POSSIBLE CONFOUNDERS IN THE REPORTED ASSOCIATION BETWEEN AUTISM SPECTRUM DISORDER (ASD) AND EXPOSURE TO SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS) DURING PREGNANCY

2015 ◽  
Vol 101 (1) ◽  
pp. e1.16-e1
Author(s):  
Pauline De Bruyne ◽  
Eran Barzilay ◽  
Gideon Koren
Keyword(s):  
Risk Factors ◽  
Maternal Depression ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Causal Relation ◽  
Meta Analysis ◽  
Underlying Disease ◽  
Autism Spectrum ◽  
Care Seeking ◽  
Increased Risk ◽  
Health Care Seeking Behaviour

BackgroundAutism has been in the forefront of public concern because of reported increase in prevalence and growing interest in the role of environmental risk factors in autism. A recent meta-analysis by Man et al. (2015) reported an increased risk of ASD in children of mothers exposed to SSRIs during pregnancy (adjusted OR 1.81, 95% CI 1.47–2.24). However, association may not imply a causal relation between SSRI exposure and ASD. We hypothesize that underlying disease might have confounded the published result.Materials and methodsA literature review was performed in order to identify possible confounders in the reported association. The list of search terms included but was not limited to following terms: ‘Pregnancy', ‘maternal', ‘depression', ‘child behaviour', ‘health care seeking behaviour'.ResultsRetrieved articles were classified in following four domains of possible confounders: 1/ direct link between depression and ASD, 2/effect of depression on interaction with the child, 3/effect of depression on other risk factors of ASD and 4/ascertainment bias. In the last domain, we examined the effect of depression on the way mothers perceive and report on the behaviour of their child and the effect of maternal depression on healthcare seeking behaviour. Analysis suggests that there are important merits to all those four domains.ConclusionBecause of obvious ethical reasons, research on exposure during pregnancy is mostly restricted to systematic review and meta-analysis of observational studies. Although this has resulted in a treasury of information, possible confounders must be taken into account when interpreting the results.

scholarly journals Greater cardiorespiratory fitness reduces incidence of atrial fibrillation: a meta-analysis

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
C Verdicchio ◽  
A Elliott ◽  
R Mahajan ◽  
D Linz ◽  
D Lau ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Risk Factor ◽  
Cardiorespiratory Fitness ◽  
Meta Analysis ◽  
Exercise Stress ◽  
Inverse Association ◽  
Exercise Interventions ◽  
Increased Risk ◽  
Statistical Heterogeneity

Abstract Funding Acknowledgements Type of funding sources: None. Introduction  Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia affecting 1-2% of the global population, with the prevalence of AF increasing dramatically over the past two decades. Although low levels of cardiorespiratory fitness (CRF) and physical activity are predictive of cardiovascular disease onset and mortality, only recently has this emerged as a potential risk factor for AF. Purpose The aim of this meta-analysis was therefore to quantify the relationship between CRF, measured by a symptom limited exercise stress test, and incident AF. We hypothesised that there would be an inverse relationship between CRF and the incidence of AF. Methods The systematic literature review was conducted using PUBMED, MEDLINE and EMBASE databases, with seven studies meeting the inclusion criteria. A random-effects meta-analysis was then used to compare the multivariate risk estimates of the lowest CRF group from each cohort with the group of the highest CRF. Results Data from 206,925 individuals (55.8% males) was used for analysis with a mean age of 55 ± 2.5 years and a mean follow-up period of 10.3 ± 5 years. The total number of AF events across the studies was 19,913. The overall pooled risk of AF in the high-CRF group versus the low-CRF group showed a significant lower risk of incident AF in those with high-CRF (OR: 0.52, 95% CI, 0.44-0.605, p < 0.001). There was evidence of statistical heterogeneity between the studies (I2 = 81%, p < 0.001). AF incidence rates demonstrated an overall decline in rates across the CRF quartiles from low to high. The mean incidence rate for low-CRF was 21 ± 13.4 compared to 6.9 ± 0.7 per 1000 person-years for the high CRF group (p = 0.03). Conclusion There is an inverse association between a lower CRF and an increased risk of AF, with a higher level of CRF protective against AF. This study highlights that low-CRF may be an additional risk factor for AF along with already other established lifestyle-based risk factors such as obesity and hypertension. Exercise interventions should be promoted as a primary prevention strategy in those at risk of developing AF with known risk factors. Future studies are warranted to identify the mechanism(s) through which improved CRF confers a reduction in AF incidence. Abstract Figure. AF risk between high and low-CRF

scholarly journals Platelet function and cardiovascular risk in adult HIV-infected patients on HAART: a protocol for a systematic review and meta-analysis

BMJ Open ◽  
2017 ◽  
Vol 7 (12) ◽  
pp. e019468 ◽  
Author(s):  
Bongani Brian Nkambule ◽  
Zibusiso Mkandla ◽  
Tinashe Mutize ◽  
Phiwayinkosi Vusi Dludla
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Cardiovascular Risk ◽  
Platelet Activation ◽  
Meta Analysis ◽  
People Living With Hiv ◽  
Qualitative Synthesis ◽  
Cvd Risk ◽  
Increased Risk ◽  
Statistical Heterogeneity

IntroductionThe incidence of cardiovascular disease (CVD) is now at least threefold higher in HIV-infected patients as compared with the general population. Although platelet activation and reactivity are implicated in the development of CVDs in HIV-infected patients, its precise role remains inconclusive. We aim to assess the association between platelet activation and selected cardiovascular risk factors in HIV-1-infected individuals on highly active antiretroviral treatment (HAART).MethodsThis will be a systematic review and meta-analysis of published studies evaluating the association between platelet activation and CVD risk factors in HAART-treated adults. The search strategy will include medical subject headings words for MEDLINE, and this will be adapted to Embase search headings (Emtree) terms for the EMBASE database. The search will cover literature published between 1 January 1996 to 30 April 2017. Studies will be independently screened by two reviewers using predefined criteria. Relevant eligible full texts will be screened; data will be extracted, and a qualitative synthesis will be conducted. Data extraction will be performed using Review Manager V.5.3. To assess the quality and strengths of evidence across selected studies, the Grading of Recommendations Assessment Development and Evaluation approach will be used. The Cochran’s Q statistic and the I2statistics will be used to analyse statistical heterogeneity between studies. If included studies show high levels of homogeneity, a random effects meta-analysis will be performed using R statistical software.Ethics and disseminationThis will be a review of existing studies and will not require ethical approval. The findings will be disseminated through peer-reviewed publication and presented at local and international conferences. An emerging patient management dilemma is that of the increased incidence of CVD in people living with HIV on HAART. This review may inform treatment and cardiovascular risk stratification of HIV-infected patients at increased risk of developing CVD.PROSPERO registration numberCRD42017062393.

scholarly journals Investigating alexithymia in autism: A systematic review and meta-analysis

2019 ◽  
Vol 55 ◽  
pp. 80-89 ◽  
Author(s):  
Emma Kinnaird ◽  
Catherine Stewart ◽  
Kate Tchanturia
Keyword(s):  
Systematic Review ◽  
Emotional Processing ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Autistic People ◽  
Increased Risk ◽  
Popu Lations ◽  
Specific Subgroup ◽  
New Research ◽  
Meta Analyses

AbstractBackground:New research suggests that, rather than representing a core feature of autism spectrum disorder (ASD), emotional processing difficulties reflect co-occurring alexithymia. Autistic individuals with alexithymia could therefore represent a specific subgroup of autism who may benefit from tailored interventions. The aim of this systematic review and meta-analysis was to explore the nature and prevalence of alexithymia in autism using the Toronto Alexithymia Scale (TAS).Methods:Online scientific databases were searched systematically for studies on ASD popu lations using the TAS. Meta-analyses were performed to evaluate differences in scores between the ASD and neurotypical groups, and to determine the prevalence of alexithymia in these populations.Results:15 articles comparing autistic and neurotypical (NT) groups were identified. Autistic people scored significantly higher on all scores compared to the NT group. There was also a higher prevalence of alexithymia in the ASD group (49.93% compared to 4.89%), with a significantly increased risk of alexithymia in autistic participants.Conclusions:This review highlights that alexithymia is common, rather than universal, in ASD, supporting a growing body of evidence that co-occurring autism and alexithymia represents a specific subgroup in the ASD population that may have specific clinical needs. More research is needed to understand the nature and implications of co-occurring ASD and alexithymia.

scholarly journals Prevalence and impact of frailty in patients with atrial fibrillation: a systematic review and meta-analysis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Proietti ◽  
G.F Romiti ◽  
V Raparelli ◽  
I Diemberger ◽  
G Boriani ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Systematic Review ◽  
Meta Analysis ◽  
Frailty Index ◽  
Prevalence Odds Ratio ◽  
Frail Patients ◽  
Pooled Prevalence ◽  
Increased Risk ◽  
Inconsistency Index

Abstract Background Frailty is a clinical syndrome characterized by a reduced physiologic function, increased vulnerability to stressors, and an increased risk of adverse outcomes. Patients with Atrial Fibrillation (AF) are often burdened with a high number of comorbidities and prone to frailty. The prevalence of frailty, its management and association with major outcomes in patients with AF are still unclear. Purpose To estimate the pooled prevalence of frailty in patients with AF, as well as its association with AF-related risk factors and comorbidities, oral anticoagulants (OAC) prescription, and major outcomes. Methods We systematically searched PubMed and EMBASE, from inception to 31st January 2021, for studies reporting the prevalence of frailty (irrespective of the tool used for assessment). Pooled prevalence, odds ratio (OR), and 95% Confidence Intervals (CI) were computed using random-effect models; heterogeneity was assessed through the inconsistency index (I2). This study was registered in PROSPERO: CRD42021235854. Results A total of 1,116 studies were retrieved from the literature search, and 31 were finally included in the systematic review (n=842,521 patients). The frailty pooled prevalence was 39.6% (95% CI=29.2%-51.0%, I2=100%; Figure 1). Significant subgroup differences were observed according to geographical location (higher prevalence found in European-based cohorts; p=0.003) and type of tool used for the assessment (higher prevalence in studies using the Clinical Frailty Scale and Tilburg Frailty Index tools; p<0.001). Meta-regressions showed that study-level mean age and prevalence of hypertension, diabetes, and history of stroke were directly associated with frailty prevalence. Frailty was significantly associated with a 29% reduced probability of OAC prescription in observational studies (OR=0.71, 95% CI=0.62–0.81). Frail patients with AF were at higher risk of all-cause death (OR=4.12, 95% CI=3.15–5.41), ischemic stroke (OR=1.55, 95% CI=1.01–2.38), and bleeding (OR=1.55, 95% CI=1.12–2.14), compared to non-frail patients with AF. Conclusions In this systematic review and meta-analysis analysis, the prevalence of frailty was high in patients with AF, and associated with study-level mean age and prevalence of several stroke risk factors. Frailty may influence the management of patients, and worsening the prognosis for all major AF-related outcomes. FUNDunding Acknowledgement Type of funding sources: None. Prevalence of Frailty among AF patients

scholarly journals Primary CNS tumors in adults and environmental factors: an update

2020 ◽  
pp. 176-181
Author(s):  
S.G. Berntsson ◽  
Keyword(s):  
Risk Factors ◽  
Brain Tumor ◽  
Mobile Phone ◽  
Meta Analysis ◽  
Cns Tumors ◽  
Acoustic Neurinoma ◽  
Low Grade ◽  
Mobile Phone Use ◽  
Increased Risk

The incidence of adult primary brain tumors is increasing in some European countries. High-dose ionizing irradiation, rare genetic syndromes, and genetic predisposition in 5 % of families are a few established environmental risk factors for brain tumor. Mobile phone use that causes near brain exposure to radiofrequency electromagnetic waves and thus creates risks of CNS tumors has been the focus of many studies. Nine meta-analyses were available on this subject. The Interphone multi-center case-control study is the largest one to date; it included 2.708 glioma and 2.409 meningioma cases and matched controls in 13 countries. Studies exploring metals (cadmium, lead), pesticides, outdoor pollution, virus, and risk of glioma created by exposure to them were reviewed. Interphone study did not show increased risk of glioma or meningioma in mobile-phone users. One recent meta-analysis in 2017 found that prolonged exposure i.e.,> 10 years of all phone types was associated with increased risk of ipsilateral CNS tumor locations. In another meta-analysis, long-term use of mobile-phones was found to be a risk factor for low-grade glioma. In case of all durations regarding mobile phone use and both sides of the head, the results of pooling data were more discordant. A large prospective study in 2014 showed that long term use vs never use increased risks of acoustic neurinoma (10+ years: RR = 2.46, 95 % CI = 1.07–5.64, P = 0.03), but not of glioma or meningioma. Studies of other risk factors showed no/weak/contradictory association with brain tumor risk. In the absence of robust and consistent evidence, a causal relation between radiofrequency exposure and CNS tumors was not found. Large prospective studies of this kind regarding a disease with low incidence require a high number of participants and a long follow-up period.

Endemic Cryptosporidium infection and drinking water source: a systematic review and meta-analyses

2006 ◽  
Vol 54 (3) ◽  
pp. 231-238 ◽  
Author(s):  
F.A.S. Gualberto ◽  
L. Heller
Keyword(s):  
Risk Factors ◽  
Drinking Water ◽  
Meta Analysis ◽  
Water Source ◽  
Drinking Water Source ◽  
Cryptosporidium Infection ◽  
Water Users ◽  
Increased Risk ◽  
Unsafe Water ◽  
Meta Analyses

Cryptosporidium is a well-known cause of diarrhoea in humans. Little is known about risk factors associated with endemic cryptosporidiosis, which constitutes the majority of cases. We carried out meta-analyses to verify if drinking water is also associated with endemic infection and to assess the magnitude of the associations. The global meta-analysis suggests that there is an increased risk of Cryptosporidium infection among unsafe water users (OR 1.40 [1.15, 1.72]). Studies were stratified, according to the exposure to different sources of safe drinking water, due to the heterogeneity presented. The consumption of non-well and unboiled water was associated with an increased chance of endemic cryptosporidiosis, though only the latter was significant (OR 1.45 [0.95, 2.20]; OR 1.61 [1.09, 2.38]). Drinking non-bottled water did not present a risk factor associated with endemic cryptosporidiosis (OR 0.87 [0.72, 1.05]). These meta-analyses present results that could be useful to clarify the epidemiology of Cryptosporidium. We recommend that other risk factors could also be studied by this approach.

scholarly journals Risk factors for post-thyroidectomy haemorrhage: a meta-analysis

2017 ◽  
Vol 176 (5) ◽  
pp. 591-602 ◽  
Author(s):  
Jinhao Liu ◽  
Wei Sun ◽  
Wenwu Dong ◽  
Zhihong Wang ◽  
Ping Zhang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Neck Dissection ◽  
Thyroid Surgery ◽  
Meta Analysis ◽  
Older Age ◽  
Graves Disease ◽  
Malignant Tumours ◽  
Antithrombotic Agents ◽  
Increased Risk ◽  
Male Sex

BackgroundPost-thyroidectomy haemorrhage is a rare but potentially life-threatening and unpredictable complication of thyroid surgery. In this study, we analysed the potential risk factors for the occurrence of post-thyroidectomy haemorrhage.MethodsThe PubMed and SCIE databases were comprehensively searched for studies published before June 30, 2016. Studies on patients who underwent an open thyroidectomy with or without neck dissection were included, and RevMan 5.3 software was used to analyse the data.ResultsTwenty-five studies and 424 563 patients were included in this meta-analysis, and post-thyroidectomy haemorrhage occurred in 6277 patients (incidence rate = 1.48%). The following variables were associated with an increased risk of post-thyroidectomy haemorrhage: older age (MD = 4.30, 95% CI = 3.09–5.52,P < 0.00001), male sex (OR = 1.73, 95% CI = 1.54–1.94,P < 0.00001), Graves’ disease (OR = 1.76, 95% CI = 1.44–2.15,P < 0.00001), antithrombotic agents use (OR = 1.96, 95% CI 1.55–2.49,P < 0.00001), bilateral operation (OR = 1.71, 95% CI = 1.50–1.96,P < 0.00001), neck dissection (OR = 1.53, 95% CI = 1.11–2.11,P = 0.01) and previous thyroid surgery (OR = 1.62, 95% CI = 1.12–2.34,P = 0.01). Malignant tumours (OR = 1.07, 95% CI = 0.89–1.28,P = 0.46) and drainage device use (OR = 1.27, 95% CI = 0.74–2.18,P = 0.4) were not associated with post-thyroidectomy haemorrhage.ConclusionOur systematic review identified a number of risk factors for post-thyroidectomy haemorrhage, including older age, male sex, Graves’ disease, antithrombotic agents use, bilateral operation, neck dissection and previous thyroid surgery. Early control of modifiable risk factors could improve patient outcomes and satisfaction.

scholarly journals Clinical Characteristics and Outcomes of COVID-19–Infected Cancer Patients: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Hua Zhang ◽  
Han Han ◽  
Tianhui He ◽  
Kristen E Labbe ◽  
Adrian V Hernandez ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Case Fatality Rate ◽  
Meta Analysis ◽  
Univariate Analysis ◽  
Case Fatality ◽  
The United States ◽  
Fatality Rate ◽  
Patients With Cancer ◽  
Increased Risk

Abstract Background Previous studies have indicated coronavirus disease 2019 (COVID-19) patients with cancer have a high fatality rate. Methods We conducted a systematic review of studies that reported fatalities in COVID-19 patients with cancer. A comprehensive meta-analysis that assessed the overall case fatality rate and associated risk factors was performed. Using individual patient data, univariate and multivariable logistic regression analyses were used to estimate odds ratios (OR) for each variable with outcomes. Results We included 15 studies with 3019 patients, of which 1628 were men; 41.0% were from the United Kingdom and Europe, followed by the United States and Canada (35.7%), and Asia (China, 23.3%). The overall case fatality rate of COVID-19 patients with cancer measured 22.4% (95% confidence interval [CI] = 17.3% to 28.0%). Univariate analysis revealed age (OR = 3.57, 95% CI = 1.80 to 7.06), male sex (OR = 2.10, 95% CI = 1.07 to 4.13), and comorbidity (OR = 2.00, 95% CI = 1.04 to 3.85) were associated with increased risk of severe events (defined as the individuals being admitted to the intensive care unit, or requiring invasive ventilation, or death). In multivariable analysis, only age greater than 65 years (OR = 3.16, 95% CI = 1.45 to 6.88) and being male (OR = 2.29, 95% CI = 1.07 to 4.87) were associated with increased risk of severe events. Conclusions Our analysis demonstrated that COVID-19 patients with cancer have a higher fatality rate compared with that of COVID-19 patients without cancer. Age and sex appear to be risk factors associated with a poorer prognosis.

scholarly journals High BMI and Insulin Resistance Are Risk Factors for Spontaneous Abortion in Patients With Polycystic Ovary Syndrome Undergoing Assisted Reproductive Treatment: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 11 ◽  
Author(s):  
Yi-Fei Sun ◽  
Jie Zhang ◽  
Yue-Ming Xu ◽  
Zi-Yu Cao ◽  
Yi-Zhuo Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Spontaneous Abortion ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Abortion Rate ◽  
Ovary Syndrome ◽  
Assisted Reproductive Treatment ◽  
Increased Risk ◽  
High Bmi

BackgroundThe risk of spontaneous abortion in patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive treatment (ART) is higher than that in patients without PCOS, however, no definitive risk factors have been confirmed to associate with the high spontaneous abortion rate in PCOS patients undergoing ART. This study was performed to assess the impact of relevant risk factors on spontaneous abortion in patients with PCOS. Clinical questions were formulated and organized according to the PICOS principle.MethodsA systematic review and meta-analysis were conducted on all published studies on PCOS and spontaneous abortion in Embase, PubMed, Web of Science and Cochrane Library. Related risk factors included body mass index (BMI), age, insulin resistance (IR), hyperandrogenism, and chromosome aberrations. All patients were diagnosed as PCOS using the Rotterdam criteria. The primary endpoint was miscarriage and live birth rate. Fixed-effect models were used to analyze homogeneous data, and subgroup and sensitivity analyses were performed on heterogeneous data. The source of heterogeneity was evaluated, and the random effect model was used to summarize the heterogeneity.ResultsAmong 1836 retrieved articles, 22 were eligible and included in the analysis with 11182 patients. High BMI (OR = 1.48, 95% CI [1.32, 1.67], MD = 1.35, 95% CI [0.58,2.12]) and insulin resistance (MD = 0.32, 95% CI [0.15, 0.49]) were associated with an increased risk of spontaneous abortion in PCOS patients undergoing ART. Older age (OR = 0.29, 95% CI [0.29, 0.44], MD = 2.01, 95% CI [0.04, 4.18]), embryonic chromosomal aberrations (OR = 0.75, 95%CI [0.31,1.77]), and hyperandrogenism (MD = 0.10, 95% CI [- 0.02, 0.22]) were not associated with the high spontaneous abortion rate in patients with PCOS. A subgroup analysis of BMI showed that there was no statistically significant difference in the effect between overweight and obesity on spontaneous abortion in PCOS patients undergoing ART (OR = 1.34, 95% [0.97, 1.85]).ConclusionHigh BMI and insulin resistance are two risk factors for an increased risk of spontaneous abortion in PCOS patients undergoing ART, and losing weight and mitigating insulin resistance may decrease the spontaneous abortion rate in these patients undergoing ART.

Lifestyle and sociodemographic risk factors for gastroschisis: a systematic review and meta-analysis

2020 ◽  
Vol 105 (8) ◽  
pp. 756-764 ◽  
Author(s):  
Silvia Baldacci ◽  
Michele Santoro ◽  
Alessio Coi ◽  
Lorena Mezzasalma ◽  
Fabrizio Bianchi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Illicit Drugs ◽  
Meta Analysis ◽  
Genetic Risk Factors ◽  
Epidemiological Studies ◽  
Black Mothers ◽  
Increased Risk ◽  
Sociodemographic Risk ◽  
Meta Analyses

BackgroundGastroschisis is strongly associated with young maternal age. This association suggests the need for further investigations on non-genetic risk factors. Identifying these risk factors is a public health priority in order to develop prevention strategies aimed at reducing the prevalence and health consequences in offspring.ObjectiveTo systematically assess and quantitatively synthesise the available epidemiological studies to evaluate the association between non-genetic risk factors and gastroschisis.MethodsLiterature from PubMed, EMBASE and Scopus was searched for the period 1990–2018. Epidemiological studies reporting risk estimates between lifestyle and sociodemographic risk factors and gastroschisis were included. Two pairs of reviewers independently extracted information on study characteristics following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and MOOSE (Meta-analysis Of Oservational Studies in Epidemiology) guidelines. Relative risk (RR) estimates were calculated across the studies and meta-analysis was performed using random-effects model.ResultsWe identified 58 studies. Meta-analyses were conducted on 29 studies. Maternal smoking (RR 1.56, 95% CI 1.40 to 1.74), illicit drug use (RR 2.14, 95% CI 1.48 to 3.07) and alcohol consumption (RR 1.40, 95% CI 1.13 to 1.70) were associated with an increased risk of gastroschisis. A decreased risk among black mothers compared with non-Hispanic white mothers (RR 0.49, 95% CI 0.38 to 0.63) was found. For Hispanic mothers no association was observed.ConclusionsExposure to smoking, illicit drugs and alcohol during pregnancy is associated with an increased risk of gastroschisis. A significantly decreased risk for black mothers was observed. Further epidemiological studies to assess the potential role of other environmental factors are strongly recommended.PROSPERO registration numberCRD42018104284.

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