London School of Hygiene & Tropical Medicine

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    69832 research outputs found

    Exploring how to widen the acceptability of public health interventions: a systematic review protocol.

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    INTRODUCTION: Health interventions that require significant change to individual lifestyles or social norms can pose a challenge for widespread public acceptability and uptake. At the same time, over the last two decades, there has been increasing attention paid to the rise of populist movements globally, defined by 'the people' pushing against 'an elite' viewed as depriving the people of their sovereignty. To understand potential overlap in these two areas, this study aims to synthesise existing international evidence on linkages between populist attitudes and reduced uptake, acceptability, adherence and/or effectiveness of public health interventions. The goal of this work is to create a conceptual framework that can be used to inform policy strategies aimed at widening the impact of public health interventions. METHODS AND ANALYSIS: A systematic review will be performed via searches across databases and websites relevant to public health and social science research, informed by preliminary searches on the topic. There will be no language restrictions, but included studies will be limited to those produced since 2008, the year of the global financial crisis, from which most current literature on populism dates. Risk of bias will be assessed using validated tools according to study design. Due to expected heterogeneity across included studies, this will be a systematic review without meta-analysis. Findings will be synthesised narratively, and the strength of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The review will be reported according to the Systematic Reviews without Meta-Analysis reporting guidelines. ETHICS AND DISSEMINATION: Ethical review is not required for this study. Public dissemination will be informed via consultation with our Patient and Public Involvement and Engagement Strategy Group, along with reporting via peer-reviewed publication, relevant international conferences, a policy brief and a workshop with public health and communications experts. PROSPERO REGISTRATION NUMBER: CRD42024513124

    Airway inflammation accelerates pulmonary exacerbations in cystic fibrosis.

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    Airway inflammation underlies cystic fibrosis (CF) pulmonary exacerbations. In a prospective multicenter study of randomly selected, clinically stable adolescents and adults, we assessed relationships between 24 inflammation-associated molecules and the future occurrence of CF pulmonary exacerbation using proportional hazards models. We explored relationships for potential confounding or mediation by clinical factors and assessed sensitivities to treatments including CF transmembrane regulator (CFTR) protein synthesis modulators. Results from 114 participants, including seven on ivacaftor or lumacaftor-ivacaftor, representative of the US CF population during the study period, identified 10 biomarkers associated with future exacerbations mediated by percent predicted forced expiratory volume in 1 s. The findings were not sensitive to anti-inflammatory, antibiotic, and CFTR modulator treatments. The analyses suggest that combination treatments addressing RAGE-axis inflammation, protease-mediated injury, and oxidative stress might prevent pulmonary exacerbations. Our work may apply to other airway inflammatory diseases such as bronchiectasis and the acute respiratory distress syndrome

    Carriage and antimicrobial susceptibility of commensal Neisseria species from the human oropharynx.

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    Commensal Neisseria (Nc) mainly occupy the oropharynx of humans and animals. These organisms do not typically cause disease; however, they can act as a reservoir for antimicrobial resistance genes that can be acquired by pathogenic Neisseria species. This study characterised the carriage and antimicrobial susceptibility profiles of Nc from the oropharynx of 50 participants. Carriage prevalence of Nc species was 86% with 66% of participants colonised with more than one isolate. Isolates were identified by MALDI-ToF and the most common species was N. subflava (61.4%). Minimum inhibitory concentrations (MICs) to penicillin, ceftriaxone, ciprofloxacin, azithromycin, tetracycline, and gentamicin were determined by agar dilution and E-test was used for cefixime. Using Ng CLSI/EUCAST guidelines, Nc resistance rates were above the WHO threshold of 5% resistance in circulating strains for changing the first line treatment empirical antimicrobial: 5% (CLSI) and 13 (EUCAST) for ceftriaxone and 29.3% for azithromycin. Whole genome sequencing of 30 Nc isolates was performed, which identified AMR genes to macrolides and tetracycline. Core gene MLST clustered Nc into three main groups. Gonococcal DNA uptake sequences were identified in two Nc clusters. This suggests that Nc have the potential AMR gene pool and transfer sequences that can result in resistance transfer to pathogenic Neisseria within the nasopharyngeal niche

    Economic cost of a case of diarrhoea in Uvira, Democratic Republic of the Congo: A cost of illness study.

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    BACKGROUND: Diarrhoea is one of the leading causes of disability-adjusted life years (DALYs) among children below five years, though the proportion of the burden occurring amongst those aged over 70 is increasing. The cost of treating and managing diarrhoea can place a burden on individuals, their households, and society in general. The cost can be high but is often undocumented, and many studies focus on children or hospitalised patients only. This study aimed to estimate the economic cost per case of diarrhoea amongst individuals of any age in Uvira, Democratic Republic of the Congo. METHODS: The study was cross-sectional and retrospective, and based on a household survey approximately representative of the city undertaken in September 2021. Data on quantities and prices of resources were collected in the survey, as well as from interviews with staff at the Cholera Treatment Centre in the Uvira general hospital and their records on resource use and patient numbers. Direct and indirect costs were measured from the societal perspective, and generalised linear regression used to identify factors associated with higher costs. RESULTS: Of 2,820 members of the 528 households surveyed, 175 people (6.2%) were reported to have had diarrhoea in the previous seven days. The majority sought care (91%) of which most (64%) visited a pharmacy. The average economic cost of illness (COI) for an episode of diarrhoea was 33,816 Congolese Francs (CDF) (US17.0)in2021prices.ThemedianwasCDF14,000(US 17.0) in 2021 prices. The median was CDF 14,000 (US 7.0). The average out of pocket COI to patients was CDF 15,579 (US$ 7.8), representing 9% of the estimated average monthly income of households. On average caregivers and patients lost 4 days per episode. A concentration index suggested a lower economic COI among poorer households (p=0.099). A regression analysis identified that being older than 5 years (p=0.001) or being water insecure (p=0.032) were associated with higher COI. CONCLUSION: Households in Uvira experience many diarrhoeal episodes per year, and the COI is an important burden for them and society. These costs could be avoided if diarrhoea were prevented through public health interventions to reduce prevalence and care-seeking was better managed to avert this public health burden

    Informing HPV vaccine pricing for government-funded vaccination in mainland China: a modelling study.

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    BACKGROUND: The high price of HPV vaccines remains a significant barrier to vaccine accessibility in China, hindering the country's efforts toward cervical cancer elimination and exacerbating health inequity. We aimed to inform HPV vaccine price negotiations by identifying threshold prices that ensure that a government-funded HPV vaccination programme is cost-effective or cost-saving. METHODS: We used a previously validated transmission model to estimate the health and economic impact of HPV vaccination over a 100-year time horizon from a healthcare payer perspective. Threshold analysis was conducted considering different settings (national, rural, and urban), cervical cancer screening scenarios (cytology-based or HPV DNA-based, with different paces of scale-up), vaccine types (four types available in China), vaccine schedules (two-dose or one-dose), mode of vaccination (routine vaccination with or without later switching to high-valency vaccines), willingness-to-pay thresholds, and decision-making criteria (cost-effective or cost-saving). Furthermore, we examined the budget impact of introducing nationwide vaccination at the identified threshold prices. FINDINGS: Using the current market price, national routine HPV vaccination with any currently available vaccine is unlikely cost-effective. Under a two-dose schedule, the prices of the four available HPV vaccine types cannot exceed 2626-36 per dose (44.1%-80.2% reduction from current market prices) depending on vaccine type to ensure the cost-effectiveness of the national programme. Adopting vaccination at threshold prices would require an annual increase of 72.18%-96.95% of the total annual National Immunization Programme (NIP) budget in China. A cost-saving routine vaccination programme requires vaccine prices of 55-10 per dose (depending on vaccine type), producing a 21.38%-34.23% increase in the annual NIP budget. Adding the second dose is unlikely to be cost-effective compared to a one-dose schedule, with the threshold price approaching or even falling below zero. Rural pilot vaccination programmes require lower threshold prices compared with a national programme. INTERPRETATION: Our study could inform vaccine price negotiation and thus facilitate nationwide scale-up of current HPV vaccination pilot programmes in China. The evidence may potentially be valuable to other countries facing HPV introduction barriers due to high costs. This approach may also be adapted for other contexts that involve the introduction of a pricy vaccine. FUNDING: CAMS Innovation Fund for Medical Sciences (CIFMS); Bill & Melinda Gates Foundation

    Rapid antibiotic susceptibility testing for urinary tract infections in secondary care in England: a cost-effectiveness analysis.

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    OBJECTIVES: To perform a model-based cost-effectiveness evaluation of a rapid antimicrobial susceptibility test. DESIGN: A Markov model of a cohort of hospital inpatients with urinary tract infection (with inpatient numbers based on national administrative data from 1 April 2017 to 31 March 2019). SETTING: Urinary tract infections (UTI) in acute National Health Service (NHS) Trusts in England, from the perspective of the NHS Healthcare system, at a national level. PARTICIPANTS: A simulated cohort of approximately 280 000 non-pregnant adult inpatients within secondary care with a clinical suspicion of UTI. INTERVENTIONS: Evaluation of the implementation of a fast bacterial impedance cytometry test (BICT) compared with current practice. PRIMARY AND SECONDARY OUTCOME MEASURES: Incremental cost, quality-adjusted life years, net monetary benefit, and bed days and appropriateness of antibiotic use per patient. Costs are presented in 2022 GBP. RESULTS: Considering benefits arising from reduced time on inappropriate treatment, BICT gives an average net monetary benefit (NMB) over the simulation period of approximately £4.3 million and dominates culture methods (from the healthcare system perspective and with a willingness to pay threshold of £20 000 per quality-adjusted life year). Total inappropriate prescribing days due to the BICT test are reduced by 57%. The extent of the benefit from BICT implementation was strongly dependent on prevalence of resistance, with the NMB increasing sevenfold to over £30 million in a high (40%) resistance prevalence scenario. At the population level, the patient groups with the highest cost and quality-adjusted life year impacts were 65-100-year-old females, followed by males, with uncomplicated UTIs. At an individual patient level, however, 16-64-year-old females with complicated UTIs with oral treatment, followed by 65-100-year-old males with complicated UTIs with oral treatment, were impacted to the greatest degree by the rapid BICT. CONCLUSIONS: Under conservative assumptions and for wide parameter sensitivity, the implementation of BICT would be cost-effective from the NHS healthcare system perspective

    Novel Plasmodium falciparum histidine-rich protein 2/3 repeat type in Ethiopian malaria infection: does this affect performance of HRP2-based malaria RDT?

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    BACKGROUND: Rapid diagnostic tests (RDTs) provide quick, easy, and convenient early diagnosis of malaria ensuring better case management particularly in resource-constrained settings. Nevertheless, the efficiency of HRP2-based RDT can be compromised by Plasmodium falciparum histidine-rich protein 2/3 gene deletion and genetic diversity. This study explored the genetic diversity of PfHRP2/3 in uncomplicated malaria cases from Ethiopia. METHODS: A cross-sectional study was conducted from June 2022 to March 2023 at Metehara, Zenzelema and Kolla Shele health centres, Ethiopia. Finger-prick blood samples were collected for RDT testing and microscopic examination. For molecular analysis, parasite genomic DNA was extracted from venous blood. Plasmodium falciparum was confirmed using VarATS real time PCR. Additionally, PfHRP2/3 was amplified, and DNA amplicons were sequenced using Oxford Nanopore technology. RESULTS: PfHRP2/3 sequences revealed small variations in the frequency and number of amino acid repeat types per isolate across the three health centres. Twelve and eight types of amino acid repeats were identified for PfHRP2 and PfHRP3, respectively, which had been previously characterized. Repeat type 1, 4 and 7 were present in both PfHRP2 and PfHRP3 amino acid sequences. Type 2 and 7 repeats were commonly dispersed in PfHRP2, while repeat types 16 and 17 were found only in PfHRP3. A novel 17 V repeat type variant, which has never been reported in Ethiopia, was identified in six PfHRP3 amino acid sequences. The majority of the isolates, as determined by the Baker's logistic regression model, belonged to group C, of which 86% of them were sensitive to PfHRP2-based RDT. Likewise, PfHRP2-based RDT detected 100% of the isolates in group A (product of type 2 × type 7 repeats ≥ 100) and 85.7% in group B (product of types 2 × type 7 repeats 50-99) at a parasitaemia level > 250 parasite/μl. CONCLUSION: This study highlights the significant diversity observed in PfHRP2 and PfHRP3 among clinical isolates of Plasmodium falciparum in Ethiopia. This emphasizes the necessity for monitoring of PfHRP2- based RDT efficacy and their repeat type distribution using a large sample size and isolates from various ecological settings

    Breaking the threshold: Developing multivariable models using computer-aided chest X-ray analysis for tuberculosis triage.

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    OBJECTIVES: Computer-aided detection (CAD) software packages quantify tuberculosis (TB)-compatible chest X-ray (CXR) abnormality as continuous scores. In practice, a threshold value is selected for binary CXR classification. We assessed the diagnostic accuracy of an alternative approach to applying CAD for TB triage: incorporating CAD scores in multivariable modeling. METHODS: We pooled individual patient data from four studies. Separately, for two commercial CAD, we used logistic regression to model microbiologically confirmed TB. Models included CAD score, study site, age, sex, human immunodeficiency virus status, and prior TB. We compared specificity at target sensitivities ≥90% between the multivariable model and the current threshold-based approach for CAD use. RESULTS: We included 4,733/5,640 (84%) participants with complete covariate data (median age 36 years; 45% female; 22% with prior TB; 22% people living with human immunodeficiency virus). A total of 805 (17%) had TB. Multivariable models demonstrated excellent performance (areas under the receiver operating characteristic curve [95% confidence interval]: software A, 0.91 [0.90-0.93]; software B, 0.92 [0.91-0.93]). Compared with threshold scores, multivariable models increased specificity (e.g., at 90% sensitivity, threshold vs model specificity [95% confidence interval]: software A, 71% [68-74%] vs 75% [74-77%]; software B, 69% [63-75%] vs 75% [74-77%]). CONCLUSION: Using CAD scores in multivariable models outperformed the current practice of CAD-threshold-based CXR classification for TB diagnosis

    Discrepancies between the Spatial Distribution of Cancer Incidence and Mortality as an Indicator of Unmet Needs in Cancer Prevention and/or Treatment in Hungary.

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    There is a rich body of literature on the distribution of cancer incidence and mortality in socioeconomically different world regions, but none of the studies has compared the spatial distribution of mortality and incidence to see if they are consistent with each other. All malignant neoplasms combined and cervical, colorectal, breast, pancreatic, lung, and oral cancers separately were studied in the Hungarian population aged 25-64 years for 2007-2018 at the municipality level by sex. In each case, the spatial distribution of incidence and mortality were compared with each other and with the level of deprivation using disease mapping, spatial regression, risk analysis, and spatial scan statistics. A positive association between deprivation and mortality was found for each type of cancer, but there was no significant association for male colorectal cancer (relative risk (RR) 1.00; 95% credible interval (CI) 0.99-1.02), pancreatic cancer (RR: 1.01; 95%CI 0.98-1.04), and female colorectal cancer incidence (RR: 1.01; 95%CI 0.99-1.03), whereas a negative association for breast cancer (RR: 0.98; 95%CI 0.96-0.99) was found. Disease mapping analyses showed only partial overlap between areas of high incidence and mortality, often independent of deprivation. Our results highlight not only the diverse relationship between cancer burden and deprivation, but also the inconsistent relationship between cancer incidence and mortality, pointing to areas with populations that require special public health attention

    Suggested solutions to barriers in accessing healthcare by persons with disability in Uganda: a qualitative study.

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    BACKGROUND: There are 1.3 billion people with disabilities globally, and they frequently face barriers to accessing healthcare, contributing to their worse health and higher mortality. However, little research has explored patient-reported approaches to improve healthcare for persons with disabilities. Consequently, this study aimed to explore possible solutions and recommendations to address the existing barriers to access to healthcare for persons with disabilities in rural Uganda. METHODS: We conducted 27 semi-structured interviews with individuals with various disabilities in rural Luuka district, Eastern Uganda, between September and November 2022. The participants included individuals with visual impairment (n = 5), physical impairment (n = 5), hearing impairment (n = 6), multiple impairments (n = 5), intellectual/cognitive impairment (n = 5), and albinism (n = 1). Interviews were recorded, transcribed verbatim, and thematically analysed. We categorized the solutions using the Missing Billion disability-inclusive health systems framework. RESULTS: Our findings, framed within the health systems framework, revealed several critical themes. On the demand side, suggested solutions emphasized advocacy and sensitization for persons with disabilities, their communities, and caregivers about healthcare needs. Socio-economic empowerment and community-based health services were also highlighted as essential. On the supply side, participants stressed the importance of training healthcare workers on disability, facilitating dialogue and experience-sharing sessions, and employing health workers with disabilities. Additional recommendations included improving accessibility and reasonable accommodation, organizing inclusive services like special clinic days and outreaches, ensuring representation in health facility management, and establishing comprehensive rehabilitation services with affordable assistive devices. CONCLUSION: The multifaceted solutions proposed by persons with disabilities highlight the complex challenges they face in accessing healthcare services and highlight the necessity for comprehensive, sustainable interventions. The call to action for policymakers and healthcare providers is to prioritise the incorporation of disability-inclusive practices and explore multi-dimensional approaches that foster a more inclusive healthcare environment that adequately meets the needs of persons with disabilities

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