Propensity Score-adjusted Cox Regression Research Articles

Radiotherapy for Metastatic Epidural Spinal Cord Compression with Increased Doses: Final Results of the RAMSES-01 Trial.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 × 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 × 2.633 Gy (41.6 Gy10) or 18 × 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score-adjusted Cox regression) to a historical control group (n = 266) receiving 10 × 3.0 Gy (32.5 Gy10). In the phase 2 cohort, 50 (of 62 planned) patients were evaluated for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 × 2.633 Gy or 18 × 2.333 Gy was well tolerated and appeared superior to 10 × 3.0 Gy.

Radiotherapy for Metastatic Spinal Cord Compression with Increased Doses: Final Results of the RAMSES-01 Trial

To investigate the outcomes of precision-radiotherapy (RT) with 15 × 2.633 Gy (EQD2 = 41.6 Gy for tumor cell kill, α/β = 10 Gy) or 18 × 2.333 Gy (EQD2 = 43.2 Gy) in patients with metastatic spinal cord compression (MSCC) and favorable survival prognoses (>35 points on a validated survival score). In addition, these patients were compared to a historical control group of patients with favorable prognoses treated with 10 × 3 Gy (EQD2 = 32.5 Gy). In a multi-center phase 2 study (RAMSES-01), patients with MSCC and favorable survival prognoses receiving 15 × 2.633 Gy or 18 × 2.333 Gy of precision-RT alone (no upfront surgery) were mainly evaluated for local progression-free survival (LPFS), defined as no deterioration of motor function during RT and no in-field recurrence of MSCC following RT, at 12 months (primary endpoint). Secondary endpoints included improvement of motor and sensory functions, post-RT ambulatory status, relief of pain and distress, toxicity, and survival (OS). The maximum relative doses allowed to the spinal cord were 101.5 % of the prescribed dose for 18 × 2.333 Gy and 101.2% for 15 × 2.633 Gy, respectively (both representing an EQD2 of 46.6 Gy for myelopathy, α/β = 2 Gy). In addition, the RAMSES-cohort was compared to a historical control group (N = 266) irradiated with 10 × 3 Gy (propensity score adjusted Cox regression). In the RAMSES-cohort, 50 (of 62 planned) patients were evaluable for LPFS and included in the analyses. Since OS was worse than expected, a new survival score was developed, which was more precise in predicting OS than a previous tool. As a consequence, the RAMSES-trial, which was based on the previous score, was terminated. In the 50 patients included so far, 12-month rates of LPFS and OS were 97.6% and 69.9%, respectively. Improvement of motor function occurred in 28 patients (56.0%), and 47 patients (94.0%) were ambulatory following RT. Within 3 months following RT, 12 of 21 patients (57.2%) with pre-RT sensory deficits improved, 38 of 45 patients (84.4%) with pre-RT pain experienced at least partial relief, and 39 of 50 patients (78.0%) reported relief of distress. Ten of 50 patients (20.0%) experienced grade 2 toxicities (mainly esophagitis/dysphagia) and another two patients (4.0%) grade 3 toxicities (1 diarrhea, 1 esophagitis). After propensity score adjustment, the RAMSES-cohort showed significantly better LPFS than the control group (hazard ratio = 0.125, 95% confidence interval = 0.016 - 0.962, p = 0.046) and a strong trend regarding improvement of motor function (hazard ratio = 1.943, 95% confidence interval = 0.981 - 3.850, p = 0.057). Post-RT ambulatory rates (p = 0.56) and OS rates (p = 0.62) were not significantly different. Precision-RT with 15 × 2.633 Gy or 18 × 2.333 Gy was sufficiently well tolerated and resulted in significantly better long-term LPFS than 10 × 3 Gy in patients with MSCC and favorable survival prognoses. Thus, the dose-fractionation regimens of the RAMSES-01 trial appear preferable for these patients.

The long-term outcomes of surgical ablation for atrial fibrillation during redo left-sided valvular surgery.

This study evaluated the outcome of surgical ablation (SA) for atrial fibrillation (AF) concomitant with redo left-sided valvular surgery. The study enrolled 224 AF patients (paroxysmal: 13 patients, persistent: 76 patients, long-standing persistent AF: 135 patients) undergoing redo open heart surgery for left-sided valve disease. The early results and long-term clinical outcomes were compared between those who underwent concomitant SA for AF (SA group) and did not (NSA group). Propensity score adjusted Cox regression analysis of overall survival and competing risk analysis of the other clinical outcomes were performed. Seventy-three patients were classified as the SA group and 151 as the NSA group. The median follow-up duration was 124 (1.0-249.5) months. The median ages of the patients in the SA and NSA groups were 54.1±11.3 and 58.4±11.1 years, respectively. There were no significant differences between the groups in the early in-hospital mortality rate (5.5% vs. 9.3%, P=0.474) or postoperative complications, except for low cardiac output syndrome (11.0% vs. 23.8%, P=0.036). Overall survival was better in the SA group [hazard ratio, 0.452; 95% confidence interval (CI): 0.218-0.936, P=0.032]. The incidence of recurrent AF was significantly higher in the SA group on multivariate analysis [hazard ratio, 3.440; 95% CI: 1.987-5.950, P<0.001]. The cumulative incidence of the composite of thromboembolism and bleeding was lower in the SA than NSA group [hazard ratio, 0.338; 95% CI: 0.127-0.897, P=0.029]. The concomitant surgical arrhythmia ablation with redo cardiac surgery for left-sided heart disease resulted in a better overall survival, higher incidence of sinus conversion, and lower incidence of a composite of thromboembolism and major bleeding. Concomitant SA procedure should be considered in patients undergoing redo cardiac surgery.

Ablation therapy for patients with colorectal liver metastases with and without extrahepatic metastases: evaluation of long-term outcomes and prognostic factors.

Ablation is a valuable treatment alternative to surgery for colorectal liver metastases. This study reports the long-term clinical outcomes in patients treated with ablation for colorectal liver metastases with or without extrahepatic metastases. Patients with colorectal liver metastases treated with ultrasound-guided ablation at Herlev Hospital, Denmark were included in this retrospective study. This study included 284 patients with 582 metastases. Complete ablation was obtained in 258 patients (91%) evaluated within 6 weeks. During follow-up, 94 patients (33%) developed local recurrence. The median survival for all patients was 31 months, with 1-, 3-, and 5-year survival rates of 82%, 45%, and 21%, respectively. The median survival for patients with extrahepatic metastases (n=49, 17%) was 24 months compared with 33 months for patients without (P=0.142). Propensity score-adjusted Cox regression showed that extrahepatic metastases were associated with increased mortality, with a hazard ratio (HR) of 1.45 (95% confidence interval [CI], 1.02 to 2.05; P=0.039). In multivariate Cox regression analysis for all patients, increased mortality risk was found for a diameter ≥2.6 cm (HR, 1.59; 95% CI, 1.23 to 2.05), >1 metastasis (HR, 1.66; 95% CI, 1.28 to 2.16), and extrahepatic metastases (HR, 1.45; 95% CI, 1.04 to 2.03). Male sex (HR, 0.75; 95% CI, 0.58 to 0.98) and receiving chemotherapy (HR, 0.69; 95% CI, 0.52 to 0.92) were associated with decreased mortality. Ablation for colorectal liver metastases offers acceptable survival rates, including for patients with extrahepatic metastases. In addition, chemotherapy was associated with improved survival for both patients with and without extrahepatic metastases.

T-wave alternans poorly prognostic in primary prophylactic ICD patients: a prospective EU-CERT-ICD study

Abstract Background New methods to identify patients who truly benefit from primary prophylactic implantable cardioverter defibrillation (ICD) are urgently needed. T-wave alternans (TWA) represents a beat-to-beat fluctuation in the morphology of the ST-segment and T-wave. It has been shown to associate with arrhythmogenesis of heart and sudden cardiac death [1]. We hypothised that TWA might associate with benefit from ICD implantation in primary prevention. Methods In EU-CERT-ICD study, we prospectively enrolled 2327 primary prophylactic ICD candidates from 15 European countries. A 24-hours Holter-monitoring was taken from all recruited patients at enrolment. TWA was assessed from Holter-monitoring using MMA method with Getemed Cardioday software. To assess the benefit from ICD treatment, we used outcomes all-cause mortality, appropriate shock and survival benefit. We conducted Cox regression model, competing risk regression model and propensity score adjusted Cox regression model. TWA was assessed both as contiguous variable and with cut-off points &amp;lt;47 μV and &amp;lt;60 μV. Results Final cohort included 1,734 valid T-wave alternans samples, 1,211 patients with ICD and 523 control patients with conservative treatment, with mean follow-up time 2.3 years. TWA &amp;lt;60 μV predicted lower all-cause mortality in ICD patients in univariate cox regression model (HR 1.484, 95% CI 1.024–2.151, p=0.0374). In multivariate models, TWA did not predict death or appropriate shocks in ICD patients. In addition, TWA did not predict death in control patients. In propensity score adjusted Cox regression model, TWA did not predict ICD benefit. Conclusion T-wave alternans is poorly prognostic in primary prophylactic ICD patients. Altough it may predict life-threatening arrhythmias and sudden cardiac death in several patient populations, it cannot be used in assessing benefit from implantable cardioverter defibrillator in primary prevention among patients with ejection fraction ≤35%. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Community's 7th Framework Program FP7/2007-2013

Real-World Effectiveness of Lipid-Lowering Medications on Outcomes after Stroke: Potential Implications of the New-User Design

Introduction: Observational studies are increasingly being used to provide evidence on the real-world effectiveness of medications for preventing vascular diseases, such as stroke. We investigated whether the real-world effectiveness of treatment with lipid-lowering medications after ischemic stroke is affected by prevalent-user bias. Methods: An observational cohort study of 90-day survivors of ischemic stroke using person-level data from the Australian Stroke Clinical Registry (2012–2016; 45 hospitals) linked to administrative (pharmaceutical, hospital, death) records. The use of, and adherence to (proportion of days covered <80% [poor adherence] vs. ≥80% [good adherence]), lipid-lowering medications within 90 days post-discharge was determined from pharmaceutical records. Users were further classified as prevalent (continuing) or new users, based on dispensing within 90 days prior to stroke. A propensity score-adjusted Cox regression was used to evaluate the effectiveness of lipid-lowering medications on outcomes (all-cause mortality, all-cause and cardiovascular disease readmission) within the subsequent year. Analyses were undertaken using prevalent-user (all users vs. nonusers) and new-user designs (new users vs. nonusers). Results: Of 11,217 eligible patients (median age 72 years, 42% female), 9,294 (83%) used lipid-lowering medications within 90 days post-discharge, including 5,479 new users. In both prevalent-user and new-user designs, nonusers (vs. users) had significantly greater rates of mortality (hazard ratio [HR] 2.35, 95% CI: 1.89–2.92) or all-cause readmissions (HR 1.22, 95% CI: 1.05–1.40) but not cardiovascular disease readmission. In contrast, associations between having poor (vs. good) adherence on outcomes were stronger among new users than all users. Among new users, having poor adherence was associated with greater rates of mortality (HR 1.48, 95% CI: 1.12–1.96), all-cause readmission (HR 1.14, 95% CI: 1.02–1.27), and cardiovascular disease readmission (HR 1.20, 95% CI: 1.01–1.42). Conclusions: The real-world effectiveness of treatment with lipid-lowering medications after stroke is attenuated when evaluated based on prevalent-user rather than new-user design. These findings may have implications for designing studies on the real-world effectiveness of secondary prevention medications.

Safety, adherence and efficacy of PCSK9 inhibitors: a retrospective real-world study

Introduction PCSK9 inhibitors demonstrated their effectiveness in reducing low-density lipoprotein cholesterol (LDL-C) and cardiovascular events in landmark trials. It remains unclear whether the results can be translated to Asian populations. This study was designed to assess the real-world safety, adherence and efficacy of PCSK9 inhibitors. Methods A retrospective review for patients newly initiated on PCSK9 inhibitors between 1st June 2017 and 31st July 2021 was conducted in a tertiary cardiology centre. Patients aged ≥ 21 years with a minimum one-month follow-up were included. Adverse drug reactions (ADRs), drug discontinuation, adherence patterns and efficacy between evolocumab and alirocumab groups were compared. Multivariable and propensity score adjusted Cox regression analyses were applied to analyse the outcomes. Results Of 87 patients screened, 80 (51 evolocumab; 29 alirocumab) were included. There were no significant differences between evolocumab and alirocumab groups in ADRs (11.8% vs 3.4%, adjusted HR, 2.97; 95% CI, 0.34 – 25.89 in multivariable analysis; adjusted HR, 3.24; 95% CI, 0.38–27.69 after propensity score adjustment) and discontinuation rates (27.5% vs 34.5%, adjusted HR, 0.89; 95% CI, 0.40–2.02 in multivariable analysis; adjusted HR, 0.88; 95% CI, 0.39–1.99 after propensity score adjustment). High medication cost was the main reason for discontinuation. One-third of patients had inadequate adherence to PCSK9 inhibitors. Both groups showed significant reductions of LDL-C compared to baseline. Conclusions PCSK9 inhibitors are efficacious, safe and well tolerated. Further studies are warranted to examine the cost-effectiveness of PCSK9 inhibitors to rationalise their sustainable use for cardiovascular prevention.

MP57-16 IMPACT OF EXTENT OF LYMPHADENECTOMY ON ALL CAUSE MORTALITY IN PATIENTS WITH INTERMEDIATE AND HIGH-RISK PROSTATE CANCER MANAGED WITH RADICAL PROSTATECTOMY

You have accessJournal of UrologyCME1 May 2022MP57-16 IMPACT OF EXTENT OF LYMPHADENECTOMY ON ALL CAUSE MORTALITY IN PATIENTS WITH INTERMEDIATE AND HIGH-RISK PROSTATE CANCER MANAGED WITH RADICAL PROSTATECTOMY Furkan Dursun, Ahmed Elshabrawy, Hanzhang Wang, Michael A. Liss, Ronald Rodriguez, Dharam Kaushik, and Ahmed M. Mansour Furkan DursunFurkan Dursun More articles by this author , Ahmed ElshabrawyAhmed Elshabrawy More articles by this author , Hanzhang WangHanzhang Wang More articles by this author , Michael A. LissMichael A. Liss More articles by this author , Ronald RodriguezRonald Rodriguez More articles by this author , Dharam KaushikDharam Kaushik More articles by this author , and Ahmed M. MansourAhmed M. Mansour More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002640.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The role of limited versus extended pelvic lymph node dissection (PLND) in the surgical management of prostate cancer (PCa) remains controversial. We sought to evaluate the impact of the extent of PNLD on survival outcomes for patients with intermediate and high-risk PCa. METHODS: The NCDB was queried for patients with intermediate and high-risk PCa (according to AUA guidelines risk stratification), who were treated by radical prostatectomy (RP) and PLND from 2004 to 2013. We limited our cohort to men <70 years of age with a CCI=0. Patients were divided into 3 groups according to the number of excised LN as a surrogate for the extent of PLND (Group 1:1–9, Group 2:10–19, and Group 3:≥20 nodes). Primary outcome was overall survival (OS). All-cause mortality was evaluated using propensity score weighted Kaplan-Meir (KM) Curves and Cox regression models. RESULTS: 103,250 men had a new diagnosis of PCa, and 25.8% of those had high-risk PCa. The number of LN excised was <10 for 80.5%, 10-19 for 15.9%, and ≥20 for 3.6% of the patients. Figure 1 illustrates the KM curves in the propensity score-weighted cohorts. In intermediate-risk PCa patients, propensity score adjusted cox regression analysis showed OS benefit for group 2 compared to group 1 (HR0.86, CI0.79-0.93, p <0.001). Similarly, in high-risk patients, group 3 had better OS compared to group 1 (HR0.61, CI 0.47-0.78, p <0.001) (Table 1). pN+ disease rates were significantly higher in group 3 compared to group 1 and 2 in both intermediate and high-risk diseases. (Intermediate risk 9.3% vs. 1.5% and 4.5%, p <0.001; high risk 25.3% vs. 5.7% and 15.5%, p <0.001, respectively). CONCLUSIONS: Removal of ≥20 LNs during RP was associated with better OS for men with high-risk PCa. Similar survival benefit was noted in the intermediate-risk group with removal of 10-19 lymph nodes. Increased number of removed nodes was associated with increased likelihood of lymph node positivity and more accurate pathologic staging. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e988 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Furkan Dursun More articles by this author Ahmed Elshabrawy More articles by this author Hanzhang Wang More articles by this author Michael A. Liss More articles by this author Ronald Rodriguez More articles by this author Dharam Kaushik More articles by this author Ahmed M. Mansour More articles by this author Expand All Advertisement PDF DownloadLoading ...

Optimal dual antiplatelet therapy duration for bioresorbable scaffolds: an individual patient data pooled analysis of the ABSORB trials.

Compared with everolimus-eluting metallic stents, the Absorb bioresorbable scaffold (BRS) results in increased rates of myocardial infarction (MI) and scaffold thrombosis (ST) during its three-year bioresorption phase. It is unknown whether prolonged dual antiplatelet therapy (DAPT) duration might decrease the risk of ischaemic events. We sought to evaluate the impact of DAPT duration on ischaemic and bleeding outcomes following BRS implantation. We conducted an individual patient data pooled analysis from four ABSORB randomised trials and one prospective ABSORB registry. Study endpoints were MI, ST, bleeding, and death up to three-year follow-up. Propensity score-adjusted Cox regression analysis was used to account for baseline differences related to DAPT duration. The five ABSORB studies included 2,973 patients. DAPT use was 91.7%, 53.2%, and 48.0% at 1, 2, and 3 years, respectively. DAPT use within the first year after BRS implantation was associated with markedly lower risks of MI (adjusted hazard ratio [aHR] 0.17, 95% CI: 0.10-0.32; p<0.0001) and ST (aHR 0.08, 95% CI: 0.03-0.19; p<0.0001). Conversely, DAPT use between 1 and 3 years did not significantly affect the risk of MI (aHR 1.04, 95% CI: 0.70-1.55; p=0.84) or ST (aHR 0.86, 95% CI: 0.42-1.75; p=0.67). DAPT did not have major effects upon bleeding or death in either period. DAPT use during the first year after BRS implantation was strongly associated with lower risks of ST and MI. However, a benefit of ongoing DAPT use between 1 and 3 years after BRS implantation was not apparent.

Diabetes mellitus was not associated with lower amputation-free survival after open revascularization for chronic limb-threatening ischemia - A nationwide propensity score adjusted analysis.

The risk of major amputation is higher after urgently planned endovascular therapy for chronic limb-threatening ischemia (CLTI) in patients with diabetes mellitus (DM). The aim of this nationwide cohort study was to compare outcomes between patients with and without DM following urgently planned open revascularization for CLTI from 2010 to 2014. Out of 1537 individuals registered in the Swedish Vascular Registry, 569 were registered in the National Diabetes Register. A propensity score adjusted Cox regression analysis was conducted to compare outcome between the groups with and without DM. Median follow-up was 4.3 years and 4.5 years for patients with and without DM, respectively. Patients with DM more often had foot ulcers (p = 0.034) and had undergone more previous amputations (p = 0.001) at baseline. No differences in mortality, cardiovascular death, major adverse cardiovascular events (MACE), or major amputation were observed between groups. The incidence rate of stroke was 70% higher (95% CI: 1.11–2.59; p = 0.0137) and the incidence rate of acute myocardial infarction (AMI) 39% higher (95% CI: 1.00–1.92; p = 0.0472) among patients with DM in comparison to those without. Open vascular surgery remains a first-line option for a substantial number of patients with CLTI, especially for limb salvage in patients with DM. The higher incidence rates of stroke and AMI among patients with DM following open vascular surgery for infrainguinal CLTI require specific consideration preoperatively with the aim of optimizing medical treatment to improve cardiovascular outcome postoperatively.

Age Is Associated With the Efficacy of Anticoagulant Therapies Against Sepsis-Induced Disseminated Intravascular Coagulation.

Disseminated Intravascular Coagulation (DIC) commonly complicates sepsis and considerably worsens mortality. Recent studies suggested that anticoagulant therapies improved mortality only in specific sepsis populations, and key pathologies for selecting optimal targets needed to be identified. Anticoagulant activities were naturally altered with aging. This study aimed to evaluate age-related differences in efficacy of anticoagulant therapies in sepsis. This post hoc analysis of a nationwide multicenter cohort study was conducted in 42 intensive care units in Japan. Adult patients with septic DIC were divided into anticoagulant and control groups. Age-related changes in predicted mortality in both groups were compared using a logistic regression model including 2-way interaction terms. Patients were also stratified into 3 subsets based on age, and propensity score-adjusted Cox regression analyses were conducted to examine survival effect of anticoagulants in each subset. We included 1432 patients with septic DIC; 867 patients received anticoagulants and 565 received none. Age-related change in predicted mortality was significantly different between groups (P for interaction = 0.013), and the gap between groups was broad in the younger population. Similarly, in Cox regression analyses, anticoagulant therapies were associated with significantly lower mortality in the subsets of age ≤ 60 and 60-79 (hazard ratios = 0.461, 0.617, P = 0.007, 0.005, respectively), whereas there was no difference in survival between the groups in the subsets of age ≥ 80. The efficacy of anticoagulant therapies for septic DIC might be associated with patient age.

The impact of diabetes mellitus on major amputation among patients with chronic limb threatening ischemia undergoing elective endovascular therapy- a nationwide propensity score adjusted analysis.

To investigate the risk of major amputation after elective endovascular therapy in patients with chronic limb threatening ischemia (CLTI) comparing patients with and without diabetes mellitus (DM). In this nationwide cohort study, all patients registered in the Swedish Vascular Register after elective endovascular therapy for CLTI caused by infra-inguinal arterial disease from 2010 to 2014 were included. Among 4578 individuals, 2251 had DM and were registered in the National Diabetes Register between 2009 and 2014. A propensity score adjusted Cox regression analysis was conducted to compare outcomes between groups. Median follow-up was 4.0 and 3.6 years for patients with DM and without DM, respectively. The incidence rates of major amputation and acute myocardial infarction (AMI) were 43% (95% CI 1.23-1.67) and 37% (95% CI 1.13-1.67) higher, respectively, among patients with DM compared to patients without DM. There was no difference in mortality (HR 1.04, 95% CI 0.95-1.14). Patients with DM had a higher risk of major amputation and AMI compared to those without DM after elective endovascular therapy for CLTI. Prevention of DM with CLTI is of utmost importance to reduce the risk of adverse limb and cardiovascular outcomes.

Contemporary outcomes of aortic and mitral valve surgery for rheumatic heart disease in sub-Saharan Africa

ObjectivesRheumatic heart disease is endemic in sub-Saharan Africa. There is a paucity of data on the outcomes of valvular surgery for rheumatic heart disease in the developing world. The objective of this study was to evaluate the outcomes of aortic and mitral valve surgery for rheumatic heart disease in Ethiopia. MethodsBetween 2009 and 2017, 240 consecutive patients with rheumatic heart disease underwent aortic and/or mitral surgery at the Cardiac Center of Ethiopia in Addis Ababa. These surgeries were performed in the context of 22 international humanitarian missions. Median follow-up was 2.3 (interquartile range, 0.5-4.0) years and 96% complete. Outcomes were compared between patients who underwent mechanical valve implantation (n = 90, 38%), bioprosthetic valve implantation (n = 58, 24%), and valve repair (n = 92, 38%). ResultsMean age of patients was 19 ± 8 years, and 136 patients (57%) were female. Operative mortality occurred in 5 patients (2.1%) and was not significantly different between the groups. Eleven additional patients (5%) died at follow-up, and 55 patients (23%) had at least 1 major adverse valve-related event. Propensity score–adjusted Cox regression analysis demonstrated higher rates of death in the bioprosthetic group compared with the mechanical group (hazard ratio, 8.82; 95% confidence interval, 1.64-47.39; P = .011). Survival was not significantly different between the repair and mechanical groups (hazard ratio, 1.09; 95% confidence interval, 0.17-7.16; P = .93). Likewise, rates of major adverse valve-related event were higher in the bioprosthetic group compared with the mechanical group (hazard ratio, 2.71; 995% confidence interval, 1.13-6.49; P = .025), but not significantly different between the repair and mechanical groups (hazard ratio, 1.98; 95% confidence interval, 0.89-4.39; P = .092). ConclusionsLeft-sided valve surgery for rheumatic heart disease in sub-Saharan Africa is associated with acceptable perioperative outcomes, but a high incidence of major adverse valve-related event at follow-up. The use of bioprosthetic valves is associated with poor outcomes in this patient population.

Worse cardiovascular prognosis after endovascular surgery for intermittent claudication caused by infrainguinal atherosclerotic disease in patients with diabetes.

Background:Diabetes mellitus (DM) is an established risk factor for intermittent claudication (IC) and other manifestations of atherosclerotic peripheral arterial disease. Indications for surgery in infrainguinal IC are debated, and there are conflicting reports regarding its outcomes in patients with DM. Aims of this study were to compare both short- and long-term effects on total- and cardiovascular (CV) mortality, major adverse cardiovascular events (MACEs), acute myocardial infarction (AMI), stroke, and major amputation following infrainguinal endovascular surgery for IC in patients with and without DM. We also evaluated potential relationships between diabetic control and outcomes in patients with DM.Methods:Nationwide observational cohort study of patients registered in the Swedish Vascular Registry and the Swedish National Diabetes Registry. Propensity score adjusted comparison of total and CV mortality, MACE, AMI, stroke, and major amputation after elective infrainguinal endovascular surgery for IC in 626 patients with and 1112 without DM at 30 postoperative days and after median 5.2 [interquartile range (IQR) 4.2–6.3] years of follow-up for patients with DM, and 5.4 (IQR 4.3–6.5) years for those without.Results:In propensity score adjusted Cox regression after 30 postoperative days, there were no differences between groups in morbidity or mortality. At last follow-up, patients with DM showed higher rates of MACE [hazard ratio (HR) 1.26, confidence interval (CI) 1.07–1.48; p < 0.01], AMI (HR 1.48, CI 1.09–2.00; p = 0.01), and major amputation (HR 2.31, CI 1.24–4.32; p < 0.01). Among patients with DM, higher HbA1c was associated with higher total mortality during follow-up (HR 1.01, CI 1.00–1.03; p = 0.045).Conclusion:Patients with DM have higher rates of MACE, AMI, and major amputation in propensity score adjusted analysis during 5 years of follow-up after infrainguinal endovascular surgery for IC. Furthermore, HbA1c is associated with total mortality in patients with DM. Prevention and treatment of DM is important to improve cardiovascular and limb outcomes.

Estimating the risk of acute kidney injury associated with use of diuretics and renin angiotensin aldosterone system inhibitors: A population based cohort study using the clinical practice research datalink

BackgroundThe risk of acute kidney injury (AKI) attributable to renin angiotensin aldosterone (RAAS) inhibitors and diuretics remains unclear.MethodsWe conducted a prospective cohort study using the Clinical Practice Research Datalink (2008–2015) linked to Hospital Episode Statistics – Admitted Patient Care and Office for National Statistics mortality data. Patients were included if they had one or more chronic diagnoses requiring medication. Exposed patients had a first ever prescription for RAAS inhibitors/diuretics during the study period. AKI risk associated with exposure was determined by multivariable Cox regression, propensity score-adjusted Cox regression and a prior event rate ratio (PERR) analysis.ResultsOne hundred forty thousand nine hundred fifty-two individuals were included. Increased AKI risk in the exposed group was demonstrated in both the multivariable and propensity score-adjusted cox regressions (HR 1.23 (95% CI 1.04–1.45) and HR 1.24 (1.05–1.47) respectively). The PERR analysis provided a similar overall hazard ratio with a wider confidence interval (HR 1.29 (0.94–1.63)). The increased AKI risk in the exposed group was present only in those receiving two or more antihypertensives. Absolute AKI risk was small.ConclusionsRAAS inhibitors/diuretics result in an increased risk of AKI. The absolute increase in AKI risk is small, however, and needs to be considered in the context of any potential benefits.

Impact of Prior Cancer History on the Clinical Outcomes in Advanced Breast Cancer: A Propensity Score-Adjusted, Population-Based Study.

PurposeDespite the rapid growing of cancer survivors, prior cancer history is a commonly adopted exclusion criterion. Whether prior cancer will impact the survival of patients with advanced breast cancer (ABC) remains uncertain.Materials and MethodsPatients with ABC diagnosed between 2004 and 2010 were identified using Surveillance, Epidemiology, and End Results (SEER) database. Timing, stage, and type were used to characterize prior cancer. Multivariable analyses using propensity score–adjusted Cox regression and competing risk regression were conducted to evaluate the prognostic effect of prior cancer on overall survival (OS) and breast cancer-specific survival (BCSS).ResultsA total of 14,176 ABC patients were identified, of whom 10.5% carried a prior cancer history. The most common type of prior cancer was female genital cancer (32.4%); more than half (51.7%) were diagnosed at localized stage; most were diagnosed more than 5 years (42.9%) or less than 1 year (28.3%) prior to the index cancer. In multivariate analyses, patients with prior cancer presented a slightly worse OS (hazard ratio, 1.18; 95% confidence interval [CI], 1.07 to 1.30; p=0.001) but a better BCSS (subdistribution hazard ratio, 0.64; 95% CI, 0.56 to 0.74; p < 0.001). In subset analyses, no survival detriment was observed in patients with prior malignancy from head and neck or endocrine system, at in situ or localized stage, or diagnosed more than 4 years.ConclusionPrior cancer provides an inferior OS but a superior BCSS for patients with ABC. It does not affect the survival adversely in some subgroups and these patients should not be excluded from clinical trials.

Effect of Timing and Duration of Statin Exposure on Risk of Hip or Knee Revision Arthroplasty: A Population-based Cohort Study.

To determine whether the timing and duration of statin exposure following total hip/knee arthroplasty (THA/TKA) influence the risk of revision arthroplasty. Subjects from the Clinical Practice Research Datalink, a large population-based clinical database, who had THA/TKA from 1988 to 2016, were included. Propensity score adjusted Cox regression models were used to determine the association between statin exposure and the risk of revision THA/TKA, (1) at any time, and (2) if first exposed 0-1, 1-5, or > 5 years following THA/TKA. We also investigated the effect of duration of statin exposure (< 1, 1-2, 2-3, 3-4, 4-5, > 5 yrs). The study included 151,305 participants. There were 65,032 (43%) exposed to statins during followup and 3500 (2.3%) had revision arthroplasty. In a propensity score adjusted model, exposure to statins was associated with a reduced risk of revision arthroplasty (HR 0.82, 95% CI 0.75-0.90). Participants first exposed within 1 year and between 1 and 5 years following THA/TKA (vs unexposed) had a reduced risk of revision arthroplasty (HR 0.82, 95% CI 0.74-0.91 and HR 0.76, 95% CI 0.65-0.90, respectively). In relation to duration of statin therapy, participants exposed for more than 5 years in total (vs < 1 yr) had a reduced risk of revision (HR 0.74, 95% CI 0.62-0.88). Statin therapy initiated up to 5 years following THA/TKA may reduce the risk of revision arthroplasty.

Comparison of cholinesterase inhibitor safety in real-world practice

IntroductionCholinesterase inhibitors (ChEIs) are widely used to treat mild to moderate Alzheimer's disease and related dementia. Clinical trials have focused on placebo comparisons, inadequately addressing within-class comparative safety. MethodsNew users of ChEIs in British Columbia were categorized into five study cohorts: low-dose donepezil, high-dose donepezil, galantamine, rivastigmine patch, and oral rivastigmine. Comparative safety of ChEIs assessed hazard ratios using propensity score adjusted Cox regression. ResultsCompared with low-dose donepezil, galantamine use was associated with a lower risk of mortality (adjusted hazard ratio: 0.84, 95% confidence interval: 0.60–1.18), cardiovascular serious adverse events (adjusted hazard ratio: 0.78, 95% confidence interval: 0.62–0.98), and entry into a residential care facility (adjusted hazard ratio: 0.72, 95% confidence interval: 0.59–0.89). DiscussionGiven the absence of randomized trial data showing clinically meaningful benefit of ChEI therapy in Alzheimer's disease, our study suggests preferential use of galantamine may at least be associated with fewer adverse events than treatment with donepezil or rivastigmine.

New-generation drug-eluting stents for left main coronary artery disease according to the EXCEL trial enrollment criteria: Insights from the all-comers, international, multicenter DELTA-2 registry

BackgroundPercutaneous coronary intervention (PCI) has been established as an alternative treatment option to coronary artery by-pass graft (CABG) surgery in patients with left main coronary artery disease (LMCAD). Whether the findings of randomized controlled trials are applicable to a real-world patient population is unclear. MethodsWe compared the outcomes of PCI with new-generation DES in the all-comer, international, multicenter DELTA-2 registry retrospectively evaluating mid-term clinical outcomes with the historical CABG cohort enrolled in the DELTA-1 registry according to the EXCEL key inclusion or exclusion criteria. The primary endpoint was the composite of death, myocardial infarction, or stroke at the median time of follow-up time of 501 days. The consistency of the effect of DELTA-2 PCI versus DELTA-1 CABG according to the EXCEL enrollment criteria was tested using propensity score-adjusted Cox regression models. ResultsOut of 3986 patients enrolled in the DELTA-2 PCI registry, 2418 were EXCEL candidates and 1568 were not EXCEL candidates. The occurrence of the primary endpoint was higher among non-EXCEL candidates compared with EXCEL candidates (15.4% vs. 6.9%; hazard ratio 2.52; 95% confidence interval 2.00–3.16; p < 0.001). Among 901 patients enrolled in the historical DELTA-1 CABG cohort, 471 were EXCEL candidates and 430 were not EXCEL candidates. When comparing the DELTA-2 PCI with the DELTA-1 CABG cohort, the occurrence of the primary endpoint was lower in the PCI group compared with the historical CABG cohort among EXCEL candidates (6.9% vs. 10.7%; adjusted hazard ratio: 0.65; 95% confidence interval: 0.45–0.92), while no significant difference was observed among non-EXCEL candidates (15.4% vs. 12.5%; adjusted hazard ratio: 0.94; 95% confidence interval: 0.67–1.33) with evidence of statistical interaction (adjusted interaction p-value = 0.002). ConclusionsIn a real-world population, PCI can be selected more favorably as an alternative to CABG in patients fulfilling the enrollment criteria of the EXCEL trial.

Long-term clinical outcome and graft patency of radial artery and saphenous vein grafts in multiple arterial revascularization

ObjectiveThe long-term benefits of multiple arterial revascularization (MAR) in coronary artery bypass grafting remain uncertain. The aim of this study was to investigate the clinical outcome, graft patency, and need for subsequent target revascularization of radial artery (RA) versus saphenous vein graft in patients undergoing MAR in both patient- and graft-specific analyses. MethodsBetween 2001 and 2016, we followed 1654 patients over a median of 7.4 years in a prospective, longitudinal study. Major adverse cardiac and cerebrovascular events, graft patency, and need for revascularization were assessed through clinical manifestation, coronary angiography, or coronary computed tomography and analyzed with propensity score–adjusted Cox regression, general estimating equation, and competing risk models. ResultsBilateral internal thoracic artery (BITA) grafting was performed in 910 patients (55.0%), and 744 patients (45.0%) received a left internal thoracic artery graft together with at least 1 RA graft. Patients receiving BITA, of whom 187 received an additional RA, showed improved survival (hazard ratio, 0.57; 95% confidence interval [CI], 0.38-0.86; P = .009), major adverse cardiac and cerebrovascular event–free survival (hazard ratio, 0.33; 95% CI, 0.23-0.46; P < .001), and lower need for repeat revascularization (subhzhard ratio, 0.59; 95% CI, 0.39-0.90; P = .015). In a subgroup of 512 patients, comparing 419 RA with 487 saphenous vein grafts, RA grafting showed a lower risk for graft occlusion (odds ratio, 0.59; 95% CI, 0.47-0.73; P < .001) and target revascularization (subhazard ratio, 0.58; 95% CI, 0.43-0.78; P < .001). ConclusionsMAR with BITA and RA grafting revealed to be the recommended strategy in coronary artery bypass grafting to achieve long-term beneficial results. The use of saphenous vein graft showed less favorable outcomes regarding patency and the need for target-vessel revascularization.