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Cerebral manifestations of falciparum malaria in adults: more than meets the eye.
Get PDFThe application of neuroimaging techniques to patients with Plasmodium falciparum infection has uncovered a wide range of brain changes not only in cerebral malaria but also in noncomatose patients. We propose several hypotheses to unify findings across the spectrum of clinical malaria in adults and highlight the urgent need to evaluate potential long-term effects of cerebral alterations on neurocognition in this understudied age group
Cohort Profile: Basse Health and Demographic Surveillance System, the Gambia.
Get PDFThe Basse Health and Demographic Surveillance System (BHDSS) in rural Gambia was established to support population-based epidemiological research. Studies have used the Medical Research Council Unit, The Gambia (MRCG) Basse Field Station, to conduct large-scale, laboratory-linked disease surveillance, clinical trials, and intervention evaluations
Measuring the WHO Global Breast Cancer Initiative Pillars' key performance indicators in Sub-Saharan Africa: experience in the African Breast Cancer-Disparities in Outcomes hospital-based cohort study.
Get PDFBACKGROUND: The World Health Organization Global Breast Cancer Initiative aims to reduce breast cancer (BC) mortality through three pillars, whose key performance indicators (KPIs) and benchmarks are: (KPI-1) ≥60% BC diagnosed at early stage (I/II), (KPI-2) all suspected BC diagnosed ≤60 days from health system presentation, and (KPI-3) ≥80% of BC patients completing recommended treatment. We aimed to inform measurement of these KPIs in the context of a multi-country hospital-based study. METHODS: We included all women who participated to the African Breast Cancer-Disparities in Outcomes (ABC-DO) prospective cohort study (excluding South Africa), recruited between 2014 and 2017, across five population-race groups spanning low to high survival: Nigeria, Uganda, Zambia, Namibian black and Namibian non-black women. Follow-up was up to five years post-diagnosis. For each KPI, we reported challenges, assumptions and consistencies in measuring them; completeness and group-level estimations of each KPI were assessed using descriptive analyses. To evaluate their discriminatory ability, we assessed group-level correlations between KPI estimates and five-year net survival. FINDINGS: KPI-1 was extracted from study or medical records for 1389/1473 (94%). KPI-2 relied upon the woman's recall of her date of first contact with the healthcare system and a pathology date, both of which were available for 1222/1473 (83%) but inconsistent for 114/1222 (9.3%). KPI-3, estimated using dates of receipt of multiple therapies from medical records and patient interviews over 12 months, was estimated for 1129/1188 (95%), but uncertain in 113/1129 (10%). For each population group, KPIs achievements were similar for KPI-1 and KPI-2, at 22-49%, and lowest for KPI-3 (<30%). Highest KPIs values were observed in Namibian non-black women who had the highest survival. INTERPRETATION: Data collection systems specifically set up for prospective hospital-based studies can be used to collect the necessary data to measure these three GBCI KPIs. FUNDING: National Cancer Institute (United States)
Global impact of 10- and 13-valent pneumococcal conjugate vaccines on pneumococcal meningitis in all ages: The PSERENADE project.
Get PDFBACKGROUND: Pneumococcal conjugate vaccines (PCVs) introduced in childhood national immunization programs lowered vaccine-type invasive pneumococcal disease (IPD), but replacement with non-vaccine-types persisted throughout the PCV10/13 follow-up period. We assessed PCV10/13 impact on pneumococcal meningitis incidence globally. METHODS: The number of cases with serotyped pneumococci detected in cerebrospinal fluid and population denominators were obtained from surveillance sites globally. Site-specific meningitis incidence rate ratios (IRRs) comparing pre-PCV incidence to each year post-PCV10/13 were estimated by age (<5, 5-17 and ≥18 years) using Bayesian multi-level mixed effects Poisson regression, accounting for pre-PCV trends. All-site weighted average IRRs were estimated using linear mixed-effects regression stratified by age, product (PCV10 or PCV13) and prior PCV7 impact (none, moderate, or substantial). Changes in pneumococcal meningitis incidence were estimated overall and for product-specific vaccine-types and non-PCV13-types. RESULTS: Analyses included 10,168 cases <5 y from PCV13 sites and 2849 from PCV10 sites, 3711 and 1549 for 5-17 y and 29,187 and 5653 for ≥18 y from 42 surveillance sites (30 PCV13, 12 PCV10, 2 PCV10/13) in 30 countries, primarily high-income (84%). Six years after PCV10/PCV13 introduction, pneumococcal meningitis declined 48-74% across products and PCV7 impact strata for children <5 y, 35-62% for 5-17 y and 0-36% for ≥18 y. Impact against PCV10-types at PCV10 sites, and PCV13-types at PCV13 sites was high for all age groups (<5 y: 96-100%; 5-17 y: 77-85%; ≥18 y: 73-85%). After switching from PCV7 to PCV10/13, increases in non-PCV13-types were generally low to none for all age groups. CONCLUSION: Pneumococcal meningitis declined in all age groups following PCV10/PCV13 introduction. Plateaus in non-PCV13-type meningitis suggest less replacement than for all IPD. Data from meningitis belt and high-burden settings were limited
Feasibility and Applicability of Implementing the Framework for Comprehensive Understanding of Structural Stigma in Mental Healthcare Systems: A Case Example of Nepal.
Get PDFINTRODUCTION: Mental health-related structural stigma is a multifaceted issue that significantly impacts access to quality mental healthcare, particularly in low-resource settings like Nepal. Therefore, there is a clear need to understand the complexities and identify gaps for targeted interventions through evaluations of various dimensions of structural stigma within healthcare systems. This study aimed to assess the feasibility and applicability of a mental health-related structural stigma measurement framework through its implementation in Nepal's healthcare system. METHODS: A mixed-methods approach was employed, involving data mapping, key informant interviews and rating exercises with diverse stakeholders, including policymakers, health workers and people with lived experience (PWLEs). A visual analogue scale or Red/Amber/Green (RAG) rating scale was used to rate each indicator within the framework for the level of structural stigma based on the mapped information and their experiences. Data collection was carried out from May to June 2024. RESULTS: Twenty key informants were interviewed for this exercise. Most indicators within the framework were endorsed as yellow, followed by red by participants referring to mid to high levels of structural stigma within the healthcare system. The findings also revealed that the stakeholders perceived the framework as acceptable and applicable for measuring mental health-related structural stigma in the healthcare system. However, challenges were noted regarding the clarity of some indicators, limitations of the three-coloured visual analogue rating and the need for comparator conditions. CONCLUSION: The study underscores the measurement framework's value as a tool for identifying and addressing structural stigma in a mental healthcare system in a low-resource setting. Stakeholder engagement and contextual adaptation are crucial for its successful implementation. The insights gained can inform structural reforms and improve mental health service delivery, ultimately promoting greater equity and access for PWLEs. PATIENT PUBLIC CONTRIBUTION: This framework being assessed in this study (FOCUS-MHS) was developed through extensive consultation with People with Lived Experiences (PWLEs) in Nepal and globally with the Global Mental Health Peer Network along with other stakeholders. Identification of documents, policies and studies, along with qualitative information mapped within the indicators, was informed by PWLEs involved in local study sites and by policymakers and health administrators. The reflections of the study participants-PWLEs, health administrators and policymakers, have guided further refinement of the framework for future use
Glucagon-like peptide-1 receptor agonists, but not dipeptidyl peptidase-4 inhibitors, reduce alcohol intake.
Get PDFBACKGROUNDDespite growing preclinical evidence that glucagon-like peptide1 receptor agonists (GLP-1RAs) could be repurposed to treat alcohol use disorder (AUD), clinical evidence is scarce. Additionally, the potential impact of dipeptidyl peptidase-4 inhibitors (DPP-4Is) on alcohol intake is largely unknown.METHODSWe conducted a large cohort study using 2008-2023 electronic health records data from the U.S. Department of Veterans Affairs. Changes in Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores were compared between propensity-score-matched GLP-1RA recipients, DPP-4I recipients, and unexposed comparators. We further tested the effects of 2 DPP-4Is, linagliptin and omarigliptin, on binge-like alcohol drinking in mice and operant oral alcohol self administration in alcohol-dependent rats, models previously used to show a significant effect of the GLP-1RA semaglutide in reducing alcohol intake.RESULTSGLP-1RA recipients reported a greater reduction in AUDIT-C scores than unexposed individuals (difference-in-difference [DiD]: 0.09 [95% CI: 0.03, 0.14], P = 0.0025) and DPP-4I recipients (DiD: 0.11 [95% CI: 0.05,0.17], P = 0.0002). Reductions in drinking were more pronounced among individuals with baseline AUD (GLP-1RA versus unexposed: 0.51 [95% CI: 0.29,0.72], P < 0.0001; GLP-1RA versus DPP-4I: 0.65 [95% CI: 0.43,0.88], P < 0.0001) and baseline hazardous drinking (GLP-1RA versus unexposed: 1.38 [95% CI: 1.07,1.69], P < 0.0001; GLP-1RA versus DPP-4I: 1.00 [95% CI: 0.68,1.33], P < 0.0001). There were no differences between DPP-4I recipients and unexposed individuals. The latter results were confirmed via a reverse translational approach. Specifically, neither linagliptin nor omarigliptin reduced alcohol drinking in mice or rats. The rodent experiments also confirmed target engagemhent, as both DPP-4Is reduced blood glucose levels.CONCLUSIONConvergent findings across humans, mice, and rats indicated that GLP-1RAs, but not DPP-4Is, reduce alcohol consumption and may be efficacious in treating AUD.FUNDINGThis work was supported by the National Institutes of Health Intramural Research Program (ZIA DA000635, ZIA DA000644, ZIA DA000602), National Institute on Alcohol Abuse and Alcoholism extramural funding (R01 AA030041, P01 AA029545, U01 AA026224, U24 AA020794, U01 AA020790, U10 AA013566), the U.S. Department of Veterans Affairs (I01BX004820), and an Alkermes Pathways Research Award
Are evidence-based guidelines translating into clinical practice? A national population-based study of the use of treatment intensification in metastatic hormone-sensitive prostate cancer (mHSPC) in England.
Get PDFBACKGROUND AND OBJECTIVE: International guidelines recommend treatment intensification combining docetaxel or androgen receptor pathway inhibitors with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer (mHSPC). However, evidence suggests underuse in many high-income countries. This study evaluates the use of treatment intensification in the English National Health Service (NHS) and explores patient and hospital-level factors associated with variation. METHODS: All men diagnosed with mHSPC in England between January 2018 and December 2022 were identified through the national cancer registry. Treatment intensification within six months of diagnosis was assessed using hospital and systemic anti-cancer therapy data. Multilevel regression models explored associations between treatment intensification and sociodemographic factors including age, comorbidities, frailty, ethnicity, socioeconomic status, rurality, and year of diagnosis. Variation among the 47 specialist multidisciplinary teams (sMDTs), responsible for coordinating prostate cancer care in England, was also evaluated. KEY FINDINGS AND LIMITATIONS: Among 29,713 mHSPC patients, treatment intensification use was 39.0 %. Treatment intensification use decreased with age, comorbidities, frailty, socioeconomic deprivation, and among black patients (p always < 0.05). 59.8 % (n = 9184) of men aged 75 or younger had a record of treatment intensification, compared to only 16.8 % (n = 2404) of men older than 75. The use of treatment intensification across sMDTs ranged from 20.3 % to 53.7 %, with greater variation in older patients, particularly those older than 75. CONCLUSIONS AND CLINICAL IMPLICATIONS: There is potential underuse of treatment intensification for mHSPC patients, particularly among older, black, and socioeconomically deprived patients. Significant variation in practice exists between specialist prostate cancer teams (sMDTs) nationally, especially in older populations, indicating that many patients may not receive optimal care
Condomless sexual encounters among female sex workers included in a longitudinal coital diary study in Zimbabwe.
Get PDFBACKGROUND: Compared with the general female population, female sex workers (FSWs) experience a greater burden of STIs, including HIV. Consistent condom use reduces HIV risk; however, while many FSWs are aware of condom efficacy, this knowledge does not consistently translate into use. We aimed to estimate the prevalence and patterns of condomless sex by partner type at the sexual encounter level, as well as identify factors associated with condomless sex among FSWs recruited into a diary study in Zimbabwe. METHODS: We conducted a longitudinal coital diary study in site A and site B between 25 November 2020 and 30 December 2021. Pictorial diaries were developed in collaboration with FSWs. We recruited participants using snowball sampling and asked them to complete a daily diary of their sexual encounters with each partner for one month, repeated over three non-consecutive months within 12 months. The following FSW characteristics were recorded: FSW age, Key Populations (KP) Programme contact, partner type and age, condom use categorized as none, partial, or full, types of sexual activity, and violence experiences. To identify factors associated with condomless sex, we used hierarchical Poisson regression modelling. RESULTS: 404 FSWs documented 62,559 sex encounters, with 17,325 (27.7%) reported as condomless. Our adjusted analysis showed that encounters with permanent partners had the highest likelihood of being condomless (59.5%; adjusted relative risk [aRR] 3.83, 95% CI: 3.38-4.35), followed by regular partners (25.6%; aRR 1.63, 95% CI: 1.50-1.78), compared to new partners (15.0%). Compared with FSWs aged < 25 years (29.7%), those aged ≥ 35 years were less likely to have condomless sex (22.1%; aRR 0.79, 95% CI: 0.66-0.94), while sex without violence was less likely (24.1%) to be condomless than sex with violence (57.7%; aRR 2.32, 95% CI: 2.00-2.70). FSWs with the KP programme contact reported fewer condomless encounters (25.9%; aRR 0.81, 95% CI: 0.90-0.94) than those without (32.9%). CONCLUSION: Condomless sex was common and varied based on FSW age, partner type, experiencing violence during sex, and KP programme contact. These findings emphasize the need for continued condom promotion, counseling, violence mitigation, and training in condom negotiation skills especially given the heightened risk of HIV transmission among FSWs
Converging perspectives on the processes exacerbating adolescent obesity: An integrative systems approach.
Get PDFAdolescent obesity is a complex public health challenge with steadily increasing and variable prevalence among countries. This paper synthesises the driving feedback mechanisms of adolescent obesity studied in the CO-CREATE project, furthering our understanding of the complexity of this issue. Using systems thinking principles and causal loop diagramming, we integrated the following knowledge and perspectives derived from diverse sources into a causal loop diagram (CLD): a systems map generated by adolescents through participatory modelling workshops, a comprehensive literature review, and input from subject-matter experts during validation workshops. We used a structured and iterative approach to include drivers and to identify feedback loops exacerbating adolescent obesity. The CLD identified 27 key feedback loops across four themes: twelve related to the commercial food environment, six to the physical activity environment, four to mental wellbeing and five to social norms. These loops indicate not only diet and physical activity as drivers of obesity but also stress and other emotional and social pressures. Recognising the imperative need to integrate the perspectives and experiences of adolescents into our analysis, this work advocates for the synthesis of experiential insights with empirical research. The integrated CLD can be used as a visual tool that fosters collaboration among stakeholders and engenders a more comprehensive and inclusive system understanding that can provide holistic intervention considerations to tackle adolescent obesity. Additionally, the CLD lays a foundation for subsequent quantitative modelling works to further address this issue and develop context-based approaches to prevention and evaluation of adolescent obesity
Prevalence and risk factors for Staphylococcus aureus colonisation among healthy individuals in low- and middle-income countries: A systematic review and meta-analysis.
Get PDFBACKGROUND: Staphylococcus aureus is capable of asymptomatic colonisation, which can progress to opportunistic and potentially life-threatening infection. The data on S. aureus colonisation in low- and middle-income countries (LMIC) are limited. This systematic review and meta-analysis estimates the prevalence of S. aureus colonisation in asymptomatic individuals in LMIC, with secondary objectives of assessing antimicrobial resistance, colonisation risk factors, and the molecular epidemiology of colonising strains. METHODS: Articles published up to July 2023 were identified by searching four electronic databases. Studies that presented S. aureus colonisation prevalence in healthy individuals from a community setting in LMIC were included. Data extraction was performed independently by two reviewers with disagreement resolved through consensus. Studies were critically appraised using the Joanna Briggs Institute Prevalence tool. Random effects meta-analysis was conducted where appropriate. This study was registered in advance with PROSPERO (CRD42019147780). FINDINGS: A total of 16 610 citations were identified of which 138 studies (59 732 participants) met the eligibility criteria. The majority of studies had a low risk of bias. The pooled prevalence of S. aureus colonisation at nose and/or throat sites was 26·4% (95% CI 23·8 - 29·1%). The prevalence of methicillin-resistance in colonising S. aureus strains was 15·0% (95% CI: 11·8 to 18·6%), with a higher prevalence observed in Africa compared to Asia and South America (22·5% vs. 13·1% vs. 5·4% respectively). Panton-Valentine leukocidin genes were present in 26·4% (95% CI: 17·1% to 32·8%) of 2531 isolates. INTERPRETATION: While the prevalence of asymptomatic S. aureus colonisation in LMIC mirrors that found in high-income countries, there was a higher prevalence of antimicrobial resistance and other virulence factors. Variability in study methods and sparsity of data from many LMIC, underscore the need for a global approach to S. aureus surveillance. This will be critical for informing effective infection prevention strategies