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Long-term survival after invasive pneumococcal disease: a matched cohort study using electronic health records in England.
Get PDFBACKGROUND: Invasive pneumococcal disease (IPD) is associated with increased long-term mortality, but it is unclear if this is explained by pre-existing comorbidities. We aimed to estimate the long-term survival following IPD in comparison with the general population, adjusting for potential confounders such as underlying comorbidities. METHODS: We conducted a matched cohort study comparing long-term survival (>120 days after infection) in individuals with IPD and comparators without IPD. Cases were individuals aged 65 years or older with laboratory-confirmed IPD (2012-19) identified through enhanced national surveillance. Comparators matched on age, sex, and calendar date of laboratory-confirmed diagnosis were drawn from primary care electronic health records in Clinical Practice Research Datalink GOLD. We used Cox regression, stratified by matched set, to compare mortality in people with and without IPD, adjusting for relevant comorbidities, socioeconomic deprivation, and ethnicity. FINDINGS: We included 13 401 IPD cases and 67 005 comparators without IPD. There were 5038 (53·5%) female and 4380 (46·5%) male IPD cases and 19 927 (53·5%) female and 17 351 (46·5%) male comparators without IPD. After adjusting for comorbidities, socioeconomic deprivation, and ethnicity, we found increased all-cause mortality in IPD cases compared with comparators without IPD (hazard ratio 3·74 [95% CI 3·50-3·99]). The predicted median survival was 4·7 years (IQR 2·9-7·4) for IPD cases and more than 11·9 years (IQR 8·7 to >11·9) for comparators without IPD. This increased mortality was consistent across subgroups defined by age, vaccination history, and comorbidity status (including diabetes, chronic respiratory disease, and chronic heart disease). INTERPRETATION: IPD was associated with increased mortality at least 5 years after infection. These findings emphasise the value of IPD prevention and the need for more research into the clinical management of people who have had IPD. Long-term mortality should be incorporated in cost-effectiveness analyses for pneumococcal vaccines. FUNDING: National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Vaccines and Immunisation (NIHR200929)
Kaupapa Māori approaches to improve Māori eye health: a protocol for a scoping review.
Get PDFINTRODUCTION AND AIM: Māori experience higher rates of disease and poorer health outcomes than non-Māori, highlighting inequities in the health system in Aotearoa New Zealand (Aotearoa). Māori eye health has historically been under-researched. Kaupapa Māori (by Māori, with Māori, for Māori) approaches to research have been recognised as critical for developing and informing equitable and inclusive health service solutions for Māori. This scoping review aims to summarise the literature on interventions to improve Māori eye health and investigate the extent to which Kaupapa Māori approaches have been used within these studies.
METHODS AND ANALYSIS: This scoping review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews Checklist and informed by Kaupapa Māori research and strengths-based methodologies. Electronic searches of MEDLINE (Ovid), Embase (Ovid) and Google Scholar were performed using keywords focused on Māori eye health, Kaupapa Māori and eye health interventions. The search was performed by an information specialist without language or time restrictions. Peer-reviewed and grey literature reports will be included if they report any intervention that aimed to improve eye health for Māori. Two reviewers will independently screen abstracts and full texts, followed by data charting in Covidence. Data items will include publication, study and intervention characteristics and whether a Kaupapa Māori approach was used, in which case the characteristics of the approach will be charted. The responsiveness to Māori of each included study will be assessed using the MĀORI framework and CONSIDER statement. Data will be summarised in tables, graphs, maps and text.
ETHICS AND DISSEMINATION: To the best of our knowledge, the scoping review is the first to investigate published and publicly accessible literature related to interventions for improving Māori eye health and Kaupapa Māori approaches. Ethical approval is not required for this review as we will include information available in the public domain. We anticipate that the findings will be useful for Hauora Māori providers, organisations, education training and research providers of eyecare services. The scoping review also informs a more extensive project examining Indigenous perspectives in optometry to achieve equitable outcomes. Dissemination will include publication of the scoping review findings in an open-access peer-reviewed journal, as well as presentations at conferences, to Māori community and service organisations, scholars and staff working in the field of Māori eye health.
REGISTRATION: Open science framework (https://osf.io/4vqaw/). On 27 February 2025
Association between hyperglycaemia, diabetes complications and development of fibrotic conditions among people living with type 1 and type 2 diabetes in England: a retrospective cohort study using UK Clinical Resource Datalink Aurum and Hospital Episode Statistics.
Get PDFOBJECTIVE: Fibrosis is a pathological feature that can occur in a wide range of diseases including diabetes mellitus. We investigated whether in people with type 1 (T1DM) or type 2 diabetes mellitus (T2DM), glycaemia or diabetes-related complications are associated with fibrotic diseases.
DESIGN AND SETTING: Retrospective cohort study using UK Clinical Resource Datalink (CPRD) Aurum and Hospital Episode Statistics.
PARTICIPANTS: We included people with prevalent T1DM or T2DM as of 31 December 2015 (recorded in CPRD Aurum), eligible for linkage with Hospital Episode Statistics and followed up for 3 years.
OUTCOME MEASURES: We defined diabetes status using blood/urine biomarkers and complications. In the T2DM cohort, we also investigated exposures of hyperglycaemia, insulin resistance and metformin prescription. Fibrotic condition diagnoses were determined from both primary and secondary care records. Logistic regression analyses were undertaken to understand the strength of association between diabetes status/diabetic complications and fibrotic conditions, respectively.
RESULTS: The T1DM cohort consisted of 9669 people while the T2DM cohort included 504 066 people. In T1DM, we found that albuminuria was associated with lung fibrosis (ORadj: 2.07, 99% CI 1.35 to 2.17), and microvascular complications were associated with atherosclerosis (ORadj: 1.81, 99% CI 1.18 to 2.77) and cardiomyopathy (ORadj 1.53, 99% CI:1.15 to 2.04). In the T2DM cohort, both glycaemia above target and diabetes complications were associated with most fibrotic conditions.
CONCLUSIONS: Within the T1DM population, no consistent association between diabetes status and all fibrotic diseases was observed. More research is required to understand whether the association between diabetes complications and fibrotic diseases is due to shared risk factors or whether glycaemia in T2DM may be influenced by fibrotic pathology
Causal Relationships Between Major Depressive Disorder and Coronary Artery Disease Across Diverse Populations: A Bidirectional Mendelian Randomisation Study.
Get PDFBACKGROUND AND OBJECTIVES: Coronary artery disease remains the leading cause of cardiovascular mortality worldwide, with a disproportionate burden in low- and middle-income countries. Although observational studies have established a bidirectional relationship between depression and coronary artery disease, the underlying genetic basis of this association remains unclear, particularly in underrepresented diverse-ancestry populations. Establishing whether this relationship is causal and whether it differs by ancestry is critical for informing targeted and equitable prevention strategies. METHODOLOGY: This study employed a bidirectional two-sample Mendelian randomisation framework to investigate the causal relationship between major depressive disorder and coronary artery disease across East Asian, European and African populations. Using summary statistics from large-scale genome-wide association studies, we assessed both the direction and strength of genetic associations between major depressive disorder and coronary artery disease. Sensitivity analyses were conducted to test the robustness of the findings. RESULTS: Genetically predicted major depressive disorder was associated with increased coronary artery disease risk in European populations, confirming a causal effect consistent with prior evidence. In East Asians, we found a potentially false-positive result suggesting an inverse association between genetic liability to coronary artery disease and major depressive disorder (IVW OR = 0.942; p = 0.040), which was not supported across Mendelian randomisation sensitivity analyses and did not hold true after Bonferroni correction. In African ancestry populations, no significant causal effects were detected in either direction, due to wide confidence intervals resulting from limited sample sizes. CONCLUSIONS: Our findings provide evidence for a causal relationship between depression and coronary artery disease in Europeans and suggest potential ancestry-specific variation in this relationship, with a novel inverse association between coronary artery disease and major depressive disorder observed in East Asians requiring further replication and validation. These results highlight how limited data availability in underrepresented populations constrains causal inference, underscoring the need for more inclusive genetic research to inform equitable, population-relevant public health strategies
Epstein-Barr Virus Central Nervous System Infections and Mortality Risk in Patients Presenting With Suspected Meningitis: Results From the Botswana National Meningitis Survey and the Harare Meningitis Aetiology Study.
Get PDFBACKGROUND: Epstein-Barr virus (EBV) central nervous system (CNS) infection in immunocompromised hosts and among meningitis cohorts is well recognized. The clinical significance of EBV CNS infection, however, is poorly understood. METHODS: Data were collected as part of the Botswana National Meningitis Survey and the Harare Meningitis Aetiology Study. The prevalence of EBV CNS infection (EBV DNA detected in cerebrospinal fluid [CSF] by means of quantitative polymerase chain reaction) was determined, alongside associations with baseline covariates and the in-hospital mortality rate. RESULTS: A total of 581 participants with suspected meningitis were recruited. Of these, 54% were male, the median age (interquartile range) was 38 (29-46) years, and 76% were persons living with human immunodeficiency virus (HIV). Cryptococcal meningitis was the most common microbiologically confirmed infectious meningitis (12.0%), and 6.4% of participants had definite tuberculous meningitis. EBV CNS infection was common (26% [152 of 581]) and was associated with older age, being HIV positive, and CSF pleocytosis (P < .001). It was also associated with increased in-hospital mortality rate (odds ratio, 1.64, [95% confidence interval, 1.10-2.43]; P = .01), but after adjustment for sex, age, and HIV status, there was no longer evidence of an association (adjusted odds ratio, 1.29 [.84-1.98]; P = .25). In subgroup analyses, there was an indication that the association between EBV CNS infection and mortality rate may differ by meningitis subgroup. CONCLUSIONS: EBV CNS infection was common among our cohort, and it was strongly associated with CSF pleocytosis. Following multivariable analyses, EBV CNS infection overall was not associated with in-hospital mortality rate. EBV CNS infection in the context of meningitis is most likely a "bystander" virus that reflects heightened CSF inflammation
Political priority of adolescent mental health in Mexico: An exploratory mixed-methods study.
Get PDFOBJECTIVES: Despite suicide being the third leading cause of death among individuals aged 15-24 in Mexico, mental health services are neglected. This study examines the specific challenges encountered by key stakeholders in Mexico for the political prioritization of adolescent mental health (AMH).
STUDY DESIGN: A mixed-methods exploratory sequential design was applied to derive a two-round policy Delphi from the thematic analysis of semi-structured interviews. Interview themes were initially selected from Shiffman's global health networks framework.
METHODS: The research was conducted between 2022 and 2023. Semi-structured interviews were conducted using purposive sampling, followed by a two-round policy Delphi study. Participants included policymakers, civil society representatives, academics, and young advocates with experience at international, national, or local levels. Interview data underwent thematic analysis guided by Shiffman's policy framework, and Delphi results were analysed using descriptive statistics and consensus measurement.
RESULTS: We conducted 24 interviews and obtained 19 responses in the first policy Deplhi round and 18 in the second. Concerning problem definition, participants agreed that suicide, self-harm, depression, anxiety, and substance abuse are the most urgent issues. Regarding positioning, there are few strategies to communicate the urgency of addressing AMH at the national level. For coalition-building, there is collaboration within governmental institutions, but we could not identify consistent intersectoral collaboration. Finally, concerning governance, most non-public sector participants could not identify clear leadership for AMH.
CONCLUSION: This research identifies the obstacles key stakeholders face in their efforts to prioritize AMH in Mexico, which can be addressed through strategic coalition building interventions. Key to these strategies is the expansion of advocacy networks beyond governmental bodies and the cultivation of strong leadership
Greater benefits of immediate nirmatrelvir-ritonavir initiation for post-COVID outcomes: a population-based retrospective cohort study.
Get PDFNirmatrelvir-ritonavir is generally recommended to be initiated within five days of COVID-19 symptom onset. This study examined the association between the timing of nirmatrelvir-ritonavir initiation and post-acute outcomes more precisely using territory-wide data in Hong Kong. We included patients aged ≥18 years who tested positive for SARS-CoV-2 between March 16, 2022, and November 9, 2023, and were hospitalized with COVID-19. Treatment groups were formed based on the time from the positive RT-PCR date to nirmatrelvir-ritonavir initiation. Among 15,978 patients who received nirmatrelvir-ritonavir, 10,028 (62.8%) patients were included in Day 0 group, 4973 (31.1%) in Day 1 group, and 977 (6.1%) in Day 2 or later group. The control group comprised 22,312 patients who did not receive nirmatrelvir-ritonavir. Compared with the control group, the risks of post-acute mortality were significantly lower in Day 0 group (hazard ratio [HR] 0.51, 95% CI 0.46-0.56; p < 0.0001) and Day 1 group (HR 0.66, CI 0.59-0.74; p < 0.0001), but not in Day 2 or later group. Meta-regression results showed that more immediate initiation was associated with lower risks of death and all-cause hospitalization. Our findings suggested that the antiviral should be prescribed immediately after COVID-19 diagnosis for achieving its greatest benefit on improving post-COVID outcomes
Deciphering Microscopic Agglutination Test (MAT) Serogroup Cross-Reactivity in Leptospirosis: The Influence of Age and Antibody Titers.
Get PDFLeptospirosis is a zoonotic disease caused by Leptospira spp., with over 250 serovars classified into 24 serogroups. Control measures depend on understanding serovar-specific epidemiology, yet the microscopic agglutination test (MAT) is only serogroup specific, and classification is complicated by cross-reactivity. While MAT is the reference standard for leptospirosis serodiagnosis and seroepidemiological studies, factors influencing serogroup cross-reactivity remain poorly characterized. We investigated the relationship between age, antibody titer, and serogroup diversity among seropositive individuals in a population-based serosurvey in the Dominican Republic. Between June and October 2021, we conducted a multistage national serosurvey, enrolling 6683 participants across 134 clusters. MAT was performed on sera from 2091 participants in two provinces using a 20-serovar panel. MAT positivity was defined as titers ≥ 1:100. Generalized Additive Models were used to assess associations between age, maximum titer, and serogroup diversity. Of 2091 tested samples, 237 (11.3%) were seropositive. Older individuals and those with higher titers reacted to a greater number of serogroups (p = 0.005 and p < 0.0001, respectively). However, mean maximum titer decreased with age, suggesting that broader serogroup reactivity in older individuals reflects cumulative exposure rather than higher titers. Maximum titer was the strongest predictor of serogroup breadth, while gender, study region, and urban/rural setting were not significant. Overall, our findings demonstrate that serogroup cross-reactivity in MAT was significantly influenced by antibody titer and prior exposure, with older individuals displaying broader serogroup reactivity despite lower titers. These findings highlight key considerations for interpreting MAT results in seroepidemiological studies and underscore the limitations of MAT in serogroup-level classification
Left behind in primary healthcare: A qualitative exploration of healthcare experiences of people with disabilities in Ethiopia.
Get PDFPeople with disabilities, who make up 1.3 billion globally, frequently face systemic exclusion from healthcare due to a range of barriers. This qualitative study explored the healthcare access experiences of 30 adults with disabilities in Bahir Dar City, Ethiopia, aiming to identify barriers, facilitators, and context-driven solutions. Both purposive and snowball sampling was conducted to identify participants. In-depth interviews were conducted in the local language. Data were analysed using reflexive thematic analysis in NVivo 14, guided by the Missing Billion Health System Framework service delivery components. The study identified five key themes each for barriers, facilitators, and coping strategies. Major barriers included low health literacy, unaffordable care, negative provider attitudes, inaccessible infrastructure, and lack of assistive technologies and rehabilitation services. Facilitators included family support, community-based health insurance, disability-sensitive training of healthcare workers, presence of a rehabilitation centre, and initiation of renovation infrastructure in model facilities. Participants proposed actionable strategies such as increasing awareness, insurance coverage, local production of assistive technologies, assigning personal assistants in health facilities, improving accessibility, and establishing disability units within governance structures. People with disabilities experienced persistent, intersecting barriers to healthcare access in Ethiopia. However, scaling disability-inclusive training, infrastructure improvemnts, and governance reforms-rooted in lived experience and aligned with human rights of people with disabilities-can help drive progress toward Universal Health Coverage
Wartime food availability in the Gaza Strip, October 2023 to August 2024: a retrospective analysis.
Get PDFOBJECTIVES: To estimate food availability and the contribution of different food sources during the first 10 months (7 October 2023 to 31 August 2024) of the Israeli military operation in the Gaza Strip.
DESIGN: Retrospective statistical modelling analysis.
SETTING: War-affected population in the Gaza Strip, occupied Palestinian Territories, with stratification into northern and south-central governorates.
PARTICIPANTS: Entire population.
MAIN OUTCOME MEASURES: Calories available per capita; proportional contribution to food availability, by source including baseline stocks, agricultural output, trucks and air/sea-borne deliveries.
RESULTS: Between October 2023 and April 2024, food trucked into Gaza remained below prewar levels. Israeli data offered higher weight estimates than the United Nations' (UN) but appeared to feature extreme approximation. The share of food categories changed little during the period analysed, but trucked-in food's caloric value was lowest just as food was scarcest (February-March 2024). Trucks accounted for three-fourths of food in south-central Gaza, but <20% in the north; air and sea deliveries contributed little. As of May 2024, when Israel took control of crossings, caloric availability had been insufficient during 8 weeks in northern and 3 weeks in south-central Gaza. Thereafter, UN data featured under-reporting, but even Israeli data indicated declining deliveries.
CONCLUSIONS: Israel, as occupying power, did not ensure sufficient food availability throughout the analysis period, and its data appear unreliable. Existing stocks probably mitigated caloric deficits resulting from insufficient deliveries, but air and sea routes added little. Strengthened coordination of food deliveries may be warranted to optimise caloric quantity and dietary diversity