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IntroductionConcerns have been raised regarding the potential association between proton pump inhibitor (PPI) use and dementia.ObjectiveThis study aimed to examine this association in an Asian population.MethodsPatients initiating PPI therapy between January 1, 2000 and December 31, 2003 without a prior history of dementia were identified from Taiwan’s National Health Insurance Research Database. The outcome of interest was all-cause dementia. Cox regression models were applied to estimate the hazard ratio (HR) of dementia. The cumulative PPI dosage stratified by quartiles of defined daily doses and adjusted for baseline disease risk score served as the primary variables compared against no PPI use.ResultsWe analyzed the data of 15726 participants aged 40 years or older and free of dementia at baseline. PPI users (n = 7863; average follow-up 8.44 years) had a significantly increased risk of dementia over non—PPI users (n = 7863; average follow-up 9.55 years) (adjusted HR [aHR] 1.22; 95% confidence interval: 1.05–1.42). A significant association was observed between cumulative PPI use and risk of dementia (P for trend = .013). Subgroup analysis showed excess frequency of dementia in PPI users diagnosed with depression (aHR 2.73 [1.91–3.89]), hyperlipidemia (aHR 1.81 [1.38–2.38]), ischemic heart disease (aHR 1.55 [1.12–2.14]), and hypertension (aHR 1.54 [1.21–1.95]).ConclusionsAn increased risk for dementia was identified among the Asian PPI users. Cumulative PPI use was significantly associated with dementia. Further investigation into the possible biological mechanisms underlying the relationship between dementia and PPI use is warranted.

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ObjectiveAlthough studies have shown an association between pioglitazone and bladder cancer, the associated factors have not been identified. The aim of this study was to investigate the factors that may link pioglitazone to bladder cancer.Materials and MethodsIn total, 34,970 study subjects were identified from the National Health Insurance Research Database in 2003 with follow-up from 2005 to 2009. The demographic characteristics of patients who had used and had never used pioglitazone, including age, sex, diabetes duration, urinary tract disease, nephropathy, bladder cancer, and cumulative dose and duration of pioglitazone therapy, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of pioglitazone on bladder cancer and newly developed chronic kidney disease.ResultsAmong 3,497 ever users and 31,473 never users of pioglitazone, the respective incident cases of bladder cancer were 12 (0.4%) and 72 (0.2%), and for newly developed chronic kidney disease 245 (8.1%) and 663 (2.3%), respectively. Ever use of pioglitazone [1.59(1.32–1.91)], cumulative dose of pioglitazone <10,500 mg [1.69 (1.37–2.01)] and >10,500 mg [1.34 (1.04–1.73)], and duration of therapy <12 months [1.68 (1.36–2.08)] and >12 months [1.39 (1.09–1.76)] were associated with the development of chronic kidney disease.ConclusionsThere was no association of pioglitazone use with bladder cancer development, however, there was an association with an increased risk of newly developed chronic kidney disease.

Objective: We studied the association between the statin dosage and the risk of Parkinson disease (PD) in diabetic patients in Taiwan. Methods: One million patients were randomly sampled from a National Health Insurance (NHI) database and followed from 2001 to 2008. Diabetic patients were screened by diagnosis of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and statin dosage was determined according to the NHI pharmacy database. PD was diagnosed on the basis of ICD-9-CM codes and anti-Parkinson medication use. Statin users was classified by statin dose-duration-day > 28 and matched with nonusers of statins using a coarsened exact matching method. There were 50,432 patients, and half of them were statin users. We examined the risk of PD between statin users and nonusers of statins and further tested the trends of the relative risk between the statin dosage and PD. Results: The PD incidence rate was lower in statin users than in nonusers of statins. The crude hazard ratio of PD incidence in statin users was 0.65 (95% confidence interval [CI] 5 0.57-0.74) in females and 0.60 (95% CI 5 0.51-0.69) in males compared with nonusers of statins. After Cox regression analysis, all statins except lovastatin exerted protective effects on PD incidence and had a significant dose-dependent trend. Interpretation: In Taiwanese diabetic patients, the risk of PD is lower in statin users than in nonusers of statins. Statin users, except lovastatin users, are dose-dependently associated with a decreased incidence of PD compared with nonusers of statins. This finding provides a new indication for statin beyond lipid control and cardiovascular events in diabetic patients. ANN NEUROL 2016;80:532-540 P arkinson disease (PD) is the second most common neurodegenerative disease. It causes irreversible, progressive disability that is characterized by muscle rigidity, slowing of physical movements, behavioral abnormalities, and autonomic impairments. 1,2 PD causes progressive disability and imposes a burden on patients and their families. The etiology of PD is inconclusive but is associated with multiple factors, such as genetic variety, oxidative stress, and progressive neuroinflammation. 3 According to recent reports, diabetes mellitus (DM) and elevated cardiovascular risk factors might play a role in the development of PD. 4-6 Some studies on animal and human models have indicated that tumor necrosis factora, nitric oxide, inducible nitric oxide synthase (iNOS), and oxygen-derived free radicals play a role in the development of PD. 3,7,8 Statin is a competitive 3-hydroxy-3-methylglutarylcoenzyme A reductase competitive inhibitor and is widely used for treating hypercholesterolemia, particularly for maintaining low-density lipoprotein (LDL) cholesterol View this article online at wileyonlinelibrary.com.

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Our study suggests that RAS blockers achieve their beneficial effects by their enhancement of adipocyte secretion of apelin.

The COronaVIrus Disease 2019 (COVID-19), which developed into a pandemic in 2020, has become a major healthcare challenge for governments and healthcare workers worldwide. Despite several medical treatment protocols having been established, a comprehensive rehabilitation program that can promote functional recovery is still frequently ignored. An online consensus meeting of an expert panel comprising members of the Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation was held to provide recommendations for rehabilitation protocols in each of the five COVID-19 stages, namely (1) outpatients with mild disease and no risk factors, (2) outpatients with mild disease and epidemiological risk factors, (3) hospitalized patients with moderate to severe disease, (4) ventilator-supported patients with clear cognitive function, and (5) ventilator-supported patients with impaired cognitive function. Apart from medications and life support care, a proper rehabilitation protocol that facilitates recovery from COVID-19 needs to be established and emphasized in clinical practice.