A Standardized Approach for Collection of Objective Data to Support Outcome Determination for Late-Phase Tuberculosis Clinical Trials.

Rationale: We developed a standardized method, possible poor treatment response (PPTR), to help ascertain efficacy endpoints in Study S31/A5349 (NCT02410772), an open-label trial comparing two 4-month rifapentine-based regimens with a standard 6-month regimen for the treatment of pulmonary tuberculosis (TB). Objectives: We describe the use of the PPTR process and evaluate whether the goals of minimizing bias in efficacy endpoint assessment and attainment of relevant data to determine outcomes for all participants were achieved. Methods: A PPTR event was defined as the occurrence of one or more prespecified triggers. Each PPTR required initiation of a standardized evaluation process that included obtaining multiple sputum samples for microbiology. Measurements and Main Results: Among 2,343 participants with culture-confirmed drug-susceptible TB, 454 individuals (19.4%) had a total of 534 individual PPTR events, of which 76.6% were microbiological (positive smear or culture at or after 17 wk). At least one PPTR event was experienced by 92.4% (133 of 144) of participants with TB-related unfavorable outcome and between 13.8% and 14.7% of participants with favorable and not-assessable outcomes. A total of 75% of participants with TB-related unfavorable outcomes had microbiological confirmation of failure to achieve a disease-free cure. Conclusions: Standardized methodologies, such as our PPTR approach, could facilitate unbiased efficacy outcome determinations, improve discrimination between outcomes that are related and unrelated to regimen efficacy, and enhance the ability to conduct pooled analyses of contemporary trials.

Effect of defibrillation threshold testing on effectiveness of the subcutaneous implantable cardioverter defibrillator.

BACKGROUND: Defibrillation threshold (DFT) testing is recommended with the subcutaneous implantable cardioverter defibrillator (SICD). OBJECTIVE: To describe first shock efficacy for appropriate SICD therapies stratified by the presence of implant DFT testing. METHODS: We reviewed all patients receiving SICDs at our institution and stratified them based on whether implant DFT testing was performed. Appropriate shocks were reviewed to see if ventricular tachycardia/ventricular fibrillation (VT/VF) terminated with a single shock. First shock efficacy was stratified by implant DFT status. RESULTS: 178 patients implanted with SICDs and followed in our center were included in this study. Of these, 135 (76%) underwent DFT testing (DFT (+) group). In the DFT (+), 80 appropriate shocks were needed to treat 69 episodes of VT/VF. The first shock was effective in 61 out of 69 episodes (88.4%), whereas multiple shocks were required to terminate VT/VF in the remaining eight episodes. Among 43 patients without implant DFT testing (DFT (-) group), 20 appropriate shocks to treat 17 episodes of VT/VF occurred in seven patients. VT/VF was successfully terminated with the first shock in 16 out of 17 episodes (first shock efficacy 94.1 %). There was no significant difference in first shock effectiveness between those with and without implant DFT testing (P  =  0.97). CONCLUSION: A strategy that omits DFT testing at implant did not appear to compromise the effectiveness of the SICD. These data suggest that routine DFT testing at SICD implant might not be necessary. Randomized trials are needed to confirm this finding.

Prevalence, predictors, and outcomes of advance directives in implantable cardioverter-defibrillator recipients.

BACKGROUND: Little is known about advance directive (AD) utilization in implantable cardioverter-defibrillator (ICD) recipients. OBJECTIVE: The purpose of this study was to define the prevalence and predictors of ADs in patients with ICDs. METHODS: We identified ICD recipients with ADs at our institution. The primary end point was the prevalence of an AD documented up to 1 year after device implant and the secondary end point was the cumulative prevalence of an AD. RESULTS: Of 2549 patients with ICDs, 701 (27.5%) were followed for at least 1 year after device implant, and of those 701 patients, 164 (23.4%) had ADs documented before or within 1 year of ICD implant. The prevalence of ICD recipients with ADs increased overtime, reaching approximately 10% in the most recent years of analysis. However, only 1 AD specifically addressed the ICD as part of end-of-life decision making. In multivariable analysis, more recent year of device implant and prior cardiovascular hospitalization were positively associated with having an AD within 1 year of implant. The cumulative prevalence of an AD at any time after implant reached about 30%, with more recent implant year, prior cardiovascular hospitalization, and palliative care consultation positively associated with the presence of an AD and black race associated with a lower cumulative prevalence. CONCLUSION: In a tertiary academic medical center, most patients with ICDs still do not have ADs, and even when they do, the ICDs are rarely addressed as part of the directive. Several predictors of ADs emerged, which may provide opportunities to improve utilization of ADs in ICD recipients.

Procedural outcomes and long-term survival following trans-venous defibrillator lead extraction in patients with end-stage renal disease.

AIMS: End-stage renal disease (ESRD) increases the risk of implantable cardioverter-defibrillator (ICD) infection. We sought to define outcomes of lead extraction in patients with ESRD. METHODS AND RESULTS: Implantable cardioverter-defibrillator lead extractions at our institution from January 2006 to March 2014 were stratified by absence (Control-Ex, n = 465) or presence (ESRD-Ex, n = 43) of ESRD. Procedural outcomes and survival were determined by medical records review. Survival in the ESRD-Ex group was compared with a contemporaneous cohort with ESRD undergoing ICD lead implantation (ESRD-I, n = 127). Among extraction patients, those with ESRD were more likely to be extracted for infection (74.4% vs. 28.6%, P < 0.001). Extraction procedure success (Control-Ex: 97% vs. ESRD-Ex: 93%, P = 0.17) and procedural deaths (Control-Ex: 1.1% vs. ESRD-Ex: 2.3%, P = 0.413) were similar. Survival 1 year following extraction was worse in the ESRD-Ex group compared with the Control-Ex, with a survival rate of 65.6% vs. 92.6% (P < 0.001); these curves continued to diverge through year 3. One-year survival in the ESRD-Ex group was worse than among ESRD patients undergoing ICD implant (ESRD-I), but these curves converged and survival was similar by year 3. CONCLUSIONS: Implantable cardioverter-defibrillator lead extraction can be performed safely and effectively in patients with ESRD. However, despite high rates of procedural success, long-term mortality following extraction in ESRD patients is substantial. Much of the long-term mortality risk appears to be accounted for by the presence of ESRD and an indication for an ICD.