69832 research outputs found
Sort by
Harnessing artificial intelligence for predictive modeling in combating antimicrobial resistance: a call for integration and innovation
Antimicrobial resistance (AMR) represents a critical global health challenge with profound socioeconomic and public health implications. The rise of resistant microorganisms undermines the effectiveness of antibiotics, antivirals, antifungals, and other antimicrobial agents, leading to increased mortality, prolonged illnesses, and escalating medical costs. This study underscores the urgent need for innovative solutions, focusing on the integration of artificial intelligence (AI) to combat AMR. AI, with its rapid data processing, predictive modeling capabilities, and cost-effectiveness, emerges as a transformative tool in mitigating this global crisis. AI-driven predictive models have demonstrated remarkable accuracy in identifying AMR patterns by analyzing vast datasets encompassing patient demographics, antibiotic usage, and environmental factors. These models enhance the precision of antibiotic therapy, guide antimicrobial stewardship programs, and provide early warnings for resistance outbreaks. Furthermore, AI facilitates the development of novel antimicrobial agents, accelerates drug discovery, and supports precision medicine by tailoring treatments to individual patients' profiles. The effective application of AI in addressing AMR necessitates interdisciplinary collaboration among healthcare professionals, microbiologists, policymakers, and AI specialists. This paper calls for robust policy frameworks, dedicated funding, and global partnerships to integrate AI into healthcare systems for AMR surveillance, prevention, and control. Embracing AI innovation is pivotal to safeguarding global public health and ensuring a sustainable future free from the threat of antimicrobial resistance
Targeting de novo purine biosynthesis for tuberculosis treatment.
Tuberculosis remains the leading cause of death from an infectious disease1,2. Here we report the discovery of a first-in-class small-molecule inhibitor targeting PurF, the first enzyme in the mycobacterial de novo purine biosynthesis pathway. The lead candidate, JNJ-6640, exhibited nanomolar bactericidal activity in vitro. Comprehensive genetic and biochemical approaches confirmed that JNJ-6640 was highly selective for mycobacterial PurF. Single-cell-level microscopy demonstrated a downstream effect on DNA replication. We determined the physiologically relevant concentrations of nucleobases in human and mouse lung tissue, showing that these levels were insufficient to salvage PurF inhibition. Indeed, proof-of-concept studies using a long-acting injectable formulation demonstrated the in vivo efficacy of the compound. Finally, we show that inclusion of JNJ-6640 could have a crucial role in improving current treatment regimens for drug-resistant tuberculosis. Together, we demonstrate that JNJ-6640 is a promising chemical lead and that targeting de novo purine biosynthesis represents a novel strategy for tuberculosis drug development
Mobile phone survey estimates of perinatal mortality in Malawi: A comparison of data from truncated and full pregnancy histories.
OBJECTIVES: In many low- and middle-income countries, perinatal mortality estimates are derived retrospectively from periodically conducted household surveys. Mobile phone surveys offer advantages in terms of cost and ease of implementation. However, their suitability for monitoring perinatal mortality has not been established. METHODS: We use data from the Malawi Rapid Mortality Mobile Phone Survey (RaMMPS) to estimate perinatal mortality rates from two versions of the survey instrument: a full pregnancy history and a shorter truncated pregnancy history. Female respondents of reproductive age were randomly allocated to either of these instruments. The sample was generated through random digit dialling with active strata monitoring. Post-stratification weighting was used to correct for sample selection bias, and estimates are reported with bootstrap confidence intervals. We estimated the stillbirth rate as the synthetic cohort probability of a foetal death with 28+ weeks of gestation over all pregnancies reaching the same gestational age. The perinatal and extended perinatal mortality rates were defined as the probabilities of dying between 28 weeks and 7 or 28 days of life, respectively. RaMMPS estimates are compared to the 2015-2016 Malawi Demographic and Health Survey and estimates published by the United Nations Inter-agency Group for Child Mortality Estimation. RESULTS: Truncated and full pregnancy histories were administered for 2093 and 2067 women, respectively. Weighted point estimates of the stillbirth (19.81 deaths per 1000 pregnancies, 95%-confidence interval (CI): 14.11-25.62), perinatal (42.41, 95%-CI: 33.91-50.92), and extended perinatal mortality rates (50.11, 95%-CI: 41.56-58.84) from the full pregnancy history instrument are in line with Demographic and Health Survey and United Nations Inter-agency Group for Child Mortality Estimation estimates. In comparison, the mortality estimates from the truncated pregnancy history instrument are higher, but this difference only approaches statistical significance in the case of the stillbirth rate. Post-stratification weighting produces a small upwards adjustment in the estimates. CONCLUSION: Mobile phone surveys are a promising method for collecting perinatal mortality data. The full pregnancy history instrument produces more plausible results than the shorter truncated pregnancy history questionnaire where the window of retrospection is restricted
Measuring responsiveness and respectful treatment in maternity care in sub-Saharan Africa: a questionnaire validation and development of a score.
INTRODUCTION: The importance of respectful maternity care on optimal maternal outcomes is increasingly acknowledged globally. However, mistreatment and abuse are still experienced by women during hospital childbirth in many parts of the world, with sub-Saharan Africa being one of the places where it is most common. Interventions aiming to improve respectful maternity care must be able to assess the prevalence of responsiveness and mistreatment women experience. This is usually done with questionnaires, though these are not always validated. Scores to represent the level of responsiveness and mistreatment experienced can be created from questionnaire results and have many uses, though no score is consistently used in this field. A new questionnaire measuring responsiveness and respectful treatment was developed for use in the ALERT project, as a questionnaire covering both of these concepts did not exist. This study aimed to validate this questionnaire and to create a scoring method.
METHODS: Psychometric analyses, including exploratory and confirmatory factor analysis, were performed on cross-sectional data collected from the ALERT study to identify and confirm underlying factors. Using these factors, simple summation and factor-weighted methods were used to create scores and their results compared.
RESULTS: Six factors were identified: "Communication & supportive care", "Hospital environment", "Maintained respect & dignity", "Social support", "Maintained privacy & confidentiality" and "Lack of physical & verbal abuse". The results of the two scoring methods developed were similar.
CONCLUSIONS: The responsiveness and respectful treatment questionnaire has high validity in the ALERT study population for the six factors identified. The two scoring methods developed are useful for different aspects of the ALERT intervention and can be used to facilitate comparisons or measure progress towards improving respectful maternity care in these settings
School Meals Case Study: Bangladesh
This school meals case study forms part of a collection led by the Research Consortium for School Health and Nutrition’s "Good Examples" Community of Practice. The School Meals Case Study of Bangladesh serves to document how the national school meals programme is organized, funded, and monitored throughout the country. The objectives of this case study include presenting an introduction to the country profile, outlining the design and implementation of school feeding programmes, describing their monitoring and evaluation processes, and highlighting lessons learned, best practices, and challenges. This case study is written as a working paper, and can be updated to reflect evolving circumstances. The ‘Good Examples’ Community of Practice supports the evidence generation of the Research Consortium for School Health and Nutrition, the evidence-generating arm of the School Meals Coalition. The Research Consortium’s objective is to carry out independent research across diverse sectors and generate solid, compelling, and actionable evidence regarding the benefits of school food programs to inform evidence-based decision-making on school health and nutrition policies and practices
Quantifying Spatial variation in environmental and sociodemographic drivers of leptospirosis in the Dominican Republic using a geographically weighted regression model.
Spatial variation in drivers of leptospirosis transmission in the Dominican Republic is poorly understood. To inform targeted public health interventions, we aimed to characterise risk factors and drivers of transmission on a fine spatial scale. We analysed data from 2078 participants in two provinces, Espaillat and San Pedro de Macoris (SPM), collected from a 2021 cross-sectional survey. We used geographically weighted regression to quantify associations between leptospirosis seropositivity and spatial environmental and sociodemographic data. In Espaillat, higher odds of seropositivity were associated with exposure to freshwater (OR 6.51, ranging between 5.95 and 6.99), bare ground coverage above 1.44% (OR 3.70;3.49-3.92), river density surrounding the household at the highest quartile (OR 2.43;2.41-2.45) and average precipitation in the last five years at the highest quartile (2.57; 2.52-2.65). In SPM, rat exposure was associated with higher odds of seropositivity (OR 2.59;1.23-3.14). By identifying locally important drivers of transmission, our study provides evidence to support more tailored public health interventions to optimise the control and prevention of leptospirosis
The impact of 10-valent pneumococcal conjugate vaccine on the incidence of admissions to hospital with hypoxaemic and non-hypoxaemic pneumonia in Kenyan children.
Observational evidence suggests that pneumococcal conjugate vaccines (PCVs) are more effective at reducing the incidence of hypoxaemic pneumonia compared to non-hypoxaemic pneumonia. We examined the impact of 10-valent PCV (PCV10, Synflorix) on hypoxaemic pneumonia hospital admissions using data from an existing PCV impact study of clinical and radiographic pneumonia. PCV10 was introduced, with catch-up among children under 5 years, in the Kilifi Health and Demographic Surveillance System (KHDSS) in January 2011. We undertook an interrupted time-series (ITS) analysis using seasonally-adjusted segmented Poisson regression of hypoxaemic and non-hypoxaemic pneumonia, accounting for secular trends, from January 2007 to December 2019 among KHDSS residents aged 2-59 months. The median monthly crude incidence of hypoxaemic pneumonia per 100,000 person-years was 95 (IQR 80-139) in the pre-PCV10 period. Time-series regression estimated PCV10 introduction was associated with an increase in the incidence of hypoxaemic pneumonia in children aged 2-59 months (IRR 1.63, 95% CI 1.10-2.41), whereas it was associated with a decrease in the incidence of non-hypoxaemic pneumonia (IRR 0.61, 95% CI 0.48-0.77). Despite the consistent pneumonia surveillance and robust ITS analysis which accounted for pre-PCV10 secular trend and seasonality, the apparent association with hypoxaemic pneumonia is likely due to unmeasured time-varying confounders around the time of vaccine introduction, such as the epidemiology of other respiratory pathogens. This study highlights limitations in the analysis and interpretation of observational data in vaccine impact studies against pneumonia
Evaluating the implementation of the Transforming Children and Young People’s Mental Health Provision Green Paper programme: Findings from surveys of schools and colleges and Mental Health Support Teams (2024)
In 2018, the Transforming Children and Young People’s Mental Health Provision Green Paper
programme was launched. This funded the creation of Mental Health Support Teams (MHSTs) to work
in schools and colleges across England, and specific training in whole-school/college approaches to
mental health and wellbeing for senior mental health leads in schools and colleges. The MHSTs were
designed to have three core functions: 1) to provide direct support, through evidence-based
interventions (e.g., low-intensity cognitive behavioural therapy), to individual children and young
people with ‘mild to moderate’ mental health problems and/or their parents/carers; 2) to support
schools and colleges with their whole-school/college approach to mental health and wellbeing; and
3) to work with education staff and liaising with external specialist mental health services to ensure
that children and young people get the support they need. It was intended that each MHST would
support approximately 8,000 children and young people across a selection of schools in their local
area.
An early evaluation of the pilot wave of the programme (‘the Trailblazers’) found that the support
from MHSTs was welcomed, and many schools and colleges were optimistic about what the
programme could achieve. There were several initial implementation challenges, including those
related to workforce and delivery, such as gaps in the training for the new Education Mental Health
Practitioner (EMHP) role and high staff turnover. Additionally, there were challenges relating to the
scope of the support that MHSTs could provide in relation to the needs of children and young people
and ensuring that the impacts of the programme were experienced equitably across all who needed
support.
In 2023, the longer-term national evaluation of the roll-out of the programme (up to the seventh
wave) began. This evaluation comprises several research components, including quantitative and
qualitative work. This report presents the findings from the first part of this research – a survey of
staff in schools and colleges that are supported by an MHST (n = 1,189), as well as a survey of
individuals involved in the local delivery of MHSTs (n = 303) conducted in 2024.
The survey respondents indicated that the core functions of MHSTs were being delivered well, and
the majority of schools and colleges were satisfied with the support provided by their local MHST.
MHSTs spent around half of their staff time on provision of direct support through evidence-based
interventions and splitting their remaining time equally between supporting whole-school/college
approach activities and working with education staff and external specialist services. This was
consistent with the pattern found in the pilot wave. There was variation in how MHSTs operate,
including the number of schools and colleges that EMHPs work with as well as the number of children
and young people they deliver interventions to; the time that MHSTs spend in schools and colleges;
their way of working with schools/colleges. Both school and college staff and respondents in MHSTs
reported broadly good partnership working and integration between the teams and local schools and
colleges, although some schools and colleges reported lower levels of MHST integration.
Most respondents in MHSTs reported that their team accepted referrals for children and young people
with needs that were outside ‘mild to moderate’ low mood, social anxiety and common behavioural
issues at least some of the time, and in some cases, more frequently. Half of respondents in MHSTs
reported that the interventions they used were not suitable for all children and young people, such
as those with neurodiversity, special educational needs and disabilities, and those who have
experienced trauma. The findings also show that staff turnover was still an issue within MHSTs,
especially of EMHPs.
Overall, the two surveys provided a broad overview of how the Green Paper programme was being
delivered across the country, including successes and challenges, and showed that there was
considerable variation in how the service was delivered across teams and education settings.
Inevitably, surveys are limited in depth as they balance participant burden with the volume of
questions, and answers options are pre-specified. The ongoing evaluation will probe further with
detailed research in six case study MHSTs and the schools and colleges that they work with, covering
programme implementation, costs, and outcomes. The surveys will be repeated in autumn 2025,
informed by the findings from the case study research. The evaluation will report its full findings from
all packages of research in 2026
Catalyzing sustainable development goals through the water-energy-food nexus.
Water, energy, and food (WEF) are central to sustainable development as they are vital for socio-ecological and socio-economic sustainability and human and environmental wellbeing. How the three are used and managed is central to either the aggravation of climate change or the enhancement of resilience and adaptation strategies. This mixed transdisciplinary study developed a WEF nexus-based framework to guide strategic policy decisions to catalyze progress toward achieving sustainable development goals. The aim is to guide the cross-sectoral management of resources for sustainable development under climate change, increasing demand, depletion, degradation, and uncertainty. Past and present data on resource management was assessed to comprehend future availability toward achieving sustainable development outcomes for people and the planet. The fundamentals of holistic WEF resources management were assessed, highlighting the significance of transformative, cross-sectoral, and circular approaches in enhancing resource use efficiency and sustainability. This is critical for informing sustainable natural resources management decisions
Salience and perceptions of epidemic-prone diseases in two communities: Findings from freelisting interviews in Khartoum State, Sudan.
The frequency and severity of disease outbreaks disproportionately impacts settings affected by conflict or with weak health systems. Sudan, facing frequent and recurrent epidemics, struggles with limited resources. Understanding local perceptions of epidemic-prone diseases is vital for designing effective epidemic responses. This study describes the salience and perceptions of epidemic-prone diseases in two urban Sudanese communities. We conducted a cross-sectional qualitative study using freelisting in two communities in Khartoum State: Om Doum in Sharg al Neel locality and a neighbourhood in the Sixth Quarter of Ombadda locality. We purposively selected and interviewed consenting adults and recorded their responses to seven freelisting prompts. We analysed the data using Smith's salience index in Excel to evaluate the frequency and importance of terms, and used a relative salience index to compare terms between lists and sites. We interviewed 32 people in Om Doum and 30 in Ombadda. Epidemic-prone diseases, especially malaria, nose, sinus and throat infections (NSTIs), typhoid and COVID-19, were highly salient as common illnesses, recent outbreaks, and future infections and threats. Cancer and chronic diseases, while less salient, were important. Diseases highly salient as future threats, such as COVID-19 and cancer, were less salient, as likely future infections. Conversely, diseases highly salient as future infections, such as NSTIs and malaria, held lower salience for their future impact. This pattern was more pronounced in Ombadda. Infection prevention measures such as environmental hygiene were highly salient in both sites. Epidemic-prone diseases consistently emerged as significant concerns across sites, with local disease patterns shaping, but not fully explaining, perceived risks. While emphasising local disease burdens in risk communication is important, it may not be sufficient in all sites or for all diseases. Freelisting is useful for rapidly capturing the salience and perceptions of epidemic-prone diseases but requires complementary methods to explore nuanced patterns