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 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. CONCLUSIONS: TAAR1 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. REGISTRATION: PROSPERO-ID: CRD42023451628.</p

Integrated management of HIV, diabetes and hypertension in sub Saharan Africa: a pragmatic multi-country cluster-randomised 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

Prevalence and factors associated with major depression among female sex workers in post-conflict Gulu district: a cross-sectional study

Abstract Background Female sex workers operating in conflict-affected settings could be at a much greater risk of major depression. However, the epidemiology of major depression in this population remains understudied. We aimed to determine the prevalence and the factors associated with major depression among FSWs in the post-conflict Gulu district in Northern Uganda. Methods We conducted a cross-sectional study among 300 randomly selected adult female sex workers in Gulu. We utilized a pre-tested semi-structured questionnaire, embedded with MINI 7.0.0, to gather information from each participant through face-to-face interviews. We collected data on socio-demographic characteristics, sex-work-related characteristics, alcohol and drug use, HIV status, and major depression. Then, data were entered into EPI INFO 7 and analyzed using logistic regression with the aid of STATA 14.0. Results The mean age (SD) of the study participants was 26.4 (± 6) years, 57.7% attained primary education, 51.7% never married, and 42.1% were living with HIV. The prevalence of major depression among FSWs in the district was 47.7%. In addition, the majority of the FSWs with major depression (91.0%) had either severe (50.4%) or moderate (40.6%) depressive symptoms. Independently, life stress (adjusted OR = 10.8, 95%CI: 5.67–20.57), living with HIV (adjusted OR = 2.25, 95%CI: 1.25–4.05), verbal abuse (adjusted OR = 2.27, 95%CI: 1.27–4.08), and older age (adjusted OR = 1.06, 95%CI: 1.01–1.12) all showed positive associations with major depression. Conversely, provision of sexual services from clients’ homes (adjusted OR = 0.50, 95%CI: 0.25–0.97), use of a non-barrier modern family planning method (adjusted OR = 0.44, 95%CI: 0.24–0.82), and daily intake of alcohol (adjusted OR = 0.50, 95%CI: 0.28–0.88) all showed negative associations with major depression. Conclusions There is a high prevalence of major depression among female sex workers in post-conflict Gulu. The high prevalence of major depression underscores the need for government and development partners to urgently and adequately address the mental health needs of female sex workers

Victimization among adolescents of female sex workers: findings from the children of at-risk parents (CARP) study in Uganda

Abstract Background Female sex workers (FSWs) live and work in high-risk environments, experience high levels of adversity, and have multigenerational trauma that can negatively affect their children. Yet not much is known about the prevalence of victimization (i.e., exposure to maltreatment and trauma) among children of FSWs. This study compared the prevalence of lifetime victimization among adolescents of FSWs and adolescents of non-FSWs in Gulu City, Northern Uganda. Methods A comparative cross-sectional study was conducted among adolescents (10–17 years) enrolled in the Children of At-Risk Parents (CARP) study. This study included 147 adolescents of FSWs and 147 adolescents of non-FSWs selected for comparison in Gulu City, Northern Uganda. The adolescents of FSWs were identified through their mothers using respondent-driven sampling. Data on the residence of FSWs guided a proportionate stratified sampling of adolescents of non-FSWs. Using the Juvenile Victimization Questionnaire, we screened for 34 different types of victimization during participants’ lifetimes. Percentage point differences within groups of adolescents and comparison between adolescents of FSWs and non-FSWs were calculated using STATA version 14.1. Statistical significance was set to p < 0.05. Results 99.3% of the participants experienced at least one form of lifetime victimization. The median number of lifetime victimizations was 12.4. Overall, lifetime victimization was higher among adolescents of FSWs than non-FSWs (13.4 vs. 11.5), male vs. female adolescents (13.4 vs. 11.9), and older [14–17 years] vs. younger (10–13 years) adolescents (14.0 vs. 11.7). Further, more adolescents of FSWs experienced lifetime victimization in the following domains and subdomains, all of which were statistically significant: kidnap (15.8% vs. 4.8%), emotional abuse (65.8% vs. 50.0%), emotional neglect (37.4% vs. 21.1%), physical intimidation (10.2% vs. 4.1%), relational aggression (36.4% vs. 18.4%), verbal aggression (68.7% vs. 46.9%), sexual victimization (31.3% vs. 17.7%), verbal sexual harassment (20.4% vs. 5.4%), exposure to murder scene (42.9% vs. 26.5%), witness to domestic violence (39.5% vs. 26.5%), and witness to the murder of relatives (31.3% vs. 21.1%). Conversely, more adolescents of non-FSWs experienced caregiver victimization than the adolescents of FSWs (98.0 vs. 92.5; p < 0.05). Conclusions Childhood victimization is highly prevalent in Northern Uganda and disproportionately affects the adolescents of FSWs. Therefore, government and development partners should urgently develop policies and interventions targeting prevention, early detection, and timely management of victimization in this vulnerable population

Efficacy of the Gulu University Reproductive Health Simulation Training for final year medical students and interns: a before-and-after study

Background: Reproductive health emergencies, such as postpartum hemorrhage, contribute significantly to maternal and neonatal morbidity and mortality in Uganda due to knowledge and skills gaps. Medical interns, intern midwives, and nurses are crucial as frontline healthcare workers in responding to these emergencies. Our proposed hands-on strategy involves comprehensive simulation-based training (SBT) to equip these healthcare workers with the essential knowledge to manage common reproductive health emergencies and procedures in the country. Objectives: The study aimed to assess the effectiveness of comprehensive SBT in improving the knowledge of interns and fifth-year medical students on reproductive health emergencies and procedures at Gulu University and its Teaching Hospitals in Uganda. Design: A before-and-after study. Methods: A 4-day SBT was conducted for fifth-year medical students and interns (nurses, midwives, and doctors) at Gulu University Teaching Hospitals, focusing on reproductive health emergencies. Pre- and post-tests with 40 multiple-choice questions were used to evaluate knowledge enhancement, the scores were summarized as medians and interquartile ranges. Paired sample t -tests was used to test the difference in pre- and post-test scores. Independent sample t -tests compared median post-test results between interns and students, with a p -value <0.05 considered significant. Results: A total of 153 participants were enrolled, the majority being males (78.4%, n  = 120) and medical students (73.9%, n  = 113). Among the 40 interns, 55% ( n  = 22) were doctors, 30% ( n  = 12) were midwives, and 15% ( n  = 6) were nurses. The study participants showed an increase in knowledge, with median post-test scores higher than pre-test scores for all participants [63% (interquartile ranges, IQR: 57–71%) versus 49% (42–54%), with a median difference of 14% (8–23%), p  < 0.001]. Conclusion: The SBT effectively imparts key knowledge competencies to the interns and fifth-year medical students. We recommend that SBT be included as part of the course units that students should take and for continuous medical education for qualified healthcare workers in resource-limited settings

Dual contraceptive use and associated factors among female sex workers in Gulu City, Uganda in 2023

Abstract Background Dual contraception is an essential approach to mitigating the heightened risks of unintended pregnancies and sexually transmitted infections faced by female sex workers (FSWs). We determined the prevalence and factors associated with dual contraceptive use among FSWs in Northern Uganda. Methods A cross-sectional study was conducted in Gulu city, Uganda between February, and March 2023. Purposively selected FSWs aged 18 years or older who provided verbal informed consent were enrolled in the study. A sample size of 374 was estimated. Data on sociodemographic and reproductive health characteristics were collected using an interviewer-administered semi-structured questionnaire. Current dual contraception was defined the as concurrent use of a barrier and any other modern contraceptive methods within the last 3 months. Continuous variables were summarized using mean and standard deviation and categorical variables were summarized using frequencies and percentages. Modified Poisson regression analysis was used to determine factors associated with dual contraceptive use. Results We enrolled 314 FSWs, with a mean age of 28.8 ± 6.4 years. About 13.8% (n = 41) were living with HIV. In total, 66.2% (95%CI 60.8–71.3) of the participants (n = 208) reported current dual contraceptive use. The most common modern contraceptive method used was the implants (52.4%, n = 109), followed by injectable contraceptives (22.6.0%, n = 47), and bilateral tubal ligation (0.5%, n = 1) was the least utilized. Having had at least one previous pregnancy was positively associated with dual contraceptive use (adjusted PR: 1.87, 95%CI 1.40–2.51, p < 0.001). Conclusions A high proportion of FSWs in Gulu city were currently using dual contraceptives. Interventions are needed to facilitate the use of dual contraception, particularly among FSWs without a history of previous pregnancies