Experiences of core outcome set developers on including stakeholders from low- and middle-income countries: An online survey.

Core outcome set (COS) development and use enhances comparability of research findings. It may also enhance the translation of research into practice and reduce research waste. However, there is limited involvement of stakeholders from low- and middle-income countries (LMICs) in COS development and use. In this study, we explored the experiences of researchers in COS development projects who included stakeholders from LMICs. Online survey conducted in English of 70 COS developers from HICs who had included LMIC stakeholders in the process of developing a COS, published before the end of 2019. Respondents were identified from the COMET database and sent a link to the survey via a personalised email. Quantitative data were analysed using simple descriptive statistics. Qualitative data analysis was based on qualitative content analysis. There were 37 respondents yielding a 53% overall response rate. Analysis was limited to the responses related to 29 COS developed in the years 2015 to 2019, to reduce the potential for recall bias for earlier COS. Most respondents 20/29 (69%) were researchers. Determining 'what to measure' was reported as the most common stage of inclusion of LMIC stakeholders. Respondents cited (24/29, 83%) their ongoing collaborations with LMIC stakeholders such as clinicians or researchers as their main rationale for including LMICs stakeholders and reported that translation of the Delphi into languages other than English may be useful to enhance wider stakeholder participation. Involvement of LMIC stakeholders only in the later stages of COS development, lack of adequate resources to support their involvement, and lack of networks and contacts were thought to limit fuller participation of stakeholders from LMICs. To improve the involvement of LMIC stakeholders in COS development and use, COS developers need to raise awareness on the utility of COS. The need for and feasibility of translation into multiple languages warrants further discussion.

Awareness and experiences on core outcome set development and use amongst stakeholders from low- and middle- income countries: An online survey.

Harmonization of outcomes to be measured in clinical trials can reduce research waste and enhance research translation. One of the ways to standardize measurement is through development and use of core outcome sets (COS). There is limited involvement of low- and middle-income country (LMIC) stakeholders in COS development and use. This study explores the level of awareness and experiences of LMIC stakeholders in the development and use of COS. We conducted an online survey of LMIC stakeholders. Three existing COS (pre-eclampsia, COVID-19, palliative care) were presented as case scenarios, and respondents asked to state (with reason(s)) if they would or would not use the COS if they were working in that area. Quantitative data were analyzed descriptively while qualitative data were analyzed thematically. Of 81 respondents, 26 had COS experience, 9 of whom had been involved in COS development. Personal research interests and prevalence of disease are key drivers for initiation/participation in a given COS project. Most respondents would use the COS for pre-eclampsia (18/26) and COVID-19 (19/26) since the development process included key stakeholders. More than half of the respondents were not sure or would not use the palliative care COS as they felt stakeholder engagement was limited and it was developed for a different resource setting. Respondents reported that use of COS can be limited by (i) feasibility of measuring the outcomes in the COS, (ii) knowledge on the usefulness and availability of COS and (iii) lack of wide stakeholder engagement in the COS development process including having patients and carers in the development process. To ensure the development and use of COS in LMICs, collaborations are essential in awareness raising on COS utility, training, and COS development. The COS also needs to be made accessible in locally understandable languages and feasible to measure in LMICs.

To adopt or adapt an existing neonatal core outcome set in Kenya: a study protocol.

BACKGROUND: Development and use of core outcome set(s) (COS) in research can reduce research wastage by ensuring that a minimum set of outcomes are always reported on. Neonatal morbidity and mortality are a big burden in low- and middle-income countries (LMICs). Research is continuously being undertaken to reduce this burden. Currently, there is no COS for neonatal research in LMICs but there exists one for neonatal research in high-income countries (HICs). OBJECTIVES: To determine outcomes that are useful for neonatal care in Kenya to inform whether an existing COS should be adopted or adapted. To assess the feasibility of a routine data collection system to collect data of the agreed-on COS. METHODS: A review of existing literature on neonatal research in LMICs followed by a qualitative study of key stakeholders in neonatal care. To explore whether to adapt or adopt, in two hospitals, two focus group discussions with 6-8 parents/caregivers will be undertaken (one each in two hospitals). Key informant interviews will also be conducted with 6 health care providers in each of the hospitals. At the policy-making level, we will conduct 10 key informant interviews. Qualitative data will be analyzed thematically. A consensus meeting will be undertaken with key stakeholders, who will be presented with an overview of the COS developed for HICs, key findings from the literature, and the qualitative study to determine context-appropriate COS. The agreed-on outcomes will be counterchecked against the case records in the two hospitals. The feasibility of collecting the outcomes on a routine electronic research database, the Clinical Information Network that collects standardized data at admission and discharge, will be explored. The congruence (or not) of the outcomes will be documented and be used to enrich the discussion and provide a snapshot of the feasibility of the health information system to collect routine data on the COS. CONCLUSIONS: A COS for use in neonatal care in Kenya will help enhance outcome measurements and reporting not just in research but also in routine practice. This will enhance the comparability of interventions in trials and routine settings leading to reduced research wastage and likely improved quality of care. Additionally, the methodology used for this work can be adopted in other settings as a means of adopting or adapting an existing COS.

Inclusion of participants from low-income and middle-income countries in core outcome sets development: a systematic review.

OBJECTIVE: Our study aims to describe differences or similarities in the scope, participant characteristics and methods used in core outcome sets (COS) development when only participants from high-income countries (HICs) were involved compared with when participants from low-income and middle-income countries (LMICs) were also involved. DESIGN: Systematic review. DATA SOURCES: Annual Core Outcome Measures in Effectiveness Trials systematic reviews of COS which are updated based on SCOPUS and MEDLINE, searches. The latest systematic review included studies published up to the end of 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included studies reporting development of a COS for use in research regardless of age, health condition or setting. Studies reporting the development of a COS for patient-reported outcomes or adverse events or complications were also included. DATA EXTRACTION AND SYNTHESIS: Data were extracted in relation to scope of the COS study, participant categories and the methods used in outcome selection. RESULTS: Studies describing 370 COS were identified in the database. Of these, 75 (20%) included participants from LMICs. Only four COS were initiated from an LMIC setting. More than half of COS with LMIC participants were developed in the last 5 years. Cancer and rheumatology were the dominant disease domains. Overall, over 259 (70%) of COS explicitly reported including clinical experts; this was higher where LMIC participants were also included 340 (92%). Most LMIC participants were from China, Brazil and South Africa. Mixed methods for consensus building were used across the two settings. CONCLUSION: Progress has been made in including LMIC participants in the development of COS, however, there is a need to explore how to enable initiation of COS development from a range of LMIC settings, how to ensure prioritisation of COS that better reflects the burden of disease in these contexts and how to improve public participation from LMICs.

Sub-Standard Pharmaceutical Services in Private Healthcare Facilities Serving Low-Income Settlements in Nairobi County, Kenya.

Background: Quality pharmaceutical services are an integral part of primary healthcare and a key determinant of patient outcomes. The study focuses on pharmaceutical service delivery among private healthcare facilities serving informal settlements within Nairobi County, Kenya and aims at understanding the drug procurement practices, task-shifting and ethical issues associated with drug brand preference, competition and disposal of expired drugs. Methods: Forty-five private facilities comprising of hospitals, nursing homes, health centres, medical centres, clinics and pharmacies were recruited through purposive sampling. Structured electronic questionnaires were administered to 45 respondents working within the study facilities over an 8-week period. Results: About 50% of personnel carrying out drug procurement belonged to non-pharmaceutical cadres namely; doctors, clinical officers, nurses and pharmacy assistants. Drug brand preferences among healthcare facilities and patients were mainly pegged on perceived quality and price. Unethical business competition practices were recorded, including poor professional demeanour and waiver of consultation fees veiled to undercut colleagues. Government subsidized drugs were sold at 100% profit in fifty percent of the facilities stocking them. In 44% of the facilities, the disposal of expired drugs was not in conformity to existing government regulatory guidelines. Conclusions: There is extensive task-shifting and delegation of pharmaceutical services to non-pharmaceutical cadres and poor observance of ethical guidelines in private facilities. Strict enforcement of regulations is required for optimal practices.

Preventing female genital mutilation in high income countries: a systematic review of the evidence.

BACKGROUND: Female genital mutilation (FGM) is prevalent in communities of migration. Given the harmful effects of the practice and its illegal status in many countries, there have been concerted primary, secondary and tertiary prevention efforts to protect girls from FGM. However, there is paucity of evidence concerning useful strategies and approaches to prevent FGM and improve the health and social outcomes of affected women and girls. METHODS: We analysed peer-reviewed and grey literature to extract the evidence for FGM prevention interventions from a public health perspective in high income countries by a systematic search of bibliographic databases and websites using appropriate keywords. Identified publications were screened against selection criteria, following the PRISMA guidelines. We examined the characteristics of prevention interventions, including their programmatic approaches and strategies, target audiences and evaluation findings using an apriori template. FINDINGS: Eleven documents included in this review described primary and secondary prevention activities. High income countries have given attention to legislative action, bureaucratic interventions to address social injustice and protect those at risk of FGM, alongside prevention activities that favour health persuasion, foster engagement with the local community through outreach and the involvement of community champions, healthcare professional training and capacity strengthening. Study types are largely process evaluations that include measures of short-term outcomes (pre- and post-changes in attitude, knowledge and confidence or audits of practices). There is a dearth of evaluative research focused on empowerment-oriented preventative activities that involve individual women and girls who are affected by FGM. Beattie's framework provides a useful way of articulating negotiated and authoritative prevention actions required to address FGM at national and local levels. CONCLUSION: FGM is a complex and deeply rooted sociocultural issue that requires a multifaceted response that encompasses socio-economic, physical and environmental factors, education and learning, health services and facilities, and community mobilisation activities. Investment in the rigorous longitudinal evaluation of FGM health prevention efforts are needed to provide strong evidence of impact to guide future decision making. A national evidence-based framework would bring logic, clarity, comprehension, evidence and economically more effective response for current and future prevention interventions addressing FGM in high income countries.

Medicine Prices, Availability, and Affordability in Private Health Facilities in Low-Income Settlements in Nairobi County, Kenya.

Medicine prices are a major determinant of access to healthcare. Owing to low availability of medicines in the public health facilities and poor accessibility to these facilities, most low-income residents pay out-of-pocket for health services and transport to the private health facilities. In low-income settlements, high retail prices are likely to push the population further into poverty and ill health. This study assessed the retail pricing, availability, and affordability of medicines in private health facilities in low-income settlements within Nairobi County. Medicine prices and availability data were collected between September and December 2016 at 45 private healthcare facilities in 14 of Nairobi's low-income settlements using electronic questionnaires. The International Medical Products Price Guide provided international medicine reference prices for comparison. Affordability and availability proxies were calculated according to existing methods. Innovator brands were 13.8 times more expensive than generic brands. The lowest priced generics and innovator brands were, on average, sold at 2.9 and 32.6 times the median international reference prices of corresponding medicines. Assuming a 100% disposable income, it would take 0.03 to 1.33 days' wages for the lowest paid government employee to pay for treatment courses of selected single generic medicines. Medicine availability in the facilities ranged between 2% and 76% (mean 43%) for indicator medicines. Prices of selected medicines varied within the 14 study regions. Retail medicine prices in the low-income settlements studied were generally higher than corresponding international reference prices. Price variations were observed across different regions although the regions comprise similar socioeconomic populations. These factors are likely to impact negatively on healthcare access.

The need for pragmatic clinical trials in low and middle income settings - taking essential neonatal interventions delivered as part of inpatient care as an illustrative example.

BACKGROUND: Pragmatic randomized trials aim to examine the effects of interventions in the full spectrum of patients seen by clinicians who receive routine care. Such trials should be employed in parallel with efforts to implement many interventions which appear promising but where evidence of effectiveness is limited. We illustrate this need taking the case of essential interventions to reduce inpatient neonatal mortality in low and middle income countries (LMIC) but suggest the arguments are applicable in most clinical areas. DISCUSSION: A set of basic interventions have been defined, based on available evidence, that could substantially reduce early neonatal deaths if successfully implemented at scale within district and sub-district hospitals in LMIC. However, we illustrate that there remain many gaps in the evidence available to guide delivery of many inpatient neonatal interventions, that existing evidence is often from high income settings and that it frequently indicates uncertainty in the magnitude or even direction of estimates of effect. Furthermore generalizing results to LMIC where conditions include very high patient staff ratios, absence of even basic technologies, and a reliance on largely empiric management is problematic. Where there is such uncertainty over the effectiveness of interventions in different contexts or in the broad populations who might receive the intervention in routine care settings pragmatic trials that preserve internal validity while promoting external validity should be increasingly employed. Many interventions are introduced without adequate evidence of their effectiveness in the routine settings to which they are introduced. Global efforts are needed to support pragmatic research to establish the effectiveness in routine care of many interventions intended to reduce mortality or morbidity in LMIC. Such research should be seen as complementary to efforts to optimize implementation.

Directly observed therapy for treating tuberculosis.

BACKGROUND: Tuberculosis (TB) requires at least six months of treatment. If treatment is incomplete, patients may not be cured and drug resistance may develop. Directly Observed Therapy (DOT) is a specific strategy, endorsed by the World Health Organization, to improve adherence by requiring health workers, community volunteers or family members to observe and record patients taking each dose. OBJECTIVES: To evaluate DOT compared to self-administered therapy in people on treatment for active TB or on prophylaxis to prevent active disease. We also compared the effects of different forms of DOT. SEARCH METHODS: We searched the following databases up to 13 January 2015: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; EMBASE; LILACS and mRCT. We also checked article reference lists and contacted relevant researchers and organizations. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs comparing DOT with routine self-administration of treatment or prophylaxis at home. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias of each included trial and extracted data. We compared interventions using risk ratios (RR) with 95% confidence intervals (CI). We used a random-effects model if meta-analysis was appropriate but heterogeneity present (I(2) statistic > 50%). We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: Eleven trials including 5662 participants met the inclusion criteria. DOT was performed by a range of people (nurses, community health workers, family members or former TB patients) in a variety of settings (clinic, the patient's home or the home of a community volunteer). DOT versus self-administered Six trials from South Africa, Thailand, Taiwan, Pakistan and Australia compared DOT with self-administered therapy for treatment. Trials included DOT at home by family members, community health workers (who were usually supervised); DOT at home by health staff; and DOT at health facilities. TB cure was low with self-administration across all studies (range 41% to 67%), and direct observation did not substantially improve this (RR 1.08, 95% CI 0.91 to 1.27; five trials, 1645 participants, moderate quality evidence). In a subgroup analysis stratified by the frequency of contact between health services in the self-treatment arm, daily DOT may improve TB cure when compared to self-administered treatment where patients in the self-administered group only visited the clinic every month (RR 1.15, 95% CI 1.06 to 1.25; two trials, 900 participants); but with contact in the control becoming more frequent, this small effect was not apparent (every two weeks: RR 0.96, 95% CI 0.83 to 1.12; one trial, 497 participants; every week: RR 0.90, 95% CI 0.68 to 1.21; two trials, 248 participants).Treatment completion showed a similar pattern, ranging from 59% to 78% in the self-treatment groups, and direct observation did not improve this (RR 1.07, 95% CI 0.96 to 1.19; six trials, 1839 participants, moderate quality evidence). DOT at home versus DOT at health facility In four trials that compared DOT at home by family members, or community health workers, with DOT by health workers at a health facility there was little or no difference in cure or treatment completion (cure: RR 1.02, 95% CI 0.88 to 1.18, four trials, 1556 participants, moderate quality evidence; treatment completion: RR 1.04, 95% CI 0.91 to 1.17, three trials, 1029 participants, moderate quality evidence). DOT by family member versus DOT by community health workerTwo trials compared DOT at home by family members with DOT at home by community health workers. There was also little or no difference in cure or treatment completion (cure: RR 1.02, 95% CI 0.86 to 1.21; two trials, 1493 participants, moderate quality evidence; completion: RR 1.05, 95% CI 0.90 to 1.22; two trials, 1493 participants, low quality evidence). Specific patient categoriesA trial of 300 intravenous drug users in the USA evaluated direct observation with no observation in TB prophylaxis to prevent active disease and showed little difference in treatment completion (RR 1.00, 95% CI 0.88 to 1.13; one trial, 300 participants, low quality evidence). AUTHORS' CONCLUSIONS: From the existing trials, DOT did not provide a solution to poor adherence in TB treatment. Given the large resource and cost implications of DOT, policy makers might want to reconsider strategies that depend on direct observation. Other options might take into account financial and logistical barriers to care; approaches that motivate patients and staff; and defaulter follow-up.

Moving towards routine evaluation of quality of inpatient pediatric care in Kenya.

BACKGROUND: Regular assessment of quality of care allows monitoring of progress towards system goals and identifies gaps that need to be addressed to promote better outcomes. We report efforts to initiate routine assessments in a low-income country in partnership with government. METHODS: A cross-sectional survey undertaken in 22 'internship training' hospitals across Kenya that examined availability of essential resources and process of care based on review of 60 case-records per site focusing on the common childhood illnesses (pneumonia, malaria, diarrhea/dehydration, malnutrition and meningitis). RESULTS: Availability of essential resources was 75% (45/61 items) or more in 8/22 hospitals. A total of 1298 (range 54-61) case records were reviewed. HIV testing remained suboptimal at 12% (95% CI 7-19). A routinely introduced structured pediatric admission record form improved documentation of core admission symptoms and signs (median score for signs 22/22 and 8/22 when form used and not used respectively). Correctness of penicillin and gentamicin dosing was above 85% but correctness of prescribed intravenous fluid or oral feed volumes for severe dehydration and malnutrition were 54% and 25% respectively. Introduction of Zinc for diarrhea has been relatively successful (66% cases) but use of artesunate for malaria remained rare. Exploratory analysis suggests considerable variability of the quality of care across hospitals. CONCLUSION: Quality of pediatric care in Kenya has improved but can improve further. The approach to monitoring described in this survey seems feasible and provides an opportunity for routine assessments across a large number of hospitals as part of national efforts to sustain improvement. Understanding variability across hospitals may help target improvement efforts.

Tuberculosis as a cause or comorbidity of childhood pneumonia in tuberculosis-endemic areas: a systematic review.

Pneumonia is a major cause of morbidity and mortality in infants and children worldwide, with most cases occurring in tuberculosis-endemic settings. Studies have emphasised the potential importance of Mycobacterium tuberculosis in acute severe pneumonia in children as a primary cause or underlying comorbidity, further emphasised by the changing aetiological range with rollout of bacterial conjugate vaccines in high mortality settings. We systematically reviewed clinical and autopsy studies done in tuberculosis-endemic settings that enrolled at least 100 children aged younger than 5 years with severe pneumonia, and that prospectively included a diagnostic approach to tuberculosis in all study participants. We noted substantial heterogeneity between studies in terms of study population and diagnostic methods. Of the 3644 patients who had culture of respiratory specimens for M tuberculosis undertaken, 275 (7·5%) were culture positive, and an acute presentation was common. Inpatient case-fatality rate for pneumonia associated with tuberculosis ranged from 4% to 21% in the four clinical studies that reported pathogen-related outcomes. Prospective studies are needed in high tuberculosis-burden settings to address whether tuberculosis is a cause or comorbidity of childhood acute severe pneumonia.

Assessment of neonatal care in clinical training facilities in Kenya.

OBJECTIVE: An audit of neonatal care services provided by clinical training centres was undertaken to identify areas requiring improvement as part of wider efforts to improve newborn survival in Kenya. DESIGN: Cross-sectional study using indicators based on prior work in Kenya. Statistical analyses were descriptive with adjustment for clustering of data. SETTING: Neonatal units of 22 public hospitals. PATIENTS: Neonates aged <7 days. MAIN OUTCOME MEASURES: Quality of care was assessed in terms of availability of basic resources (principally equipment and drugs) and audit of case records for documentation of patient assessment and treatment at admission. RESULTS: All hospitals had oxygen, 19/22 had resuscitation and phototherapy equipment, but some key resources were missing­for example kangaroo care was available in 14/22. Out of 1249 records, 56.9% (95% CI 36.2% to 77.6%) had a standard neonatal admission form. A median score of 0 out of 3 for symptoms of severe illness (IQR 0-3) and a median score of 6 out of 8 for signs of severe illness (IQR 4-7) were documented. Maternal HIV status was documented in 674/1249 (54%, 95% CI 41.9% to 66.1%) cases. Drug doses exceeded recommendations by >20% in prescriptions for penicillin (11.6%, 95% CI 3.4% to 32.8%) and gentamicin (18.5%, 95% CI 13.4% to 25%), respectively. CONCLUSIONS: Basic resources are generally available, but there are deficiencies in key areas. Poor documentation limits the use of routine data for quality improvement. Significant opportunities exist for improvement in service delivery and adherence to guidelines in hospitals providing professional training.

Evidence review of hydroxyurea for the prevention of sickle cell complications in low-income countries.

Hydroxyurea is widely used in high-income countries for the management of sickle cell disease (SCD) in children. In Kenyan clinical guidelines, hydroxyurea is only recommended for adults with SCD. Yet many deaths from SCD occur in early childhood, deaths that might be prevented by an effective, disease modifying intervention. The aim of this review was to summarise the available evidence on the efficacy, effectiveness and safety of hydroxyurea in the management of SCD in children below 5 years of age to support guideline development in Kenya. We undertook a systematic review and used the Grading of Recommendations Assessment, Development and Evaluation system to appraise the quality of identified evidence. Overall, available evidence from 1 systematic review (n=26 studies), 2 randomised controlled trials (n=354 children), 14 observational studies and 2 National Institute of Health reports suggest that hydroxyurea may be associated with improved fetal haemoglobin levels, reduced rates of hospitalisation, reduced episodes of acute chest syndrome and decreased frequency of pain events in children with SCD. However, it is associated with adverse events (eg, neutropenia) when high to maximum tolerated doses are used. Evidence is lacking on whether hydroxyurea improves survival if given to young children. Majority of the included studies were of low quality and mainly from high-income countries. Overall, available limited evidence suggests that hydroxyurea may improve morbidity and haematological outcomes in SCD in children aged below 5 years and appears safe in settings able to provide consistent haematological monitoring.

Topical umbilical cord care for prevention of infection and neonatal mortality.

Umbilical cord care varies often reflecting community or health-worker beliefs. We undertook a review of current evidence on topical umbilical cord care. Study quality was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system, and a meta-analysis was conducted for comparable trials. Available moderate-quality to high-quality evidence indicate that cord cleansing with 4% chlorhexidine may reduce the risk of neonatal mortality and sepsis (omphalitis) in low-resource settings.