Lower mortality risk associated with remdesivir + dexamethasone versus dexamethasone alone for the treatment of patients hospitalized for COVID-19.

BACKGROUND: Treatment guidelines were developed early in the pandemic when much about COVID-19 was unknown. Given the evolution of SARS-CoV-2, real-world data can provide clinicians with updated information. The objective of this analysis was to assess mortality risk in patients hospitalized for COVID-19 during the Omicron period receiving remdesivir+dexamethasone versus dexamethasone alone. METHODS: A large, multicenter US hospital database was used to identify hospitalized adult patients, with a primary discharge diagnosis of COVID-19 also flagged as "present on admission" treated with remdesivir+dexamethasone or dexamethasone alone from December 2021 to April 2023. Patients were matched 1:1 using propensity score matching and stratified by baseline oxygen requirements. Cox proportional hazards model was used to assess time to 14- and 28-day in-hospital all-cause mortality. RESULTS: A total of 33 037 patients were matched, with most patients ≥65 years old (72%), White (78%), and non-Hispanic (84%). Remdesivir+dexamethasone was associated with lower mortality risk versus dexamethasone alone across all baseline oxygen requirements at 14 days (no supplemental oxygen charges: adjusted hazard ratio [95% CI]: 0.79 [0.72-0.87], low flow oxygen: 0.70 [0.64-0.77], high flow oxygen/non-invasive ventilation: 0.69 [0.62-0.76], invasive mechanical ventilation/extracorporeal membrane oxygen (IMV/ECMO): 0.78 [0.64-0.94]), with similar results at 28 days. CONCLUSIONS: Remdesivir+dexamethasone was associated with a significant reduction in 14- and 28-day mortality compared to dexamethasone alone in patients hospitalized for COVID-19 across all levels of baseline respiratory support, including IMV/ECMO. However, the use of remdesivir+dexamethasone still has low clinical practice uptake. In addition, these data suggest a need to update the existing guidelines.

Characterizing Imbalance in the Tails of the Propensity Score Distribution.

Understanding characteristics of patients with propensity scores in the tails of the propensity score (PS) distribution has relevance for inverse-probability-of-treatment-weighted and PS-based estimation in observational studies. Here we outline a method for identifying variables most responsible for extreme propensity scores. The approach is illustrated in 3 scenarios: 1) a plasmode simulation of adult patients in the National Ambulatory Medical Care Survey (2011-2015) and 2) timing of dexamethasone initiation and 3) timing of remdesivir initiation in patients hospitalized for coronavirus disease 2019 from February 2020 through January 2021. PS models were fitted using relevant baseline covariates, and tails of the PS distribution were defined using asymmetric first and 99th percentiles. After fitting of the PS model in each original data set, values of each key covariate were permuted and model-agnostic variable importance measures were examined. Visualization and variable importance techniques were helpful in identifying variables most responsible for extreme propensity scores and may help identify individual characteristics that might make patients inappropriate for inclusion in a study (e.g., off-label use). Subsetting or restricting the study sample based on variables identified using this approach may help investigators avoid the need for trimming or overlap weights in studies.

Hydroxychloroquine in lupus or rheumatoid arthritis pregnancy and risk of major congenital malformations: a population-based cohort study.

OBJECTIVES: To assess the infant risk of major congenital malformations (MCM) associated with first-trimester exposure to hydroxychloroquine (HCQ) among mothers with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). METHODS: This population-based cohort study utilised Swedish nationwide registers and included all singleton births (2006-2021) among individuals with prevalent SLE or RA in Sweden. The exposure was filling ≥1 HCQ prescription during the first trimester. The outcome was infant MCM within one year of birth. Inverse probability of treatment weighting was applied to adjust for potential confounders (e.g. maternal smoking, body mass index, pregestational diabetes, and corticosteroids). Modified Poisson regression models with robust variance estimated risk ratios and 95% confidence intervals (RR 95%CI). RESULTS: We included 1,007 births (453 exposed) and 2,500 births (144 exposed) in the SLE and RA cohorts, respectively. The MCM risks in the SLE overall cohort, exposed, and unexposed groups were 3.6%, 3.7%, and 3.4%, respectively. The corresponding figures in the RA cohort were 4.4%, 5.6%, and 4.3%, respectively. The adjusted RRs (95%CI) were 1.29 (0.65-2.56) in the SLE cohort, 1.32 (0.56-3.13) in the RA cohort, and 1.30 (0.76-2.23) in the pooled analysis. The adjusted risk difference (exposed vs unexposed) was small (0.9% in SLE and 1.3% in RA). Sensitivity analyses examining different exposure and outcome windows yielded similar findings. CONCLUSIONS: First-trimester exposure to HCQ was not associated with a significantly increased risk of MCM. HCQ's benefits may outweigh the risks in managing SLE or RA during pregnancy.

Survival Outcome Superiority of Total Pharyngolaryngectomy Compared with Chemoradiotherapy for T4aM0 Hypopharyngeal Squamous Cell Carcinoma: A Nationwide Database Study of Japan.

BACKGROUND: The purpose of this study is to elucidate whether total pharyngolaryngectomy (TPL) or chemoradiotherapy (CRT) provides a better prognostic outcome in patients with T4aM0 hypopharyngeal carcinoma (HPSCC) using a nationwide database. METHODS: All data were obtained from the Head and Neck Cancer Registry of Japan, and information from patients who were newly diagnosed with T4aM0 HPSCC between 2011 and 2015 was extracted. The primary endpoint was disease-specific survival (DSS), and the secondary endpoint was overall survival (OS). The inverse probability of treatment weighting (IPTW) adjustments was used for survival analyses. RESULTS: Our cohort included 1143 patients. The TPL and CRT groups included 724 and 419 patients, respectively. Following IPTW adjustments, both the OS and DSS of the TPL group were significantly longer than those of the CRT group (P = .02 and P = .002, respectively). CONCLUSIONS: Survival superiority was demonstrated for patients with T4aM0 HPSCC treated with TPL compared with those treated with CRT.

Gross Hematuria Does not Affect the Selection of Nephrectomy Types for Clinical Stage 1 Clear Cell Renal Cell Carcinoma: A Multicenter, Retrospective Cohort Study.

PURPOSE: This study aimed to discuss the correlation between gross hematuria and postoperative upstaging (from T1 to T3a) in patients with cT1 clear cell renal cell carcinoma (ccRCC) and to compare oncologic outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) in patients with gross hematuria. METHODS: A total of 2145 patients who met the criteria were enrolled in the study (including 363 patients with gross hematuria). The least absolute selection and shrinkage operator logistic regression was used to evaluate the risk factor of postoperative pathological upstaging. The propensity score matching (PSM) and stable inverse probability of treatment weighting (IPTW) analysis were used to balance the confounding factors. The Kaplan-Meier analysis and multivariate Cox proportional risk regression model were used to assess the prognosis. RESULTS: Gross hematuria was a risk factor of postoperative pathological upstaging (odds ratio [OR] = 3.96; 95% confidence interval [CI] 2.44-6.42; P < 0.001). After PSM and stable IPTW adjustment, the characteristics were similar in corresponding patients in the PN and RN groups. In the PSM cohort, PN did not have a statistically significant impact on recurrence-free survival (hazard ratio [HR] = 1.48; 95% CI 0.25-8.88; P = 0.67), metastasis-free survival (HR = 1.24; 95% CI 0.33-4.66; P = 0.75), and overall survival (HR = 1.46; 95% CI 0.31-6.73; P = 0.63) compared with RN. The results were confirmed in sensitivity analyses. CONCLUSIONS: Although gross hematuria was associated with postoperative pathological upstaging in patients with cT1 ccRCC, PN should still be the preferred treatment for such patients.

Propensity weighting plus adjustment in proportional hazards model is not doubly robust.

Recently, it has become common for applied works to combine commonly used survival analysis modeling methods, such as the multivariable Cox model and propensity score weighting, with the intention of forming a doubly robust estimator of an exposure effect hazard ratio that is unbiased in large samples when either the Cox model or the propensity score model is correctly specified. This combination does not, in general, produce a doubly robust estimator, even after regression standardization, when there is truly a causal effect. We demonstrate via simulation this lack of double robustness for the semiparametric Cox model, the Weibull proportional hazards model, and a simple proportional hazards flexible parametric model, with both the latter models fit via maximum likelihood. We provide a novel proof that the combination of propensity score weighting and a proportional hazards survival model, fit either via full or partial likelihood, is consistent under the null of no causal effect of the exposure on the outcome under particular censoring mechanisms if either the propensity score or the outcome model is correctly specified and contains all confounders. Given our results suggesting that double robustness only exists under the null, we outline 2 simple alternative estimators that are doubly robust for the survival difference at a given time point (in the above sense), provided the censoring mechanism can be correctly modeled, and one doubly robust method of estimation for the full survival curve. We provide R code to use these estimators for estimation and inference in the supporting information.

Statistical inference for time-to-event data in non-randomized cohorts with selective attrition.

In multi-season clinical trials with a randomize-once strategy, patients enrolled from previous seasons who stay alive and remain in the study will be treated according to the initial randomization in subsequent seasons. To address the potentially selective attrition from earlier seasons for the non-randomized cohorts, we develop an inverse probability of treatment weighting method using season-specific propensity scores to produce unbiased estimates of survival functions or hazard ratios. Bootstrap variance estimators are used to account for the randomness in the estimated weights and the potential correlations in repeated events within each patient from season to season. Simulation studies show that the weighting procedure and bootstrap variance estimator provide unbiased estimates and valid inferences in Kaplan-Meier estimates and Cox proportional hazard models. Finally, data from the INVESTED trial are analyzed to illustrate the proposed method.

Evaluation and comparison of covariate balance metrics in studies with time-dependent confounding.

Marginal structural models have been increasingly used by analysts in recent years to account for confounding bias in studies with time-varying treatments. The parameters of these models are often estimated using inverse probability of treatment weighting. To ensure that the estimated weights adequately control confounding, it is possible to check for residual imbalance between treatment groups in the weighted data. Several balance metrics have been developed and compared in the cross-sectional case but have not yet been evaluated and compared in longitudinal studies with time-varying treatment. We have first extended the definition of several balance metrics to the case of a time-varying treatment, with or without censoring. We then compared the performance of these balance metrics in a simulation study by assessing the strength of the association between their estimated level of imbalance and bias. We found that the Mahalanobis balance performed best. Finally, the method was illustrated for estimating the cumulative effect of statins exposure over one year on the risk of cardiovascular disease or death in people aged 65 and over in population-wide administrative data. This illustration confirms the feasibility of employing our proposed metrics in large databases with multiple time-points.

Chemotherapy reduces long-term quality of life in recurrence-free colon cancer survivors (LaTE study)-a nationwide inverse probability of treatment-weighted registry-based cohort study and survey.

AIM: Stage III colon cancer is routinely treated with adjuvant chemotherapy, which causes significant short-term morbidity. Its effect on long-term quality of life (QoL) is poorly investigated. The aim of this study was to investigate long-term QoL after curative treatment for colon cancer and explore the impact of chemotherapy on general and disease-specific QoL. METHOD: All patients aged under 75 years operated on for colon cancer between 30 September 2007 and 1 October 2019 were identified by the Cancer Registry of Norway. Exclusion criteria were distant metastasis, recurrence, dementia and rectal/rectosigmoid cancer operation. The primary outcome measure was Gastrointestinal Quality of Life Index (GIQLI). Secondary outcome measures included the Short Form Health Survey (SF-36). To achieve balanced groups when assessing differences in outcome measures the analyses were weighted by inverse probability weights based on a multiple logistic regression model with prechosen confounders. RESULTS: A total of 8627 patients were invited and 3109 responded (36% response rate). After exclusions 3025 patients were included, of whom 1148 (38%) had received adjuvant chemotherapy and 1877 (62%) had surgery alone, with mean follow-up of 75.5 versus 74.5 months, respectively. The GIQLI differed significantly between the groups [mean 111.0 (SD 18.4) vs. 115.6 (SD 17.8), respectively; mean difference: -4.6 (95% CI -5.9; -3.2); p < 0.001]. Those with the highest neurotoxicity exhibited the lowest GIQLI. The adjuvant chemotherapy group scored significantly lower in six of eight SF-36 domains compared with the surgery alone group. The main differences were found in social, physical and emotional function. CONCLUSION: Long-term QoL was significantly lower in patients who received adjuvant chemotherapy than in patients who did not. Neurotoxicity was closely related to reduced QoL in these patients. The low response rate limits the generalizability of the results.

Medical therapy has similar hemostatic efficacy with endoscopic treatment for PUB patients with adherent clot (FIIb ulcers).

BACKGROUND: Currently, there is no clear consensus on whether medical treatment or endoscopic treatment should be used for peptic ulcer bleeding patients with adherent clot. The aim of this study is to investigate the hemostatic effects of medical treatment, single endoscopic treatment, and combination endoscopic treatment for peptic ulcer bleeding (PUB) patients with adherent clot. METHODS: We retrospectively analyzed PUB patients with adherent clot who underwent endoscopic examination or treatment in our center from March 2014 to January 2023 and received intravenous administration of proton pump inhibitors. Patients were divided into medical treatment (MT) group, single endoscopic treatment (ST) group, and combined endoscopic treatment (CT) group. Subsequently, inverse probability of treatment weighting (IPTW) was performed to calculate the rebleeding rate. RESULTS: A total of 605 eligible patients were included in this study. After IPTW, the rebleeding rate in the MT group on days 3, 7, 14, and 30 were 13.3 (7.3), 14.2 (7.8), 14.5 (7.9), and 14.5 (7.9), respectively; the rebleeding rates in the ST group were 17.4 (5.1), 20.8 (6.1), 20.8 (6.1), and 20.8 (6.1), respectively; the rebleeding rates in the CT group were 0.4 (0.9), 1.7 (3.3), 2.3 (4.5), and 2.3 (4.5), respectively. Although the rebleeding rate in the medical treatment group was higher, there was no significant difference among the three groups on days 3, 7, 14, and 30 (P = 0.132, 0.442, 0.552, and 0.552). CONCLUSIONS: Medical therapy has similar hemostatic efficacy with endoscopic treatment for PUB patients with adherent clot (FIIb ulcers). However, for patients with more risk factors and access to well-equipped endoscopy centers, endoscopic treatment may be considered. The choice of treatment approach should be based on the individual conditions of the patient, as well as other factors such as medical resources available.

Final analyses of the prospective controlled trial on the efficacy of uracil and tegafur/leucovorin as an adjuvant treatment for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201).

BACKGROUND: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes. METHODS: In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery. RESULTS: Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS. CONCLUSION: The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012).

Propensity Score Analysis With Baseline and Follow-Up Measurements of the Outcome Variable.

A common feature in cohort studies is when there is a baseline measurement of the continuous follow-up or outcome variable. Common examples include baseline measurements of physiological characteristics such as blood pressure or heart rate in studies where the outcome is post-baseline measurement of the same variable. Methods incorporating the propensity score are increasingly being used to estimate the effects of treatments using observational studies. We examined six methods for incorporating the baseline value of the follow-up variable when using propensity score matching or weighting. These methods differed according to whether the baseline value of the follow-up variable was included or excluded from the propensity score model, whether subsequent regression adjustment was conducted in the matched or weighted sample to adjust for the baseline value of the follow-up variable, and whether the analysis estimated the effect of treatment on the follow-up variable or on the change from baseline. We used Monte Carlo simulations with 750 scenarios. While no analytic method had uniformly superior performance, we provide the following recommendations: first, when using weighting and the ATE is the target estimand, use an augmented inverse probability weighted estimator or include the baseline value of the follow-up variable in the propensity score model and subsequently adjust for the baseline value of the follow-up variable in a regression model. Second, when the ATT is the target estimand, regardless of whether using weighting or matching, analyze change from baseline using a propensity score that excludes the baseline value of the follow-up variable.

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OBJECTIVES: To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects (VSD) in offspring. METHODS: A case-control study was conducted, recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants. A questionnaire survey collected data on maternal exposures, and blood samples were analyzed for genetic polymorphisms. Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD. Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake. RESULTS: The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD (P<0.05). The GC and CC genotypes at rs3768139, AG and GG at rs1050993, AT and TT at rs4659743, GG at rs3768142, and GT and TT at rs3820571 were associated with a decreased risk of VSD (P<0.05). The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD (P<0.05). CONCLUSIONS: Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring. Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period, suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.

Causal inference for recurrent event data using pseudo-observations.

Recurrent event data are commonly encountered in observational studies where each subject may experience a particular event repeatedly over time. In this article, we aim to compare cumulative rate functions (CRFs) of two groups when treatment assignment may depend on the unbalanced distribution of confounders. Several estimators based on pseudo-observations are proposed to adjust for the confounding effects, namely inverse probability of treatment weighting estimator, regression model-based estimators, and doubly robust estimators. The proposed marginal regression estimator and doubly robust estimators based on pseudo-observations are shown to be consistent and asymptotically normal. A bootstrap approach is proposed for the variance estimation of the proposed estimators. Model diagnostic plots of residuals are presented to assess the goodness-of-fit for the proposed regression models. A family of adjusted two-sample pseudo-score tests is proposed to compare two CRFs. Simulation studies are conducted to assess finite sample performance of the proposed method. The proposed technique is demonstrated through an application to a hospital readmission data set.

Anatomic versus non-anatomic resection for early-stage intrahepatic cholangiocarcinoma: a propensity score matching and stabilized inverse probability of treatment weighting analysis.

BACKGROUND: Radical resection is still the most cost-effectiveness curative strategy for intrahepatic cholangiocarcinoma (ICC), but it remains controversial on the survival benefit of anatomic resection (AR). In this study, we sought to compare the oncologic outcomes between AR versus non-AR (NAR) as the primary treatment for early-stage ICC patients. METHODS: Data of ICC patients who underwent hepatectomy and staged at AJCC I were retrospectively collected from 12 hepatobiliary centers in China between Dec 2012 and Dec 2015. Propensity score matching (PSM) and stabilized inverse probability of treatment weighting (IPTW) analysis were performed to minimize the effect of potential confounders, and the perioperative and long-term outcomes between AR and NAR groups were compared. RESULTS: Two hundred seventy-eight ICC patients staged at AJCC I were eligible for this study, including 126 patients receiving AR and 152 patients receiving NAR. Compared to the NAR group, the AR group experienced more intraoperative blood loss before and after PSM or stabilized IPTW (all P > 0.05); AR group also experienced more intraoperative transfusion after stabilized IPTW (P > 0.05). In terms of disease-free survival (DFS) and overall survival (OS), no significant differences were observed between the two groups before and after PSM or stabilized IPTW (all P > 0.05). Multivariable Cox regression analyses found that AR was not an independent prognostic factor for either DFS or OS (all P > 0.05). Further analysis also showed that the survival benefit of AR was not found in any subgroup stratified by Child-Pugh grade (A or B), cirrhosis (presence or absence), tumor diameter (≤ 5 cm or > 5 cm) and pathological type (mass-forming or non-mass-forming) with all P > 0.05. CONCLUSION: Surgical approach does not influence the prognosis of patients with stage I primary ICC, and NAR might be acceptable and oncological safety.

A marginal structural model to estimate the effect of antidepressant medication treatment on major cardiovascular events among people with post-traumatic stress disorder.

BACKGROUND: Previous evidence on antidepressant medication and cardiovascular disease (CVD) among patients with posttraumatic stress disorder (PTSD) has been inconclusive. We estimated the association between antidepressant medication and CVD by applying a marginal structural model. METHODS: We analyzed medical utilization records of 27 170 people with PTSD without prior major cardiovascular events in the Korean National Health Insurance Database (NHID). PTSD and CVD were defined in accordance with the recorded ICD-10 diagnostic codes. We acquired information on antidepressant use from the NHID and categorized them by medication type. A composite major adverse cardiovascular events (MACE) outcome was defined as coronary artery disease with revascularization, ischaemic stroke, and/or haemorrhagic stroke. We used inverse probability of treatment weighting to estimate the parameters of a marginal structural discrete-time survival analysis regression model, comparing the resulting estimates to those derived from traditional time-fixed and time-varying Cox proportional hazards regression. We calculated cumulative daily defined doses to test for a dose-response relationship. RESULTS: People exposed to antidepressants showed a higher hazard of MACE [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.18-1.53]. The estimated effects were strongest for selective serotonin reuptake inhibitors (HR 1.24, 95% CI 1.08-1.44) and TCAs (HR 1.33, 95% CI 1.13-1.56). Exposure to serotonin-norepinephrine reuptake inhibitors did not appear to increase the risk of MACE. People exposed to higher doses of antidepressants showed higher risk of MACE. CONCLUSIONS: In a national cohort of people with PTSD, exposure to antidepressant medications increased the risk of MACE in a dose-response fashion.

Thiamine supplementation may be associated with improved prognosis in patients with sepsis.

Sepsis is a clinical syndrome characterised by a severe disorder of pathophysiology caused by infection of pathogenic micro-organisms. The addition of antioxidant micronutrient therapies such as thiamine to sepsis treatment remains controversial. This study explored the effect of thiamine on the prognosis of patients with sepsis. This study was a retrospective study involving patients with sepsis from the Medical Information Mart for Intensive Care IV. Patients were divided into two groups, the thiamine received group (TR) and the thiamine unreceived group (TUR), according to whether they were supplemented with thiamin via intravenous while in the intensive care unit (ICU). The primary outcome was ICU mortality. The association between thiamine and outcome was analysed using the Cox proportional hazards regression model, propensity score matching (PSM), generalised boosted model-based inverse probability of treatment weighting (IPTW) and doubly robust estimation. A total of 11 553 sepsis patients were enrolled in this study. After controlling for potential confounders using Cox regression models, the TR group had a statistically significantly lower ICU mortality risk than the TUR group. The hazard ratio of ICU mortality for the TR group was 0·80 (95 % CI 0·70, 0·93). We obtained the same results after using PSM, IPTW and doubly robust estimation. Supplementation with thiamine has a beneficial effect on the prognosis of patients with sepsis. More randomised controlled trials are needed to confirm the effectiveness of thiamine supplementation in the treatment of sepsis.

Effect of antimicrobial de-escalation strategy on 14-day mortality among intensive care unit patients: a retrospective propensity score-matched cohort study with inverse probability-of-treatment weighting.

PURPOSE: This study aimed to investigate the prevalence of antimicrobial de-escalation (ADE) strategy and assess its effect on 14-day mortality among intensive care unit patients. METHODS: A single-center retrospective cohort study was conducted on patients admitted to the intensive care unit (ICU) with infectious diseases between January 2018 and December 2020. Patients were stratified into three groups based on the initial treatment regimen within 5 days of antimicrobial administration: ADE, No Change, and Other Change. Confounders between groups were screened using one-way ANOVA and Chi-square analysis. Univariate and multivariate analyses were performed to identify risk factors for 14-day mortality. Potential confounders were balanced using propensity score inverse probability of treatment weighting (IPTW), followed by multivariate logistic regression analysis to evaluate the effect of ADE strategy on 14-day mortality. RESULTS: A total of 473 patients met the inclusion criteria, with 53 (11.2%) in the ADE group, 173 (36.6%) in the No Change group, and 247 (52.2%) in the Other Change group. The 14-day mortality rates in the three groups were 9.4%, 11.6%, and 21.9%, respectively. After IPTW, the adjusted odds ratio for 14-day mortality comparing No Change with ADE was 1.557 (95% CI 1.078-2.247, P = 0.0181) while comparing Other Change with ADE was 1.282(95% CI 0.884-1.873, P = 0.1874). CONCLUSION: The prevalence of ADE strategy was low among intensive care unit patients. The ADE strategy demonstrated a protective effect or no adverse effect on 14-day mortality compared to the No Change or Other Change strategies, respectively. These findings provide evidence supporting the implementation of the ADE strategy in ICU patients.

Association between prolonged corticosteroids use in COVID-19 and increased mortality in hospitalized patients: a retrospective study with inverse probability of treatment weighting analysis.

BACKGROUND: Previous studies have demonstrated a beneficial effect of early use of corticosteroids in patients with COVID-19. This study aimed to compare hospitalized patients with COVID-19 who received short-course corticosteroid treatment with those who received prolonged-course corticosteroid treatment to determine whether prolonged use of corticosteroids improves clinical outcomes, including mortality. METHODS: This is a retrospective cohort study including adult patients with positive testing for Sars-CoV-2 hospitalized for more than 10 days. Data were obtained from electronic medical records. Patients were divided into two groups, according to the duration of treatment with corticosteroids: a short-course (10 days) and a prolonged-course (longer than 10 days) group. Inverse probability treatment weighting (IPTW) analysis was used to evaluate whether prolonged use of corticosteroids improved outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were hospital infection and the association of different doses of corticosteroids with hospital mortality. Restricted cubic splines were used to assess the nonlinear association between mortality and dose and duration of corticosteroids use. RESULTS: We enrolled 1,539 patients with COVID-19. Among them, 1127 received corticosteroids for more than 10 days (prolonged-course group). The in-hospital mortality was higher in patients that received prolonged course corticosteroids (39.5% vs. 26%, p < 0.001). The IPTW revealed that prolonged use of corticosteroids significantly increased mortality [relative risk (RR) = 1.52, 95% confidence interval (95% CI): 1.24-1.89]. In comparison to short course treatment, the cubic spline analysis showed an inverted U-shaped curve for mortality, with the highest risk associated with the prolonged use at 30 days (RR = 1.50, 95% CI 1.21-1.78). CONCLUSIONS: Prolonged course of treatment with corticosteroids in hospitalized patients with COVID-19 was associated with higher mortality.

Differences in target estimands between different propensity score-based weights.

PURPOSE: Propensity score weighting is a popular approach for estimating treatment effects using observational data. Different sets of propensity score-based weights have been proposed, including inverse probability of treatment weights whose target estimand is the average treatment effect, weights whose target estimand is the average treatment effect in the treated (ATT), and, more recently, matching weights, overlap weights, and entropy weights. These latter three sets of weights focus on estimating the effect of treatment in those subjects for whom there is clinical equipoise. We conducted a series of simulations to explore differences in the value of the target estimands for these five sets of weights when the difference in means is the measure of treatment effect. METHODS: We considered 648 scenarios defined by different values of the prevalence of treatment, the c-statistic of the propensity score model, the correlation between the linear predictors for treatment selection and the outcome, and by the magnitude of the interaction between treatment status and the linear predictor for the outcome in the absence of treatment. RESULTS: We found that, when the prevalence of treatment was low or high and the c-statistic of the propensity score model was moderate to high, that matching weights, overlap weights, and entropy weights had target estimands that differed meaningfully from the target estimand of the ATE weights. CONCLUSIONS: Researchers using matching weights, overlap weights, and entropy weights should not assume that the estimated treatment effect is comparable to the ATE.