Mass deworming to improve developmental health and wellbeing of children in low-income and middle-income countries: a systematic review and network meta-analysis

Background: Soil-transmitted helminthiasis and schistosomiasis, considered among the neglected tropical diseases by WHO, affect more than a third of the world’s population, with varying intensity of infection. We aimed to evaluate the eff ects of mass deworming for soil-transmitted helminths (with or without deworming for schistosomiasis or cointerventions) on growth, educational achievement, cognition, school attendance, quality of life, and adverse effects in children in endemic helminth areas. Methods: We searched 11 databases up to Jan 14, 2016, websites and trial registers, contacted authors, and reviewed reference lists. We included studies published in any language of children aged 6 months to 16 years, with mass deworming for soil-transmitted helminths or schistosomiasis (alone or in combination with other interventions) for 4 months or longer, that reported the primary outcomes of interest. We included randomized and quasi-randomized trials, controlled before–after studies, interrupted time series, and quasi-experimental studies. We screened in duplicate, then extracted data and appraised risk of bias in duplicate with a pre-tested form. We conducted random effects meta-analysis and Bayesian network meta-analysis. Findings: We included 52 studies of duration 5 years or less with 1 108 541 children, and four long-term studies 8–10 years after mass deworming programmes with more than 160 000 children. Overall risk of bias was moderate. Mass deworming for soil-transmitted helminths compared with controls led to little to no improvement in weight over a period of about 12 months (0·99 kg, 95% credible interval [CrI] −0·09 to 0·28; moderate certainty evidence) or height (0·07 cm, 95% CrI −0·10 to 0·24; moderate certainty evidence), little to no difference in proportion stunted (eight fewer per 1000 children, 95% CrI −48 to 32; high certainty evidence), cognition measured by short-term attention (−0·23 points on a 100 point scale, 95% CI −0·56 to 0·14; high certainty evidence), school attendance (1% higher, 95% CI −1 to 3; high certainty evidence), or mortality (one fewer per 1000 children, 95% CI −3 to 1; high certainty evidence). We found no data on quality of life and little evidence of adverse effects. Mass deworming for schistosomiasis might slightly increase weight (0·41 kg, 95% CrI −0·20 to 0·91) and has little to no effect on height (low certainty evidence) and cognition (moderate certainty evidence). Our analyses do not suggest indirect benefits for untreated children from being exposed to treated children in the community. We are uncertain about effects on long-term economic productivity (hours worked), cognition, literacy, and school enrolment owing to very low certainty evidence. Results were consistent across sensitivity and subgroup analyses by age, worm prevalence, baseline nutritional status, infection status, impact on worms, infection intensity, types of worms (ascaris, hookworm, or trichuris), risk of bias, cluster versus individual trials, compliance, and attrition. Interpretation: Mass deworming for soil-transmitted helminths with or without deworming for schistosomiasis had little eff ect. For schistosomiasis, mass deworming might be eff ective for weight but is probably ineffective for height, cognition, and attendance. Future research should assess which subset of children do benefit from mass deworming, if any, using individual participant data meta-analysis

GRADE equity guidelines 4: guidance on how to assess and address health equity within the evidence to decision process

Objective: The aim of this paper is to provide detailed guidance on how to incorporate health equity within the GRADE (Grading Recommendations Assessment and Development Evidence) evidence to decision process. Study design and setting: We developed this guidance based on the GRADE evidence to decision (EtD) framework, iteratively reviewing and modifying draft documents, in person discussion of project group members and input from other GRADE members. Results: Considering the impact on health equity may be required, both in general guidelines, and guidelines that focus on disadvantaged populations. We suggest two approaches to incorporate equity considerations: 1) assessing the potential impact of interventions on equity and; 2) incorporating equity considerations when judging or weighing each of the evidence to decision criteria. We provide guidance and include illustrative examples. Conclusion: Guideline panels should consider the impact of recommendations on health equity with attention to remote and underserviced settings and disadvantaged populations. Guideline panels may wish to incorporate equity judgments across the evidence to decision framework

How effects on health equity are assessed in systematic reviews of interventions.

BACKGROUND: Enhancing health equity has now achieved international political importance with endorsement from the World Health Assembly in 2009.  The failure of systematic reviews to consider effects on health equity is cited by decision-makers as a limitation to their ability to inform policy and program decisions.  OBJECTIVES: To systematically review methods to assess effects on health equity in systematic reviews of effectiveness. SEARCH STRATEGY: We searched the following databases up to July 2 2010: MEDLINE, PsychINFO, the Cochrane Methodology Register, CINAHL, Education Resources Information Center, Education Abstracts, Criminal Justice Abstracts, Index to Legal Periodicals, PAIS International, Social Services Abstracts, Sociological Abstracts, Digital Dissertations and the Health Technology Assessment Database. We searched SCOPUS to identify articles that cited any of the included studies on October 7 2010. SELECTION CRITERIA: We included empirical studies of cohorts of systematic reviews that assessed methods for measuring effects on health inequalities. DATA COLLECTION AND ANALYSIS: Data were extracted using a pre-tested form by two independent reviewers. Risk of bias was appraised for included studies according to the potential for bias in selection and detection of systematic reviews.  MAIN RESULTS: Thirty-four methodological studies were included.  The methods used by these included studies were: 1) Targeted approaches (n=22); 2) gap approaches (n=12) and gradient approach (n=1).  Gender or sex was assessed in eight out of 34 studies, socioeconomic status in ten studies, race/ethnicity in seven studies, age in seven studies, low and middle income countries in 14 studies, and two studies assessed multiple factors across health inequity may exist.Only three studies provided a definition of health equity. Four methodological approaches to assessing effects on health equity were identified: 1) descriptive assessment of reporting and analysis in systematic reviews (all 34 studies used a type of descriptive method); 2) descriptive assessment of reporting and analysis in original trials (12/34 studies); 3) analytic approaches (10/34 studies); and 4) applicability assessment (11/34 studies). Both analytic and applicability approaches were not reported transparently nor in sufficient detail to judge their credibility. AUTHORS' CONCLUSIONS: There is a need for improvement in conceptual clarity about the definition of health equity, describing sufficient detail about analytic approaches (including subgroup analyses) and transparent reporting of judgments required for applicability assessments in order to assess and report effects on health equity in systematic reviews

Mass deworming to improve developmental health and wellbeing of children in low-income and middle-income countries: a systematic review and network meta-analysis

Background Soil-transmitted helminthiasis and schistosomiasis, considered among the neglected tropical diseases by WHO, aff ect more than a third of the world’s population, with varying intensity of infection. We aimed to evaluate the eff ects of mass deworming for soil-transmitted helminths (with or without deworming for schistosomiasis or cointerventions) on growth, educational achievement, cognition, school attendance, quality of life, and adverse eff ects in children in endemic helminth areas. Methods We searched 11 databases up to Jan 14, 2016, websites and trial registers, contacted authors, and reviewed reference lists. We included studies published in any language of children aged 6 months to 16 years, with mass deworming for soil-transmitted helminths or schistosomiasis (alone or in combination with other interventions) for 4 months or longer, that reported the primary outcomes of interest. We included randomised and quasi-randomised trials, controlled before–after studies, interrupted time series, and quasi-experimental studies. We screened in duplicate, then extracted data and appraised risk of bias in duplicate with a pre-tested form. We conducted randomeff ects meta-analysis and Bayesian network meta-analysis. Findings We included 52 studies of duration 5 years or less with 1 108 541 children, and four long-term studies 8–10 years after mass deworming programmes with more than 160 000 children. Overall risk of bias was moderate. Mass deworming for soil-transmitted helminths compared with controls led to little to no improvement in weight over a period of about 12 months (0·99 kg, 95% credible interval [CrI] −0·09 to 0·28; moderate certainty evidence) or height (0·07 cm, 95% CrI −0·10 to 0·24; moderate certainty evidence), little to no diff erence in proportion stunted (eight fewer per 1000 children, 95% CrI −48 to 32; high certainty evidence), cognition measured by short-term attention (−0·23 points on a 100 point scale, 95% CI −0·56 to 0·14; high certainty evidence), school attendance (1% higher, 95% CI −1 to 3; high certainty evidence), or mortality (one fewer per 1000 children, 95% CI −3 to 1; high certainty evidence). We found no data on quality of life and little evidence of adverse eff ects. Mass deworming for schistosomiasis might slightly increase weight (0·41 kg, 95% CrI −0·20 to 0·91) and has little to no eff ect on height (low certainty evidence) and cognition (moderate certainty evidence). Our analyses do not suggest indirect benefi ts for untreated children from being exposed to treated children in the community. We are uncertain about eff ects on long-term economic productivity (hours worked), cognition, literacy, and school enrolment owing to very low certainty evidence. Results were consistent across sensitivity and subgroup analyses by age, worm prevalence, baseline nutritional status, infection status, impact on worms, infection intensity, types of worms (ascaris, hookworm, or trichuris), risk of bias, cluster versus individual trials, compliance, and attrition. Interpretation Mass deworming for soil-transmitted helminths with or without deworming for schistosomiasis had little eff ect. For schistosomiasis, mass deworming might be eff ective for weight but is probably ineff ective for height, cognition, and attendance. Future research should assess which subset of children do benefi t from mass deworming, if any, using individual participant data meta-analysis

“Interest-holders”: A new term to replace “stakeholders” in the context of health research and policy

BackgroundGiven the colonial connotations of the term “stakeholder”, its continued use may be perceived as disrespectful to Indigenous Peoples. While several groups have introduced alternative terms, each has its own limitations. The objective of this article is to introduce “interest-holders” as an alternative term to “stakeholders” and describe the discussions underpinning the adoption of the new term by the MuSE Consortium.MethodsThe MuSE Consortium is an international network of over 160 individuals with interest and expertise in different aspects relevant to engagement in research. Members of MuSE explored alternative terms and considered their respective merits and limitations. The deliberations considered the literature on the topic and the results of two consultations with the wider MuSE membership on the alternative terms.ResultsWe define “interest-holders” as groups with legitimate interests in the health issue under consideration. The interests arise and draw their legitimacy from the fact that people from these groups are responsible for or affected by health-related decisions that can be informed by research evidence.ConclusionAs groups other than the MuSE Consortium have started to adopt “interest-holders,” we hope its use will reduce confusion related to the multitude of terms used and convey the intended meaning without any negative connotations

Mass deworming to improve developmental health and wellbeing of children in low-income and middle-income countries: a systematic review and network meta-analysis.

BACKGROUND: Soil-transmitted helminthiasis and schistosomiasis, considered among the neglected tropical diseases by WHO, affect more than a third of the world's population, with varying intensity of infection. We aimed to evaluate the effects of mass deworming for soil-transmitted helminths (with or without deworming for schistosomiasis or co-interventions) on growth, educational achievement, cognition, school attendance, quality of life, and adverse effects in children in endemic helminth areas. METHODS: We searched 11 databases up to Jan 14, 2016, websites and trial registers, contacted authors, and reviewed reference lists. We included studies published in any language of children aged 6 months to 16 years, with mass deworming for soil-transmitted helminths or schistosomiasis (alone or in combination with other interventions) for 4 months or longer, that reported the primary outcomes of interest. We included randomised and quasi-randomised trials, controlled before-after studies, interrupted time series, and quasi-experimental studies. We screened in duplicate, then extracted data and appraised risk of bias in duplicate with a pre-tested form. We conducted random-effects meta-analysis and Bayesian network meta-analysis. FINDINGS: We included 52 studies of duration 5 years or less with 1 108 541 children, and four long-term studies 8-10 years after mass deworming programmes with more than 160 000 children. Overall risk of bias was moderate. Mass deworming for soil-transmitted helminths compared with controls led to little to no improvement in weight over a period of about 12 months (0·99 kg, 95% credible interval [CrI] -0·09 to 0·28; moderate certainty evidence) or height (0·07 cm, 95% CrI -0·10 to 0·24; moderate certainty evidence), little to no difference in proportion stunted (eight fewer per 1000 children, 95% CrI -48 to 32; high certainty evidence), cognition measured by short-term attention (-0·23 points on a 100 point scale, 95% CI -0·56 to 0·14; high certainty evidence), school attendance (1% higher, 95% CI -1 to 3; high certainty evidence), or mortality (one fewer per 1000 children, 95% CI -3 to 1; high certainty evidence). We found no data on quality of life and little evidence of adverse effects. Mass deworming for schistosomiasis might slightly increase weight (0·41 kg, 95% CrI -0·20 to 0·91) and has little to no effect on height (low certainty evidence) and cognition (moderate certainty evidence). Our analyses do not suggest indirect benefits for untreated children from being exposed to treated children in the community. We are uncertain about effects on long-term economic productivity (hours worked), cognition, literacy, and school enrolment owing to very low certainty evidence. Results were consistent across sensitivity and subgroup analyses by age, worm prevalence, baseline nutritional status, infection status, impact on worms, infection intensity, types of worms (ascaris, hookworm, or trichuris), risk of bias, cluster versus individual trials, compliance, and attrition. INTERPRETATION: Mass deworming for soil-transmitted helminths with or without deworming for schistosomiasis had little effect. For schistosomiasis, mass deworming might be effective for weight but is probably ineffective for height, cognition, and attendance. Future research should assess which subset of children do benefit from mass deworming, if any, using individual participant data meta-analysis. FUNDING: Canadian Institutes of Health Research and WHO

GRADE equity guidelines 3: considering health equity in GRADE guideline development: rating the certainty of synthesized evidence

Objectives: The aim of this paper is to describe a conceptual framework for how to consider health equity in the Grading Recommendations Assessment and Development Evidence (GRADE) guideline development process. Study Design and Setting: Consensus-based guidance developed by the GRADE working group members and other methodologists. Results: We developed consensus-based guidance to help address health equity when rating the certainty of synthesized evidence (i.e., quality of evidence). When health inequity is determined to be a concern by stakeholders, we propose five methods for explicitly assessing health equity: (1) include health equity as an outcome; (2) consider patient-important outcomes relevant to health equity; (3) assess differences in the relative effect size of the treatment; (4) assess differences in baseline risk and the differing impacts on absolute effects; and (5) assess indirectness of evidence to disadvantaged populations and/or settings. Conclusion: The most important priority for research on health inequity and guidelines is to identify and document examples where health equity has been considered explicitly in guidelines. Although there is a weak scientific evidence base for assessing health equity, this should not discourage the explicit consideration of how guidelines and recommendations affect the most vulnerable members of society

Systematic scoping review of cluster randomised trials conducted exclusively in low-income and middle-income countries between 2017 and 2022

Objective: Cluster randomised trials (CRTs) are used for evaluating health-related interventions in low-income and middle-income countries (LMICs) but raise complex ethical issues. To inform the development of future ethics guidance, we aim to characterise CRTs conducted exclusively in LMICs by examining the types of clusters, settings, author affiliations and primary clinical focus and to evaluate adherence to trial registration and ethics reporting requirements over time. Design: A systematic scoping review using the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews. Data sources: We searched MEDLINE between 1 January 2017 and 17 August 2022. Eligibility criteria for selecting studies: We included primary reports of CRTs evaluating health-related interventions, conducted exclusively in LMICs and published in English between 2017 and 2022. Data extraction and synthesis. Data were extracted by one reviewer; a second reviewer verified accuracy by extracting data from 10% of the reports. Results were summarised overall and categorised by country’s economic level or publication year. Results: Among 800 identified CRTs, 400 (50.0%) randomised geographical areas and 373 (46.6%) were conducted in Africa. 30 (3.7%) had no authors with an LMIC affiliation, and 246 (30.8%) had neither first nor last author with an LMIC affiliation. The relative frequency of first or last authors holding an LMIC affiliation increases as a country’s economic level increases. Most CRTs focused on reducing maternal and neonatal disorders (106, 13.3%). 670 (83.8%) CRTs reported trial registration, 786 (98.2%) reported research ethics committee review and 757 (94.6%) reported consent statements. Among the 757 CRTs, 46 (6.1%) reported a waiver or no consent and, among these, 10 (21.7%) did not provide a rationale. Gatekeepers were identified in 403 (50.4%) CRTs. No meaningful trends were observed in adherence to trial registration or ethics reporting requirements over time. Conclusion: Our findings suggest existing inequity in authorship practices. There is high adherence to trial registration and ethics reporting requirements, although greater attention to reporting a justification for using a waiver of consent is needed

Protocol: Barriers and facilitators to stakeholder engagement in health guideline development: a qualitative evidence synthesis

Background There is a need for the development of comprehensive, global, evidence-based guidance for stakeholder engagement in guideline development. Stakeholders are any individual or group who is responsible for or affected by health- and healthcare-related decisions. This includes patients, the public, providers of health care and policymakers for example. As part of the guidance development process, Multi-Stakeholder Engagement (MuSE) Consortium set out to conduct four concurrent systematic reviews to summarise the evidence on: (1) existing guidance for stakeholder engagement in guideline development, (2) barriers and facilitators to stakeholder engagement in guideline development, (3) managing conflicts of interest in stakeholder engagement in guideline development and (4) measuring the impact of stakeholder engagement in guideline development. This protocol addresses the second systematic review in the series. Objectives The objective of this review is to identify and synthesise the existing evidence on barriers and facilitators to stakeholder engagement in health guideline development. We will address this objective through two research questions: (1) What are the barriers to multi-stakeholder engagement in health guideline development across any of the 18 steps of the GIN-McMaster checklist? (2) What are the facilitators to multi-stakeholder engagement in health guideline development across any of the 18 steps of the GIN-McMaster checklist? Search Methods A comprehensive search strategy will be developed and peer-reviewed in consultation with a medical librarian. We will search the following databases: MEDLINE, Cumulative Index to Nursing & Allied Health Literature (CINAHL), EMBASE, PsycInfo, Scopus, and Sociological Abstracts. To identify grey literature, we will search the websites of agencies who actively engage stakeholder groups such as the AHRQ, Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR), INVOLVE, the National Institute for Health and Care Excellence (NICE) and the PCORI. We will also search the websites of guideline-producing agencies, such as the American Academy of Pediatrics, Australia's National Health Medical Research Council (NHMRC) and the WHO. We will invite members of the team to suggest grey literature sources and we plan to broaden the search by soliciting suggestions via social media, such as Twitter. Selection Criteria We will include empirical qualitative and mixed-method primary research studies which qualitatively report on the barriers or facilitators to stakeholder engagement in health guideline development. The population of interest is stakeholders in health guideline development. Building on previous work, we have identified 13 types of stakeholders whose input can enhance the relevance and uptake of guidelines: Patients, caregivers and patient advocates; Public; Providers of health care; Payers of health services; Payers of research; Policy makers; Program managers; Product makers; Purchasers; Principal investigators and their research teams; and Peer-review editors/publishers. Eligible studies must describe stakeholder engagement at any of the following steps of the GIN-McMaster Checklist for Guideline Development. Data Collection and Analysis All identified citations from electronic databases will be imported into Covidence software for screening and selection. Documents identified through our grey literature search will be managed and screened using an Excel spreadsheet. A two-part study selection process will be used for all identified citations: (1) a title and abstract review and (2) full-text review. At each stage, teams of two review authors will independently assess all potential studies in duplicate using a priori inclusion and exclusion criteria. Data will be extracted by two review authors independently and in duplicate according to a standardised data extraction form. Main Results The results of this review will be used to inform the development of guidance for multi-stakeholder engagement in guideline development and implementation. This guidance will be official GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group guidance. The GRADE system is internationally recognised as a standard for guideline development. The findings of this review will assist organisations who develop healthcare, public health and health policy guidelines, such as the World Health Organization, to involve multiple stakeholders in the guideline development process to ensure the development of relevant, high quality and transparent guidelines