Nationwide Population-based Longitudinal Study Research Articles

A nation-wide population-based longitudinal study on life expectancy and cause specific mortality in patients with bipolar disorder and their siblings

ObjectiveMortality is increased in bipolar disorder due to both suicide and death by physical disorders, but it has never been investigated whether these mortalities translate into relatives to patients with bipolar disorder. The aim was to present the life expectancy and the overall mortality and mortality due to suicide and physical disorders among patients with bipolar disorder and their unaffected full siblings, respectively, compared with control individuals from the general population. MethodsWe used Danish nation-wide population-based longitudinal register linkage to identify 19.955 patients with bipolar disorder, their 13.923 siblings and 20 sex, age and calendar matched control individuals from the general population. Follow-up was from 1995 to 2017. ResultsBipolar disorder was associated with a decreased life expectancy of 7.7 (95% CI: 7.4-8.1) years and increased mortality overall (hazard ratio (HR): 2.11 (95% CI: 2.04-2.18)) and due to suicide (HR: 18.23 (95% CI: 15.81-21.02) and physical disorders (HR: 2.01 (95% CI: 1.94-2.08). In contrast, siblings to patients with bipolar disorder who were unaffected by bipolar disorder did not have decreased life expectancy (0.45 (95% CI: -6.62-2.46)) or increased mortality overall (HR: 1.00 (95% CI: 0.88-1.14) or due to suicide (HR: 1.50 (95% CI: 0.95-2.36) or physical disorders (HR: 0.99 (95% CI: 0.87-1.34). ConclusionsIncreased mortality in bipolar disorder is mainly due to the impact of bipolar psychopathology and to a lesser degree to familial transmitted factors, highlighting the urgent need for preventive intervention studies in relation to suicide and physical disorders following onset of bipolar disorder.

Socio-economic functioning in patients with bipolar disorder and their unaffected siblings - results from a nation-wide population-based longitudinal study.

Few studies have reported real-life data on socio-economic functioning in patients with bipolar disorder and their unaffected first-degree relatives. We used Danish nation-wide population-based longitudinal register linkage to investigate socio-economic functioning in 19 955 patients with bipolar disorder, their 13 923 siblings and 20 sex, age and calendar-matched control individuals from the general population. Follow-up was from 1995 to 2017. Patients with a diagnosis of bipolar disorder had lower odds of having achieved the highest educational level [OR 0.75 (95% confidence interval (CI) 0.73-0.77)], being employed [OR 0.16 (95% CI 0.159-0.168)], having achieved the 80% highest quartile of income [OR 0.33 (95% CI 0.32-0.35)], cohabitating [OR 0.44 (95% CI 0.43-0.46)] and being married [OR 0.54 (95% CI 0.52-0.55)] at first contact to hospital psychiatry as inpatient or outpatient compared with control individuals from the general population. Similarly, siblings to patients with bipolar disorder had a lower functioning within all five socio-economic areas than control individuals. Furthermore, patients and partly siblings showed substantially decreased ability to enhance their socio-economic functioning during the 23 years follow-up compared to controls. Socio-economic functioning is substantially decreased in patients with bipolar disorder and their siblings and does not improve during long-term follow-up after the initial hospital contact, highlighting a severe and overlooked treatment gap.

Higher Dispositional Optimism Predicts Better Health-Related Quality of Life After Esophageal Cancer Surgery: A Nationwide Population-Based Longitudinal Study

PurposeTo assess whether higher dispositional optimism could predict better health-related quality of life (HRQL) after esophageal cancer surgery.MethodsThis Swedish nationwide longitudinal study included 192 patients who underwent esophagectomy for cancer. The exposure was dispositional optimism measured by the Life Orientation Test-Revised (LOT-R) at 1 year post-surgery. Patients were categorized into four subgroups (very low, moderately low, moderately high, and very high dispositional optimism) based on the quartile of the LOT-R sum score. The outcome was HRQL assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and Quality of Life Questionnaire-Esophago-Gastric module 25 (QLQ-OG25) at 1, 1.5, and 2 years post-surgery. Linear mixed-effects models, adjusted for potential confounders, were used to examine the mean score difference (MSD) with 95% confidence interval of HRQL among the four patient subgroups.ResultsPatients with very high dispositional optimism reported clinically relevantly better global quality of life, emotional function, and social function (MSD range 10–16) and less severe symptoms in pain, dyspnea, diarrhea, eating difficulty, anxiety, dry mouth, trouble with taste, worry about weight loss, and self-doubt about body image (MSD range − 9 to − 22) than patients with lower dispositional optimism. Patients with moderately high dispositional optimism reported clinically and statistically significantly better global quality of life (MSD 10) and less severe diarrhea (MSD − 9) than patients with lower dispositional optimism. Adjusted MSDs were constant over the three time points in all aspects except for eating difficulty.ConclusionsMeasuring dispositional optimism could help identify patients at higher risk of poor HRQL recovery after esophageal cancer surgery.

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The cover image is based on the Original Article A nationwide population-based longitudinal study mapping psychiatric disorders during lifetime in siblings to patients with bipolar disorder by Lars Vedel Kessing et al., https://doi.org/10.1111/acps.13263.

Psychological distress and health-related quality of life up to 2 years after oesophageal cancer surgery: nationwide population-based study.

BackgroundPatients are at higher risk of suffering from psychological distress and reduced health-related quality of life (HRQoL) after oesophageal cancer surgery. This Swedish nationwide population-based longitudinal study aimed to evaluate the association between psychological distress and HRQoL up to 2 years after oesophageal cancer surgery.MethodsThe study included patients with oesophageal cancer who had survived for 1 year after oesophageal cancer surgery. The exposure was psychological distress measured using the Hospital Anxiety and Depression Scale. Patients scoring at least 8 on either the anxiety or the depression subscale were classified as having psychological distress. The outcome was HRQoL assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire generic and disease-specific questionnaires (EORTC QLQ-C30 and QLQ-OG25). Exposure and outcome were measured at 1, 1.5, and 2 years after operation. Fixed-effects models with adjustment for all time-invariant confounding and potential time-varying confounders were used to examine the mean score difference in HRQoL between patients with and without psychological distress.ResultsIn total, 180 patients were analysed. Clinically relevant, statistically significant and time-constant mean score differences were found in emotional function, social function, dyspnoea, anxiety, eating difficulty, eating in front of others, and weight loss (mean score difference range 10–29). Mean score differences for global quality of life, cognitive function, appetite loss, EORTC QLQ-C30 summary score, and trouble with taste increased over time, and reached clinical and statistical significance at 1.5 and/or 2 years after surgery. For body image, there was a clinically relevant decrease in mean score difference over time.ConclusionPsychological distress was associated with several aspects of poor HRQoL up to 2 years after surgery for oesophageal cancer.

Female Reproductive Factors and Risk of Bronchiectasis: A Nationwide Population-Based Longitudinal Study

Background: Although oestrogen level is thought to be involved in the occurrence of non-cystic fibrosis bronchiectasis (bronchiectasis), limited data is available on the relationship between female reproductive factors and the risk of bronchiectasis. Therefore, we aimed to evaluate whether female reproductive factors are associated with bronchiectasis. Methods: We performed a population-based retrospective cohort study of 959,523 premenopausal women and 1,362,401 postmenopausal women without previous history of bronchiectasis who participated in a health screening exam in 2009 in South Korea. Outcomes were measured until December 31, 2018. The exposures were female reproductive factors (age at menarche, age at menopause, parity, breastfeeding, or exogenous hormone use), and the main outcome was the incidence of bronchiectasis. Findings: The mean follow-up duration was 8.3 years in premenopausal women and 8.1 years in postmenopausal women. In premenopausal women, compared with later age at menarche (> 16 years), earlier menarche (≤ 12 years) was associated with reduced risk of bronchiectasis, with an adjusted hazard ratio (aHR [95% confidence interval (CI)]) of 0.74 [0.67–0.81]). However, there were no significant associations between other reproductive factors (breastfeeding, parity, or oral contraceptive use) and the risk of bronchiectasis. In postmenopausal women, earlier menarche (adjusted HR [95% CI] = 0.79 [0.72–0.87] for ≤12 years vs. >16 years), later menopause (0.90 [0.88–0.91] ≥ 55years vs. < 40 years), and longer reproductive period (0.90 [0.86–0.94] for ≥ 40 years vs. < 30 years) were associated with reduced risk of bronchiectasis. While breastfeeding < 1year (aHR [95% CI] = 0.93 [0.88–0.97]) and oral contraceptive use < 1year (0.97 [0.94–0.99]) reduced the risk of bronchiectasis, hormone replacement therapy ≥ 5 years increased risk of bronchiectasis (1.24 [1.18–1.30]). Interpretation: Female reproductive factors are risk factors of developing bronchiectasis, showing a higher risk associated with shorter endogenous oestrogen exposure regardless of menopausal status. Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, Information and Communications Technologies (NRF350 2020R1F1A1070468 and 2021M3E5D1A01015176) and the Korea Medical Device Development Fund grant funded by the Korean government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (Project Number: 1711138447, KMDF_PR_20200901_0214). Declaration of Interests: All authors have no conflict of interest to disclose Ethics Approval Statement: Our study protocol was approved by the Institutional Review Board of Chungbuk National University Hospital (No. 2021-08-016). The requirement for informed consent was waived because the NHIS database uses an anonymous patient identification system

Increased risk of valvular heart disease in patients with ankylosing spondylitis: a nationwide population-based longitudinal cohort study.

Aims:We aimed to evaluate the risk of valvular heart disease (VHD) among patients with ankylosing spondylitis (AS).Methods:This was a population-based cohort study utilizing the Longitudinal Health Insurance Research Database of the National Health Insurance in Taiwan. Patients with and without coding of newly diagnosed AS from 1999 to 2013 were assigned to the AS and non-AS groups, respectively. Primary outcome was the incidental risk of VHD. Multiple Cox regression was used to estimate the adjusted hazard ratio of VHD. Subgroup analysis and sensitivity tests were also conducted.Results:The AS group included 3780 patients, and 22,680 matched subjects without an AS diagnosis were identified as controls. The AS group had an increased risk of VHD compared with non-AS controls (adjusted hazard ratio: 1.63; 95% confidence interval: 1.43–1.86; p < 0.001). Subgroup analysis also revealed an increased risk of individual types of VHD, including aortic, mitral, and tricuspid valve disease. Patients in the AS group had a higher incidence of valve replacement surgery after the onset of VHD.Conclusion:Patients with AS had a significant risk of VHD compared to non-AS controls in this population-based cohort study. Screening for VHD may be needed in caring patients with AS. We suggest that echocardiography may be performed when patients are diagnosed with AS.

A nation-wide population-based longitudinal study mapping physical diseases in patients with bipolar disorder and their siblings

BackgroundPatients with bipolar disorder may have increased risk of physical diseases due to genetic and environmental factors, but no study has systematically mapped all physical comorbidities in such subjects. The aim was to map rates of all physical diseases among patients and siblings to patients with bipolar disorder. MethodsWe used Danish nation-wide population-based longitudinal register linkage to identify 19.955 patients with bipolar disorder, their 13.923 siblings and 20 sex, age and calendar matched control individuals from the general population. Follow-up was from 1995 to 2017. ResultsBipolar disorder was associated with increased rates of all physical disease categories compared with rates for control individuals, except for cancer. Further, bipolar disorder was associated with increased rates of separate disorders including ischemic heart disease, diabetes, dementia, hypertension, hypercholesterolemia and hyperlipidemia, hypothyroidism and infections. In contrast, siblings to patients with bipolar disorder who were unaffected by bipolar disorder had increased rates of certain disorders, only, comprising infectious and parasitic diseases, and diseases of the nervous system, digestive system and genitourinary system. LimitationsUnderdetection of physical disorders is likely because data are not available for persons who do not seek help for their disorders. ConclusionsBipolar disorder was associated with increased rates of all physical diseases categories, except cancer, and with separate disorders, likely involving inflammatory components in the pathogenesis. In contrast, unaffected siblings to patients with bipolar disorder had increased rates of certain disorders, only.

A nationwide population-based longitudinal study mapping psychiatric disorders during lifetime in siblings to patients with bipolar disorder.

The aim was to map rates and cumulative incidences of psychiatric disorders during lifetime for siblings to patients with a diagnosis of bipolar disorder compared with the general population. Danish nationwide population-based longitudinal register linkage study including 13,923 unaffected siblings to 19,955 patients with bipolar disorder and 278,460 unaffected control individuals from the general population matched according to year of birth and sex. Follow-up covered 22years from 1995 to 2017. Rates of 'any psychiatric disorder' among siblings compared with control individuals were constantly around twofold increased throughout lifespan whereas there was a bimodal age distribution of hazard ratios of bipolar disorder, unipolar disorder and use of alcohol or psychoactive drugs with the highest hazard ratios up to age 20 and above 60years of age. Cumulative incidences from age 15years of any psychiatric disorder were 44.2% at age 80years for siblings versus 27.6% for control individuals and the corresponding numbers for bipolar disorder was 8.7% for siblings compared with 1.6% for control individuals. Strategies to prevent onset of psychiatric illness in individuals with a first-generation family history of bipolar disorder should not be limited to adolescence and early adulthood but should be lifetime, likely with differentiated age-specific strategies.

Continuity of care: evaluating a multidisciplinary care model for people with early CKD via a nationwide population-based longitudinal study

ObjectivesTo control and prevent the burdens associated with chronic kidney disease (CKD), Taiwan’s National Health Insurance Administration (NHIA) launched the ‘early-CKD programme’ in 2011 to extend care and education to...

The association between SGLT2 inhibitors and new-onset arrhythmias: a nationwide population-based longitudinal cohort study

Abstract Background/Introduction Clinical trials have shown the cardiovascular protective effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors and reduced hospitalization for heart failure. However, no study has investigated the association between SGLT2 inhibitors and the risk of arrhythmias. Purpose To evaluate the risk of new-onset arrhythmias (NOA) and all-cause mortality with the use of SGLT2 inhibitors. Methods This was a population-based cohort study utilizing Taiwan's National Health Insurance Research Database. Each patient aged 20 years and older who took SGLT2 inhibitors was assigned to the SGLT2 inhibitor group, whereas sex-, age-, diabetes mellitus duration-, drug index date-, and propensity score-matched randomly selected patients without SGLT2 inhibitors were assigned to the non-SGLT2 inhibitor group. The study outcome was all-cause mortality and NOA. Results A total of 399,810 patients newly diagnosed with type 2 diabetes mellitus (T2DM) were enrolled. A 1:1 matching propensity method was used to match 79,150 patients to 79,150 controls in the non-SGLT2 inhibitors group for analysis. The SGLT2 inhibitor group was associated with a lower risk of all-cause mortality (adjusted hazard ratio [aHR] 0.547; 95% confidence interval [CI] 0.482–0.621; P=0.0001) and NOA (aHR 0.830; 95% CI 0.751–0.916; P=0.0002). Subgroup analysis revealed that the SGLT2 inhibitor group was associated with a lower risk of all-cause mortality in all age and severity of the adapted Diabetes Complication Severity Index (aDCSI) subgroups. Furthermore, NOA and atrial fibrillation were associated with a lower risk in subgroups with an aDCSI score of between 1 and 2. Conclusions Patients with T2DM prescribed with SGLT2 inhibitors were associated with a lower risk of all-cause mortality and NOA compared with those not taking SGLT2 inhibitors in real-world practice. The potential protective effect of NOA and atrial fibrillation is observed, especially in individuals with T2DM and an aDCSI score of between 1 and 2. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): This study was supported in parts by grants from Chung Shan Medical University Hospital.

Hepatic and cardiovascular safety of acarbose among type 2 diabetes patients with end-stage renal disease: A nationwide population-based longitudinal study

AimTo assess the relationship between acarbose and hepatotoxicity, cardiovascular disease (CVD), and mortality among type 2 diabetes (T2D) patients with end-stage renal disease (ESRD). Methods32,531 T2D patients with ESRD were identified from Taiwan’s National Health Insurance Research Database in 2000~∼2012 and followed up until 2013. 19.3% of subjects were newly initiated with acarbose during the follow-up. The use of acarbose was quantified as the numbers of the 30-day drug’s supplies and dosages (measured by defined daily doses; DDDs), respectively. Time-varying Cox models were applied to evaluate the association of acarbose use with hepatic, cardiovascular and mortality outcomes, with adjustment for patients’ demographics, comorbidities, diabetes severity, and co-medications. ResultsFor each 30-day supply increase in acarbose exposure, the risks of hepatic injury, composite CVD events, and all-cause mortality were significantly lowered by 9% (95% confidence interval: 6–12%), 7% (6–7%) and 7% (7–8%), respectively, while for each 30-day DDD increase in acarbose exposure, the risks for three aforementioned outcomes were significantly reduced by 45% (33–54%), 33% (29–36%) and 35% (32–39%), respectively. In subgroup analyses, the favorable study outcomes of acarbose use were more apparent among patients with more severe diabetes, a longer diabetes duration, or absence of established CVD at baseline. ConclusionAcarbose used in real-world T2D patients with ESRD may have hepatic and cardiovascular safety.

Cataract and the increased risk of depression in general population: a 16-year nationwide population-based longitudinal study

Cataract is the primary cause of visual impairment and can be corrected by cataract surgery. We investigated the impact of cataract on the risk of depression along with the benefits of cataract surgery. Patients newly diagnosed with cataract by ophthalmologists between 2001 and 2015 were identified from the National Health Insurance Research Database (NHIRD) in Taiwan. Non-cataract individuals were recruited by 1:1 matching for age, sex and index year. After propensity score matching, 233,258 patients in total were included in our study: 116,629 in each of the cataract and non-cataract cohorts. The primary outcome was the new diagnosis of depression by psychiatrists. In a mean follow-up period of 7.8 years, cataract was significantly associated with increased risk of developing depression (adjusted hazard ratio [aHR] = 1.78, 95% confidence interval [CI] 1.70–1.87, p < 0.001). We further divided the cataract cohort into surgery and non-surgery groups. Notably, cataract surgery group was associated with a decreased risk of depression compared with non-surgery patients (aHR = 0.75, 95% CI 0.71–0.79, p < 0.001). Our results emphasise the importance of regular screening for depression among cataract patients and the beneficial effect of cataract surgery in reducing the risk of depression.

Relationship between Helicobacter pylori infection and psoriasis: a nationwide population-based longitudinal cohort study.

Background:In the current literature, studies assessing the role of Helicobacter pylori (HP) infection in psoriasis have reported conflicting data. Therefore, we investigated the association between HP infection and psoriasis using a nationwide population-based longitudinal cohort study.Methods:We identified 41,539 patients with HP infection and 83,078 matched controls between 2000 and 2013 from the Longitudinal Health Insurance Research Database of the National Health Insurance Research Database in Taiwan. Propensity score analysis was used to match age, sex, comorbidities, and medical visits at a ratio of 1:2. Multiple Cox regression analysis was used to estimate the adjusted hazard ratio of psoriasis. Furthermore, sensitivity tests and a stratified analysis were conducted.Results:The incidence rates of psoriasis did not differ significantly between the HP and control cohorts (4.58 vs 4.20 per 100,000 person-months, crude relative risk: 1.092, 95% confidence interval: 0.917–1.302). After multivariate adjustment, no significant difference in psoriasis risk was observed in patients with HP infection (adjusted hazard ratio: 1.081, 95% confidence interval: 0.907–1.288). Risk of psoriasis was significantly higher in men and the elderly, and in those with diabetes, hyperlipidemia, chronic obstructive pulmonary disease, or tuberculosis. Stratified analysis also confirmed that HP infection was not correlated with an increased risk of psoriasis based on follow-up duration, sex, and age.Conclusion:This retrospective population-based longitudinal cohort study, conducted in Taiwan, found no association between HP infection and risk of psoriasis. Further research may be warranted.

The association between SGLT2 inhibitors and new-onset arrhythmias: a nationwide population-based longitudinal cohort study

BackgroundClinical trials have shown the cardiovascular protective effect of sodium–glucose cotransporter-2 (SGLT2) inhibitors and reduced hospitalization for heart failure. However, no study has investigated the association between SGLT2 inhibitors and the risk of arrhythmias. This study aimed to evaluate the risk of new-onset arrhythmias (NOA) and all-cause mortality with the use of SGLT2 inhibitors.MethodsThis was a population-based cohort study utilizing Taiwan’s National Health Insurance Research Database. Each patient aged 20 years and older who took SGLT2 inhibitors was assigned to the SGLT2 inhibitor group, whereas sex-, age-, diabetes mellitus duration-, drug index date-, and propensity score-matched randomly selected patients without SGLT2 inhibitors were assigned to the non-SGLT2 inhibitor group. The study outcome was all-cause mortality and NOA.ResultsA total of 399,810 patients newly diagnosed with type 2 DM were enrolled. A 1:1 matching propensity method was used to match 79,150 patients to 79,150 controls in the non-SGLT2 inhibitors group for analysis. The SGLT2 inhibitor group was associated with a lower risk of all-cause mortality [adjusted hazard ratio (aHR) 0.547; 95% confidence interval (CI) 0.482–0.621; P = 0.0001] and NOA (aHR 0.830; 95% CI 0.751–0.916; P = 0.0002).ConclusionsPatients with type 2 DM prescribed with SGLT2 inhibitors were associated with a lower risk of all-cause mortality and NOA compared with those not taking SGLT2 inhibitors in real-world practice.

Prepregnancy Endocrine, Autoimmune Disorders and the Risks of Gestational Hypertension-Preeclampsia in Primiparas: A Nationwide Population-Based Study in Taiwan.

(1) Objective: To assess the risks of gestational hypertension/preeclampsia (GH-PE) in women with prepregnancy endocrine and autoimmune disorders such as polycystic ovarian syndrome (PCOS) and systemic lupus erythematosus (SLE). (2) Methods: In a nationwide population-based longitudinal study, data were retrieved from the 1998 to 2012 Taiwan National Health Insurance Research Database. ICD9-CM codes 256.4, 710.0, and 642.X were identified for the corresponding diagnoses of PCOS, SLE, and GH-PE, respectively, which were further confirmed by inspection of medical claims data for ultrasonography findings, laboratory tests, blood pressure measurements and examinations of urine protein to ensure the accuracy of the diagnoses. To clarify the risks of primiparous GH-PE, the study excluded women diagnosed with PCOS or SLE at <15 or >45 years of age, pre-existing chronic hypertension, GH-PE before PCOS and SLE, and abortion or termination before 20 weeks’ gestation. For women affected by prepregnancy PCOS or SLE individually, each pregnant woman was age-matched to four pregnant women without PCOS or SLE. Logistic regression analyses were applied to report odds ratios (ORs) for the risks of GH-PE after adjustment for age, occupation, urbanization, economic status, and other co-morbidities. (3) Results: Among 8070 and 2430 women with prepregnancy PCOS and SLE retrieved from a population of 1,000,000 residents, 1953 (24.20%) and 820 (33.74%) had subsequent primiparous pregnancies that were analyzable and compared with 7812 and 3280 pregnancies without prepregnancy PCOS and SLE, respectively. GH-PE occurred more frequently in pregnancies with prepregnancy PCOS (5.79% vs. 2.23%, p < 0.0001) and SLE (3.41% vs. 1.80%, p < 0.01) as compared to those without PCOS and SLE. Further analysis revealed that prepregnancy PCOS (adjusted OR = 2.36; 95%CI: 1.83–3.05) and SLE (adjusted OR = 1.95; 95%CI: 1.23–3.10) were individually associated with GH-PE. The risk of GH-PE was not reduced in women with prepregnancy PCOS receiving metformin treatment (p = 0.22). (4) Conclusions: Prepregnancy PCOS and SLE are independent and significant risk factors for the occurrence of GH-PE. Because the peripartum complications are much higher among pregnancies with GH-PE, the at-risk woman should be informed and well-prepared during her pregnancy and delivery.

Non-alcoholic fatty liver disease among patients with sleep disorders: a Nationwide study of Taiwan

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Studies have shown that sleep apnea is associated with NAFLD. However, studies on the association between sleep disorders in general and NAFLD are limited. We conducted a nationwide population-based longitudinal study to evaluate this potential association.MethodsWe identified patients diagnosed with sleep disorders in the years 2000 through 2005 in Taiwan using the National Health Insurance Research Database and selected an equal number of patients without sleep disorders from the same database as the comparison cohort. The patients were followed from the index date to the diagnosis of NAFLD or the end of 2013. We used Cox proportional hazards models to estimate the risk of NAFLD associated with sleep disorders.ResultsA total of 33,045 patients with sleep disorders were identified. The incidence of NAFLD was 14.0 per 10,000 person-year in patients with sleep disorders and 6.2 per 10,000 person-year in the comparison cohort. The adjusted hazard ratio (AHR) of NAFLD associated with sleep disorders was 1.78 (95% confidence interval [95%CI]: 1.46–2.16), and other independent risk factors included male sex (AHR = 1.31, 95%CI: 1.12–1.54), age 40–59 years (AHR = 1.49, 95%CI: 1.21–1.82), and dyslipidemia (AHR = 2.51, 95%CI: 2.08–3.04). In the subgroup analyses, both patients with (AHR = 2.24, 95%CI: 1.05–4.77) and without (AHR = 1.77, 95%CI: 1.46–2.15) sleep apnea had an increased risk of NAFLD.ConclusionsSleep disorders are associated with NAFLD, even in patients without sleep apnea. Further studies are warranted to explore the mechanisms of the association.

High exposure to statins decrease the risk of new-onset dementia: A nationwide population-based longitudinal cohort study.

Several studies have shown that statin users have a lower risk of new-onset dementia (NOD) compared nonusers. However, other studies have shown opposite results. In this study, we investigated the association between the use of statins and the development of NOD.This was a longitudinal cohort study using data from claim forms submitted to the Taiwanese Bureau of National Health Insurance. The study included patients with NOD and non-NOD subjects from January 2002 to December 2013. We estimated the hazard ratios (HRs) of NOD associated with statin use, whereas nonuser subjects were used as a reference group.A total of 19,522 NOD cases were identified in 100,610 hyperlipidemic patients during the study period. The risk of NOD, after adjusting for sex, age, comorbidities, and concurrent medication, was lower among statin users than nonusers (HR 0.95, 95% CI [confidence interval] 0.94–0.96; P < .001). The adjusted HRs for NOD were 1.53 (95% CI, 1.45–1.62), 0.63 (95% CI, 0.57–0.71), and 0.34 (95% CI, 0.30–0.38) when the cumulative defined daily doses ranged from 28 to 365, 366 to 730, and more than 730 relative to nonusers, respectively.We concluded that statin use is associated with a decreased NOD risk. The protective effect of statins for NOD seemed to be related to high exposure to statins. This study also highlights that high exposure to statins has a dose-response effect on lowering NOD risk.

New drug candidates for bipolar disorder-A nation-wide population-based study.

Drug repurposing is an increasingly promising idea in many fields of medicine. We systematically used Danish nation-wide population-based registers to investigate whether continued use of non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, high-dose aspirin, statins, allopurinol, and angiotensin agents decrease the rate of incident mania/bipolar disorder. A nation-wide population-based longitudinal study using Poisson regression analyses including all persons in Denmark who purchased the exposure medication of interest and a random sample of 30% of the Danish population. The follow-up period comprised a 10years period from 2005 to 2015. Two different outcome measures were included, (1) a diagnosis of mania/bipolar disorder at a psychiatric hospital contact as inpatient or outpatient and (2) a combined measure of a diagnosis of mania/bipolar disorder or initiation of lithium use. A total of 1,605,365 subjects were exposed to one of the six drugs of interest during the exposure period from 2005 to 2015, median age 57years [quartiles: 43;69], and female proportion of 53.1%. Continued use of low-dose aspirin, statins, and angiotensin agents were associated with decreased rates of incident mania/bipolar disorder on both outcome measures. Continued uses of non-aspirin NSAIDs as well as high-dose aspirin were associated with an increased rate of incident bipolar disorder. There were no statistically significant associations for allopurinol. The study supports the potential of agents acting on inflammation and the stress response system in bipolar disorder and illustrates that population-based registers can be used to systematically identify drugs with repurposing potentials.

Increased risk of sleep apnoea among primary headache disorders: a nationwide population-based longitudinal study

BackgroundPrimary headache disorders (PHDs) are associated with sleep problems. It is suggested that headache and sleep disorder share anatomical and physiological characteristics. We hypothesised that patients with PHDs were exposed...