk Of Death ◽

The Impact

The role of immunomodulatory agents in the treatment of hospitalized patients with COVID-19 has been of increasing interest. Anakinra, an interleukin-1 inhibitor, has been shown to offer significant clinical benefits in patients with COVID-19 and hyperinflammation. An updated systematic review and meta-analysis regarding the impact of anakinra on the outcomes of hospitalized patients with COVID-19 was conducted. Studies, randomized or non-randomized with adjustment for confounders, reporting on the adjusted risk of death in patients treated with anakinra versus those not treated with anakinra were deemed eligible. A search was performed in PubMed/EMBASE databases, as well as in relevant websites, until 1 August 2021. The meta-analysis of six studies that fulfilled the inclusion criteria (n = 1553 patients with moderate to severe pneumonia, weighted age 64 years, men 66%, treated with anakinra 50%, intubated 3%) showed a pooled hazard ratio for death in patients treated with anakinra at 0.47 (95% confidence intervals 0.34, 0.65). A meta-regression analysis did not reveal any significant associations between the mean age, percentage of males, mean baseline C-reactive protein levels, mean time of administration since symptoms onset among the included studies and the hazard ratios for death. All studies were considered as low risk of bias. The current evidence, although derived mainly from observational studies, supports a beneficial role of anakinra in the treatment of selected patients with COVID-19.

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PIK3CA Mutations and Their Impact on Survival Outcomes of Patients with Cervical Cancer: A Systematic Review

Acta Cytologica ◽

10.1159/000509095 ◽

2020 ◽

Vol 64 (6) ◽

pp. 547-555

Author(s):

Vasilios Pergialiotis ◽

Christina Nikolaou ◽

Dimitrios Haidopoulos ◽

Maximos Frountzas ◽

Nikolaos Thomakos ◽

...

Keyword(s):

Systematic Review ◽

Cervical Cancer ◽

Cancer Progression ◽

Meta Analysis ◽

Current Evidence ◽

Survival Outcomes ◽

Cochrane Central Register ◽

Wild Type ◽

Pik3ca Mutations ◽

The Impact

Introduction: Several studies have implicated the PIK3/AKT pathway in the pathophysiology of cancer progression as its activation seems to be aberrant in several forms of cancer. The purpose of the present systematic review is to evaluate the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer. Methods: We used the Medline (1966–2020), Scopus (2004–2020), ClinicalTrials.gov (2008–2020), EMBASE (1980–2020), Cochrane Central Register of Controlled Trials (CENTRAL) (1999–2020), and Google Scholar (2004–2020) databases in our primary search along with the reference lists of electronically retrieved full-text papers. Statistical meta-analysis was performed with the RevMan 5.3 software. Results: Overall, 12 articles were included in the present study that comprised 2,196 women with cervical cancer. Of those, 3 studies did not report significant differences in survival outcomes among patients with mutated versus wild-type PIK3CA tumors, 5 studies reported decreased survival outcomes, and 3 studies revealed increased survival rates. The meta-analysis revealed that patients with the mutated PIK3CA genotypes had worse overall survival compared to patients with wild-type PIK3CA (HR 2.31; 95% CI: 1.51, 3.55; 95% PI: 0.54, 9.96; data from 3 studies) and the same was observed in the case of DFS rates (HR 1.82; 95% CI: 1.47, 2.25; 95% PI: 1.29, 2.56; data from 4 studies). Conclusion: Current evidence concerning the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer is inconclusive, although the majority of included studies support a potential negative effect, primarily among those with squamous cell carcinoma tumors.

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The effect of ageing on presentation, management and outcomes in degenerative cervical myelopathy: a systematic review

Age and Ageing ◽

10.1093/ageing/afaa236 ◽

2020 ◽

Author(s):

Ben Grodzinski ◽

Rory Durham ◽

Oliver Mowforth ◽

Daniel Stubbs ◽

Mark R N Kotter ◽

...

Keyword(s):

Systematic Review ◽

Functional Status ◽

Cervical Myelopathy ◽

Older Patients ◽

Meta Analysis ◽

Current Evidence ◽

Clinical Aspects ◽

Similar Amount ◽

Degenerative Cervical Myelopathy ◽

The Impact

Abstract Objective Degenerative cervical myelopathy (DCM) is a disabling neurological condition. The underlying degenerative changes are known to be more common with age, but the impact of age on clinical aspects of DCM has never been synthesised. The objective of this study is to determine whether age is a significant predictor in three domains—clinical presentation, surgical management and post-operative outcomes of DCM. Methods a systematic review of the Medline and Embase databases (inception to 12 December 2019), registered with PROSPERO (CRD42019162077) and reported in accordance with preferred reporting items of systematic reviews and meta-analysis (PRISMA) guidelines, was conducted. The inclusion criteria were full text articles in English, evaluating the impact of age on clinical aspects of DCM. Results the initial search yielded 2,420 citations, of which 206 articles were eventually included. Age was found to be a significant predictor in a variety of measures. Within the presentation domain, older patients have a worse pre-operative functional status. Within the management domain, older patients are more likely to undergo posterior surgery, with more levels decompressed. Within the outcomes domain, older patients have a worse post-operative functional status, but a similar amount of improvement in functional status. Because of heterogenous data reporting, meta-analysis was not possible. Conclusion the current evidence demonstrates that age significantly influences the presentation, management and outcomes of DCM. Although older patients have worse health at all individual timepoints, they experience the same absolute benefit from surgery as younger patients. This finding is of particular relevance when considering the eligibility of older patients for surgery.

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Length of stay, cost, and mortality of healthcare-acquired bloodstream infections in children and neonates: A systematic review and meta-analysis

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2019.353 ◽

2020 ◽

Vol 41 (3) ◽

pp. 342-354 ◽

Cited By ~ 1

Author(s):

Sofia Karagiannidou ◽

Christos Triantafyllou ◽

Theoklis E. Zaoutis ◽

Vassiliki Papaevangelou ◽

Nikolaos Maniadakis ◽

...

Keyword(s):

Systematic Review ◽

Mortality Rate ◽

Length Of Stay ◽

Healthcare Cost ◽

Meta Analysis ◽

Random Effect ◽

Bloodstream Infections ◽

Attributable Mortality ◽

Study Selection ◽

Critical Appraisal Skills

AbstractObjective:To estimate the attributable mortality, length of stay (LOS), and healthcare cost of pediatric and neonatal healthcare-acquired bloodstream infections (HA-BSIs).Design:A systematic review and meta-analysis.Methods:A systematic search (January 2000–September 2018) was conducted in PubMed, Cochrane, and CINAHL databases. Reference lists of selected articles were screened to identify additional studies. Case–control or cohort studies were eligible for inclusion when full text was available in English and data for at least 1 of the following criteria were provided: attributable or excess LOS, healthcare cost, or mortality rate due to HA-BSI. Study quality was evaluated using the Critical Appraisal Skills Programme Tool (CASP). Study selection and quality assessment were conducted by 2 independent researchers, and a third researcher was consulted to resolve any disagreements. Fixed- or random-effect models, as appropriate, were used to synthesize data. Heterogeneity and publication bias were evaluated.Results:In total, 21 studies were included in the systematic review and 13 studies were included in the meta-analysis. Attributable mean LOS ranged between 4 and 27.8 days; healthcare cost ranged between $1,642.16 and $160,804 (2019 USD) per patient with HA-BSI; and mortality rate ranged between 1.43% and 24%. The pooled mean attributable hospital LOS was 16.91 days (95% confidence interval [CI], 13.70–20.11) and the pooled attributable mortality rate was 8% (95% CI, 6–9). A meta-analysis was not conducted for cost due to lack of eligible studies.Conclusions:Pediatric HA-BSIs have a significant impact on mortality, LOS, and healthcare cost, further highlighting the need for implementation of HA-BSI prevention strategies.

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Long-Term Growth in Phenylketonuria: A Systematic Review and Meta-Analysis

Nutrients ◽

10.3390/nu11092070 ◽

2019 ◽

Vol 11 (9) ◽

pp. 2070 ◽

Cited By ~ 1

Author(s):

Fatma Ilgaz ◽

Alex Pinto ◽

Hülya Gökmen-Özel ◽

Julio César Rocha ◽

Esther van Dam ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Normal Growth ◽

Optimal Growth ◽

Current Evidence ◽

Eligibility Criteria ◽

Dietary Practices ◽

Dietary Treatments ◽

The Impact

There is an ongoing debate regarding the impact of phenylketonuria (PKU) and its treatment on growth. To date, evidence from studies is inconsistent, and data on the whole developmental period is limited. The primary aim of this systematic review was to investigate the effects of a phenylalanine (Phe)-restricted diet on long-term growth in patients with PKU. Four electronic databases were searched for articles published until September 2018. A total of 887 results were found, but only 13 articles met eligibility criteria. Only three studies had an adequate methodology for meta-analysis. Although the results indicate normal growth at birth and during infancy, children with PKU were significantly shorter and had lower weight for age than reference populations during the first four years of life. Impaired linear growth was observed until the end of adolescence in PKU. In contrast, growth impairment was not reported in patients with mild hyperphenylalaninemia, not requiring dietary restriction. Current evidence indicates that even with advances in dietary treatments, “optimal” growth outcomes are not attained in PKU. The majority of studies include children born before 1990s, so further research is needed to show the effects of recent dietary practices on growth in PKU.

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The Impact of Enhanced Recovery After Surgery on Total Joint Arthroplasty: Protocol for a Systematic Review and Meta-analysis

JMIR Research Protocols ◽

10.2196/25581 ◽

2021 ◽

Vol 10 (3) ◽

pp. e25581

Author(s):

Siddharth Rele ◽

Cade Shadbolt ◽

Chris Schilling ◽

Nicholas F Taylor ◽

Michelle M Dowsey ◽

...

Keyword(s):

Systematic Review ◽

Health Service ◽

Enhanced Recovery ◽

Enhanced Recovery After Surgery ◽

Recovery Of Function ◽

Meta Analysis ◽

Current Evidence ◽

Cochrane Library ◽

Economic Evaluations ◽

The Impact

Background The number of total joint arthroplasties (TJAs) being performed is increasing worldwide. To match this increasing demand, there has been focus on hastening patients’ recovery of function. This effort has culminated in the formulation of enhanced recovery after surgery (ERAS) strategies. However, with evolving ERAS programs and new recommendations, a review of current evidence is required to provide clinicians with up-to-date information about its effect on outcomes for TJA. Objective The objective of this study is to assess the utility of ERAS programs on patient, health service, and economic outcomes for primary, elective total hip arthroplasty (THA) and total knee arthroplasty (TKA). Methods A systematic search will be conducted in Medline (Ovid), EMCARE (Ovid), EMBASE (Ovid), Web of Science, CINAHL, National Health Service Economic Evaluations Database, and the Cochrane Library. Analytical, observational, and experimental designs will be included in this systematic review. Only studies including patients undergoing primary TKA and THA comparing ERAS programs with conventional surgery and postoperative care will be included. Data related to patient outcomes, health service outcomes, safety, and economic evaluation will be extracted. Results The search terms and primary database searches have been finalized. Findings will be reported in narrative and tabular form. Where appropriate, random effects meta-analyses will be conducted for each outcome, and heterogeneity quantified with Cochran Q test and I2 statistic. Measures of effect or mean differences will be reported with 95% confidence intervals. The results of this systematic review will be disseminated in a peer-reviewed journal. Conclusions This protocol will guide a systematic review assessing outcomes associated with ERAS surgery in primary THA and TKA. Trial Registration Open Science Framework osf.io/y4bhs; https://osf.io/y4bhs International Registered Report Identifier (IRRID) PRR1-10.2196/25581

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Recruitment and retention of fathers with young children in early childhood health intervention research: a systematic review and meta-analysis protocol

Systematic Reviews ◽

10.1186/s13643-019-1215-1 ◽

2019 ◽

Vol 8 (1) ◽

Author(s):

Elizabeth M. Keys ◽

Jill M. Norris ◽

Emily E. Cameron ◽

Katherine S. Bright ◽

Lianne M. Tomfohr-Madsen ◽

...

Keyword(s):

Systematic Review ◽

Early Childhood ◽

Meta Analysis ◽

Intervention Research ◽

Current Evidence ◽

Retention Strategies ◽

Childhood Health ◽

Recruitment And Retention ◽

Early Childhood Health ◽

The Impact

Abstract Background Fathers are under-represented in research and programs addressing early childhood health and development. Recruiting fathers into these interventions can be hampered for multiple reasons, including recruitment and retention strategies that are not tailored for fathers. The primary aim of this systematic review and meta-analysis is to determine the effectiveness of recruitment and retention strategies used to include fathers of children (from conception to age 36 months) in intervention studies. The secondary aim is to investigate study-level factors that may influence recruitment and retention. Methods We will conduct searches for scholarly peer-reviewed randomized controlled trials, quasi-experimental studies, and pre-post studies that recruited fathers using the following databases: MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), and CINAHL. English-language articles will be eligible if they recruited self-identified fathers of children from conception to age 36 months for health-promoting interventions that target healthy parents and children. Two reviewers will independently screen titles/abstracts and full texts for inclusion, as well as grading methodological quality. Recruitment and retention proportions will be calculated for each study. Where possible, we will calculate pooled proportional effects with 95% confidence intervals using random-effects models and conduct a meta-regression to examine the impact of potential modifiers of recruitment and retention. Discussion Findings from this review will help inform future intervention research with fathers to optimally recruit and retain participants. Identifying key factors should enable health researchers and program managers design and adapt interventions to increase the likelihood of increasing father engagement in early childhood health interventions. Researchers will be able to use this review to inform future research that addresses current evidence gaps for the recruitment and retention of fathers. This review will make recommendations for addressing key target areas to improve recruitment and retention of fathers in early childhood health research, ultimately leading to a body of evidence that captures the full potential of fathers for maximizing the health and wellbeing of their children. Systematic review registration PROSPERO CRD42018081332.

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Epidemiology and aetiologies of cryptococcal meningitis in Africa, 1950–2017: protocol for a systematic review

BMJ Open ◽

10.1136/bmjopen-2017-020654 ◽

2018 ◽

Vol 8 (7) ◽

pp. e020654 ◽

Cited By ~ 5

Author(s):

Tinashe K Nyazika ◽

Joseph Kamtchum Tatuene ◽

Alain Kenfak-Foguena ◽

Paul E Verweij ◽

Jacques F Meis ◽

...

Keyword(s):

Systematic Review ◽

Cryptococcal Meningitis ◽

Data Extraction ◽

Meta Analysis ◽

Random Effect ◽

Epidemiological Data ◽

Incidence Density ◽

Final Report ◽

Quality Of Reporting ◽

The Impact

IntroductionCryptococcal meningitis is a neglected disease and an AIDS-defining illness, responsible for 15% of all AIDS-related deaths globally. In 2014, the estimated number of incident cryptococcal meningitis cases was 223 100, with 73% of them occurring in Africa. Currently available data on the prevalence, incidence, aetiologies and mortality of cryptococcal meningitis across Africa are sparse and of limited quality. We propose to conduct the first systematic review to summarise the epidemiological data available on cryptococcal meningitis and its aetiological causes in Africa.Methods and analysisWe will search PubMed, MEDLINE, Excerpta Medica Database, ISI Web of Science, Africa Index Medicus, Cumulative Index to Nursing and Allied Health for studies on cryptococcal meningitis published between 1st January 1950 and 31st December 2017, involving adults and/or children residing in Africa. After study selection, full text paper acquisition and data extraction, we will use validated tools and checklists to assess the quality of reporting and risk of bias for each study. Heterogeneity across studies will be assessed using the χ2test on Cochrane’s Q statistic and a random effect meta-analysis will be used to estimate the overall prevalence, incidence density and mortality of cryptococcal meningitis across studies with similar characteristics. This protocol is prepared and presented in accordance with the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Reporting of the results will be compliant with the Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) guidelines.Ethics and disseminationThere is no requirement for ethical approval since we will be using data from published studies. The final report will be published in a peer-reviewed journal and further presented at conferences. This study is expected to provide useful contextual estimates needed to inform treatment policies on the African continent and assess the impact of diagnostic and prevention strategies on the burden of cryptococcal meningitis in the post antiretroviral therapy era.PROSPERO registration numberCRD42017081312.

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