A joint model of cancer incidence, metastasis, and mortality.

Many diseases, especially cancer, are not static, but rather can be summarized by a series of events or stages (e.g. diagnosis, remission, recurrence, metastasis, death). Most available methods to analyze multi-stage data ignore intermediate events and focus on the terminal event or consider (time to) multiple events as independent. Competing-risk or semi-competing-risk models are often deficient in describing the complex relationship between disease progression events which are driven by a shared progression stochastic process. A multi-stage model can only examine two stages at a time and thus fails to capture the effect of one stage on the time spent between other stages. Moreover, most models do not account for latent stages. We propose a semi-parametric joint model of diagnosis, latent metastasis, and cancer death and use nonparametric maximum likelihood to estimate covariate effects on the risks of intermediate events and death and the dependence between them. We illustrate the model with Monte Carlo simulations and analysis of real data on prostate cancer from the SEER database.

Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors.

PURPOSE: Aromatase inhibitors (AI), which decrease circulating estradiol concentrations in post-menopausal women, are associated with toxicities that limit adherence. Approximately one-third of patients will tolerate a different AI after not tolerating the first. We report the effect of crossover from exemestane to letrozole or vice versa on patient-reported outcomes (PROs) and whether the success of crossover is due to lack of estrogen suppression. METHODS: Post-menopausal women enrolled on a prospective trial initiating AI therapy for early-stage breast cancer were randomized to exemestane or letrozole. Those that discontinued for intolerance were offered protocol-directed crossover to the other AI after a washout period. Changes in PROs, including pain [Visual Analog Scale (VAS)] and functional status [Health Assessment Questionnaire (HAQ)], were compared after 3 months on the first versus the second AI. Estradiol and drug concentrations were measured. RESULTS: Eighty-three patients participated in the crossover protocol, of whom 91.3% reported improvement in symptoms prior to starting the second AI. Functional status worsened less after 3 months with the second AI (HAQ mean change AI #1: 0.2 [SD 0.41] vs. AI #2: -0.05 [SD 0.36]; p = 0.001); change in pain scores was similar between the first and second AI (VAS mean change AI #1: 0.8 [SD 2.7] vs. AI #2: -0.2 [SD 2.8]; p = 0.19). No statistical differences in estradiol or drug concentrations were found between those that continued or discontinued AI after crossover. CONCLUSIONS: Although all AIs act via the same mechanism, a subset of patients intolerant to one AI report improved PROs with a different one. The mechanism of this tolerance remains unknown, but does not appear to be due to non-adherence to, or insufficient estrogen suppression by, the second AI.

Perceptions of 24/7 In-house Attending Coverage on Fellow Education and Autonomy in a Pediatric Cardiothoracic Intensive Care Unit.

BACKGROUND: The 24/7 in-house attending coverage is emerging as the standard of care in intensive care units. Implementation costs, workforce feasibility, and patient outcomes resulting from changes in physician staffing are widely debated topics. Understanding the impact of staffing models on the learning environment for medical trainees and faculty is equally warranted, particularly with respect to trainee education and autonomy. OBJECTIVE: This study aims to elicit the perceptions of pediatric cardiology fellows and attendings toward 24/7 in-house attending coverage and its effect on fellow education and autonomy. METHODS: We surveyed pediatric cardiology fellows and attendings practicing in the pediatric cardiothoracic intensive care unit (PCTU) of a large, university-affiliated medical center, using structured Likert response items and open-ended questions, prior to and following the transition to 24/7 in-house attending coverage. RESULTS: All (100%) trainees and faculty completed all surveys. Both prior to and following transition to 24/7 in-house attending coverage, all fellows, and the majority of attendings agreed that the overnight call experience benefited fellow education. At baseline, trainees identified limited circumstances in which on-site attending coverage would be critical. Preimplementation concerns that 24/7 in-house attending coverage would negatively affect the education of fellows were not reflected following actual implementation of the new staffing policy. However, based upon open-ended questions, fellow autonomy was affected by the new paradigm, with fellows and attendings reporting decreased "appropriateness" of autonomy after implementation. CONCLUSIONS: Our prospective study, showing initial concerns about limiting the learning environment in transitioning to 24/7 in-house attending coverage did not result in diminished perceptions of the educational experience for our fellows but revealed an expected decrease in fellow autonomy. The study indirectly facilitated open discussions about methods to preserve fellow education and warranted autonomy in our PCTU; however, continued efforts are needed to achieve the optimal balance between supervised training and the transition to autonomous practice.

Comprehensive breast reconstruction in an academic surgical practice: an evaluation of the financial impact.

BACKGROUND: This study assessed the financial implications of providing all forms of breast reconstruction at a single academic institution with insurance as the primary mode of reimbursement. METHODS: Billing records of 152 patients who underwent postmastectomy breast reconstruction offered at the University of Michigan for the 2012 fiscal year were reviewed. Professional and facility revenue, cost, and earnings for the first stage of reconstruction were calculated by applying actual collections and charges. Similar financial data were compiled for a subset of 49 patients who went on to complete reconstruction. RESULTS: The professional revenue and expenses allocated to breast reconstruction were $647,437 and $591,184, respectively (8.7 percent margin). Health care system facility revenue and costs were $2,762,797 and $2,773,131, respectively (-0.4 percent margin). Physician reimbursement by surgical time was highest for delayed tissue expander placement ($3505 per operating room hour). Abdominal free flap reconstructions resulted in greater professional revenue for the first stage of reconstruction ($7801 versus $2961) and for completed reconstructions ($14,943 versus $7703) relative to implant reconstructions. The facility also did better fiscally after the first stage of abdominally based reconstruction compared with implant reconstructions (10 percent versus -10.4 percent margin). CONCLUSIONS: Postmastectomy breast reconstruction for this academic surgical practice remains fiscally profitable. Implant-based reconstruction compared with abdominal flap reconstruction produces greater revenue per operative hour but ultimately generates less total revenue and results in financial losses for the facility. Abdominally based perforator flap reconstruction reimbursed through standard insurance plans can be financially advantageous for the academic surgical practice and health care system.

Morphomic analysis for preoperative donor site risk assessment in patients undergoing abdominal perforator flap breast reconstruction: a proof of concept study.

BACKGROUND: Morphomics are three-dimensional measurements of aspects of the human anatomy generated by computed tomographic (CT) imaging. The purpose of this study was to generate preliminary data on the efficacy of morphomics, as a potential risk stratification tool, in predicting abdominal donor site wound-healing complications in patients undergoing abdominal perforator flap breast reconstruction. Patients and METHODS: In total, 58 consecutive patients undergoing deep inferior epigastric perforator (DIEP) flap breast reconstruction were evaluated. Using preoperative CT scan data, we quantified patients' body area, visceral and subcutaneous fat, fascia area, and body depth between T12 and L4. Associations between morphomic measures and complication rates were examined using t-tests and logistic regression. RESULTS: Of the 58 patients, 11 (19%) patients developed a wound dehiscence and 47 (81%) patients healed their abdominal incision without complications. Patients with a dehiscence had a significantly higher body mass index (BMI) (34.32 vs. 29.26 kg/m(2), p = 0.014) than patients without a dehiscence. Multiple morphometric measures including higher visceral fat area (p = 0.003) were significant predictors of abdominal donor site wound dehiscence. BMI (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.03-1.32; p = 0.017) and visceral fat area (OR, 1.24; 95% CI, 1.08-1.42; p = 0.002) were independently significant predictors for wound dehiscence in the entire sample. Only visceral fat area retained its predictive ability in patients with a BMI > 30 kg/m(2). CONCLUSIONS: Morphomic measurements correlate with the likelihood of developing postoperative donor site dehiscence after DIEP flap breast reconstruction. As a proof of concept study, this demonstrates that objective data obtained from CT scans may help in preoperatively assessing the risk for donor site wound healing complications in patients undergoing DIEP flap breast reconstruction.

Weighted log-rank statistic to compare shared-path adaptive treatment strategies.

Adaptive treatment strategies (ATSs) more closely mimic the reality of a physician's prescription process where the physician prescribes a medication to his/her patient, and based on that patient's response to the medication, modifies the treatment. Two-stage randomization designs, more generally, sequential multiple assignment randomization trial designs, are useful to assess ATSs where the interest is in comparing the entire sequence of treatments, including the patient's intermediate response. In this paper, we introduce the notion of shared-path and separate-path ATSs and propose a weighted log-rank statistic to compare overall survival distributions of multiple two-stage ATSs, some of which may be shared-path. Large sample properties of the statistic are derived and the type I error rate and power of the test are compared with the standard log-rank test through simulation.

The nurse's role in the causation of compensable injury.

Mistakes can be life-threatening and result in malpractice claims. There are few studies that discuss malpractice claims and nursing. The purpose was to identify possible relationships between the actions, behaviors, or characteristics of RNs and the injury suffered by a patient involved in a compensable event. Claims were analyzed retrospectively. Using the Fischer exact test, nurse inaction yielded a higher patient outcome severity score. No single nurse behavior or characteristic was significantly related to the patient outcome severity score. Findings support the belief that system problems may be a contributing factor.