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Proton pump inhibitors and dementia risk: Evidence from a cohort study using linked routinely collected national health data in Wales, UK.

ABSTRACT: OBJECTIVES:Proton pump inhibitors (PPIs) are commonly prescribed for prevention and treatment of gastrointestinal conditions or for gastroprotection from other drugs. Research suggests they are linked to increased dementia risk. We use linked national health data to examine the association between PPI use and the development of incident dementia. METHODS AND FINDINGS:A population-based study using electronic health-data from the Secure Anonymised Information Linkage (SAIL) Databank, Wales (UK) from 1999 to 2015. Of data available on 3,765,744 individuals, a cohort who had ever been prescribed a PPI was developed (n = 183,968) for people aged 55 years and over and compared to non-PPI exposed individuals (131,110). Those with prior dementia, mild-cognitive-impairment or delirium codes were excluded. Confounding factors included comorbidities and/or drugs associated with them. Comorbidities might include head injury and some examples of medications include antidepressants, antiplatelets and anticoagulants. These commonly prescribed drugs were investigated as it was not feasible to explore all drugs in this study. The main outcome was a diagnosis of incident dementia. Cox proportional hazard regression modelling was used to calculate the Hazard ratio (HR) of developing dementia in PPI-exposed compared to unexposed individuals while controlling for potential confounders. The mean age of the PPI exposed individuals was 69.9 years and 39.8% male while the mean age of the unexposed individuals was 72.1 years and 41.1% male. The rate of PPI usage was 58.4% (183,968) and incident dementia rate was 11.8% (37,148/315,078). PPI use was associated with decreased dementia risk (HR: 0.67, 95% CI: 0.65 to 0.67, p<0.01). CONCLUSIONS:This study, using large-scale, multi-centre health-data was unable to confirm an association between PPI use and increased dementia risk. Previously reported links may be associated with confounders of people using PPI's, such as increased risk of cardiovascular disease and/or depression and their associated medications which may be responsible for any increased risk of developing dementia.

SUBMITTER: Cooksey R

PROVIDER: S-EPMC7500586 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Proton pump inhibitors and dementia risk: Evidence from a cohort study using linked routinely collected national health data in Wales, UK.

Cooksey Roxanne R Kennedy Jonathan J Dennis Michael S MS Escott-Price Valentina V Lyons Ronan A RA Seaborne Michael M Brophy Sinead S

PloS one 20200918 9

<h4>Objectives</h4>Proton pump inhibitors (PPIs) are commonly prescribed for prevention and treatment of gastrointestinal conditions or for gastroprotection from other drugs. Research suggests they are linked to increased dementia risk. We use linked national health data to examine the association between PPI use and the development of incident dementia.<h4>Methods and findings</h4>A population-based study using electronic health-data from the Secure Anonymised Information Linkage (SAIL) Databan ...[more]

PMID: 32946449

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Project description:Introduction: Prescribing cascade refers to use of a medication to treat a drug-related adverse event. Prescribing cascades increase medication use, cost, and risk of adverse events. Objective: Our objective was to use administrative health data to identify whether use of medications from the anticholinergic cognitive burden scale was associated with proton pump inhibitor (PPI) prescribing consistent with a prescribing cascade in older adults with dementia. Method: The cohort was comprised of Nova Scotia Seniors' Pharmacare beneficiaries identified to have dementia and medication dispensation data recorded between 1 April 2010, or cohort entry and 31 March 2015. Anticholinergic medications from the anticholinergic cognitive burden scale (ACB) were abstracted. A look back period of 365 days identified if a PPI had been dispensed preceding anticholinergic dispensation. PPI initiation within 30, 60, 90, or 180 days of the anticholinergic medication was assessed. Demographic description of those dispensed anticholinergic medications or PPIs were reported. Risk factors for the prescribing cascade were investigated with logistic regression and Cox proportional hazards modelling including a sex-stratified analysis. Results: We identified 28,952 Nova Scotia Seniors' Pharmacare beneficiaries with dementia and prescription dispensation data. Anticholinergic medications were frequently dispensed with 63.4% of the cohort dispensed at least one prescription for an anticholinergic medication. The prescribing cascade defined as up to 180-days between anticholinergic medication inititation and PPI dispensation, occurred in 1,845 Nova Scotia Seniors' Pharmacare beneficiaries with dementia (incidence 6.4%). Multivariate regression showed those experiencing the prescribing cascade after initiating any anticholinergic were younger (OR 0.98, 95%CI [0.97-0.98]), less likely to live in an urban location (OR 0.82, 95%CI [0.74-0.91]), or to be men (OR 0.74, 95%CI [0.67-0.82]). Cox regression demonstrated an increased risk of starting a PPI within 180 days when initiating any medication from the ACB (HR 1.38, 95%CI [1.29-1.58]). Discussion: Regression modelling suggested that anticholinergic medications increased the risk of PPI dispensation consistent with a prescribing cascade in the cohort. The identification of the prescribing cascade in this population of older Nova Scotia Seniors' Pharmacare Program beneficiaries with dementia using administrative health data highlights how routinely collected health data can be used to identify prescribing cascades.

Project description:BackgroundTherapeutic hypothermia is standard of care in high-income countries for babies born with signs of hypoxic ischaemic encephalopathy, but optimal feeding during treatment is uncertain and practice is variable. This study aimed to assess the association between feeding during therapeutic hypothermia and clinically important outcomes.MethodsWe did a population-level retrospective cohort study using the UK National Neonatal Research Database. We included all babies admitted to National Health Service neonatal units in England, Scotland, and Wales between Jan 1, 2010, and Dec 31, 2017, who received therapeutic hypothermia for 72 h or died during this period. For analysis, we created matched groups using propensity scores and compared outcomes in babies who were fed versus unfed enterally during therapeutic hypothermia. The primary outcome was severe necrotising enterocolitis, either confirmed at surgery or causing death. Secondary outcomes include pragmatically defined necrotising enterocolitis (a recorded diagnosis of necrotising enterocolitis in babies who received at least 5 consecutive days of antibiotics while also nil by mouth during their neonatal unit stay), late-onset infection (pragmatically defined as 5 consecutive days of antibiotic treatment commencing after day 3), survival to discharge, measures of breastmilk feeding, and length of stay in neonatal unit.Findings6030 babies received therapeutic hypothermia, of whom 1873 (31·1%) were fed during treatment. Seven (0·1%) babies were diagnosed with severe necrotising enterocolitis and the number was too small for further analyses. We selected 3236 (53·7%) babies for the matched feeding analysis (1618 pairs), achieving a good balance for all recorded background variables. Pragmatically defined necrotising enterocolitis was rare in both groups (incidence 0·5%, 95% CI 0·2-0·9] in the fed group vs 1·1% [0·7-1·4] in the unfed group). The enterally fed group had fewer pragmatically defined late-onset infections (difference -11·6% [95% CI -14·0 to -9·3]; p<0·0001), higher survival to discharge (5·2% [3·9-6·6]; p<0·0001), higher proportion of breastfeeding at discharge (8·0% [5·1-10·8]; p<0·0001), and shorter neonatal unit stays (-2·2 [-3·0 to -1·2] days; p<0·0001) compared with the unfed group.InterpretationNecrotising enterocolitis is rare in babies receiving therapeutic hypothermia. Enteral feeding during hypothermia is safe and associated with beneficial outcomes compared with not feeding, although residual confounding could not be completely ruled out. Our findings support starting milk feeds during therapeutic hypothermia.FundingUK National Institute for Health Research Health Technology Assessment programme 16/79/13.

Dataset Information

Proton pump inhibitors and dementia risk: Evidence from a cohort study using linked routinely collected national health data in Wales, UK.

Publications

Proton pump inhibitors and dementia risk: Evidence from a cohort study using linked routinely collected national health data in Wales, UK.

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