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The utility of infectious disease modelling in informing decisions for outbreak response: A scoping review.
Get PDFInfectious disease modelling plays a critical role in guiding decisions during outbreaks. However, ongoing debates over the utility of these models highlight the need for a deeper understanding of their exact role in decision-making. In this scoping review we sought to fill this gap, focusing on challenges and facilitators of translating modelling insights into actionable policies. We searched the Ovid database to identify modelling studies that included an assessment of utility in informing policy and decision-making from January 2019 onwards. We further identified studies based on expert judgement. Results were analysed descriptively. The study was registered on the Open Science Framework platform. Out of 4007 screened and 12 additionally suggested studies, a total of 33 studies were selected for our review. None of the included articles provided objective assessments of utility but rather reflected subjectively on modelling efforts and highlighted individual key aspects for utility. 27 of the included articles considered the COVID-19 pandemic and 25 of the articles were from high-income countries. Most modelling efforts aimed to forecast outbreaks and evaluate mitigation strategies. Participatory stakeholder engagement and collaboration between academia, policy, and non-governmental organizations were identified as key facilitators of the modelling-for-decisions pathway. However, barriers such as data inconsistencies and quality, uncoordinated decision-making, limited funding and misinterpretation of uncertainties hindered effective use of modelling in decision-making. While our review identifies crucial facilitators and barriers for the modelling-for-decisions pathway, the lack of rigorous assessments of the utility of modelling for decisions highlights the need to systematically evaluate the impact of infectious disease modelling on decisions in future
Heart failure outcomes and empagliflozin effects in patients with heart failure and reduced ejection fraction in sinus rhythm or atrial fibrillation: Data from EMPEROR-Reduced.
Get PDFAIMS: Empagliflozin reduces cardiovascular death (CVD) or hospitalization for heart failure (HHF), slows estimated glomerular filtration rate (eGFR) decline and improves quality of life (QoL) in heart failure with reduced ejection fraction (HFrEF). Whether the effect of empagliflozin is consistent according to atrial fibrillation (AF) status is worth exploring.
METHODS AND RESULTS: The impact of AF versus sinus rhythm (SR) on outcomes as well as on eGFR decline and QoL were studied post-hoc in EMPEROR-Reduced. Of patients with available rhythm analyses and after exclusion of patients with missing or paced rhythms, 2785 were included (AF, n = 928, SR, n = 1857). Differences were not significant for the primary endpoint (p = 0.66), first (p = 0.19) and recurrent HHF (p = 0.45). On placebo, alcohol consumption (interaction p = 0.32), body mass index (interaction p = 0.93), diabetes (interaction p = 0.52), hypertension (interaction p = 0.24) were not different between AF and SR. Low ejection fraction and high Kidney Disease: Improving Global Outcomes (KDIGO) class had higher event rates but without interaction between SR and AF, respectively. After a median follow-up of 20 months, empagliflozin reduced CVD or HHF compared to placebo in AF and SR (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.63-1.08; and HR 0.69, 95% CI 0.56-0.84; interaction p = 0.29). The same applied to time to first HHF (interaction p = 0.20), while there was a borderline but insignificant interaction for first and recurrent HHF (p = 0.10). The effect on annual eGFR decline and QoL scores was not different. Incident AF was numerically lower but formally not significantly different (HR 0.66, 95% CI 0.40-1.09, p = 0.11, empagliflozin vs. placebo).
CONCLUSIONS: In HFrEF, AF did not significantly modify outcomes after adjustment and did not associate with eGFR slopes. Empagliflozin reduced outcomes, eGFR decline and improved QoL regardless of AF or SR and probably reduced incident AF
Using operational research as a tool to improve eye health services and systems in low-and middle-income settings: lessons from India and Nepal.
Get PDFBACKGROUND: Operational Research (OR), as part of a quality assurance program, has become a standard feature of most health institutions in most high-income countries. In contrast, in low-income settings, operational research is less common, and almost no one has asssed operational research capacity building (ORCB) as a tool to improve efficacy, efficiency and quality in these settings. This study evaluated the impact of an ORCB program on participants' research competencies and the extent to which research findings were implemented in practice.
MATERIALS AND METHODS: This study combined quantitative and qualitative data to evaluate an ORCB intervention in eye hospitals in Nepal (3 sites) and northern India (1 site) from 2019 to 2022. A self-reported questionnaire was administered at the end of the study period, and formal interviews were conducted. The questionnaire covered knowledge improvement, practice implementation, and motivating and challenging factors. Statistical analysis included paired t-tests to compare pre- and post-training scores. Qualitative data were gathered through interviews and observations and analysed thematically.
RESULTS: The program demonstrated significant improvements in participants' research knowledge gain. Quantitative analysis revealed substantial gains in knowledge (p-values < 0.05 for all domains). Post-training, 66.7% developed study protocols, and 60% trained other staff or students. Qualitative feedback indicated overall positive impacts, including enhanced research and operational activities. However, reported challenges such as inconsistent mentorship quality, poor internet connectivity during online sessions, and difficulty in balancing clinical work with research. Despite these challenges, there was notable improvement in research practice and internal training within hospitals, and the program's approach was appreciated for its effectiveness.
CONCLUSION: The study highlights the need for standardized training modules, consistent mentorship, and stronger institutional support. Building operational research capacity in resource-poor settings with limited administrative staff and weak data infrastructure improves individual staff knowledge and skills. Participants learned about scientific principles of reliability and validity and their importance to efforts to improve service equity, efficiency, and effectiveness
Understanding the Implementation of CareCoach-A Blended eHealth Intervention for Carers of People Living with Dementia: A Qualitative Process Evaluation Using Normalisation Process Theory.
Get PDFCareCoach seeks to enhance self-efficacy in family caregivers of people living with dementia and has been feasibility tested in a multicentre randomised controlled trial. The intervention offers two face-to-face sessions with a trained coach and access to an online platform with nine modules. This paper reports findings from an embedded qualitative process evaluation assessing implementation from the implementer's ('coach's') (n = 8) perspective using individual interviews and implementer group discussions. Qualitative data were transcribed verbatim, inductively coded and analysed using Normalisation Process Theory. Implementers demonstrated (1) 'Coherence' by seeking to understand how CareCoach compared to current practice, highlighting the importance of supporting coaches to differentiate and identify boundaries between their new 'coach role' and usual practice; (2) 'Cognitive Participation' by reviewing training and resources to understand their role own responsibilities and facilitate delivery of coaching sessions; group supervision and peer support were also emphasised; (3) 'Collective Action' through interactions with carers to deliver key behavioural aspects such as goal setting, problem solving, and providing feedback; and (4) 'Reflexive Monitoring' by appraising the intervention to gain useful insights that could facilitate refinement of CareCoach training and delivery. This study provides a theoretically informed understanding of the implementation of CareCoach for caregivers of people living with dementia and provides recommendations to enhance training for coaches, intervention delivery and carer engagement
Backtranslation of human RNA biosignatures of tuberculosis disease risk into the preclinical pipeline is condition dependent.
Get PDFIt is unclear whether human progression to active tuberculosis disease (TB) risk signatures are viable endpoint criteria for evaluations of treatments in development. TB is the deadliest infectious disease globally and more efficacious vaccines are needed to reduce this mortality. However, the immune correlates of protection for either preventing infection with Mycobacterium tuberculosis or preventing TB disease have yet to be completely defined, making the advancement of candidate vaccines through the pipeline slow, costly, and fraught with risk. Human-derived correlate of risk (COR) gene signatures, which identify an individual's risk of progressing to active TB disease, provide an opportunity for evaluating new therapies for TB with clear and defined endpoints. Though prospective clinical trials with longitudinal sampling are prohibitively expensive, the characterization of COR gene signatures is practical with preclinical models. Using a 3Rs (replacement, reduction, and refinement) approach we reanalyzed heterogeneous publicly available transcriptional data sets to determine whether a specific set of COR signatures are viable endpoints in the preclinical pipeline. We selected RISK6, Sweeney3, and BATF2 human-derived blood-based RNA biosignatures because they require relatively few genes and have been carefully evaluated across several clinical cohorts. These data suggest that in certain experimental designs and in several tissue types, human COR signatures correlate with disease progression as measured by the bacterial burden in the preclinical TB model pipeline. We observed the best performance when the model most closely reflected human infection or disease conditions. Human-derived COR signatures offer an opportunity for high-throughput preclinical endpoint criteria of vaccine and drug therapy evaluations. IMPORTANCE: Understanding the strengths or limitations of back-translating human-derived correlate of risk (COR) RNA signatures into the preclinical pipeline may help streamline down-selection of therapeutic vaccine and drug candidates and better align preclinical models with proposed clinical trial efficacy endpoints
Effectiveness of measures taken by governments to support hand hygiene in community settings: a systematic review.
Get PDFINTRODUCTION: This systematic review aimed to identify and evaluate the implementation of government measures that support equitable and sustained hand hygiene practices in community settings.
METHODS: We systematically searched 12 databases, including PubMed, Web of Science, EMBASE, CINAHL, Global Health, Cochrane Library, Global Index Medicus, Scopus, PAIS Index, WHO IRIS, UN Digital Library and World Bank eLibrary for peer-reviewed and grey literature published through late March 2023. Additional sources were identified through expert consultations and manual reference list checks of related reviews. Studies employing quantitative, qualitative or mixed-methods designs were eligible. Study quality was assessed using the Mixed Method Appraisal Tool. Government measures were categorised according to the Sanitation and Water for All Building Blocks framework: sector policy strategy; institutional arrangements; sector financing; planning, monitoring, review; and capacity development. Hand hygiene outcomes were classified as access, behaviour change or enabling environment and impact as positive, null or not evaluated.
RESULTS: Thirty-one studies (24 journal articles and 7 grey literature) from 19 countries-mostly middle income (71%)-were included. Most focused on household (58%), schools (19%) or both (13%). A total of 75 government measures were identified, with sector policy strategy and capacity development being the most common (each 31%), followed by institutional arrangements (17%), planning, monitoring, review (13%) and sector financing (8%). Positive impacts were linked to 45 measures across all five Building Blocks in 17 studies.
CONCLUSION: This systematic review highlights diverse government measures supporting hand hygiene in community settings, with sector policy strategy and capacity development being the most frequently reported. While many government measures showed positive impacts, gaps remain in financing, implementation and sustainability beyond households and schools. Strengthening governance, increasing investment and expanding research on cost-effectiveness and implementation barriers are essential to improve hygiene initiatives and ensure equitable access.
PROSPERO REGISTRATION NUMBER: CRD42023429145
Evidence-based decision making for malaria elimination applying the Freedom From Infection statistical framework in five malaria eliminating countries: an observational study.
Get PDFBACKGROUND: Routine surveillance is a pillar of malaria programmes, and the primary source of data used for decision making. However, any inference when relying on routine data to inform decision making is limited by how effective the system is at measuring the actual malaria burden. Here, we aimed to extend the Freedom From Infection (FFI) framework to produce species-specific estimates of surveillance system sensitivity and probability of freedom from malaria, combine multiple surveillance components including community case management and active case detection, and apply the FFI model in five malaria eliminating settings.
METHODS: Monthly routine data on Plasmodium falciparum and Plasmodium vivax and health system factors were collected from 1515 facilities across five countries. Additionally, data from 12 community health workers and from 10 767 individuals from cross-sectional surveys (active case detection) were available. The data were analysed using FFI models accounting for multiple malaria species and surveillance components. The primary outcomes were the sensitivity of the surveillance system and the probability of malaria freedom.
FINDINGS: Strong surveillance systems were characterised by access to testing and treatment supplies, training on diagnostics and case management within the previous 12 months, and shorter estimated travel times to facilities. Only half of the facilities (841 of 1515 facilities for P falciparum and 771 of 1455 facilities for P vivax) had sufficient sensitivity to achieve and maintain a high probability of freedom, consistent with having achieved malaria elimination, with either passive case detection data alone or when combined with active case detection.
INTERPRETATION: Applying the FFI model framework to malaria surveillance data can provide programmes with information to support decision making, specific to malaria species. When routine malaria surveillance systems are strong, they are sufficient to achieve and maintain a high probability of freedom. Including additional surveillance components such as community case management and active case detection with multiple diagnostic tools can help improve estimates for which routine malaria data alone are not sufficient to ensure confidence in elimination.
FUNDING: The Bill and Melinda Gates Foundation, the Global Institute for Disease Elimination, and the Carter Center
Efficacy and safety of 8-week regimens for the treatment of rifampicin-susceptible pulmonary tuberculosis (TRUNCATE-TB): a prespecified exploratory analysis of a multi-arm, multi-stage, open-label, randomised controlled trial.
Get PDFBACKGROUND: WHO recommends a 2-month optimal duration for new drug regimens for rifampicin-susceptible tuberculosis. We aimed to investigate the efficacy and safety of the 8-week regimens that were assessed as part of the TRUNCATE management strategy of the TRUNCATE-TB trial.
METHODS: TRUNCATE-TB was a multi-arm, multi-stage, open-label, randomised controlled trial in which participants aged 18-65 years with rifampicin-susceptible pulmonary tuberculosis were randomly assigned via a web-based system, using permuted blocks, to 24-week standard treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol) or the TRUNCATE management strategy comprising initial 8-week treatment, then post-treatment monitoring and re-treatment where needed. The four 8-week regimens comprised five drugs, modified from standard treatment: high-dose rifampicin and linezolid, or high-dose rifampicin and clofazimine, or bedaquiline and linezolid, all given with isoniazid, pyrazinamide, and ethambutol; and rifapentine, linezolid, and levofloxacin, given with isoniazid and pyrazinamide. Here, we report the efficacy (proportion with unfavourable outcome; and difference from standard treatment, assessed via Bayesian methods) and safety of the 8-week regimens, assessed in the intention-to-treat population. This prespecified exploratory analysis is distinct from the previously reported 96-week outcome of the strategy in which the regimens were deployed. This trial is registered with ClinicalTrials.gov (NCT03474198).
FINDINGS: Between March 21, 2018, and March 26, 2020, 675 participants (674 in the intention-to-treat population) were enrolled and randomly assigned to the standard treatment group or one of the four 8-week regimen groups. Two 8-week regimens progressed to full enrolment. An unfavourable outcome (mainly relapse) occurred in seven (4%) of 181 participants on standard treatment; 46 (25%) of 184 on the high-dose rifampicin and linezolid-containing regimen (adjusted difference 21·0%, 95% Bayesian credible interval [BCI] 14·3-28·1); and 26 (14%) of 189 on the bedaquiline and linezolid-containing regimen (adjusted difference 9·3% [4·3-14·9]). Grade 3-4 adverse events occurred in 24 (14%) of 181 participants on standard treatment, 20 (11%) of 184 on the rifampicin-linezolid regimen, and 22 (12%) of 189 on the bedaquiline-linezolid regimen.
INTERPRETATION: Efficacy was worse with 8-week regimens, although the difference from standard treatment varied between regimens. Even the best 8-week regimen (bedaquiline-linezolid) should only be used as part of a management strategy involving post-treatment monitoring and re-treatment if necessary.
FUNDING: Singapore National Medical Research Council; UK Department of Health and Social Care; UK Foreign, Commonwealth, and Development Office; UK Medical Research Council; Wellcome Trust; and UK Research and Innovation Medical Research Council
Pesticide safety behavior among vegetable farmers in Bangladesh: Evaluating the role of market aggregation services.
Get PDFPesticide use in Bangladesh is disproportionately high in vegetable farming compared to other crops like cereals, pulses, and cash crops. This study delves into the knowledge, attitudes, and practices regarding pesticide use among vegetable farmers, focusing on the impact of a digital aggregation service implemented by Digital Green. Based on interviews with 120 vegetable farmers in the LOOP aggregation scheme and 120 non-LOOP vegetable farmers this study indicates that the farmers using the aggregation service have a moderately higher level of food safety knowledge. LOOP farmers scored higher in pesticide safety knowledge (67.83 %) compared to non-LOOP farmers (55 %). Regarding pesticide safety attitudes, LOOP farmers scored 17.39 %, while non-LOOP farmers 4.17 %, reflecting a generally poor attitude toward pesticide application. Regarding practices, 65.55 % of LOOP farmers adhered to scientifically sound methods, compared to 43.10 % of non-LOOP farmers. Although participation in the LOOP program significantly influenced farmers' pesticide-related knowledge, attitudes, and practices, this study still identifies the need for targeted interventions and training to improve food safety practices among both groups
Implementing an artificial intelligence system into a diabetic eye screening programme in Tanzania.
Get PDFTanzania has the highest age-adjusted prevalence of diabetes in sub-Saharan Africa. Diabetic retinopathy, a common complication, is a significant cause of vision loss; but with effective screening and treatment this often can be prevented. However, with very few specialist eye care staff in Tanzania this is a major challenge. Artificial intelligence (AI) systems, which automate clinical decision making and therefore task-shift away from specialist staff, could contribute to improved diabetic retinopathy screening services in low-resource settings. This article describes our experiences of selecting, procuring and implementing an AI system into a regional diabetic eye screening programme in northern Tanzania