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Background Although PD-1 antibodies (PD1 Ab) are the standard of care for advanced non-small-cell lung cancer (ansclc), most patients will progress. We compared survival outcomes for patients with ansclc who received systemic therapy (st) after progression and for those who did not. Additionally, clinical characteristics that predicted receipt of st after PD1 Ab failure were evaluated. Methods All patients with ansclc in British Columbia initiated on nivolumab or pembrolizumab between June 2015 and November 2017, with subsequent progression, were identified. Eligibility criteria for additional st included an Eastern Cooperative Oncology Group (ecog) performance status (ps) of 3 or less and survival for more than 30 days from the last PD1 Ab treatment. Post-progression survival (pps) was assessed by landmark analysis. Baseline characteristics associated with pps were identified by multivariable analysis. Results Of 94 patients meeting the eligibility criteria, 33 received st after progression. In 75.6%, a PD1 Ab was received as first- or second-line treatment. The most common sts were erlotinib (36.4%) and docetaxel (27.3%). No statistically significant difference in median pps was observed between patients who did and did not receive st within 30 days of their last PD1 Ab treatment (6.9 months vs. 3.6 months, log-rank p = 0.15.) In multivariable analysis, factors associated with increased pps included an ecog ps of 0 or 1 compared with 2 or 3 [hazard ratio (hr): 0.42; 95% confidence interval (ci): 0.24 to 0.73; p = 0.002] and any response compared with no response to PD1 Ab (hr: 0.54; 95% ci: 0.33 to 0.90; p = 0.02). Conclusions In this cohort, only 35.1% of patients eligible for post-PD1 Ab therapy received st. Post-progression survival was not significantly affected by receipt of post-progression therapy. Prospective trials are needed to clarify the benefit of post-PD1 Ab treatments. [ABSTRACT FROM AUTHOR]

Benford’s Law is a probability distribution for the first significant digits of numbers, for example, the first significant digits of the numbers 871 and 0.22 are 8 and 2 respectively. The law is particularly remarkable because many types of data are considered to be consistent with Benford’s Law and scientists and investigators have applied it in diverse areas, for example, diagnostic tests for mathematical models in Biology, Genomics, Neuroscience, image analysis and fraud detection. In this article we present and compare statistically sound methods for assessing conformance of data with Benford’s Law, including discrete versions of Cramér-von Mises (CvM) statistical tests and simultaneous confidence intervals. We demonstrate that the common use of many binomial confidence intervals leads to rejection of Benford too often for truly Benford data. Based on our investigation, we recommend that the CvM statistic , Pearson’s chi-square statistic and 100(1 − α)% Goodman’s simultaneous confidence intervals be computed when assessing conformance with Benford’s Law. Visual inspection of the data with simultaneous confidence intervals is useful for understanding departures from Benford and the influence of sample size. [ABSTRACT FROM AUTHOR]

SUMMARY We investigate the efficiency of likelihood methods for estimating the regression parameters of mixed-effects logistic regression models. One approach uses a conditional likelihood which eliminates the random intercept terms. A second uses the likelihood generated from the marginal distribution of the data where the random intercepts are integrated out. Parametric estimates result from assuming a parametric form for the intercept distribution, whereas we obtain semiparametric estimates when the intercept distribution is left unspecified. We present an expression which shows that the asymptotic relative efficiency of conditional likelihood estimators relative to parametric estimators is a decreasing function of within-cluster covariate correlation. Simulation results show the same for the asymptotic relative efficiency of the semiparametric estimator relative to the conditional. For fixed covariate correlation, the asymptotic relative efficiency of the parametric versus the conditional increases as cluster sizes increase. Example data further illustrate our findings. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated whether there is a difference in the trend of the Kurtzke values for individuals with multiple sclerosis in the treatment and control groups during the two-year period. Several covariates considered in the study are age, duration and baseline Kurtzke value (KBase). The method used to determine the effect of the treatment when covariates are included is a regression analysis.

Acceptance sampling techniques are used to monitor the accuracy of gas meters. Random samples of meters are taken from homogeneous lots, and two accuracy measurements are recorded for each meter. In the past, the two measurements were averaged, and an acceptance sampling test applied to the sample of averages. In 1987, the plan was modified so that virtually the same test is applied to the two measurements individually. This new procedure is more stringent than the old procedure. In a study of data sampled over three years, the new plan rejects more lots than does the old plan, leading to greatly increased costs to the gas industry and therefore to the consumer. Theoretical reasons are given for why this occurs, and an alternative plan is proposed. [ABSTRACT FROM AUTHOR]

The article comments on the study "Patients Subsets With T1-T2 Node-Negative Breast Cancer at High Locoregional Recurrence Risk After Mastectomy," by P. T. Troung et al. It cites that the study aims to identify combinations of pathologic factors that predict for locoregional recurrence (LRR) rates of ≥20% among patients with small tumors treated with mastectomy. It notes that data about the risk of LRR among patients is critical in knowing which patients may benefit from adjuvant radiation.

With changes in bowel function being a common and often distressful issue for palliative care patients, the ability to easily monitor and record changes in bowel status would be helpful in addressing quality of care. Most bowel tools record either constipation or diarrhea, but not both. A new tool, the Victoria Bowel Performance Scale (BPS), was designed as an ordinal nine-point scale from -4 (severe constipation) to +4 (severe diarrhea) and includes three parameters: visual stool characteristics, bowel pattern, and ability to control defecation. This study tested the reliability of BPS using case scenarios in a test-retest format. Sixty-seven raters in Time Period 1 and 54 raters in Time Period 2 ranked the 18 cases. The intraclass correlation coefficients for absolute agreement were 0.822 and 0.853 for Time Periods 1 and 2, respectively. Results showed that the raters were consistent in their scoring over time, with an average Cohen's kappa of 0.70 over all of the raters. The average Pearson correlation coefficient between Time Periods 1 and 2 scores was 0.92. Further prospective testing in day-to-day clinical care is needed to further confirm the reliability and clinical utility of the BPS. A BPS management guideline has been developed to assist with decision making for each BPS score, which also requires validation. © 2007 U.S. Cancer Pain Relief Committee. [ABSTRACT FROM AUTHOR]

Induction ipilimumab and nivolumab followed by maintenance nivolumab improve overall survival compared with ipilimumab alone in patients with advanced melanoma, but immune-related adverse events (irAE) occur commonly. The need for induction discontinuation because of irAE and the relationship between irAE and survival in non-trials patients are unclear. Patients with unresectable stage III–IV melanoma receiving first-line combination immunotherapy at one of six centres between December 2017 and February 2020 outside of trials were identified retrospectively. Landmark 12-week Kaplan–Meier analyses and log-rank tests were used to evaluate associations between discontinuation of induction therapy on overall survival and time to treatment failure (TTF). Multivariable analysis of factors influencing overall survival and TTF was undertaken. Among 95 patients, the median age was 62 years, 38.9% had Eastern Cooperative Oncology Group performance status ≥1 and 22.1% had brain metastases. The median follow-up for the whole cohort was 19.8 months by the reverse Kaplan–Meier method. Any grade and grade 3–4 irAE were noted in 78.9% and 44.2% of the cohort, respectively. 44.2% of patients completed induction immunotherapy, whereas 41.1% did not due to irAE. Twelve-week landmark overall survival and TTF were similar in patients who completed induction versus those who did not due to irAE. On multivariable analysis, any grade irAE (versus none) was associated with longer overall survival (hazard ratio = 0.35, 95% confidence interval 0.15–0.82, P = 0.02) and TTF (hazard ratio = 0.38, 95% confidence interval = 0.17–0.81, P = 0.01). Grade 3–4 irAE correlated with longer TTF (hazard ratio = 0.45, 95% confidence interval = 0.20–1.01, P = 0.05). In this population-based cohort, discontinuation of induction immunotherapy as a result of irAE did not adversely affect overall survival or TTF. irAE observed during ipilimumab and nivolumab induction were associated with improved survival outcomes. • In this population-based study, incidence of immune-related adverse events (irAE) was similar to trials. • 41.1% of patients discontinued induction immunotherapy for advanced melanoma due to irAE. • Survival outcomes were similar for patients who did and did not complete induction due to irAE. • Early onset irAE were associated with improved overall survival and time to treatment failure. [ABSTRACT FROM AUTHOR]

The purpose of this study was to characterize postural sway in quiet standing under eyes-open and eyes-closed conditions, and to obtain a measure of postural stiffness during quiet standing in adults with Down syndrome (DS) versus control subjects. We obtained descriptive measures from centre-of-pressure (COP) data and analysed and compared COP trajectories and postural stiffness estimates from two stochastic models, the “pinned polymer” (PP) and “inverted pendulum” (IP) models. These estimates were correlated with clinical measures of muscle tone. Our results showed that overall, estimated values for postural stiffness from both models were larger for the DS group than for normal controls. In addition, average stiffness measures were greater under the eyes-closed condition than under the eyes-open condition for the DS group. The IP model detected significant trends over trials whereas the PP model did not. Clinical assessment of muscle tone for the DS group ranged from low to high-normal and there was no significant correlation with the postural stiffness measures obtained from either model. These results suggest that individuals with DS have the ability to modulate their underlying “stiffness” under conditions of quiet standing. Furthermore, there appears to be no strong relationship between clinical measures of muscle tone and postural stiffness measures under dynamic conditions. [ABSTRACT FROM AUTHOR]