ABSTRACT
Infectious etiologies have previously been proposed as causes of both melanoma and non-melanoma skin cancer. This exploratory overview explains and presents the evidence for the hypothesis that a microorganism excreted in infected ruminant animal feces, Mycobacterium avium subspecies paratuberculosis (MAP), is the cause of some cases of cutaneous melanoma (CM). Occupational, residential, and recreational contact with MAP-contaminated feces, soil, sand, and natural bodies of water may confer a higher rate of CM. Included in our hypothesis are possible reasons for the differing rates and locations of CM in persons with white versus nonwhite skin, why CM develops underneath nails and in vulvar skin, why canine melanoma is an excellent model for human melanoma, and why the Bacille Calmette-Guérin (BCG) vaccine has demonstrated efficacy in the prevention and treatment of CM. The pathogenic mechanisms and etiologic aspects of MAP, as a transmittable agent underlying CM risk, are carefully deliberated in this paper. Imbalances in gut and skin bacteria, genetic risk factors, and vaccine prevention/therapy are also discussed, while acknowledging that the evidence for a causal association between MAP exposure and CM remains circumstantial.
ABSTRACT
Often in the planning phase of a clinical trial, a researcher will need to choose between a standard versus weighted log-rank test (LRT) for investigating right-censored survival data. While a standard LRT is optimal for analyzing evenly distributed but distinct survival events (proportional hazards), an appropriately weighted LRT test may be better suited for handling non-proportional, delayed treatment effects. The "a priori" misspecification of this alternative may result in a substantial loss of power when determining the effectiveness of an experimental drug. In this paper, the standard unweighted and inverse log-rank tests (iLRTs) are compared with the multiple weight, default Max-Combo procedure for analyzing differential late survival outcomes. Unlike combination LRTs that depend on the arbitrary selection of weights, the iLRT by definition is a single weight test and does not require implicit multiplicity correction. Empirically, both weighted methods have reasonable flexibility for assessing continuous survival curve differences from the onset of a study. However, the iLRT may be preferable for accommodating delayed separating survival curves, especially when one arm finishes first. Using standard large-sample methods, the power and sample size for the iLRT are easily estimated without resorting to complex and timely simulations.
Subject(s)
Clinical Trials as Topic , Proportional Hazards Models , Computer Simulation , Sample Size , Survival AnalysisABSTRACT
Background: The detection of pulmonary nodules significantly impacts the lives and mental health of patients. Although the 2020 National Comprehensive Cancer Network (NCCN) guidelines recommend scheduled surveillance for nodules ≤8 mm, patients often opt to have their nodules surgically removed. Methods: A cross-sectional questionnaire was administered to patients with small pulmonary nodules who presented to a local grade 3 hospital with small pulmonary nodules and decided to receive surgery versus prescribed monitoring. The questionnaire included four aspects: (I) patient characteristics; (II) nodule-specific knowledge; (III) doctor-patient communication; and (IV) nodular-specific distress. Nodular-specific distress was measured by the Impact of Event Scale-Revised (IES-R). Results: A total of 234 (69%) patients responded to the survey and were included in the final analysis. Poor performance in activities of daily living (ADLs), the presence of solid nodules, multifocal disease, and a family history of lung cancer were significantly associated with reported anxiety. Most notably, facilitating patient choice for surgery was the computed tomography (CT) scan results, with reference to lung nodule size and number of nodules, where concerns related to lung nodule, cancer risk, and fear of surgery or death had a significant psychological impact on patients. Conclusions: In this cohort of patients who elected to have their small pulmonary nodules surgically removed, we identified key factors underlying their anxiety toward guideline recommended surveillance. Our findings will be useful for clinicians when discussing treatment options with their patients.