Thiazolidinediones Decrease the Recurrence of Intracerebral Hemorrhage in Type 2 Diabetes Mellitus Patients: A Nested Case-Control Study.

INTRODUCTION: Preclinical evidence demonstrated the therapeutic potential of thiazolidinediones (TZDs) for the treatment of intracerebral hemorrhage (ICH). The present study conducted an investigation of cerebrovascular and cardiovascular outcomes following ICH in patients with type 2 diabetes mellitus (T2DM) treated with or without TZDs. METHODS: This retrospective nested case-control study used data from the Taiwan National Health Insurance Research Database. A total of 62,515 T2DM patients who were hospitalized with a diagnosis of ICH were enrolled, including 7,603 TZD users. Data for TZD non-users were extracted using propensity score matching. Primary outcomes included death and major adverse cardiovascular events (MACEs), which were defined as a composite of ischemic stroke, hemorrhagic stroke (HS), acute myocardial infarction, and congestive heart failure. Patients aged <20 years with a history of traumatic brain injury or any prior history of MACEs were excluded. RESULTS: TZD users had significantly lower MACE risks compared with TZD non-users following ICH (adjusted hazard ratio [aHR]: 0.90, 95% confidence interval [CI]: 0.85-0.94, p < 0.001). The most significant MACE difference reported for TZD users was HS, which possessed lower incidence than in TZD non-users, especially for the events that happened within 3 months following ICH (aHR: 0.74, 95% CI: 0.62-0.89 within 1 month, p < 0.01; aHR: 0.68, 95% CI: 0.54-0.85 between 1 and 3 month). CONCLUSION: The use of TZD in patients with T2DM was associated with a lower risk of subsequent HS and mortality following ICH.

Comparing the Long-Term Cardiovascular Outcomes of Lumbo-Peritoneal, Ventriculo-Peritoneal, or Non-Shunting Treatment after Idiopathic Normal Pressure Hydrocephalus: A Nationwide Retrospective Cohort Study.

Purpose: With advances in medical technology, the average lifespan has increased, leading to a growing significance of idiopathic normal pressure hydrocephalus (iNPH), particularly in the elderly population. Most patients with iNPH have been treated either with ventriculo-peritoneal shunts (VPS) or conservative measures. However, lumbo-peritoneal shunts (LPS) have emerged as an alternative treatment option for iNPH in recent decades, extensive research still lacks comparing outcomes with LPS to those with VPS or non-surgical treatment. The aim of the resent study is to disclose the long-term therapeutic outcomes of LPS, VPS, and non-shunting in patients with iNPH. Methods: We used the National Health Insurance Research Database in Taiwan to assess the long-term outcomes of these treatment options. We enrolled 5,537 iNPH patients who received shunting surgery, of which 5,254 were VPS and 283 were LPS. To compare the difference between each group, matching was conducted by propensity score matching using a 1:1 ratio based on LPS patients. Primary outcomes included death and major adverse cardiovascular events (MACEs) Results: Our findings show that VPS resulted in significantly more MACEs than non-surgical treatment (Odds ratio: 1.83, 95% confidence interval: 1.16-2.90). In addition, both VPS and LPS groups had significantly lower overall mortality rates than non-shunting group. Moreover, LPS had lower overall mortality but similar MACEs rates to VPS. Conclusions: Based on these findings, we propose that the LPS is preferable to the VPS, and surgical treatment should be considered the primary choice over conservative treatment unless contraindications are present.

Presence of depression and anxiety with distinct patterns of pharmacological treatments before the diagnosis of chronic fatigue syndrome: a population-based study in Taiwan.

OBJECTIVE: An increased prevalence of psychiatric comorbidities (including depression and anxiety disorder) has been observed among patients with chronic fatigue syndrome (CFS). However, few studies have examined the presence of depression and anxiety disorder before the diagnosis of CFS. This study aimed to clarify the preexisting comorbidities and treatments associated with patients with subsequent CFS diagnosis in a population-based cohort in Taiwan. METHODS: An analysis utilizing the National Health Insurance Research Database of Taiwan was conducted. Participants included were 6303 patients with CFS newly diagnosed between 2000 and 2010 and 6303 age-/sex-matched controls. RESULTS: Compared with the control group, the CFS group had a higher prevalence of depression and anxiety disorder before the diagnosis of CFS. Sampled patients who took specific types of antidepressants, namely, selective serotonin reuptake inhibitors (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] 1.04-1.39), serotonin antagonists and reuptake inhibitors (SARI; aOR = 1.87, 95% CI 1.59-2.19), and tricyclic antidepressants (aOR = 1.46, 95% CI 1.09-1.95), had an increased risk of CFS. CFS risk was also higher among participants taking benzodiazepine, muscle relaxants, and analgesic drugs. A sub-group analysis revealed that SARI use was related to an increased risk of CFS in the depression, anxiety disorder, male, and female groups. In the depression and anxiety disorder groups, analgesic drug use was associated with an increased CFS risk. Nonpharmacological treatment administration differed between men and women. CONCLUSION: This population-based retrospective cohort study revealed an increased risk of CFS among populations with preexisting depression and anxiety disorder, especially those taking SARI and analgesic drugs.

Metformin use and the risks of herpes zoster and postherpetic neuralgia in patients with type 2 diabetes.

Herpes zoster and postherpetic neuralgia cause substantial pain in patients. Persons with type 2 diabetes (T2D) are prone to zoster infection and postherpetic neuralgia due to compromised immunity. We conducted this study to evaluate the risks of herpes zoster and postherpetic neuralgia between metformin users and nonusers. Propensity score matching was utilized to select 47 472 pairs of metformin users and nonusers from Taiwan's National Health Insurance Research Database between January 1, 2000, and December 31, 2017. The Cox proportional hazards models were used for comparing the risks of herpes zoster and postherpetic neuralgia between metformin users and nonusers in patients with T2D. Compared with no-use of metformin, the adjusted hazard ratios (95% confidence interval) for metformin use in herpes zoster and postherpetic neuralgia were 0.70 (0.66, 0.75) and 0.510 (0.39, 0.68), respectively. A higher cumulative dose of metformin had further lower risks of herpes zoster and postherpetic neuralgia than metformin no-use. This nationwide cohort study demonstrated that metformin use was associated with a significantly lower risk of herpes zoster and postherpetic neuralgia than metformin no-use. Moreover, a higher cumulative dose of metformin was associated with further lower risks of these outcomes.

Herpes zoster associated with stroke incidence in people living with human immunodeficiency virus: a nested case-control study.

BACKGROUND: The incidence of stroke is increasing among younger people with human immunodeficiency virus (HIV). The burden of stroke has shifted toward the young people living with HIV, particularly in low- and middle-income countries. People infected with herpes zoster (HZ) were more likely to suffer stroke than the general population. However, the association of HZ infection with the incidence of stroke among patients with HIV remains unclear. METHODS: A nested case-control study was conducted with patients with HIV registered in the Taiwan National Health Insurance Research Database in 2000-2017. A total of 509 stroke cases were 1:10 matched to 5090 non-stroke controls on age, sex, and date of first stroke diagnosis. Logistic regression models were used to estimate the odds ratio and 95% confidence intervals (CI) of stroke incidence. RESULTS: The odds ratio of stroke was significantly higher in the HIV-infected population with HZ (adjusted odds ratio [AOR]: 1.85, 95% CI: 1.42-2.41). A significantly increased AOR of stroke was associated with hypertension (AOR: 3.53, 95% CI: 2.86-4.34), heart disease (AOR: 2.32, 95% CI: 1.54-3.48), chronic kidney disease (AOR: 1.82, 95% CI: 1.16-2.85), hepatitis C virus infection (AOR: 1.49, 95% CI: 1.22-1.83), hyperlipidemia (OR: 1.41, 95% CI: 1.12-1.78), and treatment with protease inhibitors (AOR: 1.33, 95% CI: 1.05-1.69). CONCLUSIONS: Our findings suggest that HZ concurrent with HIV may increase the risk of stroke. The incidence rates of stroke were independent of common risk factors, suggesting strategies for early prevention of HZ infection among people living with HIV.

Patient and hospital characteristics associated with do-not-resuscitate/do-not-intubate orders: a cross-sectional study based on the Taiwan stroke registry.

BACKGROUND: Previous studies of do-not-resuscitate (DNR) or do-not-intubate (DNI) orders in stroke patients have primarily been conducted in North America or Europe. However, characteristics associated with DNR/DNI orders in stroke patients in Asia have not been reported. METHODS: Based on the Taiwan Stroke Registry, this nationwide cross-sectional study enrolled hospitalized stroke patients from 64 hospitals between 2006 and 2020. We identified characteristics associated with DNR/DNI orders using a two-level random effects model. RESULTS: Among the 114,825 patients, 5531 (4.82%) had DNR/DNI orders. Patients with acute ischemic stroke (AIS) had the highest likelihood of having DNR/DNI orders (adjusted odds ratio [aOR] 1.76, 95% confidence interval [CI] 1.61-1.93), followed by patients with intracerebral hemorrhage (ICH), and patients with subarachnoid hemorrhage (SAH) had the lowest likelihood (aOR 0.53, 95% CI 0.43-0.66). From 2006 to 2020, DNR/DNI orders increased in all three types of stroke. In patients with AIS, women were significantly more likely to have DNR/DNI orders (aOR 1.23, 95% CI 1.15-1.32), while patients who received intravenous alteplase had a lower likelihood (aOR 0.74, 95% CI 0.65-0.84). Patients with AIS who were cared for by religious hospitals (aOR 0.55, 95% CI 0.35-0.87) and patients with SAH who were cared for by medical centers (aOR 0.40, 95% CI 0.17-0.96) were significantly less likely to have DNR/DNI orders. CONCLUSIONS: In Taiwan, DNR/DNI orders increased in stroke patients between 2006 and 2020. Hospital characteristics were found to play a significant role in the use of DNR/DNI orders.

The Sizes and Composition of HDL-Cholesterol Are Significantly Associated with Inflammation in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA), a chronic inflammatory disease, carries a significant burden of atherosclerotic cardiovascular diseases (ASCVD). With their heterogeneous composition, high-density lipoprotein (HDL) particles have varied athero-protective properties, and some may even increase ASCVD risk. In this prospective and cross-sectional study, we aimed to examine the relationship between HDL sizes/metabolites and inflammation in RA. Using 1H-NMR-based lipid/metabolomics, differential HDL-related metabolites were identified between RA patients and healthy control (HC) subjects and between RA patients with and without anti-citrullinated peptide antibodies (ACPA). The correlation between the discriminative HDL-related metabolites and C-reactive protein (CRP) was evaluated in RA patients. RA patients demonstrated higher particle number, lipids, cholesterol, cholesterol ester, free cholesterol, and phospholipids in large/very large-sized HDLs. ACPA-positive patients had higher L-HDL-C and L-HDL-CE but lower small-/medium-sized HDL-TG levels than ACPA-negative patients. An inverse correlation was found between CRP levels and small-sized HDLs. Janus kinase inhibitor treatment was associated with increased serum small-sized HDL-related metabolites and decreased CRP levels. We are the first to reveal the significant associations between RA inflammation and HDL sizes/metabolites. A potential link between ACPA positivity and changes in serum levels of HDL-related metabolites was also observed in RA patients.

Protective Effects of Statins on Limb and Cardiovascular Outcomes in Patients with Peripheral Artery Disease and End-Stage Renal Disease.

Background: Previous studies have reported that statins have inconsistent and marginal cardiovascular (CV) benefits in patients with end-stage renal disease (ESRD). However, whether statins play a secondary preventive role in patients with peripheral artery disease (PAD) and ESRD remains unclear. Objectives: This study aimed to compare the long-term clinical outcomes between statin users and nonusers with PAD and ESRD. Methods: This retrospective cohort study assessed the long-term protective effects of statins using data from the National Health Insurance Research Database in Taiwan. Propensity score matching was performed according to sex, age, index year, related comorbidities, and medications. The main outcomes were limb events and major adverse CV events (MACEs). Results: The statin user group (n = 4,460) was compared with the propensity score-matched statin nonuser group (n = 4,460). The mean age of the matched patients was 64 years, and 40% of the patients were men. The baseline characteristics of the groups were well-balanced. The overall limb event and MACE rates were not different between the two groups. However, the statin user group had lower rates of limb amputation [adjusted hazard ratio (aHR): 0.85, 95% confidence interval (CI): 0.73-0.99], stroke (aHR: 0.71, 95% CI: 0.62-0.83), CV death (aHR: 0.46, 95% CI: 0.32-0.66), and all-cause death (aHR: 0.45, 95% CI: 0.42-0.48) despite having a higher rate of percutaneous transluminal angioplasty for PAD. Conclusions: This population-based retrospective cohort study demonstrated that statin therapy was associated with a lower risk of limb amputation, nonfatal stroke, CV death, and all-cause death in patients with PAD and ESRD.

Treatments of chronic fatigue syndrome and its debilitating comorbidities: a 12-year population-based study.

BACKGROUND: This study aims to provide 12-year nationwide epidemiology data to investigate the epidemiology and comorbidities of and therapeutic options for chronic fatigue syndrome (CFS) by analyzing the National Health Insurance Research Database. METHODS: 6306 patients identified as having CFS during the 2000-2012 period and 6306 controls (with similar distributions of age and sex) were analyzed. RESULT: The patients with CFS were predominantly female and aged 35-64 years in Taiwan and presented a higher proportion of depression, anxiety disorder, insomnia, Crohn's disease, ulcerative colitis, renal disease, type 2 diabetes, gout, dyslipidemia, rheumatoid arthritis, Sjogren syndrome, and herpes zoster. The use of selective serotonin receptor inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), Serotonin antagonist and reuptake inhibitors (SARIs), Tricyclic antidepressants (TCAs), benzodiazepine (BZD), Norepinephrine-dopamine reuptake inhibitors (NDRIs), muscle relaxants, analgesic drugs, psychotherapies, and exercise therapies was prescribed significantly more frequently in the CFS cohort than in the control group. CONCLUSION: This large national study shared the mainstream therapies of CFS in Taiwan, we noticed these treatments reported effective to relieve symptoms in previous studies. Furthermore, our findings indicate that clinicians should have a heightened awareness of the comorbidities of CFS, especially in psychiatric problems.

The impact of multidisciplinary pre-dialysis care on the outcomes of incident peritoneal dialysis patients.

BACKGROUND: This study aims to evaluate the impact of multidisciplinary pre-dialysis care (MDPC) on the risks of peritonitis, technique failure and mortality in peritoneal dialysis (PD) patients. METHODS: Incident end-stage kidney disease patients who received peritoneal dialysis (PD) for more than 90 days were recruited in this study from 1 January 1, 2007 to December 31, 2018. Patients were classified into two groups, the MDPC group and the control group, that received the usual care by nephrologists. Risks of the first episode of peritonitis, technique failure and mortality were compared between the two groups. RESULTS: There were 126 patients under the usual care and 546 patients under the MDPC. Patients in the MDPC group initiated dialysis earlier than those in the non-MDPC group. There was no significant difference between these two groups in time to the first episode of peritonitis. Compared to the non-MDPC group, the MDPC group was at similar risks of technique failure (adjusted HR = 0.85, 95% CI = 0.64-1.15) and mortality (adjusted HR = 0.66, 95% CI = 0.42-1.02). Among patients with diabetes, the risk of mortality was significantly reduced in the MDPC group with an adjusted HR of 0.45 (95% CI = 0.25-0.80). CONCLUSIONS: There was no significant difference in time to develop the first episode of peritonitis, and risks of technique failure and mortality between these two groups. Diabetic PD patients under MDPC had a lower risk of mortality than those under the usual care.

High-Intensity Post-Stroke Rehabilitation Is Associated with Lower Risk of Pressure Ulcer Development in Patients with Stroke: Real-World Evidence from a Nationwide, Population-Based Cohort Study.

Background and Objectives: Multiple factors are associated with pressure ulcer (PU) development, including limited mobility following stroke. We performed a nationwide cohort study to investigate the impact of rehabilitation intensity on the incidence of post-stroke PU. Materials and Methods: Data of patients diagnosed with stroke between 2000 and 2012 were collected from the 2000 Longitudinal Health Insurance Database (Taiwan). Based on the number of rehabilitation sessions attended within 90 days of discharge, the rehabilitation intensity was classified as low, medium, or high. After adjusting for sociodemographic factors and comorbidities, the Cox proportional hazards model evaluated the risk of PU development during the 12-year follow-up period. Kaplan−Meier curves were used to estimate the cumulative incidence of PUs. Results: Our study included 18,971 patients who had their first episode of stroke. Of these, 9829 (51.8%) underwent rehabilitation therapy after discharge. Female patients and patients with a National Institutes of Health Stroke Scale (NIHSS) score >13 points, who commenced high-intensity post-stroke rehabilitation after discharge had a significantly lower risk of PU development than those who underwent low-intensity post-stroke rehabilitation after discharge. Cumulative survival analysis showed a significantly lower cumulative incidence of PU during the 12-year follow-up period in the high-intensity rehabilitation group. Conclusion: Compared with low-intensity post-stroke rehabilitation, high-intensity post-stroke rehabilitation after discharge from hospital is associated with a lower risk of post-stroke PU development, especially in female stroke patients and patients with a NIHSS score >13 points. High-intensity rehabilitation is also associated with a significantly lower cumulative incidence of PU events during the 12-year follow-up period.

The Impact of Human Papillomavirus Infection on Skin Cancer: A Population-Based Cohort Study.

BACKGROUND: This study investigated the correlation between a history of human papillomavirus (HPV) infection and skin cancer risk. MATERIALS AND METHODS: The study cohort comprised 26,919 patients with newly diagnosed HPV infection between 2000 and 2012; with the use of computer-generated numbers, patients without previous HPV infection were randomly selected as the comparison cohort. The patients in the HPV infection cohort were matched to comparison individuals at a 1:4 ratio by demographic characteristics and comorbidities. All study individuals were followed up until they developed skin cancer, withdrew from the National Health Insurance program, were lost to follow-up, or until the end of 2013. The primary outcome was subsequent skin cancer development. Cox proportional hazards regression analysis was used to analyze the risk of skin cancer with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort. RESULTS: The adjusted HR of skin cancer for patients with HPV relative to controls was 2.45 after adjusting sex, age and comorbidities. (95% CI, 1.44-4.18, p < .01). The subgroup analysis indicated that a patient with HPV infection had a significantly greater risk of skin cancer if they were aged >40 years. Notably, a risk of skin cancer was found in the group diagnosed with HPV within the first 5 years after the index date (adjusted HR, 3.12; with 95% CI, 1.58-5.54). Sensitivity analysis by propensity score, matching with balanced sex, age, and comorbidities, showed consistent results. CONCLUSION: A history of HPV infection is associated with the development of subsequent skin cancer in Taiwanese subjects, and the risk wanes 5 years later. IMPLICATIONS FOR PRACTICE: In this Taiwan nationwide cohort study, there was a 2.45-fold increased risk of developing new-onset skin cancers for patients with incident human papillomavirus (HPV) infection, compared with the matched controls. Furthermore, the risk was noticeably significant among patients aged >40 years. A prominent risk of skin cancers was found in the group diagnosed with HPV within the first 5 years after the index date in this study. The results of this analysis may raise consensus on the effect of HPV infection on the risk of skin cancers. Clinicians are encouraged to implement prudently on the differential diagnosis of skin cancers and HPV prevention and treatment, especially in older patients.

Human papillomavirus symptomatic infection associated with increased risk of new-onset alopecia areata: A nationwide population-based cohort study.

BACKGROUND: We investigated the correlation between a history of human papillomavirus (HPV) infection and alopecia areata risk. METHODS: The study cohort comprised 30,001 patients with newly diagnosed HPV infection between 2000 and 2012; and with use of computer-generated randomly numbers, patients not had HPV infection were randomly selected as the comparison cohort. HPV infection cohort were matched to comparison individuals at a 1:1 ratio by age, gender and index year. All study individuals were followed up until they developed alopecia areata, withdraw from the insurance program, lost to follow-up, or until the end of 2013. Cox proportional hazards regression analysis was used to analyze the risk of alopecia areata with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort. RESULTS: The adjusted hazard ratio (aHR) of alopecia areata for HPV patients relative to controls was 2.55 (95% C.I. = 1.88-3.47) after adjusting sex, age and comorbidities. Subgroup analysis indicated that patients with HPV infections had a significantly greater risk of alopecia areata for both genders, all age subgroups, and those with mental disorder diseases. CONCLUSIONS: A history of HPV infection is associated with the development of subsequent alopecia areata in Taiwanese subjects.

Tonsillectomy and the subsequent risk of psoriasis: A nationwide population-based cohort study.

BACKGROUND: Tonsillectomy has been suggested as an intervention to resolve psoriasis. OBJECTIVE: This study aimed to investigate the subsequent risk of psoriasis in patients who received tonsillectomy. METHODS: We used data from the Taiwan National Health Insurance Research Database. The tonsillectomy group (case group) and the tonsillectomy-free group (comparison group) were matched at a ratio of 1:4 by demographic data, comorbidities, medical confounders, and the index date. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 2021 patients as the case group and matched 8084 individuals as the comparison group. The adjusted HR (aHR) of psoriasis was 0.43 (95% CI, 0.22-0.87; P < .05). The study population is composed of a mainly male (65%) and young population (mostly younger than 50 years). Notably, patients with rheumatoid arthritis increased the risk of psoriasis (aHR, 3.97; 95% CI, 1.17-13.48; P < .05). In our stratification analysis, the risk of psoriasis decreased in almost all subgroups. LIMITATION: Our database did not include information on genome and the subtypes of psoriasis. CONCLUSION: Our study showed a decreased risk of psoriasis in the tonsillectomy group after adjustment for baseline characteristics, comorbidities, and medical confounders compared with the reference group.

Risk of non-typhoidal Salmonella infection in patients with cholecystectomy: Results from a nationwide matched cohort study in Taiwan.

BACKGROUND: The current study was designed to investigate the association between cholecystectomy and the risk of non-typhoidal Salmonella (NTS) infection. METHODS: We obtained claims-based data from the Taiwan National Health Insurance Research Database (NHIRD) to perform a nationwide cohort study. A propensity score (PS)-matching analysis was performed with a ratio of 1:2 in the cholecystectomy cohort and cholecystectomy-free group to reduce selection bias. Both groups were followed until NTS diagnosis, a dropout from the insurance programme or the end of 2013. Cox proportional hazard regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of NTS infection between the cholecystectomy and cholecystectomy-free groups. RESULTS: Our study enrolled 197 444 patients who had undergone cholecystectomy and 394 888 patients who did not receive cholecystectomy. The adjusted HR (aHR) of NTS infection was 1.34 (95% CI, 1.13-1.58; P < .001) for the cholecystectomy group after adjusting for demographical characteristics and relevant comorbidities. The study population is predominantly female patients (55%) and older (58% older than 50 years). The subgroup analysis revealed that both sexes and notably, patients aged >50, who underwent cholecystectomy had a higher risk of NTS infection than the matched controls. Follow-up of patients who underwent cholecystectomy showed that they had a significantly higher risk of NTS infection for more than 6 months after the procedure. CONCLUSIONS: Our study showed that cholecystectomy might be an independent risk factor for subsequent NTS infection.

Incidence of dementia after dengue fever: Results of a longitudinal population-based study.

OBJECTIVE: To investigate the epidemiological relationship between dengue fever and the subsequent development of dementia. METHODS: Using nationwide Taiwan registries from the National Health Insurance Research (NHIRD), we identified adults aged over 40 years who received a dengue fever diagnosis from 1 January 2000 to 31 December 2012 and who did not have a history of dementia. We used a propensity score match (PSM) to balance the baseline characteristics between groups. All eligible adults were sorted into either the dengue group or non-dengue group at a ratio of 1:4, matching by age, sex, index years, income level, and relevant comorbidities. Using Cox regression with proportional hazards models, we estimated the risk of dementia. The study period started from 1 January 2000 to 31 December 2013. We conducted sensitivity analyses to cross-validate study results. RESULTS: With a median of 8.01 years of follow-up, patients in the dengue group were more at risk of developing dementia than the non-dengue group. The estimated cumulative incidence of dementia was 7.21% in the dengue group and 4.03% in the non-dengue group (adjusted hazard ratio (aHR), 1.71; 95% CI, 1.03 to 2.83). Sensitivity analyses yielded consistent findings. We excluded any stroke cases before the end of the study, and subgroup analysis by follow-up time showed that the dengue group has a significantly higher risk of new-onset dementia >6 years after the index date (aHR 3.24; 95% CI, 1.42 to 7.37). The P value for interaction was significant (<.0001). CONCLUSIONS: This study demonstrated a significantly higher risk of dementia in patients with dengue fever in Taiwan than in those without dengue fever.

Cost-effectiveness and drug wastage of bevacizumab biosimilar with or without chemotherapy for platinum-resistant recurrent ovarian cancer.

INTRODUCTION: The cost-effectiveness of adding bevacizumab biosimilar with or without chemotherapy (CT) and drug wastage in treating platinum-resistant recurrent ovarian cancer (PRrOC) was assessed. METHODS: A three-state partitioned-survival model to compare the clinical and economic outcomes in the treatment of patients with PRrOC from a Taiwan healthcare prospective, extrapolated to two years based on data obtained from the JGOG3023 clinical trial. The primary outcomes of the model were incremental cost-effectiveness ratios (ICERs). RESULTS: In the base-case scenario, using vials of bevacizumab biosimilar (Bevbiol) plus chemotherapy, the ICER was (new Taiwan dollar) NT$ 4,555,878 per QALY gained. The incremental cost savings of an incremental 2.02 QALYs were NT$ 1,605,828 if weight-based Bevbiol plus chemotherapy were used, but the ICER remained high at the willingness-to-pay (WTP) threshold. If the cost of Bevbiol were reduced to 50% per vial, adding it to CT would be cost-effective at an acceptable WTP threshold of NTD 2,994,200, with an ICER of NT$ 2,975,484. CONCLUSIONS: Bevacizumab biosimilars in mg/kg dosage form with chemotherapy are still not cost-effective in Taiwan, but using weight-based dosing will reduce drug waste and save treatment costs.

Chinese herbal medicine decreases incidence of hepatocellular carcinoma in diabetes mellitus patients with regular insulin management.

BACKGROUND: Type 2 diabetes mellitus (DM) is an independent risk factor for hepatocellular carcinoma (HCC), while insulin is a potent mitogen. Identifying a new therapeutic modality for preventing insulin users from developing HCC is a critical goal for researchers. AIM: To investigate whether regular herbal medicine use can decrease HCC risk in DM patients with regular insulin control. METHODS: We used data acquired from the Taiwanese National Health Insurance research database between 2000 and 2017. We identified patients with DM who were prescribed insulin for > 3 months. The herb user group was further defined as patients prescribed herbal medication for DM for > 3 months per annum during follow-up. We matched the herb users to nonusers at a 1:3 ratio according to age, sex, comorbidities and index year by propensity score matching. We analyzed HCC incidence, HCC survival rates, and the herbal prescriptions involved. RESULTS: We initially enrolled 657144 DM patients with regular insulin use from 2000 to 2017. Among these, 46849 patients had used a herbal treatment for DM, and 140547 patients were included as the matched control group. The baseline variables were similar between the herb users and nonusers. DM patients with regular herb use had a 12% decreased risk of HCC compared with the control group [adjusted hazard ratio (aHR) = 0.88, 95%CI = 0.80-0.97]. The cumulative incidence of HCC in the herb users was significantly lower than that of the nonusers. Patients with a herb use of > 5 years cumulatively exhibited a protective effect against development of HCC (aHR = 0.82, P < 0.05). Of patients who developed HCC, herb users exhibited a longer survival time than nonusers (aHR = 0.78, P = 0.0001). Additionally, we report the top 10 herbs and formulas in prescriptions and summarize the potential pharmacological effects of the constituents. Our analysis indicated that Astragalus propinquus (Huang Qi) plus Salvia miltiorrhiza Bunge (Dan Shen), and Astragalus propinquus (Huang Qi) plus Trichosanthes kirilowii Maxim. (Tian Hua Fen) were the most frequent combination of single herbs. Meanwhile, Ji Sheng Shen Qi Wan plus Dan Shen was the most frequent combination of herbs and formulas. CONCLUSION: This large-scale retrospective cohort study reveals that herbal medicine may decrease HCC risk by 12% in DM patients with regular insulin use.

Association between colchicine use and the risk of dementia among patients with gout: A nationwide retrospective cohort study.

BACKGROUND: Recent findings suggest a link between gout and the development of dementia. Early treatment with colchicine is recommended as a first-line therapy for gout flares. Animal studies demonstrate that colchicine could induce cognitive impairment. This cohort study aimed to investigate the association between colchicine use and the risk of developing dementia. METHODS: In this nationwide cohort study, we performed comparative analysis on 6147 patients ≥40 years, with gout and colchicine new users against 6147 controls to assess subsequent dementia risk. The colchicine group and the control group (urate lowering therapy group) were matched on the bases of age, sex, index year, and comorbidities. All participants were followed for up to 14 years for a diagnosis of dementia considering medical records were retrospectively checked over this period. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Sensitivity analyses were performed to validate our findings. RESULTS: The adjusted hazard ratio (aHR) of dementia for colchicine users was 1.45 (95% CI = 1.05, 1.99) relative to comparison group after adjusting for sex, age, and comorbidities. Sensitivity analysis aiming to minimize underdiagnosed occult dementia at the time of index year yielded consistent positive association. In higher accumulative dose colchicine group (cumulative defined daily dose [cDDD] >30), the aHR of dementia risk for colchicine users was 1.42 (95% CI = 1.03, 1.97) compared with nonusers. For those duration of colchicine use >30 days, the aHR was 1.53 (95% CI = 1.01-2.32) compared to the nonuser group. CONCLUSIONS: A significant risk of dementia was observed in this study in patients with gout using colchicine at higher cDDD and for a longer period. Further research is needed to elucidate the relationship between colchicine, gout, and dementia.