Marginal Cox Proportional Hazards Models Research Articles

Long-term Mortality and Reinterventions Following Repair of Ruptured Abdominal Aortic Aneurysms Using Vascular Quality Initiative Matched Medicare Claims

The optimal treatment modality for ruptured infrarenal abdominal aortic aneurysm (rAAA) repair remains debated. This study sought to evaluate the impact of treatment type on long-term mortality and reintervention after rAAA repair in the Vascular Quality Initiative (VQI) registry. VQI (2004-2018) rAAA repairs were matched with eligible Medicare claims data. The primary outcome was long-term survival. Secondary outcomes were reintervention rates and the impact of receiving a reintervention on survival. Inverse probability weighting was used to adjust for treatment selection. Marginal Cox proportional hazards models were used to compare survival and marginal negative binomial regressions were used to compare the rate of reintervention between groups. Additional landmark analysis at hospital discharge was used owing to high perioperative mortality. Among 1885 VQI/Medicare rAAA patients, 790 underwent open aortic repair (OAR) and 1095 underwent EVAR. Median age was 76 years and 73% were male. Inverse probability weighting produced comparable groups for analysis. In hospital mortality was lower for EVAR (21% vs 36%; odds ratio [OR], 0.52; 95% confidence interval [CI], 0.4-0.7). Crude mortality at 1, 2, and 5 years For OAR versus EVAR was 48% versus 40%, 54% versus 48%, and 71 versus 63%, respectively (Figure). Mortality within 1 year was lower for EVAR versus OAR (hazard ratio [HR], 0.74; 95% CI, 0.6-0.9), but similar after 1 year (HR, 0.95; 95% CI, 0.8-1.2) (Table). Compared with OAR, reintervention rates were higher after EVAR at 2 and 5 years (risk ratio, 1.8 [95% CI, 1.2-2.7] and risk ratio, 2.0 [95% CI, 1.4-3.0]), but not within the first year. Receiving a reintervention was associated with higher mortality risk for both OAR (HR, 1.66; 95% CI, 1.1-2.5) and EVAR (HR, 2.14; 95% CI, 1.6-2.9). When excluding in-hospital deaths, long-term mortality was similar between repair types (HR, 0.99; 95% CI, 0.8-1.2). The result of reinterventions and their impact on mortality was unchanged in landmark analysis. Within the VQI/Medicare patients undergoing rAAA repair, the perioperative benefit of EVAR dissipated after 1 year. Reintervention rates are more common after EVAR and are associated with higher mortality despite repair modality. These data highlight the need to improve long-term treatment after rAAA and to better define high-risk groups for reintervention.TableOverall mortality of open aneurysm repair (OAR) versus endovascular aneurysm repair (EVAR)MortalityOAREVARP valueIn-hospital Count (%), unweighted288 (36.46)233 (21.28)<.001 Odds ratio (95% CI)UnweightedRef0.47 (0.38-0.58)<.001WeightedRef0.52 (0.41-0.67)<.001 Hazard ratio (95% CI)Unweighted≤1 yearRef0.73 (0.63-0.84)<.001>1 yearRef0.95 (0.76-1.18)Not significantWeighted≤1 yearRef0.74 (0.63-0.87)<.01>1 yearRef0.95 (0.75-1.20)Not significantCI, confidence interval. Open table in a new tab

Contralateral Breast Screening with Preoperative MRI: Long-Term Outcomes for Newly Diagnosed Breast Cancer.

Background The diagnostic value of screening the contralateral breast with MRI in patients with newly diagnosed breast cancer is poorly understood. Purpose To assess the impact of MRI for screening the contralateral breast on long-term outcomes in patients with newly diagnosed breast cancer and to determine whether subgroups with unfavorable prognoses would benefit from MRI in terms of survival. Materials and Methods Data on consecutive patients with newly diagnosed breast cancer seen from January 2008 to December 2010 were reviewed retrospectively. Patients with neoadjuvant chemotherapy, previous breast cancer, distant metastasis, absence of contralateral mammography at diagnosis, and no planned surgical treatment were excluded. Groups that did and did not undergo preoperative MRI were compared. Survival analysis was performed using the Kaplan-Meier method for propensity score-matched groups to estimate cause-specific survival (CSS) and overall survival (OS). A marginal Cox proportional hazards model was used to evaluate association of MRI and clinicopathologic variables with OS. Results Of 1846 patients, 1199 fulfilled the inclusion criteria. Median follow-up time was 10 years (range, 0-14 years). The 2:1 matched sample comprised 705 patients (470 in the MRI group and 235 in the no-MRI group); median ages at surgery were 59 years (range, 31-87 years) and 64 years (range, 37-92 years), respectively. MRI depicted contralateral synchronous disease more frequently (27 of 470 patients [5.7%] vs five of 235 patients [2.1%]; P = .047) and was associated with a higher OS (hazard ratio [HR], 2.51; 95% CI: 1.25, 5.06; P = .01). No differences were observed between groups in metachronous disease rate (MRI group: 21 of 470 patients [4.5%]; no-MRI group: 10 of 235 patients [4.3%]; P > .99) or CSS (HR, 1.34; 95% CI: 0.56, 3.21; P = .51). MRI benefit was greater in patients with larger tumor sizes (>2 cm) (HR, 2.58; 95% CI: 1.11, 5.99; P = .03) and histologic grade III tumors (HR, 2.94; 95% CI: 1.18, 7.32; P = .02). Conclusion Routine MRI screening of the contralateral breast after first diagnosis of breast cancer improved overall survival; the most pronounced benefit was found in patients with larger primary tumor size and primary tumors of histologic grade III. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Taourel in this issue.

Adherence to a priori-Defined Diet Quality Indices Throughout the Early Disease Course Is Associated With Survival in Head and Neck Cancer Survivors: An Application Involving Marginal Structural Models.

No studies, to date, have scrutinized the role of a priori dietary patterns on prognosis following a head and neck squamous cell carcinoma (HNSCC) diagnosis. The purpose of this analysis was to evaluate the associations between adherence to six a priori defined diet quality indices (including AHEI-2010, aMED, DASH, and three low-carbohydrate indices) throughout the first 3 years of observation and all-cause and cancer-specific mortalities in 468 newly diagnosed HNSCC patients from the University of Michigan Head and Neck Specialized Program of Research Excellence (UM-SPORE). The dietary intake data were measured using a food frequency questionnaire administered at three annual time points commencing at study entry. Deaths and their causes were documented throughout the study using various data sources. Marginal structural Cox proportional hazards models were used to evaluate the role of diet quality, as a time-varying covariate, on mortality. There were 93 deaths from all causes and 74 cancer-related deaths adjudicated throughout the observation period. There was a strong inverse association between adherence to the AHEI-2010, all-cause mortality (HRQ5–Q1:0.07, 95% CI:0.01–0.43, ptrend:0.04), and cancer-specific mortality (HRQ5–Q1:0.15, 95% CI:0.02–1.07, ptrend:0.04). Other more modest associations were noted for the low-carbohydrate indices. In sum, higher adherence to the AHEI-2010 and a plant-based low-carbohydrate index throughout the first 3 years since diagnosis may bolster survival and prognosis in newly diagnosed patients with HNSCC.

KMSubtraction: reconstruction of unreported subgroup survival data utilizing published Kaplan-Meier survival curves

BackgroundData from certain subgroups of clinical interest may not be presented in primary manuscripts or conference abstract presentations. In an effort to enable secondary data analyses, we propose a workflow to retrieve unreported subgroup survival data from published Kaplan-Meier (KM) plots.MethodsWe developed KMSubtraction, an R-package that retrieves patients from unreported subgroups by matching participants on KM plots of the overall cohort to participants on KM plots of a known subgroup with follow-up time. By excluding matched patients, the opposing unreported subgroup may be retrieved. Reproducibility and limits of error of the KMSubtraction workflow were assessed by comparing unmatched patients against the original survival data of subgroups from published datasets and simulations. Monte Carlo simulations were utilized to evaluate the limits of error of KMSubtraction.ResultsThe validation exercise found no material systematic error and demonstrates the robustness of KMSubtraction in deriving unreported subgroup survival data. Limits of error were small and negligible on marginal Cox proportional hazard models comparing reconstructed and original survival data of unreported subgroups. Extensive Monte Carlo simulations demonstrate that datasets with high reported subgroup proportion (r = 0.467, p < 0.001), small dataset size (r = − 0.374, p < 0.001) and high proportion of missing data in the unreported subgroup (r = 0.553, p < 0.001) were associated with uncertainty are likely to yield high limits of error with KMSubtraction.ConclusionKMSubtraction demonstrates robustness in deriving survival data from unreported subgroups. The limits of error of KMSubtraction derived from converged Monte Carlo simulations may guide the interpretation of reconstructed survival data of unreported subgroups.

Depressive symptoms are no longer a barrier to HCV treatment initiation in the HIV–HCV co-infected population in Canada

Background Psychiatric illness was a major barrier for HCV treatment during the Interferon (IFN) treatment era due to neuropsychiatric side effects. While direct acting antivirals (DAA) are better tolerated, patient-level barriers persist. We aimed to assess the effect of depressive symptoms on time to HCV treatment initiation among HIV–HCV co-infected persons during the IFN (2003–2011) and second-generation DAA (2013–2020) eras. Methods We used data from the Canadian Co-infection Cohort, a multicentre prospective cohort, and its associated sub-study on Food Security (FS). We predicted Center for Epidemiologic Studies Depression Scale-10 (CES-D-10) classes for depressive symptoms indicative of a depression risk using a random forest classifier and corrected for misclassification using predictive value-based record-level correction. We used marginal structural Cox proportional hazards models with inverse weighting for competing risks (death) to assess the effect of depressive symptoms on treatment initiation among HCV RNA-positive participants. Results We included 590 and 1127 participants in the IFN and DAA eras. The treatment initiation rate increased from 9 (95% confidence interval (CI): 7–10) to 21 (95% CI: 19–22) per 100 person-years from the IFN to DAA era. Treatment initiation was lower among those with depressive symptoms compared to those without in the IFN era (hazard ratio: 0.81 (95% CI: 0.69–0.95)) and was higher in the DAA era (1.19 (95% CI: 1.10–1.27)). Conclusion Depressive symptoms no longer appear to be a barrier to HCV treatment initiation in the co-infected population in the DAA era. The higher rate of treatment initiation in individuals with depressive symptoms suggests those previously unable to tolerate IFN are now accessing treatment.

Association Between Nonselective Beta-Blocker Use and Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Without Cirrhosis and Decompensation.

Background: Nonselective beta-blockers (NSBBs) can reduce the incidence or mortality of certain types of cancers, and NSBBs exert a protective effect on hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the potential preventive effect of NSBBs has not yet been investigated in patients with chronic hepatitis B (CHB) who have a high HCC risk regardless of the presence of underlying cirrhosis. Aim: This study evaluated the association between NSBB use and HCC incidence in patients with CHB without cirrhosis and decompensation. Methods: From the 2000 Longitudinal Generation Tracking Database, we enrolled patients who were newly diagnosed as having CHB from January 2001 to December 2011 and then followed them up for at least 5 years. To estimate the causal effect of NSBBs on the time-to-event outcomes of HCC, a marginal Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: After adjustment, no significant benefit of HCC risk reduction was observed between the NSBB users and nonusers (adjusted HR, 0.82; 95% CI, 0.52–1.31). The cumulative defined daily dose (cDDD) analysis revealed no significant dose correlation among the three groups [adjusted HR (95% CI): 1.08, (0.56–2.05), 0.54 (0.17–1.77), and 0.76 (0.40–1.42) in the <90 cDDD, 90 to <180 cDDD, and ≥180 cDDD groups, respectively]. Duration-dependent associations were not observed. Multivariable stratified analysis results demonstrated that HCC risk markedly decreased in the patients aged >55 years (adjusted HR, 0.49; 95% CI, 0.25–0.96; p = 0.04). Conclusion: NSBB did not significantly prevent HCC in the patients with CHB infection without cirrhosis and decompensation. This study provided one of valuable results that it is not clinically required to use NSBBs as recommended chemoprevention for HCC in high-risk patients who have CHB.

Impact of Anti-tumour Necrosis Factor Agents on the Risk of Colorectal Cancer in Patients with Ulcerative Colitis: Nationwide French Cohort Study.

Patients with ulcerative colitis [UC] are at increased risk of colorectal cancer. Anti-tumour necrosis factor agents [anti-TNF] aim to reduce chronic colonic inflammation and may lower the risk of colorectal cancer [CRC], but the impact of anti-TNF exposure has not yet been assessed in population-based cohort studies. The aim of this nationwide study was to assess the risk of CRC in patients with UC exposed to anti-TNF. Based on the French health insurance database, patients aged 18 years or older with a diagnosis of UC, previously exposed to or initiating immunosuppressive treatment, were followed from January 1, 2009, until December 31, 2018. The risk of CRC associated with anti-TNF exposure was assessed using marginal structural Cox proportional hazard models adjusting for baseline and time-varying comorbidities including primary sclerosing cholangitis, UC disease activity, colonoscopic surveillance, and other medications. Among 32 403 patients with UC, 15 542 [48.0%] were exposed to anti-TNF. During a median follow-up of 6.1 years [198 249 person-years], 246 incident CRC occurred (incidence rate per 1000 person-years, 1.24; 95% confidence intrval [CI], 1.10-1.41). Whereas the risk of CRC associated with anti-TNF exposure was not decreased in the overall group of patients with UC (hazard ratio [HR], 0.85; 95% CI, 0.58-1.26), anti-TNF exposure was associated with a decreased risk of CRC in patients with long-standing colitis [disease duration ≥10 years] [HR, 0.41; 95% CI, 0.20-0.86]. In a nationwide cohort of patients with UC, anti-TNF exposure was associated with a decreased risk of CRC in patients with long-standing colitis.

Treatment Persistence in Patients Cycling on Subcutaneous Tumor Necrosis Factor-Alpha Inhibitors in Inflammatory Arthritis: A Retrospective Study.

Biologic treatments including subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) have greatly improved disease management of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) (collectively inflammatory arthritis, IA). Nevertheless, some patients discontinue their first-line treatment; for them, one option may be a subsequent line of the same treatment class (i.e., cycling). The aim of this study was to assess treatment persistence between first- and second-line therapy in Swedish IA patients cycling on SC-TNFis. Using data from the Swedish Health Data Registers, adult IA patients filling prescriptions between May 1, 2010, and October 31, 2016, for a SC-TNFi (adalimumab, etanercept, certolizumab and golimumab) were included. Treatment persistence was derived based on information from filled prescriptions and a 60-day grace period. Unadjusted and adjusted marginal Cox proportional hazards models were fitted to estimate the relative risk of discontinuation across treatment lines, using robust sandwich covariance matrix estimates to account for intrapatient dependence (i.e., multiple treatment lines per patient). The analysis was restricted to the first two lines of treatment. Of the eligible patients, 3181 were identified as cyclers. Among these, most were female (68%), and 46%, 28% and 26% were diagnosed with RA, AS and PsA, respectively. Both the unadjusted and adjusted analyses showed that the relative risk of discontinuing SC-TNFi treatment was significantly lower in second compared to first line (hazard ratio; 0.60 [0.57, 0.63] and HR; 0.59 [0.56, 0.62]). This finding was also consistent across IA indications. In this study of patients cycling on SC-TNFis in IA, persistence was greater in second- compared to first-line treatment. The finding was consistent across all IA indications. Hence, patients who discontinue their first-line treatment may still benefit from treatment with an alternative SC-TNFi as a second-line therapy in IA.

Sunscreens With High Versus Low Sun Protection Factor and Cutaneous Squamous Cell Carcinoma Risk: A Population-Based Cohort Study.

Evidence on sunscreen use and cutaneous squamous cell carcinoma (cSCC) risk is limited. Most studies have not taken sun protection factor (SPF) into consideration and used nonusers of sunscreen as the reference group. Nonusers are likely a priori at lower cSCC risk than users. No study has investigated the effect of high- versus low-SPF sunscreens on cSCC, appropriately adjusting for time-varying confounding. Using data from the Norwegian Women and Cancer Study (1991–2016), we investigated whether use of SPF ≥15 versus SPF <15 sunscreens reduces cSCC risk. We used a marginal structural Cox proportional hazards model with inverse probability of treatment and censoring weights to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During follow-up of 148,781 women (mean follow-up, 14.3 years), 653 women were diagnosed with cSCC. The effect on cSCC risk of sunscreens with SPF ≥15 versus SPF <15 was close to the null when used at any latitudes (HR = 1.02, 95% CI: 0.82, 1.27) and when used in lower-latitude settings (HR = 1.05, 95% CI: 0.84, 1.32). In conclusion, we found no indication that sunscreens with SPF ≥15 reduced Norwegian women’s cSCC risk more than sunscreens with SPF <15, suggesting that either there is no difference in their effects long-term or the difference is diluted by incorrect application.

Immunosuppression does not prevent severe gastrointestinal tract involvement in systemic sclerosis.

We aimed to test the hypothesis that exposure to immunosuppression in early systemic sclerosis (SSc) could modify the risk of developing new onset severe gastrointestinal (GIT) involvement. A total of 762 subjects with <3 years of disease duration and without severe GIT disease at baseline study visit were identified from combined longitudinal cohort data from the Canadian Scleroderma Research Group (CSRG) and Australian Scleroderma Interest Group (ASIG). The primary exposure was ever use of methotrexate, cyclophosphamide, mycophenolate mofetil and/or azathioprine during the study period. Severe GIT disease was defined as: 1-malabsorption, 2-hyperalimentation, 3-pseudo-obstruction, and/or 4-≥10% weight loss in association with the use of antibiotics for bacterial overgrowth or oesophageal stricture. The change in the hazard of severe GIT disease due to exposure was estimated using a marginal structural Cox proportional hazards model fit by inverse probability of treatment weights (IPTW) to address potential confounding. Study subjects were 81.5% female, had a mean age of 53.7±13.0 years and mean disease duration at baseline of 1.4±0.8 years. During a mean follow-up of 4.0±2.6 years, severe GIT involvement developed in 11.6% of the 319 subjects exposed to immunosuppression and in 6.8% of the 443 unexposed subjects. In an IPTW-adjusted analysis, exposure to immunosuppression was not associated with severe GIT disease (weighted hazard ratio 0.91, 95% confidence interval 0.52-1.58). In this large inception SSc cohort, the risk of severe GIT involvement was not modified by exposure to immunosuppression.

Prognostic Implications of Comprehensive Whole Vessel Plaque Quantification Using Coronary Computed Tomography Angiography.

The prognostic value of whole vessel plaque quantification has not been fully understood. We aimed to investigate the clinical relevance of whole vessel plaque quantification on coronary computed tomography angiography. In a total of 1,013 vessels with fractional flow reserve (FFR) measurement and available coronary computed tomography angiography, high-risk plaque characteristics (HRPC) included minimum lumen area<4mm2, plaque burden≥70%, low attenuation plaque, positive remodeling, spotty calcification, and napkin-ring sign; and high-risk vessel characteristics (HRVC) included total plaque volume≥306.5 mm3, fibrofatty and necrotic core volume≥4.46 mm3, or percent total atheroma volume≥32.2% in a target vessel, based on corresponding optimal cutoff values. Survival analysis for vessel-oriented composite outcome (VOCO) (a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization) at 5 years was performed using marginal Cox proportional hazard models. Whole vessel plaque quantification had incremental predictability in addition to % diameter stenosis and HRPC (P< 0.001) in predicting FFR≤0.80. Among 517 deferred vessels based on FFR >0.80, the number of HRVC was significantly associated with the risk of VOCO (HR: 2.54; 95%CI: 1.77-3.64) and enhanced the predictability for VOCO of % diameter stenosis and the number of HRPC (P< 0.001). In a landmark analysis at 2 years, the number of HRVC showed sustained prognostic implications beyond 2 years, but the number of HRPC did not. Whole vessel plaque quantification can provide incremental predictability for low FFR and additive prognostic value in deferred vessels with high FFR over anatomical severity and lesion plaque characteristics. (CCTA-FFR Registry for Risk Prediction; NCT04037163).

Comparative Risk of Serious Infections With Tumor Necrosis Factor α Antagonists vs Vedolizumab in Patients With Inflammatory Bowel Diseases

We conducted a retrospective cohort study comparing the risk of serious infections between patients treated with tumor necrosis factor-a (TNFa) antagonists vs. vedolizumab in patients with inflammatory bowel diseases (IBD). Using an administrative claims database, we identified patients with IBD who were new-users of either TNFa antagonists or vedolizumab between 2014-2018 and had insurance coverage for at least 1y before and after treatment initiation. We compared the risk of serious infections (infections requiring hospitalization) between patients treated with vedolizumab or TNFa antagonists using marginal structural Cox proportional hazard models adjusted for baseline disease characteristics, healthcare utilization, comorbidities, and time-varying use of corticosteroids, immunomodulators and opiates. We included 4881 patients treated with TNFa antagonists (age, 41 ± 15y, 60% with Crohn's disease [CD]) of whom 434 developed serious infections over 5786 person-year [PY] follow-up, and 1106 patients treated with vedolizumab (age, 44 ± 16y, 39% with CD) of whom 86 developed serious infections over 1040-PY follow-up. Vedolizumab was associated with 46% lower risk of serious infections as compared with TNFa antagonists in patients with ulcerative colitis (HR,0.54 [95% CI,0.35-0.83), but no significant differences were observed in patients with CD (HR,1.30 [0.80-2.11]). Vedolizumab was associated with lower risk of extra-intestinal serious infections in patients with UC, but higher risk of gastrointestinal serious infections in patients with CD. In an observational study of patients with IBD, vedolizumab was associated with lower risk of serious infections as compared with TNFa antagonists, in patients with UC, but not in patients with CD.

Effect of Hospital Linens on Unit-Acquired Pressure Injuries for Adults in Medical ICUs: A Cluster Randomized Controlled Trial.

Objectives:Researchers have shown in laboratory studies that different types of fabrics were associated with changes in skin moisture, friction, shear, and temperature that may predispose patients to pressure injury. There was an association between type of fiber used in hospital linens and pressure injury development in previous clinical studies. We examined if bed linens made from a newly developed synthetic fiber fabric affected occurrence rate, time to development, and severity of unit-acquired pressure injury in critically ill adult inpatients.Design:Cluster randomized controlled trial.Setting:Five adult medical ICUs within one quaternary care center in the Midwest United States.Patients:Patients were assigned to a unit based on bed availability. In total, there were 3,332 patients in the study.INTERVENTIONS:Participating medical ICUs were randomly assigned to cotton fiber or synthetic fiber linens for the first 6 months of the study period, and assignment reversed after a 14-day washout period for the final 6 months.Measurements and Main Results:Unit-acquired pressure injury occurrence rate, time to first unit-acquired pressure injury, and severity were evaluated using generalized mixed effect models with patient as a random effect, and a marginal Cox proportional hazards model with repeated admissions from the same patient accounted for by use of a sandwich estimator of the variance. There were 1,706 patients on cotton fiber linens and 1,626 patients on synthetic fiber linens. Groups were similar on demographics except race and admitting diagnosis groupings. Occurrence rate (p = 0.99), time to development (p = 0.99), and maximum severity of unit-acquired pressure (p = 0.86) were similar between groups before and after controlling for race and admitting diagnosis groupings.Conclusions:Linen type did not affect unit-acquired pressure injury occurrence rate, severity, or timing. Standard unit-acquired pressure injury prevention efforts may be more cost-effective than investment in synthetic fiber linens.

Concurrent prescriptions for opioids and benzodiazepines and risk of opioid overdose: protocol for a retrospective cohort study using linked administrative data

IntroductionOpioid overdoses have increased substantially over the last 20 years, with over 400 000 deaths in North America. While opioid prescribing has been a target of research, benzodiazepine and opioid...

Survival on four compared with three times per week haemodialysis in high ultrafiltration patients: an observational study.

BackgroundThe harm caused by the long interdialytic interval in three-times-per-week haemodialysis regimens (3×WHD) may relate to fluid accumulation and associated high ultrafiltration rate (UFR). Four-times-per-week haemodialysis (4×WHD) may offer a solution, but its impact on mortality, hospitalization and vascular access complications is unknown.MethodsFrom the AROii cohort of incident in-centre haemodialysis patients, 3×WHD patients with a UFR >10 mL/kg/h were identified. The hazard for the outcomes of mortality, hospitalization and vascular access complications in those who switched to 4×WHD compared with staying on 3×WHD was estimated using a marginal structural Cox proportional hazards model. Adjustment included baseline patient and treatment characteristics with inverse probability weighting used to adjust for time-varying UFR and cardiovascular comorbidities.ResultsFrom 10 637 European 3×WHD patients, 3842 (36%) exceeded a UFR >10 mL/kg/h. Of these, 288 (7.5%) started 4×WHD and at baseline were more comorbid. Event rates while receiving 4×WHD compared with 3×WHD were 12.6 compared with 10.8 per 100 patient years for mortality, 0.96 compared with 0.65 per year for hospitalization and 14.7 compared with 8.0 per 100 patient years for vascular access complications. Compared with 3×WHD, the unadjusted hazard ratio (HR) for mortality on 4×WHD was 1.05 [95% confidence interval (CI) 0.78–1.42]. Following adjustment for baseline demographics, time-varying treatment probability and censoring risks, this HR was 0.73 (95% CI 0.50–1.05; P = 0.095). Despite these adjustments on 4×WHD, the HR for hospitalization remained elevated and vascular access complications were similar to 3×WHD.ConclusionsThis observational study was not able to demonstrate a mortality benefit in patients switched to 4×WHD. To demonstrate the true benefits of 4×WHD requires a large, well-designed clinical trial. Our data may help in the design of such a study.

Permanent discontinuation of different anticoagulants in patients with atrial fibrillation and the impact on clinical outcome: data from the GARFIELD-AF registry

Abstract Background Non-Vitamin K Antagonists (NOAC) are replacing vitamin K Antagonists (VKA) as first line oral anticoagulant therapy (OAC) in patients with non-valvular atrial fibrillation (NVAF). Discontinuation of OAC might put patients at increased risk. It was anticipated that patients who were on NOAC would discontinue OAC less. Purpose We compare the rates and impact on outcome of the discontinuation of NOAC and VKA using data from the GARFIELD-AF registry. Methods Patients included in GARFIELD-AF, had a new diagnosis of NVAF and at least 1 stroke risk factor. In this analysis 26,299 patients (VKA: 13,012; NOAC: 13,287) that received OAC were included. Permanent discontinuation was defined as stopping OAC for at least 7 consecutive days (whether or not restarted during follow-up). Marginal structural Cox proportional hazards models estimated the effect of discontinuation on death, cardiovascular (CV) death, non-haemorrhagic stroke + systemic embolism (NHS+SE), myocardial infarction (MI), or combined endpoints. Adjustments were made for both baseline factors and time dependent variables. Results Of all patients, 15.6% discontinued OAC (VKA: 15.4%; NOAC: 15.8%) over a median follow-up of 181 days (IQR: 359). Most discontinued early (67.0% of patients on VKA and 47.1% of patients on NOAC ≤4 months). Significantly higher discontinuation risk was seen with worsening kidney function, coronary artery disease, history of bleeding (baseline factors), as well as with all types of bleeding (time dependent factors). Lower discontinuation rates were seen with history of stroke/TIA, hypertension, increasing age, permanent AF (all p&amp;lt;0.01). Mean CHA2DS2-VASc score was 3 in all groups. Patients in both treatment arms who discontinued were at increased risk for death, NHS+SE, MI as well as combined endpoints of death/NHS+SE/MI, death/NHS+SE and a trend towards higher CV death (Figure 1). All interaction tests for the interaction of treatment and discontinuation had a p value &amp;gt;0.4. The association between discontinuation and outcomes did not change when a 30 day discontinuation window was used. Conclusion The rate of discontinuation in this study was 15.8% and comparable for VKA and NOAC over a 2-year follow-up. Discontinuation rates were the highest soon after the initiation of treatment. When VKA or NOAC was stopped for ≥7 consecutive days, the risk of NHS+SE, death, MI or any combined endpoints were significantly worse in both treatment arms. These data suggest that discontinuation of anticoagulant treatment with VKA or NOAC should be discouraged. HR of patients who discontinued OAC Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): The GARFIELD-AF registry is funded by an unrestricted research grant from Bayer AG.

The Academic Facility Is Associated with Higher Utilization of Esophagectomy and Improved Overall Survival for Esophageal Carcinoma

BackgroundOperable esophageal carcinoma is potentially curable with surgical resection. The short-term outcomes and overall survival rate for operable esophageal carcinoma may be impacted by the healthcare facility type where patients receive care. MethodsA total of 37, 271 cases with the American Joint Committee on Cancer clinical stage I, II, and III esophageal carcinoma that were reported to the National Cancer Data Base at over 12,721 facilities were analyzed. Healthcare facilities were dichotomized into the community and academic facility types. Marginal multivariable Cox proportional hazard models were used to evaluate differences in overall survival between facility types, which accounted for facility esophageal cancer volume. Propensity score methodology with inverse probability of treatment weighting was used to adjust for patient related baseline differences between facility types. ResultsPatients with clinical stage I–III esophageal carcinoma who underwent esophagectomy at academic healthcare facilities had a significantly better overall survival compared with patients who underwent esophagectomy at community healthcare facilities [HR = 0.89: CI [0.84–0.95] (p = 0.0005)]. The rate of esophagectomy was significantly higher at the academic facilities (49.0% versus 26.5%; p < 0.0001). The 30-day and 90-day mortality rates for esophagectomy were significantly better for patients who underwent esophagectomy for esophageal cancer at the academic facility types. ConclusionPatients with clinical stage I–III esophageal carcinoma who received care at academic facility types had significantly better overall survival compared with community facility types. The utilization of esophagectomy was significantly higher and the short-term surgical outcomes were better for patients treated at academic facility types.

S0861 Comparative Risk of Serious Infections With Tumor Necrosis Factor-α Antagonists vs Vedolizumab in Patients With Inflammatory Bowel Diseases

INTRODUCTION: Comparative safety of therapies is an important attribute in choosing optimal therapy in patients with inflammatory bowel diseases (IBD). We conducted a retrospective cohort study comparing the risk of serious infections between patients treated with tumor necrosis factor-α (TNFα) antagonists and those treated with vedolizumab. METHODS: Using an administrative claims database (OptumLabs Data Warehouse) we identified patients with IBD who were new-users of either TNFα antagonists or vedolizumab between 2014 and 2019 and had insurance coverage for at least 1y before and 1y after treatment initiation. We compared the risk of serious infections between patients treated with TNFα antagonists and those treated with vedolizumab using marginal structural Cox proportional hazard models adjusted for ulcerative colitis (UC) versus Crohn’s disease (CD), baseline demographics, healthcare utilization, comorbidities and time-varying use of IBD-related medications including corticosteroids and immunomodulators. RESULTS: We included 4896 patients treated with TNFα antagonists (age, 41 ± 15 y, 51% male, 60% with CD) of whom 434 developed serious infections over a 6009 person-year [py] follow-up, and 1106 patients treated with vedolizumab (age, 44 ± 16 y, 49% male, 39% with CD) of whom 86 developed serious infections over a 1077 py follow-up. On adjusted analysis, TNFα antagonists were associated with 2.4-fold higher risk of serious infections (hazard ratio [HR], 2.38 [95% CI, 1.38–4.13]) when compared with vedolizumab in all patients with IBD, and in subgroup analyses of patients with CD (HR, 2.28 [1.13–4.62]) and UC (HR, 1.62 [1.03–2.5]). This was primarily driven by increased risk of extra-intestinal serious infections (HR, 3.13 [1.48–6.63]), without any increase in risk of serious gastrointestinal infections (HR, 0.60 [0.33–1.08]). CONCLUSION: In a large claims-based study, TNFα antagonists were associated with increased risk of serious infections as compared with vedolizumab, in patients with CD and UC, particularly risk of extra-intestinal infections.

The Academic Facility Type Is Associated With Improved Overall Survival for Early-Stage Lung Cancer

Early-stage non-small cell lung cancer (NSCLC) is potentially curable with surgical resection. The overall survival rate for early-stage NSCLC may be determined by the healthcare facility type where patients receive their lung cancer treatment. A total of 103,748 cases with the American Joint Committee on Cancer clinical stage I and II NSCLC that were reported to the National Cancer Database at over 1150 facilities were analyzed in this study. Healthcare facilities were dichotomized into the community and academic facility types. Marginal multivariable Cox proportional hazards models were used to evaluate differences in overall survival. Propensity score methodology with inverse probability of treatment weighting was used to adjust for facility volume and patient-related baseline differences between facility types. Patients with early-stage NSCLC who were treated at academic facility types had a significantly better median overall survival (63.2 months) compared with patients who received care at community healthcare facilities (54.2 months) (hazard ratio, 0.86; 95% confidence interval, 0.82-0.91; P < .0001). The surgical quality outcomes for NSCLC surgery, including 30-day mortality, 90-day mortality, and the median number of lymph nodes removed were significantly better for patients treated at the academic facility types. Patients with early-stage NSCLC who were treated at academic facility types had a significantly higher overall median survival compared with patients treated at community facility types. The short-term surgical quality outcomes were significantly better for patients who underwent surgery for early-stage NSCLC at academic facility types.

Combination therapy with rifampicin or fosfomycin in patients with Staphylococcus aureus bloodstream infection at high risk for complications or relapse: results of a large prospective observational cohort

To investigate whether Staphylococcus aureus bloodstream infection (SAB) patients at high risk for complications or relapse benefit from combination therapy with adjunctive rifampicin or fosfomycin. In this post hoc analysis, SAB patients with native valve infective endocarditis, osteoarticular infections or implanted foreign devices were included. The co-primary endpoints were all-cause 90 day mortality and death or SAB-related late complications within 180 days. To overcome treatment selection bias and account for its time dependence, inverse probability of treatment weights were calculated and included in marginal structural Cox proportional hazard models (MSCMs). A total of 578 patients were included in the analysis, of which 313 (54%) received combination therapy with either rifampicin (n = 242) or fosfomycin (n = 58). In the multivariable MSCM, combination therapy was associated with a better outcome, that is, a lower rate of death or SAB-related late complications within 180 days (HR 0.65, 95% CI 0.46-0.92). This beneficial effect was primarily seen in patients with implanted foreign devices, in which combination therapy was associated with a lower rate of death or SAB-related late complications within 180 days (HR 0.53, 95% CI 0.35-0.79) and a lower 90 day mortality (HR 0.57, 95% CI 0.36-0.91). Upon agent-specific stratification, we found no significant differences in outcomes between combination therapy containing rifampicin and fosfomycin; however, the number of patients in most subgroups was not large enough to draw firm conclusions. In patients with implanted foreign devices, combination therapy was associated with a better long-term outcome. Larger prospective studies are needed to validate these findings.