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Aim: Previous studies on the association between proton pump inhibitor (PPI) intake and the increased risk of dementia has shown discrepancies in their conclusions. We aimed to provide updated evidence based on extensive bias assessments and quantitative sensitivity analyses. Methods: We searched the databases PubMed, EMBASE, SCOPUS, CENTRAL and clinicaltrials.gov for prospective studies that examined an association between PPI use and dementia, up to February 2022. Each study was assessed using the Cochrane risk of bias assessment tools for non‐randomized studies of interventions (ROBINS‐I) or randomized trials (RoB2). Pooled risk ratios (RRs) and 95% prediction intervals were computed using random‐effects models. Sensitivity analyses were adjusted for small‐study bias. Results: We included nine observational studies with 204 108 dementia cases in the primary analysis on the association between PPI use vs. non‐use and dementia, and the RR was 1.16 (95% CI = 1.00; 1.35). After adjusting for small‐study bias by Copas selection model and Rücker's shrinkage procedure, the RR was 1.16 (1.02; 1.32) and 1.15 (1.13; 1.17), respectively. A subgroup analysis of PPI use vs. non‐use regarding Alzheimer's disease risk yielded an RR of 1.15 (0.89; 1.50). The secondary analysis on the risk of dementia by use of PPI vs. histamine‐2 receptor antagonist showed an RR of 1.03 (0.66; 1.62). Conclusion: This meta‐analysis provided no clear evidence for an association between PPI intake and the risk of dementia. Due to discrepancies in sensitivity analyses, however, some risk of dementia by PPI use cannot be ruled out. Since an unequivocal conclusion is still pending, further research is warranted. [ABSTRACT FROM AUTHOR]

Background and purpose: Understanding the adverse effects of proton pump inhibitors (PPIs) is important due to their widespread use, but the available evidence for an increased dementia risk amongst patients taking PPIs is inconclusive. The present study aimed to estimate the causal effect of PPIs on the risk of dementia by target trial emulation and time‐varying exposure modeling. Methods: Using claims data of 2,698,176 insured people of a large German statutory health insurer, a target trial was conceptualized in which individuals aged 40 years and older were classified as PPI initiators or non‐initiators between 2008 and 2018, and were followed until diagnosis of dementia, death, loss to follow‐up or end of study. Incidence of dementia (International Classification of Diseases 10 codes F00, F01, F03, F05.1, G30, G31.0, G31.1, G31.9 and F02.8+G31.82) was defined applying a 1‐year lag window. Weighted Cox models were used to estimate the effect of PPI initiation versus non‐initiation on dementia risk and weighted pooled logistic regression was used to estimate the effect of time‐varying use versus non‐use. Results: In all, 29,746 PPI initiators (4.4%) and 26,830 non‐initiators (1.3%) were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio for dementia was 1.54 (95% confidence interval 1.51–1.58). The hazard ratio for time‐dependent PPI use versus non‐use was 1.56 (95% confidence interval 1.50–1.63). Differentiated subtypes, including unspecified dementia, Alzheimer's disease and vascular dementia, showed increased risk by PPI initiation and time‐varying PPI use. Conclusions: This study suggests that PPI initiation and time‐varying PPI use may increase overall dementia risk. [ABSTRACT FROM AUTHOR]

Summary: Background: Proton pump inhibitors (PPIs) are well tolerated in the short term but have recently been associated with increased long‐term cardiovascular risk in observational studies. Aims: To evaluate long‐term risks of myocardial infarction (MI) and ischaemic stroke (IS) associated with PPI vs H2‐receptor antagonist (H2RA) therapy in adults without pre‐existing cardiovascular or cerebrovascular disease Methods: Using administrative claims data (2008–2018), we emulated a target trial comparing MI and IS risks in new users of PPIs vs H2RAs. Treatment was identified using dispensed prescriptions. MI and IS were defined using hospital discharge codes. Inverse probability weighting was used to adjust for confounding, and Cox models to estimate hazard ratios (HRs). Survival curves were estimated using weighted Kaplan‐Meier estimators. Results: We identified 1 143 948 new users of PPIs and 36 229 new users of H2RAs who were free of prevalent cardiovascular or cerebrovascular disease. The mean follow‐up time was 6.2 years for PPI initiators and 5.3 years for H2RA initiators. After 10 years, the HRs for MI and IS were 0.96 (95% confidence interval (CI): 0.80‐1.16) and 0.98 (95% CI: 0.89‐1.08), respectively. Conclusions: This analysis of claims data of a large German health insurer did not provide evidence that PPI therapy increased the risk of MI or IS in the first decade after treatment initiation. [ABSTRACT FROM AUTHOR]

Study Objective: Long‐term intake of proton pump inhibitors (PPIs) might increase the risk of cardiovascular events. One suggested mechanism is that PPIs inhibit the enzyme dimethylarginine dimethylaminohydrolase (DDAH) and thereby block the degradation of endothelial asymmetrical dimethylarginine (ADMA). Excess ADMA in turn leads to impaired endothelial nitric oxide (NO) generation. So far, this mechanism has only been established in human cell cultures. Previous studies that examined this pathway in human populations measured circulating ADMA and found no association with PPI use and excess plasma ADMA. But in a recent study, plasma ADMA was not correlated with intracellular ADMA. We therefore focused on changes in plasma citrulline as an indicator for potential DDAH inhibition. Design: We analyzed the association between regular daily PPI intake and flow‐mediated dilation (FMD) of the brachial artery as well as plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine using inverse probability weighting to adjust for confounding and censoring. Data Source: Data of 1298 participants from two independent cohorts of the population‐based Study of Health in Pomerania were used. Patients: Participants of the population‐based Study of Health in Pomerania are a stratified random sample of the study region. Intervention: Regular daily intake of PPIs. Measurements: FMD of the brachial artery and plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine. Main Results: Eighty‐seven participants (57.5% female) were regular daily users of PPIs. In the fully adjusted models, associations were identified for FMD and plasma citrulline concentrations. PPI users revealed a 0.99% (95% CI: −1.96 to −0.02) lower FMD and 3.03 µmol/L (95% CI: −4.96 to −1.10) lower plasma citrulline levels as compared to non‐users. Conclusion: Our data provide evidence that long‐term intake of PPIs might inhibit human DDAH activity, resulting in impaired endothelial NO production and reduced vascular function. In the long run, this might explain an increased risk for cardiovascular diseases associated with long‐term PPI use. [ABSTRACT FROM AUTHOR]

Background and aims: Unrealistic comparative optimism (UO), as the erroneous judgement of personal risks to be lower than the risks of others, could help explain differences in diabetes self‐management. The present study tested the hypothesis that individuals with type 2 diabetes who underestimate their comparative heart attack risk, have a lower adherence regarding recommended self‐management. Methods: We used data from individuals with type 2 diabetes participating in the German KORA (Cooperative Health Research in the Region of Augsburg) GEFU 4 (self‐administered health questionnaire 2016) study. UO was estimated by comparing participants' subjective comparative risk for having a heart attack within the next 5‐years (ie, “higher than others,” “average,” “lower than others”), with their objective comparative 10‐year cardiovascular disease risk based on the Framingham equations. We estimated binary logistic and linear regression models to analyze which characteristics were associated with UO and to test the association between UO and participants' self‐management behaviors (ie, regular self‐monitoring of body weight, blood sugar, and blood pressure, regular foot care, keeping a diabetes diary, and having a diet plan), and their sum score, respectively. All models were adjusted for socio‐demographic and disease‐related variables. Results: The studied sample included n = 633 individuals with type 2 diabetes (mean age 70.7 years, 45% women). Smokers and males were more likely to show UO than nonsmokers and females. Furthermore, a higher blood pressure and a higher body mass index were associated with a higher likelihood of UO regarding heart attack risk. However, UO was not significantly associated with patient self‐management. Conclusions: Unfavorable health behavior and risk factors are associated with UO. However, our results suggest that UO with regard to perceived heart attack risk may not be a relevant factor for patient self‐management in those with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: We evaluated the pharmacological treatment of distal sensorimotor polyneuropathy (DSPN) among older subjects from the general population. Methods: The study included subjects aged 61 to 82 years from the KORA F4 survey (2006‐2008). DSPN was defined as the presence of bilaterally impaired foot‐vibration perception and/or bilaterally impaired foot‐pressure sensation. Pain intensity was assessed with the painDETECT questionnaire. Results: From the included 1076 older persons, 172 (16%) persons reported pain in the lower extremities and DSPN was present in 150 (14%) subjects. Forty‐eight people with pain in the lower extremities reported DSPN. Only 38% of the subjects with DSPN reporting an average pain level of ≥4 during the past 4 weeks received medical treatment, predominantly nonsteroidal anti‐inflammatory drugs (NSAIDs 20% and opioids 12%). The medication of choice for neuropathic pain, antidepressants, anticonvulsants, and opioids was relatively being underused. However, opioids and neuropathy preparations were prescribed preferably for subjects with painful DSPN. Conclusions: In the older general population, only a small proportion of subjects with painful DSPN receive analgesic pharmacotherapy. Although not recommended by guidelines for the treatment of neuropathic pain, NSAIDs were the most frequently used class of analgesic drugs. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Nolde et al papers. To view these articles, visit https://doi.org/10.1111/apt.16565 and https://doi.org/10.1111/apt.16644 [ABSTRACT FROM AUTHOR]