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Item Viral load suppression and retention in care among children and adolescents receiving multi-month anti-retroviral therapy refills: a program data review in Uganda(BioMed Central Ltd, 2024-12) Ainembabazi, Bridget; Ssebunya, Rogers N; Akobye, Winnie; Mugume, Alexander; Nahirya-Ntege, Patricia; Birungi, Denise J; Maganda, Albert K; Elyanu, Peter J; Kiragga, DithanAbstract Background In July 2022, Uganda’s Ministry of Health extended the 2021 WHO guidelines that recommended 3–6 monthly dispensing of antiretroviral therapy (ART) to include all children and adolescents living with HIV (CALHIV). Treatment outcomes following this recommendation have not yet been documented. We compared viral load (VL) suppression and retention in HIV care rates among CALHIV receiving 1, 2–5, and > = 6 monthly ART dispensation in Uganda. Methods A cross-sectional study of electronic medical records in 118 health facilities was conducted. Data for CALHIV 10–19 years captured at their most recent five clinic visits as of 15th May 2023 were analysed. Most recent two VL < 1000 copies/ml were used as measures for VL suppression and sustained VL suppression. A client was considered retained in care if they visited the clinic within 28 days from their expected return visit date. We used margins plots and a modified poisson model adjusting for facility level clustering to assess VL suppression and retention across multi-month ART categories. Results A total of 2864 CALHIV, 1609 (56.2%) being females and with a median age of 12 years (inter quartile range, iqr = 7) were included. Overall suppression and retention rates were 80.4% (2133/2654) and 87.8% (2514/2864) respectively. A significant number had been dispensed ART for ≥ 2 months (50%, 2–5 months and 43.5%, ≥ 6 months). Probability of having a suppressed VL was higher among CALHIV that had received ≥ 6 months and 2–5 months of ART compared to those of 1 month i.e., 83% vs 79% vs 41% respectively. Probability of being retained in care didn’t differ across multi-month ART categories. CALHIV who received ART for 2–5 months and ≥ 6 months compared to 1 month were more likely to have a suppressed VL; (adj.PR = 1.98; 95%CI:1.41, 2.80) and (adj.PR = 2.21; 95% CI:1.59, 3.05) respectively. CALHIV with a Tuberculosis diagnosis history were less likely to have a suppressed VL (adj.PR = 0.73; 95%CI:0.65,0.81), however this was not statistically significantly different between multi-month categories. Conclusion CALHIV receiving multi-month ART including 6 months dispensation had better VL suppression rates. Retention rates however didn’t differ by multi-month dispensing categories as observed among adults in the interval trial. We recommend multi-month ART dispensation including more than 6 months among CALHIV irrespective of their age, clinical stage, and history of prior co-morbidities.Item HIV Knowledge and Sexual Behaviors in Perinatally Infected Ugandan Youth: A Cross-Sectional Survey(SAGE Publications, 2024-12) Becker, Greta; Namanya, Paul; Kiganda, Charles; Nabukenya, Josephine; Wendt, Linder; Rukundo, Gordon; Yoyeta, Irene; Motevalli, Mahnaz; Mooberry, Megan; Voss, Natalie; Jackson, J Brooks; Etima, JulianeOur objective was to assess human immunodeficiency virus (HIV) knowledge and sexual behaviors in 294 perinatally HIV-infected youth aged 18 to 25 years from a psychosocial support group in Kampala using a self-administered survey. Seventy-nine percent reported an undetectable viral load, 9.5% detectable, and 12% did not know. Of those with sexual partners, 19% did not know the HIV status of their partner, 64% knew negative, and 22% knew positive. Sixty-two percent disclosed their HIV status to their partner. Seventy-two percent of participants previously had sex, and of those, 57% were sexually active in the last three months. Sixty-eight percent of participants used methods to prevent pregnancy. Seventy percent of participants denied physical, sexual, or emotional intimate partner violence. There was good adherence to antiretroviral therapy and a high proportion of contraceptive use, highlighting the importance of integrating these topics into psychosocial support programs for youth living with HIV.Item High recent PrEP adherence with point-of-care urine tenofovirtesting and adherence counselling among young African women:results from the INSIGHT cohort(John Wiley and Sons Inc, 2024-12) Gati Mirembe, Brenda; Donnell, Deborah; Krows, Meighan; Zwane, Zinhle; Bukusi, Elizabeth; Panchia, Ravindre; Louw, Cheryl; Mwelase, Noluthando; Selepe, Pearl; Senne, Melissa; Naidoo, Logashvari; Chihana, Rachel; Kasaro, Margaret; Nuwagaba-Biribonwoha, Harriet; Kotze, Philip; Gill, Katherine; MacDonald, Pippa; vanHeerden, Alastair; Bosman, Shannon; Jaggernath, Manjeetha; du Preez, Phillip; Ward, Amy; Peters, Remco P H; Delany-Moretlwe, Sinead; Et.alAdolescent girls and young women (AGYW) account for two-thirds of new HIV infections in Africa. African AGYW have had high uptake of oral HIV pre-exposure prophylaxis (PrEP) but low adherence, which might be improved by point-of-care adherence monitoring with tailored counselling. From August 2022 to July 2023, we conducted a PrEP demonstration project with sexually active AGYW ages 16-30 years from 20 sites in South Africa, Eswatini, Kenya, Malawi, Uganda and Zambia. Participants were offered oral tenofovir-based PrEP at enrolment and followed up at 1, 3 and 6 months. PrEP adherence was assessed by a point-of-care qualitative lateral flow urine tenofovir (TFV) assay indicating PrEP use in the prior 4 days, which accompanied real-time adherence counselling that incorporated urine TFV results when testing was available (70.8% of month 1, 35.3% of month 3 and 83.9% of month 6 visits). We estimated overall adherence, correcting for missing test results, and analysed the association of having received urine TFV results at month 1 or 3 with subsequent urine TFV test positivity, using modified Poisson regression. Of the 3087 AGYW enrolled, the median age was 24 years (interquartile range 21-27), 75.7% were from South Africa, 2878 (93.2%) initiated PrEP at enrolment and 107 (3.5%) after enrolment. Visit retention was 92.0-96.2% for months 1, 3 and 6, and 2518 (90.1%) exited the study with a PrEP refill. Adherence, based on the point-of-care urine tenofovir test positivity rate, was estimated as 72%, 71% and 65% at months 1, 3 and 6, respectively. Women who received one prior urine TFV test had a 42% higher likelihood of a subsequent positive urine TFV test (adjusted odds ratio, OR = 1.42, 95% confidence interval, CI 1.27-1.60), and those having received two prior tests had a 67% higher likelihood (adjusted OR = 1.67; 95% CI 1.41-1.98). Observed HIV incidence was 1.38/100 person-years (95% CI 0.97-2.08). Oral PrEP uptake, recent adherence and persistence were high in a multisite cohort of young African women over 6 months of follow-up. The use of a novel point-of-care tenofovir assay with tailored real-time adherence counselling was associated with increased adherence to PrEP at subsequent visits, warranting further study. clinicaltrials.gov NCT05746065.Item Causal Inference for Continuous Multiple TimePoint Interventions(Wiley Subscription Services, Inc, 2024-12) Schomaker, Michael; McIlleron, Helen; Denti, Paolo; Díaz, IvánThere are limited options to estimate the treatment effects of variables which are continuous and measured at multiple time points, particularly if the true dose-response curve should be estimated as closely as possible. However, these situations may be of relevance: in pharmacology, one may be interested in how outcomes of people living with-and treated for-HIV, such as viral failure, would vary for time-varying interventions such as different drug concentration trajectories. A challenge for doing causal inference with continuous interventions is that the positivity assumption is typically violated. To address positivity violations, we develop projection functions, which reweigh and redefine the estimand of interest based on functions of the conditional support for the respective interventions. With these functions, we obtain the desired dose-response curve in areas of enough support, and otherwise a meaningful estimand that does not require the positivity assumption. We develop -computation type plug-in estimators for this case. Those are contrasted with g-computation estimators which are applied to continuous interventions without specifically addressing positivity violations, which we propose to be presented with diagnostics. The ideas are illustrated with longitudinal data from HIV positive children treated with an efavirenz-based regimen as part of the CHAPAS-3 trial, which enrolled children years in Zambia/Uganda. Simulations show in which situations a standard g-computation approach is appropriate, and in which it leads to bias and how the proposed weighted estimation approach then recovers the alternative estimand of interest.Item Association of COVID-19-related perceptions and experiences with depression and anxiety in Ugandan caregivers of young children with malaria and iron deficiency: A cross-sectional study(Public Library of Science, 2024-12-10) Park, Saeun; Bangirana, Paul; Mupere, Ezekiel; Baluku, Reagan I; Helgeson, Erika S; Cusick, Sarah ECaregivers of young children may have been particularly vulnerable to mental health challenges during the COVID-19 pandemic due to its negative impacts on their housing, finances, and childcare demands. This study explored the associations between COVID-19-related experiences and symptoms of depression and anxiety among Ugandan caregivers. This cross-sectional study included 100 Ugandan caregivers of young children aged 6-59 months with uncomplicated malaria and iron deficiency (N = 85) and without malaria or anemia (N = 15) who were enrolled in the Optimizing Iron Status in Malaria-Endemic Areas (OptiM) study. Sociodemographic data and COVID-19 experiences were collected using an internally developed survey and symptoms of depression and anxiety were measured using the Hopkins Symptom Checklist (HSCL-25) and the Center for Epidemiologic Studies Depression (CESD-20) scale. Multiple linear regression models were used to assess the associations between COVID-19 survey scores with HSCL-25 or CESD-20 scores. Nearly half of caregivers reported clinically meaningful symptoms of depression (46%) and/or anxiety (49%). Caregivers had more severe symptoms of depression and/or anxiety if they experienced greater changes in living situations or decreases in physical activity (CESD-20: [beta] = 3.35, 95% CI [1.00, 5.70], p = .01), food insecurity (HSCL-25: [beta] = 3.25, 95% CI [0.41, 6.10], p = .03, CESD-25: [beta] = 3.09, 95% CI [0.79, 5.39], p = .01), and domestic violence (HSCL-25: [beta] = 3.82, 95% CI [0.94, 6.70], p = .01) during COVID-19. These associations did not vary depending on whether the caregivers had children with malaria. Negative COVID-19 experiences were significantly associated with more severe depression and anxiety in Ugandan caregivers, regardless of their children's malaria status. Urgent attention and action are needed to support the mental well-being of this vulnerable population. Further prospective studies should investigate the long-term impact of COVID-19 on caregivers and their children.Item Outcomes of an integrated knowledge translation approach in five African countries: a mixed-methods comparative case study(BioMed Central Ltd, 2024-12) Sell, Kerstin; Rehfuess, Eva; Osuret, Jimmy; Bayiga-Zziwa, Esther; Geremew, Bezinash; Pfadenhauer, LisaIntegrated knowledge translation (IKT) aims to enhance evidence-informed decision-making in public health and healthcare by establishing continuous relationships between researchers and knowledge users, in particular decision-makers. The Collaboration for Evidence-Based Healthcare and Public Health in Africa (CEBHA+) undertook research on noncommunicable diseases in Ethiopia, Malawi, Rwanda, South Africa and Uganda. Alongside the research activities, we implemented an IKT approach, which entailed training and the development and implementation of site-specific IKT strategies. We evaluated these strategies according to a predefined programme theory. Drawing on our published protocol (https://rdcu.be/dyfBP), we interviewed and surveyed CEBHA+ researchers and their decision-making counterparts during two project stages (3/2020-2/2021; 9/2022-5/2023) and collected IKT-related documents. Transcripts and documents were analysed using qualitative content analysis and surveys were analysed descriptively, with subsequent integration, cross-case analysis and revision of the programme theory. A total of 36 researchers and 19 decision-makers participated in surveys, focus groups and/or interviews, and we collected 92 documents. Relationship building, capacity building and collaborative research were the most proximal intervention outcomes: CEBHA+ researchers and their counterparts built mutual appreciation and partnerships, accessed contacts and networks, and expanded skills in conducting and using research and in IKT. The level of trust between partners varied. Intermediate outcomes were changes in attitudes and knowledge; beyond the conceptualization in our initial programme theory, researchers substantially increased their understanding of the decision-making context and developed a vision for "research impact". While it was challenging to evaluate distal outcomes, the IKT approach was linked to the production of research perceived as addressing local priorities and being highly applicable and contextualized, and some consideration of evidence among decision-makers. Unintended effects included high opportunity costs associated with undertaking IKT. An unanticipated outcome was the heightened interest of the research funder in policy engagement. Our updated programme theory constitutes a low-level theory for IKT. Whilst this study faced many challenges common to the evaluation of knowledge translation interventions, it presents rich, theory-informed insights into IKT outcomes. These are based on documented IKT activities and participants' views, particularly in-depth insights of researchers' experiences with implementing the CEBHA+ IKT approach.Item Successful Transduction of Liver in Hemophilia By AAV-Factor IX and Limitations Imposed by The Host Immune Response(Nature medicine, 2006-02-12) Manno, Catherine S.; Arruda, Valder R.; Kaye, Robin; Nakai, Hiroyuki; Sabatino, DeniseWe have previously shown that a single portal vein infusion of a recombinant adeno-associated viral vector (rAAV) expressing canine Factor IX (F.IX) resulted in long-term expression of therapeutic levels of F.IX in dogs with severe hemophilia B1. We carried out a phase 1/2 dose-escalation clinical study to extend this approach to humans with severe hemophilia B. rAAV-2 vector expressing human F.IX was infused through the hepatic artery into seven subjects. The data show that: (i) vector infusion at doses up to 2 × 1012 vg/kg was not associated with acute or long-lasting toxicity; (ii) therapeutic levels of F.IX were achieved at the highest dose tested; (iii) duration of expression at therapeutic levels was limited to a period of ∼8 weeks; (iv) a gradual decline in F.IX was accompanied by a transient asymptomatic elevation of liver transaminases that resolved without treatment. Further studies suggested that destruction of transduced hepatocytes by cell-mediated immunity targeting antigens of the AAV capsid caused both the decline in F.IX and the transient transaminitis. We conclude that rAAV-2 vectors can transduce human hepatocytes in vivo to result in therapeutically relevant levels of F.IX, but that future studies in humans may require immunomodulation to achieve long-term expression.Item Glypican-1 Identifies Cancer Exosomes and Detects Early Pancreatic Cancer(Nature, 2015-06-24) Melo, Sonia A.; Luecke, Linda B.; Kaye, Judith; Mittendorf, Elizabeth A.; Fraga, Mario F.; Kalluri, RaghuExosomes are lipid-bilayer-enclosed extracellular vesicles that contain proteins and nucleic acids. They are secreted by all cells and circulate in the blood. Specific detection and isolation of cancer-cell-derived exosomes in the circulation is currently lacking. Using mass spectrometry analyses, we identify a cell surface proteoglycan, glypican-1 (GPC1), specifically enriched on cancer-cell-derived exosomes. GPC1+ circulating exosomes (crExos) were monitored and isolated using flow cytometry from the serum of patients and mice with cancer. GPC1+ crExos were detected in the serum of patients with pancreatic cancer with absolute specificity and sensitivity, distinguishing healthy subjects and patients with a benign pancreatic disease from patients with early- and late-stage pancreatic cancer. Levels of GPC1+ crExos correlate with tumour burden and the survival of pre- and post-surgical patients. GPC1+ crExos from patients and from mice with spontaneous pancreatic tumours carry specific KRAS mutations, and reliably detect pancreatic intraepithelial lesions in mice despite negative signals by magnetic resonance imaging. GPC1+ crExos may serve as a potential non-invasive diagnostic and screening tool to detect early stages of pancreatic cancer to facilitate possible curative surgical therapy.Item Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment(New England Journal of Medicine, 2005-04-13) Petersen, Ronald C.; Thomas, Ronald G.; Kaye, Jeffrey; Sano, MaryMild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer’s disease. In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer’s disease; secondary outcomes were cognition and function.Item Cardiopulmonary Resuscitation of Adults in the Hospital: A Report Of 14 720 Cardiac Arrests from the National Registry of Cardiopulmonary Resuscitation(Resuscitation, 2003-09-12) Peberdy, Mary Ann; Kaye, William; Ornato, Joseph P.; Larkin, Gregory L.; Nichol, GrahamThe National Registry of Cardiopulmonary Resuscitation (NRCPR) is an American Heart Association (AHA)-sponsored, prospective, multisite, observational study of in-hospital resuscitation. The NRCPR is currently the largest registry of its kind. The purpose of this article is to describe the NRCPR and to provide the first comprehensive, Utstein-based, standardized characterization of in-hospital resuscitation in the United States. All adult (≥18 years of age) and pediatric (<18 years of age) patients, visitors, employees, and staff within a facility (including ambulatory care areas) who experience a resuscitation event are eligible for inclusion in the NRCPR database. Between January 1, 2000, and June 30, 2002, 14 720 cardiac arrests that met inclusion criteria occurred in adults at the 207 participating hospitals. An organized emergency team is available 24 h a day, 7 days a week in 86% of participating institutions. The three most common reasons for cardiac arrest in adults were (1) cardiac arrhythmia, (2) acute respiratory insufficiency, and (3) hypotension. Overall, 44% of adult in-hospital cardiac arrest victims had a return of spontaneous circulation (ROSC); 17% survived to hospital discharge. Despite the fact that a primary arrhythmia was one of the precipitating events in nearly one half of adult cardiac arrests, ventricular fibrillation (VF) was the initial pulseless rhythm in only 16% of in-hospital cardiac arrest victims. ROSC occurred in 58% of VF cases, yielding a survival-to-hospital discharge rate of 34% in this subset of patients. An automated external defibrillator was used to provide initial defibrillation in only 1.4% of patients whose initial cardiac arrest rhythm was VF. Neurological outcome in discharged survivors was generally good. Eighty-six percent of patients with Cerebral Performance Category-1 (CPC-1) at the time of hospital admission had a postarrest CPC-1 at the time of hospital discharge.Item Responsible, Safe, and Effective Prescription of Opioids for Chronic non-cancer pain: American society of interventional pain physicians (ASIPP) guidelines(Pain physician, 2017-01-02) Laxmaiah, Manchikanti; Kaye, Adam M.; Heath, McAnally; Trescot, Andrea M.Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Item The Ageing Systemic Milieu Negatively Regulates Neurogenesis and Cognitive Function(Nature, 2011-08-31) Villeda,Saul.A; Luo, Jian; Bieri, Gregor; Kaye, Jeffrey A.; Rando,Thomas A.In the central nervous system, ageing results in a precipitous decline in adult neural stem/progenitor cells and neurogenesis, with concomitant impairments in cognitive functions1. Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise1. Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired contextual fear conditioning and spatial learning and memory. We identify chemokines—including CCL11 (also known as eotaxin)—the plasma levels of which correlate with reduced neurogenesis in heterochronic parabionts and aged mice, and the levels of which are increased in the plasma and cerebrospinal fluid of healthy ageing humans. Lastly, increasing peripheral CCL11 chemokine levels in vivo in young mice decreased adult neurogenesis and impaired learning and memory. Together our data indicate that the decline in neurogenesis and cognitive impairments observed during ageing can be in part attributed to changes in blood-borne factors.Item Epithelial-to-Mesenchymal Transition is Dispensable for Metastasis but Induces Chemoresistance in Pancreatic Cancer(Macmillan Publishers Limited, 2015-11-26) Xiaofeng Zheng,Julienne L. Carstens,Jiha Kim,Kaye Judith,Hikaru Sugimoto,Raghu KalluriDiagnosis of pancreatic ductal adenocarcinoma (PDAC) is associated with a dismal prognosis despite current best therapies; therefore new treatment strategies are urgently required. Numerous studies have suggested that epithelial-to-mesenchymal transition (EMT) contributes to early-stage dissemination of cancer cells and is pivotal for invasion and metastasis of PDAC1–4. EMT is associated with phenotypic conversion of epithelial cells into mesenchymallike cells in cell culture conditions, although such defined mesenchymal conversion (with spindle-shaped morphology) of epithelial cells in vivo is rare, with quasi-mesenchymal phenotypes occasionally observed in the tumour (partial EMT)5,6. Most studies exploring the functional role of EMT in tumours have depended on cell-culture-induced loss-of-function and gain-of-function experiments involving EMT-inducing transcription factors such as Twist, Snail and Zeb1 (refs 2,3,7–10). Therefore, the functional contribution of EMT to invasion and metastasis remains unclear4,6, and genetically engineered mouse models to address a causal connection are lacking. Here we functionally probe the role of EMT in PDAC by generating mouse models of PDAC with deletion of Snail or Twist, two key transcription factors responsible for EMT. EMT suppression in the primary tumour does not alter the emergence of invasive PDAC, systemic dissemination or metastasis. Suppression of EMT leads to an increase in cancer cell proliferation with enhanced expression of nucleoside transporters in tumours, contributing to enhanced sensitivity to gemcitabine treatment and increased overall survival of mice. Collectively, our study suggests that Snail- or Twist-induced EMT is not rate-limiting for invasion and metastasis, but highlights the importance of combining EMT inhibition with chemotherapy for the treatment of pancreatic cancer.Item EEG background activity, seizure burden and early childhood outcomes in neonatal encephalopathy in Uganda: a prospective feasibility cohort study(Elsevier B.V, 2024-12) Mathieson, Sean R.; Nanyunja, Carol; Sadoo, Samantha; Nakalembe, Sherinah; Duckworth, Eleanor; Muryasingura, Stella; Niombi, Natalia; Proietti, Jacopo; Busingye, Mariam; Nakimuli, Annettee; Livingstone, Vicki; Webb, Emily L.; Mambule, Ivan; Boylan, Geraldine B.; Tann, Cally J.ntrapartum-related neonatal encephalopathy (NE) is a leading cause of childhood mortality and morbidity. Continuous electroencephalography (EEG) is gold standard for neonatal brain monitoring; however, low-income country data is lacking. We examined EEG in a Ugandan cohort with NE to describe feasibility, background activity, seizure prevalence and burden, and associations with clinical presentation and outcome. Neonates with NE were recruited from a single hospital referral centre in Kampala, Uganda (Oct 2019–Oct 2020) and underwent EEG monitoring. Feasibility was assessed as to whether EEG monitoring of diagnostic quality could be achieved from days 1–5. Evolution of clinical presentation was assessed by Sarnat classification and daily Thompson score was performed. EEG background severity was graded at 12, 24, 48 and 72 h after birth, and at time of Thompson score. Seizures were annotated remotely by experts and assessed for frequency, duration, burden, and status epilepticus. Early childhood outcome was assessed at follow up, and adverse outcome defined as death or neurodevelopmental impairment (NDI) at 18–24 months of age. In this prospective feasibility cohort study, diagnostic quality EEGs were recorded for 50 of 51 recruited neonates (median duration 71.4 h, IQR 52.4–72.2), indicating feasibility. Of 39 participants followed to 18–24 months, 13 died and 7 had NDI. Daily Thompson score and EEG background grade were strongly correlated across all timepoints (days 1–5). Thompson score of ≥7 was most predictive of moderate-severe EEG background abnormality (AUC 0.83). Prognostic accuracy of moderate-severe EEG background grade to predict NDI was high (AUC 0.74). Electrographic seizures were seen in 52% (26); median seizure burden was high at 264 min (IQR 27.8–523.7, range 1.3–1374.1); half (13) had status epilepticus. EEG monitoring was feasible as a research tool in this sub-Saharan Africa setting. EEG background activity correlated strongly with scored neurological assessment and predicted adverse early childhood outcome. Seizure prevalence and burden, including status epilepticus, were high in this uncooled cohort with important potential longer-term implications for survivors. Bill & Melinda Gates Foundation grant number OPP1210890; Wellcome Trust Innovator award (209325/Z/17/Z).Item A cross-sectional study of point-of-care lactate testing in integrated community care management (ICCM) for children with acute respiratory illness in rural uganda(2024-11) Matte, Michael; Koyama, Natsumi; Giandomenico, Dana; Baguma, Emmanuel; Kibaba, Georget; Ntaro, Moses; Reyes, Raquel; Mulogo, Edgar M; Boyce, Ross M; Ciccone, Emily JxxAbstract Background Integrated community case management (iCCM) programs leverage lay village health workers (VHWs) to carry out the initial evaluation of children with common conditions including malaria, pneumonia and diarrhea. Therefore, it is imperative that VHWs are able to identify children who are critically ill and require referral to a health facility. Elevated venous lactate levels have been associated with severe illness and adverse health outcomes, including death. However, lactic acidosis may not be recognized in rural settings because it is not routinely measured outside of hospitals and research studies. Point-of-care lactate tests may help identify patients in need of a higher level of care and improve VHWs’ ability to make timely and appropriate referrals. Methods The study was a cross-sectional evaluation of children aged <5 y presenting to VHWs in rural southwestern Uganda with complaints of fever and cough. Demographics, clinical presentation, evaluation, management and disposition were recorded. VHWs were trained and instructed to perform lactate testing using a point-of-care assay in eligible participants. Results During the study period, 238 children were enrolled and completed an initial assessment. Of the 204 participants included in the analysis, 113 (55.4%) were female, and the median (IQR) age was 23 (9–36) months. Most participants, 139/200 (69.5%), had negative results on the malaria rapid diagnostic test. The median lactate level was 2.1 mmol/L; 12% (24/204) had a lactate ≥3.5 mmol/L and only nine participants (4.4%) had a lactate ≥5 mmol/L. Having a lactate level above either cut-off was not associated with the presence of danger signs at presentation. Conclusions Few children presenting with fever and cough to VHWs in western Uganda had elevated lactate levels. However, most of the children with elevated lactate levels did not otherwise satisfy established iCCM criteria based on physical examination findings for referral to a health facility. Therefore, while elevated lactate was not associated with danger signs in this small study, it is possible that there is under-recognition of severe illness using current iCCM guidelines.Item Combining a guided self-help and brief alcohol intervention to improve mental health and reduce substance use among refugee men in Uganda: a cluster-randomized feasibility trial(Cambridge University Press, 2024-11) Greene, M. Claire; Andersen, Lena S; Leku, Marx R; Au, Teresa; Akellot, Josephine; Upadhaya, Nawaraj; Odokonyero, Raymond; White, Ross; Ventevogel, Peter; Garcia-Moreno, Claudia; Tol, Wietse AAbstract Evidence on the effectiveness and implementation of mental health and psychosocial support (MHPSS) interventions for men in humanitarian settings is limited. Moreover, engagement and retention of men in such interventions has been challenging. Adaptations may therefore be required to improve the appropriateness and acceptability of these interventions for men. This study conducted formative research and examined the feasibility of combining an MHPSS intervention, Self-Help Plus, with a brief intervention to reduce harmful alcohol use among refugee men in Uganda. We conducted a cluster randomized feasibility trial comparing the combined alcohol intervention and Self-Help Plus, Self-Help Plus alone and enhanced usual care. Participants were 168 South Sudanese refugee men in Rhino Settlement who reported moderate or high levels of psychological distress. Session attendance was adequate: all sessions had at least 69% of participants present. Participant outcome measures, including symptoms of psychological distress, functional impairment, self-defined problems, depressive symptoms, post-traumatic stress symptoms, overall substance use risk, substance specific risk (alcohol, cannabis, stimulants and sedatives) and well-being, were sensitive to change. A combined approach to addressing mental health and alcohol use appears feasible among men in refugee settings, but further research is needed to examine the effectiveness of combined interventions among men.Item The prevalence of occupational-related low back pain among working populations in sub-saharan Africa: a systematic review and meta-analysis(2024-10) Atalay, Yibeltal Assefa; Gebeyehu, Natnael Atnafu; Gelaw, Kelemu AbebeWork-related musculoskeletal disorders represent a major public health problem, contributing significantly to the global burden of disability-adjusted life years and affecting the quality of life of all population groups. The main problem in most musculoskeletal disorders is low back pain. Therefore, our study aims to identify the overall prevalence of work-related low back pain among the working population in sub-Saharan Africa. Research published between 2010 and 2023 in English, conducted in Sub-Saharan Africa was included in this systematic review and meta-analysis. Using Boolean logic operators and targeted keywords, we searched for publications on a number of electronic databases (Web of Science, PubMed, Google Scholar, African Journals Online (AJOL), and Science Direct). The Joanna Briggs Institute Critical Appraisal techniques were utilized to conduct a quality assessment of the papers and ascertain their relevance to the study. The degree of heterogeneity among the included studies, the 95% confidence interval, and the pooled prevalence were estimated using a random effects model. Sensitivity studies were carried out to determine the causes of heterogeneity and the impact of outliers. In this study, a total of 970 articles were retrieved, and 35 studies were included in the systematic review and meta-analysis. The overall estimated pooled prevalence of low back pain among the working population in sub-Saharan Africa was (55.05% [95% CI: 49.34, 60.76]). Based on a sub-group analysis by countries, the higher pooled prevalence of low back pain was found in Uganda at (61.48% [95% CI: 40.39, 82.57]), while the lower pooled prevalence of low back pain was in Ghana at (34.48% [95% CI: 17.96, 51.01]). This systematic review and meta-analysis found that 55.05% of the included study participants experienced low back pain in the previous years. Therefore, it is recommended that policymakers incorporate and enhance strategies for the prevention and management of low back pain within the health system management guidelines of each country.Item Participatory research with youth with disabilities: Experiences from sub-Saharan Africa(African Online Scientific Information Systems (Pty) Ltd t/a AOSIS, 2024-10) Bannink Mbazzi, Femke; Hameed, Shaffa; Ganle, John K; Shakespeare, Tom; Polack, SarahBackground: Disability inclusive youth research, involving youth with disabilities in the design, implementation and dissemination of study data, is still limited in Africa.Objectives: To describe and reflect on the experiences of involving youth with disabilities in an exploratory research study, focused on disability-inclusive education and employment in 7 African countries.Method: 12 youths with different impairments, aged 18 to 35, were employed as researchers in Ethiopia, Ghana, Kenya, Nigeria, Rwanda, Senegal and Uganda. Youth researchers contributed to the data collection and analysis of interviews with 210 youth with disabilities. 24 youth advisors with disabilities formed two youth advisory groups (YAG) of 12 advisors each in the regional hub countries Ghana and Uganda. The YAGs met 4 times during the project and contributed to the study design, data collection, data analysis and dissemination activities. In addition, 4 workshops were held with the Ugandan YAG to develop a participatory film.Results: Together with the youth participants, we reflected on the experiences of involving youth with disabilities and conducting research with, by and on youth with disabilities. We highlighted ethics and safeguarding, recruitment and representation, exploring experiences and data quality, participatory dissemination, accessibility, capacity building and networking as key areas of consideration and benefit in this project.Conclusion: Participatory research with youth with disabilities is feasible, enriching, and key to inclusive research that informs education and employment policy and practices.Contribution: Lessons learned from youth involvement in a disability inclusive research programme, focused on education and employment in 7 African countries.Item Irrational acts: Maternal death, women’s agency, and the obligation to care in Uganda(PubMed, 2024-04-21) Boyd, LydiaFollowing the recommendation of the WHO in the mid-2000s, the Ugandan government banned traditional birth attendants (TBAs) and encouraged all women to give birth in biomedical clinics. Yet in rural Luuka district, about half of women still give birth at home or with the assistance of lay providers. This article examines women's healthcare behavior to better understand decisions that are characterized as irrational by officials, in particular women's choices to delay care, move between providers, and defer health decisions to others. Building on anthropological interest in the relationality of care, this article explores how women compel the care of others, especially under conditions of healthcare scarcity and in contexts outside clinical settings. A focus on the gendered nature of kin-based care provides insight into how acts often characterized as irrational can be modes of action for women in ways that exceed a policy focus on healthcare choice and autonomy.Item Prevalence of teenage pregnancy and associated factors in Uganda: a meta-analysis and systematic reviews protocol(BMJ Publishing Group LTD, 2024-10) Aremu, Abdulmujeeb Babatunde; Afolabi, Ismail Bamidele; Awunor, Nyemike Simeon; Sumayah, Nakitende; Mujeeb, Salaam; Mahjub, Atiku SaadTeenage pregnancy is a major public health problem with huge consequences for maternal health and pregnancy outcomes. More than 90% of these live births are estimated to occur in developing countries. The objective of this review is to estimate the prevalence of teenage pregnancy and its associated factors in Uganda. This review protocol will be registered with the PROSPERO database and will be designed following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. A literature search will be conducted in PubMed, African Journals OnLine, Science Direct and Google Scholar in December 2023. Observational studies that report the prevalence of teenage pregnancy will be included. Studies will be assessed for the risk of bias in duplicate. The data will be pooled using random-effects models to estimate the prevalence of teenage pregnancy, with a 95% CI and I statistic capturing heterogeneity. This review will not require ethical approval. The findings from the data synthesis will be published in relevant peer-reviewed journals and conferences targeting adolescent and reproductive health. CRD42023486460. MEDLINE