Herpes Zoster and Risk of Incident Parkinson's Disease in US Veterans: A Matched Cohort Study.

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.

Developing survey weights to ensure representativeness in a national, matched cohort study: results from the children and young people with Long Covid (CLoCk) study.

BACKGROUND: Findings from studies assessing Long Covid in children and young people (CYP) need to be assessed in light of their methodological limitations. For example, if non-response and/or attrition over time systematically differ by sub-groups of CYP, findings could be biased and any generalisation limited. The present study aimed to (i) construct survey weights for the Children and young people with Long Covid (CLoCk) study, and (ii) apply them to published CLoCk findings showing the prevalence of shortness of breath and tiredness increased over time from baseline to 12-months post-baseline in both SARS-CoV-2 Positive and Negative CYP. METHODS: Logistic regression models were fitted to compute the probability of (i) Responding given envisioned to take part, (ii) Responding timely given responded, and (iii) (Re)infection given timely response. Response, timely response and (re)infection weights were generated as the reciprocal of the corresponding probability, with an overall 'envisioned population' survey weight derived as the product of these weights. Survey weights were trimmed, and an interactive tool developed to re-calibrate target population survey weights to the general population using data from the 2021 UK Census. RESULTS: Flexible survey weights for the CLoCk study were successfully developed. In the illustrative example, re-weighted results (when accounting for selection in response, attrition, and (re)infection) were consistent with published findings. CONCLUSIONS: Flexible survey weights to address potential bias and selection issues were created for and used in the CLoCk study. Previously reported prospective findings from CLoCk are generalisable to the wider population of CYP in England. This study highlights the importance of considering selection into a sample and attrition over time when considering generalisability of findings.

The association between proton pump inhibitor use and risk of post-hospitalization acute kidney injury: a multicenter prospective matched cohort study.

BACKGROUND: Proton Pump Inhibitors (PPI) are among the most commonly used drugs to treat acid-related gastrointestinal disorders in the USA. Although PPI use has been linked to acute interstitial nephritis, the side effects of post-hospitalization acute kidney injury (AKI) and the progression of kidney disease still are controversial. We conducted a matched cohort study to examine the associations between PPI use and the side effects, especially in post-hospitalization AKI. METHODS: We investigated 340 participants from the multicenter, prospective, matched-cohort ASSESS-AKI study, which enrolled participants from December 2009 to February 2015. After the baseline index hospitalization, follow-up visits were conducted every six months, and included a collection of self-reported PPI use by participants. Post-hospitalization AKI was defined as the percentage increase from the nadir to peak inpatient SCr value was ≥ 50% and/or absolute increase ≥ 0.3 mg/dL in peak inpatient serum creatinine compared with baseline outpatient serum creatinine. We applied a zero-inflated negative binomial regression model to test the relationship between PPI use and post-hospitalization AKI. Stratified Cox proportional hazards regression models also were conducted to examine the association between PPI use and the risk of progression of kidney disease. RESULTS: After controlling for demographic variables, baseline co-morbidities and drug use histories, there was no statistically significant association between PPI use and risk of post-hospitalization AKI (risk ratio [RR], 0.91; 95% CI, 0.38 to 1.45). Stratified by AKI status at baseline, no significant relationships were confirmed between PPI use and the risk of recurrent AKI (RR, 0.85; 95% CI, 0.11 to 1.56) or incidence of AKI (RR, 1.01; 95% CI, 0.27 to 1.76). Similar non-significant results also were observed in the association between PPI use and the risk of progression of kidney diseases (Hazard Ratio [HR], 1.49; 95% CI, 0.51 to 4.36). CONCLUSION: PPI use after the index hospitalization was not a significant risk factor for post-hospitalization AKI and progression of kidney diseases, regardless of the AKI status of participants at baseline.

Cox regression can be collapsible and Aalen regression can be non-collapsible.

It is well-known that the additive hazards model is collapsible, in the sense that when omitting one covariate from a model with two independent covariates, the marginal model is still an additive hazards model with the same regression coefficient or function for the remaining covariate. In contrast, for the proportional hazards model under the same covariate assumption, the marginal model is no longer a proportional hazards model and is not collapsible. These results, however, relate to the model specification and not to the regression parameter estimators. We point out that if covariates in risk sets at all event times are independent then both Cox and Aalen regression estimators are collapsible, in the sense that the parameter estimators in the full and marginal models are consistent for the same value. Vice-versa, if this assumption fails, then the estimates will change systematically both for Cox and Aalen regression. In particular, if the data are generated by an Aalen model with censoring independent of covariates both Cox and Aalen regression is collapsible, but if generated by a proportional hazards model neither estimators are. We will also discuss settings where survival times are generated by proportional hazards models with censoring patterns providing uncorrelated covariates and hence collapsible Cox and Aalen regression estimates. Furthermore, possible consequences for instrumental variable analyses are discussed.

Cardiovascular disease risk in long-term breast cancer survivors: A population-based cohort study.

BACKGROUND: Breast cancer survival is increasing, making late effects such as cardiovascular disease (CVD) more relevant. The purpose of this study was to evaluate incident CVD following breast cancer diagnosis among long-term survivors and to investigate possible risk factors for CVD. METHODS: A population-based cohort of 6641 breast cancer survivors diagnosed between 1997 and 2009 who survived at least 10 years was identified within the Utah Cancer Registry. In addition, 36,612 cancer-free women from the general population, matched by birth year and state, were identified within the Utah Population Database. Cox proportional hazards models were used to calculate CVD hazard ratios (HRs) for >10 to 15 and >15 years. RESULTS: Long-term breast cancer survivors had an increased risk of newly diagnosed diseases of the circulatory system (HR, 1.32; 99% confidence interval [CI], 1.00-1.75) from 10 to 15 years following cancer diagnosis compared with the general population. No increased CVD risks were observed after 15 years. Breast cancer survivors with Charlson Comorbidity Index score ≥2 had a significantly higher risk of diseases of the circulatory system (HR, 2.64; 95% CI, 1.08-6.45) beyond 10 years following breast cancer diagnosis. Similarly, older age, obesity, lower education, and family history of CVD and breast cancer were risk factors for heart and circulatory system diseases among long-term breast cancer survivors. CONCLUSION: Risk of CVD compared to the general population was moderate among this cohort of long-term breast cancer survivors between 10 to 15 years since cancer diagnosis. Awareness of CVD risks is important for breast cancer survivors.

Hospitalizations During the COVID-19 Pandemic Among Recently Homeless Individuals: a Retrospective Population-Based Matched Cohort Study.

BACKGROUND: Hospitalizations fell precipitously among the general population during the COVID-19 pandemic. It remains unclear whether individuals experiencing homelessness experienced similar reductions. OBJECTIVE: To examine how overall and cause-specific hospitalizations changed among individuals with a recent history of homelessness (IRHH) and their housed counterparts during the first wave of the COVID-19 pandemic, using corresponding weeks in 2019 as a historical control. DESIGN: Population-based cohort study conducted in Ontario, Canada, between September 30, 2018, and September 26, 2020. PARTICIPANTS: In total, 38,617 IRHH, 15,022,368 housed individuals, and 186,858 low-income housed individuals matched on age, sex, rurality, and comorbidity burden. MAIN MEASURES: Primary outcomes included medical-surgical, non-elective (overall and cause-specific), elective surgical, and psychiatric hospital admissions. KEY RESULTS: Average rates of medical-surgical (rate ratio: 3.8, 95% CI: 3.7-3.8), non-elective (10.3, 95% CI: 10.1-10.4), and psychiatric admissions (128.1, 95% CI: 126.1-130.1) between January and September 2020 were substantially higher among IRHH compared to housed individuals. During the peak period (March 17 to June 16, 2020), rates of medical-surgical (0.47, 95% CI: 0.47-0.47), non-elective (0.80, 95% CI: 0.79-0.80), and psychiatric admissions (0.86, 95% CI: 0.84-0.88) were significantly lower among housed individuals relative to equivalent weeks in 2019. No significant changes were observed among IRHH. During the re-opening period (June 17-September 26, 2020), rates of non-elective hospitalizations for liver disease (1.41, 95% CI: 1.23-1.69), kidney disease (1.29, 95% CI: 1.14-1.47), and trauma (1.19, 95% CI: 1.07-1.32) increased substantially among IRHH but not housed individuals. Distinct hospitalization patterns were observed among IRHH even in comparison with more medically and socially vulnerable matched housed individuals. CONCLUSIONS: Persistence in overall hospital admissions and increases in non-elective hospitalizations for liver disease, kidney disease, and trauma indicate that the COVID-19 pandemic presented unique challenges for recently homeless individuals. Health systems must better address the needs of this population during public health crises.

Healthcare resource use and costs for people with type 2 diabetes mellitus with and without severe mental illness in England: longitudinal matched-cohort study using the Clinical Practice Research Datalink.

BACKGROUND: Approximately 60 000 people in England have coexisting type 2 diabetes mellitus (T2DM) and severe mental illness (SMI). They are more likely to have poorer health outcomes and require more complex care pathways compared with those with T2DM alone. Despite increasing prevalence, little is known about the healthcare resource use and costs for people with both conditions. AIMS: To assess the impact of SMI on healthcare resource use and service costs for adults with T2DM, and explore the predictors of healthcare costs and lifetime costs for people with both conditions. METHOD: This was a matched-cohort study using data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics for 1620 people with comorbid SMI and T2DM and 4763 people with T2DM alone. Generalised linear models and the Bang and Tsiatis method were used to explore cost predictors and mean lifetime costs respectively. RESULTS: There were higher average annual costs for people with T2DM and SMI (£1930 higher) than people with T2DM alone, driven primarily by mental health and non-mental health-related hospital admissions. Key predictors of higher total costs were older age, comorbid hypertension, use of antidepressants, use of first-generation antipsychotics, and increased duration of living with both conditions. Expected lifetime costs were approximately £35 000 per person with both SMI and T2DM. Extrapolating nationally, this would generate total annual costs to the National Health Service of around £250 m per year. CONCLUSIONS: Our estimates of resource use and costs for people with both T2DM and SMI will aid policymakers and commissioners in service planning and resource allocation.

Modelling multiple time-scales with flexible parametric survival models.

BACKGROUND: There are situations when we need to model multiple time-scales in survival analysis. A usual approach in this setting would involve fitting Cox or Poisson models to a time-split dataset. However, this leads to large datasets and can be computationally intensive when model fitting, especially if interest lies in displaying how the estimated hazard rate or survival change along multiple time-scales continuously. METHODS: We propose to use flexible parametric survival models on the log hazard scale as an alternative method when modelling data with multiple time-scales. By choosing one of the time-scales as reference, and rewriting other time-scales as a function of this reference time-scale, users can avoid time-splitting of the data. RESULT: Through case-studies we demonstrate the usefulness of this method and provide examples of graphical representations of estimated hazard rates and survival proportions. The model gives nearly identical results to using a Poisson model, without requiring time-splitting. CONCLUSION: Flexible parametric survival models are a powerful tool for modelling multiple time-scales. This method does not require splitting the data into small time-intervals, and therefore saves time, helps avoid technological limitations and reduces room for error.

Unspecified pain and other soft tissue disorders following electrical injuries: a register-based matched cohort study.

OBJECTIVE: This study investigates whether individuals who have sustained an electrical injury (EI) are diagnosed with unspecified pain or pain related to the musculoskeletal system in the years following the injury. METHODS: Individuals listed in Danish registers as having sustained EIs were matched for sex, age, and year of injury in a cohort study with individuals having experienced dislocations/sprains (match 1), eye injuries (match 2), and a sample of individuals with the same occupation without a history of electrical injuries (match 3). Outcomes were unspecified pain and unspecified soft tissue disorders. Conditional logistic regression and conditional Cox regression were applied. RESULTS: We identified 14,112 individuals who sustained EIs. A higher risk of both outcomes was observed for all three matches, and was highest at the 6- and 12-month follow-ups. The risk of both outcomes was considerably higher for match 3. CONCLUSIONS: This study confirms that exposure to EIs increases the risk of being diagnosed with unspecified pain or unspecified soft tissue disorders both at short and long terms. Our results also showed that the risk of unspecified pain as sequelae is related to the severity of the injury.

NB housing study protocol: investigating the relationship between subsidized housing, mental health, physical health and healthcare use in New Brunswick, Canada.

BACKGROUND: Income and housing are pervasive social determinants of health. Subsidized housing is a prominent affordability mechanism in Canada; however, waitlists are lengthy. Subsidized rents should provide greater access to residual income, which may theoretically improve health outcomes. However, little is known about the health of tenants who wait for and receive subsidized housing. This is especially problematic for New Brunswick, a Canadian province with low population density, whose inhabitants experience income inequality, social exclusion, and challenges with healthcare access.  METHODS: This study will use a longitudinal, prospective matched cohort design. All 4,750 households on New Brunswick's subsidized housing wait list will be approached to participate. The survey measures various demographic, social and health indicators at six-month intervals for up to 18 months as they wait for subsidized housing. Those who receive housing will join an intervention group and receive surveys for an additional 18 months post-move date. With consent, participants will have their data linked to a provincial administrative database of medical records.  DISCUSSION: Knowledge of housing and health is sparse in Canada. This study will provide stakeholders with a wealth of health information on a population that is historically under-researched and underserved.