The risk of PPIs being associated with dementia may be overestimated. Further pharmacoepidemiological studies are needed to identify the risk of dementia with PPI use.

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Polypharmacy is associated with adverse drug reactions and represents an economic burden on the health insurance system. The objective of our study was to assess the trends in polypharmacy and its associated factors in South Korea. This cross-sectional study used a nationwide sampled database between 2002 and 2013, including outpatients of all ages who received at least 1 prescription in the same period. Polypharmacy was defined as the concomitant prescription of ≥6 distinct medications on a single prescription at least once without a given duration. The yearly prescribing trends were calculated and plotted. We conducted comparative analyses to identify the changes in social gradients of polypharmacy between the first 2 years, 2002‒2003, and the final 2 years, 2012‒2013. We repeated logistic regressions for pediatrics <20 years of age and adults ≥20 years of age to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI). The distributions of polypharmacy in the respective periods were examined according to patient economic status (0 = most deprived and 10 = most affluent). The age-standardized prevalence of polypharmacy decreased from 65.8% in 2002 to 43.7% in 2013. Our study included 1,108,298 outpatients throughout 2002–2013. Pediatric patients aged 1–9 years had the highest number of medications among all age groups (mean: 5.1 ± 1.1 in 2002–2003 vs. 4.1 ± 1.1 in 2012–2013) in both periods. Changes in the association between deprivation and polypharmacy over 10 years were observed in adults (aOR = 0.68; 95% CI = 0.62–0.75 in 2002–2003 vs. 1.60; 95% CI = 1.54–1.66 in 2012–2013) and pediatrics (aOR = 0.60; 95% CI = 0.52–0.68 in 2002–2003 vs. 1.07; 95% CI = 1.01–1.14 in 2012–2013) compared with those in the most affluent patients. The high level of polypharmacy in pediatric patients is a public health concern that warrants policymaker attention.

Recent evidence suggests that gut microbiota dysbiosis adversely affects the efficacy of immune checkpoint inhibitors (ICIs). Our objective was to investigate the association between concomitant use of proton pump inhibitors (PPIs) and ICIs, and poor prognosis in patients with nonsmall cell lung cancer (NSCLC). We conducted a cohort study using a completely enumerated lung cancer cohort from a nationwide healthcare database in South Korea. We identified 2963 patients treated with ICIs as second-line or later therapy for stage ≥IIIB NSCLC. PPI use was ascertained within 30-days before and on the date of ICI initiation, and nonuse was defined as no prescription of PPIs during this period. Using national vital statistics in South Korea, we assessed the risk of all-cause mortality associated with concomitant PPI use through a propensity score-matched Cox proportional hazard model. Among 1646 patients included after 1:1 propensity score-matching, concomitant PPI use was associated with a 28% increased risk of all-cause mortality, compared to nonuse (adjusted hazard ratio [HR] 1.28; 95% confidence intervals [CIs],1.13-1.46). We observed an increased risk when we restricted the analysis to new users of PPI (adjusted HR = 1.64; 95% CI = 1.25-2.17). Subgroup analysis showed that PPI use was associated with high mortality risk among patients with viral hepatitis (adjusted HR = 2.72; 95% CI = 1.54-4.78; P interaction = .048). Our study indicates that PPI use is associated with poor prognosis in NSCLC patients treated with ICIs. Further prospective studies are required to determine the risk-benefit balance of concomitant use of PPIs and ICIs.

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