Association between thiazolidinedione use and rheumatoid arthritis risk in patients with type II diabetes, a population-based, case-control study.

AIM: A previous study revealed that PPARγ agonists have anti-inflammatory effects in rheumatoid arthritis (RA). Furthermore, some studies have shown that type 2 diabetes mellitus (T2DM) may elicit the development of RA. In this study, we aimed to investigate whether the use of thiazolidinediones (TZDs) is associated with a lower risk of developing RA in patients with T2DM. METHODS: Based on the Taiwan National Health Insurance Research Database, we conducted a nationwide case-control study. The selected cases were patients with T2DM who were diagnosed with RA between 2000 and 2013. The controls were retrieved at a ratio of 1:4 by propensity score matching. Logistic regression was conducted to evaluate whether TZD use lowers the risk of RA in patients with T2DM. The dose-response effect was examined according to the total TZD dose, within 2 years before the index date (the first diagnosis date of RA), and TZD doses were divided into four groups by cumulative Defined Daily Dose (cDDD): <30, 31-90, 91-365, and >365 cDDDs. RESULTS: A total of 3605 cases and 14 420 controls were included in this study. After adjusting for age, sex, baseline comorbidities, the results demonstrated that TZD use did not significantly reduce the risk of RA in patients with T2DM (adjusted OR = 0.91, 95% CI 0.81-1.02). In the subgroup analysis by total TZD exposure dose within 2 years, 91-365 cDDDs of TZD had a lower risk of RA development, aOR = 0.87 (95% CI 0.71-1.06) and >365 cDDDs of TZD, aOR = 0.85 (95% CI 0.73-1.01). In the trend test, P was <.05. CONCLUSIONS: TZD use might reduce the risk of RA in patients with T2DM, but it was non-statistically significant. Further research is necessary to assess this association.

Neurotransmitter-Responsive Nanosensors for T2-Weighted Magnetic Resonance Imaging.

Neurotransmitter-sensitive contrast agents for magnetic resonance imaging (MRI) have recently been used for mapping signaling dynamics in live animal brains, but paramagnetic sensors for T1-weighted MRI are usually effective only at micromolar concentrations that themselves perturb neurochemistry. Here we present an alternative molecular architecture for detecting neurotransmitters, using superparamagnetic iron oxide nanoparticles conjugated to tethered neurotransmitter analogs and engineered neurotransmitter binding proteins. Interactions between the nanoparticle conjugates result in clustering that is reversibly disrupted in the presence of neurotransmitter analytes, thus altering T2-weighted MRI signals. We demonstrate this principle using tethered dopamine and serotonin analogs, together with proteins selected for their ability to competitively bind either the analogs or the neurotransmitters themselves. Corresponding sensors for dopamine and serotonin exhibit target-selective relaxivity changes of up to 20%, while also operating below endogenous neurotransmitter concentrations. Semisynthetic magnetic particle sensors thus represent a promising path for minimally perturbative studies of neurochemical analytes.

Delayed time from first medical visit to diagnosis for breast cancer patients in Taiwan.

BACKGROUND/PURPOSE: Delay in diagnosis may affect the survival of breast cancer patients. The purpose of this study was to investigate delayed diagnosis for breast cancer patients in Taiwan. METHODS: This study was conducted via one-to-one interviews with structured questionnaires in hospital outpatient visit. Included were 600 breast cancer patients seeking medical care in two medical centers in central Taiwan. RESULTS: Average delay in breast cancer diagnosis was 27.8 days. Service level of the patients' first visit and number of hospitals patients visited before obtaining a correct diagnosis were significantly associated with delay in diagnosis. Logistic regression analysis found that patients who had visited two, and three or more hospitals before getting a correct diagnosis had longer delays in diagnosis than patients who had visited one hospital (odds ratio = 2.23 and 9.26, 95% confidence interval 1.37-3.63 and 95% CI:3.87-22.15, respectively). CONCLUSION: Results of this study are anticipated to serve as a reference for the government and medical institutions to develop policies to reduce the number of hospitals visited before diagnosis for breast cancer patients, and ultimately to achieve the goal of early detection and treatment.

Endoscopic Versus Microscopic Type I Tympanoplasty: An Updated Systematic Review and Meta-analysis.

OBJECTIVE: Our objective was to perform a systematic review and meta-analysis comparing the clinical outcomes after endoscopic and microscopic type I tympanoplasty. STUDY DESIGN: Randomized controlled trials, two-arm prospective studies, and retrospective studies were included. SETTING: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until March 1, 2022 using the combinations of search terms: "endoscopic," "microscopic," and "tympanoplasty." METHODS: Two independent reviewers utilized the abovementioned search strategy to identify eligible studies. If any uncertainty existed regarding eligibility, a third reviewer was consulted. Primary outcome measures were graft success rate, air-bone gap (ABG) improvement, and operative time. Secondary outcomes were the rate of need for canalplasty, the proportion of self-rated excellent cosmetic results, and pain visual analog scale (VAS). RESULTS: Forty-three studies enrolled a total of 3712 patients who were undergoing type I tympanoplasty and were finally included. The pooled result showed endoscopic approach was significantly associated with shorter operative time (difference in means: -20.021, 95% confidence interval [CI]: -31.431 to -8.611), less need for canalplasty (odds ratio [OR]: 0.065, 95% CI: 0.026-0.164), more self-rated excellent cosmetic results (OR: 87.323, 95% CI: 26.750-285.063), and lower pain VAS (difference in means: -2.513, 95% CI: -4.737 to -0.228). No significant differences in graft success rate or ABG were observed between the two procedures. CONCLUSION: Endoscopic type I tympanoplasty provides a similar graft success rate, improvement in ABG, and reperforation rate to microscopic tympanoplasty with a shorter operative time, better self-rated cosmetic results, and less pain. Unless contraindicated, the endoscopic approach should be the procedure of choice in type I tympanoplasty.

Utilizing the National Early Warning Score 2 (NEWS2) to confirm the impact of emergency department management in sepsis patients: a cohort study from taiwan 1998-2020.

BACKGROUND: Most sepsis patients could potentially experience advantageous outcomes from targeted medical intervention, such as fluid resuscitation, antibiotic administration, respiratory support, and nursing care, promptly upon arrival at the emergency department (ED). Several scoring systems have been devised to predict hospital outcomes in sepsis patients, including the Sequential Organ Failure Assessment (SOFA) score. In contrast to prior research, our study introduces the novel approach of utilizing the National Early Warning Score 2 (NEWS2) as a means of assessing treatment efficacy and disease progression during an ED stay for sepsis. OBJECTIVES: To evaluate the sepsis prognosis and effectiveness of treatment administered during ED admission in reducing overall hospital mortality rates resulting from sepsis, as measured by the NEWS2. METHODS: The present investigation was conducted at a medical center from 1997 to 2020. The NEWS2 was calculated for patients with sepsis who were admitted to the ED in a consecutive manner. The computation was based on the initial and final parameters that were obtained during their stay in the ED. The alteration in the NEWS2 from the initial to the final measurements was utilized to evaluate the benefit of ED management to the hospital outcome of sepsis. Univariate and multivariate Cox regression analyses were performed, encompassing all clinically significant variables, to evaluate the adjusted hazard ratio (HR) for total hospital mortality in sepsis patients with reduced severity, measured by NEWS2 score difference, with a 95% confidence interval (adjusted HR with 95% CI). The study employed Kaplan-Meier analysis with a Log-rank test to assess variations in overall hospital mortality rates between two groups: the "improvement (reduced NEWS2)" and "non-improvement (no change or increased NEWS2)" groups. RESULTS: The present investigation recruited a cohort of 11,011 individuals who experienced the first occurrence of sepsis as the primary diagnosis while hospitalized. The mean age of the improvement and non-improvement groups were 69.57 (± 16.19) and 68.82 (± 16.63) years, respectively. The mean SOFA score of the improvement and non-improvement groups were of no remarkable difference, 9.7 (± 3.39) and 9.8 (± 3.38) years, respectively. The total hospital mortality for sepsis was 42.92% (4,727/11,011). Following treatment by the prevailing guidelines at that time, a total of 5,598 out of 11,011 patients (50.88%) demonstrated improvement in the NEWS2, while the remaining 5,403 patients (49.12%) did not. The improvement group had a total hospital mortality rate of 38.51%, while the non-improvement group had a higher rate of 47.58%. The non-improvement group exhibited a lower prevalence of comorbidities such as congestive heart failure, cerebral vascular disease, and renal disease. The non-improvement group exhibited a lower Charlson comorbidity index score [4.73 (± 3.34)] compared to the improvement group [4.82 (± 3.38)] The group that underwent improvement exhibited a comparatively lower incidence of septic shock development in contrast to the non-improvement group (51.13% versus 54.34%, P < 0.001). The improvement group saw a total of 2,150 patients, which represents 38.41% of the overall sample size of 5,598, transition from the higher-risk to the medium-risk category. A total of 2,741 individuals, representing 48.96% of the sample size of 5,598 patients, exhibited a reduction in severity score only without risk category alteration. Out of the 5,403 patients (the non-improvement group) included in the study, 78.57% (4,245) demonstrated no alteration in the NEWS2. Conversely, 21.43% (1,158) of patients exhibited an escalation in severity score. The Cox regression analysis demonstrated that the implementation of interventions aimed at reducing the NEWS2 during a patient's stay in the ED had a significant positive impact on the outcome, as evidenced by the adjusted HRs of 0.889 (95% CI = 0.808, 0.978) and 0.891 (95% CI = 0.810, 0.981), respectively. The results obtained from the Kaplan-Meier analysis indicated that the survival rate of the improvement group was significantly higher than that of the non-improvement group (P < 0.001) in the hospitalization period. CONCLUSION: The present study demonstrated that 50.88% of sepsis patients obtained improvement in ED, ascertained by means of the NEWS2 scoring system. The practical dynamics of NEWS2 could be utilized to depict such intricacies clearly. The findings also literally supported the importance of ED management in the comprehensive course of sepsis treatment in reducing the total hospital mortality rate.

Robust measurement of membrane bending moduli using light sheet fluorescence imaging of vesicle fluctuations.

The mechanical rigidity of lipid membranes is a key determinant of the energetics of cellular membrane deformation. Measurements of membrane bending moduli remain rare, however, and show a large variance, a situation that can be addressed by the development of improved techniques and by comparisons between disparate techniques applied to the same systems. We introduce here the use of selective plane illumination microscopy (SPIM, also known as light sheet fluorescence microscopy) to image thermal fluctuations of giant vesicles. The optical sectioning of SPIM enables high-speed fluorescence imaging of freely suspended vesicles and quantification of edge localization precision, yielding robust fluctuation spectra and rigidity estimates. For both lipid-only membranes and membranes bound by the intracellular trafficking protein Sar1p, which lowers membrane rigidity in a concentration-dependent manner, we show that the resulting bending modulus values are in close agreement with those derived from an independent assay based on membrane tether pulling. We also show that the fluctuation spectra of vesicles bound by the mammalian Sar1A protein, which stiffens membranes at high concentrations, are not well fit by a model of homogeneous quasi-spherical vesicles, suggesting that SPIM-based analysis can offer insights into spatially inhomogeneous properties induced by protein assemblies.

Bridging geographical disparities across 368 townships with healthcare system and socioeconomic factors in Taiwan.

A universal health insurance program such as the National Health Insurance in Taiwan offers a wide coverage and increased access to healthcare services. Despite its ongoing efforts to enhance healthcare accessibility, differences in health for people living in urban and resource-deprived areas remain substantial. To investigate the longitudinal impact of the healthcare system and other potential structural drivers such as education and economic development on geographical disparities in health, we designed a panel study with longitudinal open secondary data, covering all 368 townships in Taiwan between 2013 and 2017. Our findings indicated higher mortality rates in the mountainous and rural areas near the east and south regions of the island in both years. Multivariate analyses showed an increase in the density of primary care physicians (PCP) was associated with lower all-cause mortality (ß = - 0.72, p < 0.0001) and cardiovascular disease mortality (ß = - 0.41, p < 0.0001). Effect of PCP is evident, but merely focusing on access to healthcare is still not enough. Additional measures are warranted to address the health disparities existing between urban and underprivileged areas.

Effect of end-stage kidney disease on the return of spontaneous circulation in Taiwanese adults with out-of-hospital cardiac arrest.

Rescuing patients with out-of-hospital cardiac arrest (OHCA), especially those with end-stage kidney disease (ESKD), is challenging. This study hypothesizes that OHCA patients with ESKD undergoing maintenance hemodialysis have (1) higher rates of return of spontaneous circulation (ROSC) during cardio-pulmonary resuscitation (CPR) and (2) lower rates of hyperkalemia and less severe acidosis than those without ESKD. OHCA patients who received CPR between 2011 and 2020 were dichotomized into ESKD and non-ESKD groups. The association of ESKD with "any" and "sustained" ROSC were examined using logistic regression analysis. Furthermore, the effect of ESKD on hospital outcomes for OHCA patients who survived to admission was evaluated using Kaplan-Meier analysis. ESKD patients without "any" ROSC displayed lower potassium and higher pH levels than non-ESKD patients. ESKD was positively associated with "any" ROSC (adjusted-OR: 4.82, 95% CI 2.70-5.16, P < 0.01) and "sustained" ROSC (adjusted-OR: 9.45, 95% CI 3.83-24.13, P < 0.01). Kaplan-Meier analysis demonstrated ESKD patients had a non-inferior hospital survival than non-ESKD patients. OHCA patients with ESKD had lower serum potassium level and less severe acidosis compared to the general population in Taiwan; therefore, should not be treated under the stereotypical assumption that hyperkalemia and acidosis always occur.

Modulation of membrane rigidity by the human vesicle trafficking proteins Sar1A and Sar1B.

The sculpting of membranes into highly curved vesicles is central to intracellular cargo trafficking, yet the mechanical activities of trafficking proteins remain poorly understood. Using an optical trap based assay that measures in vitro membrane response to imposed deformations, we examined the behavior of the two human paralogs of Sar1, a key component of the COPII family of vesicle coat proteins. Like their yeast counterpart, the human Sar1 proteins can lower the mechanical rigidity of the membranes to which they bind. Unlike the yeast Sar1, the rigidity is not a monotonically decreasing function of concentration. At high concentrations, we find increased bending rigidity and decreased protein mobility. These features imply a model in which protein clustering governs membrane mechanical properties.

Referral-free health care and delay in diagnosis for lung cancer patients.

OBJECTIVE: Lung cancer is not only one of the most prevalent cancers but is also a lethal disease with a very low 5-year survival rate. Delay in diagnosis further reduces the chance of early treatment and worsens patients' survival. The purpose of this study was to understand the delay in the diagnosis of lung cancer under the healthcare system in Taiwan, and to identify the factors associated with it. METHODS: A total of 840 patients diagnosed with lung cancer who had completed or were undergoing cancer treatments were recruited from a medical center in central Taiwan from July 2007 to January 2011. Structured questionnaires were administered regarding demographic characteristics, factors associated with their time to diagnosis and the length of delay in days. RESULTS: Mean age was 62.68 years with 52.16 days to diagnosis on average. Number of hospital visits before confirmation of diagnosis differed significantly with the level of healthcare institution initially visited (P < 0.001). Compared with patients who had three or more hospital visits, patients who only visited two and one hospital(s) had a significant 34.91-day (95% confidence interval: 16.29-53.53) and 42.25-day (95% confidence interval: 20.76-63.76) reduction in their time to diagnosis (P < 0.001). CONCLUSIONS: As the number of hospital visits increased, the delay in diagnosis also increased. It is vital to shorten the time to diagnosis for lung cancer patients by limiting the number of medical visits and educating the public to restrict excessive use of medical resources and strengthen their trust in medical professionals.

Association between medication adherence and disease outcomes in patients with hepatitis B-related cirrhosis: a population-based case-control study.

OBJECTIVE: To evaluate medication adherence among patients with hepatitis B-related cirrhosis who developed decompensation and mortality, and to examine the association between medication adherence and patients' disease outcomes. DESIGN: In this retrospective case-control study, patients aged over 20 years old and diagnosed with both chronic hepatitis B and cirrhosis from 2007 to 2016 are identified using a population-based medical claims database. Two prognosis endpoints (decompensation and mortality) are used, respectively, to classify subjects into two different case-control sets. Study groups are propensity-score matched. Medication possession ratio (MPR) is used as a measure of treatment adherence for oral antiviral drugs, and conditional logistic regression models are used to estimate the odds of decompensation and mortality after accounting for MPR and other covariates. RESULTS: Between decompensated and compensated patients, longer term treatment adherence is seen higher in the compensated group versus the decompensated group: 1-year MPR (0.65±0.43 vs 0.57±0.53) and 6-month MPR (0.79±0.52 vs 0.76±0.79). On the contrary, 3-month adherence is higher in the decompensated group (1.00±1.15 vs 0.96±0.79). For patients with and without mortality, drug adherence is ubiquitously higher in the alive group regardless of follow-up length: 1-year MPR (0.62±0.44 vs 0.50±0.51), 6-month MPR (0.78±0.62 vs 0.69±0.72) and 3-month MPR (0.97±0.91 vs 0.96±1.12). After accounting for confounding variables, we find that the likelihood of complicated cirrhosis is significantly lower in more adherent patients and the benefit increases with more persistent adherence (log 1-year MPR OR: 0.75, 95% CI: 0.73 to 0.77). Similar results are observed for the adjusted likelihood of mortality (log 1-year MPR OR: 0.70, 95% CI: 0.68 to 0.72). CONCLUSIONS: Long-term patient adherence to oral antiviral therapy remains inadequate in patients with hepatitis B virus-related cirrhosis. Their adherence to oral antiviral therapy appears to be inversely associated with decompensation and mortality.

Universal masking to prevent SARS-CoV-2 transmission from Taiwan's practices.

In the fight against the COVID-19 pandemic, Taiwan, with its universal masking policy, slowed down the spread of cases and flattened its epidemic curve without enforcing lockdown or mass quarantine in 2020. This study identifies the distinguishing features of Taiwan's universal masking policy practice, such as priority, continuous improvement, multi-stakeholder partnership, transparency and accountability, and altruism and social solidarity. By confronting uncertainty through the COVID-19 crisis, this study suggests that face masking, rather than being just a physical barrier of non-pharmacological intervention, can be adopted as an interactive policy platform to empower the public for stimulating cross-sector collaboration towards social innovation and creating spillover effects, such as acts of public trust, altruism, and solidarity.

Long-Term Exposures to Air Pollutants and Risk of Peripheral Arterial Occlusive Disease: A Nationwide Cohort Study in Taiwan.

Air pollution is one of the most alarming environmental issues which causes multiple health hazards. An association between air pollution and cardiovascular diseases has been established through many prior studies. In this study, we aimed to evaluate the risk of long-term exposure to air pollution (PM2.5, CO, and NO2) and its association with the risk of developing peripheral arterial occlusive disease (PAOD). PAOD is a condition involving impairment of perfusion of blood in the distal parts of the aorta due to narrowing of the arteries (arterial stenosis) and has been reported as a risk factor for developing cardiovascular diseases. Furthermore, the risk of PAOD increases with age, and hence is a serious public health issue and a cause for concern, especially for an aging society such as Taiwan. Two national-scale databases from Taiwan, the national health insurance database (NHIRD) and the Taiwan air quality-monitoring database (TAQMD), were linked to conduct this cohort study between 2003 and 2013. Cox proportional hazards regression with time-dependent modeling was used to evaluate the hazard ratio (HR) for PAOD with respect to daily exposure to air pollutants. The concentrations of each of the pollutants of interest (PM2.5, NO2, and CO) were categorized into four categories according to the daily average concentration of air pollutants for every quarter of the year, Q1 to Q4 (Q4 = highest). The cumulative incidence of PAOD was examined by Kaplan-Meier analysis with two-tailed log-rank test. A total of 1,598 PAOD cases were identified during the 10-year follow-up period, along with 98,540 non-PAOD controls. In the multivariate analysis, after adjusting for age, gender, urbanization level, residential area, baseline comorbidities, and medications, the adjusted HRs were PM2.5 = 1.14 (95% CI 1.13-1.16), NO2 = 1.03 (95% CI 1.02-1.04), and CO = 2.35 (95% CI 1.95-2.84). Kaplan-Meier analysis showed that CO (P < 0.0001) and PM2.5 (P < 0.0001) concentrations were strongly and positively associated with the cumulative incidence of PAOD during the follow-up period. Findings from this study established that prolonged exposure to air pollutants CO and PM2.5 are significant factors that, among other well-known causes, may also play a potential role in PAOD pathogenesis.

Risk for hypoglycemic emergency with levofloxacin use, a population-based propensity score matched nested case-control study.

Potential association between oral levofloxacin use and hypoglycemic emergency (HE) have been established. However, a large epidemiological study is required to verify this observation. This study aimed to determine if use of oral levofloxacin increased the risk of HE. The nationwide database between 1999 and 2013, including 1.6 million patients with type 2 diabetes (T2D), was used to conduct a nested case-control study. Cases and controls comprised of patients with and without HE, respectively. To avoid indication bias the control subjects were chosen through propensity score matching with cases in a 10-fold ratio. T2D severity was classified based on the adjusted diabetic complication severity index score. 26,695 and 266,950 matched patients with T2D, were finally used as cases and controls, respectively, for the analysis. Multivariate logistic regression analysis showed that antibiotic use was associated with an increased risk for HE (adjusted odds ratio (aOR) = 6.08, 95% confidence interval (95% CI): 5.79-6.38). When compared with antibiotic non-users, those who used fluoroquinolones and sulfonamides displayed the highest (aOR = 12.05, 95% CI: 10.66-13.61) and second highest (aOR = 7.20, 95% CI: 6.29-8.24) risks of HE, respectively. The associated risk for HE was significantly higher with levofloxacin than that with cephalosporins (aOR = 5.13, 95% CI: 2.28-11.52) and penicillin (aOR = 9.40, 95% CI: 2.25-39.24). In the joint effect analyses, the risk for HE increased with the combination of levofloxacin with insulin (aOR = 8.42, 95% CI: 1.91-37.00) or sulfonylurea (aOR = 3.56, 95% CI: 1.12-11.33). Use of oral levofloxacin, compared to that of other antibiotics, was found to be significantly associated with HE in T2D patients. Clinicians should exercise caution while prescribing levofloxacin, especially when combined with insulin or sulfonylurea.

End-Stage Renal Disease Patients Undergoing Hemodialysis Have Higher Possibility of Return of Spontaneous Circulation during Out-of-Hospital Cardiac Arrest and Non-Inferior Short-Term Survival.

End-stage renal disease (ESRD) patients on long-term hemodialysis (HD) have an elevated risk of sudden cardiac death. This study hypothesizes, for the first time, that these patients have a higher odds of return of spontaneous circulation (ROSC) and subsequent better hospital-outcomes, post out-of-hospital cardiac arrest (OHCA), as opposed to non-ESRD patients. A national database from Taiwan was utilized, in which 101,876 ESRD patients undergoing HD and propensity score-matched non-ESRD patients were used to conduct two analyses: (i) Cox-proportional-hazards-regression for OHCA incidence and (ii) logistic-regression analysis of attaining ROSC after OHCA, both for ESRD patients in comparison to non-ESRD patients. Kaplan-Meier analyses were conducted to determine the difference of survival rates after ROSC between the two cohorts. ESRD patients were found to be at a higher risk of OHCA (adjusted-HR = 2.11, 95% CI: (1.89−2.36), p < 0.001); however, they were at higher odds of attaining ROSC (adjusted-OR = 2.47, 95% CI: 1.90−3.21, p < 0.001), as opposed to non-ESRDs. Further, Kaplan-Meier analysis demonstrated ESRD patients with a better 30-day hospital survival rate than non-ESRD patients. Although ESRD patients had a higher risk of OHCA, they demonstrated higher possibility of ROSC and a better short-term hospital outcome than non-ESRDs. Chronic toxin tolerance and the training of vascular-compliance during regular HD may be possible explanations for better outcomes in ESRD patients.

Type 2 Diabetic Sepsis Patients Have a Lower Mortality Rate in Pioglitazone Use: A Nationwide 15-Year Propensity Score Matching Observational Study in Taiwan.

BACKGROUND: Pioglitazone use via the PPARγ agonist in sepsis patients is inconclusive. It was based on a great number of animal studies. However, except for information from animal studies, there are merely any data of human studies for reference. METHODS: This study was conducted by a unique database including 1.6 million diabetic patients. From 1999 to 2013, a total of 145,327 type 2 diabetic patients, first admitted for sepsis, were enrolled. Propensity score matching was conducted in a 1 : 5 ratio between pioglitazone users and nonusers. Multivariate logistic regression was conducted to evaluate the adjusted odds ratios (aORs) of hospital mortality in pioglitazone users. Further stratification analysis was done and Kaplan-Meier plot was used. RESULTS: A total of 9,310 sepsis pioglitazone users (defined as "ever" use of pioglitazone in any dose within 3 months prior to the first admission for sepsis) and 46,550 matched nonusers were retrieved, respectively. In the multivariate logistic regression model, the cohort of pioglitazone users (9,310) had a decreased aOR of 0.95 (95% CI, 0.89-1.02) of sepsis mortality. Further stratification analysis demonstrated that "chronic pioglitazone users" (defined as "at least" 4-week drug use within 3 months) (3,399) were more associated with significant aOR of 0.80 (95% CI, 0.72-0.89) in reducing sepsis mortality. CONCLUSIONS: This first human cohort study demonstrated the potential protective effect of chronic pioglitazone use in type 2 diabetic sepsis patients.

Mortality Risk and Decompensation in Hospitalized Patients with Non-Alcoholic Liver Cirrhosis: Implications for Disease Management.

Here we aimed to assess the mortality risk and distribution of deaths from different complications and etiologies for non-alcoholic liver cirrhosis (NALC) adult inpatients and compare them with that of the general hospitalized adult population. Hospitalized patients with a primary diagnosis of NALC and aged between 30 and 80 years of age from 1999 to 2010 were identified using a population-based administrative claims database in Taiwan. They were matched with a general, non-NALC population of hospitalized patients. Causes of death considered were variceal hemorrhage, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatocellular carcinoma, jaundice, and hepatorenal syndrome. A total of 109,128 NALC inpatients were included and then matched with 109,128 inpatients without NALC. Overall mortality rates were 21.2 (95% CI: 21.0-21.4) and 6.27 (95% CI: 6.17-6.37) per 100 person-years, respectively. Among complications that caused death in NALC patients, variceal hemorrhage was the most common (23.7%, 11.9 per 100 person-years), followed by ascites (20.9%, 10.4 per 100 person-years) and encephalopathy (18.4%, 9.21 per 100 person-years). Among all etiologies, mortality rates were highest for NALC patients with HBV infection (43.7%, 21.8 per 100 person-years), followed by HBV-HCV coinfection (41.8%, 20.9 per 100 person-years), HCV infection (41.2%, 20.6 per 100 person-years), and NAFLD (35.9%, 17.9 per 100 person-years). In this study, we demonstrated that mortality risks in NALC patients may differ with their etiology and their subsequent complications. Patients' care plans, thus, should be formulated accordingly.

Occurrence and Impact of Gastrointestinal Bleeding and Major Adverse Cardiovascular Events during Sepsis: A 15-Year Observational Study.

OBJECTIVE: Sepsis patients are at risk of gastrointestinal bleeding (GIB) and major adverse cardiovascular events (MACEs), but few data are available on the occurrence of GIB and MACEs and their impact on sepsis outcomes. METHODS: The medical claims records of 220,082 patients admitted for sepsis between 1999 and 2013 were retrieved from the nationwide database. The adjusted odds ratios (aORs) of composite outcomes including the hospital mortality, intensive care unit (ICU) admission, and mechanical ventilation (MV) in patients with a MACE or GIB were estimated by multivariate logistic regression and joint effect analyses. RESULTS: The enrollees were 70.15 ± 15.17 years of age with a hospital mortality rate of 38.91%. GIB developed in 3.80% of the patients; MACEs included ischemic stroke in 1.54%, intracranial hemorrhage (ICH) in 0.92%, and acute myocardial infarction (AMI) in 1.59%. Both ICH and AMI significantly increased the risk of (1) ICU admission (aOR = 8.02, 95% confidence interval (CI): 6.84-9.42 for ICH and aOR = 4.78, 95% CI: 4.21-5.42 for AMI, respectively), (2) receiving MV (aOR = 3.92, 95% CI: 3.52-4.40 and aOR = 1.99, 95% CI: 1.84-2.16, respectively), and (3) the hospital mortality (aOR = 1.08, 95% CI: 0.98-1.19 and aOR = 1.11, 95% CI: 1.03-1.19, respectively). However, sepsis with GIB or ischemic stroke increased only the risk of ICU admission and MV but not the hospital mortality (aOR = 0.98, 95% CI: 0.93-1.03 for GIB and aOR = 0.84, 95% CI: 0.78-0.91 for ischemic stroke, respectively). CONCLUSIONS: GIB and MACEs significantly increased the risk of ICU admission and receiving MV but not the hospital mortality, which was independently associated with both AMI and ICH. Early prevention can at least reduce the complexity of clinical course and even the hospital mortality.

Preadmission Antihypertensive Drug Use and Sepsis Outcome: Impact of Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs).

BACKGROUND: Several studies have reported improved sepsis outcomes when certain preadmission antihypertensive drugs, namely, calcium channel blockers (CCBs), are used. This study aims to determine whether preadmission antihypertensive drug use, especially angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), is associated with decreased total hospital mortality in sepsis. METHODS: This study was conducted using the unique database of a sepsis cohort from the National Health Insurance Research Database in Taiwan. Frequency matching for age and sex between preadmission antihypertensive drug users (study cohort) and nonusers (comparison cohort) was conducted. The primary outcome was total hospital mortality. Logistic regression analyses were performed to calculate the odds ratios (ORs) of important variables. Further joint effect analyses were carried out to examine the impacts of different combinations of antihypertensive drugs. RESULTS: A total of 33,213 sepsis antihypertensive drug use patients were retrieved as the study cohort, and an equal number of matched sepsis patients who did not use antihypertensive drugs were identified as the comparison cohort. The study cohort had a higher incidence rate of being diagnosed with septic shock compared with the comparison cohort (4.36%-2.31%, P < 0.001) and a higher rate of total hospital mortality (38.42%-24.57%, P < 0.001). In the septic shock condition, preadmission antihypertensive drug use was associated with a decreased adjusted OR (OR = 0.66, 95% confidence interval [CI], 0.55-0.80) for total hospital mortality, which was not observed for the nonseptic shock condition. Compared with antihypertensive drug nonusers, both ACEI and ARB users had decreased adjusted ORs for total hospital mortality in sepsis (adjusted OR = 0.93, 95% CI, 0.88-0.98 and adjusted OR = 0.85, 95% CI, 0.81-0.90); however, CCB, beta-blocker, and diuretic users did not. In the septic shock condition, ACEI, ARB, CCB, and beta-blocker users all had decreased ORs for total hospital mortality. Joint effect analysis showed ACEI use, except in combination with diuretics, to be associated with a decreased adjusted OR for total hospital mortality in sepsis. Similar results were observed for ARB users. CONCLUSIONS: Preadmission ACEI or ARB use is associated with a decreased risk of total hospital mortality, regardless of a nonshock or septic shock condition.