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INTRODUCTION: Telomeres are a measure of cellular ageing with potential links to diseases such as cardiovascular diseases and cancer. Studies have shown that some infections may be associated with telomere shortening, but whether an association exists across all types and severities of infections and in which populations is unclear. Therefore we aim to collate available evidence to enable comparison and to inform future research in this field. METHODS AND ANALYSIS: We will search for studies involving telomere length and infection in various databases including MEDLINE (Ovid interface), EMBASE (Ovid interface), Web of Science, Scopus, Global Health and the Cochrane Library. For grey literature, the British Library of electronic theses databases (ETHOS) will be explored. We will not limit by study type, geographical location, infection type or method of outcome measurement. Two researchers will independently carry out study selection, data extraction and risk of bias assessment using the ROB2 and ROBINS-E tools. The overall quality of the studies will be determined using the Grading of Recommendations Assessment, Development and Evaluation criteria. We will also evaluate study heterogeneity with respect to study design, exposure and outcome measurement and if there is sufficient homogeneity, a meta-analysis will be conducted. Otherwise, we will provide a narrative synthesis with results grouped by exposure category and study design. ETHICS AND DISSEMINATION: The present study does not require ethical approval. Results will be disseminated via publishing in a peer-reviewed journal and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023444854.
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Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Humanos , Acortamiento del Telómero , Telómero/genética , InfeccionesRESUMEN
INTRODUCTION: 4.2 million individuals in the UK have type 2 diabetes, a known risk factor for dementia and mild cognitive impairment (MCI). Diabetes treatment may modify this association, but existing evidence is conflicting. We therefore aimed to assess the association between metformin therapy and risk of incident all-cause dementia or MCI compared with other oral glucose-lowering therapies (GLTs). RESEARCH DESIGN AND METHODS: We conducted an observational cohort study using the Clinical Practice Research Datalink among UK adults diagnosed with diabetes at ≥40 years between 1990 and 2019. We used an active comparator new user design to compare risks of dementia and MCI among individuals initially prescribed metformin versus an alternative oral GLT using Cox proportional hazards regression controlling for sociodemographic, lifestyle and clinical confounders. We assessed for interaction by age and sex. Sensitivity analyses included an as-treated analysis to mitigate potential exposure misclassification. RESULTS: We included 211 396 individuals (median age 63 years; 42.8% female), of whom 179 333 (84.8%) initiated on metformin therapy. Over median follow-up of 5.4 years, metformin use was associated with a lower risk of dementia (adjusted HR (aHR) 0.86 (95% CI 0.79 to 0.94)) and MCI (aHR 0.92 (95% CI 0.86 to 0.99)). Metformin users aged under 80 years had a lower dementia risk (aHR 0.77 (95% CI 0.68 to 0.85)), which was not observed for those aged ≥80 years (aHR 0.95 (95% CI 0.87 to 1.05)). There was no interaction with sex. The as-treated analysis showed a reduced effect size compared with the main analysis (aHR 0.90 (95% CI 0.83 to 0.98)). CONCLUSIONS: Metformin use was associated with lower risks of incident dementia and MCI compared with alternative GLT among UK adults with diabetes. While our findings are consistent with a neuroprotective effect of metformin against dementia, further research is needed to reduce risks of confounding by indication and assess causality.
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Demencia , Diabetes Mellitus Tipo 2 , Metformina , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Metformina/efectos adversos , Estudios de Cohortes , Hipoglucemiantes/efectos adversos , Glucosa , Demencia/epidemiología , Demencia/prevención & control , Atención Primaria de Salud , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Although some systemic infections are associated with Parkinson's disease (PD), the relationship between herpes zoster (HZ) and PD is unclear. OBJECTIVE: The objective is to investigate whether HZ is associated with incident PD risk in a matched cohort study using data from the US Department of Veterans Affairs. METHODS: We compared the risk of PD between individuals with incident HZ matched to up to five individuals without a history of HZ using Cox proportional hazards regression. In sensitivity analyses, we excluded early outcomes. RESULTS: Among 198,099 individuals with HZ and 976,660 matched individuals without HZ (median age 67.0 years (interquartile range [IQR 61.4-75.7]); 94% male; median follow-up 4.2 years [IQR 1.9-6.6]), HZ was not associated with an increased risk of incident PD overall (adjusted HR 0.95, 95% CI 0.90-1.01) or in any sensitivity analyses. CONCLUSION: We found no evidence that HZ was associated with increased risk of incident PD in this cohort. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Herpes Zóster , Enfermedad de Parkinson , Veteranos , Humanos , Masculino , Anciano , Femenino , Estudios de Cohortes , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/complicaciones , Factores de Riesgo , Herpes Zóster/complicaciones , Herpes Zóster/epidemiologíaRESUMEN
BACKGROUND: Better understanding of risk factors for influenza could help improve seasonal and pandemic planning. There is a dearth of literature on area-level risk factors such as population density and rural/urban living. METHODS: We used data from Flusurvey, an online community-based cohort that records influenza events. The study outcome was symptoms of influenza-like illness (ILI). Multivariable Poisson regression analysis was used to explore associations of both population density and rural/urban status with rate of ILI symptoms and whether these effects differed by vaccination status. RESULTS: Of the 6177 study participants, the median age was 45 (IQR 32-57), 65.73% were female, and 66% reported at least one episode of ILI symptoms between 2011 and 2016. We found no evidence to suggest that the rate of ILI symptoms was higher in the medium [RR 1.02 (95% CI 0.95-1.09)] or high [RR 1.02 (95% CI 0.96-1.09)] population density group versus the low population density group. This was the same for the effect of urban living [RR 0.96 (95% CI 0.90-1.03)] versus rural living on symptom rate. There was weak evidence to suggest that the ILI symptom rate was lower in urban areas compared with rural areas among unvaccinated individuals only [RR 0.90 (95% CI 0.83-0.99)], whereas no difference was seen among vaccinated individuals [1.04 (95% CI 0.94-1.16)]. CONCLUSIONS: Although neither population density nor rural/urban status was associated with ILI symptom rate in this community cohort, future research that incorporates activity and contact patterns will help to elucidate this relationship further.
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Gripe Humana , Virosis , Inglaterra/epidemiología , Femenino , Humanos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Masculino , Persona de Mediana Edad , Densidad de Población , Gales/epidemiologíaRESUMEN
BACKGROUND: Many clinical trial procedures were often undertaken in-person prior to the COVID-19 pandemic, which has resulted in adaptations to these procedures to enable trials to continue. The aim of this study was to understand whether the adaptations made to clinical trials by UK Clinical Trials Units (CTUs) during the pandemic have the potential to improve the efficiency of trials post-pandemic. METHODS: This was a mixed methods study, initially involving an online survey administered to all registered UK CTUs to identify studies that had made adaptations due to the pandemic. Representatives from selected studies were qualitatively interviewed to explore the adaptations made and their potential to improve the efficiency of future trials. A literature review was undertaken to locate published evidence concerning the investigated adaptations. The findings from the interviews were reviewed by a group of CTU and patient representatives within a workshop, where discussions focused on the potential of the adaptations to improve the efficiency of future trials. RESULTS: Forty studies were identified by the survey. Fourteen studies were selected and fifteen CTU staff were interviewed about the adaptations. The workshop included 15 CTU and 3 patient representatives. Adaptations were not seen as leading to direct efficiency savings for CTUs. However, three adaptations may have the potential to directly improve efficiencies for trial sites and participants beyond the pandemic: a split remote-first eligibility assessment, recruitment outside the NHS via a charity, and remote consent. There was a lack of published evidence to support the former two adaptations, however, remote consent is widely supported in the literature. Other identified adaptations may benefit by improving flexibility for the participant. Barriers to using these adaptations include the impact on scientific validity, limitations in the role of the CTU, and participant's access to technology. CONCLUSIONS: Three adaptations (a split remote-first eligibility assessment, recruitment outside the NHS via a charity, and remote consent) have the potential to improve clinical trials but only one (remote consent) is supported by evidence. These adaptations could be tested in future co-ordinated 'studies within a trial' (SWAT).