Genome-wide association study of primary dysmenorrhea in the Taiwan Biobank validates associations near the NGF and IL1 gene loci.

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 × 10-8, which clustered in 2 regions. The first SNP cluster was on chromosome 1, and included 24 high LD (R2 > 0.88) variants around the NGF gene (lowest P value of 3.83 × 10-13 for rs2982742). Most SNPs occurred within NGF introns, and were predicted to alter regulatory binding motifs. The second SNP cluster was on chromosome 2, including 7 high LD (R2 > 0.94) variants around the IL1A and IL1B loci (lowest P value of 7.43 × 10-10 for rs11676014) and 22 SNPs that did not reach significance after conditional analysis. Most of these SNPs resided within IL1A and IL1B introns, while 2 SNPs may be in the promoter histone marks or promoter flanking regions of IL1B. To conclude, data from this study suggest that NGF, IL1A, and IL1B may be involved in the pathogenesis of primary dysmenorrhea in the Han Chinese in Taiwan.

Temporal Trends in the Microbiological Characteristics of Sepsis in the United States: A Population Based Study.

BACKGROUND: Epidemiologic studies are needed for monitoring population-level trends in sepsis. This study examines sepsis-causing microorganisms from 2006 to 2014 in the United States using data from the Nationwide Inpatient Sample database. METHODS: 7 860 686 adults hospitalized with sepsis were identified using a validated ICD-9 coding approach. Associated microorganisms were identified by ICD-9 code and classified by major groups (Gram-positive, Gram-negative, fungi, anaerobes) and specific species for analysis of their incidence and mortality. RESULTS: The rate of sepsis incidence has increased for all four major categories of pathogens, while the mortality rate decreased. In 2014, Gram-negative pathogens had a higher incidence than Gram-positives. Anaerobes increased the fastest with an average annual increase of 20.17% (p < 0.001). Fungi had the highest mortality (19.28%) and the slowest annual decrease of mortality (-2.31%, p = 0.006) in 2013, while anaerobic sepsis had the highest hazard of mortality (adjusted HR 1.60, 95% CI 1.53-1.66). CONCLUSIONS: Gram-negative pathogens have replaced Gram-positives as the leading cause of sepsis in the United States in 2014 during the study period (2006-2014). The incidence of anaerobic sepsis has an annual increase of 20%, while the mortality of fungal sepsis has not decreased at the same rate as other microorganisms. These findings should inform the diagnosis and management of septic patients, as well as the implementation of public health programs.

Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction : An International Collaborative Meta-analysis.

BACKGROUND: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION: Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION: The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS: A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays. LIMITATION: Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies. CONCLUSION: The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI. PRIMARY FUNDING SOURCE: National Taiwan University Hospital.

Temporal Trends in Sepsis Incidence and Mortality in Patients With Cancer in the US Population.

BACKGROUND: Few population-based studies assess the impact of cancer on sepsis incidence and mortality. OBJECTIVES: To evaluate epidemiological trends of sepsis in patients with cancer. METHODS: This retrospective cohort study included adults (≥20 years old) identified using sepsis-indicator International Classification of Diseases codes from the Nationwide Inpatient Sample database (2006-2014). A generalized linear model was used to trend incidence and mortality. Outcomes in patients with cancer and patients without cancer were compared using propensity score matching. Cox regression modeling was used to calculate hazard ratios for mortality rates. RESULTS: The study included 13 996 374 patients, 13.6% of whom had cancer. Gram-positive infections were most common, but the incidence of gram-negative infections increased at a greater rate. Compared with patients without cancer, those with cancer had significantly higher rates of lower respiratory tract (35.0% vs 31.6%), intra-abdominal (5.5% vs 4.6%), fungal (4.8% vs 2.9%), and anaerobic (1.2% vs 0.9%) infections. Sepsis incidence increased at a higher rate in patients with cancer than in those without cancer, but hospital mortality rates improved equally in both groups. After propensity score matching, hospital mortality was higher in patients with cancer than in those without cancer (hazard ratio, 1.25; 95% CI, 1.24-1.26). Of patients with sepsis and cancer, those with lung cancer had the lowest survival (hazard ratio, 1.65) compared with those with breast cancer, who had the highest survival. CONCLUSIONS: Cancer patients are at high risk for sepsis and associated mortality. Research is needed to guide sepsis monitoring and prevention in patients with cancer.

Morbid obesity but not obesity is associated with increased mortality in patients undergoing endoscopic retrograde cholangiopancreatography: A national cohort study.

BACKGROUND: The relationship between body weight and outcomes of endoscopic retrograde cholangiopancreatography (ERCP) is unclear. OBJECTIVES: This study aimed to investigate the impact of obesity and morbid obesity on mortality and ERCP-related complications in patients who underwent ERCP. METHODS: We conducted a US population-based retrospective cohort study using the Nationwide Readmissions Databases (2013-2014). A total of 159,264 eligible patients who underwent ERCP were identified, of which 137,158 (86.12%) were normal weight, 12,522 (7.86%) were obese, and 9584 (6.02%) were morbidly obese. The primary outcome was in-hospital mortality. The secondary outcomes were the length of stay, total cost, and ERCP-related complications. Multivariate analysis and propensity score (PS) matching analysis were performed. The analysis was repeated in a restricted cohort to eliminate confounders. RESULTS: Patients with morbid obesity, as compared to normal-weight patients, were associated with a significantly higher in-hospital mortality (hazard ratio [HR]: 5.54; 95% confidence interval [CI]: 1.23-25.04). Obese patients were not associated with significantly different mortality comparing to normal weight (HR: 1.00; 95% CI: 0.14-7.12). Patients with morbid obesity were also found to have an increased length of hospital stay and total cost. The rate of ERCP-related complications was comparable among the three groups except for a higher cholecystitis rate after ERCP in obese patients. CONCLUSIONS: Morbid obesity but not obesity was associated with increased mortality, length of stay, and total cost in patients undergoing ERCP.

Accuracy and comparison of two rapid multiplex PCR tests for gastroenteritis pathogens: a systematic review and meta-analysis.

OBJECTIVES: The primary aim is to provide a summary of evidence for the diagnostic accuracies of multiplex PCR gastrointestinal (GI) panels-BioFire FilmArray and Luminex xTAG on the detection of gastroenteritis pathogens. The secondary aim is to compare the performance of these GI panels head to head. METHODS: A comprehensive search up to 1 December 2019 was conducted on PubMed, Embase, Ovid Medline and Web of Science for studies that used FilmArray or Luminex xTAG Gastrointestinal Pathogen Panel (GPP) for diagnosis of acute gastroenteritis. A summary of diagnostic accuracies for the 16 pathogens were calculated by comparing the GI panels to the current gold standards (conventional standard microbiology techniques such as culture or PCR for bacteria, PCR or enzyme immunoassay (EIA) for viruses, microscopy or EIA for parasite). Hierarchical summary receiver operating characteristic (HSROC) curve analysis, pretest and post-test probabilities were used for estimating the pathogen detection performance. RESULTS: A total of 11 studies with 7085 stool samples were eligible for analysis. Multiplex PCRs demonstrated high diagnostic accuracy, with specificity ≧0.98 and area under the ROC curve (AUROC) ≧0.97 for all the pathogens except for Yersinia enterocolitica (AUROC 0.91). The FilmArray panel demonstrated a higher sensitivity than xTAG GPP for most of the pathogens with the exception of Rotavirus A (xTAG GPP and FilmArray were both 0.93). CONCLUSIONS: This is the first meta-analysis that is a head-to-head comparison examining the performance of the novel multiplex PCR-based tests Luminex xTAG GPP and FilmArray GI panel in detecting each pathogen. Point estimates calculated from eligible studies showed that both GI panels are highly accurate and may provide important diagnostic information for early identification of gastroenteritis. In addition, although FilmArray has higher sensitivity and post-test probability than xTAG GPP for most of the pathogens, how this will translate to a clinical setting remains unclear.

Mortality association between obesity and pneumonia using a dual restricted cohort model.

BACKGROUND: An obesity survival paradox has been reported among obese patients with pneumonia. AIMS: To determine the impact of obesity on pneumonia outcomes and analyze the correlation between in-hospital all-cause mortality and obesity among patients with pneumonia. METHODS: The United States Nationwide Readmissions Database (NRD) was retrospectively analyzed for patients with pneumonia from 2013 to 2014. We used a step-wise restricted and propensity score matching cohort model (dual model) to compare mortality rates and other outcomes among pneumonia patients based on BMI. Mortality was calculated by a Cox proportional hazard model, adjusted for potential confounders with propensity score matched analysis. RESULTS: A total of 70,886,775 patients were registered in NRD during the study period. Of these, 7,786,913 patients (11.0%) were considered obese and 1,652,456 patients (2.3%) were admitted to the hospital with pneumonia. Based on the step-wise restricted cohort model, the hazard ratio comparing the mortality rates among obese pneumonia patients to mortality rates among normal BMI pneumonia patients was 0.75 (95% CI 0.60-0.94). The propensity score matched analysis estimated a hazard rate of 0.84 (95% CI 0.79-0.90) and the hazard ratio estimated from the dual model was 0.82 (95% CI 0.63-1.07). CONCLUSIONS: With the application of a dual model, there appears to be no significant difference in mortality of obese patients with pneumonia compared to normal BMI patients with pneumonia.

Mortality association between obesity and pneumonia using a dual restricted cohort model.

BACKGROUND: An obesity survival paradox has been reported among obese patients with pneumonia. AIMS: To determine the impact of obesity on pneumonia outcomes and analyze the correlation between in-hospital all-cause mortality and obesity among patients with pneumonia. METHODS: The United States Nationwide Readmissions Database (NRD) was retrospectively analyzed for patients with pneumonia from 2013 to 2014. We used a step-wise restricted and propensity score matching cohort model (dual model) to compare mortality rates and other outcomes among pneumonia patients based on BMI. Mortality was calculated by a Cox proportional hazard model, adjusted for potential confounders with propensity score matched analysis. RESULTS: A total of 70,886,775 patients were registered in NRD during the study period. Of these, 7,786,913 patients (11.0%) were considered obese and 1,652,456 patients (2.3%) were admitted to the hospital with pneumonia. Based on the step-wise restricted cohort model, the hazard ratio comparing the mortality rates among obese pneumonia patients to mortality rates among normal BMI pneumonia patients was 0.75 (95% CI 0.60-0.94). The propensity score matched analysis estimated a hazard rate of 0.84 (95% CI 0.79-0.90) and the hazard ratio estimated from the dual model was 0.82 (95% CI 0.63-1.07). CONCLUSIONS: With the application of a dual model, there appears to be no significant difference in mortality of obese patients with pneumonia compared to normal BMI patients with pneumonia.