London School of Hygiene & Tropical Medicine

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    Lifestyle Modification Programs and Interventions on Prediabetes in Saudi Arabia: A Systematic Scoping Review.

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    Prediabetes is characterized by elevated blood glucose and glycated hemoglobin levels (HbA1c) that remain below the diagnostic threshold for type 2 diabetes. It increases the risk of diabetes, all-cause mortality, and chronic diseases. Saudi Arabia has one of the highest global diabetes rates. This review evaluates interventions targeting prediabetes in Saudi Arabia and provides recommendations based on their effectiveness. A systematic scoping review was conducted across 12 databases for intervention studies published through March 2024. Study quality was assessed using the Academy of Nutrition and Dietetics Evidence Analysis Library Manual Quality Criteria. Six lifestyle intervention studies in Saudi Arabia, lasting from six months to over a year, were analyzed. All demonstrated good quality with minimal selection bias. Intervention groups showed significant improvements in metabolic syndrome components, fasting glucose, Homeostatic Model Assessment of Insulin Resistance, and HbA1c. One study reported prediabetes reversal and type 2 diabetes remission following lifestyle modifications. Multi-center interventions combining education, counseling, and physical activity were more effective than general advice alone in improving metabolic outcomes. Lifestyle modifications are an effective first-line approach for prediabetes management. In addition to the health benefits associated with improving glycemic control, lifestyle modification has the potential to reduce individual and public healthcare costs associated with prediabetes. This review supports the efficacy of lifestyle modification programs, conducted in Saudi Arabia, in controlling or reversing prediabetes

    Reinvigorating AMR resilience: leveraging CRISPR-Cas technology potentials to combat the 2024 WHO bacterial priority pathogens for enhanced global health security-a systematic review.

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    BACKGROUND: Antimicrobial resistance (AMR) poses a global health threat, particularly in low- and middle-income countries (LMICs). Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system technology offers a promising tool to combat AMR by targeting and disabling resistance genes in WHO bacterial priority pathogens. Thus, we systematically reviewed the potential of CRISPR-Cas technology to address AMR. METHODS: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was conducted using the Scopus and PubMed databases, focusing on publications from 2014 to June 2024. Keywords included "CRISPR/Cas," "antimicrobial resistance," and "pathogen." The eligibility criteria required original studies involving CRISPR/Cas systems that targeted AMR. Data were extracted from eligible studies, qualitatively synthesized, and assessed for bias using the Joanna Briggs Institute (JBI)-standardized tool. RESULTS: Data from 48 eligible studies revealed diverse CRISPR-Cas systems, including CRISPR-Cas9, CRISPR-Cas12a, and CRISPR-Cas3, targeting various AMR genes, such as blaOXA-232, blaNDM, blaCTX-M, ermB, vanA, mecA, fosA3, blaKPC, and mcr-1, which are responsible for carbapenem, cephalosporin, methicillin, macrolide, vancomycin, colistin, and fosfomycin resistance. Some studies have explored the role of CRISPR in virulence gene suppression, including enterotoxin genes, tsst1, and iutA in Staphylococcus aureus and Klebsiella pneumoniae. Delivery mechanisms include bacteriophages, nanoparticles, electro-transformation, and conjugative plasmids, which demonstrate high efficiency in vitro and in vivo. CRISPR-based diagnostic applications have demonstrated high sensitivity and specificity, with detection limits as low as 2.7 × 102 CFU/mL, significantly outperforming conventional methods. Experimental studies have reported significant reductions in resistant bacterial populations and complete suppression of the targeted strains. Engineered phagemid particles and plasmid-curing systems have been shown to eliminate IncF plasmids, cured plasmids carrying vanA, mcr-1, and blaNDM with 94% efficiency, and restore antibiotic susceptibility. Gene re-sensitization strategies have been used to restore fosfomycin susceptibility in E. coli and eliminate blaKPC-2-mediated carbapenem resistance in MDR bacteria. Whole-genome sequencing and bioinformatics tools have provided deeper insights into CRISPR-mediated defense mechanisms. Optimization strategies have significantly enhanced gene-editing efficiencies, offering a promising approach for tackling AMR in high-priority WHO pathogens. CONCLUSIONS: CRISPR-Cas technology has the potential to address AMR across priority WHO pathogens. While promising, challenges in optimizing in vivo delivery, mitigating potential resistance, and navigating ethical-regulatory barriers must be addressed to facilitate clinical translation

    Addiction Lives: Shekhar Saxena.

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    A survey weighted analysis of HPTN 071 (PopART) primary outcome of HIV incidence.

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    INTRODUCTION: HPTN 071 (PopART) implemented a comprehensive HIV prevention package which aimed to reduce HIV incidence within 21 communities of Zambia and South Africa: Arm A, PopART intervention of universal HIV testing and treatment; Arm B, PopART intervention of universal HIV testing with ART provided according to local guidelines; and Arm C, standard of care. Analyses so far have not accounted for the sampling design of the enrolled cohort. We performed a sample-weighted re-analysis of the primary outcome of the PopART trial to derive a population-based estimate of the intervention effect. METHODS: Enrollment used a two-stage sampling design: household and adult participant within each household. We constructed post-stratification weights to match the age and sex distribution of the target population in these communities. Weighted Poisson regression was used to estimate community-level HIV incidence. The PopART intervention effect was estimated using log-transformed community-level incidence estimates in an ANCOVA model. RESULTS: The analysis based on community-level incidence shows a 25% reduction in incidence for Arm B communities compared to standard of care (RR: 0.75, 95% CI: 0.56-1.02, p = 0.06) while Arm A communities show no difference in HIV incidence compared to standard of care (RR: 1.08, 95% CI: 0.81-1.46, p = 0.56). CONCLUSIONS: Our re-analysis shows 25% reduction in HIV incidence comparing Arm B to Arm C communities. No effect was observed comparing Arm A communities to Arm C communities. These results align with the primary results of the PopART trial. CLINICALTRIALS: gov number, NCT01900977, HPTN 071 [PopArt]

    Health, wealth, or equity? Trade-offs from households’ allocative decisions

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    Households’ allocative decisions have potentially large implications for the health and welfare of their members. We analyze a dataset of rural Bangladeshi households to estimate: (i) a benchmark level of nutritional adequacy that households could afford by selecting different foods and reallocating them among members, and (ii) the associated trade-offs in terms of income and equity preferences. Using a novel set of non-linear health production functions, we show that households can afford adequate diets that meet the clinical needs of nearly all nutrients. Micronutrient adequacy is primarily achieved by changing household-level food choices, while caloric adequacy depends more on intra-household food allocation. We further show that households do not face a clear health-income trade-off. Instead, we find a degree of inequality aversion (for energy) and inequality preference (for micronutrients) that leads to intra-household allocations that are not fully efficient from the perspective of the production of health

    Development and Validation of the Global Diet Quality Score (GDQS) for Children 24 to 59 Months of Age.

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    OBJECTIVES: To develop the Global Diet Quality Score (GDQS) for children aged 24-59 months and evaluate its performance in predicting outcomes related to nutrient adequacy and diet-related noncommunicable disease (NCD) risk. BACKGROUND: The GDQS is a food-based metric developed and validated for capturing diets' contributions to nutrient adequacy and NCD risk among adult men and nonpregnant and nonlactating women aged ≥15 years globally. Despite the importance of ensuring healthy diets in preschool children and the need for systematic monitoring, no food-based metrics exist that holistically measure diet quality among children aged 24-59 months in diverse populations. METHODS: We developed candidate versions of the GDQS for children aged 24-59 months by adapting the gram cutoff values used for adults to account for children's lower energy requirements. Using dietary data sets from Bangladesh, Burkina Faso, China, Ethiopia, Mexico, the United Kingdom, and the United States, we evaluated candidate versions' performance in predicting energy-adjusted nutrient intakes and adequacy, nutritional biomarkers, and overweight using Spearman's correlation and multivariable-adjusted regression models, and we statistically compared performance of the strongest candidate with that of the Minimum Dietary Diversity-Women (MDD-W) indicator and Global Dietary Recommendations (GDR) score. RESULTS: The GDQS exhibited significant (P < .05) positive correlations with energy-adjusted intakes of protein, fiber, and most micronutrients in most data sets; significant negative correlations with added sugar and saturated fat in 2 data sets; and inconsistent correlations with monounsaturated and polyunsaturated fat. In multivariable-adjusted models, the GDQS, MDD-W, and GDR were positively associated with serum folate in Ethiopia (and the GDQS was in the United Kingdom), and the GDR was positively associated with high-density lipoprotein cholesterol in China (P < .05). The GDQS was more strongly associated with the mean probability of adequacy of 8 nutrients than the GDR in 2 data sets, whereas the MDD-W outperformed the GDQS in 3 data sets (P < .05). CONCLUSION: The GDQS is a useful metric for measuring diet quality among children aged 24-59 months in diverse populations

    What works to reduce loneliness: a rapid systematic review of 101 interventions.

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    This review evaluates the effectiveness of interventions aimed at reducing loneliness across all age groups. Studies were eligible if alleviation of loneliness was one of ≤ 3 aims, and loneliness was assessed pre- and post-intervention using a validated quantitative measure. Random-effects meta-analyses of standardised mean differences (SMD) assessed pre-post-intervention differences in loneliness, including comparing control and intervention groups. A comprehensive search of peer-reviewed and grey literature sources identified 95 studies covering 101 interventions. Psychological interventions had the largest SMD effect size (n = 23: - 0.79 [95%CI: - 1.19, - 0.38]), followed by social interaction-based interventions (n = 23; - 0.50 [- 0.78, - 0.17]), social support-based interventions (n = 46; - 0.34 [- 0.45, - 0.22]), and finally interventions involving multiple themes (n = 9). Findings highlight the effectiveness of psychological and social interaction strategies in reducing loneliness. Future research should address gaps related to intervention types and populations, emphasising randomised controlled designs. Policymakers and practitioners can use these insights to prioritise interventions fostering social connections and psychological support across diverse settings

    Prevalence of advanced HIV disease in sub-Saharan Africa: a multi-country analysis of nationally representative household surveys.

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    BACKGROUND: Advanced HIV disease (AHD) is a critical stage in the progression of HIV infection and is associated with heightened susceptibility to opportunistic infections, malignancies, and other life-threatening complications. Estimates of the burden of AHD in sub-Saharan Africa are scarce but are needed for programme planning which includes the allocation of resources and the monitoring of outcomes. The aim of the study was to assess the prevalence of and the number of people living with HIV with AHD. METHODS: In this nationally representative study, we analysed data from 13 Population-based HIV Impact Assessment (PHIA) household surveys conducted between 2016 and 2021 to determine the proportion of adults living with HIV who have AHD (defined as CD4 count <200 cells per mm3). We analysed the prevalence of AHD by various demographic and socioeconomic factors; we then estimated the number of individuals with AHD in sub-Saharan Africa by combining these proportions with the latest UNAIDS HIV estimates for the region by the treatment and care cascade. We also assessed policies related to the provision of the recommended package of care for the diagnosis and management of AHD. FINDINGS: A total of 28 040 people living with HIV were included in this study from 13 PHIA surveys. 19 364 were females (weighted percentage 64·5%) and 8676 (35·5%) were males, and the median age of participants was 38 years (IQR 30-47). Pooled across the 13 countries, 9·8% (95% CI 9·3-10·3) had a CD4 cell count of less than 200 cells per mm3. AHD was more common among males than females (13·2% vs 8·0%) and differed across the treatment cascade: 15·4% among people living with HIV who did not know their HIV status, 20·9% among people who knew their status but were not on antiretroviral treatment (ART), 29·5% among people who were on ART but not virally suppressed, and 4·3% among people who were virally suppressed. Extrapolating these results to sub-Saharan Africa yielded an estimated 1·88 million people living with AHD (uncertainty interval [UI] 1·58-2·20); 920 000 (UI 770 000-1·07 million) females and 970 000 (UI 810 000-1·13 million) males. INTERPRETATION: Despite advances in ART that have transformed HIV into a manageable chronic condition, a substantial number of people continue to develop AHD. These figures highlight the need for urgent and innovative programmatic improvements in monitoring, prevention, testing, and diagnosis of AHD in the context of well-established and maturing ART programmes. FUNDING: None

    Perinatal outcomes of symptomatic chikungunya, dengue and Zika infection during pregnancy in Brazil: a registry-based cohort study.

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    The previous literature shows mixed conclusions regarding the risk of adverse perinatal outcomes in pregnant women with symptomatic chikungunya, dengue, and Zika. We investigated this topic using a linked population-based Brazilian cohort from 2015 to 2020. The study included 6,993,395 live births. Among these, 6066 ( < 0.1%) mothers were notified with chikungunya during pregnancy, 19,022 (0.3%) with dengue, and 8396 (0.1%) with Zika. Symptomatic maternal chikungunya was associated with an increased risk of preterm birth (Hazard ratio: 1.10, 95%CI 1.01-1.22), low Apgar score 5' (1.44, 1.14-1.82), and neonatal death (1.50, 1.15-1.96). Symptomatic maternal dengue was associated with preterm birth (1.07, 1.02-1.12), low birth weight (1.10, 1.04-1.15), congenital anomalies (1.19, 1.03-1.37), and low Apgar score 5' (1.26, 1.09-1.45). Symptomatic maternal Zika was associated with all adverse birth outcomes, particularly congenital anomalies, which were over twice the risk (2.36; 1.91-2.67) compared to the unexposed group. This study provides evidence of the adverse consequences of arbovirus infections during pregnancy, including critical time windows by trimester. Our findings emphasise the importance of implementing effective measures to prevent chikungunya, dengue, and Zika infections during pregnancy and the associated adverse birth and neonatal outcomes, which may have long-term health consequences for mothers and their children

    Engagement With Digital Adherence Technologies as Measures of Intervention Fidelity Among Adults With Drug-Susceptible Tuberculosis and Health Care Providers: Descriptive Analysis Using Data From Cluster-Randomized Trials in Five Countries.

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    BACKGROUND: Digital adherence technologies (DATs) are promising tools for supporting tuberculosis (TB) treatment. DATs can serve as reminders for people with TB to take their medication and act as proxies for adherence monitoring. Strong engagement with DATs, from both the person with TB and health care provider (HCP) perspectives, is essential for ensuring intervention fidelity. The Adherence Support Coalition to End TB (ASCENT) project evaluated 2 types of DATs, pillboxes and medication labels (99DOTS), in cluster-randomized trials across 5 countries. OBJECTIVE: This study aims to investigate participant and HCP engagement with DATs for TB treatment, stratified by DAT type and country. METHODS: This study is a subanalysis of data generated through the ASCENT trials, which enrolled adults with drug-susceptible TB. A digital dose was defined as either a pillbox opening (for pillbox users) or a dosing confirmation SMS text message sent by the participant (for label users), both of which were recorded on the adherence platform. Descriptive analysis was used to provide an overview of dose-day outcomes. DAT engagement was assessed from both participant and HCP perspectives. To enhance participant engagement, we summarized the frequency of digital engagement overall and by treatment phase, as well as the frequency of consecutive days without engagement. For HCP engagement, we summarized the frequency of doses added manually, the number of days between the actual dose day and when a manual dose was added, and instances of consecutive manual dosing lasting more than 3 and more than 7 days, where doses were added more than 1 week after the dose day. RESULTS: Of the 9511 participants included, 6719 (70.64%) were using the pillbox, 3544 (37.26%) were female, and the median age was 40 years. Across DAT types, there were 1,384,879 dose days, with 973,876 (70.32%) contributed by pillbox users. Of all dose days, 1,165,195 (84.14%) were recorded as digital, 156,664 (11.31%) as manual, 59,045 (4.26%) had no information, and 3975 (0.29%) were confirmed as missed. Digital dosing decreased slightly from the intensive to the continuation phase. The percentage of digital dose days was higher among pillbox users (851,496/973,876, 87.43%) compared with label users (313,699/411,003, 76.33%). Among label users, manual dosing was most common in the Philippines (37,919/171,786, 22.07%) and least common in Tanzania (11,108/76,231, 14.57%). Among pillbox users, manual dosing was most common in the Philippines (24,015/208,130, 11.54%) and Ukraine (13,209/111,901, 11.80%). Overall, 512 out of 2792 (18.34%) label users and 588 out of 6719 (8.75%) pillbox users experienced a run of more than 7 consecutive nondigital dose days that were resolved more than 1 week after the dose day. The highest occurrence was observed in the Philippines (368/1142, 32.22%, for label users and 224/1351, 16.58%, for pillbox users). CONCLUSIONS: There was considerable variation in DAT engagement across countries and DAT types, reflecting differences in how the intervention was implemented. Further refinement of the intervention and improvements in its delivery may be necessary to enhance outcomes

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