The pathophysiological mechanisms by which venous congestion and hypotension lead to acute adverse kidney events after cardiac surgery with cardiopulmonary bypass have not been elucidated. We tested the hypothesis that intraoperative hypotension and venous congestion are associated with acute kidney injury and acute kidney disease. Primary exposures were venous congestion and intraoperative hypotension defined by central venous pressure ≥12, 16, or 20 mm Hg or mean arterial pressure ≤55, 65, or 75 mm Hg. The primary outcomes were acute kidney injury and acute kidney disease. Multivariable logistic regression and Cox proportional hazard models were used, adjusted for relevant confounding factors and multiple comparisons. Of 5127 eligible subjects, 1070 (20.9%) and 327 (7.2%) developed acute kidney injury and acute kidney disease, respectively. The occurrence of acute kidney injury was statistically associated with both venous congestion and intraoperative hypotension. The cumulative incidence rate for new onset acute kidney disease was 1.34 (95% confidence interval [CI], 1.21-1.60) per 100 person-days. Acute kidney disease was significantly associated with each 10 min epoch of central venous pressure ≥12 mm Hg (hazard ratio [HR]=1.03; 99% CI, 1.01-1.06; P<0.001), ≥16 mm Hg (HR=1.04; 99% CI, 1.01-1.07; P<0.001), and ≥20 mm Hg (HR=1.07; 99% CI, 1.02-1.13; P<0.001). Venous congestion was associated with an 8-17% increased risk for de novo renal replacement therapy. In contrast, intraoperative hypotension was not associated with development of acute kidney disease. Although both venous congestion and intraoperative hypotension are associated with acute kidney injury, only venous congestion correlates with acute kidney disease among patients undergoing cardiac surgery requiring cardiopulmonary bypass. The reported associations are suggestive of a pathophysiological role of venous congestion in acute kidney disease.

Background: The objective of this research was to create and validate an interpretable prediction model for drug-induced liver injury (DILI) during tuberculosis (TB) treatment. Methods: A dataset of TB patients from Ningbo City was used to develop models employing the eXtreme Gradient Boosting (XGBoost), random forest (RF), and the least absolute shrinkage and selection operator (LASSO) logistic algorithms. The model's performance was evaluated through various metrics, including the area under the receiver operating characteristic curve (AUROC) and the area under the precision recall curve (AUPR) alongside the decision curve. The Shapley Additive exPlanations (SHAP) method was used to interpret the variable contributions of the superior model. Results: A total of 7,071 TB patients were identified from the regional healthcare dataset. The study cohort consisted of individuals with a median age of 47 years, 68.0% of whom were male, and 16.3% developed DILI. We utilized part of the high dimensional propensity score (HDPS) method to identify relevant variables and obtained a total of 424 variables. From these, 37 variables were selected for inclusion in a logistic model using LASSO. The dataset was then split into training and validation sets according to a 7:3 ratio. In the validation dataset, the XGBoost model displayed improved overall performance, with an AUROC of 0.89, an AUPR of 0.75, an F1 score of 0.57, and a Brier score of 0.07. Both SHAP analysis and XGBoost model highlighted the contribution of baseline liver-related ailments such as DILI, drug-induced hepatitis (DIH), and fatty liver disease (FLD). Age, alanine transaminase (ALT), and total bilirubin (Tbil) were also linked to DILI status. Conclusion: XGBoost demonstrates improved predictive performance compared to RF and LASSO logistic in this study. Moreover, the introduction of the SHAP method enhances the clinical understanding and potential application of the model. For further research, external validation and more detailed feature integration are necessary.

Background: Tuberculosis drug-induced liver injury (TB-DILI) is a common and potentially severe adverse drug reaction leading to treatment interruption and treatment failure. The real-world preventive effectiveness of hepatoprotective agents for DILI is not well described. The aim of the study was to evaluate the patterns of prophylactic therapies in real-world settings and risks of DILI among adult TB patients without known risk factors for DILI.Methods: This is a population-based retrospective cohort study of patients receiving first-line anti-tuberculosis drugs in the Chinese Center for Disease Control and Prevention (CDC) TB registry linked to the Ningbo Regional Health Care Database (NRHCD) between 2015 and 2020. The primary exposure was any use of chemopreventive agents including silymarin and/or glycyrrhetinic acid during the 30-day period prior to TB diagnosis (index date). The main outcome measure was the occurrence of newly onset DILI following TB treatment. Eligible patients were followed until the earliest of any DILI, treatment discontinuation, death, or end of the study period (30 June 2020). Marginal structural competing risk models and Cox models via inverse probability treatment weights using high-dimensional propensity scores were used to estimate subdistribution hazard risks (SHR) and 95% confidence intervals (CIs) for DILI risks, with adjustment for age, sex, TB-related characteristics, and comorbidities.Results: We identified a cohort of 6,743 adult patients with TB (mean age of 47.1 [SD 18.7] years; 65.80% male), of whom 2,886 (42.8%) patients received hepatoprotective agents. A total of 895 DILI events and 111 all-cause death events without DILI were observed over a median follow-up of 367 days post-TB diagnosis. The incidence rates of composite outcomes combining DILI and all-cause mortality were 248.9 and 222.3 per 1,000 person-years in the hepatoprotective agent exposed and unexposed groups (relative hazard ratio 1.35, 95% CI 1.11–1.64), respectively. The incidence rates of DILI were 223.7 and 196.1 per 1,000 person-years in the hepatoprotective agent exposed and unexposed groups (relative hazard ratio 1.38, 95% CI 1.12–1.71), respectively. Patients with any chemopreventive agent use had comparable liver function changes as evidenced by laboratory tests.Conclusion: A non-trivial number of adult patients received chemopreventive agents for TB-DILI. However, prophylactic utilization of hepatoprotective agents was not associated with a reduction in TB-DILI risks.

Background: Multimorbidity is defined as the existence of two or more chronic health conditions in the same individual. While patients with tuberculosis commonly have multiple conditions at diagnosis, such as HIV, diabetes, and depression, to the authors' knowledge, there is limited information on the patterns of multimorbidity, and how the types and combinations of conditions could impact the healthcare utilization, expenditure, and TB outcomes.Methods: An observational cohort study of adult patients diagnosed with tuberculosis was conducted using the Chinese Center for Disease Control and Prevention (CDC)'s National TB Information System (NTBIS) linked to the Ningbo Regional Health Care Database (NRHCD) (2015–2020). Latent class analysis was used to identify comorbidity groups among the subset with ≥2 conditions including TB. Group-level health care use, expenditure, and treatment outcomes were compared with patients without chronic conditions using multivariate regression models.Results: A total of 9,651 patients with TB were identified, of whom approximately 61.4% had no chronic conditions, 17.4% had 1 chronic condition, and 21.3% had ≥2 chronic conditions. Among those with ≥1 chronic condition other than TB, 4 groups emerged: (1) general morbidity (54.4%); (2) cardiovascular morbidity without complications (34.7%); (3) cardiovascular morbidity with complications (5.0%); (4) respiratory morbidity (5.9%). The respiratory morbidity group experienced the highest expenditures, at 16,360 CNY more overall (95% CI, CNY 12,615–21,215) after adjustment compared with TB patients without chronic conditions. The respiratory morbidity and cardiovascular morbidity with complications group also had the lowest odds of favorable TB outcomes [adjusted odds ratio (aOR), 0.68; 95% CI, 0.49–0.93] and (aOR 0.59, 95% CI 0.42–0.83), respectively. The cardiovascular morbidity without complications group had the highest odds of successful TB treatment (aOR, 1.40; 95% CI, 1.15–1.71).Conclusions: Multimorbidity is common among patients with TB. The current study identified four distinct comorbidity subgroups, all of which experienced high, yet differential, rates of health care use. These findings highlight the need for urgent reforms to transform current fragmented TB care delivery and improve access to other specialists and financial assistance.

Although nonsteroidal anti inflammatory drugs are superior to opioids in dental pain management, opioids are still prescribed for dental pain in the United States. Little is known about the serious adverse outcomes of short-acting opioids within the context of dental prescribing. The objective of this study was to evaluate adverse outcomes and persistent opioid use (POU) after opioid prescriptions by dentists, based on whether opioids were overprescribed or within recommendations. A cross-sectional analysis of adults with a dental visit and corresponding opioid prescription (index) from 2011 to 2018 within a nationwide commercial claims database was conducted. Opioid overprescribing was defined as >120 morphine milligram equivalents per Centers for Disease Control and Prevention guidelines. Generalized estimating equation models were used to assess adverse outcomes (emergency department visits, hospitalizations, newly diagnosed substance use disorder, naloxone administration, or death within 30 days from index) and POU (≥1 prescription 4-90 days postindex). Predicted probabilities are reported. Of 633,387 visits, 2.6% experienced an adverse outcome and 16.6% had POU. Adverse outcome risk was not different whether opioids were overprescribed or within recommendations (predicted probability 9.0%, confidence interval [CI]: 8.0%-10.2% vs 9.1%, CI: 8.1-10.3), but POU was higher when opioids were overprescribed (predicted probability 27.4%, CI: 26.1%-28.8% vs 25.2%, CI: 24.0%-26.5%). Visits associated with mild pain and those with substance use disorders had the highest risk of both outcomes. Findings from this study demonstrate that dental prescribing of opioids was associated with adverse outcomes and POU, even when prescriptions were concordant with guidelines. Additional efforts are required to improve analgesic prescribing in dentistry, especially in groups at high risk of opioid-related adverse outcomes.