Host blood transcriptomic biomarkers of tuberculosis disease in people living with HIV: a systematic review protocol.

INTRODUCTION: Current tuberculosis triage and predictive tools offer poor accuracy and are ineffective for detecting asymptomatic disease in people living with HIV (PLHIV). Host tuberculosis transcriptomic biomarkers hold promise for diagnosing prevalent and predicting progression to incident tuberculosis and guiding further investigation, preventive therapy and follow-up. We aim to conduct a systematic review of performance of transcriptomic signatures of tuberculosis in PLHIV. METHODS AND ANALYSIS: We will search MEDLINE (PubMed), WOS Core Collection, Biological Abstracts, and SciELO Citation Index (Web of Science), Africa-Wide Information and General Science Abstracts (EBSCOhost), Scopus, and Cochrane Central Register of Controlled Trials databases for articles published in English between 1990 and 2020. Case-control, cross-sectional, cohort and randomised controlled studies evaluating performance of diagnostic and prognostic host-response transcriptomic signatures in PLHIV of all ages and settings will be included. Eligible studies will include PLHIV in signature test or validation cohorts, and use microbiological, clinical, or composite reference standards for pulmonary or extrapulmonary tuberculosis diagnosis. Study quality will be evaluated using the 'Quality Assessment of Diagnostic Accuracy Studies-2' tool and cumulative review evidence assessed using the 'Grading of Recommendations Assessment, Development and Evaluation' approach. Study selection, quality appraisal and data extraction will be performed independently by two reviewers. Study, cohort and signature characteristics of included studies will be tabulated, and a narrative synthesis of findings presented. Primary outcomes of interest, biomarker sensitivity and specificity with estimate precision, will be summarised in forest plots. Expected heterogeneity in signature characteristics, study settings, and study designs precludes meta-analysis and pooling of results. Review reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies guidelines. ETHICS AND DISSEMINATION: Formal ethics approval is not required as primary human participant data will not be collected. Results will be disseminated through peer-reviewed publication and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42021224155.

African families' and caregivers' experiences of raising a child with intellectual disability: A narrative synthesis of qualitative studies.

BACKGROUND: The prevalence of intellectual disability was high in Africa, particularly amongst low socio-economic communities. Despite this, there was limited literature on primary caregivers and parents of people with intellectual disabilities regarding their experience raising an individual with the condition, especially within the African context. OBJECTIVES: The aim of the current systematic review was to investigate experiences of caregivers and parents of children with intellectual disability in Africa. METHOD: We used strict eligibility criteria to identify suitable studies. We identified Medical Subject Headings (MeSH) terms and other keyword terms and, after conducting searches in electronic databases, identified articles that met the inclusion criteria for articles published between 1975 and the end of 2019. RESULTS: 164 articles were assessed for eligibility. Nine studies met the review's criteria. Six major themes emerged: understanding of intellectual disability (ID), worries about the future, burden of care, lack of services, coping strategies and stigma and discrimination. CONCLUSION: Caregivers of children with intellectual disability in Africa faced substantial challenges. Current findings suggested that there was the need for both formal and alternative healthcare workers to work together towards an understanding and management of intellectual disability in Africa.

Fractional dose compared with standard dose inactivated poliovirus vaccine in children: a systematic review and meta-analysis.

BACKGROUND: Since WHO recommended introduction of at least a single dose of inactivated poliovirus vaccine (IPV) in routine immunisation schedules, there have been global IPV shortages. Fractional-dose IPV (fIPV) administration is one of the strategies to ensure IPV availability. We reviewed studies comparing the effects of fractional with full-dose IPV vaccination to determine when seroconversion proportions with each strategy become similar in children aged 5 years and younger. METHOD: In this systematic review and meta-analysis, we searched 16 databases in July, 2019, for trials and observational studies, including ongoing studies that compare immunogenicity and adverse events of fractional-dose (0·1 mL) to full-dose (0·5 mL) IPV in healthy children aged 5 years or younger regardless of study design, number of doses, and route of administration. Screening, selection of articles, data extraction, and risk of bias assessment were done in duplicate, and conflicts were resolved by discussion or arbitration by a third author. We assessed immunogenicity, the main outcome, as proportion of seroconverted participants and changes in geometric mean titres of anti-poliovirus antibodies. Timepoints were eligible for analysis if measurements were done at least 4 weeks after vaccination. Summary estimates were pooled by use of random-effects meta-analysis. Analysis was stratified by study design, type of outcome measure, type of poliovirus, and number of doses given. We assessed heterogeneity using the χ2 test of homogeneity and quantified it using the I2 statistic. We assessed risk of bias using the Cochrane risk of bias tool, and the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. The study is registered with PROSPERO, CRD42018092647. FINDINGS: 860 records were screened for eligibility, of which 36 potentially eligible full-text articles were assessed and 14 articles were included in the final analysis: two ongoing trials and 12 articles reporting on ten completed studies. For poliovirus type 2, there were no significant differences in the proportions of seroconversions between fractional and full doses of IPV for two or three doses: the risk ratio for serconversion at one dose was 0·61 (95% CI 0·51-0·72), at two doses was 0·90 (0·82-1·00), and at three doses was 0·95 (0·91-1·00). Geometric mean titres (GMTs) for poliovirus type 2 were lower for fIPV than for full-dose IPV: -0·51 (95% CI -0·87 to -0·14) at one dose, -0·49 (-0·70 to -0·28) at two doses, and -0·98 (-1·46 to -0·51) at three doses. The seroconversion meta-analysis for the three-dose comparison was homogeneous (p=0·45; I2=0%), whereas heterogeneity was observed in the two-dose (p<0·00001; I2=88%) and one-dose (p=0·0004; I2=74%) comparisons. Heterogeneity was observed in meta-analyses of GMTs for one-dose (p<0·00001; I2=92%), two-dose (p=0·002; I2=80%), and three-dose (p<0·00001; I2=93%) comparisons. Findings for types 1 and 3 were similar to those for type 2. The certainty of the evidence was high for the three-dose comparisons and moderate for the rest of the comparisons. INTERPRETATION: There is no substantial difference in seroconversion between three doses of fIPV and three doses of full-dose IPV, although the full dose gives higher titres of antibodies for poliovirus type 1, 2, and 3. Use of fractional IPV instead of the full dose can stretch supplies and possibly lower the cost of vaccination. FUNDING: South African Medical Research Council and the National Research Foundation of South Africa.

Outcomes following admission to paediatric intensive care: A systematic review.

AIM: To describe the long-term health outcomes of children admitted to a paediatric intensive care unit. METHODS: A systematic review of the literature was performed. Studies of children under 18 years of age admitted to a paediatric intensive care unit were included. Studies focussed on neonatal admissions and investigating specific paediatric intensive care unit interventions or admission diagnoses were excluded. A table was created summarising the study characteristics and main findings. Risk of bias was assessed using the Newcastle Ottawa Quality Assessment Scale for observational studies. Primary outcome was short-, medium- and long-term mortality. Secondary outcomes included measures of neurodevelopment, cognition, physical, behavioural and psychosocial function as well as quality of life. RESULTS: One hundred and eleven studies were included, most were conducted in high-income countries and focussed on short-term outcomes. Mortality during admission ranged from 1.3 to 50%. Mortality in high-income countries reduced over time but this trend was not evident for lower income countries. Higher income countries had lower standardised mortality rates than lower income countries. Children had an ongoing increased risk of death for up to 10 years following intensive care admission as well as increased physical and psychosocial morbidity compared to healthy controls, with associated poorer quality of life. CONCLUSIONS: There is limited high-level evidence for the long-term health outcomes of children after intensive care admission, with the burden of related morbidity remaining greater in poorly resourced regions. Further research is recommended to identify risk factors and modifiable factors for poor outcomes, which could be targeted in practice improvement initiatives.

Screening strategies for adults with type 2 diabetes mellitus: a systematic review protocol.

BACKGROUND: There is limited evidence on whether screening for type 2 diabetes mellitus affects health outcomes. A recent systematic review of randomised clinical trials found only one trial that met their inclusion criteria; therefore, current guidelines for screening interventions for type 2 diabetes mellitus are based on expert opinions and best practice rather than synthesised evidence. This systematic review seeks to collate evidence from non-randomised studies to investigate the effect of screening for adults with type 2 diabetes on outcomes including diabetes-related morbidity, mortality (all-cause and diabetes-related) and harms. METHODS: This systematic review will follow Effective Practice and Organisation of Care (EPOC) guidelines for the synthesis of non-randomised studies. We will search PubMed/MEDLINE, Scopus, Web of Science, CINAHL, Academic Search Premier and Health Source Nursing Academic (from inception onwards). We will include non-randomised trials, controlled before-after studies, interrupted time-series studies, repeated measures studies and concurrently controlled prospective cohort studies. The primary outcome will be diabetes-related morbidity (microvascular complications of diabetic retinopathy, nephropathy or neuropathy or macrovascular complications of non-fatal myocardial infarction, peripheral arterial disease or non-fatal stroke). The secondary outcomes will be mortality (all-cause and diabetes-related) and harms of screening strategies to patients (including psychological harms or adverse events following treatments) or to health care system (including resource allocation for false-positives or overdiagnosis). Two reviewers will independently screen all citations and full-text articles. Data will be abstracted by one reviewer and checked by a second. The risk of bias of individual studies will be appraised using the ROBINS-I tool. GRADE will be used to determine the quality of the scientific evidence. If feasible, we will conduct random effects meta-analysis where appropriate. If necessary, analyses will be conducted to explore the potential sources of heterogeneity (e.g. age, sex, socio-economic status, rural versus urban or low-middle income versus high-income country). We will disseminate the findings via publications and through relevant networks. DISCUSSION: The protocol outlines the methods for systematically reviewing and synthesising evidence of screening strategies for type 2 diabetes mellitus and their effect on health outcomes associated with the disease. The potential impact of this systematic review is improved evidence-informed decision-making for policies and practice for screening of type-2 diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020147439.

Is computer-assisted instruction more effective than other educational methods in achieving ECG competence amongst medical students and residents? A systematic review and meta-analysis.

OBJECTIVES: It remains unclear whether computer-assisted instruction (CAI) is more effective than other teaching methods in acquiring and retaining ECG competence among medical students and residents. DESIGN: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: Electronic literature searches of PubMed, databases via EBSCOhost, Scopus, Web of Science, Google Scholar and grey literature were conducted on 28 November 2017. We subsequently reviewed the citation indexes for articles identified by the search. ELIGIBILITY CRITERIA: Studies were included if a comparative research design was used to evaluate the efficacy of CAI versus other methods of ECG instruction, as determined by the acquisition and/or retention of ECG competence of medical students and/or residents. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data from all eligible studies and assessed the risk of bias. After duplicates were removed, 559 papers were screened. Thirteen studies met the eligibility criteria. Eight studies reported sufficient data to be included in the meta-analysis. RESULTS: In all studies, CAI was compared with face-to-face ECG instruction. There was a wide range of computer-assisted and face-to-face teaching methods. Overall, the meta-analysis found no significant difference in acquired ECG competence between those who received computer-assisted or face-to-face instruction. However, subanalyses showed that CAI in a blended learning context was better than face-to-face teaching alone, especially if trainees had unlimited access to teaching materials and/or deliberate practice with feedback. There was no conclusive evidence that CAI was better than face-to-face teaching for longer-term retention of ECG competence. CONCLUSION: CAI was not better than face-to-face ECG teaching. However, this meta-analysis was constrained by significant heterogeneity amongst studies. Nevertheless, the finding that blended learning is more effective than face-to-face ECG teaching is important in the era of increased implementation of e-learning. PROSPERO REGISTRATION NUMBER: CRD42017067054.

Protocol for a systematic review and meta-analysis of fractional dose compared with standard dose inactivated polio vaccination in children.

INTRODUCTION: WHO recommends the introduction of at least one single dose of inactivated polio vaccine (IPV) in routine immunisation schedules. Thus, there has been an increased demand and concurrent supply shortages of IPV worldwide. One of the strategies to improve access is the use of fractional instead of full doses of IPV. We aim to compare the effects of fractional with standard doses of IPV. METHODS AND ANALYSIS: We will include randomised trials, non-randomised trials, case-control studies and cohort studies that compared fractional with full doses of IPV among children aged 5 years or younger. We will search for eligible studies among published and grey literature. Two authors will independently screen the results of the search, select studies, extract data and assess risk of bias. We will stratify analyses by study design, type of poliovirus, type of outcome measure and number of IPV doses given. For each type of poliovirus, we will pool the outcome data from studies using random-effects meta-analyses. Statistical heterogeneity will be assessed using the χ2 test of homogeneity and quantified using the I2 statistic. To investigate statistical heterogeneity, subgroup analyses will be performed based on the timing of the first fractional dose, age of administration, immunisation schedules and country income status. Sensitivity analyses will be used to assess if the effect of IPV fractional dosing is affected by study design, risk of bias and methods of meta-analysis. ETHICS AND DISSEMINATION: We obtained approval from the University of Cape Town Human Research Ethics Committee (HREC REF: 412/2018). The findings of this review will provide evidence for decision-making with regards to IPV dosage, eventually improving access to the vaccine by stretching vaccine supplies. The results will be published in the University of Cape Town online library and in a peer reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42018092647.

Is computer-assisted instruction more effective than other educational methods in achieving ECG competence among medical students and residents? Protocol for a systematic review and meta-analysis.

INTRODUCTION: Although ECG interpretation is an essential skill in clinical medicine, medical students and residents often lack ECG competence. Novel teaching methods are increasingly being implemented and investigated to improve ECG training. Computer-assisted instruction is one such method under investigation; however, its efficacy in achieving better ECG competence among medical students and residents remains uncertain. METHODS AND ANALYSIS: This article describes the protocol for a systematic review and meta-analysis that will compare the effectiveness of computer-assisted instruction with other teaching methods used for the ECG training of medical students and residents. Only studies with a comparative research design will be considered. Articles will be searched for in electronic databases (PubMed, Scopus, Web of Science, Academic Search Premier, CINAHL, PsycINFO, Education Resources Information Center, Africa-Wide Information and Teacher Reference Center). In addition, we will review citation indexes and conduct a grey literature search. Data extraction will be done on articles that met the predefined eligibility criteria. A descriptive analysis of the different teaching modalities will be provided and their educational impact will be assessed in terms of effect size and the modified version of Kirkpatrick framework for the evaluation of educational interventions. This systematic review aims to provide evidence as to whether computer-assisted instruction is an effective teaching modality for ECG training. It is hoped that the information garnered from this systematic review will assist in future curricular development and improve ECG training. ETHICS AND DISSEMINATION: As this research is a systematic review of published literature, ethical approval is not required. The results will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement and will be submitted to a peer-reviewed journal. The protocol and systematic review will be included in a PhD dissertation. PROSPERO REGISTRATION NUMBER: CRD42017067054; Pre-results.

An assessment of obese and non obese girls' metabolic rate during television viewing, reading, and resting.

While childhood obesity has been linked to television (TV) viewing, specific mechanisms are not well understood. Obesity related to TV viewing might plausibly be related to decreased physical activity, increased food intake, reductions in metabolic rate, or combinations of these. The current investigation sought to ascertain the metabolic effects of quiet rest, listening to a story, watching a passive TV program, and watching an active TV show. Counter-balanced conditions were presented to 90 pre-pubertal girls ranging in body mass index from underweight to obese. In addition, effects between resting energy expenditure (REE) and race, body mass index, skinfold measures, physical activity, pubertal stage and average hours spent viewing TV were explored. Results indicated no significant differences in metabolic rate between weight groups nor between activity conditions (story listening and TV viewing) and rest conditions. A significant dose-response relationship was found in which REE decreased as average weekly hours of TV viewing increased, after adjusting for body mass index and puberty stage. Additionally, later stages of pubertal development compared to earlier stages were related to higher levels of REE. Results of this study suggest that metabolic rate alone cannot account for the consistently observed relationship between television viewing and obesity. Future studies should focus on energy intake, physical inactivity, or combinations of these with metabolic rate in seeking specific mechanisms responsible for television viewing related to obesity.