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Understanding the complex knowledge economy toward antimicrobial stewardship in West Bengal, India
Get PDFKnowledge dissemination and awareness raising is a common strategy for fostering antimicrobial stewardship and tackling antimicrobial resistance (AMR). However, empirical evidence suggests that the dissemination of technical/biomedical information about AMR, alone, is insufficient to improve antibiotic use in resource-poor settings. This is because antibiotic users’ decisions are based not only on biomedical knowledge but also on social and clinical information that is specific to local healthcare realities, and healthcare providers’ clinical knowledge and judgement. In this article, we propose a framework that identifies knowledge critical to deciding a course of antibiotic treatment for possible infection in resource-poor settings, and how to improve the knowledge flow to improve antibiotic use. Specifically, we focus on understanding three domains of knowledge that guide antibiotic users’ decisions: 1) scientific evidence, and evidence-based treatment guidelines; 2) local knowledge of infection patterns and risks, and the susceptibility of organisms causing infection to different antibiotics; and 3) personal and social characteristics of the patient. Drawing from the theory of information asymmetry and empirical data from West Bengal, India, we show that all three domains of knowledge demon�strated degrees of asymmetry, and community-level practitioners’ knowledge was not effectively taken into account in clinical guidance. We conclude that interventions targeting AMR need to reflect all three knowledge domains to be effective in clinical settings
The Data Monitoring Experience in Empagliflozin Randomized Clinical Trials Between 2011 and 2024.
No full textIn November 2007, a black box warning was mandated for rosiglitazone in type 2 diabetes mellitus (T2DM) based on an increased risk of ischemic cardiovascular (CV) events. The Food and Drug Administration (FDA) issued a directive that a CV outcomes trial must be done for any new diabetes drug to demonstrate no CV harm. Therefore, the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) trial was started in 2011 alongside 13 additional randomized clinical trials (RCTs) of empagliflozin in T2DM. The results of EMPA-REG OUTCOME set the stage for later RCTs in heart failure. Results from these clinical trials have changed the outlook for patients both with and without T2DM and with and without heart failure. A Program Data Monitoring Committee (DMC) with the same core members was utilized for these trials between 2011 and 2024. This committee is likely to be one of the longest serving DMCs since it served 28 trials with empagliflozin between 2011 and 2024. The committee encountered several important challenges which are discussed in this article. Moreover, the committee provides several important take-home messages which we hope will be of value in discussing issues in creating, developing and running DMCs in the future. These include: 1. Whether and when to be blinded and unblinded; 2. How to proceed when the primary endpoint shows no evidence of benefit, but there is evidence for a mortality benefit; 3. Development of presentation of data using figures and boxplots for rapid review of adverse events and laboratory data to assess clinical challenges; 4. How to manage a catastrophic serious adverse event; 5. Suggestions for an ideal structure of the report for the DMC closed session; and 6. The relation between the DMC, sponsor and Contract Research Organization. Our experience emphasizes the value of continuity with the same members serving over a 13-year period
Stillbirth in Low-Resource Settings.
No full textGlobally, 1.9 million late-gestation stillbirths occurred in 2023, 87% in low-income and middle-income countries, with sub-Saharan Africa bearing almost half the burden. Despite a global decline, progress is uneven and stalling in high-burden regions. Most are preventable but persist due to complex factors: biomedical causes (eg, hypertension and infection), societal determinants (eg, poverty, inequity, and low empowerment), and critical health system gaps limiting access to timely, high-quality antenatal, and intrapartum care. Ending preventable stillbirths requires urgent, intersectoral action: closing data gaps, strengthening health systems (especially skilled birth attendance and emergency care), addressing underlying social determinants, and providing supportive bereavement care
Machine learning to improve analysis of disability in electronic health records: an untapped opportunity for health inequities research.
No full textElectronic Health Records (EHRs) are a leading source of epidemiological data, but often lack information on a patient's disability status. This gap hampers our ability to analyse the full scope of health inequities faced by people with disabilities. Current approaches to identify disability within EHRs have limitations because of inadequate proxies for disability or issues linking data sources. Machine learning (ML) offer unprecedented opportunities to create disability markers within EHRs, such as through unsupervised learning to classify disability groups and Natural Language Processing to extract relevant information from clinical notes. These methods have the potential improve disability-disaggregated analyses within EHRs to uncover patterns and provide a more comprehensive understanding of healthcare pathways and outcomes for people with disabilities. Leveraging these approaches to improve disability data in EHRs is a critical step towards improving health inequities research, though require strong adherence to ethical guidelines and validation of these new approaches
Estimating the impact of nutritional transition and ending hunger on tuberculosis in 12 high-burden countries: a model-based scenario analysis.
Get PDFBACKGROUND: Nutrition is a critical determinant of tuberculosis (TB), providing a protective effect at high body mass index (BMI) and incurring an increased risk of TB disease at low BMI. Global nutritional transition and interventions to end hunger could directly affect the TB epidemic in high TB burden countries. METHODS: We constructed dynamic TB transmission models for 12 high TB burden countries with low HIV prevalence. We explicitly accounted for the effects of BMI on TB disease progression and treatment outcomes using a meta-analysis of longitudinal cohort studies, incorporating the effect of BMI mediated through diabetes. The models were calibrated to historical trends in TB epidemiology and mean BMI. We estimated potential changes in TB incidence and mortality between 2015 and 2030 under different scenarios of population nutrition. FINDINGS: Compared with a scenario where mean BMI remained at 2015 levels, if past trends in mean BMI continued then by 2030 TB incidence and mortality would decline by a cumulative 14.7% (95% credible interval: 12.7%-16.7%) and 15.6% (12.5%-19.2%), respectively. In comparison, achieving zero hunger by 2030 would reduce incidence and mortality by 32.0% (20.0%-43.8%) and 37.3% (26.1%-49.6%), respectively. If past trends continued and zero hunger was also achieved, incidence and mortality would be reduced by 38.2% (27.0%-49.1%) and 42.4% (32.1%-53.5%), respectively, equivalent to preventing 20.6 million people developing TB disease and averting 5.4 million TB deaths over 15 years in the 12 high-burden countries. CONCLUSIONS: Nutrition transitions and interventions to end hunger could have a major impact on the future epidemiology of TB in high-burden countries. Investment is urgently required to implement and scale up nutritional interventions
Assessing the impact of the COVID-19 pandemic on uptake of HIV treatment in Bandung and Yogyakarta, Indonesia: A retrospective cohort study.
Get PDFCOVID-19 pandemic known to affect health service deliveries including for HIV care support and treatment. In this retrospective study involving 2,780 people living with HIV (PLHIV), we evaluated impact of COVID-19 pandemic by comparing the proportion of PLHIV linked to care, started antiretroviral therapy (ART), retained in care (within the first 3 months of treatment), and adhered to ART (within the first 3 months of treatment) between the pre-pandemic period (2018-2019) and pandemic period (2020-2021) in Yogyakarta and Bandung, Indonesia. Our study showed that during the pandemic period the number of PLHIV linked to care was 18% lower (1,529 vs 1,251) and those retained in care was significantly lower (59.6% vs 53.3%, p = 0.0009) than the pre-pandemic period. Whereas, proportion in ART initiation (79.6% vs 78.3%, p = 0.3892) and ART adherence (50.0% vs 46.8%, p = 0.1010) were not statistically different. Multivariate analysis showed that ART initiation (aOR = 1.00, p = 0.996) nor retention in care (aOR = 0.90, p = 0.344) were not significantly different between two period cohorts. Adherence for the first three months of treatment, however, was significantly higher in the pandemic cohort (aOR = 1.53, p = 0.009). In the subgroup analysis, older PLHIV and those attending hospitals (tertiary versus primary care clinics) were significantly less likely to initiate ART, be retained in care, or adhere to ART. This study provides evidence of the impact of the COVID-19 pandemic on several characteristics of the HIV treatment cascade such as lower number of linkage to- and retention in care, lower number of older PLHIV, and attendance to tertiary care (hospital). General and HIV-specific mitigation strategies should be designed to minimise pandemic related disruptions and to support the continuity of HIV care to face possible future health crises
Effect of malaria chemoprevention for school-age children across transmission archetypes: a modelling study.
Get PDFBACKGROUND: Intermittent preventive treatment (IPT) of school-aged children with antimalarial drugs decreases rates of infection, anaemia, and clinical malaria. Since school-aged children are a major transmission reservoir, we estimated the effect of IPT for this group on Plasmodium falciparum transmission to younger children and adults across three epidemiological settings.
METHODS: With the use of an established malaria transmission model, we developed three epidemiological archetypes (Sahelian, Central, and Southern African) and estimated the effect of IPT of school-age children across transmission levels (P falciparum parasite rate in children aged 2-10 years [PfPR2-10]: 5-40%). Long-lasting insecticide-treated nets and clinical case management were always included as baseline interventions. We compared scenarios for three of the most widely studied drug options (dihydroartemisinin-piperaquine, artesunate-amodiaquine, and sulfadoxine-pyrimethamine-amodiaquine) and delivery options (school-based or community-based), estimating clinical cases averted.
FINDINGS: When long-acting drugs were administered frequently (monthly campaigns with dihydroartemisinin-piperaquine), modelled IPT of school-age children averted 70-90% of cases in school-aged children (up to about 2·0 cases per child per year) and 20-60% of cases in younger children and adults (up to about 0·5 cases per person per year), with greater community benefit at lower transmission levels (PfPR2-10 5-10%). Shorter-acting drugs (sulfadoxine-pyrimethamine-amodiaquine in the Sahelian archetype or artesunate-amodiaquine in the Central and Southern archetypes) administered monthly or longer-acting drugs administered once per school term averted 40-60% of cases in school-aged children (up to about 1·3 cases per child per year) and 15-50% of cases in other ages (up to about 0·5 cases per person per year).
INTERPRETATION: Our model suggests that adding IPT of school-age children to current control tools could decrease malaria burden in this group and reduce P falciparum transmission.
FUNDING: US National Institutes of Health, Doris Duke Clinical Scientist Development Award
Divergent trajectories of brain ageing across the seventh decade predict AD pathology in a UK population‐based birth cohort
Get PDFBackground
Ageing is the strongest risk factor for Alzheimer's disease (AD), but the molecular mechanisms underpinning this link are not established. In an identically aged birth cohort, we: 1) tracked proteomic brain ageing trajectories across the seventh decade; 2) tested associations between ageing trajectories and AD pathology; 3) identified which individual proteins influenced associations.
Methods
n
= 414 from the 1946 British Birth Cohort had plasma assayed with SomaScan 11k v5 at baseline (age=63.4±1.1yr) and follow‐up (70.6±0.7yr). Brain age was estimated from a proteomic clock using 202 brain‐enriched proteins. ‘Brain age gap’ (BAG) quantified whether a participant's brain age estimate was older (positive) or younger (negative) than their chronological age. ‘BAG change score’ [ (BAG at follow‐up) – (BAG at baseline) ], reflected accelerating (positive) or decelerating (negative) trajectory. Primary outcomes were amyloid‐PET positivity (CL cut‐point=11.9) and log‐transformed plasma
p
‐tau217 (ALZpath SIMOA). Secondary outcomes in a subset (
n
= 114, 72.9±0.59yr) were log‐transformed CSF
p
‐tau217 and Aβ42/40 ratio. We used linear/logistic regression for continuous/binary outcomes, adjusted for sex. Individual protein analysis used Feature Importance for Biological Ageing (FIBA).
Results
BAG at baseline ranged from ‐9.1 to +17.6yrs. Even greater divergence was seen at follow‐up (range: ‐16.93, 19.16 years). Whilst measurements were correlated (r=0.59), we observed heterogenous brain ageing trajectories across the seventh decade (BAG change score range: ‐21.3 to 17.3 years, Figure 1). Baseline BAG did not predict biomarker outcomes some ∼10yr later. BAG at follow‐up associated with higher plasma
p
‐tau217 (b=0.18,
p
= 1.4x10
‐4
) but not amyloid‐PET status. Higher BAG change score (i.e., accelerating brain ageing) was associated with amyloid‐PET positivity (OR 1.89,
p
= 6.4x10
‐3
, Figure 2), higher plasma
p
‐tau217 (b=0.26,
p
= 6.2x10
‐4
), higher CSF
p
‐tau217 (b=0.30,
p
= 9.5x10
‐3
) and lower CSF Aβ 42/40 ratio (b=‐0.35,
p
= 2.2 x10
‐3
). Associations remained significant adjusting for APOE
4
status, plasma neurofilament light and GFAP. Influential proteins in associations included Aldolase C, NPTXR and LRRTM2 (Figure 3).
Conclusion
An identically‐aged population experienced heterogenous trajectories of proteomic brain ageing across their seventh decade. Accelerating brain ageing was predictive of AD biomarker positivity, independent of non‐specific measures of neurodegeneration and genetic risk. Future research will explore how implicated proteins may couple brain ageing to AD pathology
Reach and implementation of human and AI-assisted diabetic retinopathy screening models in primary healthcare settings in India.
Get PDFDiabetic retinopathy (DR) is a leading cause of preventable vision loss. While DR screening is critical, evidence on the reach and implementation of different screening models in primary healthcare settings is limited. This study evaluated the reach and implementation of DRS models in northern India using the RE-AIM framework. A pragmatic three-arm observational study was conducted between February 2023 and January 2024 in Block Boothgarh, a rural block in District Mohali, Punjab, comprising 30 villages with an estimated 120,000 residents. Household line listing was performed to identify individuals aged 30 years or older with diabetes. Participants (n = 600) were equally allocated to three screening models: facility-based screening at Health and Wellness Centres (HWC) by non-ophthalmologists, community-based AI-assisted screening at home, and standard care. Reach and implementation were assessed through quantitative data, field observations, and qualitative interviews with healthcare providers. Refusal for screening was higher in facility-based screening (40%, 135/340) and lower in community-based screening (13%, 31/240). Older individuals were more likely to decline participation, with a mean age of 62.0 years for males and 60.3 years for females. Reported barriers included existing medical conditions, mobility limitations, perceived good eye health, travel distance, and transportation difficulties. Concerns regarding long-term medication adherence also reduced uptake. Technical issues, including power outages, hardware or software malfunctions, suboptimal image quality, and lack of cooperation, further declined implementation. Adaptations, including the use of backup power generators, on-site troubleshooting, and provision of transport support, mitigated these barriers and improved overall implementation fidelity. Assessing reach is essential for the success of public health interventions. Using the RE-AIM framework, this study identified key barriers and adaptive strategies in DRS, enhancing both reach and implementation within primary healthcare settings. These findings can inform the integration of DRS models into comparable resource-constrained contexts, thereby improving overall effectiveness.Clinical Trial Registry of India (CTRI): 2022/10/046283
Maternal vaccination service provision in London and Liverpool: Organisation, recording of vaccinations and midwife training.
Get PDFRecommended vaccinations during pregnancy are safe and can prevent serious illness in both pregnant women and newborns. Despite this, uptake remains low in England. We explored maternal vaccination services at selected maternity sites in London and Liverpool, focusing on service delivery, vaccination recording and midwife training. Services included walk-in vaccination clinics, nurse-led rather than midwife-led vaccination, telephone and text reminders with links to online vaccination booking, multilingual leaflets, posters and digital apps with vaccine information links. However, practical barriers persist. These include poor integration between maternity and primary care data systems for recording vaccinations, limited and inconsistent midwife training, and logistical constraints on vaccine administration. Midwives reported difficulties accessing electronic vaccine records, and vaccination discussions with patients were often absent, particularly in group models of antenatal care. System-level improvements such as integrated data access, protected training time, clear documentation protocols and tailored outreach are needed to strengthen maternal vaccination services