Inverse Probability Of Treatment Weighting Method Research Articles

Efficacy of corticosteroid therapy for oxygen-free coronavirus disease 2019-derived pneumonia.

Corticosteroid therapy for oxygen-free coronavirus disease 2019 (COVID-19) is not recommended due to its negative prognostic impact, but the efficacy of corticosteroids when limited to COVID-19 pneumonia is unclear. We aimed to evaluate the efficacy of corticosteroid monotherapy for patients with COVID-19 pneumonia without supplemental oxygen. We retrospectively reviewed patients with oxygen-free COVID-19 pneumonia at our institute between September 2020 and August 2021 and assessed the use of corticosteroids and the timing of initiation. We classified the patients into the following 2 groups: those who were initiated corticosteroids without developing respiratory failure (early steroid group) and those who were not (standard of care [SOC] group). We used inverse probability of treatment weighting (IPW) to balance between the groups. The primary outcome was the incidence of respiratory failure. A total of 144 patient records were reviewed; 63 patients were in the early steroid group and 81 patients were in the SOC group. Of all patients, 14 (22.2%) and 27 (33.3%) patients in the early steroid and SOC group, respectively, required supplemental oxygen (P = .192). After adjusted by the IPW method, 10 (16.0%) and 32 (40.1%) patients in the early steroid and SOC groups, respectively, required supplemental oxygen (P = .004). The logistic regression analysis indicated that early corticosteroid use was significantly associated with a decreased incidence of respiratory failure (odds ratio; 0.17, 95% confidence intervals; 0.06-0.46, P < .001). Corticosteroid monotherapy may suppress the development of exacerbation requiring oxygen supply in patients with oxygen-free COVID-19 pneumonia.

P-765 Minding the sweet spot in birth weight: Metformin and insulin versus no treatment

Abstract Study question Is the use of metformin or insulin associated with an increased risk of large or small for gestational age birth in comparison to drug-naïve GDM? Summary answer No difference in SGA / LGA odds with drug-naïve mothers versus metformin-exposed, but higher odds of SGA and lover odds of LGA compared to insulin-exposed. What is known already In Europe, the originator brand of metformin has received a label update allowing the use during pregnancy. Use of metformin during pregnancy is associated with a reduced risk of LGA, but increased risk of SGA birth compared to insulin. In CLUE, metformin only exposure demonstrated a reduced odds of LGA birth (weighted OR (wOR) 0.82, 95% CI 0.67 to 0.99), but increased risk for SGA (wOR 1.65, 95% CI 1.16 to 2.34). Insulin use during a hyperglycemic pregnancy is discussed to increase birth weight. Study design, size, duration This was a follow-up study performed on our previously published population-based register data cohort study CLUE with maternal exposure to metformin, insulin or diagnosed with GDM but drug-naïve until birth. The follow-up study included 3,964 subjects in the metformin only cohort, 5,273 in the insulin only cohort and 82,675 women diagnosed with GDM but without drug treatment during the respective pregnancy (naïve cohort). Participants/materials, setting, methods The study population included singleton children born to 18-45 year old women from Finland during 2004–2016. Exclusion criteria were maternal type 1 diabetes, exposure to glucocorticoids and antidiabetic medications except metformin and insulin during the respective pregnancy. Analyses of SGA and LGA used logistic regression to estimate ORs with 95%CIs, with naïve cohort as the reference. Inverse probability of treatment weighting (IPTW) with stabilized weights based on propensity scores (PS) was used to control for confounding. Main results and the role of chance The odds of SGA birth were significantly higher in the naïve cohort (wOR 1.41, 95% CI 1.11 to 1.79) compared to those exposed to insulin, and the odds for LGA birth were significantly lower (wOR 0.72, 95% CI 0.64 to 0.82). No difference was found in the odds for SGA or LGA when the metformin cohort was compared with naïve cohort (wOR 0.97, 95% CI 0.73 to 1.27 and wOR 0.91, 95% CI 0.75 to 1.11, respectively). Limitations, reasons for caution Drug exposure was assessed on the dispensed drug only. and not intake, also prohibiting dose and treatment duration stratification. Although IPTW methods were used to account for many characteristics, the prevalence of underlying diseases differed across treatment cohorts, the naïve cohort which was defined by indication and absence of treatment. Wider implications of the findings This analysis adds to the growing evidence that insulin exposure in pregnancy may increase the risk of LGA, which is associated with increased adult obesity. Metformin did not increase the odds of SGA or LGA. Metformin may be considered a reasonable treatment during pregnancy, e.g. at risk for LGA birth. Trial registration number not applicable

Assessing efficacy in non-inferiority trials with non-adherence to interventions: Are intention-to-treat and per-protocol analyses fit for purpose?

Non-inferiority trials comparing different active drugs are often subject to treatment non-adherence. Intention-to-treat (ITT) and per-protocol (PP) analyses have been advocated in such studies but are not guaranteed to be unbiased in the presence of differential non-adherence. The REMoxTB trial evaluated two 4-month experimental regimens compared with a 6-month control regimen for newly diagnosed drug-susceptible TB. The primary endpoint was a composite unfavorable outcome of treatment failure or recurrence within 18 months post-randomization. We conducted a simulation study based on REMoxTB to assess the performance of statistical methods for handling non-adherence in non-inferiority trials, including: ITT and PP analyses, adjustment for observed adherence, multiple imputation (MI) of outcomes, inverse-probability-of-treatment weighting (IPTW), and a doubly-robust (DR) estimator. When non-adherence differed between trial arms, ITT, and PP analyses often resulted in non-trivial bias in the estimated treatment effect, which consequently under- or over-inflated the type I error rate. Adjustment for observed adherence led to similar issues, whereas the MI, IPTW and DR approaches were able to correct bias under most non-adherence scenarios; they could not always eliminate bias entirely in the presence of unobserved confounding. The IPTW and DR methods were generally unbiased and maintained desired type I error rates and statistical power. When non-adherence differs between trial arms, ITT and PP analyses can produce biased estimates of efficacy, potentially leading to the acceptance of inferior treatments or efficacious regimens being missed. IPTW and the DR estimator are relatively straightforward methods to supplement ITT and PP approaches.

Use and reporting of inverse-probability-of-treatment weighting for multicategory treatments in medical research: a systematic review

Causal inference methods for observational data represent an alternative to randomised controlled trials when they are not feasible or when real-world evidence is sought. Inverse-probability-of-treatment weighting (IPTW) is one of the most popular approaches to account for confounding in observational studies. In medical research, IPTW is mainly applied to estimate the causal effect of a binary treatment, even when the treatment has in fact multiple categories, despite the availability of IPTW estimators for multiple treatment categories. This raises questions about the appropriateness of the use of IPTW in this context. Therefore, we conducted a systematic review of medical publications reporting the use of IPTW in the presence of a multi-category treatment. Our objectives were to investigate the frequency of use and the implementation of these methods in practice, and to assess the quality of their reporting. Using Pubmed, Embase and Web of Science, we screened 5660 articles and retained 106 articles in the final analysis that were from 17 different medical areas. This systematic review is registered on PROSPERO (CRD42022352669). The number of treatment groups varied between 3 and 9, with a large majority of articles (90 [84.9%]) including 3 or 4 groups. The most commonly used method for estimating the weights was multinomial regression (51 [48.1%]) and generalized boosted models (48 [45.3%]). The covariates of the weight model were reported in 91 articles (85.9 %). Twenty-six articles (24.5 %) did not discuss the balance of covariates after weighting, and only 16 articles (15.1 %) referred to the assumptions needed to obtain correct inferences. The results of this systematic review illustrate that medical publications scarcely use IPTW methods for more than two treatment categories. Among the publications that did, the quality of reporting was suboptimal, in particular in regard to the assumptions and model building. IPTW for multi-category treatments could be applied more broadly in medical research, and the application of the proposed guidelines in this context will help researchers to report their results and to ensure reproducibility of their research.

A multicenter study evaluating efficacy of immune checkpoint inhibitors in advanced non-colorectal digestive cancers with microsatellite instability

BackgroundOne randomized phase III trial comparing chemotherapy (CT) with immune checkpoint inhibitors (ICI) has demonstrated significant efficacy of ICI in deficient DNA mismatch repair system/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer. However, few studies have compared ICI with CT in other advanced dMMR/MSI-H digestive tumors. MethodsIn this multicenter study, we included patients with advanced dMMR/MSI-H non-colorectal digestive tumors treated with chemotherapy and/or ICIs. Patients were divided retrospectively into two groups, a CT group and an immunotherapy (IO) group. The primary endpoint was progression-free survival (PFS). A propensity score approach using the inverse probability of treatment weighting (IPTW) method was applied to deal with potential differences between the two groups. Results133 patients (45.1/27.1/27.8% with gastric/small bowel/other carcinomas) were included. The majority of patients received ICI in 1st (29.1%) or 2nd line (44.4%). The 24-month PFS rates were 7.9% in the CT group and 71.2% in the IO group. Using the IPTW method, IO treatment was associated with better PFS (HR=0.227; 95% CI 0.147–0.351; p < 0.0001). The overall response rate was 26.3% in the CT group versus 60.7% in the IO group (p < 0.001) with prolonged duration of disease control in the IO group (p < 0.001). In multivariable analysis, predictive factors of PFS for patients treated with IO were good performance status, absence of liver metastasis and prior primary tumor resection, whereas no association was found for the site of the primary tumor. ConclusionsIn the absence of randomized trials, our study highlights the superior efficacy of ICI compared with standard-of-care therapy in patients with unresectable or metastatic dMMR/MSI-H non-colorectal digestive cancer, regardless of tumor type, with acceptable toxicity.

Mortality After Alcohol Septal Ablation vs. Septal Myectomy in Patients With Obstructive Hypertrophic Cardiomyopathy.

Background: Alcohol septal ablation (ASA) and septal myectomy (SM) are 2 options for septal reduction therapy (SRT) to treat medication-resistant symptomatic obstructive hypertrophic cardiomyopathy (HCM). Because differences in mortality rates after these different SRT methods have not been extensively investigated in real-world settings, in this study compared the 1-year mortality rates after ASA and SM using population-based database. Methods and Results: Utilizing New York Statewide Planning and Research Cooperative System (SPARCS) data from 2005 to 2016, we performed a comparative effectiveness study of ASA vs. SM in patients with HCM. The outcome was all-cause death up to 360 days after SRT. We constructed a multivariable logistic regression model and performed sensitivity analysis with propensity score (PS)-matching and inverse probability of treatment weighting (IPTW) methods. We identified 755 patients with HCM who underwent SRT: 348 with ASA and 407 with SM. The multivariable analysis showed that all-cause deaths were significantly fewer in the ASA group at 360 days after SRT (adjusted odds ratio=0.34; 95% confidence interval [CI] 0.13-0.84; P=0.02). The PS-matching and IPTW methods also supported a lower mortality rate in the ASA group at 360 days post-SRT. Conclusions: In this population-based study of patients with HCM who underwent SRT in a real-world setting, the 1-year all-cause mortality rate was significantly lower in patients who underwent ASA compared with SM.

Directed Acyclic Graph Assisted Method For Estimating Average Treatment Effect

ABSTRACT Observational data, such as electronic clinical records and claims data, can prove invaluable for evaluating the Average Treatment Effect (ATE) and supporting decision-making, provided they are employed correctly. The Inverse Probability of Treatment Weighting (IPTW) method, based on propensity scores, has demonstrated remarkable efficacy in estimating ATE, assuming that the assumptions of exchangeability, consistency, and positivity are met. Directed Acyclic Graphs (DAGs) offer a practical approach to assess the exchangeability assumption, which asserts that treatment assignment and potential outcomes are independent given a set of confounding variables that block all backdoor paths from treatment assignment to potential outcomes. To ensure a consistent ATE estimator, one can adjust for a minimally sufficient adjustment set of confounding variables that block all backdoor paths from treatment assignment to the outcome. To enhance the efficiency of ATE estimators, our proposal involves incorporating both the minimally sufficient adjustment set of confounding variables and predictors into the propensity score model. Extensive simulations were conducted to evaluate the performance of propensity score-based IPTW methods in estimating ATE when different sets of covariates were included in the propensity score models. The simulation results underscored the significance of including the minimally sufficient adjustment set of confounding variables along with predictors in the propensity score models to obtain a consistent and efficient ATE estimator. We applied this proposed method to investigate whether tracheostomy was causally associated with in-hospital infant mortality, utilizing the 2016 Healthcare Cost and Utilization Project Kids’ Inpatient Database. The estimated ATE was found to be approximately 2.30%–2.46% with p-value >0.05.

Synthetic Control Arm from Clinical Trials and Real-World Data from Lysa Group for Untreated Diffuse Large B Cell Lymphoma Patients Aged over 80 Years: A Bona Fide Strategy for Innovative Clinical Trials

Introduction Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy among older patients (pts), and about 25% of new diagnoses involve population aged &amp;gt; 80y.o. Most clinical trials (CTs) exclude the very older (Kanapuru et al, 2017). Rituximab + miniCHOP is considered gold-standard for untreated DLBCL aged &amp;gt;80 y.o with an overall survival (OS) of ~60% at 2y and improving outcomes for this frail population is challenging. Synthetic control arms (SCA) may engender more innovative randomized trials, by allowing indirect comparisons with enhanced statistical confidence and by sparing a part of the control population. We present SCA built from CTs and real-world (RW) data, and their applications to a randomized phase 3 protocol in this clinical setting. Methods We used 3 CTs, with &amp;gt;80 y.o pts treated by anti-CD20+miniCHOP. Two phase 2 CTs for sourcing of SCA patients, LNH03-7B and LNH09-7B, which assessed efficacy of 6 anti-CD20+miniCHOP, preceded in the latter trial by pre-phase treatment, reducing early non-disease related mortality (Peyrade F. et al, 2011 and 2017). SENIOR trial was a phase III randomized trial comparing 6 R-miniCHOP to R-miniCHOP+Lenalidomide, showing no differences in terms of OS (HR= 0.996, 95% CI= 0.66-1.51) (Oberic L. et al, 2022). We further used prospective REALYSA cohort (Ghesquières et al, 2021) with enrolled pts with at least 18 months follow-up and treated by R-miniCHOP as RW pool. We excluded non-compliant diagnoses, as well as early deaths within 3 first months of follow-up from CTs, to avoid the bias for absence of pre-phase from LNH03-7B trial. First step was to build SCA matched with internal SENIOR control arm to check reproducibility of pts outcomes. Then, SENIOR experimental arm was used as the matching source for SCA constructions. Propensity scores (PS) were estimated for each pt using relevant baseline covariates as described in Figure 1. If data was missing, CTs pts were excluded. For RW pts, multiple imputations method was used. Pts between groups were matched using stabilized inverse probability of treatment weighting (IPTW) method, the probability of treatment being assessed by PS, after removing pts with extreme PS from analyses. We subsequently performed sensitivity analyses using 1 : 1 PS matching (PSM). Standardized mean differences (SMD) were calculated for each covariate to assess matching efficacy. The endpoint was OS. Results Control SCAs matched to SENIOR internal control arm have no significant different OS with an HR of 0.81 (95%CI= 0.51-1.27, p = 0.397) using CTs data and an HR of 1.00 (95% CI= 0.62-1.61, p = 0.998) using RW data, with stabilized IPTW. PS set is the baseline population after applying exclusion criteria and including only pts for whom PS could be assessed. For SCA-CT, PS set was composed of 91 pts from experimental SENIOR arm and 169 from LNH03-7B and LNH09-7B. Thirty one pts were excluded for early death, mostly not disease-related. IPTW and PSM methods were both efficient with all SMD &amp;lt;0.10. With SCA-CT, OS curves comparison with stabilized IPTW was very close to SENIOR results: HR of 0.98 (95%CI= 0.643-1.492, p=0.93) (Figure 2). For SCA-RW, PS set included 104 pts from SENIOR experimental arm and 93 from REALYSA database. All SMD were below 0.10 with IPTW and all but one were below 0.15 with PSM. Regarding the outcome analysis, censorship was chosen at 24 months of follow-up as too few patients were still at risk. OS was not significantly different with an HR of 0.84 (95%CI=0.51-1.39, p= 0.551) with stabilized IPTW. Sensitivity analyses with PSM, for SCA-CT and SCA-RW are consistent with results after IPTW, but exclusion process for matching led to a loss of power (84 pts in each arm for SCA-CT and 71 pts in each arm for SCA-RW) Discussion We demonstrated that well matched SCAs built from historical CTs data can achieve a high level of confidence to replicate randomized phase III results in DLBCL pts &amp;gt;80 y.o. We replicated with a SCA the internal control arm with similar OS comparisons (HR= 0.996 (95% CI= 0.66-1.51) for SENIOR, HR= 0.98 (95% CI = 0.643-1.492) for SCA-CT). Matching procedures with RWD patients were also efficient, and SCA-RW OS behaved the same way as SCA-CT and internal control arm of SENIOR trial. The loss of power due to the pool shrinkage for matching procedures could be limited by mixing 50%/50% pts from internal control arm and historical CTs pts. These complementary data will be presented during the meeting.

Comparative Efficacy and Safety of Neoadjuvant Immunotherapy with Chemotherapy versus Chemotherapy Alone in Non-Small Cell Lung Cancer: A Propensity Score and Inverse Probability Treatment Weighting Analysis.

This study aimed to compare the efficacy and safety of neoadjuvant chemotherapy (NCT) and neoadjuvant immunotherapy combined with chemotherapy (NICT) combined with radical lung cancer resection for the treatment of patients with resectable non-small cell lung cancer (NSCLC). To adjust for confounding factors, we innovatively adopted two matching methods: propensity score (PS) and inverse probability of treatment weighting (IPTW). We conducted a retrospective analysis of the clinicopathological features and prognosis of patients with resectable NSCLC treated with NCT or NICT combined with radical lung cancer resection using propensity score matching (PSM) at a ratio of 1:1 and IPTW to balance potential bias. After PSM, 116 pairs of patients who had undergone NCT or NICT were selected for the final analysis. The pathological complete remission (pCR) and major pathological remission (MPR) rates were significantly better in the NICT group than in the NCT group (pCR rate of 44.8% vs 2.6%, P< 0.001; MPR rate of 66.4% vs 20.7%, P< 0.001). No significant difference was seen between the NICT and NCT groups in terms of postoperative complications (12.1% vs 9.5%, P=0.182). Patients in the NICT group had significantly better disease-free survival (DFS) and overall survival(OS) than those in the NCT group ([3-year DFS: 75.2% vs 43.3%, P< 0.001] and [3-year OS: 91.5% vs 58.0%, P< 0.001]). Among all patients, those with postoperative pathology of pCR had better DFS (P< 0.001) and OS (P= 0.009). Patients with postoperative pathology of MPR had better DFS (P< 0.001) and OS (P< 0.001). The IPTW method yielded similar pathologic and prognostic results. Patients with resectable NSCLC treated with NICT had better pathological responses and prognosis, than those treated with NCT, and the safety profiles of NICT and NCT were similar.

Technical outcomes of robotic-assisted surgery versus laparoscopic surgery for rectal tumors: a single-center safety and feasibility study.

Robot-assisted surgery has a multi-joint function, which improves manipulation of the deep pelvic region and contributes significantly to perioperative safety. However, the superiority of robot-assisted surgery to laparoscopic surgery remains controversial. This study compared the short-term outcomes of laparoscopic and robot-assisted surgery for rectal tumors. This single-center, retrospective study included 273 patients with rectal tumors who underwent surgery with anastomosis between 2017 and 2021. In total, 169 patients underwent laparoscopic surgery (Lap group), and 104 underwent robot-assisted surgery (Robot group). Postoperative complications were compared via propensity score matching based on inverse probability of treatment weighting (IPTW). The postoperative complication rates based on the Clavien-Dindo classification (Lap vs. Robot group) were as follows: grade ≥ II, 29.0% vs. 19.2%; grade ≥ III, 10.7% vs. 5.8%; anastomotic leakage (AL), 6.5% vs. 4.8%; and urinary dysfunction (UD), 12.1% vs. 3.8%. After adjusting for the IPTW method, although AL rates did not differ significantly between groups, postoperative complications of both grade ≥ II (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.50-0.87, p < 0.01) and grade ≥ III (OR 0.29, 95% CI 0.16-0.53, p < 0.01) were significantly less frequent in the Robot group than in the Lap group. Furthermore, urinary dysfunction also tended to be less frequent in the Robot group than in the Lap group (OR 0.62, 95% CI 0.38-1.00; p = 0.05). Robot-assisted surgery for rectal tumors provides better short-term outcomes than laparoscopic surgery, supporting its use as a safer approach.

Robust causal inference of drug-drug interactions.

There is growing interest in developing causal inference methods for multi-valued treatments with a focus on pairwise average treatment effects. Here we focus on a clinically important, yet less-studied estimand: causal drug-drug interactions (DDIs), which quantifies the degree to which the causal effect of drug A is altered by the presence versus the absence of drug B. Confounding adjustment when studying the effects of DDIs can be accomplished via inverse probability of treatment weighting (IPTW), a standard approach originally developed for binary treatments and later generalized to multi-valued treatments. However, this approach generally results in biased results when the propensity score model is misspecified. Motivated by the need for more robust techniques, we propose two empirical likelihood-based weighting approaches that allow for specifying a set of propensity score models, with the second method balancing user-specified covariates directly, by incorporating additional, nonparametric constraints. The resulting estimators from both methods are consistent when the postulated set of propensity score models contains a correct one; this property has been termed multiple robustness. In this paper, we derive two multiply-robust estimators of the causal DDI, and develop inference procedures. We then evaluate their finite sample performance through simulation. The results demonstrate that the proposed estimators outperform the standard IPTW method in terms of both robustness and efficiency. Finally, we apply the proposed methods to evaluate the impact of renin-angiotensin system inhibitors (RAS-I) on the comparative nephrotoxicity of nonsteroidal anti-inflammatory drugs (NSAID) and opioids, using data derived from electronic medical records from a large multi-hospital health system.

Effect of protein underdosing on the prognosis of patients with severe acute heart failure in the early acute phase: A single-institutional retrospective cohort study

The appropriate protein dose during the early acute phase of severe acute heart failure (AHF) remains unknown. We hypothesized that protein underdosing during this period may lead to a poor prognosis. Thus, we investigated the relationship between protein sufficiency rate and prognosis during the early acute phase in patients with severe AHF. This retrospective observational study investigated patients with AHF requiring invasive mechanical ventilation who were admitted in the intensive care and cardiac care units between January 2015 and August 2021. These patients were ranked according to the tertile of protein sufficiency rate on intubation day 2. Univariate and multivariate logistic regression analyses were performed to determine whether a low protein sufficiency rate on intubation day 2 was an independent factor for in-hospital mortality. Patients were weighted using the inverse probability of treatment weighting (IPTW) method to determine the differences in baseline characteristics. A total of 118 patients were included in the study and divided into low-protein (n=40) and non-low-protein (n=78) groups with protein sufficiency rates of ≤10% and >10%, respectively.In the multivariate analysis of in-hospital mortality, low protein sufficiency on day 2 was identified as an independent factor (odds ratio [OR]=2.77, 95% confidence interval [CI]=1.05-7.27, P=0.039). After adjusting for baseline characteristics using the IPTW method, multiple logistic regression analysis of in-hospital mortality revealed low protein sufficiency on day 2 as an independent factor (OR=3.32, 95% CI=1.18-9.32, P=0.023). Protein underdosing in the early acute phase of severe AHF may be associated with increased in-hospital mortality.

Consistent inverse probability of treatment weighted estimation of the average treatment effect with mismeasured time-dependent confounders.

In longitudinal studies, the inverse probability of treatment weighted (IPTW) method is commonly employed to estimate the effect of time-dependent treatments on an outcome of interest. However, it has been documented that when the confounders are subject to measurement error, the naive IPTW method which simply ignores measurement error leads to biased treatment effect estimation. In the existing literature, there is a lack of measurement error correction methods that fully remove measurement error effect and produce consistent treatment effect estimation. In this article, we develop a novel consistent IPTW estimation procedure for longitudinal studies. The key step of the proposed method is to use the observed data to construct a corrected function that is unbiased of the unknown IPTW function. Simulation studies reveal that the proposed method outperforms the existing consistent and approximate measurement error correction methods for IPTW estimation of the average treatment effect. Finally, we apply the proposed method to analyze a real dataset.

Effect of oXiris-CVVH on the Clinical Outcomes of Patients with Septic Shock: An Inverse Probability of Treatment-Weighted Analysis

Background: Limited previous studies had proved that oXiris-continuous veno-venous hemofiltration (CVVH) could decrease endotoxins and inflammatory factors, thereby improving circulation’s stability. However, conclusive data are lacking regarding the comparison between oXiris membrane (with the function of removing endotoxins and decreasing inflammatory factors) and AN69 filters (with the only function of decreasing inflammatory) on the mortality of patients with septic shock. The potential mechanisms of oXiris that might influence the mortality of septic shock patients remain unexplored. Methods: This is a single-center, retrospective cohort study. The experimental group (30 patients with septic shock) was treated with oXiris-CVVH, and the control group (46 patients with septic shock) was treated with AN69 filter-CVVH. We employed the inverse probability of treatment-weighting method (IPTW), doubly robust estimation, and mediating effect analysis to analyze those clinical outcomes, with a special focus on the results of 28-day mortality, 72-h lactate, the need for norepinephrine (NE) in the next 72 h. Results: A total of 76 patients with septic shock who received blood purification therapies were enrolled. After IPTW, differences in patient characteristics have been minimized. The 28-day mortality in the control group is higher than in the treatment group (73.3% vs. 47.3%, p < 0.001; median survival time: 10 vs. ≥28 days, log-rank p = 0.0366). And the 25% decrease and the 50% decrease in demand for NE in the next 72 h are different between the treatment and control groups (median time of 25% decrease in demand: 24 vs. >72 h, log-rank p = 0.0126; median time of 50% decrease in demand: 24 vs. >72 h, log-rank p = 0.0322). The 72-h lactic acid level and white blood cell (WBC) counts in the oXiris group are lower than in the control group. The 72-h lactate fully mediated the effects of oXiris on 28-day mortality after confounds adjustment. Conclusions: For septic shock patients, the use of oXiris-CVVH was associated with lower mortality and appeared to reduce lactate, NE dosage, PCT, and WBC counts, as compared to AN69-CVVH.

Proton pump inhibitors affect capecitabine efficacy in patients with stage II\u2013III colorectal cancer: a multicenter retrospective study

The association between capecitabine efficacy and proton pump inhibitors (PPIs) is controversial. Here, we determined whether co-administration of PPIs affects the real-world effectiveness of capecitabine. This retrospective observational study included consecutive patients with stage II–III colorectal cancer (CRC) who received adjuvant capecitabine monotherapy or CapeOX (capecitabine and oxaliplatin) between January 2009 and December 2014 at nine participating institutions. The primary endpoint was the difference in relapse-free survival (RFS) between patients who received PPIs and those who did not and was estimated using the Kaplan–Meier method. Overall survival (OS) was the secondary endpoint. Multivariable analysis of RFS and OS was performed using a Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting (IPTW) analyses. Data from 606 patients were evaluated, 54 of whom had received a PPI. PPI-treated patients tended to have poorer RFS and OS than patients treated without PPIs. The hazard ratio for RFS with capecitabine monotherapy was 2.48 (95% confidence interval: 1.22–5.07). These results were consistent with sensitivity analyses performed using propensity score adjustment and IPTW methods. Co-administration of PPIs may reduce the effectiveness of capecitabine and negatively impact patients with stage II–III CRC.

Is Blood Loss Greater in Elderly Patients under Antiplatelet or Anticoagulant Medication for Cervical Spine Injury Surgery? A Japanese Multicenter Survey.

Introduction In elderly patients with cervical spinal cord injury, comorbidities such as cardiovascular and cerebrovascular diseases are common, with frequent administration of antiplatelet/anticoagulant (APAC) drugs. Such patients may bleed easily or unexpectedly during surgery despite prior withdrawal of APAC medication. Few reports have examined the precise relationship between intraoperative blood loss and history of APAC use regarding surgery for cervical spine injury in the elderly. The present multicenter database survey aimed to answer the question of whether the use of APAC drugs affected the amount of intraoperative blood loss in elderly patients with cervical spinal cord trauma. Methods The case histories of 1512 patients with cervical spine injury at 33 institutes were retrospectively reviewed. After excluding cases without spinal surgery or known blood loss volume, 797 patients were enrolled. Blood volume loss was the outcome of interest. We calculated propensity scores using the inverse probability of treatment weighting (IPTW) method. As an alternative sensitivity analysis, linear mixed model analyses were conducted as well. Results Of the 776 patients (mean age: 75.1±6.4 years) eligible for IPTW calculation, 157 (20.2%) were taking APAC medications before the injury. After weighting, mean estimated blood loss was 204 mL for non-APAC patients and 215 mL for APAC patients. APAC use in elderly patients was not significantly associated with surgical blood loss according to the IPTW method with propensity scoring or linear mixed model analyses. Thus, it appeared possible to perform surgery expecting comparable blood loss in APAC and non-APAC cases. Conclusions This multicenter study revealed no significant increase in surgical blood loss in elderly patients with cervical trauma taking APAC drugs. Surgeons may be able to prioritize patient background, complications, and preexisting conditions over APAC use before injury when examining the surgical indications for cervical spine trauma in the elderly.

Comparisons of Propensity Score Methods for Time to Event Outcomes: Evaluation through Simulations and Oral Squamous Cell Carcinoma Case Study

Introduction &amp; Objective: In observational studies, it is recommended to use propensity score (PS) methods or covariate adjustment for confounding effect adjustment. However, few guidelines are available regarding the choice of PS approaches or covariate adjustment for the best performance in a particular data. In this study, we compared different PS methods and conventional covariate adjustment to investigate the treatment effect for the overall population on time-to-event outcomes.&#x0D; Methods: In the Monte Carlo simulations, we compared the hazard ratio (HR) and precision estimated using covariate adjustment and eight different PS approaches, including matching, stratification, and inverse probability of treatment weighting (IPTW). In the Oral Squamous-Cell Carcinoma Cancer case study, we applied the aforementioned PS approaches to compare the effect of receiving post-operative radiation therapy (PORT) and having engraftable tumors on different time-to-event clinical outcomes.&#x0D; Results: In the simulations, both IPTW and covariate adjustment produced unbiased HR estimates with small uncertainty. In the case study, covariate adjustment showed that patients with engraftable tumors were twice as likely to have local/regional recurrence (HR 1.98 [1.23, 3.18], p-value&lt;0.005) and any recurrence or death (HR 2.02 [1.38, 2.96], p-value&lt;0.001); patients received PORT were twice as likely to develop either local, regional, or distance recurrence (HR 2.12 [1.32, 3.41], p-value&lt;0.005). Results produced by IPTW were consistent with covariate adjustment method (within ± 0.1 differences).&#x0D; Conclusion: Covariate adjustment and the IPTW method performed well across simulations and the case study. In practice, care should be taken to select the most suitable method when estimating the treatment, exposure or intervention effect on time-to-event outcomes.

Effect of renin-angiotensin system inhibitors on pemetrexed plus platinum-induced hematological toxicities: a multicenter retrospective study using three propensity score analyses.

Hematological toxicities induced by pemetrexed plus platinum therapy remain a critical issue in clinical practice. We hypothesized that inhibition of the renin-angiotensin system (RAS) can ameliorate pemetrexed-induced hematological toxicities through drug-drug interactions involving organic anion transporters. Thus, this study aimed to clarify whether RAS inhibitors (RASIs) could prevent pemetrexed plus platinum-induced hematological toxicities. We retrospectively analyzed data from 305 consecutive patients with non-small cell lung cancer or malignant pleural mesothelioma who received their first cycle of a pemetrexed plus platinum regimen and were treated with or without RASIs. The primary endpoint was the incidence of severe myelosuppression after the first cycle. Propensity score (PS)-matched, PS-adjusted, and inverse probability of treatment weighting (IPTW) analyses were used. The number of patients with grade ≥3 hematological toxicities was 27 (8.9%). PS-matched analyses revealed that the concomitant use of RASIs was slightly associated with a lower risk of grade ≥3 hematological toxicities (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.20-2.32; p = 0.536). Additionally, sensitivity analyses using PS-adjusted and IPTW methods demonstrated similar results (OR, 0.63; 95% CI, 0.19-2.15; p = 0.463 and OR, 0.37; 95% CI, 0.11-1.29; p = 0.117, respectively). These findings suggest that RASIs might prevent pemetrexed plus platinum-induced hematological toxicities.

Minimally Invasive Versus Open Pancreatectomy for Right-Sided and Left-Sided G1/G2 Nonfunctioning Pancreatic Neuroendocrine Tumors: A Multicenter Matched Analysis with an Inverse Probability of Treatment-Weighting Method.

Limited evidence exists for the safety and oncologic efficacy of minimally invasive surgery (MIS) for nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) according to tumor location. This study aimed to compare the surgical outcomes of MIS and open surgery (OS) for right- or left-sided NF-PNETs. The study collected data on patients who underwent surgical resection (pancreatoduodenectomy, distal/total/central pancreatectomy, duodenum-preserving pancreas head resection, or enucleation) of a localized NF-PNET between January 2000 and July 2017 at 14 institutions. The inverse probability of treatment-weighting method with propensity scores was used for analysis. The study enrolled 859 patients: 478 OS and 381 MIS patients. A matched analysis by tumor location showed no differences in resection margin, intraoperative blood loss, or complications between MIS and OS. However, MIS was associated with a longer operation time for right-sided tumors (393.3 vs 316.7 min; P < 0.001) and a shorter postoperative hospital stay for left-sided tumors (8.9 vs 12.9 days; P < 0.01). The MIS group was associated with significantly higher survival rates than the OS group for right- and left-sided tumors, but survival did not differ for the patients divided by tumor grade and location. Multivariable analysis showed that MIS did not affect survival for any tumor location. The short-term outcomes offered by MIS were comparable with those of OS except for a longer operation time for right-sided NF-PNETs. The oncologic outcomes were not compromised by MIS regardless of tumor location or grade. These findings suggest that MIS can be performed safely for selected patients with localized NF-PNETs.

The Impact of Primary Tumor Resection on Survival in Asymptomatic Colorectal Cancer Patients With Unresectable Metastases.

PurposeThis study was conducted to evaluate the effectiveness of primary tumor resection (PTR) in asymptomatic colorectal cancer (CRC) patients with unresectable metastases using the inverse probability of treatment weighting (IPTW) method to minimize selection bias.MethodsWe selected 146 patients diagnosed with stage IV CRC with unresectable metastasis between 2001 and 2018 from our institutional database. In a multivariate logistic regression model using the patients’ baseline covariates associated with PTR, we applied the IPTW method based on a propensity score and performed a weighted Cox proportional regression analysis to estimate survival according to PTR.ResultsUpfront PTR was performed in 98 patients, and no significant differences in baseline factors were detected. The upweighted median survival of the PTR group was 18 months and that of the non-PTR group was 15 months (P = 0.15). After applying the IPTW, the PTR was still insignificant in the univariate Cox regression (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.5–1.21). However, in the multivariate weighted Cox regression with adjustment for other covariates, the PTR showed a significantly decreased risk of cancer-related death (HR, 0.61; 95% CI, 0.40–0.94).ConclusionIn this study, we showed that asymptomatic CRC patients with unresectable metastases could gain a survival benefit from upfront PTR by analysis with the IPTW method. However, randomized controlled trials are mandatory.