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Study objectives: While zolpidem is considered as an example of a gender effect on drug response, there is insufficient evidence to reach a consensus. This study aimed to investigate gender differences in adverse events (AEs) of zolpidem. Methods: We estimated the difference between the reporting odds ratios (RORs) calculated in gender subgroups for the AEs signals detected in data mining using 2015-2019 Korea voluntary adverse drug events reporting system (KAERS) data. Different reporting risk by gender was evaluated by using the log RORs being significantly different by gender at the 5% significance level and the 95% confidence intervals of the gender ROR. Results: A total of 94 AE signals were detected. Among these, 35 signals showed significant disparities by gender at the 5% level or were detected only in one gender. When categorized by similarity of AEs, parasomnia including somnambulism and paroniria, and cardiovascular disorders including coronary thrombosis had higher reporting risks in women. Men were more likely to report cognitive disorders such as delirium, insomnia related disorders, and movement disorders. Among all AEs with gender differences in reporting risk, the difference in somnambulism was the most consistent and substantial. Conclusion: For several AEs associated with zolpidem, gender-based reporting disparities were evident. Notably, women exhibited a higher susbeptibility to somnambulism, potentially serious adverse effects of zolpidem. This underscores the need for further investigation into the underlying factors influencing these gender-specific reporting patterns.
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BACKGROUND: Fibrosing interstitial lung disease (F-ILD) is a major public health concern due to its poor prognosis. Recent clinical evidence shows that antifibrotic approaches such as pirfenidone and nintedanib provide better clinical outcome prediction in idiopathic pulmonary fibrosis (IPF) as well as selected progressive fibrosing ILD (PF-ILD) patients. Having epidemiologic insight into these diseases will be essential for the efficient utilization of these therapeutic resources. This study aimed to estimate the current prevalence, incidence, and mortality of F-ILD classified as idiopathic pulmonary fibrosis (IPF), PF-ILD other than IPF, and non-progressive F-ILD and their temporal trend in Korea. METHODS: Population-based retrospective cohort study was conducted using the Korean Health Insurance Review and Assessment (HIRA) database (2011-2018). Patients with IPF were identified using ICD-10 code, RID code, and differential diagnosis approach. By leveraging medical records available from claim data and referencing those used in clinical trials, rigorous diagnostic criteria for PF-ILD detection were implemented. RESULTS: For the past eight years, the prevalence of IPF and PF-ILD has progressively increased, while non-progressive F-ILD has remained stable. IPF, PF-ILD, and non-progressive F-ILD prevalence per 100,000 in 2018 were 16.9, 10.4, and 11.7, respectively. The incidence of IPF in 2018 was more than twice that of 2012. The incidence of PF-ILD in 2018 was 1.5 times higher than that in 2012. In 2018, the mortalites were 10.3% and 12.2% for IPF and PF-ILD, respectively. The mortality rate of PF-ILD was greater than that of IPF in all years. Unclassifiable PF-ILD and rheumatoid arthritis-PF-ILD had the highest proportion and mortality among the PF-ILD subtypes. CONCLUSION: The prevalence and incidence of IPF and PF-ILD have been steadily increasing in recent years. The mortality rate of PF-ILD remained consistently high and exceeded those of IPF in all years.
Subject(s)
Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Humans , Retrospective Studies , Lung Diseases, Interstitial/diagnosis , Idiopathic Pulmonary Fibrosis/drug therapy , Fibrosis , Republic of Korea/epidemiology , Disease ProgressionABSTRACT
N-Nitrosodimethylamine (NDMA) detected above the acceptable level in ranitidine products has been a great global concern. To examine the risk of cancer among people treated with ranitidine, we conducted a cohort study using the National Health Insurance Service-National Sample Cohort data (2002-2015) of South Korea. Patients were aged 40 or above as of January 2004 and began receiving ranitidine or other histamine-2 receptor antagonist (H2RA), active comparator, without a history of H2RAs prescription during the prior 2-years. The lag time was designated up to 6 years. The outcomes were an overall incident cancer risk and the risk of major single cancers during the follow-up. The association between ranitidine use and cancer risk was examined by Cox regression model. After exclusion and propensity score matching, 25,360 patients were available for analysis. The use of ranitidine was not associated with the overall cancer risk and major individual cancers [overall cancer: incidence rate per 1000 person-years, 2.9 vs 3.0 among the ranitidine users and other H2RAs users, respectively; adjusted hazard ratio (HR) and 95% confidence interval (95% CI) for all cancers, 0.98 (0.81-1.20)]. The higher cumulative exposure to ranitidine did not increase the cancer risk. Given the insufficient follow-up period, these findings should be interpreted carefully.
Subject(s)
Neoplasms , Ranitidine , Humans , Ranitidine/adverse effects , Dimethylnitrosamine , Cohort Studies , Neoplasms/chemically induced , Neoplasms/epidemiology , Republic of Korea/epidemiologyABSTRACT
BACKGROUND: The introduction of generics after the loss of patent exclusivity plays a major role in budget savings by significantly decreasing drug prices. The aims of this study were to estimate the budget savings from off-patent cancer drugs in 2020-2024 and to inform decision makers on how these savings could be used to improve the affordability of innovative cancer treatments in South Korea. METHODS: A model was developed to calculate budget savings from off-patent cancer drug use in Korea over 5 years (2020-2024). Cancer drugs with one or more valid patents that expire between 2020 and 2024 in Korea were selected. Key input parameters in the model included market share of generics, market growth, and prices of originators and generics. To reflect market dynamics after patent expiration, the trends of the off-patent market were estimated using historical sales volume data of IQVIA from 2012 to 2018. The study assumed that the prices of off-patent drugs decreased according to the price regulations set by the Korean government and that the off-patent market sales volume did not grow. Sensitivity analyses were performed to investigate the uncertainty in model input parameters. RESULTS: A total of 24 cancer drugs which met selection criteria were identified. In the base case analysis, patent expiration of cancer drugs between 2020 and 2024 could lead to a spending reduction of â©234,429 million ($203 million), which was 20% of the cancer drug expenditure in the 5-year period. The savings ranged from â©157,633 million ($136 million) to â©434,523 million ($376 million) depending on the scenarios in sensitivity analyses. CONCLUSIONS: The findings indicate that patent loss of cancer drugs could lead to a 20% reduction in spending on cancer drugs over the next 5 years in South Korea. The savings could be used to improve the affordability of innovative, advanced cancer drugs for 94,000 cancer patients by reallocating the budget savings from patent expiration.
Subject(s)
Antineoplastic Agents , Neoplasms , Costs and Cost Analysis , Drug Costs , Drugs, Generic , Humans , Neoplasms/drug therapy , Republic of KoreaABSTRACT
BACKGROUND: The demand for implementing a new listing scheme to expedite patient access to novel oncology drugs has increased in South Korea. This study was conducted to compare the prices of anticancer drugs between eight countries and to explore the feasibility of a 'pre-listing and post-evaluation' scheme to expedite patient access to oncology drugs. METHODS: This study included 34 anticancer drugs, which were reimbursed between 1 January 2007 and 31 December 2017. The unit price and sales volume of the study drugs were collected from eight countries and IQVIA data, respectively. The prices were adjusted to estimate the ex-factory prices using the discount/rebate rate suggested by the Health Insurance Review Agency (HIRA). The four price indices of Laspeyres, Paasche, Fisher, and the unweighted index were calculated using the price in each country, the average price, and lowest price among the study countries. Each currency was converted using the currency exchange rate and purchasing power parity (PPP). The budget impact of implementing the proposed pre-listing and post-evaluation scheme on payers was calculated. RESULTS: Based on the currency exchange rate, anticancer drug prices were higher in other countries (index range: 1.05-2.78) compared to Korea. The prices in Korea were similar to countries with the lowest prices. When the PPP was applied, prices were higher in the US, Germany, Italy, and Japan than in Korea (range: 1.10-2.13); however, the prices were lower in the UK, France, and Switzerland than in Korea (range: 0.72-0.99). The financial burden of implementing the pre-listing and post-evaluation scheme was calculated at 0.83% of the total anticancer drug sales value in Korea from 2013-2017. CONCLUSIONS: The prices of anticancer drugs in Korea were similar to the lowest prices among the seven other study countries. A pre-listing and post-evaluation scheme should be considered to improve patient access to novel anticancer drugs by reducing the reimbursement review time and uncertainties.
Subject(s)
Antineoplastic Agents , Drug Costs , France , Germany , Humans , Italy , Japan , Republic of Korea , SwitzerlandABSTRACT
BACKGROUND: Recent studies have shown that treatment with the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor class could significantly improve survival outcomes in several oncology indications. However, there is some clinical uncertainty. OBJECTIVE: This study aimed to obtain high-level estimates of the impact of treatment with PD-1/PD-L1 inhibitor class to oncology treatment on key health outcomes in real-world situations and to inform public health policy decisions about cancer care after reducing uncertainties around new immuno-oncology therapy options in South Korea. METHODS: A model was developed to estimate the impact of PD-1/PD-L1 inhibitors on outcomes in situations wherein both anti-PD-1/PD-L1s and standard of care (SOC) were available versus SOC only. A partitioned survival model was utilized to estimate the impact of introducing anti-PD-1/PD-L1s on outcomes, including life-years gained, quality-adjusted life-years gained, progression-free survival-years obtained, and grade 3 or higher adverse events avoided for six indications over 5 years. An exponential distribution was fitted to the survival function of the SOC based on visual inspection. Outcomes associated with anti-PD-1/PD-L1s were estimated using a piecewise modeling approach with Kaplan-Meier analysis followed by best-fitting survival analysis. The incident number of patients and market share of anti-PD-1/PD-L1s during 2020-2024 were projected using published literature and Korean market survey data. Sensitivity analyses were performed to test the uncertainty of input parameters. RESULTS: During the next 5-year period (2020-2024), introducing the anti-PD-1/PD-L1 class led to a gain of 22,001 life-years (+ 31%), 19,073 quality-adjusted life-years (+ 38%), and 22,893 progression-free survival-years (+ 82%); it also avoided 3610 adverse events (- 11%) compared with SOC alone. Most adverse events associated with anti-PD-1/PD-L1s were attributed to combination therapy with cytotoxic chemotherapy (91%). In a scenario wherein the time to reimbursement of the anti-PD-1/PD-L1s was accelerated by 1 year, the life-years gained increased by 14% compared with the base-case scenario. CONCLUSIONS: Anti-PD-1/PD-L1 therapy is expected to provide marked survival benefits for patients with cancer. This study demonstrated the potentially beneficial health impacts of utilizing the anti-PD-1/PD-L1 class at the population level. The findings could inform health policy decision makers about cancer care and ultimately enhance population health through rapid access to innovative cancer drugs.
Subject(s)
Lung Neoplasms , Programmed Cell Death 1 Receptor , B7-H1 Antigen , Clinical Decision-Making , Humans , Immune Checkpoint Inhibitors , Lung Neoplasms/drug therapy , Outcome Assessment, Health Care , Republic of Korea , UncertaintyABSTRACT
Background: Poor clopidogrel metabolizers, carrying a cytochrome P450 2C19 loss-of-function allele, are more frequent among East Asians than Caucasians/White. Materials & methods: The Korea adverse event reporting system database and a case/noncase study design were used to examine the disproportionality of cardiovascular events following clopidogrel use. The US FDA's adverse event reporting system database was also analyzed for comparison. Results: In the Korea adverse event reporting system data, the clopidogrel reporting odds ratio for cardiovascular events was 7.34, more than double that of ticagrelor. In the FDA's adverse event reporting system data, the clopidogrel reporting odds ratio was 4.69, lower than that of ticagrelor. Adjustment for covariates did not change the trend. Conclusion: Considering the prevalence of poor clopidogrel metabolizers and the reported cardiovascular events among Koreans, rigorous clinical management is required for clopidogrel users.
Subject(s)
Adverse Drug Reaction Reporting Systems/standards , Clopidogrel/adverse effects , Clopidogrel/pharmacokinetics , Databases, Factual , Drug-Related Side Effects and Adverse Reactions/genetics , Pharmacogenetics , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/pharmacokinetics , Adolescent , Adult , Aged , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/epidemiology , Child , Child, Preschool , Cytochrome P-450 CYP2C19/genetics , Drug-Related Side Effects and Adverse Reactions/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Odds Ratio , Prevalence , Republic of Korea/epidemiology , Ticagrelor/adverse effects , United States , United States Food and Drug Administration , Young AdultABSTRACT
Little is known about gender-specific reporting of adverse events (AEs) associated with antidiabetic drugs. This study was to assess the gender-related difference in AEs reporting associated with antidiabetic agents. The number of antidiabetic drug-AE pairs associated was identified using the Korea Adverse Event Reporting System database. Prevalence of diabetes was estimated using the Health Insurance Review and Assessment Service-National Patients Sample database. Reporting rate per 10,000 people was calculated by dividing drug-AE pairs with the number of antidiabetic drug users by gender. Gender difference was presented with risk ratio (reporting rate ratio) of women to men. Antidiabetic agent-associated AEs were more frequently reported by women than men throughout body organs and drug classes. 13 out of 17 system organ class level disorders with significant gender differences were reported more often by women than men. By drug class, gender-specific reporting rates were observed in most of the drug classes, especially in newer classes such as glucagon-like peptide-1 analog (GLP1-RA), sodium glucose co-transporter-2 inhibitor (SGLT2i), and thiazolidinedione (TZD). Looking into preferred term level for each drug class, women dominated the reports of class-specific AEs of newer antidiabetic drugs such as urinary tract/genital infection (all reported by women) in SGLT2i, edema in TZD (risk ratio (RR) 12.56), and hyperglycemia in insulin users (RR 15.35). Gender differences in antidiabetic-associated AE reporting often attributed to women. Explanations for these different report levels by gender should be further investigated.
Subject(s)
Adverse Drug Reaction Reporting Systems , Diabetes Mellitus/drug therapy , Hypoglycemic Agents/adverse effects , Sex Factors , Adult , Aged , Aged, 80 and over , Databases, Factual , Female , Glucagon-Like Peptide-1 Receptor/metabolism , Humans , Insulin/metabolism , Male , Middle Aged , Republic of Korea/epidemiology , Risk , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Thiazolidinediones/adverse effectsABSTRACT
Despite safety concerns associated with topiramate use, the pattern of adverse events and signal analysis of antiepileptic drugs remain elusive.We aimed to determine patient demographics and characteristics of reported AEs of topiramate and to detect the associated signals by comparing those of other antiepileptics.We used the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD) from 2010 to 2017 to determine patient demographics and characteristics of reported AEs for topiramate and other antiepileptics. The proportional reporting ratio, reporting odds ratio, and information component were used in signal detection. Signals were compared against drug labels in Korea, the UK, the EU, and the US.A total of 1300 adverse events cases of topiramate were reported, and the number of topiramate-adverse event pairs was 1861. For topiramate, the proportion of women of childbearing age (20-39 years) with adverse events was more than double that for other antiepileptics. A majority of the 36 detected signals were of neuropsychiatric disorders such as cognitive disorders, concentration impaired, amnesia, hypoaesthesia. Patients with topiramate-induced adverse events were likely to be young and female. Also, adverse events related to carbonic anhydrase isoenzyme showed specifically great disproportionalities.Rigorous clinical management is needed to ensure proper and safe use of topiramate. Special precautions should be taken when prescribing in women of childbearing age.
Subject(s)
Anticonvulsants/adverse effects , Topiramate/adverse effects , Adolescent , Adult , Adverse Drug Reaction Reporting Systems , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young AdultABSTRACT
To investigate the risk of mortality associated with exposure to codeine, considering various risk groups, using population-based national insurance claims data.National sample cohort data from the National Health Insurance Service of South Korea (2002-2013) was used in this case-control study. Cases were defined as patients with a death record between January 1, 2002 and December 31, 2013. Each case was matched to 10 controls based on age, sex, baseline comorbidities, and year of death. Definition of exposure was codeine prescription in 30 days prior to death and sensitivity analyses were performed for 15 and 60-day exposures. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated using conditional logistic regression adjusting for benzodiazepine, other opioids, anesthetics, hypnotics, CYP2D6 inducer, CYP3A4 inducer, and the Charlson comorbidity index.A total of 19,341 cases and 185,700 matched controls were included. The overall risk associated with codeine use and mortality risk was not significant (aOR 1.08, 95% CI 1.00-1.16). Sensitivity analyses with different exposure time window also presented similar insignificant results. However, in the subgroup analyses, codeine use was associated with an increased risk of mortality in the >85-year-old age group (aOR 2.38, 95% CI 1.26-4.48) and patients with respiratory disease (aOR 1.29, 95% CI 1.17-1.42).Although no statistically significant association was found in codeine exposure and mortality risk between cases and controls, we demonstrated that the elderly over 85 years old and patients with respiratory disease are associated with a higher risk with codeine exposure. Therefore, a more cautious practice of codeine prescription in these groups might be needed.
Subject(s)
Codeine/adverse effects , Mortality/trends , Respiratory Tract Diseases/complications , Aged, 80 and over , Case-Control Studies , Female , Humans , Male , Republic of Korea/epidemiology , Respiratory Tract Diseases/epidemiology , Retrospective Studies , RiskABSTRACT
BACKGROUND: Micronuclei (MN), nuclear bud (NBud), and nucleoplasmic bridge (NPB) are suggested as biomarkers for radiation exposure; however, they have not been extensively studied to understand the underlying mechanisms responsible for their formation. OBJECTIVES: To (1) validate NBud and NPB within the cytokinesis-blocked micronucleus (CBMN) assay as biomarkers for radiation exposure and (2) determine the effects of the DNA repair inhibitors, cytosine arabinoside (Ara C) and 3-aminobenzamide (3-AB) on radiation-induced MN, NBud, and NPB formation. METHODS: Human blood samples were irradiated with 0-3 Gy X-rays and subsequently treated with Ara C and 3-AB. CBMN and chromosome aberration assays were carried out to measure MN, NBud, and NPB and dicentric chromosomes, respectively. RESULTS: The frequency of radiation-induced MN, NBud, and NPB increased in a dose-dependent manner. The frequency of MN, NBud, and NPB was highly and positively correlated with the dicentric chromosome, a standard biomarker for biodosimetry (r > 0.98, p < 0.0001). Furthermore, Ara C increased the frequency of MN, NBud, and NPB, whereas 3-AB increased the frequency of MN and NPB, but not NBud. Further, the potentiating effect of Ara C on the frequency of MN, NBud, and NPB was greater than that of 3-AB. CONCLUSION: Our results validate NBuds and NPBs as independent valuable markers of radiation exposure. Additionally, we suggest that different mechanisms are likely involved in the formation of NBuds and NPBs following X-irradiation; however, additional studies are warranted to better understand the contribution of distinct DNA repair pathways to the formation of radiation-induced damages.
Subject(s)
Benzamides/pharmacology , Cytarabine/pharmacology , Micronuclei, Chromosome-Defective/radiation effects , Adult , Cells, Cultured , DNA Repair/drug effects , Female , Humans , Micronuclei, Chromosome-Defective/drug effects , Radiation Tolerance , X-RaysABSTRACT
OBJECTIVES: To investigate the characteristics of anticholinergic use in the elderly with Alzheimer disease (AD) compared with those in the non-AD elderly. METHODS: Using the Korean National Health Insurance Service Elderly cohort database, 388,629 adults aged 70 years and older in 2012 were included. The use of strong anticholinergic agents (ACs) in 2012 was quantified by standardized prescribed doses. Univariate and multivariate logistic regression models were applied to examine the level of their heavy use (≥90 doses of the prescribed amount in 2012) in patients with AD and potential explanations of the heavy use. RESULTS: Antihistamines and antidepressants were the most prescribed strong ACs among non-AD and AD elderly, respectively. The heavy use of strong ACs was more prevalent in patients with AD than in non-AD elderly [odds ratio (95% confidence interval)=1.48 (1.41-1.56)]. When the morbidities associated with AD were adjusted for, odds ratio were reduced [0.91 (0.85-0.96)]. CONCLUSIONS: Heavy use of strong ACs was more prevalent in patients with AD than in non-AD elderly. Multiple ACs for treating multimorbidities in AD were mainly attributable to their heavy use. In patients with AD, the integrated management of medications for reducing the preventable heavy use of these drugs should be reinforced.
Subject(s)
Alzheimer Disease/drug therapy , Cholinergic Antagonists/therapeutic use , Comorbidity , Polypharmacy , Aged , Aged, 80 and over , Antidepressive Agents/therapeutic use , Cohort Studies , Databases, Factual , Female , Humans , Male , Republic of KoreaABSTRACT
PURPOSE: Older people are especially vulnerable to negative anticholinergic effects. Although anticholinergic drugs are commonly used among older people, drugs with potent antimuscarinic properties are considered as potentially inappropriate medications for older people. Here, we examined features of anticholinergic use and investigated predictors for the high use of strong anticholinergic agents (ACs) in the elderly. METHODS: A total of 388,629 Korean elderly aged ≥70 years were recruited from the 2012 National Health Insurance Service Elderly cohort database. The use of ACs in 2012 was quantitatively assessed by calculating standardized prescribed doses. Multivariate logistic regression was conducted to identify predictors of the high use of strong ACs (≥90 doses). RESULTS: Almost half of the subjects (47.2%) used more than 15 doses of strong ACs during 2012. 17.0% of the subjects had an annual cumulative use of strong ACs over 90 doses. Morbidities such as depression (odds ratio [OR], 95% confidence interval [CI] = 2.56, 2.48-2.63), Parkinson's disease (2.41, 2.26-2.56), genitourinary diseases (2.12, 2.07-2.16), polypharmacy (3.28, 3.21-3.36), and low income (1.29, 1.25-1.33) were strong predictors of their high use. Antihistamines (chlorpheniramine) and antidepressants (amitriptyline) greatly contributed to the total prescription of strong ACs. CONCLUSIONS: Despite the vulnerability of older people to the adverse reactions of strong ACs, their use seems to be at a high level in terms of cumulative usage among some elderly. More attention should be paid to older people with predictive factors of high use of strong ACs. Key points Despite the susceptibility of older people to negative anticholinergic effects, high use of strong anticholinergic agents was is quite frequent; 17.0% of the elderly had an annual cumulative use of these drugs ≥90 doses. Parkinson's disease, depression, genitourinary diseases, low income, and polypharmacy strongly predicted the high use of strong anticholinergic agents. A few strong anticholinergic agents, including antihistamines (chlorpheniramine) and antidepressants (amitriptyline), accounted for the majority of medications prescribed. Understanding the predictors of their high use by medical practitioners may result as more appropriate anticholinergic medications.
Subject(s)
Cholinergic Antagonists/adverse effects , Drug Prescriptions/statistics & numerical data , Inappropriate Prescribing/statistics & numerical data , Potentially Inappropriate Medication List/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Age Factors , Aged , Aged, 80 and over , Antidepressive Agents/therapeutic use , Cholinergic Antagonists/administration & dosage , Cohort Studies , Comorbidity , Databases, Factual/statistics & numerical data , Dementia/drug therapy , Dementia/epidemiology , Dose-Response Relationship, Drug , Female , Health Services for the Aged/statistics & numerical data , Histamine Antagonists/therapeutic use , Humans , Inappropriate Prescribing/prevention & control , Income/statistics & numerical data , Logistic Models , Male , National Health Programs/statistics & numerical data , Odds Ratio , Parkinson Disease/drug therapy , Parkinson Disease/epidemiology , Polypharmacy , Republic of Korea/epidemiologyABSTRACT
Drugs with strong anticholinergic properties are used under a variety of conditions; however, they can cause various adverse effects including a negative impact on cognitive functions, with older adults being more susceptible to these effects. We explored whether the use of anticholinergic agents (ACs) affects the risk of Alzheimer's disease (AD) in terms of incidence by using National Health Insurance Service elderly cohort database (2002-2013). As a result, AD risk was higher in subjects with an increased amount of prescriptions for strong ACs over a long period of time (9-12 years) than that in the least-exposed reference group (0-9 dose/year) [hazard ratio (HR) (95% confidence interval (95% CI)) 0.99 (0.95-1.03), 1.19 (1.12-1.26), 1.39 (1.30-1.50); in the 10-49 doses/year, 50-119 doses/year, and ≥120 doses/year groups]. Hazard ratios were particularly high in the young-old subgroup (60-64 years old in 2002) [HR (95% CI) 1.11 (1.04-1.22), 1.43 (1.25-1.65), 1.83 (1.56-2.14); in the 10-49 doses/year, 50-119 doses/year, and ≥120 doses/year groups]. Use of strong ACs dose-dependently increased the risk of AD in terms of incidence when exposure was followed up for 9 years or more, and the association was greater in the young-old subgroup.
Subject(s)
Alzheimer Disease/epidemiology , Cholinergic Antagonists/adverse effects , Cognition/drug effects , Aged , Alzheimer Disease/chemically induced , Cholinergic Antagonists/administration & dosage , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Prognosis , Republic of Korea/epidemiologyABSTRACT
BACKGROUND: Whether constitutional low blood pressure (BP) causes substantive health problems has been controversial, and subjects with hypotension exhibit a range of symptoms, from mild typical conditions such as tiredness and dizziness to more specific psychological conditions and even cognitive disorders. This study investigated whether low BP is associated with suicidal ideation in the general population. METHODS: Four years of data from the 2010-2013 Korean National Health and Nutrition Examination Survey were used. Among the 23,163 participants, aged 19-101 years, 10,708 with normal or low BP were included in the analysis of the association between low BP and suicidal ideation. The criterion used for low BP was systolic BP (SBP) < 100 mmHg, and in comparative analyses, the criteria used for low BP were SBP < 110, < 95, and < 90 mmHg. The association of prehypertension or hypertension with suicidal ideation was also examined. Suicidal ideation was assessed by a questionnaire. RESULTS: Compared with the normotensive reference group, the odds ratios (ORs) for suicidal ideation were significantly higher in the three hypotensive groups after adjusting for sex, age, body mass index, total cholesterol level, household income, educational level, marital status, current smoking status, alcohol intake, and the interaction between sex and age (OR = 1.29, 95% confidence interval [CI], 1.08 to 1.55; OR = 1.44, 95% CI, 1.14 to 1.82; and OR = 1.71, 95% CI, 1.11 to 2.62 for SBP < 100, SBP < 95, and SBP < 90 mmHg, respectively). Adding the clinical morbidities of diabetes mellitus, stroke, myocardial infarction/angina pectoris, and depression as covariates had little effect on the strength of the associations (OR = 1.25, 95% CI, 1.04 to 1.50; OR = 1.43, 95% CI, 1.13 to 1.81; and OR = 1.74, 95% CI, 1.14 to 2.68 for SBP < 100, < 95, and < 90 mmHg, respectively). CONCLUSIONS: Low SBP showed an association with suicidal ideation in the general Korean population. The association was significant for low BP, defined as a SBP < 100 mmHg, and the strength of the association increased as the criteria for low BP increased in strictness.