A BS TRACT: Background: There are conflicting findings in the literature regarding the association of body mass index and incidence of PD.Objectives: This study aimed to investigate the association of body mass index with the risk of PD incidence while considering diabetes mellitus as a major confounding factor. Methods: We examined 6,800,601 individuals (aged ≥40 years) who were free of PD using the database of the Korean National Health Insurance Service. Cox proportional hazard regression was used to assess adjusted hazard ratios for PD with adjustment for potential confounders. Stratified analyses by diabetes status were also performed. Results: A total of 33,443 individuals were diagnosed with PD during the follow-up period (7.3 years). An increased risk of PD incidence was observed in the underweight group versus the normal group (adjusted hazard ratio: 1.28; 95% confidence interval: 1.21-1.36), whereas a decreased risk of PD incidence was observed (adjusted hazard ratio: 0.88; 95% confidence interval: 0.88-0.93) in the obese group and (adjusted hazard ratio: 0.77; 95% confidence interval: 0.72-0.82) in the severely obese group. This association consistently persisted after stratification by diabetes mellitus status, with the steepest downward slope for PD risk present with increasing body mass index in patients with severe diabetes mellitus (i.e., long duration or complication). Conclusions: Being underweight and diabetes mellitus were associated with an increased risk of PD incidence, and effect of being underweight was more prominent in those with diabetes mellitus, with a dose-response relationship existing according to diabetes mellitus status. Further research is warranted to understand the clinical implications of the significant interaction between being underweight and diabetes mellitus status in the development of PD.

To investigate the association between visit-to-visit variability in blood pressure and the incidence of dementia and its subtypes in a general population, we conducted a population-based retrospective cohort study using the Korean National Health Insurance System database. We identified 7 844 814 subjects without a history of any dementia who underwent ≥3 health examinations from 2005 to 2012 in the Korean National Health Insurance System cohort. Blood pressure variability (BPV) was measured using the variability independent of the mean, coefficient of variation, and SD. During the median follow-up of 6.2 years, there were 200 574 cases of all-cause dementia (2.8%), 165 112 cases of Alzheimer’s disease (2.1%), and 27 443 cases of vascular dementia (0.3%). There was a linear association between higher BPV and outcome measures. In the multivariable adjusted model, the hazard ratios and 95% CIs of all-cause dementia were 1.06 (1.04–1.07) for the highest quartile of variability independent of the mean of diastolic blood pressure only, 1.09 (1.08–1.11) for that of systolic blood pressure only, and 1.18 (1.16–1.19) for that of both systolic and diastolic blood pressure compared with subjects having no highest quartile for BPV. Consistent results were noted for Alzheimer’s disease and vascular dementia using other indices of variability and in various sensitivity and subgroup analyses. BPV is an independent predictor for developing dementia and its subtypes. A dose-response relationship was noted between higher BPV and dementia incidence. Reducing BPV may be a target for preventing dementia in the general population.

Osteoarthritis (OA) is the most common form of arthritis. It is characterized by progressive destruction of articular cartilage and the development of chronic pain and constitutes a considerable socioeconomic burden. Currently, pharmacological treatments mostly aim to relieve the OA symptoms associated with inflammation and pain. However, with increasing understanding of OA pathology, several potential therapeutic targets have been identified, enabling the development of disease-modifying OA drugs (DMOADs). By targeting inflammatory cytokines, matrix-degrading enzymes, the Wnt pathway, and OA-associated pain, DMOADs successfully modulate the degenerative changes in osteoarthritic cartilage. Moreover, regenerative approaches aim to counterbalance the loss of cartilage matrix by stimulating chondrogenesis in endogenous stem cells and matrix anabolism in chondrocytes. Emerging strategies include the development of senolytic drugs or RNA therapeutics to eliminate the cellular or molecular sources of factors driving OA. This review describes the current developmental status of DMOADs and the corresponding results from preclinical and clinical trials and discusses the potential of emerging therapeutic approaches to treat OA.

Background There have been conflicting results on the association between statin use and Parkinson's disease (PD) incidence. Objectives This study investigated the association between time‐varying status of statin use and incidence of PD while considering the dose–response relationship and total cholesterol level. Methods Using the database of the Korean National Health Insurance Service from 2002 to 2015, we examined 76,043 subjects (≥60 years old) free of PD, dementia, and stroke at baseline. The dose of statin use was classified into the following four 6‐month categories (<180, 180‐365, 365‐540, and ≥540 days) for each 2‐year interval. The incidence of PD was identified by the prescription records for any anti‐PD medication with a diagnosis of PD. Results During 10 years of follow‐up, 1,427 PD cases occurred. Statin “ever use” was significantly associated with a high risk of PD incidence (adjusted hazard ratio = 1.28; 95% confidence interval = 1.12‐1.46) when compared with statin nonuse. In terms of a dose–response relationship, although a duration of statin use <365 days was associated with a higher risk of PD, the duration of statin use ≥365 days was not significantly associated with an increased risk of PD. Conclusions Statin use was associated with an elevated PD risk of PD, but long‐term and adherent statin use was not significantly associated with elevated PD risk. However, there was no evidence of benefit with any statin treatment related to PD risk. Our study suggests that there is a complex relationship among cholesterol level, statin use, and PD risk that warrants further studies. © 2019 International Parkinson and Movement Disorder Society

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Background Reproductive factors and hormone use in postmenopausal women have been hypothesised to affect the risk of developing lung cancer, but the epidemiological evidence is inconsistent. Methods Using the Korean National Health Insurance System database, we identified 4,775,398 postmenopausal women older than 40 years who had undergone both cardiovascular health- and cancer screening between 1 January 2009 and 31 December 2014. Information about reproductive factors was obtained from a self-administered questionnaire. The risk of lung cancer was estimated using Cox proportional hazard regression models. Results During a median follow-up of 4.4 years, 16,556 women (15,223 non-smokers) were diagnosed with lung cancer. The risk of lung cancer was not significantly influenced by early menarche age (adjusted hazard ratio [aHR] 1.03 for menarche ≥18 vs. ≤14; 95% confidence interval [CI], 0.98–1.09) or late age at menopause (aHR 1.02 for menopause ≥55 vs. <40; 95% CI, 0.91–1.14). Furthermore, the number of children, duration of breastfeeding and use of hormone replacement therapy were not associated with the risk of lung cancer. Conclusions No statistically significant association was found between reproductive factors and the risk of lung cancer in postmenopausal Korean women.

Key Points Question Which is the more important factor in the development of gastrointestinal (GI) cancer: frequency of drinking alcohol or quantity of alcohol consumed per occasion? Findings In this cohort study of 11 737 467 participants, the risk of GI cancer was significantly associated with drinking frequency. Compared with similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking but decreased with larger amounts per occasion. Meaning This study suggests that frequent drinking may be a more important risk factor for incident GI cancers than the amount of alcohol consumed per occasion, and patients should be careful with their drinking habits, including regular consumption of small amounts of alcohol.

Anticancer effects of aspirin, metformin, and statins against gastric cancer, one of the most common cancers in the world, have been reported. This retrospective cohort study aimed to investigate independent associations of aspirin, metformin, and statin use with gastric cancer incidence and mortality after adjustment for concomitant use of other drugs, using pooled cohort data extracted from the Korean National Health Insurance claim database. Follow-up started on January 1, 2004 and ended at the date of gastric cancer diagnosis, death, or December 31, 2013. Exposures to drugs were defined as cumulative duration of use for aspirin and cumulative defined daily dose for metformin and statin, and were entered as time-dependent variables in Cox analysis models to avoid immortal time bias. Use of aspirin for longer than 182.5 and 547.5 days during 2-year interval was associated with reduced risks of gastric cancer incidence and mortality, respectively. Patients with diabetes were at higher risk of gastric cancer incidence and mortality than nondiabetic people, regardless of metformin treatment. However, metformin use among patients with diabetes was associated with a reduction in gastric cancer mortality in a dose-response manner. Statin use was also associated with a reduction of gastric cancer mortality in the general population, but not with gastric cancer incidence. In conclusion, long-term use of aspirin was independently associated with reduced incidence and mortality of gastric cancer in the general population, but metformin or statin use was only associated with a reduction of gastric cancer mortality in patients with diabetes and in the general population, respectively. Prevention Relevance: Long-term use of aspirin was independently associated with reduced incidence and mortality of gastric cancer in the general population. Metformin or statin use, however, was only associated with a reduction of gastric cancer mortality in diabetic patients and in the general population in a dose-response manner, respectively.