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Strengths and limitations of urinary sugar testing: an observational study of intestinal permeability and absorption in adults and children in Zambia and Tanzania with reference to mucosal biopsies.
BACKGROUND: Sugar-based permeability testing has been used to report changes in intestinal barrier function in clinical and public health research over 5 decades, but it is still uncertain what these tests measure at a cellular level.
OBJECTIVES: We set out to correlate recoveries of lactulose, rhamnose, xylose, 3-O-methyl-D-glucose, and the lactulose:rhamnose recovery ratio (LRR), and where possible, compare with mucosal structure. All sugar testing employed consistent doses and duration of urine collection (3 h).
METHODS: Analysis of sugar recoveries in 7 published and unpublished observational studies in adults and children with environmental enteropathy in Zambia and Tanzania over 24 y, alongside comparison with mucosal biopsy analysis in a subset in Zambia. In one of the biopsy studies, local healthy controls (n = 13) contributed data.
RESULTS: From 7 studies, we assembled a database of 1461 lactulose-based tests; in 422 of these tests, satisfactory morphometry of small intestinal biopsies was also available. Across all studies, lactulose recovery was strongly correlated with recoveries of rhamnose (Spearman's ρ = 0.64; P < 0.0001), xylose (ρ = 0.59; P < 0.0001), and 3-O-methyl-D-glucose (ρ = 0.57; P < 0.0001). LRR was inversely correlated with epithelial surface area (ESA; ρ = -0.26; P = 0.0001), and 3-O-methyl-D-glucose demonstrated the strongest positive correlation with ESA (ρ = 0.19; P = 0.007). Differences in LRR by sex and HIV serostatus were largely due to differences in rhamnose recovery. Statistical analysis was correlational and included linear and fractional polynomial regression models.
CONCLUSIONS: LRR does distinguish between healthy and enteropathic states. However, these data suggest that test sugars may all permeate through the intestinal epithelium through common pathways, not necessarily distinguishing between pore, leak, or unrestricted pathways or transcellular absorption
Coping with extreme heat in primary maternity care: An ethnography of frontline health workers in rural Zimbabwe
Highlights:
•Health workers deliver maternity care in conditions of extreme, escalating heat.
•First empirical qualitative study in Africa to examine how staff navigate extreme heat in maternity wards.
•First qualitative ethnography globally to apply Adaptive Thermal Comfort Theory to clinical labour.
•Heat adaptation emerges as a collective, resource-dependent, institutional and material process.
•Protecting frontline staff from extreme heat is essential for climate-resilient health systems
Community engagement and implementation science: a hermeneutic review for implementation scientists.
BackgroundCommunity engagement is increasingly part of implementation research. However, some implementation scientists are less familiar with how to use community engagement approaches in implementation research. This hermeneutic review explores the gaps in community engagement within implementation research and examines community engagement approaches for implementation researchers.MethodsWe conducted a hermeneutic review to synthesize information in the literature on community engagement in implementation research. We searched PubMed related to community engagement and implementation research. Articles were eligible for inclusion if they were published in English, had full-text available and were likely to add meaning and valuable insights to address our research questions. The review involved multiple, iterative rounds of interpretation. We examined commonly reported community engagement approaches in implementation research. We also reported potential benefits, risks, and epistemic considerations of each approach.ResultsA total of 477 citations were identified and 67 studies were included. Crowdsourcing, participatory modeling, qualitative research, co-creation, community capacity strengthening and community advisory boards can engage communities in implementation research. Each approach has unique benefits, risks, and epistemic considerations. Beyond the many substantive and technical reasons to engage communities, there is an epistemic rationale for robust community engagement. Researchers who deeply engage local communities may be able to provide an opportunity for transformative social change. However, tokenistic community engagement and minimal engagement are both common.ConclusionsAlthough community engagement has great potential to enhance implementation research, it has not received the attention it deserves. Community engagement can contribute to deeper alliances between researchers and communities, sparking social change needed to improve health equity
Clinical and patient-reported outcomes of cutaneous leishmaniasis treatment in Ethiopia: A prospective, observational cohort study in two referral hospitals.
BACKGROUND: Cutaneous leishmaniasis (CL) is a major public health concern, particularly in Ethiopia, where about 40,000 new cases occur annually, predominantly caused by Leishmania aethiopica. Clinical phenotypes include localized CL (LCL), mucocutaneous leishmaniasis (MCL), and diffuse CL (DCL). OBJECTIVES: Despite the high disease burden, treatment options and high-quality data on treatment outcomes remain limited. We evaluated the effectiveness of standard treatments in Ethiopia to inform future clinical trials. METHODS: We conducted an observational cohort study of patients with parasitologically confirmed cutaneous leishmaniasis at two specialized dermatology referral hospitals. Clinical and patient-reported outcomes were assessed at baseline and at standardized times during follow-up. The primary clinical outcome measure ("cure") was complete re-epithelialization or flattening of the index lesion at Day 90. Patient-reported outcomes were assessed using both skin-specific and general quality of life scores. RESULTS: We enrolled 666 participants from April 2022 to October 2023. The median age was 20 years (IQR: 14-35) and 405 were male (60.8%). More than half (55.9%) had previously received traditional treatment for CL. Most participants had LCL (58.6%) or MCL (35.2%). Intramuscular sodium stibogluconate 20mg/kg/day was the most frequently used systemic therapy, either alone or in combination with lesion-directed therapy (cryotherapy or intralesional sodium stibogluconate). At Day 90, 28.3% of participants with LCL, 23.5% with MCL, and 8.3% with DCL were cured. By Day 90, all patient-reported outcomes of skin health improved for those with LCL or MCL, but skin and CL-related quality of life scores did not improve for DCL. Most participants (81.4%) experienced at least one clinical adverse event and 7.2% had abnormal laboratory findings during treatment. CONCLUSIONS: Current treatment strategies have low cure rates in Ethiopia. Well-designed randomized controlled trials are urgently needed to improve management of CL caused by L. aethiopica
"If there was no stigma around it, I would tell people": perspectives of UK youth living with perinatally acquired HIV, their social networks and healthcare professionals on HIV status sharing.
Sharing one's HIV status with others is complex for youth with perinatally acquired HIV (PAH). However, the support from sharing one's HIV status may assist with HIV-related challenges. This study explored barriers and facilitators of HIV status sharing among UK-based youth living with PAH. Drawing on semi-structured interviews with ten youth with PAH, ten members of their social networks and five HIV professionals, this study examined the complex relational nature of disclosure. The data were examined using thematic analysis. While many youths expressed a desire to be open, sharing was shaped by stigma, cultural silence, familial secrecy, fear of rejection and lack of HIV education. Facilitators included emotional readiness, peer support, increased knowledge and positive prior experiences of disclosure. Social network participants often saw themselves as supportive, although professionals tended to focus on potential emotional risks. This study underscores disclosure as a process requiring ongoing support and suggests that empowering youth with education, skills and confidence is key. It identifies the need for better professional guidance and disclosure interventions co-designed with youth to support health and well-being. The findings have implications for stigma reduction, education and psychosocial support, contributing to improving the quality of life for youth with PAH
'No one ever asked for my suggestions…': photo-elicitation with forcibly-displaced Rohingya about humanitarian responses to mass displacement in Cox's Bazar.
Since 2017, more than 600 000 Rohingya have sought refuge in Bangladesh, as Forcibly Displaced Myanmar Nationals (FDMN), in registered camps or improvised settlements in Cox's Bazar. Although humanitarian responses have significantly improved in the past decades, coordination gaps remain between health and non-health sectors (eg, little is known about the impacts of shelter or protection responses on refugee health). We thus aimed to explore FDMN perspectives on issues affecting their health to help inform health system responses to mass displacement in Cox's Bazar.We conducted photo-elicitation interviews with 39 FDMN in Kutupalong and Balukhali camps. Each participant-researcher pair photographed three to five images of participants' lived environment, then participants described each photograph and why chosen in interviews. We analysed data thematically.Participants reflected daily difficulties and indignities, due to open sewerage and limited potable water, alongside health and safety risks (eg, flimsy and insecure shelters, gas leaks), particularly for children, older people and those with special needs. Health services were reportedly basic and sometimes unfriendly. Participants advocated for health and safety improvements, providing photographic evidence of the risks they experienced daily.Photo-elicitation was valuable for visualising participants' daily lives and provided participants with a means to advocate for improvements in undignified and risky living conditions. Interviews enabled articulation of perceived effects on physical and mental health and recurrent themes of 'abandonment', with limited services and few pathways for change. Highlighting Rohingya experiences can help identify ways to improve living conditions, services and well-being
Factors affecting the implementation of a whole-school relationships and sexual health intervention: staff perspectives from trial-nested qualitative research in English secondary schools
Whole-school relationships and sexual health interventions represent promising approaches to promoting healthy sexual development. However, data from a randomised controlled trial of the Positive Choices whole-school intervention demonstrate these may be challenging to implement in English secondary schools. We draw on qualitative data to examine staff perspectives on the implementation of the intervention and the factors affecting delivery. Interviews were conducted with 52 staff in 22 schools. Analysis was guided by May’s General Theory of Implementation, focussing on how processes of sense making, cognitive participation, collective action and reflexive monitoring were shaped by intervention capability, school capacity, and staff potential. Quality training, materials and support, alongside a strong commitment to delivery of statutory relationships and sex education promoted curriculum implementation. However, whole-school components were viewed as more challenging to implement and often beyond the ‘core business’ of schools. Successful implementation of whole-school components was facilitated by a supportive school culture, school leads having the authority to enable collective action and close alignment with school priorities and institutional processes. For whole-school interventions to succeed, sufficient time and resources must be allocated. A pragmatic approach might be to develop whole-school approaches that address health more holistically and build effectively on existing provision
Quantifying selection bias due to unobserved patients in pharmacoepidemiologic studies of severe COVID-19 cohorts.
BACKGROUND: The COVID-19 pandemic caused hospital pressures resulting in some patients with severe COVID-19 not being admitted. Studies aiming to measure treatment effects in patients with severe COVID-19 might produce biased estimates if restricted to hospitalised cohorts as a subset of the target population remained unobserved. AIM: To quantify the effects of potential selection bias due to deaths outside of hospital in a case study of inhaled corticosteroids (ICS) and COVID-19 death among people with chronic obstructive pulmonary disease (COPD) hospitalised with COVID-19.
METHODS: Using Clinical Practice Research Datalink Aurum linked to hospitalisation and death registries, we defined a cohort with COPD on 01 Mar 2020, followed up until 31st August 2020. We assessed the odds of COVID-19 death (International Classification of Diseases, 10th Revision U07) among hospitalised COVID-19 patients, comparing current users of ICS/long-acting β-agonist (LABA) and LABA/long-acting muscarinic antagonist (LAMA)). Our target population was those with COPD and severe COVID-19. We evaluated potential selection bias due to non-admission of severe COVID-19 cases using quantitative bias analysis (QBA) in four plausible scenarios, varying assumed death rates among non-hospitalised patients. Selection probabilities for deaths due to COVID-19 were known. The assumptions were: (1) equal odds of death between non-hospitalised and hospitalised groups; (2) doubled odds of death in non-hospitalised ICS/LABA group compared to hospitalised; (3) halved odds of death in non-hospitalised ICS/LABA group; and (4) doubled odds of death in both treatment groups among non-hospitalised patients. We calculated bootstrapped 95% confidence intervals (CIs).
RESULTS: During the study period, 107 ICS/LABA users and 133 LABA/LAMA users were hospitalised with COVID-19. COVID-19 deaths occurred in 42 (39.3%) ICS/LABA users versus 50 (37.6%) LABA/LAMA users. The OR after inverse probability of treatment weighting was 1.01 (95% CI 0.59–1.72). In scenario 1, the OR was unchanged (OR 1.07, 95% CI 0.70–1.67). In scenario 2, the corrected OR was 1.28 (95% CI 0.83–2.00). In scenario 3, the corrected OR was 0.81 (95% CI 0.52–1.23). In scenario 4, the corrected OR was 1.08 (95% CI 0.69–1.71).
CONCLUSION: QBA facilitated an assessment of the sensitivity of study results to potential selection bias due to non-admission of a subset of patients with severe COVID-19. The results of the four scenarios presented are in line with the null hypothesis, but CIs were wide. Death rates in the non-hospitalised would have needed to be substantially different in the treatment groups to change the study conclusions.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12874-025-02732-w
Effect of data-collection method on reporting of common mental disorder symptoms and intimate partner violence in Zimbabwe: a cluster-randomized trial.
BACKGROUND: Screening for sensitive and stigmatized conditions such as mental health or experience of violence is challenging. Audio computer-assisted self-interviewing (ACASI), administered by using a tablet and headphones, may be more sensitive for this purpose than paper-based self-administered questionnaires (SAQ) handed in to project staff. We conducted a methodological cluster-randomized trial in Zimbabwe to compare two methods of screening for common mental disorders (CMD) and intimate partner violence (IPV): ACASI versus SAQ. METHODS: Trial participants were health workers receiving occupational health checks at hospitals and primary health clinics. The unit of randomization was a working day. CMD was measured by using the Shona Symptom Questionnaire, anxiety by using the Generalised Anxiety Disorder-7 questionnaire, and IPV by using the World Health Organization screening questionnaire. The co-primary outcomes were CMD prevalence and the prevalence of any IPV, compared by arm at the cluster level, adjusting for gender and weekend. Secondary outcomes were the prevalence of anxiety and of physical, emotional, and severe physical and sexual IPV. RESULTS: Between 20 February and 10 June 2022, 1240 participants were enrolled in 71 clusters (workdays), with 77.0% female and 66.4% in clinical-facing roles. The cluster-level geometric mean prevalence of CMD was 19.4% when using ACASI and 14.1% when using SAQ [adjusted risk ratio (aRR) 1.37, 95% confidence interval (CI) 0.99, 1.89; P = .056]. ACASI yielded a higher prevalence of overall IPV than the SAQ (cluster-level geometric mean prevalence 40.6% compared with 22.4%, aRR 1.81, 95% CI 1.40, 2.35; P < .001), of emotional IPV (aRR 1.66, 95% CI 1.27, 2.17; P < .001), and of physical IPV (aRR 1.61, 95% CI 1.16, 2.25; P = .005). No differences were seen in the prevalence of severe physical or sexual IPV or anxiety across the trial arms. CONCLUSION: Screening for CMD and IPV by using a confidential ACASI method identifies more people who may benefit from care than screening by using SAQ handed in to clinic staff. This may be explained by under-reporting on the SAQ. ACASI is a promising screening method for sensitive issues in healthcare settings
Survival for Children Diagnosed With Wilms Tumour (2012-2022) Registered in the UK and Ireland Improving Population Outcomes for Renal Tumours of Childhood (IMPORT) Study.
BACKGROUND: The Improving Population Outcomes for Renal Tumours of childhood (IMPORT) is a prospective clinical observational study capturing detailed demographic and outcome data on children and young people diagnosed with renal tumours in the United Kingdom and the Republic of Ireland. METHODS: Data were extracted from the IMPORT database for all newly diagnosed cases of Wilms tumour (WT) registered between November 2012 and December 2022. Kaplan-Meier survival was estimated at one, three and five years. For children aged 0-14 years with unilateral WT, Cox proportional hazards models were used to examine patient/tumour characteristics in relation to the excess hazard of death. RESULTS: Among 620 patients, 570 had unilateral and 50 (8%) bilateral disease; 582 (94%) patients received pre-operative chemotherapy and 38 (6%) immediate surgery. Median age was 41 months (IQR: 41-65). Median tumour volume at diagnosis was 595 cm3 (IQR: 348-914) and 228 cm3 (IQR: 83-535) after pre-operative chemotherapy, with 123/443 (28%) ≥500 cm3. Of 570 patients with unilateral WT, 419 (73.5%) had localised and 151 (26.5%) metastatic disease. Five-year survival was highest for children aged 0-4 years (94.8%). Five-year survival by Toronto stage (assessed at nephrectomy) was 97.0% (stage I/yI), 93.8% (stage II/yII), 85.2% (stage III/yIII) and 88.9% (stage IV), and by histology 74.6% (high risk), 95.2% (intermediate risk) and 100% (low risk). In univariate analysis, histological risk group, age (</≥ 4 years), stage and tumour volume ≥500 cm3 after pre-operative chemotherapy were significantly associated with excess risk of death. In multivariate modelling, only high-risk histology (HR 10.8, 95% CI: 4.0-29.1) retained significance. CONCLUSIONS: Five-year survival for children with WT in the United Kingdom and Ireland is generally above 90%, with high-risk histology as the most important adverse prognostic factor. However, median tumour volume at diagnosis and after pre-operative chemotherapy remains large