Prevalence of Cardiometabolic Diseases Among Racial and Ethnic Subgroups in Adults - Behavioral Risk Factor Surveillance System, United States, 2013-2021.

Although diabetes and cardiovascular disease account for substantial disease prevalence among adults in the United States, their prevalence among racial and ethnic subgroups is inadequately characterized. To fill this gap, CDC described the prevalence of diagnosed cardiometabolic diseases among U.S. adults, by disaggregated racial and ethnic subgroups, among 3,970,904 respondents to the Behavioral Risk Factor Surveillance System during 2013-2021. Prevalence of each disease (diabetes, myocardial infarction, angina or coronary heart disease, and stroke), stratified by race and ethnicity, was based on self-reported diagnosis by a health care professional, adjusting for age, sex, and survey year. Overall, mean respondent age was 47.5 years, and 51.4% of respondents were women. Prevalence of cardiometabolic diseases among disaggregated race and ethnicity subgroups varied considerably. For example, diabetes prevalence within the aggregated non-Hispanic Asian category (11.5%) ranged from 6.3% in the Vietnamese subgroup to 15.2% in the Filipino subgroup. Prevalence of angina or coronary heart disease for the aggregated Hispanic or Latino category (3.8%) ranged from 3.1% in the Cuban subgroup to 6.3% in the Puerto Rican subgroup. Disaggregation of cardiometabolic disease prevalence data by race and ethnicity identified health disparities among subgroups that can be used to better help guide prevention programs and develop culturally relevant interventions.

Development and validation of genome-wide polygenic risk scores for predicting breast cancer incidence in Japanese females: a population-based case-cohort study.

PURPOSE: This study aimed to develop an ancestry-specific polygenic risk scores (PRSs) for the prediction of breast cancer events in Japanese females and validate it in a longitudinal cohort study. METHODS: Using publicly available summary statistics of female breast cancer genome-wide association study (GWAS) of Japanese and European ancestries, we, respectively, developed 31 candidate genome-wide PRSs using pruning and thresholding (P + T) and LDpred methods with varying parameters. Among the candidate PRS models, the best model was selected using a case-cohort dataset (63 breast cancer cases and 2213 sub-cohorts of Japanese females during a median follow-up of 11.9 years) according to the maximal predictive ability by Harrell's C-statistics. The best-performing PRS for each derivation GWAS was evaluated in another independent case-cohort dataset (260 breast cancer cases and 7845 sub-cohorts of Japanese females during a median follow-up of 16.9 years). RESULTS: For the best PRS model involving 46,861 single nucleotide polymorphisms (SNPs; P + T method with PT = 0.05 and R2 = 0.2) derived from Japanese-ancestry GWAS, the Harrell's C-statistic was 0.598 ± 0.018 in the evaluation dataset. The age-adjusted hazard ratio for breast cancer in females with the highest PRS quintile compared with those in the lowest PRS quintile was 2.47 (95% confidence intervals, 1.64-3.70). The PRS constructed using Japanese-ancestry GWAS demonstrated better predictive performance for breast cancer in Japanese females than that using European-ancestry GWAS (Harrell's C-statistics 0.598 versus 0.586). CONCLUSION: This study developed a breast cancer PRS for Japanese females and demonstrated the usefulness of the PRS for breast cancer risk stratification.

Early initiation of angiotensin-converting enzyme inhibitor in patients with scleroderma renal crisis: A nationwide inpatient database study.

OBJECTIVES: To evaluate the effectiveness of early initiation of angiotensin-converting enzyme inhibitor (ACEi) in patients with scleroderma renal crisis (SRC). METHODS: This was a retrospective cohort study using a nationwide inpatient database in Japan from July 2010 to March 2020. All hospitalized patients with SRC were divided into those who received ACEi within two days of admission (early ACEi group) and those who did not (control group). Propensity-score overlap weighting analysis was performed to adjust for confounding factors. The primary outcome was the composite of in-hospital mortality or hemodialysis dependence at discharge. RESULTS: Of the 475 eligible patients, 248 (52.2%) were in the early ACEi group and 227 (47.8%) were in the control group. After overlap weighting, the primary outcome was significantly lower in the early ACEi group than in the control group (40.1% vs. 49.0%; odds ratio, 0.69; 95% confidence interval, 0.48-1.00; P= 0.049). CONCLUSIONS: The present study showed that early initiation of ACEi was associated with lower composite outcome of in-hospital mortality or hemodialysis dependence at discharge in patients with SRC. Further prospective studies are warranted to verify the present findings.

Evaluation of heart failure admission as a surrogate for mortality in randomized clinical trials: A meta-analysis.

BACKGROUND: Heart failure (HF) admission is used as a study endpoint in clinical trials. However, it remains unclear whether it can be a valid surrogate endpoint for mortality. OBJECTIVES: To validate whether HF admission is a valid surrogate for mortality. METHODS: In PubMed and EMBASE, randomized controlled trials (RCTs) of interventions to treat patients with heart failure at the enrolment were searched on 13 April 2022. We extracted RCTs in which event numbers of both HF admission and all-cause mortality were reported as either primary or secondary outcomes. Trial-level correlations (R-squared) between HF admission and mortality were assessed. We performed subgroup analyses by study year, follow-up duration, baseline HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF), and whether the intervention was pharmacological. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. RESULTS: A total of 117 RCTs met the criteria for inclusion. Overall, the trial-level R-squared between HF admission and all-cause mortality was 0.39 (95% confidence interval (CI), 0.26 to 0.53). However, in the subgroup analyses, the trial-level R-squared was increased when the follow-up duration was ≥24 months (0.70 [95% CI: 0.55, 0.85]), when intervention was pharmacological (0.51 [95% CI: 0.34, 0.68]) and when the baseline HF type was HFrEF (0.57 [95% CI: 0.42, 0.73]). CONCLUSIONS: Our findings indicate that HF admission may not always be a valid surrogate for mortality in patients with HF. Rather, the surrogacy of HF admission may be dependent on clinical background and interventions.

Net clinical benefit of dual antiplatelet therapy in elderly patients with acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND: Contemporary dual antiplatelet therapy (DAPT) strategies, such as short-term DAPT or de-escalation of DAPT, have emerged as attractive strategies to treat patients with acute coronary syndrome (ACS). However, it remains uncertain whether they are suitable for elderly patients. METHODS: PubMed, Embase, and Cochrane CENTRAL databases were searched in September 2022. Randomized controlled trials (RCTs) investigating DAPT strategies, including standard (12 months), short-term, uniform de-escalation, and guided-selection strategies for elderly patients with ACS (age ≥ 65 years) were identified, and a network meta-analysis was conducted. The primary endpoint was the net clinical benefit outcome, a composite of major adverse cardiovascular events (MACEs: cardiovascular death, myocardial infarction, or stroke) and clinically relevant bleeding (equivalent to bleeding of at least type 2 according to the Bleeding Academic Research Consortium). The secondary outcomes were MACE and major bleeding. RESULTS: Sixteen RCTs with a combined total of 47,911 patients were included. The uniform de-escalation strategy was associated with an improved net clinical benefit compared with DAPT using potent P2Y12 inhibitors. The short-term DAPT strategy was associated with reduced risks of the primary outcome and major bleeding compared with DAPT using potent P2Y12 inhibitors, however, it was ranked as the least effective strategy for MACE compared with other DAPT strategies. CONCLUSIONS: Uniform de-escalation and short-term DAPT strategies may be advantageous for elderly patients, but need to be tailored based on individual bleeding and ischemic risks. Further RCTs of contemporary DAPT strategies specifically designed for elderly patients are warranted to confirm the findings of the present study.

Long-term outcomes after transcatheter aortic valve replacement: Meta-analysis of Kaplan-Meier-derived data.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is as an alternative treatment to surgical AVR, but the long-term outcomes of TAVR remain unclear. AIMS: This study aimed to analyze long-term outcomes following TAVR using meta-analysis. METHODS: A literature search was performed with MEDLINE, EMBASE, Cochrane Library, Web of Science, and Google Scholar through November 2022; studies reporting clinical outcomes of TAVR with follow-up periods of ≥8 years were included. The outcomes of interest were overall survival and/or freedom from structural valve deterioration (SVD). Surgical risk was assessed with the Society of Thoracic Surgeons (STS) predicted risk of mortality (PROM) score. A subgroup analysis was conducted for intermediate-/high-surgical risk patients only. RESULTS: Eleven studies including 5458 patients were identified and analyzed. The mean age was 82.0 ± 6.5 years, and mean STS PROM score ranged from 2.9 to 10.6%. Survival rate at 5 and 10 years was 47.7% ± 1.4% and 12.1 ± 2.0%. Five studies including 1509 patients were analyzed for SVD. Freedom from SVD at 5 and 8 years was 95.5 ± 0.7% and 85.1 ± 3.1%. Similar results for survival and SVD were noted in the subgroup analysis of intermediate-/high-risk patients. CONCLUSIONS: Following TAVR, approximately 88% of patients died within 10 years, whereas 85% were free from SVD at 8 years. These date suggest that baseline patient demographic have the greatest impact on survival, and SVD does not seem to have a prognostic impact in this population. Further investigations on longer-term outcomes of younger and lower-risk patients are warranted.

Association of chronic kidney disease with total and site-specific cancer incidence in participants of the Japan Public Health Center-based Prospective Study.

BACKGROUND: Although studies have found an association between chronic kidney disease (CKD) and cancer incidence, the results are inconsistent. METHODS: This study included participants in the Japan Public Health Center-based Prospective Study who had data on serum creatinine measurements. We assessed the association between estimated glomerular filtration rate (eGFR) and the risk of total and site-specific cancer incidence using a systematic survey in Japan. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for participant demographics and lifestyle factors. RESULTS: A total of 21 978 participants who met the inclusion criteria were followed up for a mean period of 12.9 years, during which a total of 2997 incident cancer cases were reported. In the multivariable adjusted models, an eGFR of <45 mL/min/1.73 m2 was not significantly associated with total cancer incidence (adjusted HR 1.22, 95% CI 0.94-1.60), compared with an eGFR of 60-89 mL/min/1.73 m2 (reference). The HR among those with eGFRs of ≥90 mL/min/1.73 m2 was 1.10 (95% CI 1.00-1.22). CONCLUSIONS: In this large prospective study, a low eGFR was not significantly associated with an increased risk of total cancer incidence in patients with CKD, which may be partly due to an underpowered sample size. This finding may be due to the many shared risk factors between CKD and cancer.

HMGB1 Is a Prognostic Factor for Mortality in Acute Kidney Injury Requiring Renal Replacement Therapy.

INSTRUCTION: High mobility group box 1 (HMGB1) is a pro-inflammatory cytokine that reportedly causes kidney injury and other organ damage in rodent acute kidney injury (AKI) models. However, it remains unclear whether HMGB1 is associated with clinical AKI and related outcomes. This study aimed to evaluate the association with HMGB1 and prognosis of AKI requiring continuous renal replacement therapy (CRRT). METHODS: AKI patients treated with CRRT in our intensive care unit were enrolled consecutively during 2013-2016. Plasma HMGB1 was measured on initiation. Classic initiation was defined as presenting at least one of the following conventional indications: hyperkalemia (K ≥6.5 mEq/L), severe acidosis (pH <7.15), uremia (UN >100 mg/dL), and diuretics-resistant pulmonary edema. Early initiation was defined as presenting no conventional indications. The primary outcome was defined as 90-day mortality. RESULTS: A total of 177 AKI patients were enrolled in this study. HMGB1 was significantly associated with the primary outcome (hazard ratio, 1.06; 95% CI, 1.04-1.08). When the patients were divided into two-by-two groups by the timing of CRRT initiation and the HMBG1 cutoff value obtained by receiver operating curve (ROC) analysis, the high HMGB1 group (>10 ng/mL) with classic initiation was significantly associated with the primary outcome compared with the others, even after adjusting for other factors including the nonrenal serial organ failure assessment (SOFA) score. CONCLUSION: HMGB1 was associated with 90-day mortality in AKI patients requiring CRRT. Notably, the highest mortality was observed in the high HMGB1 group with classic initiation. These findings suggest that CRRT should be considered for AKI patients with high HMGB1, regardless of the conventional indications.

Different Roles of Functional and Structural Renal Markers Measured at Discontinuation of Renal Replacement Therapy for Acute Kidney Injury.

INTRODUCTION: Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) has been associated with an unacceptably high mortality of 50% or more. Successful discontinuation of RRT is thought to be linked to better outcomes. Although functional and structural renal markers have been evaluated in AKI, little is known about their roles in predicting outcomes at the time of RRT discontinuation. METHODS: In this prospective single-center cohort study, we analyzed patients who received continuous RRT (CRRT) for AKI between August 2016 and March 2018 in the intensive care unit of the University of Tokyo Hospital (Tokyo, Japan). Clinical parameters and urine samples were obtained at CRRT discontinuation. Successful CRRT discontinuation was defined as neither resuming CRRT for 48 h nor receiving intermittent hemodialysis for 7 days from the CRRT termination. Major adverse kidney events (MAKEs) were defined as death, requirement for dialysis, or a decrease in the estimated glomerular filtration rate (eGFR) of more than 25% from the baseline at day 90. RESULTS: Of 73 patients, who received CRRT for AKI, 59 successfully discontinued CRRT and 14 could not. Kinetic eGFR, urine volume, urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary L-type fatty acid binding protein were predictive for CRRT discontinuation. Of these factors, urine volume had the highest area under the curve (AUC) 0.91 with 95% confidence interval [0.80-0.96] for successful CRRT discontinuation. For predicting MAKEs at day 90, the urinary NGAL showed the highest AUC 0.76 [0.62-0.86], whereas kinetic eGFR and urine volume failed to show statistical significance (AUC 0.49 [0.35-0.63] and AUC 0.59 [0.44-0.73], respectively). CONCLUSIONS: Our prospective study confirmed that urine volume, a functional renal marker, predicted successful discontinuation of RRT and that urinary NGAL, a structural renal marker, predicted long-term renal outcomes. These observations suggest that the functional and structural renal makers play different roles in predicting the outcomes of severe AKI requiring RRT.

Subanesthetic-dose propofol infusion for preventing emergence agitation in children: a retrospective observational study.

PURPOSE: Anesthesia maintenance using propofol and a propofol bolus dose at the end of surgery have been shown to prevent emergence agitation (EA). However, the preventive effect of subanesthetic propofol infusion during sevoflurane anesthesia on EA remains unknown. We aimed to evaluate the effect of subanesthetic propofol infusion on EA in children. METHODS: We retrospectively compared the incidences of severe EA requiring pharmacological intervention in children who underwent adenoidectomy, tonsillectomy with or without adenoidectomy, or strabismus surgery between maintenance with sevoflurane alone (sevoflurane group) and maintenance with subanesthetic propofol with sevoflurane (combination group). A multivariable logistic regression model adjusted for confounders was used to assess the association between anesthesia methods and the occurrence of EA. Additionally, we estimated the direct effect of anesthesia methods by a mediation analysis, excluding the indirect effects of intraoperative fentanyl and droperidol administration. RESULTS: Among 244 eligible patients, 132 and 112 were in the sevoflurane and combination groups, respectively. The crude incidence of EA was significantly lower in the combination group (17.0% [n = 19]) than in the sevoflurane group (33.3% [n = 44]) (P = 0.005). After adjusting for confounders, the incidence of EA was still significantly lower in the combination group (adjusted odds ratio [aOR]: 0.48, 95% confidence interval [CI] 0.25-0.91). The mediation analysis revealed a direct association of anesthesia methods with a lower EA incidence in the combination group (aOR: 0.48, 95% CI 0.24-0.93) than in the sevoflurane group. CONCLUSION: Subanesthetic propofol infusion may effectively prevent severe EA requiring the administration of opioids or sedatives.

Kinetics of Polymer Crystallization with Aggregating Small Crystallites.

The isothermal crystallization near the glass transition temperature from the melt state of poly(trimethylene terephthalate) has been studied by wide-angle x-ray diffraction (WAXD), small-angle x-ray scattering (SAXS), and optical microscopy. The SAXS and WAXD results show the crystallization mechanism in which the crystalline nodules cover the entire sample with the formation of aggregation regions. The analysis of the SAXS results using Kolmogorov-Johnson-Mehl-Avrami theory indicates that the formation kinetics of the aggregation regions is of three-dimensional homogeneous nucleation type. The analysis of the SAXS profiles using Sekimoto's theory provides the growth velocity and the nucleation rate of the aggregation region. The temperature dependence of the growth velocity of the aggregation region is a natural extrapolation of that of spherulite to the high supercooling region. The temperature dependence of the nucleation rate of the aggregation region is also represented by the parameters of the spherulitic growth rate. The result of the growth velocities of the aggregation region and the spherulite suggests the existence of precursors at the front of the crystal growth.

Plasma xanthine oxidoreductase is associated with carotid atherosclerosis in stable kidney transplant recipients.

AIM: Xanthine oxidoreductase (XOR) is known as an enzyme related to purine metabolism, catalysing the oxidation of hypoxanthine to xanthine and of xanthine to uric acid. We investigated the relationship between plasma XOR activity in stable kidney transplantation (KT) recipients and carotid artery lesions. METHODS: A total of 42 KT patients visiting our outpatient clinic on regular basis were recruited. Associations between plasma XOR activity and the existence of plaque in the common carotid artery (CCA) or internal carotid artery (ICA) and maximum intima-medial thickness (IMT) of CCA (max-CIMT) > 0.9 mm were examined using univariate and multivariate analyses. RESULTS: At blood sampling, the mean and SD patient age was 52.7 ± 13.8 years old. Plasma XOR(pmol/h/ml) activity was significantly higher in patients with CCA/ICA plaque or max-CIMT >0.9 mm than those without. [23.9 (11.8, 38.3) vs. 8.29 (6.67, 17.5), p < .01, 23.9 (16.9, 71.2) vs. 9.16 (6.67, 28.2), p = .01] Univariate and multivariate logistic regression analyses revealed age and plasma XOR activity as independent predictors of CCA/ICA plaque or max-CIMT >0.9 mm. Receiver operator characteristic curve analyses revealed that the cutoff value of plasma XOR activity for the diagnosis of CCA/ICA plaque or CCA-IMT > 0.9 mm was 16.3 pmol/h/ml. CONCLUSION: Plasma XOR activity is associated independently with atherosclerotic changes in the carotid artery of stable post-KT patients.

The association of remdesivir and in-hospital outcomes for COVID-19 patients treated with steroids.

BACKGROUND: Remdesivir has been shown to decrease SARS-CoV-2 viral loads and the duration of COVID-19 symptoms. However, current evidence regarding the association between remdesivir and in-hospital mortality for patients with COVID-19 steroid treatments is limited. We aimed to investigate whether remdesivir reduces in-hospital mortality among patients with COVID-19 treated with steroids. METHODS: In this retrospective multicentre study, we reviewed the medical records of 3372 patients discharged between 1 March 2020 and 30 March 2021, with laboratory confirmed COVID-19 in the Mount Sinai Health System and treated with steroids. We evaluated the effect of remdesivir on the outcomes using propensity score analyses. Subgroup analyses were conducted by stratification of patients by endotracheal intubation and COVID-19 antibody status. Acute kidney injury (AKI) was defined as an absolute serum creatinine increase of 0.3 mg/dL or a relative increase of 50%. RESULTS: Of the 3372 eligible patients, 1336 (39.6%) received remdesivir. After 1:1 propensity score matching (N = 999 pairs), in-hospital mortality was similar between those with and without remdesivir (21.4% versus 21.6%, respectively, P = 0.96). Remdesivir was not significantly associated with in-hospital mortality regardless of endotracheal intubation or COVID-19 antibody status. However, there was a signal that remdesivir was associated with a reduced risk of AKI in the propensity matched analysis (17.5% versus 23.4%, respectively, P = 0.001). CONCLUSIONS: Remdesivir was not associated with reduced risk of in-hospital mortality in patients with COVID-19 treated with steroids but potentially associated with decreased risk of AKI. These findings should be confirmed in prospective studies focusing on COVID-19 patients treated with steroids.

The association of COVID-19 antibody with in-hospital outcomes in COVID-19 infected patients.

We aimed to investigate whether hospitalizations of patients who tested positive for coronavirus disease 2019 (COVID-19) antibodies are associated with reduced in-hospital mortality. Of the 2459 patients admitted due to COVID-19 and tested for antibodies, 937 (38.1%) had positive tests. After adjustment for patient characteristics and treatments, patients with positive COVID-19 antibody test had lower in-hospital mortality compared with those with negative test results (odds ratio [OR]: 0.62; 95% confidential interval [95% CI] 0.46-0.83, p = 0.001). In conclusion, positive COVID-19 antibody test results were associated with the reduced risk of in-hospital mortality for COVID-19 patients.

Prognostic significance of concentric left ventricular hypertrophy at peritoneal dialysis initiation.

BACKGROUND: Concentric left ventricular hypertrophy (cLVH) is a common left ventricular geometric pattern in patients undergoing maintenance dialysis, including peritoneal dialysis (PD). The relationship between cLVH at PD initiation and the prognosis of patients remains unclear, however. This study aimed to investigate the impact of cLVH at PD initiation on patient survival and major adverse cardiovascular events (MACE). METHODS: The retrospective cohort study included 131 patients who underwent echocardiography during the PD initiation period. Based on echocardiographic measurements, cLVH was defined as a condition with increased LV mass index and increased relative wall thickness. The relationship between cLVH and the prognosis was assessed. RESULTS: Concentric LVH was identified in 29 patients (22%) at PD initiation, and patient survival, MACE-free survival and PD continuation were significantly reduced in the cLVH group compared with the non-cLVH group. In the Cox regression analysis, cLVH was demonstrated as an independent risk factor of mortality (HR [95%CI]: 3.32 [1.13-9.70]) for all patients. For patients over 65 years old, cLVH was significantly associated with mortality and MACE (HR [95%CI]: 3.51 [1.06-11.58] and 2.97 [1.26-7.01], respectively). Serum albumin at PD initiation was independently correlated with cLVH. CONCLUSIONS: In our study, cLVH at PD initiation was independently associated with survival in all patients and with both survival and MACE in elderly patients. Evaluation of LV geometry at PD initiation might therefore help identify high-risk patients. Further studies involving larger numbers of patients are needed to confirm the findings from this study and clarify whether treatment interventions for factors such as nutrition status could ameliorate cLVH and improve patient outcomes.

Acute respiratory effect of transpyloric feeding for respiratory exacerbation in preterm infants.

OBJECTIVES: Gastroesophageal reflux may exacerbate chronic lung disease in preterm infants. We evaluated the short-term effects of transpyloric feeding on respiratory status in preterm infants during mechanical ventilation. METHODS: We retrospectively collected data from the hospital information management system. To evaluate the effect of transpyloric feeding on oxygenation, we compared changes in SpO2/FiO2 ratios before and after commencing transpyloric feeding by a piecewise linear regression model. RESULTS: We examined 33 infants (median gestational age, 25.4 weeks; median birth weight, 656 g) who underwent transpyloric feeding. All tubes were placed at the bedside without fluoroscopy. No cases of unsuccessful placement, gastroduodenal perforation, or tracheal misinsertion occurred. Transpyloric feeding began at a median age of 18 (interquartile range, 15-23) days. Mean SpO2/FiO2 (±SD) ratios were 391 (±49), 371 (±51), 365 (±56), and 366 (±53) 72-96 h before, 0-24 h before, 48-72 h after, and 96-120 h after starting transpyloric feeding, respectively. The rate of change per hour of SpO2/FiO2 ratios increased 48-120 h after compared with 0-96 h before transpyloric feeding (0.03 [95% confidence interval, -0.10 to 0.17] vs. -0.29 [-0.47 to -0.12]) (p=0.007). No apparent changes occurred in the mean airway pressure, amplitude pressure, or pCO2. CONCLUSIONS: Transpyloric feeding during mechanical ventilation can prevent the deterioration of oxygenation without major complications at the stage of respiratory exacerbation in preterm infants.

Association Between IV Thiamine and Mortality in Patients With Septic Shock: A Nationwide Observational Study.

OBJECTIVES: To examine the effect of thiamine administration on mortality in patients with septic shock requiring norepinephrine. DESIGN: Retrospective observational cohort study from July 2010 to March 2017. SETTING: More than 1,000 acute care hospitals covering approximately 90% of all tertiary care emergency hospitals in Japan. PATIENTS: Patients with septic shock requiring norepinephrine within 2 days of admission were retrospectively reviewed. INTERVENTIONS: Patients who received greater than or equal to 100 mg of thiamine within 2 days of admission were included in the thiamine group and those who did not were included in the control group. MEASUREMENTS AND MAIN RESULTS: We identified a total of 68,571 eligible patients, including 18,780 and 49,791 patients in the thiamine and control groups, respectively. In the thiamine group, 100 and 200 mg of thiamine per day were administered to 10,143 (54.0%) and 7,679 (40.9%) patients, respectively. The 28-day mortality were 19.2% (3,609/18,780) and 17.8% (8,845/49,791) in the thiamine and control groups, respectively. After adjusting for confounders by inverse probability of treatment weighting, no significant differences were observed between the two groups (risk difference, 0.2%; 95% CI, -0.5% to 0.9%). There were also no significant differences between the 100-mg thiamine group and the control group (risk difference, 0.6%; 95% CI, -0.3% to 1.4%) or between the 200-mg thiamine group and the control group (risk difference, -0.3%; 95% CI, -1.3% to 0.8%). CONCLUSIONS: The findings of this nationwide database-based observational study did not support an association between thiamine administration early after admission and the 28-day mortality in patients with septic shock.

Pregabalin and injury: A nested case-control and case-crossover study.

PURPOSE: This study was performed to investigate the association between the use of pregabalin and injury. METHODS: The study was based on a predefined cohort of patients aged ≥20 years who had been registered for ≥6 months and contributed to the Japan Medical Data Center claims database. All patients (cases) had been treated for injuries from January 2014 to December 2016. One-to-four case-control matching was performed for age, sex, calendar day of injury (index date), and follow-up duration. A conditional logistic regression analysis was performed to calculate the odds ratio (OR) for pregabalin use within 180 days prior to the index date between the matched cases and controls, with adjustment for comorbidities and relevant drug categories associated with a risk of injury. To minimize within-individual confounding, we also performed a case-crossover analysis to compare the odds of pregabalin use between a 30-day hazard period immediately before the injury and five consecutive 30-day control periods within individuals with injury. RESULTS: Among the 2 324 974 people in the nested cohort, we identified 18 084 cases with injury and 71 885 matched controls. The proportion of pregabalin use was 1.7% (304/18 084) and 1.1% (803/71 885), respectively. The adjusted OR for injury was 1.22 (95% confidence interval [CI], 1.06-1.40). In the case-crossover analysis (n = 304), pregabalin use was also significantly associated with an increased risk of injury (adjusted OR, 1.48; 95% CI, 1.10-2.00). CONCLUSION: This large database study using two different study designs consistently suggested that the use of pregabalin may be associated with an increased risk of injury.

Urinary chloride concentration as a prognostic marker in critically ill patients.

AIM: Associations have been reported among serum chloride concentration, mortality and incidence of acute kidney injury (AKI) in intensive care units (ICU). This study aimed to examine associations among urinary chloride, mortality, and AKI incidence in ICU patients. METHODS: A retrospective observational study was conducted among medical-surgical ICU in a tertiary hospital wherein 170 consecutive ICU patients were evaluated from October 2015 to March 2016 and 116 patients were enrolled. Serial data of serum and urine electrolytes from day 1 to day 4 of ICU admission were examined. The primary and secondary outcomes were ICU mortality and incidence of AKI in the ICU, respectively. RESULTS: Among the 116 enrolled patients, 15 (13%) died during their ICU stay. Although serum and urinary sodium and potassium on day 1 did not significantly differ between ICU survivors and non-survivors, urinary chloride concentration on day 1 was significantly lower in non-survivors. Receiver operating characteristic analysis showed that the cutoff value of day 1 urinary chloride concentration for prediction of ICU mortality was 53 mEq/L. The lower urinary chloride concentration group on day 1 showed a significantly lower survival rate, even in long-term follow-up, compared with the higher urinary chloride group. Addition of day 1 urinary chloride concentration improved prediction of AKI incidence in the ICU by Sequential Organ Failure Assessment score alone. CONCLUSION: Lower urinary chloride concentration was associated with increased mortality and incidence of AKI in the ICU. Further investigation is necessary to clarify the mechanism of urinary chloride regulation.

Expanded Indication for Recombinant Tissue Plasminogen Activator from 3 to 4.5 h after Onset of Stroke in Japan.

OBJECTIVE: We examined the impact of expansion of the time window (from 3 to 4.5 hours) in the labeled indication for recombinant tissue-plasminogen activator (rt-PA) in August 2012 on the use of rt-PA for patients with acute ischemic stroke (AIS) and the outcomes of patients treated with rt-PA. MATERIALS AND METHODS: Using a Japanese nationwide inpatient claims database, we identified patients with AIS who admitted to hospitals that consecutively participated in the database from 2010 to 2014. We defined the pre-expansion period as before August 2012 and the post-expansion period as after August 2012. We conducted an interrupted time-series analysis using patient-level data to examine the association between the expansion and use of rt-PA. We also assessed the association of the expansion with outcomes in patients treated with rt-PA. RESULTS: Among 257,778 patients with AIS, 4.5% patients (5,796/129,326) were treated with rt-PA in the pre-expansion period and 5.8% patients (7,483/128,452) were treated with rt-PA in the post-expansion period. The expansion was associated with greater use of rt-PA (adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 1.24-1.48). Among patients treated with rt-PA, the expansion was associated with functional independence (modified Rankin scale of ≤2) at discharge (aOR, 1.26; 95% CI, 1.03-1.54), but not with in-hospital mortality (aOR, 0.92; 95% CI, 0.68-1.24). CONCLUSIONS: This study showed that expansion of the time window for rt-PA was associated with increased use of rt-PA in patients with AIS, while the functional outcome at discharge was improved after the expansion in patients treated with rt-PA.