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An open science framework and tools to create reproducible food composition data for use in nutrition
Get PDFFood composition tables and databases (FCTs) and Nutrient Conversion Tables (NCTs) are essential for nutrition research. Compiling a new NCT requires multiple FCTs, usually with incompatible formats. FCT cleaning and standardisation is rarely reproducible and requires significant resources. Our aim was to develop a framework and tools for compilation and reporting of reproducible FCTs/NCTs, through expanding the fish and other aquatic products in the global NCT for the Food and Agriculture Organization of the United Nations (FAO) Supply and Utilization Accounts. FAO/ International Network of Food Data Systems (INFOODS) guidelines, and open science tools were used for processing. New R functions and scripts were developed to: import and standardise 12 FCTs; re-calculate food components; perform quality checks; and format outputs (e.g., spreadsheets). This resulted in the expansion of the global NCT, providing information on 32 food components for 95 fish and other aquatic products. The workflow takes 160 s to run. The scripts are publicly available in GitHub, with a manual, and can be used or adapted. These open science tools provide a novel resource to create, update and expand FCTs/NCTs in a reproducible, reusable, efficient, and transparent manner, for use in nutrition research. food composition data for nutrition research
Implications of conflict on vaccination in the Sahel region.
Get PDFThe Sahel region is a geographical belt in Africa that stretches from the Atlantic Ocean to the Red Sea, between the Sahara Desert in the north and the Savannah in the south. It is characterised by challenging environmental crises and conflicts. This analysis highlights the potential implications of conflict on vaccination across five Sahel countries, including Burkina Faso, Chad, Mali, Niger and Sudan, from 2019 to 2023. It also presents recommendations to improve vaccination coverage in these settings. The WHO Immunisation Data Portal was used to extract data about vaccination coverage and disease outbreaks. With the increasing complexity of humanitarian access in the Sahel, there has been an accumulation of the number of zero-dose and underimmunised children. In 2023 alone, most of these countries had a significant proportion of zero-dose children, particularly Sudan (43%), Mali (22%) and Chad (16%). Nearly half of children in Sudan (49%), 33% in Chad and 23% in Mali are underimmunised. Measles vaccine coverage was consistently below 90% in these countries, except for Burkina Faso. The trend of polio outbreaks (circulating vaccine-derived poliovirus) across these countries showed fluctuations in the number of cases, with Niger having reported several cases over this period, and Chad having 101 cases reported in 2020 alone. Despite relatively high coverage, there were significant outbreaks of polio in Burkina Faso, Sudan and Mali in 2020, which reflects the potential impact of the COVID-19 pandemic. Lessons can be learnt from past diplomatic and programmatic successes, while investments in innovative and flexible approaches may help increase the reach of vaccination programmes in inaccessible areas
A contentious intervention to support the medical workforce: a case study of the policy of introducing physician associates in the United Kingdom.
Get PDFBACKGROUND: Health systems across Europe are facing a workforce crisis, with some experiencing severe shortages of doctors. In response, many are exploring greater task-sharing, across established professions, such as doctors, nurses, and pharmacists, with patients and carers, and with new occupational groups, in particular ones that can assist doctors and relieve their workload. CASE PRESENTATION: In the early 2000s the United Kingdom created a new occupational role, that of physician assistant. They had a science degree and then underwent a 2-year postgraduate training course. The name soon changed, to physician associate, and the range of roles and responsibilities expanded greatly, although in a largely unregulated manner; by 2024, some were undertaking complex procedures or managing undifferentiated patients in primary care. Catalysed by some high-profile failings, this expansion has generated major concerns, over patient safety and consent, the scope of practice and preferential employment conditions of this group, the adverse consequences for medical training, and the additional medical workload involved in supervision. This has led to a widespread grassroots backlash by the medical profession, often challenging their leaders who had supported this idea. As a consequence, professional bodies that were initially in favour are now expressing serious concerns and it seems likely that the roles and responsibilities of physician associates (and related occupations) will be curtailed. We review published literature and official documentation about this policy to understand the drivers of its development, its benefits, and risks. CONCLUSIONS: The experience in the UK offers cautionary lessons for other European countries contemplating similar ideas. It underscores the importance of maintaining trust with those affected by change, undertaking a detailed systems analysis with attention to risks of unintended consequences, agreeing clear role definitions, providing adequate regulatory oversight, and the need to avoid damaging training of future doctors. This case study highlights the need for a carefully thought-out approach that considers both the potential benefits and pitfalls of integrating new roles like physician associates into a healthcare system. The failure to do so has created a new occupational group with unrealistic expectations and has further demoralised an already unhappy medical profession
Economic evaluation of prenatal GBS immunization in China: A modeling analysis.
Get PDFInvasive Group B Streptococcus (GBS) infection is a fatal disease that causes a significant disease burden in young infants worldwide. GBS vaccines being developed are a potential means of preventing GBS; however, their cost-effectiveness in China is unknown. Using a decision analysis model, we simulated the cost-effectiveness of a GBS vaccine for pregnant women compared with no intervention over the lifetime of their newborns from the Chinese healthcare system perspective. We estimate the incremental cost-effectiveness ratio (ICER) and analyzed the impact of uncertainties in key parameters through deterministic sensitivity analysis and probabilistic sensitivity analysis. The vaccine could reduce GBS cases by 49% and yield an ICER of 23, 51, and 65, and the vaccine efficacy is 80%, 90% of iterations fell under the 33, the vaccine is cost-effective under 37,663. GBS vaccination is likely to be cost-effective in China at WTP thresholds of $37,663 (3xGDP per capita). Enhancing vaccine efficacy and lowering costs further improve cost-effectiveness. A budget impact analysis will be crucial upon licensure
Evaluating health and social care integration in England's Pioneer programme: The challenges of undertaking research in service delivery and research regulatory systems that are not fit for purpose.
Get PDFObjectives: Better integrated health and social or long-term care is high on government policy agendas in many countries. In England, successive pilot programmes, with related national evaluations, have been introduced to better integrate care to meet the needs of people requiring multi-agency help. However, researchers evaluating such programmes both in England and internationally face a daunting number of challenges produced by service delivery and research regulatory systems. This paper analyses the challenges encountered in seeking to undertake a prospective quasi-experimental evaluation of the impacts of community based multi-disciplinary teams (MDTs) on patient experience and outcomes, as part of a wider evaluation of the Integrated Care and Support Pioneers programme. The paper also identifies a number of general lessons for research commissioners, study site participants, and those tasked with undertaking such evaluative research.
Methods: We reviewed our research activities and timelines from the start of the evaluation. We created a narrative history - using reports to the funder, applications to research and ethics regulatory bodies and correspondence with Pioneer sites, regulatory bodies and data providers - to describe the challenges faced and our approaches to attempting to mitigate them.
Results: We experienced four key challenges: (1) unrealistic commissioner research specifications; (2) negotiating with and recruiting multiple organisations and services at potential study sites; (3) navigating research ethics and governance systems; and (4) recruiting participants for primary data collection and obtaining (with their consent) their linked routine service use data. The first two challenges resulted from the lack of shared understanding of evaluation feasibility and constraints between local health and care system actors and national level commissioners of evaluation, plus no clear incentive for local sites to participate. The third and fourth challenges were the product of multiple, protracted, and unnecessarily risk-averse research approval processes which affected both the nature and quantity of the data we could collect.
Conclusions: We recommend that major changes are made to the regulation of policy research to enable more robust evaluation to take place and that disproportionately high levels of risk aversion in approval processes for non-interventional, low-risk studies are addressed. In addition, the evaluation commissioning process needs to be far better informed at an early stage about which elements in programmes can feasibly be evaluated before research specifications are advertised
Diagnosis of cryptococcal meningitis in people living with HIV in low-income countries: barriers and strategies.
Get PDFINTRODUCTION: Cryptococcal meningitis (CM) is the second leading cause of AIDS-related mortality where the burden of advanced HIV disease is concentrated. Advances in diagnostics and treatment, including cryptococcal antigen (CrAg) screening and short-course antifungal regimens, have improved clinical outcomes in trials, but replicating these same benefits in routine care has proven more difficult.
AREAS COVERED: This review outlines the biological rationale for CrAg screening and examines the major operational barriers to effective CM diagnosis in low-income countries. An exploratory literature review identified peer-reviewed articles published before May 2025. We assess challenges for CD4 testing, CrAg screening, lumbar puncture (LP) performance, and routine surveillance. Novel approaches, including risk stratification with semi-quantitative CrAg testing are also described.
EXPERT OPINION: The impact of recent diagnostic and treatment advances for cryptococcal disease has been constrained by gaps in implementation. Closing the diagnostic gap requires strengthening decentralized CD4 testing; expanding reflex and point-of-care CrAg, including use of semi-quantitative CrAg assays to prioritize those at highest risk for urgent LP and/or enhanced antifungal treatment; strengthening healthcare provider training, referral systems, LP access, and enhancing community engagement. Integration of these measures into national HIV programs alongside operational research could reduce mortality for patients and costs for health systems
The Three-Gene Xpert Host Response Signature for Pediatric Tuberculosis Screening: A Prospective Diagnostic Accuracy Study.
Get PDFBACKGROUND: Blood-based gene signatures offer potential as a near point-of-care tuberculosis (TB) screening tool. We examined the accuracy of the GeneXpert MTB Host Response (Xpert-HR) cartridge to screen for TB in children. METHODS: We enrolled children under 15 years from The Gambia and Uganda being evaluated for pulmonary TB. Each child provided a blood sample for Xpert-HR and underwent standard TB assessments, including chest X-ray (CXR) and sputum Xpert Ultra testing, followed by National Institutes of Health (NIH) case classification of Confirmed, Unconfirmed, or Unlikely TB. We measured cycle threshold (Ct) values for GBP5, DUSP3, and TBP, calculated an HR TB score, and generated ROC curves. Specificity was assessed at 90% sensitivity according to strict (SRS, Confirmed vs Unlikely TB), microbiological (MRS, Confirmed TB vs Unlikely or Unconfirmed TB), and composite (CRS, Confirmed or Unconfirmed TB vs Unlikely TB) reference standards compared with other TB evaluations. RESULTS: Among 181 children (median age 4 years; 53% female; 16% with HIV; 14.4% confirmed TB), the HR TB score cut-point of -0.65 showed 88.5% sensitivity with specificity at 33.3% (SRS) and 30.3% (MRS). Sensitivity was lower for the CRS at 75.7%, with similar specificity (33.3%). Sensitivity was higher in children aged 5-9 and 10-14 years compared with those under 5 years, but specificity remained low (22.7%-28.6%). Combining Xpert-HR with CXR, Xpert Ultra, or TB treatment decision algorithms did not significantly enhance accuracy. CONCLUSIONS: GeneXpert MTB Host Response showed high sensitivity for detecting confirmed TB but had low specificity, risking overdiagnosis. Improved pediatric-specific gene signatures are necessary for better accuracy in children
The spread of molecular markers of artemisinin partial resistance and diagnostic evasion in Eritrea: a retrospective molecular epidemiology study.
Get PDFBACKGROUND: Eritrea was the first African country to discontinue the use of histidine rich protein 2 (HRP2)-detecting rapid diagnostic tests (RDTs) for malaria diagnosis following reports of a high prevalence of pfhrp2/3-deleted Plasmodium falciparum parasites causing false-negative results in the country. Eritrea was also the first African country to report partial artemisinin resistance due to the P falciparum kelch13 (pfk13) Arg622Ile mutation. We aimed to characterise the spatial distribution of pfk13 mutants and their interactions with pfhrp2/3 deletions in Eritrea and to assess the role of the use of HRP2-detecting RDTs and antimalarial (artesunate-amodiaquine) therapy in the spread of the two variants.
METHODS: We conducted a retrospective molecular epidemiological analysis of pfk13 mutations and pfhrp2/3 deletions in existing P falciparum-infected blood samples collected as part of previous pfhrp2/3 deletion and severe malaria studies. Samples were collected in March, 2016 and between September, 2018, and January, 2020, from symptomatic patients seeking care at 15 health centres in four administration zones (Semenawi Keyih Bahri, Gash Barka, Anseba, and Debub) in Eritrea. A fragment spanning the propeller region of pfk13 was amplified from samples and sequenced using Sanger sequencing or targeted amplicon sequencing to identify genetic mutations. Deletions of pfhrp2/3 genes in samples were determined using multiplex quantitative PCR. Parasite haplotypes and genetic relatedness of parasite haplotypes were determined previously using microsatellite marker typing. The primary objective was to determine the prevalence of pfk13 mutations at health centres and administrative zones. The secondary objective was to investigate whether pfk13 mutants and pfhrp2/3 deleted parasites converge.
FINDINGS: We sequenced 50 samples collected in March, 2016 from the Semenawi Keyih Bahri zone and identified no pfk13 mutations. By contrast, in 587 samples included in this study that were collected from health centres in Gash Barka, Anseba, and Debub in 2018-20, we detected five different single non-synonymous mutations: Glu605Lys, Arg622Ile, Asn657Lys, Lys658Glu, and Ser679Leu. The most prevalent mutation was pfk13 Arg622Ile, which was detected in samples collected from all nine health centres where more than five samples were available across all three administration zones, with an overall prevalence of 11·9% (70 of 587 samples; range 5·9-28·0%). We identified 22 unique pfk13 Arg622Ile mutant haplotypes among 26 samples tested, of which 13 (59·1%) were genetically related, whereas the remaining nine (40·9%) were not. The prevalence of pfk13 Arg622Ile was significantly higher in parasites with a single pfhrp3 deletion (46 [18·0%] of 255 samples) than in parasites without pfhrp2/3 deletions (ten [6·2%] of 161 samples; odds ratio 3·89 [95% CI 1·59-7·61]; p=0·0006) and with dual pfhrp2/3-deleted parasites (13 [9·0%] of 145; 2·23 [1·13-4·68]; p=0·018).
INTERPRETATION: The geographical spread of the pfk13 Arg622Ile mutation might have initially resulted from the clonal expansion and spread of pfhrp2/3 deletions under the test-and-treat policy using HRP2-detecting RDTs. Subsequently, selective pressure from artemisinin combination therapy could have further facilitated the spread of both pfk13 Arg622Ile and pfhrp2/3 deletions. Continuous monitoring of trends in pfk13 and pfhrp2/3 variants is needed to inform effective malaria control and elimination strategies in Eritrea and other African countries.
FUNDING: US Department of Defense Armed Forces Health Surveillance Division, Global Emerging Infections Surveillance Branch (AFHSD/GEIS), and Wellcome Trust
Integrated care in practice: lessons from three tiers of healthcare provider and commissioner staff in two London Integrated Care Systems.
Get PDFBACKGROUND: To better meet the growing demand and complexity of clinical need, there is a broad international trend towards greater integration of various elements of health- and social care. However, there has been a lack of research aimed at understanding how healthcare providers have experienced these changes, including facilitators and inhibitors of integration.
AIMS: This study set out to generate new understandings of this from three UK staffing 'levels': 'micro' frontline workers, a 'meso' level of those leading a healthcare organisation and a 'macro' level of commissioners.
METHOD: Using Rogers' Diffusion of Innovation framework, qualitative analysis of individual interviews from provider staff perceptions was undertaken at these three levels (total N = 33) in London.
RESULTS: English legislation and policy captured the need for change, but fail to describe problems or concerns of staff. There is little guidance that might facilitate learning. Staff identity, effective leadership and culture were considered critical in implementing effective integration, yet are often forgotten or ignored, compounded by an overall lack of organisational communication and learning. Cultural gains from integration with social care have largely been overlooked, but show promising opportunities in enhancing care delivery and experience.
CONCLUSIONS: Findings are mixed insofar as staff generally support the drivers for greater integration, but their concerns, and means for measuring change, have largely been ignored, limiting learning and optimisation of implementation. There is a need to emphasise the importance of culture and leadership in integrated care, and the benefits from closer working with social care
Stillbirth risk by fetal size among 126.5 million births in 15 countries from 2000 to 2020: A fetuses-at-risk approach.
Get PDFOBJECTIVE: To compare stillbirth rates and risks for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) pregnancies at 24-44 completed weeks of gestation using a birth-based and fetuses-at-risk approachs.
DESIGN: Population-based, multi-country study.
SETTING: National data systems in 15 high- and middle-income countries.
POPULATION: Live births and stillbirths.
METHODS: A total of 151 country-years of data, including 126 543 070 births across 15 countries from 2000 to 2020, were compiled. Births were categorised into SGA, AGA and LGA using INTERGROWTH-21st standards. Gestation-specific stillbirth rates, with total births as the denominator, and gestation-specific stillbirth risks, with fetuses still in utero as the denominator, were calculated from 24 to 44 weeks of gestation.
MAIN OUTCOME MEASURES: Gestation-specific stillbirth rates and risks according to size at birth.
RESULTS: The overall stillbirth rate was 4.22 per 1000 total births (95% CI 4.22-4.23) across all gestations. Applying the birth-based approach, the stillbirth rates were highest at 24 weeks of gestation, with 621.6 per 1000 total births (95% CI 620.9-622.2) for SGA pregnancies, 298.4 per 1000 total births (95% CI 298.1-298.7) for AGA pregnancies and 338.5 per 1000 total births (95% CI 337.9-339.0) for LGA pregnancies. Applying the fetuses-at-risk approach, the gestation-specific stillbirth risk was highest for SGA pregnancies (1.3-1.4 per 1000 fetuses at risk) prior to 29 weeks of gestation. The risk remained stable between 30 and 34 weeks of gestation, and then increased gradually from 35 weeks of gestation to the highest rate of 8.4 per 1000 fetuses at risk (95% CI 8.3-8.4) at ≥42 weeks of gestation. The stillbirth risk ratio (RR) was consistently high for SGA compared with AGA pregnancies, with the highest RR observed at ≥42 weeks of gestation (RR 9.2, 95% CI 15.2-13.2), and with the lowest RR observed at 24 weeks of gestation (RR 3.1, 95% CI 1.9-4.3). The stillbirth RR was also consistently high for SGA compared with AGA pregnancies across all countries, with national variability ranging from RR 0.70 (95% CI 0.43-0.97) in Mexico to RR 8.6 (95% CI 8.1-9.1) in Uruguay. No increased risk for LGA pregnancies was observed.
CONCLUSIONS: Small for gestational age (SGA) was strongly associated with stillbirth risk in this study based on high-quality data from high- and middle-income countries. The highest RRs were seen in preterm gestations, with two-thirds of the stillbirths born as preterm births. To advance our understanding of stillbirth, further analyses should be conducted using high-quality data sets from low-income settings, particularly those with relatively high rates of SGA