Inverse Probability Of Treatment Weighting Models Research Articles

Association between reduced risk of gastrointestinal bleeding related to proton pump inhibitor use and subsequent all-cause death in patients with percutaneous coronary intervention

Abstract Background Gastrointestinal bleeding is the leading cause of post-percutaneous coronary intervention (PCI) bleeding complications which are associated with a high risk for subsequent clinical outcomes. The aim of this study was to estimate association between risk of gastrointestinal bleeding events related to proton pump inhibitor (PPI) use and subsequent clinical outcomes in patients with PCI. Methods The Clinical Deep Data Accumulation System (CLIDAS) is a database for inclusive of patient characteristics, medications, laboratory test, physiological test, cardiac catheterization and PCI treatment, all of which were aggregated from electronic medical records in 7 tertiary hospitals in Japan. Data of 6457 patients who underwent PCI between April 2014 and March 2020 and were then followed for 30 days after the index PCI, were analyzed. These patients were divided into two groups based on use of PPI; the PPI group (n=5285; 82%) and the non-PPI group (n=1172; 18%). Clinical outcomes, defined as gastrointestinal bleeding and all-cause death, were assessed using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) models. Results Among the 6457 PCI patients, 90 (1.7%) in the PPI group and 31 (2.6%) in the non-PPI group experienced gastrointestinal bleeding events. Adjusting for baseline demographics, comorbidities, and anti-thrombotic treatments, the multivariable Cox hazard model suggested a trend towards a lower risk of gastrointestinal bleeding with PPI use (HR, 0.70; 95%CI, 0.46-1.05; p=0.087). The PSM analysis confirmed a significant association between PPI use and a lower risk of gastrointestinal bleeding (HR, 0.13; 95%CI, 0.04-0.43; p=0.001), consistent with IPTW model results (HR, 0.60; 95%CI, 0.38-0.95; p=0.031). Subgroup analysis showed that PPI use was associated with a low risk of all-cause death in patients with acute coronary syndrome (ACS) (HR, 0.58; 95%CI, 0.36-0.93; p=0.024). Causal mediation analysis indicated an indirect effect of PPI on reducing all-cause death through the suppression of gastrointestinal bleeding events. Conclusion These findings suggested that use of PPI against gastrointestinal bleeding complications might reduce the risk of subsequent all-cause death in ACS patients undergoing PCI.

251. THE COMPARISON OF UNIPORTAL VERSUS MULTIPORTAL VIDEO-ASSISTED THORACIC SURGERY FOR ESOPHAGEAL CANCER: A PROPENSITY-WEIGHTED ANALYSIS

Abstract Background Uniportal video-assisted thoracoscopic surgery (VATS) has been widely used, however, there are few studies on uniportal VATS for esophagectomy. Methods Data from patients with clinical stage T1–3/N0/M0 thoracic esophageal cancer who underwent surgery between January 2017 and December 2020 were retrospectively collected and retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to assess the outcomes. Results Overall, 55 patients who underwent uniportal, and 212 patients who underwent multiportal, VATS were identified. Surgery-related postoperative complications (Clavien-Dindo grades 1–2) occurred less frequently after uniportal than multiportal VATS in both crude and IPTW models (10.1% versus 28.8%, respectively; P = 0.018). The median postoperative length of stay was 9 (9–10) days in the uniportal VATS and 10 (9–14) days in the multiportal VATS group (P = 0.006 after IPTW). Upon IPTW analysis, in uniportal and multiportal VATS groups, the rates of pneumonia (grades 1-2) were 7.3% and 23.2% (P = 0.037). The visual analog scale (VAS) was administered on postoperative first 7 days and were significantly lower in the uniportal VATS group (P < 0.001). No surgical mortality was observed in the uniportal VATS group, and the survival benefit between the two groups was comparable before (P = 0.320) and after IPTW (P = 0.824). Conclusion Uniportal VATS for esophagectomy resulted in a lower rate of postoperative complications with less postoperative pain, and is practical for treating patients with esophageal cancer.

Prognostic value of baseline neutrophil/lymphocyte ratio in HER2-positive metastatic breast cancer: exploratory analysis of data from the CLEOPATRA trial

PurposeThis study aimed to evaluate the prognostic role of the baseline neutrophil/lymphocyte ratio (NLR) in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab/pertuzumab.Experimental designData from 780 patients from the CLEOPATRA trial and 248 local patients were collected. Patients were divided into the low and high NLR subgroups by the NLR cutoff value. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methods were used to control bias. Associations between the NLR and progression-free survival (PFS) and overall survival (OS) were analyzed.ResultsThe baseline characteristics of the subgroups were well balanced after PSM and IPTW. A low baseline NLR was associated with better PFS and OS in the trastuzumab and docetaxel (TH) group in the unadjusted, PSM and IPTW models. After IPTW, a low NLR, versus a high NLR, was associated with improved PFS (HR 1.35, 95% CI 1.07–1.70, P = 0.012) and OS (HR 1.47, 95% CI 1.12–1.94, P = 0.006) in the TH group. In patients undergoing treatment with trastuzumab and pertuzumab and docetaxel (THP), a low baseline NLR was also correlated with better PFS but not OS across the three models. After IPTW, a low NLR was associated with better PFS (HR 1.52, 95% CI 1.20–1.93, P = 0.001) than a high NLR in the THP group. Multivariate analyses showed that a low baseline NLR was a predictor for PFS and OS in the TH group and for PFS in the THP group in all three models. In the real-world setting, a low baseline NLR was a predictor of better PFS among patients treated with docetaxel plus trastuzumab without or with pertuzumab in the multivariate model (P = 0.015 and 0.008, respectively).ConclusionsA low baseline NLR is associated with better survival outcomes among HER2-positive MBC patients receiving docetaxel plus trastuzumab/pertuzumab as first-line therapy.

Oral Antibiotics for Treatment of Gram-Negative Bacteremia in Solid Organ Transplant Recipients: A Propensity Score Weighted Retrospective Observational Study.

We assessed the safety and efficacy of oral antibiotic step-down therapy for uncomplicated gram-negative blood stream infections in solid-organ transplant recipients. We identified all solid-organ transplant recipients within the Massachusetts General and Brigham and Women's Hospital systems from 2016 to 2021 with uncomplicated gram-negative bacteremia involving an organism susceptible to an acceptably bioavailable oral antibiotic agent. Using inverse probability of treatment-weighted models based on propensity scores adjusting for potential clinical confounders, we compared outcomes of those transitioned to oral antibiotics with those who continued intravenous (IV) therapy for the duration of treatment. Primary endpoints were mortality, bacteremia recurrence, and reinitiation of IV antibiotics. Secondary endpoints included length of stay, Clostridioides difficile infection, treatment-associated complications, and tunneled central venous catheter placement. A total of 120 bacteremia events from 107 patients met inclusion criteria in the oral group and 42 events from 40 patients in the IV group. There were no significant differences in mortality, bacteremia recurrence, or reinitiation of IV antibiotics between groups. Patients transitioned to oral antibiotics had an average length of stay that was 1.97 days shorter (95% confidence interval [CI], -.39 to 3.56 days; P = .005). Odds of developing C. difficile and other treatment-associated complications were 8.4 times higher (95% CI, 1.5-46.6; P = .015) and 6.4 times higher (95% CI, 1.9-20.9; P = .002), respectively, in the IV group. Fifty-five percent of patients in the IV group required tunneled catheter placement. There was no difference in treatment duration between groups. Oral step-down therapy was effective and associated with fewer treatment-related adverse events.

Preoperative prognostic nutritional index predicts postoperative delirium in aged patients after surgery: A matched cohort study

ObjectivePrognostic nutritional index (PNI) is an indicator to evaluate the nutritional immune status of patients. This study aimed to assess whether preoperative PNI could predict the occurrence of postoperative POD in aged patients undergoing non-neurosurgery and non-cardiac surgery. MethodThe aged patients undergoing non-neurosurgery and non-cardiac surgery between January 2014 and August 2019 were included in the retrospective cohort study. The correlation between POD and PNI was investigated by univariate and multivariable logistic regression analysis, propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and subgroup analysis. ResultsIn the cohort (n = 29,814), the cutoff value of PNI was 46.01 determined by the receiver operating characteristic (ROC) curve. In univariate and three multivariable regression analysis, the ORs of PNI ≤ 46.01 was 2.573(95% CI:2.261–2.929, P < 0.001),1.802 (95% CI:1.567-2.071, P < 0.001),1.463(95% CI:1.246–1.718, P < 0.001),1.370(95% CI:1.165–1.611, P < 0.001). In the PSM model and IPTW model, the ORs of PNI ≤ 46.01 were 1.424(95% CI:1.172–1.734, P < 0.001) and 1.356(95% CI:1.223–1.505, P < 0.001). ConclusionThe PNI was found to have a predictive value for POD in patients undergoing non-neurosurgery and non-cardiac surgery. Improving preoperative nutritional status may be beneficial in preventing POD for aged patients.

137. THE COMPARISON OF UNIPORTAL VERSUS MULTIPORTAL VIDEO-ASSISTED THORACIC SURGERY FOR ESOPHAGEAL CANCER: A PROPENSITY-WEIGHTED ANALYSIS

Abstract Background Uniportal video-assisted thoracoscopic surgery (VATS) has been widely used, however, there are few studies on uniportal VATS for esophagectomy. Methods Data from patients with clinical stage T1–3/N0/M0 thoracic esophageal cancer who underwent surgery between January 2017 and December 2020 were prospectively enrolled and retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to assess the outcomes. Results Overall, 55 patients who underwent uniportal, and 212 patients who underwent multiportal, VATS were identified. Surgery-related postoperative complications (Clavien-Dindo grades 1–2) occurred less frequently after uniportal than multiportal VATS in both crude and IPTW models (8.1% versus 29.3%, respectively; P = 0.009). The median postoperative length of stay was 9 (9–10) days in the uniportal VATS and 10 (9–14) days in the multiportal VATS group (P = 0.025 after IPTW). Upon IPTW analysis, in uniportal and multiportal VATS groups, the rates of pneumonia were 10.6% and 26.9% (P = 0.040), while the rates of anastomotic fistulae (grade 2) were 1.0% and 6.6% (P = 0.036), respectively. The visual analog scale (VAS) was administered on postoperative first 7 days and were significantly lower in the uniportal VATS group (P &amp;lt; 0.001). No surgical mortality was observed in the uniportal VATS group, and the survival benefit between the two groups was comparable before (P = 0.732) and after IPTW (P = 0.542). Conclusions Uniportal VATS for esophagectomy resulted in a lower rate of postoperative complications with less postoperative pain, and is practical for treating patients with esophageal cancer.

Association of Long-term Antiseizure Medication Use and Incident Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) contributes significantly to metabolic syndrome and cardiovascular events, and it may be a comorbidity of epilepsy. The objective of this study was to investigate whether long-term antiseizure medication (ASM) use is associated with the risk of developing type 2 diabetes. We analyzed data from the Chang Gung Research Database. Patients aged ≥45 years who received ASM treatment from January 2001 to May 2019 were identified. Patients with DM-associated diseases and short-term ASM use were excluded. The patients were classified into nonenzyme interaction, enzyme-inducing, enzyme-inhibiting, and mixed ASM groups. The rate of incident diabetes associated with individual ASM was further analyzed. Propensity score weighting was performed to balance between-group differences. Analyses were conducted with Cox proportional regression models and stabilized inverse probability of treatment weighting (IPTW). Hazard ratios (HRs) were calculated at 3, 4, 6, and 9 years after the index date and the end of follow-up. A total of 5,103 patients were analyzed, of whom 474 took nonenzyme interaction ASMs, 1,156 took enzyme-inducing ASMs, 336 took enzyme-inhibiting ASMs, and 3,137 took mixed ASMs. During follow-up (39,248 person-years), 663 patients developed new-onset DM, and the prevalence was 13.0%. The incidence of DM plateaued at 6-9 years after ASM initiation. Enzyme-inhibiting ASMs were significantly associated with a higher HR starting at the third year and then throughout the study period. The HRs were 1.93 (95% CI 1.33-2.80), 1.85 (95% CI 1.24-2.75), and 2.08 (95% CI 1.43-3.03) in unadjusted, adjusted, and stabilized IPTW models, respectively, at the end of follow-up. The dosing of ASM did not increase the risk of DM, and none of the individual ASM analyses reached statistical significance. The long-term use of enzyme-inhibiting ASMs was associated with an increased risk of incident DM, and the risk increased with the duration of treatment. These findings may guide the choice of drugs in those requiring long-term ASM therapy, particularly in high-risk individuals. This study provides Class IV evidence that enzyme-inhibiting ASMs were associated with an increased risk of developing DM compared with nonenzyme interaction ASMs.

A Cross-Sectional Investigation of the Association between Arterial Stiffness and Depressive Symptoms, Anxiety Symptoms, and Quality of Life

Background and Objectives: Previous studies have assessed the association between arterial stiffness and depressive and anxiety symptoms, but the results were inconsistent. We aimed to conduct a cross-sectional study to assess the relationship between arterial stiffness, depressive and anxiety symptoms, and quality of life. Materials and Methods: We analyzed the 2014-2015 Korea Institute of Sport Science Fitness Standards project data. Brachial-ankle pulse wave velocity (baPWV) was measured to assess arterial stiffness. High baPWV was defined as a baPWV higher than 1400 cm/s. Participants completed Beck's depressive symptoms inventory (BDI), Beck's anxiety symptoms inventory (BAI), and the World Health Organization's Quality of Life Questionnaire (WHOQOL-Bref). We performed a logistic regression analysis by adjusting confounding factors and used the inverse probability of treatment weighting (IPTW) method. Results: 1936 participants were included in the analysis (men 43.9%, median age 47). Participants with a high baPWV had higher odds of depressive symptoms compared to those with a normal baPWV (aOR 1.920, 95% CI 1.062-3.472, p = 0.031; IPTW OR 2.637, 95% CI 1.219-5.704, p = 0.014). In addition, baPWV was significantly associated with depressive symptoms in the IPTW model in men but not in women (OR 2.497, 95% CI 1.004-6.207, p = 0.049). High baPWV was not associated with anxiety symptoms in all models, but it was associated with poor QOL in women (OR 4.561, 95% CI 1.465-14.199, p = 0.009). Conclusions: High baPWV was associated with higher odds of depressive symptoms, especially in men. Our study suggests a modest association between arterial stiffness and depressive symptoms in Korean adults.

Association between early vasopressor administration and in-hospital mortality in critically ill patients with acute pancreatitis: A cohort study from the MIMIC-IV database.

This study aims to explore the association between early administration of vasopressors and in-hospital mortality in acute pancreatitis (AP) patients admitted to the ICU. The MIMIC-IV database was used to identify AP patients who had and had not received vasopressors. Univariate and multivariate logistic regression, propensity score matching (PSM), and inverse probability of treatment weighting (IPTW) were used for statistical analysis. A total of 894 AP patients admitted to the ICU were included in the study. Among them, AP patients who received vasopressors were associated with an increased risk of in-hospital mortality in the unadjusted model (OR: 7.77, 95% CI 4.92-12.61, p<0.001), multivariable-adjusted model (OR: 2.51,95% CI 1.1-5.76, p<0.05), PSM model (OR: 2.58, 95% CI 1.03-6.85, p<0.05) and IPTW model (OR: 1.82, 95% CI 1.06-3.15, p<0.05) compared with patients who did not receive vasopressors. In the subgroup analysis, age (≥ 65 years old: OR: 2.5, 95% CI 0.82-7.91; <65 years old: OR: 4.63, 95% CI 0.84-26.41), male (OR: 1.19, 95% CI 0.35-4.03), ethnicity (white: OR: 2.49, 95% CI 0.81-7.62; non-white: OR: 4.28, 95% CI 0.85-23.7), usage of norepinephrine (OR: 2.29, 95% CI 0.91-5.78), and single-use of vasopressor (OR: 1.48, 95% CI 0.43-4.95) were not associated with in-hospital mortality in patients with AP, whereas vasopressin (OR: 4.27, 95% CI 1.24-15.13; p<0.05) and phenylephrine usage (OR: 4.75, 95% CI 1.66-13.95; p<0.05), combined vasopressor usage (OR: 4.41, 95% CI 1.55-12.96; p<0.01), and female usage (OR: 7.89, 95% CI 2.03-34.2; p<0.01) were associated with in-hospital mortality. Early vasopressor use is significantly associated with increased in-hospital mortality among critically ill AP patients. This association might be greater in females, vasopressin, phenylephrine, and combined vasopressor users. Our results may benefit clinicians as they can guide the rational use of vasopressors in critically ill AP patients admitted to the ICU.

UNTREATED OBSTRUCTIVE SLEEP APNEA INCREASES HOSPITALIZATION RISK IN MEDICARE BENEFICIARIES 65+ WITH HEART DISEASE

Abstract Cardiovascular disease (CVD) is a leading cause of death and disability in the United States and worldwide. Untreated obstructive sleep apnea (OSA) is common among older adults with CVD and may increase their risk of hospitalization. However, prior research has been limited by smaller samples of participants undergoing diagnostic sleep testing. Our objective was to estimate the effect of untreated OSA on the risk of hospitalization among older Medicare beneficiaries with CVD age 65+. Using a 5% sample of Medicare administrative claims data from 2006 to 2013, beneficiaries were identified as cases diagnosed with OSA or controls without any sleep-related diagnoses. Then, we restricted only to beneficiaries with a CVD diagnosis by the index date (i.e., OSA diagnosis date or matched date in controls). Next, we assessed the risk of hospitalization, counting only one per beneficiary, during the year before the index date. Because OSA is typically present long before it is diagnosed, the year before OSA diagnosis was assumed to represent a period of untreated OSA. Covariates were balanced between cases and controls using inverse probability of treatment weighting (IPTW). Then using logistic regression, we estimated the risk of hospitalizations the year prior to the index date. Of the 142,893 beneficiaries with CVD, only 19,390 were diagnosed with OSA. In the IPTW model, beneficiaries with untreated OSA were more likely to be hospitalized (odds ratio, 1.82; 95% CI 1.77–1.87). Results suggest screening for OSA among Medicare beneficiaries with CVD may identify older adults at increased risk of hospitalization.

Simultaneous splenectomy improving the outcomes of patients with hepatocellular carcinoma, cirrhosis and portal hypertension treated with hepatectomy

AbstractAimsPatients with cirrhosis and clinically significant portal hypertension (CSPH) usually have concomitant secondary hypersplenism, and splenectomy (Spx) is an option for treating these patients in the Asia‐Pacific region. CSPH is the most important risk factor for postoperative liver dysfunction (PLD) in patients with hepatocellular carcinoma (HCC) and cirrhosis undergoing liver resection. However, the impact of simultaneous Spx and hepatectomy in patients with HCC and CSPH remains unclear. In this study, we aimed to determine the impact of simultaneous Spx on the posthepatectomy outcomes in these patients.MethodsThis study included 691 consecutive patients with hepatitis B virus‐related HCC, cirrhosis, and CSPH. These included 565 patients who underwent hepatectomy only (non‐Spx group) and 126 who underwent simultaneous hepatectomy and splenectomy (Spx group). We analyzed the effect of 25 preoperative and 5 intraoperative factors on postoperative outcomes using logistic regression. To overcome any possible selection bias, confounders were balanced by propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses, and subgroup analyses were performed within the PSM‐matched groups.ResultsLogistic regression analyses revealed that Spx was an independent protective factor for severe postoperative liver dysfunction (SPLD; odds ratio [OR] = 0.22, 95% confidence interval [CI]: 0.11–0.43, p &lt; 0.001) and 90‐day SPLD‐related mortality (OR = 0.21, 95% CI: 0.06–0.55, p = 0.004), respectively. Spx was also independently associated with a higher overall survival rate (hazard ratio = 0.63, 95% CI = 0.47–0.85, p = 0.002) based on Cox regression analysis. PSM and IPTW models showed that the benefit of Spx was also consistent across the major and minor hepatectomy subgroups examined.ConclusionSimultaneous Spx improved the outcomes of patients with HCC, cirrhosis, and CSPH treated with hepatectomy, including patients who underwent major and minor hepatectomies.

Adjuvant radiation versus observation with salvage radiation after gross-total resection of WHO grade II meningiomas: a propensity score-adjusted analysis.

After gross-total resection (GTR) of a newly diagnosed WHO grade II meningioma, the decision to treat with radiation upfront or at initial recurrence remains controversial. A comparison of progression-free survival (PFS) between observation and adjuvant radiation fails to account for the potential success of salvage radiation, and a direct comparison of PFS between adjuvant and salvage radiation is hampered by strong selection bias against salvage radiation cohorts in which only more aggressive, recurrent tumors are included. To account for the limitations of traditional PFS measures, the authors evaluated radiation failure-free survival (RFFS) between two treatment strategies after GTR: adjuvant radiation versus observation with salvage radiation, if necessary. The authors performed a retrospective review of patients who underwent GTR of newly diagnosed WHO grade II meningiomas at their institution between 1996 and 2019. They assessed traditional PFS in patients who underwent adjuvant radiation, postoperative observation, and salvage radiation. For RFFS, treatment failure was defined as time from initial surgery to failure of first radiation. To assess the association between treatment strategy and RFFS while accounting for potential confounders, a multivariable Cox regression analysis adjusted for the propensity score (PS) and inverse probability of treatment weighted (IPTW) Cox regression analysis were performed. A total of 160 patients underwent GTR and were included in this study. Of the 121 patients who underwent observation, 32 (26.4%) developed recurrence and required salvage radiation. PFS at 3, 5, and 10 years after observation was 75.1%, 65.6%, and 45.5%, respectively. PFS at 3 and 5 years after salvage radiation was 81.7% and 61.3%, respectively. Of 160 patients, 39 received adjuvant radiation, and 3- and 5-year PFS/RFFS rates were 86.1% and 59.2%, respectively. In patients who underwent observation with salvage radiation, if necessary, the 3-, 5-, and 10-year RFFS rates were 97.7%, 90.3%, and 87.9%, respectively. Both PS and IPTW Cox regression models demonstrated that patients who underwent observation with salvage radiation treatment, if necessary, had significantly longer RFFS (PS model: hazard ratio [HR] 0.21, p < 0.01; IPTW model: HR 0.21, p < 0.01). In this retrospective, nonrandomized study, adjuvant radiation after GTR of a WHO II meningioma did not add significant benefit over a strategy of observation and salvage radiation at initial recurrence, if necessary, but results must be considered in the context of the limitations of the study design.

Ticagrelor Versus Clopidogrel in the treatment of Elderly Chinese Chronic Total Occlusion Patients Undergoing Percutaneous Coronary Intervention

Background: Taking thrombosis and bleeding risks into consideration, little real world study data is available to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in elderly Chinese chronic total occlusion (CTO) patients. Objective: This study was designed to investigate the effectiveness and safety of Ticagrelor in comparison with Clopidogrel as an add-on therapy to Aspirin for elderly Chinese CTO patients who underwent elective PCI. Materials and Methods: We retrospectively enrolled 504 CTO patients (aged ≥75 years) who received PCI from December 2009 to May 2020 and DAPT for up to 12 months. The effectiveness endpoints were evaluated by major adverse cardiac events (MACE) including all-cause death, nonfatal myocardial infarction (MI) and clinically driven revascularization. The safety endpoints were recorded as the incidence of Bleeding Academic Research Consortium (BARC) bleeding. Results: Patients in Clopidogrel group, as was evidenced in our study, were older, and had a higher percentage of BMI, diastolic blood pressure and HDL-C than those in Ticagrelor group. Clopidogrel group had a lower percentage of hyperlipidemia, prior PCI, glucose, TG and LDL-C. No significant difference was found as to the Angiographic and procedural characteristics (P＞0.05 for all). After 12 months' follow-up, the incidence of MACE (12.19% vs. 11.04%, P=0.763) and bleeding (9.38% vs. 13.64%, P=0.205) showed no significant difference. After clinical characteristics balanced matching by inverse probability of treatment weighting (IPTW) model, we found that Ticagrelor had an unfavorable effect on reducing the incidence of bleeding with the IPTW model (IPTW-OR, 1.81, 95% CI: 1.18-2.76, P=0.006). Conclusions: Clopidogrel and Ticagrelor present similar effectiveness and safety to elderly Chinese CTO-PCI patients, yet Ticagrelor should be prescribed with caution to patients with a high bleeding risk.

680NSAID use and ovarian cancer survival

Abstract Background Observational studies have reported survival benefits associated with non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, and non-aspirin NSAIDs (NA-NSAIDs), especially new use post-diagnosis, in women with ovarian cancer (OC). Methods Participants were women aged 18-79 diagnosed with OC in Australia, 2012-2015. Information was gathered through self-completed 3-monthly questionnaires and prescription records. Exposure was defined as any use (NA-NSAIDs/regular-dose aspirin □1/week or daily low-dose aspirin) during the year pre-diagnosis and first year post-diagnosis. We measured overall survival from start of primary treatment (surgery/neoadjuvant chemotherapy) (pre-diagnosis use) or from 12 months after the start of therapy (post-diagnosis) until the earliest of date of death/last follow-up/5 years. Cox proportional hazards regression was used to estimate survival. We also applied inverse-probability of treatment weighting (IPTW), which balances comparison groups regarding potential confounders. Results We observed improved survival associated with pre-diagnosis use of aspirin/NA-NSAIDs ≥4 days/week (frequent-users) compared to &amp;lt; 1/week (hazard ratio [HR] =0.72, 95% confidence interval [CI]=0.54-0.97). The association was close to null for those who used medications 1-3 days/week. Similarly, we saw a 30-40% improvement in survival associated with post-diagnosis aspirin/NA-NSAID use, again driven by frequent users (HR = 0.61, 95%CI=0.42-0.88). Results were similar when we excluded pre-diagnosis users, restricted to women who received chemotherapy, or assessed cancer-specific and progression-free survival. Results from IPTW models were similar to adjusted models. Conclusions Our findings suggest aspirin/NA-NSAID use might improve survival in women with OC. Larger cohorts or, preferably, a randomised controlled trial could clarify these findings. Key messages Use of aspirin/NA-NSAIDs may improve OC survival.

Paraplegia After Open Surgical Repair Versus Thoracic Endovascular Aortic Repair for Thoracic Aortic Disease: A Retrospective Analysis of Japanese Administrative Data

To comparatively examine the risk of postoperative paraplegia between open surgical descending aortic repair and thoracic endovascular aortic repair (TEVAR) among patients with thoracic aortic disease. Retrospective cohort study. Acute-care hospitals in Japan. A total of 6,202 patients diagnosed with thoracic aortic disease. None. The main outcome of this study was the incidence of postoperative paraplegia. Multiple logistic regression models, using inverse probability of treatment weighting and an instrumental variable (ratio of TEVAR use to open surgical repair and TEVAR uses), showed that the odds ratios of paraplegia for TEVAR (relative to open surgical descending aortic repair) were 0.81 (95% confidence interval: 0.42-1.59; p=0.55) in the inverse probability of treatment-weighted model and 0.88 (0.42-1.86; p=0.75) in the instrumental-variable model. There were no statistical differences in the risk of paraplegia between open surgical repair and TEVAR in patients with thoracic aortic disease. Improved perioperative management for open surgical repair may have contributed to the similarly low incidence of paraplegia in these two surgery types.

Time-varying effect of sex on prognosis of lung adenocarcinoma surgical patients in China.

BackgroundLittle is known about the prognostic advantage of sex for pulmonary adenocarcinoma among Chinese patients. In this study, we aimed to investigate the true sex differences in prognosis by adjusting for confounders and to explore whether the differences were time‐varying.MethodsWe identified 4438 lung adenocarcinoma patients who underwent surgery at a regional Cancer Center of China from 2008 to 2016, retrospectively. Sex, age group, smoking history, year of diagnosis and pathological stage were collected. Time‐dependent Cox regression models with inverse probability of treatment weighting (IPTW) based on propensity score were used to assess the effect of sex and account for confounders. Landmark analyses were conducted to assess survival before, and after, five years.ResultsOf these patients, 1761 (39.7%) were men and 2677 (60.3%) were women. Median follow‐up time was 52.6 months. After IPTW adjustment, women were found to have significantly better survival than men varying with time in both crude and IPTW models (hazard ratio [HR] [t] = 0.453*1.015t, where t is the length of time from treatment and its unit is month, p < 0.001). Women had significantly better survival than men within 0–5 years after surgery (HR = 0.763, 95% CI: 0.649–0.897, p = 0.001), whereas there was no difference after five years (HR = 1.135, 95% CI: 0.803–1.605, p = 0.472). In subgroup analysis, women in the 61–71+ age group, in the more than 20 year packs group, pathological stage 0–IB group, and 2013–2016 diagnosis period group revealed the same prognostic pattern.ConclusionsCompared with men, women had better survival after surgical resection of lung adenocarcinoma, especially those who were older and nonsmokers or heavy‐smokers and were pathological stage 0–IB in early years, while the advantage for women diminished with time.

The Effect of Different National Treatment Strategies on Disability Outcome in Relapsing-Remitting Multiple Sclerosis: A Propensity Score Adjusted Comparison between Denmark and Sweden

Background: Treatment strategies for relapsing-remitting multiple sclerosis (RRMS) vary markedly between Denmark and Sweden. The objective was to investigate the influence of such differences on disease modifying treatment (DMT) and disability outcome. Methods: Patients with RRMS commencing their first DMT 2013-2016 were retrospectively included from the Swedish and Danish MS registries. Time to the 24-week confirmed disability worsening (CDW, primary outcome) and 24-week confirmed disability improvement (CDI, secondary outcome) and milestone expanded disability status scale (EDSS) score 3 and 4 end-points (secondary outcomes) were analyzed using Inverse Probability of Treatment Weighting (IPTW)-based Cox regression models with robust standard errors. The IPTW model used a propensity score to weight and correct the comparison for the imbalance of confounders observed at baseline between the two countries. Findings: A total of 2700 patients from the Swedish registry and 2161 patients from the Danish MS registry commencing a first DMT between 2013 and 2016 were included in the analysis and observed for an average of 4 years. The proportion of patients initiating with a low-moderate as compared to highly effective DMT was 92.4% (teriflunomide 42%) and 7.6% in Denmark and 62.4% (teriflunomide 2.4%) and 35% in Sweden, respectively. Swedish patients were associated with a 29% reduction in the rate of post-baseline 24-week CDW relative to Danish patients (IPTW HR 0.71; 95% CI 0.57-0.90; p=0.004). The Swedish cohort was associated with a 27% and 26% reduction in the rate of reaching EDSS 3 and 4 respectively, relative to Danish patients (HR 0.73; 95% CI 0.62-0.85; p<0.001; and 0.74; 95% CI 0.59-0.93; p=0.009, reference = Denmark). Interpretation: We show for the first time that differences in treatment strategies of RRMS have an impact on disability outcomes at a national level. Escalation of treatment efficacy seemed inferior to using more efficacious DMT as initial treatment. Funding Statement: This study was supported by the Swedish Research Council, the Swedish Brain foundation, the Karolinska University Hospital & the Patient-Centered Outcomes Research Institute (PCORI), the Swedish Multiple Sclerosis Research Foundation, the Swedish Federal Government (LUA/ALF Agreement ALFGBG-722081), the Swedish Association of Persons with Neurological Disabilities, the Research Foundation of the Multiple Sclerosis Society of Gothenburg, the Edit Jacobson Foundation, and NEURO Sweden. Declaration of Interests: TS has received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen Inc; speaker honoraria from Novartis. MM has served on scientific advisory board for Biogen, Sanofi, Roche, Novartis, Merck, Abbvie, has received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, has received research support and support for congress participation from Biogen, Genzyme, Roche, Merck, Novartis. FP has received research grants from Biogen and Novartis. AS reports no conflicts of interest FS has served on scientific advisory boards for, served as consultant for, received support for congress participation or received speaker honoraria from Alexion, Biogen, Merck, Novartis, Roche and Sanofi Genzyme. His laboratory has received research support from Biogen, Merck, Novartis, Roche and Sanofi Genzyme. PVR has served on scientific advisory board for Biogen, Sanofi, Roche, Novartis, Merck, and Alexion, has received honoraria for lecturing from Biogen, Merck, Novartis, Roche, has received support for congress participation from Biogen, Genzyme, Roche, Merck, Novartis. MK reports no conflicts of interest HJ has received honoraria for participating in advisory board from Biogen. JH has received honoraria for serving on advisory boards for Biogen, Sanofi-Genzyme and Novartis and speaker’s fees from Biogen, Novartis, Merck-Serono, Bayer-Schering, Teva and Sanofi-Genzyme. He has served as P.I. for projects, or received unrestricted research support from, BiogenIdec, Merck- Serono, TEVA, Sanofi-Genzyme and Bayer-Schering. His MS research is funded by the Swedish Research Council and the Swedish Brain foundation JL has received travel support and/or lecture honoraria from Biogen, Novartis, Merck, Alexion, Roche and SanofiGenzyme; has served on scientific advisory boards for Biogen, Novartis, Merck, Roche, BSM and SanofiGenzyme; serves on the editorial board of the Acta Neurologica Scandinavica; has received unconditional research grants from Biogen, and Novartis. Ethics Approval Statement: The study was approved by the The Swedish Ethical Review Authority (Dnr: 2019-00839/1199-18), and The Danish Data Protection Authority (Org. number 202100 2973).

Chronic Metformin Therapy is Associated with a Lower Risk of Hemorrhoid in Patients with Type 2 Diabetes Mellitus.

Background: Metformin has anti-inflammatory property and reduces the risk of varicose vein in our previous study. Aim: To investigate the risk of hemorrhoid, another common disease involving the hemorrhoidal venous plexus, in ever vs. never users of metformin in patients with type 2 diabetes mellitus. Methods: This is a population-based retrospective cohort study. Patients with new-onset type 2 diabetes mellitus during 1999–2005 were enrolled from Taiwan’s National Health Insurance. All patients who were alive on January 1, 2006 were followed up until December 31, 2011. Analyses were conducted in both an unmatched cohort of 152,347 ever users and 19,523 never users and in 19,498 propensity score (PS)-matched pairs of ever and never users. Traditional Cox regression and Cox regression incorporated with the inverse probability of treatment weighting (IPTW) using the PS were used to estimate hazard ratios. Results: New-onset hemorrhoid was diagnosed in 8,211 ever users and 2025 never users in the unmatched cohort and in 1,089 ever users and 2022 never users in the matched cohort. The hazard ratio for ever vs. never users derived from the traditional Cox regression was 0.464 (95% confidence interval: 0.440–0.488) in the unmatched cohort; and was 0.488 (0.453–0.525) in the matched cohort. In the IPTW models, the hazard ratio was 0.464 (0.442–0.487) in the unmatched cohort and was 0.492 (0.457–0.530) in the matched cohort. A dose-response pattern was observed while comparing the tertiles of cumulative duration, cumulative dose and defined daily dose of metformin therapy to never users in all analyses. A risk reduction of approximately 40–50% was consistently observed in various sensitivity analyses. Conclusion: Chronic therapy with metformin in patients with type 2 diabetes mellitus is associated with a lower risk of hemorrhoid.

Abstract PS13-52: Preoperative systemic therapy versus upfront surgery in HER2-positive early breast cancer: A prospective nested case-control study in the real world

Abstract Purpose: To comparing the survival in different strategies, preoperative systemic treatment (PST) versus upfront surgery (US) in patients of HER2-positive early breast cancer in real-world.Methods: Eligible patients from 2012 to 2015 were classified as PST or US group prospectively, according to the real upfront treatment. The primary endpoint is disease-free survival (DFS), the second endpoint is overall survival (OS). All the outcomes were examined in unadjusted model, propensity score matching (PSM) model, and inverse probability of treatment weighting (IPTW) model. Results: Finally, 1067 eligible patients (215 in PST group, 852 in US group) were included into analysis (Table 1). In unweighted analysis, the cumulative DFS of PST group was significantly lower than US group (78.1% vs 87.7%, P&amp;lt;0.001), especially for those did not reach pathological complete response after PST. After adjusting the parameters, in PSM model (matching at 1:1 ratio), the DFS of PST group was significantly higher than the DFS of US group (HR, 0.57s2, 95%CI, 0.371~0.881, P, 0.012). In IPTW model, there was no significant difference of DFS between two groups (HR, 0.946, 95%CI, 0.763~1.172, P, 0.609). For OS, there were no significant difference between two groups in all three models. Conclusions: The patients in PST group have worse DFS than those in US group, mainly because of the unbalancing stage and biological risk. By real-world statistic method, after adjusting and making parameters comparable, the DFS of PST group is non-inferiority to the DFS of US group in IPTW model and even superior to US group in PSM model. *Proportions and medians are weighted using IPTW, all covariates included in the propensity analysis. Abbreviations: PSM, propensity score matching, IPTW, inverse probability of treatment weighting, PST, preoperative systemic treatment, US, upfront surgery, SMD, standardized mean difference, ER, estrogen receptor, PR, progesterone receptor.In IPTW model, the DFS rate of the PST group was 81.3% versus 80.8% of the US group, and the OS rate of the PST group was 92.1% versus 90.3% (Figure 2E, 2F), both having no significantly differences (Table 4). In further stratified analysis (Figure 3E, 3F), as in PSM model, the DFS and OS rate of the patients without pCR after PST (73.1%, 88.4%) were worse than those with pCR (96.6%, 99.3%) and US group (80.8%, 90.3%), respectively. Table 1. The clinicopathologic characteristics of two groups in PSM and IPTW modelsCharacteristicsNumber of casesUnweighted primary samplePSM modelIPTW model*PST group (215)US group (852)SMDPST group (145)US group (145)SMDPST group (765)US group (1021)SMDN (%)N (%)N (%)N (%)N (%)N (%)Age (years, medium, 95%CI)50, 39~6150, 33~640.0550, 40~6549, 34~620.1049, 39~6750, 31~640.03Stage T14588 (3.7)450 (52.8)0.7018(3.7)10 (6.9)0.03280 (10.5)450 (44.1)0.4672529157 (73.0)372 (43.7)118 (81.4)116 (80.0)635 (83.0)458 (44.9)38050 (23.3)30 (3.5)19 (13.1)19 (13.1)50 (6.5)113 (11.1)Stage N057137 (17.2)534 (62.7)1.04837 (17.2)32 (22.1)0.081310 (40.5)538 (52.7)0.2461596178 (82.8)318 (37.3)108 (81.4)113 (77.9)455 (59.5)483 (47.3)Grade1 and 252292 (42.8)430 (50.5)0.15477 (53.1)89 (61.4)0.168345 (45.1)493 (48.3)0.0643545123 (57.2)422 (49.5)68 (46.9)56 (38.6)420 (54.9)528 (51.7)ERNegative536142 (66.0)394 (46.2)0.40787 (60.0)68 (46.9)0.265386 (50.5)513 (50.2)0.004Positive53173 (34.0)458 (53.8)58 (40.0)77 (53.1)379 (49.5)508 (49.8)PRNegative649171 (79.5)478 (56.1)0.418108 (74.5)113 (77.9)0.081499 (65.2)625 (61.2)0.083Positive41844 (20.5)374 (43.9)37 (25.5)32 (22.1)266 (34.8)396 (38.8) Citation Format: Yang Hongjian, Xingfei Yu, Chen Wang, Zheng Yabing, Hu Jiejie, Xiying Shao, Liming Sheng, Juan Lin, Yuqin Ding, Haojun Xuan, Lijie Gong, Weiliang Feng, Chengdong Qin, Daobao Chen, Yang Yu. Preoperative systemic therapy versus upfront surgery in HER2-positive early breast cancer: A prospective nested case-control study in the real world [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-52.

Comparative risk of adverse outcomes associated with nonselective and selective antimuscarinic medications in older adults with dementia and overactive bladder.

The differential muscarinic receptor selectivity could cause selective antimuscarinics to offer advantages over nonselective agents with respect to adverse effects. The objective was to examine the comparative risk of falls/fractures and all-cause hospitalizations among older adults with dementia and overactive bladder (OAB) using nonselective and selective antimuscarinics METHODS/DESIGN: A retrospective cohort study design was conducted among older patients with dementia and OAB using incident antimuscarinics. The primary exposure was classified as nonselective (oxybutynin, tolterodine, trospium, and fesoterodine) and selective (solifenacin and darifenacin). Cox proportional-hazards regression using inverse probability of treatment weighting (IPTW) evaluated the risk of falls/fractures and all-cause hospitalizations within 6 months of nonselective and selective antimuscarinic use. The study cohort consisted of 13,896 (76.9%) nonselective and 4,179 (23.1%) selective antimuscarinic incident users. The unadjusted falls/fractures rate was 27.14% (3,772) for nonselective and 24.55% (1,026) for selective users (p-value< 0.01). The unadjusted all-cause hospitalizations rate was 24.14% (3,354) for nonselective and 21.58% (902) for selective users (p-value <0.01). The IPTW models did not find a significant difference in the risk of falls/fractures (Hazard Ratio [HR] 1.03; 95% Confidence Interval [CI] 0.99-1.07) and risk of all-cause hospitalizations (HR 1.04; 95% CI 0.99-1.08) between nonselective and selective antimuscarinics. Several sensitivity analyses corroborated the main findings. The study did not find a differential risk of falls/fractures and all-cause hospitalizations in older adults with dementia and OAB using nonselective and selective antimuscarinics. More research is needed to understand the role of pharmacodynamics and pharmacokinetics in the safety profile of antimuscarinics in dementia.