Client-perpetrated gender-based violence among female sex workers in conflict-affected northern Uganda: a cross-sectional study

Study objective: To determine the prevalence and associated factors of client-perpetrated gender-based violence among female sex workers in conflict-affected Northern Uganda. Design and settings: We conducted a cross-sectional study among female sex workers in Gulu district in conflict-affected Northern Uganda. Participants: The study participants included 300 female sex workers aged 18+ years. The participants were selected using simple random sampling from a database of female sex workers maintained at a national non-governmental organisation in Gulu. Outcome: measure The outcome measure was self-reported exposure to client-perpetrated gender-based violence. Methods: We used a pretested semistructured questionnaire to collect data on sociodemographic characteristics, sex work-related characteristics, alcohol use, illicit drug use, HIV status and self-reported exposure to client-perpetrated gender-based violence. Then, data were entered into Epi Info V.7 and analysed using Stata V.14.0. Results: Among participants, 61.0% reported client-perpetrated gender-based violence. Economic (58.7%) and emotional (52.0%) violence were the most common forms of client-perpetrated gender-based violence in this population. Independently, being: street-based (adjusted OR=9.66, 95% CI 2.78 to 33.5), mobile (adjusted OR=3.21, 95% CI 1.83 to 5.64), HIV-positive (adjusted OR=1.90, 95% CI 1.09 to 3.31) and a low-income earner (<USh200 000 monthly) (adjusted OR=2.26, 95% CI 1.18 to 4.30) were positively associated with exposure to client-perpetrated gender-based violence. Conclusions: There is a high prevalence of client-perpetrated gender-based violence among female sex workers in conflict-affected Northern Uganda. Furthermore, female sex workers who were street-based, mobile, HIV-positive and low-income earners were more likely to experience client-perpetrated gender-based violence. The ministry of health and the development partners need to provide targeted public health interventions to prevent and manage the rampant gender-based violence among this underserved population

Academic proficiency in Ugandan children with sickle cell anemia: a cross-sectional study

Introduction: Academic proficiency is crucial for advancing learning goals, school advancement, and future economic security. Children with sickle cell anemia (SCA) in sub-Saharan Africa (SSA) may be at risk of disease-associated learning difficulties. Limited data exist on this topic among school-age children in the region. We aimed to assess academic proficiency in a sample of children with SCA in Uganda compared with unaffected controls. Methods: This cross-sectional study was conducted in Kampala, Uganda. Participants were school-going children with SCA, aged 6–12 years, attending Mulago Hospital SCA Clinic, and age-matched sibling controls without SCA. Academic proficiency was assessed by the Wide Range Achievement Test, Fourth Edition (WRAT4) using outcome measures of spelling, mathematical computation, word reading, and sentence comprehension by age-normalized z-scores. Results: Among 68 children with SCA and 69 controls tested; the mean age for each group was 9.4±2.0 years; 38 (55.9%) with SCA and 32 (46.4%) controls were male. Mean hemoglobin was 7.9 ± 0.9 g/dL for the SCA group versus 12.8 ± 1.0 g/dL for controls (p \u3c 0.001). Compared with the control sample, children with SCA scored significantly lower in mathematical computation (median [interquartile range]: −0.47 [−1.11 to 0.08] versus −0.02 [−0.46 to 0.61], p = 0.0012). Spelling but not mathematic proficiency decreased with age in the SCA group. No significant differences by group were found in spelling, word reading, or sentence comprehension. Discussion: School-aged children with SCA are at risk of poor academic proficiency, especially in mathematical computation. Our findings suggest that children with SCA in Uganda need educational evaluation and may benefit from support for learning

Prevalence and factors associated with violence against women who exchange sex for money in Gulu City, Northern Uganda: a cross-sectional study.

BackgroundGender-based violence (GBV) is a public health concern disproportionately affecting female sex workers (FSWs) globally. We investigated the prevalence and factors associated with GBV against women engaged in sex work in Gulu City, Uganda.MethodsIn this community-based study, we included FSWs purposely selected from hotspots within Gulu City, Uganda, between February and April 2023. Data on participants' characteristics and history of GBV in the past 1 year prior to the interview were collected using a structured questionnaire. Bivariate logistic regression analyses were performed to identify the factors associated with GBV.ResultsOf the 314 participants, 222 (70.7%) reportedly experienced GBV in the past year, most frequently economic violence (66.9%, n=210), followed by verbal violence (41.4%, n=130), physical violence (27.7%, n=87) and sexual violence (27.4%, n=86). Factors associated with GBV were secondary education level (adjusted OR (AOR): 0.17, 95% CI 0.03 to 0.87, p=0.034), history of pregnancy (AOR: 3.41, 95% CI 1.05 to 11.04, p=0.041) and places of sex work at bars (AOR: 5.59, 95% CI 2.03 to 15.38, p=0.001), night clubs (AOR: 3.69, 95% CI 1.26 to 10.61, p=0.017) and client's place (AOR: 3.62, 95% CI 1.21 to 10.86, p=0.022).ConclusionGBV against FSWs in Gulu City, Uganda, is unacceptably high. Therefore, there is an urgent need to address violence in sex work in Uganda and similar settings worldwide through multisectoral targeted interventions and creating safer working environments by the Ministry of Health and other concerned entities

Mechanisms through which exercise reduces symptom severity and/or functional impairment in posttraumatic stress disorder (PTSD): Protocol for a living systematic review of human and non-human studies

BackgroundExercise can play an important role in reducing symptom severity and improving functional impairment in patients with posttraumatic stress disorder (PTSD). However, the precise mechanisms underpinning the effect of exercise in PTSD management are not fully understood. This living systematic review aims to synthesize and triangulate the evidence from non-human and human studies to gain insight into the biopsychosocial mechanisms through which exercise reduces symptom severity and functional impairment.MethodsIndependent searches will be conducted in electronic databases to identify eligible studies. Two reviewers will independently conduct the study selection, data extraction, and risk of bias assessment. We will extract outcome data and variables that can act as effect modifiers or as mediators of the effect of exercise. For the non-human studies, outcome data will include the non-human equivalents of PTSD symptom clusters. For human studies, the primary outcome will be PTSD symptom severity. The secondary outcomes will be avoidance symptom severity, reexperiencing symptom severity, hyperarousal symptom severity, negative cognitions and mood severity, functional impairment, loss of PTSD diagnosis, and dropout rates.To explain the biopsychosocial mechanisms through which exercise affects the outcome of interest, we will extract effects that relate to the impact of exercise on potential mediating variables and the effect of the later outcomes. Comparison of within-study direct and indirect effects obtained from mediation analysis, when reported, will provide insight into the importance of the examined mediator.If appropriate, we will synthesize study results using meta-analyses. We will examine potential effect modifiers of the total exercise effect to understand better the impact of exercise on PTSD symptoms and function impairment (when possible). The evidence about the potential mediators of the association between exercise and PTSD-related outcomes will be considered in a consensus meeting when sufficient evidence is available.Protocol registrationPROSPERO-ID: 453615

The therapeutic potential of exercise in post-traumatic stress disorder and its underlying mechanisms: A living systematic review of human and non-human studies

BackgroundExercise for post-traumatic stress disorder (PTSD) is a potentially effective adjunct to psychotherapy. However, the biopsychosocial mechanisms of exercise are not well understood. This co-produced living systematic review synthesizes evidence from human and non-human studies.MethodsWe Included controlled human and non-human studies involving searches of multiple electronic databases (until 31.10.23). Records were screened, extracted, assessed for risk of bias, and reconciled by two independent reviewers. The primary outcome for human studies was PTSD symptom severity, while outcomes of interest for non-human studies included freezing behaviour, fear memory, fear generalization, startle response, and locomotion. Data were synthesised with random-effects meta-analysis.ResultsEleven human studies met the eligibility criteria. Overall, exercise was not associated with symptom severity improvement compared to control (standardized mean difference [SMD] -0.08, 95% confidence interval [CI] -0.24 to 0.07; 8 studies, one at low risk of bias). High-intensity exercise reduced PTSD symptoms scores more than moderate-intensity exercise. There was insufficient data to examine the effects of exercise on functional impairment, PTSD symptom clusters, and PTSD remission. Only three studies, all at high risk of bias, examined mechanisms of exercise with inconclusive results. Exercise was associated with improvement in all behavioural outcomes, including locomotor activity (SMD 1.30, 95% CI 0.74 to 1.87, 14 studies), and changes in several neurobiological markers, including increase in brain-derived neurotrophic factor (SMD 1.79, 95% CI 0.56 to 3.01).ConclusionsWhile non-human studies provide compelling evidence for the beneficial effects of exercise, human trials do not. Evidence from non-human studies suggest that exercise might increase the levels of brain-derived neurotrophic factor, enhance cognitive appraisal, and improve perceived exertion. Overall, the paucity of data on the effectiveness of exercise in PTSD and mechanisms of action underscore the need for rigorous trials.RegistrationThe protocol was registered with PROSPERO (ID:453615; 22.08.2023)

Trace amine-associated receptor 1 (TAAR1) agonism for psychosis: a living systematic review and meta-analysis of human and non-human data

BackgroundTrace amine-associated receptor 1 (TAAR1) agonism shows promise for treating psychosis, prompting us to synthesise data from human and non-human studies.MethodsWe co-produced a living systematic review of controlled studies examining TAAR1 agonists in individuals (with or without psychosis/schizophrenia) and relevant animal models. Two independent reviewers identified studies in multiple electronic databases (until 17.11.2023), extracted data, and assessed risk of bias. Primary outcomes were standardised mean differences (SMD) for overall symptoms in human studies and hyperlocomotion in animal models. We also examined adverse events and neurotransmitter signalling. We synthesised data with random-effects meta-analyses.ResultsNine randomised trials provided data for two TAAR1 agonists (ulotaront and ralmitaront), and 15 animal studies for 10 TAAR1 agonists. Ulotaront and ralmitaront demonstrated few differences compared to placebo in improving overall symptoms in adults with acute schizophrenia (N=4 studies, n=1291 participants; SMD=0.15, 95%CI: -0.05, 0.34), and ralmitaront was less efficacious than risperidone (N=1, n=156, SMD=-0.53, 95%CI: -0.86, -0.20). Large placebo response was observed in ulotaront phase-III trials. Limited evidence suggested a relatively benign side-effect profile for TAAR1 agonists, although nausea and sedation were common after a single dose of ulotaront. In animal studies, TAAR1 agonists improved hyperlocomotion compared to control (N=13 studies, k=41 experiments, SMD=1.01, 95%CI: 0.74, 1.27), but seemed less efficacious compared to dopamine D 2 receptor antagonists (N=4, k=7, SMD=-0.62, 95%CI: -1.32, 0.08). Limited human and animal data indicated that TAAR1 agonists may regulate presynaptic dopaminergic signalling.ConclusionsTAAR1 agonists may be less efficacious than dopamine D 2 receptor antagonists already licensed for schizophrenia. The results are preliminary due to the limited number of drugs examined, lack of longer-term data, publication bias, and assay sensitivity concerns in trials associated with large placebo response. Considering their unique mechanism of action, relatively benign side-effect profile and ongoing drug development, further research is warranted.RegistrationPROSPERO-ID: CRD42023451628

New living evidence resource of human and non-human studies for early intervention and research prioritisation in anxiety, depression and psychosis

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying mechanisms of mental health conditions, develop safe and effective interventions that target these mechanisms, and improve our capabilities in timely diagnosis and reliable prediction of symptom trajectories. Better synthesis of existing evidence is one way to reduce waste and improve efficiency in research towards these ends. Living systematic reviews produce rigorous, up-to-date and informative evidence summaries that are particularly important where research is emerging rapidly, current evidence is uncertain and new findings might change policy or practice. Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis (GALENOS) aims to tackle the challenges of mental health science research by cataloguing and evaluating the full spectrum of relevant scientific research including both human and preclinical studies. GALENOS will also allow the mental health community-including patients, carers, clinicians, researchers and funders-to better identify the research questions that most urgently need to be answered. By creating open-access datasets and outputs in a state-of-the-art online resource, GALENOS will help identify promising signals early in the research process. This will accelerate translation from discovery science into effective new interventions for anxiety, depression and psychosis, ready to be translated in clinical practice across the world

New living evidence resource of human and non-human studies for early intervention and research prioritisation in anxiety, depression and psychosis

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying mechanisms of mental health conditions, develop safe and effective interventions that target these mechanisms, and improve our capabilities in timely diagnosis and reliable prediction of symptom trajectories. Better synthesis of existing evidence is one way to reduce waste and improve efficiency in research towards these ends. Living systematic reviews produce rigorous, up-to-date and informative evidence summaries that are particularly important where research is emerging rapidly, current evidence is uncertain and new findings might change policy or practice. Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis (GALENOS) aims to tackle the challenges of mental health science research by cataloguing and evaluating the full spectrum of relevant scientific research including both human and preclinical studies. GALENOS will also allow the mental health community-including patients, carers, clinicians, researchers and funders-to better identify the research questions that most urgently need to be answered. By creating open-access datasets and outputs in a state-of-the-art online resource, GALENOS will help identify promising signals early in the research process. This will accelerate translation from discovery science into effective new interventions for anxiety, depression and psychosis, ready to be translated in clinical practice across the world

Integrated management of HIV, diabetes, and hypertension in sub-Saharan Africa (INTE-AFRICA): a pragmatic cluster-randomised, controlled trial

BACKGROUND: In sub-Saharan Africa, health-care provision for chronic conditions is fragmented. The aim of this study was to determine whether integrated management of HIV, diabetes, and hypertension led to improved rates of retention in care for people with diabetes or hypertension without adversely affecting rates of HIV viral suppression among people with HIV when compared to standard vertical care in medium and large health facilities in Uganda and Tanzania. METHODS: In INTE-AFRICA, a pragmatic cluster-randomised, controlled trial, we randomly allocated primary health-care facilities in Uganda and Tanzania to provide either integrated care or standard care for HIV, diabetes, and hypertension. Random allocation (1:1) was stratified by location, infrastructure level, and by country, with a permuted block randomisation method. In the integrated care group, participants with HIV, diabetes, or hypertension were managed by the same health-care workers, used the same pharmacy, had similarly designed medical records, shared the same registration and waiting areas, and had an integrated laboratory service. In the standard care group, these services were delivered vertically for each condition. Patients were eligible to join the trial if they were living with confirmed HIV, diabetes, or hypertension, were aged 18 years or older, were living within the catchment population area of the health facility, and were likely to remain in the catchment population for 6 months. The coprimary outcomes, retention in care (attending a clinic within the last 6 months of study follow-up) for participants with either diabetes or hypertension (tested for superiority) and plasma viral load suppression for those with HIV (>1000 copies per mL; tested for non-inferiority, 10% margin), were analysed using generalised estimating equations in the intention-to-treat population. This trial is registered with ISCRTN 43896688. FINDINGS: Between June 30, 2020, and April 1, 2021 we randomly allocated 32 health facilities (17 in Uganda and 15 in Tanzania) with 7028 eligible participants to the integrated care or the standard care groups. Among participants with diabetes, hypertension, or both, 2298 (75·8%) of 3032 were female and 734 (24·2%) of 3032 were male. Of participants with HIV alone, 2365 (70·3%) of 3365 were female and 1000 (29·7%) of 3365 were male. Follow-up lasted for 12 months. Among participants with diabetes, hypertension, or both, the proportion alive and retained in care at study end was 1254 (89·0%) of 1409 in integrated care and 1457 (89·8%) of 1623 in standard care. The risk differences were -0·65% (95% CI -5·76 to 4·46; p=0·80) unadjusted and -0·60% (-5·46 to 4·26; p=0·81) adjusted. Among participants with HIV, the proportion who had a plasma viral load of less than 1000 copies per mL was 1412 (97·0%) of 1456 in integrated care and 1451 (97·3%) of 1491 in standard care. The differences were -0·37% (one-sided 95% CI -1·99 to 1·26; pnon-inferiority<0·0001 unadjusted) and -0·36% (-1·99 to 1·28; pnon-inferiority<0·0001 adjusted). INTERPRETATION: In sub-Saharan Africa, integrated chronic care services could achieve a high standard of care for people with diabetes or hypertension without adversely affecting outcomes for people with HIV. FUNDING: European Union Horizon 2020 and Global Alliance for Chronic Diseases

Trace amine-associated receptor 1 (TAAR1) agonism for psychosis: a living systematic review and meta-analysis of human and non-human data

BACKGROUND: Trace amine-associated receptor 1 (TAAR1) agonism shows promise for treating psychosis, prompting us to synthesise data from human and non-human studies. METHODS: We co-produced a living systematic review of controlled studies examining TAAR1 agonists in individuals (with or without psychosis/schizophrenia) and relevant animal models. Two independent reviewers identified studies in multiple electronic databases (until 17.11.2023), extracted data, and assessed risk of bias. Primary outcomes were standardised mean differences (SMD) for overall symptoms in human studies and hyperlocomotion in animal models. We also examined adverse events and neurotransmitter signalling. We synthesised data with random-effects meta-analyses. RESULTS: Nine randomised trials provided data for two TAAR1 agonists (ulotaront and ralmitaront), and 15 animal studies for 10 TAAR1 agonists. Ulotaront and ralmitaront demonstrated few differences compared to placebo in improving overall symptoms in adults with acute schizophrenia (N=4 studies, n=1291 participants; SMD=0.15, 95%CI: -0.05, 0.34), and ralmitaront was less efficacious than risperidone (N=1, n=156, SMD=-0.53, 95%CI: -0.86, -0.20). Large placebo response was observed in ulotaront phase-III trials. Limited evidence suggested a relatively benign side-effect profile for TAAR1 agonists, although nausea and sedation were common after a single dose of ulotaront. In animal studies, TAAR1 agonists improved hyperlocomotion compared to control (N=13 studies, k=41 experiments, SMD=1.01, 95%CI: 0.74, 1.27), but seemed less efficacious compared to dopamine D2 receptor antagonists (N=4, k=7, SMD=-0.62, 95%CI: -1.32, 0.08). Limited human and animal data indicated that TAAR1 agonists may regulate presynaptic dopaminergic signalling. CONCLUSIONS: TAAR1 agonists may be less efficacious than dopamine D2 receptor antagonists already licensed for schizophrenia. The results are preliminary due to the limited number of drugs examined, lack of longer-term data, publication bias, and assay sensitivity concerns in trials associated with large placebo response. Considering their unique mechanism of action, relatively benign side-effect profile and ongoing drug development, further research is warranted. REGISTRATION: PROSPERO-ID:CRD42023451628