Sodium-glucose co-transporter-2 inhibitors and the risk of venous thromboembolism: A nationwide population-based study and meta-analysis.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have off-target effects on haemoconcentration and anti-inflammation. The impact of SGLT-2i on the risk of venous thromboembolism (VTE) in patients with diabetes mellitus (DM) remains unclear. This study aimed to evaluate the risk of newly diagnosed VTE in patients with DM using SGLT-2i in comparison to dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1RA). MATERIALS AND METHODS: In this nationwide retrospective cohort study, we used data from Taiwan's National Health Insurance Research Database. Patients with diabetes aged 20 years or older who received SGLT-2i, DPP-4i, or GLP-1RA between 1 May 2016, and 31 December 2020, were included. The risks of VTE in SGLT-2i users were compared with those of DPP-4i and GLP-1RA users. A Cox regression model with stabilised inverse probability of treatment weighting was used to calculate hazard ratio (HR) for VTE risk. Additionally, a meta-analysis of relevant articles published before 23 May 2023, was conducted. RESULTS: Data from 136,530 SGLT-2i, 598,280 DPP-4i, and 5760 GLP-1RA users were analysed. SGLT-2i use was associated with a lower risk of VTE than DPP-4i (HR, 0.70; 95% CI, 0.59-0.84; p < 0·001), but not with GLP-1RA (HR, 1.39; 95% CI, 0.32-5.94; p = 0.66). Our meta-analysis further supported these findings (SGLT-2i vs. DPP-4i: HR, 0.71; 95% CI, 0.62-0.82; p < 0·001; SGLT-2i vs. GLP-1RA: HR, 0.91; 95% CI, 0.73-1.15; p = 0.43), suggesting the robustness of our retrospective analysis. CONCLUSIONS: In patients with DM, SGLT-2i was associated with a lower risk of VTE compared to DPP-4i, but not GLP-1RA.

Risk of heart failure in elderly patients with atrial fibrillation and diabetes taking different oral anticoagulants: a nationwide cohort study.

BACKGROUND: Heart failure (HF) is a critical complication in elderly patients with atrial fibrillation (AF) and diabetes mellitus (DM). Recent preclinical studies suggested that non-vitamin K antagonist oral anticoagulants (NOACs) can potentially suppress the progression of cardiac fibrosis and ischemic cardiomyopathy. Whether different oral anticoagulants influence the risk of HF in older adults with AF and DM is unknown. This study aimed to evaluate the risk of HF in elderly patients with AF and DM who were administered NOACs or warfarin. METHODS: A nationwide retrospective cohort study was conducted based on claims data from the entire Taiwanese population. Target trial emulation design was applied to strengthen causal inference using observational data. Patients aged ≥ 65 years with AF and DM on NOAC or warfarin treatment between 2012 and 2019 were included and followed up until 2020. The primary outcome was newly diagnosed HF. Propensity score-based fine stratification weightings were used to balance patient characteristics between NOAC and warfarin groups. Hazard ratios (HRs) were estimated using Cox proportional hazard models. RESULTS: The study included a total of 24,835 individuals (19,710 NOAC and 5,125 warfarin users). Patients taking NOACs had a significantly lower risk of HF than those taking warfarin (HR = 0.80, 95% CI 0.74-0.86, p < 0.001). Subgroup analyses for individual NOACs suggested that dabigatran (HR = 0.86, 95% CI 0.80-0.93, p < 0.001), rivaroxaban (HR = 0.80, 95% CI 0.74-0.86, p < 0.001), apixaban (HR = 0.78, 95% CI 0.68-0.90, p < 0.001), and edoxaban (HR = 0.72, 95% CI 0.60-0.86, p < 0.001) were associated with lower risks of HF than warfarin. The findings were consistent regardless of age and sex subgroups and were more prominent in those with high medication possession ratios. Several sensitivity analyses further supported the robustness of our findings. CONCLUSIONS: This nationwide cohort study demonstrated that elderly patients with AF and DM taking NOACs had a lower risk of incident HF than those taking warfarin. Our findings suggested that NOACs may be the preferred oral anticoagulant treatment when considering the prevention of heart failure in this vulnerable population. Future research is warranted to elucidate causation and investigate the underlying mechanisms.

Association of bisphosphonates with diabetes risk and glycemic control: a meta-analysis.

Previous evidence suggests that bisphosphonates may improve glycemic control. The present meta-analysis, comprising seven studies with 1,233,844 participants, demonstrated that bisphosphonate use was significantly associated with a lower risk of diabetes. However, in the randomized controlled trial subgroup, a non-significant association was found. Further studies are needed to determine causality. PURPOSE: This study aimed to evaluate the impact of bisphosphonates on glycemic control and the risk of incident diabetes. METHODS: MEDLINE, Embase, and Cochrane Library were searched from inception to February 15, 2022. Experimental or observational studies that compared fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) levels and the diabetes risk with and without bisphosphonates were included. Studies without relevant outcomes, only providing crude estimates, or the absence of a control group were excluded. Two reviewers independently screened the articles, extracted data, and appraised studies. The pooled relative risk (RR) and weighted mean difference (WMD) were calculated using random effects models. RESULTS: Seven studies (n = 1,233,844) on diabetes risk were included, including two post hoc analyses of randomized controlled trials (RCTs) and five observational studies. Compared with controls, bisphosphonates (BPs) were associated with a significant decrease in the risk of diabetes (RR = 0.77; 95% CI, 0.65 to 0.90; P = 0.002). However, in the subgroup of post hoc analyses of RCTs, the association was non-significant (RR = 0.93; 95% CI, 0.74 to 1.18; P = 0.576). Moreover, three studies (n = 4906) on FBG and one (n = 60) on HbA1c were included. We observed non-significant association between BPs and changes in FBG (WMD = - 0.61 mg/dL; 95% CI, - 2.72 to 1.49; P = 0.567) and HbA1c (WMD = - 0.11%; 95% CI, - 0.23 to 0.01; P = 0.083). CONCLUSION: Patients taking BPs may have a lower risk of incident diabetes than those without BPs. However, due to the high between-study heterogeneity and inconsistent findings between post hoc analyses of RCTs and observational studies, further rigorous RCTs are required to determine whether the findings are causal.

Association between bisphosphonate use and stroke risk: a meta-analysis.

Previous studies have suggested that bisphosphonates may reduce stroke risk. This meta-analysis, which included 21 studies with 741,274 participants, revealed that bisphosphonates might be associated with lower stroke risk. However, evidence derived from randomized controlled trials identified no statistically significant association. Future high-quality studies are still required to determine causality. PURPOSE: Whether bisphosphonates may reduce the risk of stroke remains inconclusive. We conducted a systematic review and meta-analysis to evaluate the association between bisphosphonate use and the risk of stroke based on up-to-date evidence. METHODS: We searched for studies evaluating the effects of bisphosphonate on the risk of stroke from inception until January 3, 2022, on PubMed, Embase, Scopus, and Cochrane libraries and updated our search until August 22, 2022, using PubMed to identify any new potential published studies. Two or more reviewers independently screened articles, extracted data, and assessed the study quality. We retrieved the data to synthesize the pooled relative risk (RR) of stroke associated with bisphosphonate use compared with controls; random-effects models were used for meta-analysis. RESULTS: A total of 21 studies (7 randomized controlled trials [RCTs] and 14 observational studies) involving 741,274 participants were included in our meta-analysis. Overall, bisphosphonate use was associated with a lower risk of stroke, but the result was only borderline significant (pooled RR = 0.87, 95% confidence interval [CI]: 0.76-0.99, p = 0.048), and high between-study heterogeneity was found (I2 = 83.7%). Subgroup analyses showed that the evidence derived from RCTs suggested no significant association between bisphosphonate use and stroke risk (pooled RR = 0.93, 95% CI: 0.76-1.13, p = 0.462; I2 = 13.4%). CONCLUSION: Our results suggest that bisphosphonate use is associated with a lower risk of stroke. However, the current evidence does not lead to a definite conclusion due to the borderline statistical significance and high between-study heterogeneity. Future studies, especially RCTs, are necessary to assess causality.

Diabetes-Related Complications and Mortality in Patients With Atrial Fibrillation Receiving Different Oral Anticoagulants : A Nationwide Analysis.

BACKGROUND: Evidence about the association between types of oral anticoagulants and hazards of diabetes complications is limited in patients with atrial fibrillation (AF) and diabetes mellitus (DM). OBJECTIVE: To compare the hazards of diabetes complications and mortality between patients with AF and DM receiving non-vitamin K antagonist oral anticoagulants (NOACs) and those receiving warfarin. DESIGN: A retrospective cohort study. SETTING: Nationwide data obtained from Taiwan's National Health Insurance Research Database. PATIENTS: Patients with AF and DM receiving NOACs or warfarin between 2012 and 2017 in Taiwan were enrolled. Treatment groups were determined by patients' first initiation of oral anticoagulants. MEASUREMENTS: Hazards of diabetes complications (macrovascular complications, microvascular complications, and glycemic emergency) and mortality in the NOAC and warfarin users were investigated with a target trial design. Cause-specific Cox proportional hazards models were used to estimate hazard ratios (HRs). Propensity score methods with stabilized inverse probability of treatment weighting were applied to balance potential confounders between treatment groups. RESULTS: In total, 19 909 NOAC users and 10 300 warfarin users were included. Patients receiving NOACs had significantly lower hazards of developing macrovascular complications (HR, 0.84 [95% CI, 0.78 to 0.91]; P < 0.001), microvascular complications (HR, 0.79 [CI, 0.73 to 0.85]; P < 0.001), glycemic emergency (HR, 0.91 [CI, 0.83 to 0.99]; P = 0.043), and mortality (HR, 0.78 [CI, 0.75 to 0.82]; P < 0.001) than those receiving warfarin. Analyses with propensity score matching showed similar results. Several sensitivity analyses further supported the robustness of our findings. LIMITATION: The claims-based data did not allow for detailed data on patients' lifestyles and laboratory examinations to be obtained. CONCLUSION: Non-vitamin K antagonist oral anticoagulants were associated with lower hazards of diabetes complications and mortality than warfarin in patients with AF and DM. PRIMARY FUNDING SOURCE: Hualien Tzu Chi Hospital.

Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: 2022 update.

Osteoporosis greatly increases the risk of fractures. Osteoporotic fractures negatively impact quality of life, increase the burden of care, and increase mortality. Taiwan is an area with a high prevalence of osteoporosis. This updated summary of guidelines has been developed by experts of the Taiwan Osteoporosis Association with the intention of reducing the risks of osteoporotic fractures and improving the quality of care for patients with osteoporosis. The updated guidelines compile the latest evidence to provide clinicians and other healthcare professionals with practical recommendations for the prevention, diagnosis, and management of osteoporosis under clinical settings in Taiwan.

Association of alpha-1-adrenergic antagonist use with the risk of gout development in benign prostatic hyperplasia patients: a population-based cohort study.

BACKGROUND: Men are more likely to develop benign prostatic hyperplasia (BPH) and gout as they age. However, the role of alpha-1-adrenergic antagonists, the medication for BPH, in the development of gout is uncertain. OBJECTIVE: To investigate the effect of alpha-1-adrenergic antagonist use on the risk of developing gout in BPH patients. METHODS: Data of patients with newly diagnosed BPH were retrieved from Taiwan's 2000-2013 National Health Insurance Research Database (total number: 15,390 patients; 7,695 patients in each cohort). Propensity score matching was conducted according to age, comorbidities, medication history for cohorts that received or did not receive alpha-1-adrenergic antagonists. Hazard ratios (HRs) were assessed for gout development using Cox proportional hazards regression models. RESULTS: Use of alpha-1-adrenergic antagonists was not associated with gout development in BPH patients (HR = 0.92; 95% confidence interval [CI], 0.78-1.10; P = 0.35). However, after stratification according to the average number of days of alpha-1-adrenergic antagonist use per year, patients with an average of >300 days had a significantly higher risk of gout development than patients who did not receive alpha-1-adrenergic antagonists (adjusted HR = 1.57; 95% CI, 1.25-1.97; P < 0.001). Patients with more days of medication use per year had a higher risk of gout development than those with fewer days of medication use (P < 0.001). CONCLUSION: Patients who received more doses of alpha-1-adrenergic antagonists per year had a higher risk of developing gout. A causal proof of the role of alpha-1-adrenergic antagonists use in gout development should be analysed in future studies designed as double blind randomized controlled trials.

Efficacy of atropine, orthokeratology, and combined atropine with orthokeratology for childhood myopia: A systematic review and network meta-analysis.

BACKGROUND/PURPOSE: Orthokeratology (Ortho-K), atropine eye drops and combined atropine with Ortho-K are proven to be effective ways to prevent myopic progression in many studies, but there is scarce evidence regarding the comparative efficacy of different dosages of atropine,Ortho-K, and combined atropine with Ortho-K for childhood myopia. METHODS: We performed a network meta-analysis (NMA) to assess the relative efficacy of the aforementioned interventions for myopic progression; moreover, we calculated the surface under cumulative ranking area (SUCRA) to determine the relative ranking of treatments. RESULTS: We identified 19 randomized controlled trials (3435 patients). NMA revealed that 0.01%-1% atropine, Ortho-K, and 0.01% atropine combined with Ortho-K inhibited axial elongation (AL) over one year. For refractive change, SUCRA analysis revealed that the hierarchy was high-dose (0.5%-1%), moderate-dose (0.1%-0.25%), and low-dose (0.01%-0.05%) atropine. Regarding AL, SUCRA analysis revealed the following hierarchy: Ortho-K combined with 0.01% atropine, high-dose atropine, moderate-dose atropine, Ortho-K, and low-dose atropine. CONCLUSION: In conclusion, we found that atropine (0.01%-1%), Ortho-K, and 0.01% atropine combined with Ortho-K could significantly slow down myopia progression. The atropine efficacy followed a dose-related pattern; moreover, Ortho-K and low-dose atropine showed similar efficacy. There was a synergistic effect of using 0.01% atropine combined with Ortho-K, and it showed comparable efficacy to that of high-dose atropine.

Risk of developing diabetes in patients with atrial fibrillation taking non-vitamin K antagonist oral anticoagulants or warfarin: A nationwide cohort study.

AIM: To compare the risk of diabetes development in patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. MATERIALS AND METHODS: We conducted a nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. Adult patients with new onset of AF, treated with NOACs or warfarin between 2012 and 2016, were included. The NOAC cohort was further divided into dabigatran, rivaroxaban and apixaban groups. The primary outcome was incident diabetes requiring treatment with antidiabetic drugs. Fine and Gray subdistribution hazards models were used to estimate the adjusted hazard ratio (aHR). Propensity score matching was performed for each head-to-head comparison. RESULTS: A total of 10 746 new-onset AF patients were included in our study. During the mean 2.4-year follow-up, NOACs were associated with a lower risk of developing diabetes than warfarin (aHR = 0.80, 95% confidence interval [CI]: 0.68-0.94, P = .007). Subgroup analyses confirmed that dabigatran, rivaroxaban and apixaban each had a reduced diabetes risk. Stratified analyses showed that the lower risk of diabetes associated with NOAC treatment was specific to patients aged 65 years or older (aHR = 0.74, 95% CI: 0.62-0.89, P = .002) and those with good medication adherence (aHR = 0.70, 95% CI: 0.58-0.84, P < .001). CONCLUSIONS: Taking an NOAC was associated with a lower risk of developing diabetes than taking warfarin in patients with AF.

Risk of developing pneumonia associated with clinically diagnosed hypothyroidism: a nationwide population-based cohort study.

BACKGROUND: Hypothyroidism has a detrimental effect on the immune system, which may predispose patients to infection. However, evidence about the risk of developing either community- or hospital-acquired pneumonia in patients with hypothyroidism is scarce. OBJECTIVE: To evaluate the association between hypothyroidism and the risk of developing pneumonia. METHODS: This was a retrospective population-based cohort study from Taiwan's National Health Insurance Research Database. After 1:1 propensity score matching, 9749 patients (age ≥20 years) newly diagnosed with hypothyroidism between 2001 and 2014 and 9749 patients without hypothyroidism or other thyroid diseases were included in the hypothyroidism and non-hypothyroidism cohorts, respectively, and followed up until 2015. The development of pneumonia was defined as the primary outcome. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) of developing pneumonia between hypothyroidism and non-hypothyroidism cohorts after adjusting for age, sex and baseline comorbidities. To evaluate whether thyroxine replacement therapy (TRT) modified the risk for pneumonia, we divided patients with hypothyroidism into subgroups: patients who received TRT and those who did not. RESULTS: Hypothyroidism was associated with a higher risk of pneumonia [adjusted HR (aHR) 1.38, 95% confidence interval (CI) 1.29-1.49, P < 0.001]. Patients with hypothyroidism who received TRT had a lower risk of pneumonia than patients who did not (aHR 0.85, 95% CI 0.76-0.93, P = 0.001). Similar results were obtained in the age- and sex-stratified analyses. CONCLUSIONS: Clinically diagnosed hypothyroidism was independently associated with the risk of pneumonia. In patients with hypothyroidism, TRT was associated with a lower risk of pneumonia.

Hypothyroidism has a detrimental effect on the immune system, which may predispose patients to infection. The risk factors for pneumonia include older age, chronic lung diseases and, most importantly, a decreased immune response against respiratory pathogens. However, evidence of the risk for pneumonia in patients with hypothyroidism is scarce. The high prevalence of hypothyroidism, high annual incidence rate of pneumonia and their interrelationship through the immune system emphasize the importance of understanding the association between the two diseases. This study aimed to determine whether patients diagnosed with hypothyroidism conferred a predisposition to the development of pneumonia. In this 15-year population-based retrospective cohort study, we found that patients clinically diagnosed with hypothyroidism might be at increased risk for the future development of pneumonia. Moreover, in patients with hypothyroidism, the risk of pneumonia may be reduced by thyroxine replacement treatment. Additional prospective cohort studies, which include thyroid function tests and a more accurate clinical diagnosis of pneumonia based on radiological findings, are needed to confirm the effects of hypothyroidism on the risk of developing pneumonia.

Fracture risks among patients with atrial fibrillation receiving different oral anticoagulants: a real-world nationwide cohort study.

AIMS: To evaluate the fracture risk among patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. METHODS AND RESULTS: We conducted a real-world nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. All adult patients in Taiwan newly diagnosed with AF between 2012 and 2016 who received NOACs or warfarin were enrolled and followed up until 2017. Patients treated with NOACs were sub-grouped according to the NOAC used (dabigatran, rivaroxaban, and apixaban). Propensity score matching was performed for each head-to-head comparison. Cox regression analysis, with a shared frailty model, was used to calculate the adjusted hazard ratios (aHRs) for hip, vertebral, and humerus/forearm/wrist fractures. After matching, 19 414 patients were included (9707 in each NOAC and warfarin groups). The median follow-up time was 2.4 years. Compared with warfarin, NOACs were associated with a reduced fracture risk [aHR = 0.84, 95% confidence interval (CI) = 0.77-0.93; P < 0.001]. Sub-analyses revealed that each NOAC, namely dabigatran (aHR = 0.88, 95% CI = 0.78-0.99; P = 0.027), rivaroxaban (aHR = 0.81, 95% CI = 0.72-0.90; P < 0.001), and apixaban (aHR = 0.67, 95% CI = 0.52-0.87; P = 0.003), had a reduced fracture risk. Analyses including all eligible patients, without propensity score matching, generated similar results. CONCLUSION: Compared with warfarin, NOAC was associated with a reduced fracture risk among AF patients. Therefore, if oral anticoagulants are indicated, NOACs rather than warfarin should be considered to lower the risk of fractures. However, further studies are needed to investigate the underlying mechanisms and elucidate causality.

Herpes zoster and the risks of osteoporosis and fracture: a nationwide cohort study.

This study aimed to investigate the association between herpes zoster (HZ) and the risks of osteoporosis and fracture. We conducted a nationwide retrospective cohort study using the National Health Insurance Research Database of Taiwan. The study enrolled 63,786 patients: 31,893 diagnosed with HZ between 2000 and 2012 were included in the HZ cohort, and 31,893 matched controls without HZ were included in the non-HZ cohort, with 1:1 exact matching for age, sex, and index year. Hazard ratios (HRs) were calculated for the risks of osteoporosis and fracture according to the HZ status using the Cox proportional hazards regression models. During a mean follow-up period of 6.0 years, 5597 and 4639 patients in the HZ and non-HZ cohorts, respectively, developed osteoporosis or fractures (incidence rate: 29.8 vs. 23.8 per 1000 person-years). HZ diagnosis was significantly associated with an elevated risk of developing osteoporosis or fracture (adjusted HR [aHR] = 1.20, p < 0.001). On analyses for each individual event, the HZ cohort had significantly increased risks for all events, including osteoporosis (aHR = 1.32, p < 0.001), hip fracture (aHR = 1.34, p < 0.001), vertebral fracture (aHR = 1.38, p < 0.001), and other fractures (aHR = 1.10, p < 0.001) compared with the non-HZ cohort. Patients with postherpetic neuralgia had especially higher risks of osteoporosis and fracture. Age- and sex-stratified analyses also revealed similar patterns. In conclusion, HZ was independently associated with an increased risk of osteoporosis and fracture. Further studies are required to investigate its underlying mechanisms.

Hysterectomy associated with de novo lower urinary tract symptoms in a Taiwanese population: a nationwide, population-based study.

INTRODUCTION AND HYPOTHESIS: The effect of hysterectomy on vesicourethral functions remains controversial. The objective of this study was to examine the association between hysterectomy and de novo lower urinary tract symptoms (LUTSs). METHODS: We identified 8514 patients who had undergone hysterectomy between January 1, 2000, and December 31, 2012, from Taiwan's National Health Insurance (NHI) Research Database. A control cohort, comprising 34,056 age-matched patients who had not undergone hysterectomy, was created for comparison. All hysterectomy and control patients were followed up until diagnosis as having LUTSs (dysuria, urinary retention, incontinence, and increased urinary frequency and urgency), withdrawal from the NHI system, death, or December 31, 2013. Patients were excluded if LUTSs were diagnosed before or at the time of hysterectomy. RESULTS: The adjusted hazard ratio (aHR) of subsequent de novo LUTSs was higher in the hysterectomy patients [1.57, 95% confidence interval (CI) 1.46-1.70] than in the controls during the follow-up period. Compared with the controls, the highest risk of de novo LUTSs was noted in patients who had undergone vaginal hysterectomy (VH; aHR 1.89, 95% CI 1.57-2.28) followed by those who had undergone laparoscopy-assisted VH (LAVH; aHR 1.74, 95% CI 1.56-1.94). CONCLUSIONS: We found that undergoing hysterectomy was associated with increased risks of developing lower urinary tract symptoms in women. This association was more pronounced for women undergoing the vaginal or laparoscopically assisted hysterectomy. Further large-scale prospective studies or clinical trials are needed to explore whether causality exists.

Association between diuretic use and the risk of vertebral fracture after stroke: a population-based retrospective cohort study.

BACKGROUND: Stroke is a major risk factor for osteoporosis and fractures. No study has evaluated the association between diuretic use and risk of vertebral fracture in stroke patients, although a considerable proportion of stroke patients are prescribed diuretics for hypertension. Our study aimed to investigate whether treatment with thiazides or loop diuretics affects the risk of vertebral fracture after stroke. METHODS: A population-based propensity score-matched retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. Patients with a new diagnosis of stroke between 2000 and 2011 were included. After propensity score matching, 9468 patients were included in the analysis of the effect of thiazides, of who 4734 received thiazides within 2 years after stroke. To analyze the loop diuretic effect, 4728 patients were included, of who 2364 received loop diuretics. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) of vertebral fractures among patients according to thiazide or loop diuretic use within 2 years following stroke. Sensitivity analyses based on the duration of thiazide or loop diuretic use were further conducted. RESULTS: There was no significant difference in vertebral fracture risk between thiazide users and non-users (adjusted HR [aHR] = 1.14, 95% confidence interval [CI] = 0.88-1.47, p = 0.316). Loop diuretic users had a significantly higher vertebral fracture risk than non-users (aHR = 1.45, 95% CI = 1.06-1.98, p = 0.019). However, the sensitivity analysis revealed that short-term thiazide use (exposure duration < 90 days within 2 years after stroke) significantly increased the risk of vertebral fracture versus non-use (aHR = 1.38, 95% CI = 1.02-1.88, p = 0.039). Only short-term loop diuretic users had significantly higher risk of vertebral fracture (aHR = 1.56, 95% CI = 1.11-2.20, p = 0.011). The other two subgroups with longer exposure duration in analyses for both thiazides and loop diuretics revealed no significant effect. CONCLUSIONS: Short-term thiazide or loop diuretic use was associated with an increased risk of vertebral fracture after stroke. Further prospective clinical trials are required to confirm this finding.

Pelvic organ prolapse surgery following hysterectomy with benign indication: a national cohort study in Taiwan.

INTRODUCTION AND HYPOTHESIS: Hysterectomy and pelvic organ prolapse (POP) surgeries are two of the most common gynecologic surgeries conducted for benign conditions. This nationwide retrospective cohort study explored the risk of subsequent POP surgery following hysterectomy without simultaneous POP surgery. METHODS: This study identified 7298 patients who underwent hysterectomy between January 1, 2000, and December 31, 2012, from the Taiwan National Health Insurance (NHI) Research Database. A comparison cohort was constructed comprising 29,192 age-matched patients who had not undergone hysterectomy. All hysterectomy and control patients were followed until they required POP surgery, withdrew from the NHI system, died, or December 31, 2012. Patients were excluded if they underwent POP surgery before or at the time of hysterectomy. RESULTS: The adjusted hazard ratio (aHR) of subsequent POP surgery in subjects with hysterectomy was higher [2.60, 95% confidence interval (CI) 1.79-3.78] than that of controls during the follow-up period. Compared with patients who had not undergone hysterectomy, the highest risks of subsequent POP surgery was noted in those who had undergone vaginal hysterectomy (VH; HR 6.29, 95% CI 1.54-25.79) followed by those who underwent laparoscopy-assisted VH (LAVH; HR 3.77, 95% CI 2.43-5.85). CONCLUSIONS: Hysterectomy may increase the risk of subsequent POP surgery, and various hysterectomy techniques, particularly VH and LAVH, may increase the risk of subsequent POP surgery.

MACE and Hyperthyroidism Treated With Medication, Radioactive Iodine, or Thyroidectomy.

Importance: Excessive thyroid hormones from hyperthyroidism increase cardiovascular risks. Among 3 available treatments for hyperthyroidism, comparisons of long-term outcomes associated with antithyroid drugs (ATDs), radioactive iodine (RAI), and surgery to treat newly diagnosed hyperthyroidism are lacking. Objective: To compare risks of major adverse cardiovascular events (MACE) and all-cause mortality among patients with hyperthyroidism treated with ATDs, RAI, or surgery. Design, Setting, and Participants: This nationwide cohort study used the Taiwan National Health Insurance Research Database. Patients aged 20 years or older with newly diagnosed hyperthyroidism between 2011 and 2020 were enrolled. Treatment groups were determined within 18 months from diagnosis, with follow-up until the development of MACE, death, or the end date of the database, whichever came first. Data were analyzed from October 2022 through December 2023. Exposures: The ATD group received ATDs only. RAI and surgery groups could receive ATDs before treatment. Anyone who underwent thyroid surgery without RAI was classified into the surgery group and vice versa. Main Outcomes and Measures: The primary outcomes included MACE (a composite outcome of acute myocardial infarction, stroke, heart failure, and cardiovascular mortality) and all-cause mortality. Results: Among 114 062 patients with newly diagnosed hyperthyroidism (mean [SD] age, 44.1 [13.6] years; 83 505 female [73.2%]), 107 052 patients (93.9%) received ATDs alone, 1238 patients (1.1%) received RAI, and 5772 patients (5.1%) underwent surgery during a mean (SD) follow-up of 4.4 (2.5) years. Patients undergoing surgery had a significantly lower risk of MACE (hazard ratio [HR] = 0.76; 95% CI, 0.59-0.98; P = .04), all-cause mortality (HR = 0.53; 95% CI, 0.41-0.68; P < .001), heart failure (HR = 0.33; 95% CI, 0.18-0.59; P < .001), and cardiovascular mortality (HR = 0.45; 95% CI, 0.26-0.79; P = .005) compared with patients receiving ATDs. Compared with ATDs, RAI was associated with lower MACE risk (HR = 0.45; 95% CI, 0.22-0.93; P = .03). Risks for acute myocardial infarction and stroke did not significantly differ between treatment groups. Conclusions and Relevance: In this study, surgery was associated with lower long-term risks of MACE and all-cause mortality, while RAI was associated with a lower MACE risk compared with ATDs.

Denosumab and the Risk of Diabetes in Patients Treated for Osteoporosis.

Importance: Denosumab, a humanized monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), is a widely used antiresorptive medication for osteoporosis treatment. Recent preclinical studies indicate that inhibition of RANKL signaling improves insulin sensitivity, glucose tolerance, and ß-cell proliferation, suggesting that denosumab may improve glucose homeostasis; however, whether denosumab reduces the risk of incident diabetes remains unclear. Objective: To evaluate whether denosumab use is associated with a lower risk of developing diabetes in patients with osteoporosis. Design, Setting, and Participants: This nationwide, propensity score-matched cohort study used administrative data from Taiwan's National Health Insurance Research Database. Adult patients who received denosumab for osteoporosis therapy in Taiwan between 2012 and 2019 were included. To eliminate the inherent bias from confounding by indication, the patients were categorized into a treatment group (34 255 patients who initiated denosumab treatment and adhered to it) and a comparison group (34 255 patients who initiated denosumab treatment but discontinued it after the initial dose) according to the administration status of the second dose of denosumab. Propensity score matching was performed to balance patient characteristics and to control for confounders. Exposure: Treatment with denosumab. Main Outcomes and Measures: The primary outcome was incident diabetes requiring treatment with antidiabetic drugs. A Cox proportional hazards model was used to estimate the hazard ratio (HR) for incident diabetes. Data were analyzed from January 1 to November 30, 2023. Results: After propensity score matching, 68 510 patients were included (mean [SD] age, 77.7 [9.8] years; 57 762 [84.3%] female). During a mean (SD) follow-up of 1.9 (1.6) years, 2016 patients developed diabetes in the treatment group and 3220 developed diabetes in the comparison group (incidence rate, 35.9 vs 43.6 per 1000 person-years). Compared with the comparison group, denosumab treatment was associated with a lower risk of incident diabetes (HR, 0.84; 95% CI, 0.78-0.90). Several sensitivity analyses also demonstrated similar results of lower diabetes risk associated with denosumab treatment. Conclusions and relevance: The results from this cohort study indicating that denosumab treatment was associated with lower risk of incident diabetes may help physicians choose an appropriate antiosteoporosis medication for patients with osteoporosis while also considering the risk of diabetes.