Search

Using the Taiwan Biobank, we aimed to identify traits and genetic variations that could predispose Han Chinese women to primary dysmenorrhea. Cases of primary dysmenorrhea included those who self-reported "frequent dysmenorrhea" in a dysmenorrhea-related Taiwan Biobank questionnaire, and those who have been diagnosed with severe dysmenorrhea by a physician. Controls were those without self-reported dysmenorrhea. Customized Axiom-Taiwan Biobank Array Plates were used to perform whole-genome genotyping, PLINK was used to perform association tests, and HaploReg was used to conduct functional annotations of SNPs and bioinformatic analyses. The GWAS analysis included 1186 cases and 24,020 controls. We identified 53 SNPs that achieved genome-wide significance (P 5 × 10

Objectives: Predictors for post-sepsis myocardial infarction (MI) and stroke are yet to be identified due to the competing risk of death. Methods: This study included all hospitalized patients with sepsis from National Health Insurance Research Database of Taiwan between 2000 and 2011. The primary outcome was the first occurrence of MI and stroke requiring hospitalization within 180 days following hospital discharge from the index sepsis episode. The association between predictors and post-sepsis MI and stroke were analyzed using cumulative incidence competing risk model that controlled for the competing risk of death. Results: Among 42 316 patients with sepsis, 1012 (2.4%) patients developed MI and stroke within 180 days of hospital discharge. The leading 5 predictors for post-sepsis MI and stroke are prior cerebrovascular diseases (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.74-2.32), intra-abdominal infection (HR: 1.94, 95% CI: 1.71-2.20), previous MI (HR: 1.81, 95% CI: 1.53-2.15), lower respiratory tract infection (HR: 1.62, 95% CI: 1.43-1.85), and septic encephalopathy (HR: 1.61, 95% CI: 1.26-2.06). Conclusions: Baseline comorbidities and sources of infection were associated with an increased risk of post-sepsis MI and stroke. The identified risk factors may help physicians select a group of patients with sepsis who may benefit from preventive measures, antiplatelet treatment, and other preventive measures for post-sepsis MI and stroke.

There are limited studies that compare the cost and outcome of robotic-assisted surgery to open and laparoscopic surgery for colon cancer treatment. We aimed to compare the three surgical modalities for colon cancer treatment. We performed a cohort study using the population-based Nationwide Inpatient Sample database. Patients with a primary diagnosis of colon cancer who underwent robotic, laparoscopic, or open surgeries between 2008 and 2014 were eligible for enrollment. We compared in-hospital mortality, complications, length of hospital stay, and cost for patients undergoing one of these three procedures using a multivariate adjusted logistic regression analysis and propensity score matching. Of the 531,536 patients undergoing surgical treatment for colon cancer during the study period, 348,645 (65.6%) patients underwent open surgeries, 174,748 (32.9%) underwent laparoscopic surgeries, and 8143 (1.5%) underwent robotic surgeries. In-hospital mortality, length of hospital stay, wound complications, general medical complications, general surgical complications, and costs of the three surgical treatment modalities. Compared to those undergoing laparoscopic surgery, patients undergoing open surgery had a higher mortality rate (OR 2.98, 95% CI 2.61–3.40), more general medical complications (OR 1.77, 95% CI 1.67–1.87), a longer length of hospital stay (6.60 vs. 4.36 days), and higher total cost ($18,541 vs. $14,487) in the propensity score matched cohort. Mortality rate and general medical complications were equivalent in the laparoscopic and robotic surgery groups, but the median cost was lower in the laparoscopic group ($14641 vs. $16,628 USD). Laparoscopic colon cancer surgery was associated with a favourable short-term outcome and lower cost compared with open surgery. Robot-assisted surgery had comparable outcomes but higher cost as compared to laparoscopic surgery.

Calcium channel blockers (CCBs) are known to reduce the availability of iron—an important mineral for intracellular pathogens. Nonetheless, whether the use of CCBs modifies the risk of active tuberculosis in the clinical setting remains unclear. To determine whether CCBs may modify the risk of active tuberculosis disease, we conducted a nested case-control study using the National Health Insurance Research Database of Taiwan between January 1999 and December 2011. Conditional logistic regression and disease risk score adjustment were used to calculate the risk of active tuberculosis disease associated with CCB use. Subgroup analyses investigated the effect of different types of CCBs and potential effect modification in different subpopulations. A total of 8164 new active tuberculosis cases and 816 400 controls were examined. Use of CCBs was associated with a 32% decrease in the risk of active tuberculosis (relative risk [RR], 0.68 [95% CI, 0.58–0.78]) after adjustment with disease risk score. Compared with nonuse of CCBs, the use of dihydropyridine CCBs was associated with a lower risk of tuberculosis (RR, 0.63 [95% CI, 0.53–0.79]) than nondihydropyridine CCBs (RR, 0.73 [95% CI, 0.57–0.94]). In contrast, use of β-blockers (RR, 0.99 [95% CI, 0.83–1.12]) or loop diuretics (RR, 0.88 [95% CI, 0.62–1.26]) was not associated with lower risk of tuberculosis. In subgroup analyses, the risk of tuberculosis associated with the use of CCBs was similar among patients with heart failure or cerebrovascular diseases. Our study confirms that use of dihydropyridine CCBs decreases the risk of active tuberculosis.

Biological products are increasingly important, and therefore the industry has begun to adopt quality by design, as recommended by the ICH and the U.S. FDA. Smaller companies, however, have faced difficulties in employing full-scale experiments or the quality by design strategy. Thus, this study provides an alternative way to build a model from existing data with experimental software that does not require full-scale experiments. This empirical study hopes to provide a practical way to improve the efficiency of smaller biopharmaceutical companies and researchers. Moreover, the models provided here can be applied to process characterization in recombinant protein production.

BACKGROUND: Patients are at increased risk of cardiovascular complications while recovering from sepsis. We aimed to study the temporal change and susceptible periods for cardiovascular complications in patients recovering from sepsis by using a national database. METHODS: In this retrospective population-based cohort study, patients with sepsis were identified from the National Health Insurance Research Database in Taiwan. We estimated the risk of myocardial infarction (MI) and stroke following sepsis by comparing a sepsis cohort to a matched population and hospital control cohort. The primary outcome was first occurrence of MI or stroke requiring admission to hospital during the 180-day period following discharge from hospital after sepsis. To delineate the risk profile over time, we plotted the weekly risk of MI and stroke against time using the Cox proportional hazards model. We determined the susceptible period by fitting the 2 phases of time-dependent risk curves with free-knot splines, which highlights the turning point of the risk of MI and stroke after discharge from the hospital. RESULTS: We included 42 316 patients with sepsis; stroke developed in 831 of these patients and MI developed in 184 within 180 days of discharge from hospital. Compared with population controls, patients recovering from sepsis had the highest risk for MI or stroke in the first week after discharge (hazard ratio [HR] 4.78, 95% confidence interval [CI] 3.19 to 7.17; risk difference 0.0028, 95% CI 0.0021 to 0.0034), with the risk decreasing rapidly until the 28th day (HR 2.38, 95% CI 1.94 to 2.92; risk difference 0.0045, 95% CI 0.0035 to 0.0056) when the risk stabilized. In a repeated analysis comparing the sepsis cohort with the nonsepsis hospital control cohort, we found an attenuated but still marked elevated risk before day 36 after discharge (HR 1.32, 95% CI 1.15 to 1.52; risk difference 0.0026, 95% CI 0.0013 to 0.0039). The risk of MI or stroke was found to interact with age, with younger patients being associated with a higher risk than older patients (interaction p = 0.0004). INTERPRETATION: Compared with the general population with similar characteristics, patients recovering from sepsis had a markedly elevated risk of MI or stroke in the first 4 weeks after discharge from hospital. More close monitoring and pharmacologic prevention may be required for these patients at the specified time.

Background Previous studies raised safety concerns on the association between fluoroquinolone treatment and serious collagen disorders, aortic aneurysm and dissection (AA/AD). Objectives This study sought to evaluate this association via a case-crossover analysis in a large national administrative database. Methods A case-crossover design was used to compare the distributions of fluoroquinolone exposure for the same patient across a 60-day period before the AA/AD event (hazard period) and 1 randomly selected 60-day period (referent period) between 60 to 180 days before the AA/AD events. In the sensitivity analysis, the authors repeated the main analysis using a 1:5 ratio of hazard period to referent period, to adjust for the effect of time-variant confounders. A disease-risk score–matched time control analysis was performed to investigate the potential time-trend bias. The risks were calculated by a conditional logistic regression model. Results A total of 1,213 hospitalized AA/AD patients were identified between 2001 and 2011. In the main case-crossover analysis, exposure to fluoroquinolone was more frequent during the hazard periods than during the referent periods (1.6% vs. 0.6%; odds ratio [OR]: 2.71; 95% confidence interval [CI]: 1.14 to 6.46). In the sensitivity analysis, after adjustment for infections and co-medications, the risk remains significant (OR: 2.05; 95% CI: 1.13 to 3.71). An increased risk of AA/AD was observed for prolonged exposure to fluoroquinolones (OR: 2.41 for 3- to 14-day exposure; OR: 2.83 for >14-day exposure). Susceptible period analysis revealed that the use of fluoroquinolone within 60 days was associated with the highest risk of AA/AD. In the case-time-control analysis, there was no evidence that the observed association is due to temporal changes in fluoroquinolone exposure. Conclusions Exposure to fluoroquinolone was substantially associated with AA/AD. This risk was modified by the duration of fluoroquinolone use and the length of the hazard period.

Aim The aim of this study was to investigate the trend of incidence and outcome of paediatric sepsis in a population-based database. Methods Children with sepsis were identified from the 23 million nationwide health insurance claims database of Taiwan. Sepsis was defined by the presence of single ICD-9 code for severe sepsis or septic shock or a combination of ICD-9 codes for infection and organ dysfunction. We analysed the trend of incidence, mortality and source of infection in three age groups: infant (28 days to 1 year), child (1-9 years) and adolescent (10-18 years). Results From 2002 to 2012, we identified 38 582 paediatric patients with sepsis, of which 21.3% were infants, 52.8% were children and 25.8% were adolescents. The incidence of sepsis was 336.4 cases per 100 000 population in infants, 3.3 times higher than in children (101.5/100 000 cases) and 7.3 times higher than in adolescents (46.2/100 000 cases). While sepsis incidence decreased from 598.0 to 336.4 cases per 100 000 people in the infant population, it remained relatively unchanged in children and adolescents. For 90-day mortality, there were significant decreases in all three age groups (absolute decrease of 5.0% for infants, 3.7% for children and 14.4% for the adolescents). In the infant population, we observed a decrease in the incidence of lower respiratory tract infections, while the incidence of urinary tract infections remained unchanged. Conclusions The incidence and mortality of sepsis among paediatric patients have decreased substantially between 2002 and 2012, especially among infants. The widespread use of Haemophilus influenzae and pneumococcal vaccines in infants could be a possible explanation.

Background Several clinical trials on hypertonic fluid administration have been completed, but the results have been inconclusive. The objective of this study is to summarize current evidence for treating hypovolemic patients with hypertonic solutions by performing a systematic review and meta-analysis. Methods Major electronic databases were searched from inception through June 2014. We included only randomized controlled trials involving hemorrhagic shock patients treated with hypertonic solutions. After screening 570 trials, 12 were eligible for the final analysis. Pooled effect estimates were calculated with a random effect model. Results The 12 studies included 6 trials comparing 7.5% hypertonic saline (HS) with 0.9% saline or Ringer's lactate solution and 11 trials comparing 7.5% hypertonic saline with dextran (HSD) with isotonic saline or Ringer's lactate. Overall, there were no statistically significant survival benefits for patients treated with HS (relative risk [RR], 0.96; 95% confidence interval [CI], 0.82-1.12) or HSD (RR, 0.92; 95% CI, 0.80-1.06). Treatment with hypertonic solutions was also not associated with increased complications (RR, 1.03; 95% CI, 0.78-1.36). Subgroup analysis on trauma patients in the prehospital or emergency department settings did not change these conclusions. There was no evidence of significant publication bias. Meta-regression analysis did not find any significant sources of heterogeneity. Conclusions Current evidence does not reveal increased mortality when the administration of isotonic solutions is compared to HS or HSD in trauma patients with hemorrhagic shock. HS or HSD may be a viable alternative resuscitation fluid in the prehospital setting. Further studies are needed to determine the optimum volume and regimen of intravenous fluids for the treatment of trauma patients.

Objectives Use of calcium channel blockers has been found to improve sepsis outcomes in animal studies and one clinical study. This study determines whether the use of calcium channel blockers is associated with a decreased risk of mortality in patients with sepsis. Design Population-based matched cohort study. Setting National Health Insurance Research Database of Taiwan. Patients Hospitalized severe sepsis patients identified from National Health Insurance Research Database by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Interventions None. Measurements and main results The association between calcium channel blocker use and sepsis outcome was determined by multivariate-adjusted Cox proportional hazard models and propensity score analysis. To examine the influence of healthy user bias, beta-blocker was used as an active comparator. Our study identified 51,078 patients with sepsis, of which, 19,742 received calcium channel blocker treatments prior to the admission. Use of calcium channel blocker was associated with a reduced 30-day mortality after propensity score adjustment (hazard ratio, 0.94; 95% CI, 0.89-0.99), and the beneficial effect could extend to 90-day mortality (hazard ratio, 0.95; 95% CI, 0.89-1.00). In contrast, use of beta-blocker was not associated with an improved 30-day (hazard ratio, 1.06; 95% CI, 0.97-1.15) or 90-day mortality (hazard ratio, 1.00; 95% CI, 0.90-1.11). On subgroup analysis, calcium channel blockers tend to be more beneficial to patients with male gender, between 40 and 79 years old, with a low comorbidity burden, and to patients with cardiovascular diseases, diabetes, or renal diseases. Conclusions In this national cohort study, preadmission calcium channel blocker therapy before sepsis development was associated with a 6% reduction in mortality when compared with patients who have never received calcium channel blockers.

Objective We aim to summarize current evidence on the value of point-of-care (POC) focused echocardiography in the assessment of short-term survival in patients with cardiac arrest. Methods PubMed and EMBASE were searched from inception to July 2016 for eligible studies that evaluated the utility of POC echocardiography in patients with cardiac arrest. Modified QUADAS was used to appraise the quality of included studies. A random-effect bivariate model and a hierarchical summary receiving operating curve were used to summarize the performance characteristics of focused echocardiography. Results Initial search identified 961 citations of which 15 were included in our final analysis. A total of 1695 patients had POC echocardiography performed during resuscitation. Ultrasonography was mainly utilized to detect spontaneous cardiac movement (SCM) and identify reversible causes of cardiac arrest. Subcostal, apical and parasternal views were used to identify cardiac tamponade, pulmonary embolism, and pleural view for tension pneumothorax. Results of meta-analysis showed that SCM detected by focused echocardiography had a pooled sensitivity (0.95, 95%CI: 0.72–0.99) and specificity (0.80, 95%CI: 0.63–0.91) in predicting return of spontaneous circulation (ROSC) during cardiac arrest, with a positive likelihood ratio of 4.8 (95% CI: 2.5–9.4) and a negative likelihood ratio of 0.06 (95%CI: 0.01–0.39). Conclusion POC focused echocardiography can be used to identify reversible causes and predict short-term outcome in patients with cardiac arrest. In patients with a low pretest probability for ROSC, absence of SCM on echocardiography can predict a low likelihood of survival and guide the decision of resuscitation termination.

Objective There is limited research on afebrile bacteremia. We aimed to compare the risk factors and outcomes of patients with afebrile and febrile infections. Methods This was a retrospective cohort study of bloodstream isolates from 994 adults admitted to the emergency department of a university hospital. Afebrile infections, defined as the absence of fever history or measured fever through the emergency department course, was compared with febrile infection. Frequencies and proportions of sources of infection, comorbidities, along with organ failure and mortality were presented. The major outcome measure was 30-day survival. chi-Square or Student's t test was used for univariate analysis, and Cox proportional hazard model was used for multivariate analysis. Results We found that the risk factors and outcomes of febrile and afebrile bacteremia patients were very different. The afebrile patients were older, have higher Charlson comorbidity index, and had poorer outcomes than the febrile patients. We also found that oldest old age, nonhematologic malignancy, necrotizing fasciitis, spontaneous bacterial peritonitis, and pneumonia were each positive independent predictors of afebrile bacteremia, whereas Escherichia coli infection and liver abscess were independent negative predictors of afebrile bacteremia. Finally, the 30-day all-cause mortality was higher in the afebrile group than in the febrile group (45% versus 12%, log-rank P Conclusions This series of patients with afebrile bacteremia confirmed the previously reported associations with old age and immunocompromised conditions. Clinicians should explore the possibility of occult severe infection, and initiate early hemodynamic support and empirical antimicrobial therapy for patients with the aforementioned risk factors.

Background It remains unclear whether sepsis-related cardiovascular complications have an adverse impact on survival independent of pre-existing comorbidities. To investigate the survival impact of post-sepsis cardiovascular complications among sepsis survivors, we conducted a population-based study using the National Health Insurance Database of Taiwan. Methods We identified sepsis patients from the National Health Insurance Research Database of Taiwan using ICD-9-CM codes involving infection and organ dysfunction between 2000 and 2011. Post-sepsis incident myocardial infarction (MI) and stroke were ascertained by ICD-9-CM codes and antiplatelet treatment. We constructed a non-sepsis comparison cohort using propensity score matching to ascertain the association between sepsis and cardiovascular complications. Furthermore, we compared the 180-day mortality and 365-day mortality between patients surviving sepsis with or without post-sepsis MI or stroke within 70 days of hospital discharge. We constructed Cox regression models adjusting for pre-existing comorbidities to evaluate the independent survival impact of post-sepsis MI or stroke among sepsis survivors. Results We identified 42,316 patients hospitalized for sepsis, from which we matched 42,151 patients 1:1 with 42,151 patients hospitalized without sepsis. Compared to patients hospitalized without sepsis, patients hospitalized with sepsis had an increased risk of MI or stroke (adjusted odds ratio 1.72, 95% CI 1.60–1.85). Among 42,316 patients hospitalized for sepsis, 486 (1.15%) patients developed incident stroke and 108 (0.26%) developed incident MI within 70 days of hospital discharge. Compared to sepsis survivors without cardiovascular complications, sepsis survivors with incident MI or stroke had a higher mortality rate at 180 days (11.68% vs. 4.44%, P = 0.003) and at 365 days (16.75% vs. 7.11%, P = 0.005). Adjusting for age, sex, and comorbidities, post-sepsis MI or stroke was independently associated with increased 180-day (adjusted hazard ratio [HR] 2.16, 95% CI 1.69–2.76) and 365-day (adjusted HR 1.90, 95% CI 1.54–2.32) mortality. Conclusions Compared to sepsis patients without incident MI or stroke, sepsis patients with incident MI or stroke following hospital discharge had an increased risk of mortality for up to 365 days of follow-up. This increased risk cannot be explained by pre-sepsis comorbidities. Electronic supplementary material The online version of this article (10.1186/s13054-019-2579-2) contains supplementary material, which is available to authorized users.

There is a paucity of genome-wide association study on Han Chinese gout patients. We performed a genome-wide association meta-analysis on two Taiwanese cohorts consisting of 758 gout cases and 14166 controls of Han Chinese ancestry. All the participants were recruited from the Taiwan Biobank. For pathway analysis, we applied ICSNPathway (Identify candidate Causal SNPs and Pathways) analysis, and to investigate whether expression-associated genetic variants contribute to gout susceptibility, we systematically integrated lymphoblastoid expression quantitative trait loci (eQTL) and genome-wide association data of gout using Sherlock, a Bayesian statistical frame-work. In the meta-analysis, we found 4 SNPs that reached genome-wide statistical significance (P −8). These SNPs are in or close to ABCG2, PKD2 and NUDT9 gene on chromosome 4. ICSNPathway analysis identified rs2231142 as the candidate causal SNP, and ABCG2 as the candidate gene. Sherlcok analysis identified three genes, which were significantly associated with the risk of gout (PKD2, NUTD9, and NAP1L5). To conclude, we reported novel susceptible loci for gout that has not been previously addressed in the literature.