Change in Albuminuria and GFR Slope as Joint Surrogate End Points for Kidney Failure: Implications for Phase 2 Clinical Trials in CKD.

SIGNIFICANCE STATEMENT: Changes in albuminuria and GFR slope are individually used as surrogate end points in clinical trials of CKD progression, and studies have demonstrated that each is associated with treatment effects on clinical end points. In this study, the authors sought to develop a conceptual framework that combines both surrogate end points to better predict treatment effects on clinical end points in Phase 2 trials. The results demonstrate that information from the combined treatment effects on albuminuria and GFR slope improves the prediction of treatment effects on the clinical end point for Phase 2 trials with sample sizes between 100 and 200 patients and duration of follow-up ranging from 1 to 2 years. These findings may help inform design of clinical trials for interventions aimed at slowing CKD progression. BACKGROUND: Changes in log urinary albumin-to-creatinine ratio (UACR) and GFR slope are individually used as surrogate end points in clinical trials of CKD progression. Whether combining these surrogate end points might strengthen inferences about clinical benefit is unknown. METHODS: Using Bayesian meta-regressions across 41 randomized trials of CKD progression, we characterized the combined relationship between the treatment effects on the clinical end point (sustained doubling of serum creatinine, GFR <15 ml/min per 1.73 m 2 , or kidney failure) and treatment effects on UACR change and chronic GFR slope after 3 months. We applied the results to the design of Phase 2 trials on the basis of UACR change and chronic GFR slope in combination. RESULTS: Treatment effects on the clinical end point were strongly associated with the combination of treatment effects on UACR change and chronic slope. The posterior median meta-regression coefficients for treatment effects were -0.41 (95% Bayesian Credible Interval, -0.64 to -0.17) per 1 ml/min per 1.73 m 2 per year for the treatment effect on GFR slope and -0.06 (95% Bayesian Credible Interval, -0.90 to 0.77) for the treatment effect on UACR change. The predicted probability of clinical benefit when considering both surrogates was determined primarily by estimated treatment effects on UACR when sample size was small (approximately 60 patients per treatment arm) and follow-up brief (approximately 1 year), with the importance of GFR slope increasing for larger sample sizes and longer follow-up. CONCLUSIONS: In Phase 2 trials of CKD with sample sizes of 100-200 patients per arm and follow-up between 1 and 2 years, combining information from treatment effects on UACR change and GFR slope improved the prediction of treatment effects on clinical end points.

The Rate of Infectious Complications After Intrathecal Drug Delivery System Implant for Cancer-Related Pain Is Low Despite Frequent Concurrent Anticancer Treatment or Leukopenia.

BACKGROUND: The efficacy of intrathecal drug delivery (IDD) for cancer-related pain is well established. Cancer therapies are often associated with immunosuppression and increased risk of infection, and the rate of infection after intrathecal drug delivery system (IDDS) implant in cancer patients has been reported as 2.4%-6.3%. Our objective is to report on the rate of surgical site infections (SSI) in patients implanted with IDDS for cancer-related pain and to provide a data-driven discussion on the relationship between antineoplastic treatment, leukopenia, and other clinical or demographic characteristics and SSI. METHODS: Following local institutional review board approval, we conducted a retrospective chart review of IDDS implants from May 2014 through December 2018. Data collected included demographic data, health status, prophylactic antibiotic administration, surgery duration, presence of leukopenia (white blood cell [WBC] count of <4.0 K/µL) or moderate neutropenia (absolute neutrophil count [ANC] of <1000/µL) within the 30 days before IDDS implant, and details of antineoplastic treatment or systemic corticosteroid use in the perioperative period. This information was assessed in relation to SSI incidence up to 6 months following implant. RESULTS: Two hundred seventeen IDDS implants were identified. A majority of patients (79.3%) received ≥1 form of antineoplastic therapy within 30 days before or after implant, and 42.4% received multiple forms of antineoplastic therapy. Therapies included chemotherapy in 46.5%, immunotherapy in 28.6%, systemic steroids in 32.3%, and radiation therapy in 28.1%. One-quarter of patients (25.8%) were leukopenic within 30 days before implant, with 3.2% having moderate neutropenia. There were 2 infectious complications representing an infection rate of 0.9% (95% CI, 0.1%-3.3%), with limited shared characteristics between those experiencing SSI. CONCLUSIONS: SSI risk after IDDS placement for cancer pain is low, despite frequent concurrent antineoplastic therapy and leukopenia in the perioperative period. Concomitant cancer therapies should not be a barrier to the implementation of IDD for cancer pain.

Examining the relationship between epidural steroid injections and patient satisfaction.

BACKGROUND CONTEXT: Hospitals and policy makers have placed increasing importance on patient satisfaction with medical care. Minimal research exists on patient satisfaction in the context of epidural steroid injections (ESIs) for radicular pain. PURPOSE: Describe patient satisfaction with ESIs for the treatment of radicular pain and identify patient demographic and clinical characteristics associated with patient satisfaction. STUDY DESIGN/SETTING: This was a retrospective study conducted at a large, academic medical center. METHODS: This was a single-center retrospective study of prospectively collected registry data including patients treated with ESIs from August 2006 to May 2018. The primary outcomes were: overall Press Ganey (PG) score, patient satisfaction with the physician, and likelihood to recommend both the physician and the practice. Age, body mass index, Charlson Comorbidity Index, immediate change in pain, sex, spinal segmental level of injection, prior opioid use, insurance status, and ethnicity were compared with the four PG measures of satisfaction using both univariable and multivariable regression analysis. No sources of funding were used for this project. The authors report no conflict of interest in relation to this manuscript. RESULTS: Two-hundred ninety patients underwent 377 injections. Overall, patients were highly satisfied; 86% recommend their physician and 85% recommend the practice, each with the highest possible PG score. The median overall PG score was 97.2 (interquartile range [IQR]: 89.3, 100), and the median physician satisfaction score was 100 (IQR: 95, 100). The median immediate reduction in pain was 3 points (IQR: -5,-2) on the numerical rating scale scale postinjection. Increased age was associated with increased satisfaction with the physician (reported rate ratios [Relative Risk (RR)] for dissatisfaction: 0.73, 95% confidence interval [CI]: 0.58, 0.93, p=.011) and increased likelihood to recommend the physician (odds ratio: 1.46, 95% CI: 1.06, 2.01, p=.022) in multivariable analysis. Medicare as opposed to private insurance was associated with higher dissatisfaction with the physician (RR: 2.04, 95% CI: 1.15, 3.61, p=.014) and decreased likelihood to recommend the practice (RR: 0.38, 95% CI: 0.15, 0.94, p=.037). CONCLUSIONS: The present data, based on PG scores, demonstrated that ESIs are associated with greater patient satisfaction with increasing age, but lower satisfaction in patients with Medicare compared with private insurance when controlling for other demographic factors. Satisfaction was not associated with the degree of pain relief.

2011 ACGME Duty Hour Limits had No Association With Breast Reconstruction Complications.

BACKGROUND: In 2011, the Accreditation Council for Graduate Medical Education (ACGME) instituted further duty hour restrictions in response to concerns over long work hours and sleep deprivation in trainees and their effects on patient outcomes. The effect of duty hour restrictions on complications after breast reconstruction procedures has not been clarified. MATERIALS AND METHODS: A retrospective cross-sectional analysis was designed. The National Inpatient Sample database was queried in the 2 y before and 2 y after the 2011 duty hour changes. Patients undergoing breast reconstruction, the most common elective admission diagnosis for plastic surgery patients, were selected for analysis. Patient groups were separated by teaching hospitals (THs) and nonteaching hospitals and by pre- and post-ACGME change periods. Surgical complication rates, length of stay, and procedures were analyzed using complex survey-weighted univariate and multivariate logistic regression analysis, with additional sensitivity analysis applied. RESULTS: The number of procedures did not vary significantly in the period after duty hour restrictions in THs (n = 46,188, pre-ACGME versus n = 48,980, post-ACGME). Overall complication rates in teaching (9.54%, pre-ACGME versus 9.04%, post-ACGME; P = 0.561) and nonteaching hospitals (8.54%, pre-ACGME versus 7.70%, post-ACGME; P = 0.319) did not significantly change after the implementation of duty hour changes. On multivariate analysis, surgery performed in resident THs after duty hour changes was not associated with a significant change in overall (odds ratio [OR], 1.03; 95% confidence interval [95% CI], 0.77-1.37; P = 0.857) breast-specific complications (OR, 1.06; 95% CI, 0.77-1.46; P = 0.731) or general complications (OR, 1.11; 95% CI, 0.80-1.54; P = 0.541). CONCLUSIONS: Duty hour restrictions enacted in 2011 were not associated with postoperative complications after breast reconstruction.