Hypertension has been associated with Parkinson's disease (PD), but data on antihypertensive drugs and PD are inconclusive. We aim to evaluate antihypertensive drugs for an association with PD in ...hypertensive patients.
Hypertensive patients who were free of PD, dementia and stroke were recruited from 2005-2006 using Taiwan National Health Insurance Database. We examined the association between the use of calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) and the incidence of PD using beta-blockers as the reference. Cox regression model with time-varying medication use was applied.
Among 65,001 hypertensive patients with a mean follow-up period of 4.6 years, use of dihydropyridine CCBs, but not non-dihydropyridine CCBs, was associated with a reduced risk of PD (adjusted hazard ratio aHR = 0.71; 95% CI, 0.57-0.90). Additionally, use of central-acting CCBs, rather than peripheral-acting ones, was associated with a decreased risk of PD (aHR = .69 55-0.87. Further decreased association was observed for higher cumulative doses of felodipine (aHR = 0.54 0.36-0.80) and amlodipine (aHR = 0.60 0.45-0.79). There was no association between the use of ACEIs (aHR = 0.80 0.64-1.00) or ARBs (aHR = 0.86 0.69-1.08) with PD. A potentially decreased association was only found for higher cumulative use of ACEIs (HR = 0.52 0.34-0.80) and ARBs (HR = 0.52 0.33-0.80).
Our study suggests centrally-acting dihydropyridine CCB use and high cumulative doses of ACEIs and ARBs may associate with a decreased incidence of PD in hypertensive patients. Further long-term follow-up studies are needed to confirm the potential beneficial effects of antihypertensive agents in PD.
Aims
To examine the comparative effectiveness of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and sodium‐glucose cotransporter‐2 (SGLT2) inhibitors for select cardiovascular outcomes and to ...examine whether the relative risks varied across different patient subgroups in patients with type 2 diabetes.
Materials and Methods
We conducted a nationwide cohort study of patients with type 2 diabetes who initiated GLP‐1RAs or SGLT2 inhibitors between 2012 and 2018 in Taiwan. The study outcomes included myocardial infarction and total stroke, further classified into ischaemic or haemorrhagic stroke. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for each outcome, comparing GLP‐1RAs with SGLT2 inhibitors using Cox proportional hazards models after 1:1 propensity‐score (PS) matching. We also examined if there was effect modification by age, underlying chronic kidney disease, or coexisting cardiovascular disease in prespecified subgroup analyses.
Results
Among 26 032 PS‐matched patients, GLP‐1RA initiators and SGLT2 inhibitor initiators showed similar risks of myocardial infarction (HR 0.99, 95% CI 0.65‐1.52), total stroke (HR 0.90, 95% CI 0.69‐1.17), ischaemic stroke (HR 0.86, 95% CI 0.65‐1.14) and haemorrhagic stroke (HR 0.88, 95% CI 0.63‐1.25). However, GLP‐1RA treatment was associated with an increased risk of total stroke (HR 1.76, 95% CI 1.06‐2.94) and ischaemic stroke (HR 1.88, 95% CI 1.09‐3.23) among patients with chronic kidney disease, but not among patients without chronic kidney disease. GLP‐1RA therapy seemed to have a lower risk of haemorrhagic stroke among patients with cardiovascular disease (HR 0.64, 95% CI 0.43‐0.97), but not in patients without cardiovascular disease.
Conclusions
Glucagon‐like peptide‐1 receptor agonists and SGLT2 inhibitors appeared to have comparable effectiveness with regard to several cardiovascular outcomes overall, but their comparative effectiveness may vary in certain patient subgroups.
Background
To compare the risks of major osteoporotic, vertebral, and non‐vertebral fractures between patients who discontinued anti‐osteoporosis medications.
Methods
We conducted a comparative ...effectiveness study with a nationwide population‐based cohort study design. Patients aged ≥50 years admitted between 2012 and 2015 for incident hip fractures and receiving denosumab or bisphosphonates with sufficient compliance for at least 1 year were included. Patients were categorized into persistent or non‐persistent denosumab or bisphosphonates users based on their subsequent use pattern. The main outcomes were subsequent hospitalizations for a major osteoporotic, vertebral or non‐vertebral fracture. Multivariate, time‐varying Cox proportional hazards model was used to evaluate the risk of major outcomes.
Results
Compared with persistent denosumab users, non‐persistent denosumab users had a significantly higher risk of major osteoporotic fractures (hazard ratio HR = 1.60; 95% confidence interval CI, 1.20–2.14), vertebral fractures (HR = 2.18; 95% CI, 1.46–3.24) and death (HR = 3.57; 95%CI, 2.63–4.84). However, the increased risk of fracture was not found in both persistent and non‐persistent bisphosphonates users. Noteworthy, the increased risk of vertebral fractures in non‐persistent denosumab users was more pronounced within 1 year post‐discontinuation (HR = 2.90; 95% CI, 1.77–4.74) and among patients who discontinued from 2‐year denosumab therapy (HR = 3.58; 95% CI, 1.74–7.40).
Discussion
Discontinuation of denosumab resulted in an increased risk of major osteoporotic fractures, especially vertebral fractures. The increased risk tends to reveal within 1 year post‐discontinuation and be greater after a longer treatment duration. Notably, only fracture with hospitalization was identified as our research outcome, the real risk of osteoporotic fracture post discontinuation is believed to be higher, especially for vertebral fracture.
Data regarding the nephrotoxicity of sofosbuvir (SOF) remain controversial. We compared the evolution of estimated glomerular filtration rate (eGFR) in patients with chronic HCV infection receiving ...SOF-based or SOF-free direct-acting antivirals (DAAs).
A total of 481 patients with compensated liver diseases and eGFR ≥30 ml/min/1.73m2, receiving SOF-based (n = 308) or SOF-free (n = 173) DAAs for 12 weeks, were prospectively enrolled. The eGFR was assessed from baseline to off-treatment week 24 using the chronic kidney disease (CKD)-epidemiology collaboration equation. Differences in the evolution of eGFR between regimens were compared by a generalized linear mixed-effects model. Multivariate analysis was performed for factors affecting eGFR evolution.
Patients receiving SOF-based DAAs experienced a significant on-treatment decline in eGFR (adjusted slope coefficient difference: −1.24 ml/min/1.73m2/month; 95% CI −1.35 to −1.13; p <0.001) and a significant off-treatment improvement (adjusted slope coefficient difference: 0.14 ml/min/1.73m2/month; 95% CI 0.08 to 0.21; p = 0.004) compared to patients receiving SOF-free DAAs. Multivariate analysis showed age per 1-year increase (adjusted slope coefficient difference: −0.05 ml/min/1.73m2/month; 95% CI −0.05 to −0.04; p <0.001), SOF-based DAAs (adjusted slope coefficient difference: −0.33 ml/min/1.73m2/month; 95% CI −0.49 to −0.17; p <0.001), and CKD stage (adjusted slope coefficient difference: −1.44 ml/min/1.73m2/month; 95% CI −1.58 to −1.30; p <0.001 for stage 3 vs. 1, and −3.59 ml/min/1.73m2/month; 95% CI −3.88 to −3.30; p <0.001 for stage 2 vs. 1) were independent factors affecting eGFR evolution from baseline to off-treatment week 24.
Patients receiving SOF-based DAAs exhibited a quadratic trend, with eGFR worsening on treatment and improving off treatment. Increasing age, SOF-based DAAs, and more advanced baseline CKD stage are independently associated with a decline in eGFR in patients with HCV receiving DAAs.
While the efficacy of sofosbuvir for the treatment of hepatitis C virus is clear, data regarding its possible nephrotoxicity are controversial. Herein, we showed that sofosbuvir worsened on-treatment kidney function but led to an off-treatment improvement. Our findings suggest that treating physicians should be alert to risk factors for kidney dysfunction before initiating direct-acting antiviral treatment for patients with hepatitis C virus infection.
NCT04047680
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•Patients receiving SOF-based DAAs exhibit a quadratic trend, with eGFR worsening on treatment and improving off treatment.•Patients receiving SOF-free DAAs have a linear trend with eGFR improving on and off treatment.•Increasing age, use of SOF-based DAAs, and more advanced baseline CKD stage are independent risk factors of eGFR decline.
Sleep disturbances are common in women, especially during pregnancy. Previous studies have confirmed the importance of sleep disturbances as a risk factor of adverse pregnancy outcomes and the need ...for screening and treatment of inadequate sleep. These reports, however, did not examine health-related quality of life which may be affected by sleep long before adverse clinical consequences are detectable in women during pregnancy.
To examine the cross-sectional and longitudinal association between sleep and health-related quality of life in pregnant women.
A prospective observational study.
A university-affiliated hospital in Taiwan and participants’ homes.
A total of 164 pregnant women completed questionnaires and wore a wrist actigraphy monitor for 7 days each trimester.
Objective sleep was measured by actigraphy, subjective sleep was measured by the Pittsburgh Sleep Quality Index, and health-related quality of life was measured using the SF-12v2 questionnaire across three trimesters. Multiple linear regression analyses were performed to evaluate the cross-sectional and longitudinal associations between sleep and health-related quality of life.
Sixty-four (39.0%) women consistently had an average sleep efficiency<85% by actigraphy and 40 (24.4%) had a Pittsburgh Sleep Quality Index global score>5 in all three trimesters. Cross-sectionally, more actigraphic daytime sleep (p=0.04) and better subjective sleep quality (p<0.01) were associated with better physical health-related quality of life in first-trimester pregnant women. Better actigraphic sleep efficiency (p=0.04) and better subjective sleep quality (p<0.01) were associated with better mental health-related quality of life in second-trimester pregnant women. Longer actigraphic total nighttime sleep (p<0.01) and better subjective sleep quality (p<0.01) were associated with better mental health-related quality of life in third-trimester pregnant women. Longitudinally, first-trimester actigraphic total nighttime sleep (p<0.05) and subjective sleep quality (p<0.01) predicted mental health-related quality of life in the second and third trimester.
Sleep disturbances are a highly prevalent and persistent problem in pregnant women. Adequate sleep is essential for women at all pregnancy stages and improving nocturnal sleep quantity and quality in early gestation is of utmost importance for an optimal health-related quality of life later in pregnancy.
The objective of this nationwide case‐control study was to evaluate the risk of specific malignancy in diabetic patients who received thiazolidinediones (TZDs). A total of 606,583 type 2 diabetic ...patients, age 30 years and above, without a history of cancer were identified from the Taiwan National Health Insurance claims database during the period between January 1 2000 and December 31 2000. As of December 31 2007, patients with incident cancer of liver, colorectal, lung, and urinary bladder were included as cases and up to four age‐ and sex‐matched controls were selected by risk‐set sampling. Logistic regression models were applied to estimate the odds ratio (OR) and 95% confidence interval (CI) between TZDs and cancer incidence. A total of 10,741 liver cancer cases, 7,200 colorectal cancer cases, and 70,559 diabetic controls were included. A significantly lower risk of liver cancer incidence was found for any use of rosiglitazone (OR: 0.73, 95% CI: 0.65‐0.81) or pioglitazone (OR: 0.83, 95% CI: 0.72‐0.95), respectively. The protective effects were stronger for higher cumulative dosage and longer duration. For colorectal cancer, rosiglitazone, but not pioglitazone, was associated with a significantly reduced risk (OR: 0.86; 95% CI: 0.76‐0.96). TZDs were not associated with lung and bladder cancer incidence, although a potential increased risk for bladder cancer with pioglitazone use ≥3 years could not be excluded (OR: 1.56; 95% CI: 0.51‐4.74). Conclusion: The use of pioglitazone and rosiglitazone is associated with a decreased liver cancer incidence in diabetic patients. The effects on occurrence of specific cancer types may be different for pioglitazone and rosiglitazone. (HEPATOLOGY 2012;)
Background and objective
The epidemiology of pediatric acquired demyelinating disorders remains to be clarified in many parts of Asia. We carry out this study to depict the epidemiology of pediatric ...multiple sclerosis (MS), neuromyelitis optica (NMO), and optic neuritis (ON) in Taiwan.
Methods
We conducted a retrospective nationwide population-based study using data from Taiwan’s National Health Insurance Research Database. Prevalent cases of pediatric MS and NMO during 2001–2015, and incident cases of pediatric MS, NMO, and ON during 2003–2015 were identified. The demographic features and comorbidities were investigated.
Results
We identified 403 MS, 42 NMO, and 1496 ON incident cases under the age of 20 during 2003–2015. The majority of pediatric MS (86.1%) and NMO (90.5%) patients were 10 years old or above. The incidence of MS and ON was relatively steady, while that of NMO increased prominently later during the study period. The average incidence of pediatric MS and NMO during 2011–2015 was 0.52 and 0.11 per 100,000 person-years, respectively. The female preponderance was evident for pediatric MS and NMO, and less so for pediatric ON. The most common autoimmune comorbidities for pediatric MS were thyrotoxicosis (1.0%) and systemic lupus erythematosus (0.7%).
Conclusion
The epidemiology of pediatric MS was largely stationary in Taiwan during 2001–2015, while the prevalence of pediatric NMO rose steeply during this period, probably reflecting better recognition of this clinical entity. Autoimmune comorbidities were uncommon for pediatric MS and NMO in Taiwan.
Study Objective
Clinical trials have suggested that glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) may be associated with a higher risk of biliary‐related diseases in patients with type 2 ...diabetes. Limited real‐world studies have examined the comparative biliary safety of GLP‐1RAs versus other antihyperglycemic drugs. We aimed to estimate the comparative risk of biliary‐related diseases between GLP‐1RAs and sodium glucose cotransporter 2 inhibitors (SGLT2is), which are indicated for patients with similar diabetes severity in Taiwan.
Design
Retrospective cohort study.
Data Source
Taiwan National Health Insurance Database during 2011 to 2018.
Patients
Patients with type 2 diabetes who initiated GLP‐1RAs or SGLT2is.
Intervention
GLP‐1RAs versus SGLT2is.
Measurements and Main Results
We used an on‐treatment approach to examine the effect of continuous use and an intention‐to‐treat approach to assess the effect of initiation of GLP‐1RAs versus SGLT2is. We used Coxregression models to estimate the hazard ratios (HRs) and 95% confidenceintervals (CIs) for the composite hospitalized biliary‐related diseases, including acute cholecystitis or cholecystectomy, choledocholithiasis, and acute cholangitis, after matching each GLP‐1RA initiator to up to 10 SGLT2iinitiators using propensity scores (PSs). Among 78,253 PS‐matched patients, GLP‐1RA use was associated with a numerically higher risk of biliary‐related diseases versus SGLT2i use in the on‐treatment analysis, with an HR of 1.20 (95% CI, 0.93–1.56) for the composite outcome, an HR of 1.22 (95% CI, 0.92–1.62) for acute cholecystitis or cholecystectomy, an HR of 1.20 (95% CI, 0.69–2.07) for choledocholithiasis, and an HR of 1.14 (95% CI,0.82–2.42) for acute cholangitis. The HRs were more pronounced in theintention‐to‐treat analysis (1.27 95% CI, 1.05–1.53 for the composite outcome, 1.29 95% CI, 1.04–1.58 foracute cholecystitis or cholecystectomy, 1.74 95% CI, 1.23–2.46 for choledocholithiasis, and 1.31 95% CI, 0.89–1.94 for acute cholangitis). The increased risk of the composite outcome associated with GLP‐1RAs was more evident in patients aged 〉60 years, women, and 120 days after treatment initiation. Liraglutide, but not dulaglutide, was associated with an elevated risk.
Conclusions
GLP‐1RAs might be associated with an elevated risk of biliary‐related diseases compared to SGLT2is in Asian patients with type 2 diabetes.
Biological plausibility suggests that fluoroquinolones may lead to mitral valve regurgitation or aortic valve regurgitation (MR/AR) through a collagen degradation pathway. However, available ...real‐world studies were limited and yielded inconsistent findings. We estimated the risk of MR/AR associated with fluoroquinolones compared with other antibiotics with similar indications in a population‐based cohort study. We identified adult patients who initiated fluoroquinolones or comparison antibiotics from the nationwide Taiwanese claims database. Patients were followed for up to 60 days after cohort entry. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of MR/AR comparing fluoroquinolones to comparison antibiotics after 1:1 propensity score (PS) matching. All analyses were conducted by type of fluoroquinolone (fluoroquinolones as a class, respiratory fluoroquinolones, and non‐respiratory fluoroquinolones) and comparison antibiotic (amoxicillin/clavulanate or ampicillin/sulbactam, extended‐spectrum cephalosporins). Among 6,649,284 eligible patients, the crude incidence rates of MR/AR ranged from 1.44 to 4.99 per 1,000 person‐years across different types of fluoroquinolones and comparison antibiotics. However, fluoroquinolone use was not associated with an increased risk in each pairwise PS‐matched comparison. HRs were 1.00 (95% CI, 0.89–1.11) for fluoroquinolones as a class, 0.96 (95% CI, 0.83–1.12) for respiratory fluoroquinolones, and 0.87 (95% CI, 0.75–1.01) for non‐respiratory fluoroquinolones, compared with amoxicillin/clavulanate or ampicillin/sulbactam. Results were similar when fluoroquinolones were compared with extended‐spectrum cephalosporins (HRs of 0.96, 95% CI, 0.82–1.12, HR, 1.05, 95% CI, 0.86–1.28, and HR, 0.88, 95% CI, 0.75–1.03, respectively). This large‐scale cohort study did not find a higher risk of MR/AR with different types of fluoroquinolones in the adult population.
Summary Background Extracorporeal life-support as an adjunct to cardiac resuscitation has shown encouraging outcomes in patients with cardiac arrest. However, there is little evidence about the ...benefit of the procedure compared with conventional cardiopulmonary resuscitation (CPR), especially when continued for more than 10 min. We aimed to assess whether extracorporeal CPR was better than conventional CPR for patients with in-hospital cardiac arrest of cardiac origin. Methods We did a 3-year prospective observational study on the use of extracorporeal life-support for patients aged 18–75 years with witnessed in-hospital cardiac arrest of cardiac origin undergoing CPR of more than 10 min compared with patients receiving conventional CPR. A matching process based on propensity-score was done to equalise potential prognostic factors in both groups, and to formulate a balanced 1:1 matched cohort study. The primary endpoint was survival to hospital discharge, and analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00173615. Findings Of the 975 patients with in-hospital cardiac arrest events who underwent CPR for longer than 10 min, 113 were enrolled in the conventional CPR group and 59 were enrolled in the extracorporeal CPR group. Unmatched patients who underwent extracorporeal CPR had a higher survival rate to discharge (log-rank p<0·0001) and a better 1-year survival than those who received conventional CPR (log rank p=0·007). Between the propensity-score matched groups, there was still a significant difference in survival to discharge (hazard ratio HR 0·51, 95% CI 0·35–0·74, p<0·0001), 30-day survival (HR 0·47, 95% CI 0·28–0·77, p=0·003), and 1-year survival (HR 0·53, 95% CI 0·33–0·83, p=0·006) favouring extracorporeal CPR over conventional CPR. Interpretation Extracorporeal CPR had a short-term and long-term survival benefit over conventional CPR in patients with in-hospital cardiac arrest of cardiac origin. Funding National Science Council, Taiwan.
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