Time-varying associations between diabetes and mortality following COVID-19: Evidence from a U.S. Veteran population

Metronidazole hydrochloride has historically been considered first-line therapy for patients with mild to moderate Clostridium difficile infection (CDI) but is inferior to vancomycin hydrochloride for clinical cure. The choice of therapy may likewise have substantial consequences on other downstream outcomes, such as recurrence and mortality, although these secondary outcomes have been less studied. To evaluate the risk of recurrence and all-cause 30-day mortality among patients receiving metronidazole or vancomycin for the treatment of mild to moderate and severe CDI. This retrospective, propensity-matched cohort study evaluated patients treated for CDI, defined as a positive laboratory test result for the presence of C difficile toxins or toxin genes in a stool sample, in the US Department of Veterans Affairs health care system from January 1, 2005, through December 31, 2012. Data analysis was performed from February 7, 2015, through November 22, 2016. Treatment with vancomycin or metronidazole. The outcomes of interest in this study were CDI recurrence and all-cause 30-day mortality. Recurrence was defined as a second positive laboratory test result within 8 weeks of the initial CDI diagnosis. All-cause 30-day mortality was defined as death from any cause within 30 days of the initial CDI diagnosis. A total of 47 471 patients (mean [SD] age, 68.8 [13.3] years; 1947 women [4.1%] and 45 524 men [95.9%]) developed CDI, were treated with vancomycin or metronidazole, and met criteria for entry into the study. Of 47 147 eligible first treatment episodes, 2068 (4.4%) were with vancomycin. Those 2068 patients were matched to 8069 patients in the metronidazole group for a total of 10 137 included patients. Subcohorts were constructed that comprised 5452 patients with mild to moderate disease and 3130 patients with severe disease. There were no differences in the risk of recurrence between patients treated with vancomycin vs those treated with metronidazole in any of the disease severity cohorts. Among patients in the any severity cohort, those who were treated with vancomycin were less likely to die (adjusted relative risk, 0.86; 95% CI, 0.74 to 0.98; adjusted risk difference, -0.02; 95% CI, -0.03 to -0.01). No significant difference was found in the risk of mortality between treatment groups among patients with mild to moderate CDI, but vancomycin significantly reduced the risk of all-cause 30-day mortality among patients with severe CDI (adjusted relative risk, 0.79; 95% CI, 0.65 to 0.97; adjusted risk difference, -0.04; 95% CI, -0.07 to -0.01). Recurrence rates were similar among patients treated with vancomycin and metronidazole. However, the risk of 30-day mortality was significantly reduced among patients who received vancomycin. Our findings may further justify the use of vancomycin as initial therapy for severe CDI.

PurposeTo investigate the associations of anion gap (AG) levels before and 1-day after hemodialysis as well as anion gap changes with the mortality in critically ill patients receiving renal replacement therapy (RRT).MethodsTotally, 637 patients from MIMIC-III were included in this cohort study. The associations between AG (T0), AG (T1), or ∆AG [AG (T0) − AG (T1)], and the risk of 30-day or 1-year mortality were examined by Cox restricted cubic spline regression models. Univariate and multivariate Cox proportional-hazards model was applied to assess the associations between AG (T0), AG (T1), ∆AG with 30-day and 1-year mortality, respectively.ResultsThe median follow-up time was 18.60 (8.53, 38.16) days and 263 (41.3%) patients were survived. There was a linear relationship between AG (T0), AG (T1) or ∆AG and the risk of 30-day or 1-year mortality, respectively. The risk of 30-day mortality was higher in AG (T0) > 21 group (HR = 1.723, 95% CI 1.263–2.350), and AG (T1) > 22.3 group (HR = 2.011, 95% CI 1.417–2.853), while lower in AG > 0 group (HR = 0.664, 95% CI 0.486–0.907). The risk of 1-year mortality was increased in AG (T0) > 21 group (HR = 1.666, 95% CI 1.310–2.119), and AG (T1) > 22.3 group (HR = 1.546, 95% CI 1.159–2.064), while decreased in AG > 0 group (HR = 0.765, 95% CI 0.596–0.981). Patients with AG (T0) ≤ 21 had higher 30-day and 1-year survival probability than those with AG (T0) > 21.ConclusionAG before and after dialysis as well as the changes of AG were important factors associated with the risk of 30-day and 1-year mortality in critically ill patients receiving RRT.

The impact of specific baseline comorbid conditions on the relative risk of postoperative mortality and periprosthetic joint infection (PJI) in elderly patients undergoing TKA has not been well defined. We calculated the relative risk of postoperative mortality and PJI associated with 29 comorbid conditions in Medicare patients undergoing TKA. The Medicare 5% sample was used to calculate the relative risk of 90-day postoperative mortality and PJI as a function of 29 preexisting comorbid conditions in 83,011 patients who underwent primary TKA between 1998 and 2007. The independent risk factors for 90-day postoperative mortality (in decreasing order of significance) were congestive heart failure, metastatic cancer, renal disease, peripheral vascular disease, cerebrovascular disease, lymphoma, cardiac arrhythmia, dementia, pulmonary circulation disorders, and chronic liver disease. The independent risk factors for PJI (in decreasing order of significance) were congestive heart failure, chronic pulmonary disease, preoperative anemia, diabetes, depression, renal disease, pulmonary circulation disorders, obesity, rheumatologic disease, psychoses, metastatic tumor, peripheral vascular disease, and valvular disease. We believe this information important when counseling elderly patients regarding the risks of mortality and PJI after TKA and risk-adjusting publicly reported TKA patient outcomes.

IntroductionSotrovimab, a recombinant human monoclonal antibody (mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had US Food and Drug Administration Emergency Use Authorization for the treatment of high-risk outpatients with mild-to-moderate coronavirus disease 2019 (COVID-19) from 26 May 2021 to 5 April 2022. Real-world clinical effectiveness of sotrovimab in reducing the risk of 30-day all-cause hospitalization and/or mortality was evaluated for the period when the prevalence of circulating SARS-CoV-2 variants changed between Delta and Omicron in the USA.MethodsA retrospective analysis was conducted of de-identified patients diagnosed with COVID-19 between 1 September 2021 to 30 April 2022 in the FAIR Health National Private Insurance Claims database. Patients meeting high-risk criteria were divided into two cohorts: sotrovimab and not treated with a mAb (“no mAb”). All-cause hospitalizations and facility-reported mortality ≤ 30 days of diagnosis (“30-day hospitalization or mortality”) were identified. Multivariable and propensity score-matched Poisson and logistic regressions were conducted to estimate the adjusted relative risk (RR) and odds of 30-day hospitalization or mortality in each cohort.ResultsCompared with the no mAb cohort (n = 1,514,868), the sotrovimab cohort (n = 15,633) was older and had a higher proportion of patients with high-risk conditions. In the no mAb cohort, 84,307 (5.57%) patients were hospitalized and 8167 (0.54%) deaths were identified, while in the sotrovimab cohort, 418 (2.67%) patients were hospitalized and 13 (0.08%) deaths were identified. After adjusting for potential confounders, the sotrovimab cohort had a 55% lower risk of 30-day hospitalization or mortality (RR 0.45, 95% CI 0.41–0.49) and an 85% lower risk of 30-day mortality (RR 0.15, 95% CI 0.08–0.29). Monthly, from September 2021 to April 2022, the RR reduction for 30-day hospitalization or mortality in the sotrovimab cohort was maintained, ranging from 46% to 71% compared with the no mAb cohort; the RR estimate in April 2022 was uncertain, with wide confidence intervals due to the small sample size.ConclusionSotrovimab was associated with reduced risk of 30-day all-cause hospitalization and mortality versus no mAb treatment. Clinical effectiveness persisted during Delta and early Omicron variant waves and among all high-risk subgroups assessed.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00755-0.

Our objective was to quantify the association between intensive care unit-acquired dysglycemia (hyperglycemia, hypoglycemia, and high variability) and in-hospital mortality. Retrospective, observational study. eICU Research Institute participating hospitals with an active tele-ICU program between January 1, 2008, and September 30, 2010, representing 784,392 adult intensive care unit patients. A total of 194,772 patients met inclusion criteria with an intensive care unit length of stay >48 hrs. None. Acute Physiology and Chronic Health Evaluation IV standardized mortality ratios were calculated for dysglycemia present at admission and acquired in the intensive care unit. Intensive care unit-acquired dysglycemia was modeled using multivariable modified Poisson regression to account for confounding not incorporated in Acute Physiology and Chronic Health Evaluation. Dysglycemia severity was assessed by the relative risk of in-hospital mortality associated with the maximum, time-weighted average daily glucose; lowest glucose value throughout the intensive care unit stay; and quintiles of variability (coefficient of variation). The association of duration beyond thresholds of dysglycemia on mortality was also modeled. The adjusted relative risk (95% confidence interval) of mortality for the maximum intensive care unit average daily glucose was 1.13 (1.04-1.58), 1.43 (1.30-1.58), 1.63 (1.47-1.81), 1.76 (1.55-1.99), and 1.89 (1.62-2.19) for 110-150 mg/dL, 151-180 mg/dL, 180-240 mg/dL, 240-300 mg/dL, and >300 mg/dL, respectively, compared to patients whose highest average daily glucose was 80-110 mg/dL. The relative risk of mortality for the lowest glucose value was 1.67 (1.37-2.03), 1.53 (1.37-1.70), 1.12 (1.04-1.21), and 1.06 (1.01-1.11) for <20 mg/dL, 20-40 mg/dL, 40-60 mg/dL, and 60-80 mg/dL, respectively, compared to patients whose lowest value was 80-110 mg/dL. The relative risk of mortality increased with greater duration of hyperglycemia and with increased variability. The relative risk for the highest compared to lowest quintile of variability was 1.61 (1.47-1.78). The association of duration of hyperglycemia on mortality was more pronounced with more severe hyperglycemia. The risk of mortality progressively increased with severity and duration of deviation from euglycemia and with increased variability. These data suggest that severe intensive care unit-acquired hyperglycemia, hypoglycemia, and variability are associated with similar risks of mortality.

Mortality after emergency abdominal operations in premature infants

This study was to investigate the association between oral anticoagulant use and 28-day mortality and in-hospital mortality in patients with acute respiratory distress syndrome (ARDS). A total of 1754 ARDS patients were identified in database from 2008 to 2022 in this cohort study. Univariable and multivariable cox regression models were applied to assess the associations of oral anticoagulant use with the risk of 28-day mortality and in-hospital mortality. Propensity score matching (PSM) was performed in ARDS patients according to whether they were taking oral anticoagulants or not to control potential bias. Subgroup analysis was performed according to severity of ARDS (mild, moderate, and severe), and comorbidities (atrial fibrillation, sepsis, and AKI). Hazards ratio (HR) and respective confidence interval (CI) were presented. In total, 7758 patients not receiving oral anticoagulant and 905 patients receiving oral anticoagulant. The reduced risk of 28-day mortality in ARDS patients was identified in those undergoing oral anticoagulant use (HR = 0.32, 95%CI: 0.24-0.44). Oral anticoagulant use was associated with reduced risk of in-hospital mortality (HR = 0.27, 95%CI: 0.20-0.37). After adjusting for the respective confounding factors, the associations of Warfarin with decreased risk of 28-day and in-hospital mortality were not significant (P > 0.05). Oral anticoagulant was related to decreased risk of 28-day/in-hospital mortality in patients with ARDS. Warfarin and novel oral anticoagulants showed no significant difference on 28-day/in-hospital mortality in patients with ARDS.

The influence of obesity on outcomes following total hip replacement is unclear. Restriction of total hip replacement on the basis of body mass index (BMI) has been suggested. The purpose of this study was to assess the influence of BMI on the risk of revision and 90-day mortality. This was a population-based, longitudinal cohort study of the National Joint Registry (NJR) for England, Wales, Northern Ireland and the Isle of Man. Using data recorded from April 2003 to December 2015, linked to Office for National Statistics data, we ascertained revision and 90-day mortality rates following primary total hip replacement by BMI category. The probability of revision was estimated using Kaplan-Meier methods. Associations of BMI with revision and mortality were explored using adjusted Cox proportional hazards regression models. We investigated revision and 90-day mortality among 415,598 and 413,741 primary total hip replacements, respectively. Each data set accounts for approximately 52% of the total number of recorded operations in the NJR. Thirty-eight percent of the patients were classified as obese. At 10 years, class-III obese patients had the highest cumulative probability of revision (6.7% [95% confidence interval (CI), 5.5% to 8.2%]), twice that of the underweight group (3.3% [95% CI, 2.2% to 4.9%]). When the analysis was adjusted for age, sex, American Society of Anesthesiologists [ASA] grade, year of operation, indication, and fixation type, compared with patients with normal BMI, significantly elevated hazard ratios (HRs) for revision were observed for patients in the BMI categories of class-I obese (≥30 to <35 kg/m) (HR, 1.14 [95% CI, 1.07 to 1.22]), class-II obese (≥35 to <40 kg/m) (HR, 1.30 [95% CI, 1.19 to 1.40]), and class-III obese (≥40 to ≤60 kg/m) (HR, 1.43 [95% CI, 1.27 to 1.61]) (p < 0.0005 for all). Underweight patients had a substantially higher cumulative probability of 90-day mortality (1.17%; 95% CI, 0.86% to 1.58%) compared with patients with normal BMI (0.43%; 95% CI, 0.39% to 0.48%). The risk of 90-day mortality was significantly higher for the underweight group (HR, 2.09 [95% CI, 1.51 to 2.89]; p < 0.0005) and significantly lower for patients who were categorized as overweight (HR, 0.70; 95% CI, 0.61 to 0.81; p < 0.0005), class-I obese (HR, 0.69 [95% CI, 0.59 to 0.81]; p < 0.0005), and class-II obese (HR, 0.79 [95% CI, 0.63 to 0.98]; p = 0.049) compared with patients with normal BMI. Although long-term revision rates following total hip replacement were higher among obese patients, we believe that the rates remained acceptable by contemporary standards and were balanced by a lower risk of 90-day mortality. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Patients with dementia are predisposed to multiple physiological abnormalities. It is uncertain if dementia associates with higher rates of perioperative mortality and morbidity. We used reimbursement claims data of Taiwan’s National Health Insurance and conducted propensity score matching analyses to evaluate the risk of mortality and major complications in patients with or without dementia undergoing major surgery between 2004 and 2013. We applied multivariable logistic regressions to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for the outcome of interest. After matching to demographic and clinical covariates, 7863 matched pairs were selected for analysis. Dementia was significantly associated with greater risks of 30-day in-hospital mortality (aOR: 1.71, 95% CI: 1.09–2.70), pneumonia (aOR: 1.48, 95% CI: 1.16–1.88), urinary tract infection (aOR: 1.59, 95% CI: 1.30–1.96), and sepsis (OR: 1.77, 95% CI: 1.34–2.34) compared to non-dementia controls. The mortality risk in dementia patients was attenuated but persisted over time, 180 days (aOR: 1.49, 95% CI: 1.23–1.81) and 365 days (aOR: 1.52, 95% CI: 1.30–1.78) after surgery. Additionally, patients with dementia were more likely to receive blood transfusion (aOR: 1.32, 95% CI: 1.11–1.58) and to need intensive care (aOR: 1.40, 95% CI: 1.12–1.76) compared to non-dementia controls. Senile dementia and Alzheimer’s disease were independently associated with higher rates of perioperative mortality and complications, but vascular dementia was not affected. We found that preexisting dementia was associated with mortality and morbidity after major surgery.

Frailty Is Associated with an Increased Risk of Complications and Need for Repeat Procedures after Sling Surgery in Older Adults.

ObjectiveTo explore the values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), neutrophil to albumin ratio (NAR), prognostic nutritional index (PNI), systemic immune inflammatory index (SII) and red cell distribution width to albumin ratio (RA) for evaluating the risk of 30-day mortality of ischemic stroke or hemorrhagic stroke patients.MethodsIn this cohort study, the data of 1,601 patients diagnosed with stroke were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Among them, 908 were hemorrhagic stroke patients and 693 were ischemic stroke patients. Demographic and clinical variables of patients were collected. Univariate and multivariable Cox regression were performed to evaluate the predictive values of NLR, PLR, SII, NAR, RA, and PNI for 30-day mortality in hemorrhagic stroke or ischemic stroke patients. The receiver operator characteristic (ROC) curves were plotted to assess the predictive values of NLR, NAR, and RA for 30-day mortality of hemorrhagic stroke patients.ResultsAt the end of follow-up, 226 hemorrhagic stroke patients and 216 ischemic stroke patients died. The elevated NLR level was associated with increased risk of 30-day mortality in hemorrhagic stroke [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.06–1.29]. The increased NAR level was associated with elevated risk of 30-day mortality in hemorrhagic stroke (HR = 1.16, 95% CI: 1.02–1.30). The high RA level was linked with increased risk of 30-day mortality (HR = 1.44, 95% CI: 1.23–1.69). No significant correlation was observed in these inflammation biomarkers with the risk of 30-day mortality in ischemic stroke patients. The area under the curves (AUCs) of NLR, RA, and NAR for evaluating the risk of 30-day mortality of hemorrhagic stroke patients were 0.552 (95% CI: 0.503–0.601), 0.644 (95% CI: 0.590–0.699) and 0.541 (95% CI: 0.490–0.592).ConclusionNLR, NAR, and RA were potential prognostic biomarkers for predicting 30-day mortality of hemorrhagic stroke patients, which might provide clinicians an easy and cheap way to quickly identify patients with high risk of mortality.

There is no consensus on the best comorbidity measure in candidates for radical cystectomy. The aim of this study was to identify tool best suited to identify patients at risk for 90-day or premature long-term non-bladder cancer mortality. We studied 1268 patients who underwent radical cystectomy to identify patients at risk for 90-day and later-than-90-day mortality, respectively. Six classifications were investigated as possible predictors of both types of mortality. Multivariable models including age as continuous variable and each classification separately were calculated. A heuristic ranking was based on the evaluation of the hazard ratios, p values, Akaike's information criteria, and concerning the logit models also the areas under the curve. The median follow-up was 5.7years. Within 90days after surgery, the mortality rate was 4.2%. The greatest independent contribution concerning the prediction of 90-day mortality was seen with the American Society of Anesthesiologists (ASA) physical status classification (classes 3-4 versus 1-2: hazard ratio 7.98, 95% confidence interval 3.54-18.01, p < 0.0001). In the longer term, countable diseases (Canadian Cardiovascular Society classification of angina pectoris, conditions contributing the Charlson score) were of greater importance. The results of heuristic ranking were confirmed by multivariate analyses including age and all classifications together. Besides to chronological age, clinicians should pay particular attention to the ASA classification to identify patients at risk for 90-day mortality after radical cystectomy, whereas long-term mortality is more determined by countable comorbid diseases.

To evaluate the association of pretrauma center (PTC) red blood cell (RBC) transfusion with outcomes in severely injured patients. Hemorrhage remains a major driver of mortality. Little evidence exists supporting PTC interventions to mitigate this. Blunt injured patients in shock arriving at a trauma center within 2 hours of injury were included from the Glue Grant database. Subjects were dichotomized by PTC RBC transfusion. Outcomes included 24-hour mortality, 30-day mortality, and trauma-induced coagulopathy [(TIC), admission international normalized ratio >1.5]. Cox regression and logistic regression determined the association of PTC RBC transfusion with outcomes. To address baseline differences, propensity score matching was used. Of 1415 subjects, 50 received PTC RBC transfusion. Demographics and injury severity score were similar. The PTC RBC group received 1.3 units of RBCs (median), and 52% were scene transports. PTC RBC transfusion was associated with a 95% reduction in odds of 24-hour mortality [odds ratio (OR) = 0.05; 95% confidence interval (CI), 0.01-0.48; P < 0.01], 64% reduction in the risk of 30-day mortality [hazard ratio = 0.36; 95% CI, 0.15-0.83; P = 0.02], and 88% reduction in odds of TIC (OR = 0.12; 95% CI, 0.02-0.79; P = 0.03). The matched cohort included 113 subjects (31% PTC RBC group). Baseline characteristics were similar. PTC RBC transfusion was associated with a 98% reduction in odds of 24-hour mortality (OR = 0.02; 95% CI, 0.01-0.69; P = 0.04), 88% reduction in the risk of 30-day mortality (hazard ratio = 0.12; 95% CI, 0.03-0.61; P = 0.01), and 99% reduction in odds of TIC (OR = 0.01; 95% CI, 0.01-0.95; P = 0.05). PTC RBC administration was associated with a lower risk of 24-hour mortality, 30-day mortality, and TIC in severely injured patients with blunt trauma, warranting further prospective study.

Association between intraoperative hypotension and 30-day mortality, major adverse cardiac events, and acute kidney injury after non-cardiac surgery: A meta-analysis of cohort studies

BackgroundSepsis is a recognized global health challenge that places a considerable disease burden on countries. Although there has been some progress in the study of sepsis, the mortality rate of sepsis remains high. The relationship between serum osmolality and the prognosis of patients with sepsis is unclear.MethodPatients with sepsis who met the criteria in the Medical Information Mart for Intensive Care IV database were included in the study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined using multivariable Cox regression. The relationship between serum osmolality and the 28-day mortality risk in patients with sepsis was investigated using curve fitting, and inflection points were calculated.ResultsA total of 13,219 patients with sepsis were enrolled in the study; the mean age was 65.1 years, 56.9 % were male, and the 28-day mortality rate was 18.8 %. After adjusting for covariates, the risk of 28-day mortality was elevated by 99% (HR 1.99, 95%CI 1.74-2.28) in the highest quintile of serum osmolality (Q5 >303.21) and by 59% (HR 1.59, 95%CI 1.39-1.83) in the lowest quintile (Q1 ≤285.80), as compared to the reference quintile (Q3 291.38-296.29). The results of the curve fitting showed a U-shaped relationship between serum osmolality and the risk of 28-day mortality, with an inflection point of 286.9 mmol/L.ConclusionThere is a U-shaped relationship between serum osmolality and the 28-day mortality risk in patients with sepsis. Higher or lower serum osmolality is associated with an increased risk of mortality in patients with sepsis. Patients with sepsis have a lower risk of mortality when their osmolality is 285.80-296.29 mmol/L.