The persistent benefits of decreasing default pill counts for postoperative narcotic prescriptions.

BACKGROUND: In 2017, a university-based academic healthcare system changed the opioid default pill count from 30 to 12 pills. Modifying the electronic default pill count influences short-term clinician prescribing practices. We sought to understand the long-term impact on postoperative opioid prescribing habits after an opioid default pill count reduction. MATERIALS AND METHODS: A retrospective electronic medical record system (EMRS) review was conducted in a healthcare system comprised of seven affiliated hospitals. Patients who underwent a surgical procedure and were prescribed an opioid on discharge between 2017-2021 were evaluated. All prescriptions were converted into morphine equivalents (MME). Analyses were performed with the chi-square test and Bonferonni adjusted t-test. RESULTS: 191,379 surgical procedures were studied. The average quantity of opioids prescribed decreased from 32 oxycodone 5 mg tablets in 2017 to 21 oxycodone 5 mg tablets in 2021 (236 MME to 154 MME, p<0.001). The percentage of patients obtaining a refill within 90 days of surgery varied between 18.3% and 19.9% (p<0.001). Patients with a pre-existing opioid prescription and opioid-naïve patients both had significant reductions in prescription quantities above the default MME (79.7% to 60.6% vs. 65.3% to 36.9%, p<0.001). There was no significant change in refills for both groups (pre-existing 36.7% to 38.3% (p = 0.1) vs naïve 15.0% to 15.3% (p = 0.29)). CONCLUSIONS: The benefits of decreasing the default opioid pill count continue to accumulate long after the original change. Physician uptake of small changes to default EMRS practices represents a sustainable and effective intervention to reduce the quantities of postoperative opioids prescribed without deleterious effects on outpatient opiate requirements.

Routine post-operative labs and healthcare system burden in acute appendicitis.

BACKGROUND: Data from the National Health Expenditure Accounts have shown a steady increase in healthcare cost paralleled by availability of laboratory tests. Resource utilization is a top priority for reducing health care costs. We hypothesized that routine post-operative laboratory utilization unnecessarily increases costs and healthcare system burden in acute appendicitis (AA) management. METHODS: A retrospective cohort of patients with uncomplicated AA 2016-2020 were identified. Clinical variables, demographics, lab usage, interventions, and costs were collected. RESULTS: A total of 3711 patients with uncomplicated AA were identified. Total costs of labs ($289,505, 99.56%) and repletions ($1287.63, 0.44%) were $290,792.63. Increased LOS was associated with lab utilization in multivariable modeling, increasing costs by $837,602 or 472.12 per patient. CONCLUSIONS: In our patient population, post-operative labs resulted in increased costs without discernible impact on clinical course. Routine post-operative laboratory testing should be re-evaluated in patients with minimal comorbidities as this likely increases cost without adding value.

Etiology of fatal thoracic aortic injuries: Secondary data analysis.

OBJECTIVES: Motor vehicle crashes remain a leading cause of death in the United States (US). Thoracic aortic dissection due to blunt trauma remains a major injury mechanism, and up to 90% of these injuries result in death on the scene. The objective of this study is to understand the modern risk factors and etiology of fatal thoracic aortic injuries in the current US fleet. METHODS: Using a unique, linked, Fatality Analysis Reporting System (FARS) and Multiple Cause of Death (MCOD) database from 2000-2010, 144,169 drivers over 16 years of age who suffered fatal injuries were identified. The merged database provides an unparalleled fidelity for identifying thoracic aortic injuries due to motor vehicle accidents. Thoracic aortic injuries were defined by ICD-10 codes S250. Univariate and multivariate logistic regression models for presence of any thoracic aortic injuries were fitted. Age, gender, BMI weight categories, vehicle class, model year, crash type/direction, severity of crash damage, airbag deployment location, and seatbelt use, fatal injury codes, and location of injury were considered. Odds ratios (OR) and corresponding 95% confidence intervals (95%CI) are calculated. RESULTS: There were 2953 deaths (2.10%) related to thoracic aortic injuries that met the inclusion criteria. Nearside crashes were associated with an increased odds (OR = 1.42, 1.1-1.83), while rollover crashes (OR =.44,.29-.66) were associated with a reduced odds of fatal thoracic aortic injury. Using backward selection on the full multivariate model, the only significant model effects that remained were vehicle type, crash type, body region, and injury type. CONCLUSIONS: The increased prevalence of fatal thoracic aortic injury in nearside crashes, increasing age, and vehicle type provide some insight into the current US fleet. Important factors, including model year, had significantly lower levels of the injury in univariate analysis, demonstrating the effect of safety improvements in newer model vehicles. Further study of this fatal injury is warranted, including comparisons of those who survive the injury.

Association Between American Board of Surgery In-Training Examination Scores and Resident Performance.

IMPORTANCE: The American Board of Surgery In-Training Examination (ABSITE) is designed to measure progress, applied medical knowledge, and clinical management; results may determine promotion and fellowship candidacy for general surgery residents. Evaluations are mandated by the Accreditation Council for Graduate Medical Education but are administered at the discretion of individual institutions and are not standardized. It is unclear whether the ABSITE and evaluations form a reasonable assessment of resident performance. OBJECTIVE: To determine whether favorable evaluations are associated with ABSITE performance. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of preliminary and categorical residents in postgraduate years (PGYs) 1 through 5 training in a single university-based general surgery program from July 1, 2011, through June 30, 2014, who took the ABSITE. EXPOSURES: Evaluation overall performance and subset evaluation performance in the following categories: patient care, technical skills, problem-based learning, interpersonal and communication skills, professionalism, systems-based practice, and medical knowledge. MAIN OUTCOMES AND MEASURES: Passing the ABSITE (≥30th percentile) and ranking in the top 30% of scores at our institution. RESULTS: The study population comprised residents in PGY 1 (n = 44), PGY 2 (n = 31), PGY 3 (n = 26), PGY 4 (n = 25), and PGY 5 (n = 24) during the 4-year study period (N = 150). Evaluations had less variation than the ABSITE percentile (SD = 5.06 vs 28.82, respectively). Neither annual nor subset evaluation scores were significantly associated with passing the ABSITE (n = 102; for annual evaluation, odds ratio = 0.949; 95% CI, 0.884-1.019; P = .15) or receiving a top 30% score (n = 45; for annual evaluation, odds ratio = 1.036; 95% CI, 0.964-1.113; P = .33). There was no difference in mean evaluation score between those who passed vs failed the ABSITE (mean [SD] evaluation score, 91.77 [5.10] vs 93.04 [4.80], respectively; P = .14) or between those who received a top 30% score vs those who did not (mean [SD] evaluation score, 92.78 [4.83] vs 91.92 [5.11], respectively; P = .33). There was no correlation between annual evaluation score and ABSITE percentile (r(2) = 0.014; P = .15), percentage correct unadjusted for PGY level (r(2) = 0.019; P = .09), or percentage correct adjusted for PGY level (r(2) = 0.429; P = .91). CONCLUSIONS AND RELEVANCE: Favorable evaluations do not correlate with ABSITE scores, nor do they predict passing. Evaluations do not show much discriminatory ability. It is unclear whether individual resident evaluations and ABSITE scores fully assess competency in residents or allow comparisons to be made across programs. Creation of a uniform evaluation system that encompasses the necessary subjective feedback from faculty with the objective measure of the ABSITE is warranted.

Characterizing the Business Skills of the Public Health Workforce: Practical Implications From the Public Health Workforce Interests and Needs Survey (PH WINS).

CONTEXT: Public health financial competencies are often overlooked or underrepresented in public health training programs. These skills are important for public health workforce members who are involved in managing resources and strategic planning and have been defined as key competencies by several national entities. OBJECTIVE: To characterize business skills among state health agency employees and examine self-reported skill levels and their association with job satisfaction, worksite training and development opportunities, and annual salary. DESIGN: A cross-sectional survey, the Public Health Workforce Interests and Needs Survey (PH WINS), of state health agency central office employees was conducted in 2014. Multivariable logistic regression analyses, controlling for job classification, supervisory status, years of public health practice, annual compensation, educational attainment, geographic region, and sociodemographic status, were used to assess the relationship between business skills and training environment and job satisfaction. Linear regression was used to correlate business skills and annual compensation. SETTING AND PARTICIPANTS: A total of 10,246 state health agency staff completed a Web-based survey. MAIN OUTCOME MEASURE: Self-reported proficiency in business skills, job satisfaction, opportunities for training, and annual salary. RESULTS: The workforce reported high levels of proficiency in applying quality improvement concepts and managing change (67.5% and 69.2%, respectively). Half of the respondents reported proficiency in budget skills (49.3%). Participants who were proficient in applying quality improvement concepts were significantly more likely to report job satisfaction (OR = 1.27). A supportive training environment was significantly associated with business competencies (range of OR = 1.08-1.11). Managing change (ß = .15) and budget skill proficiency (ß = .37) were significantly associated with increased yearly compensation. CONCLUSIONS: Public health workers who self-report proficiency with business skills report increased job satisfaction, higher annual salary, and a supportive training environment. These findings support the need for the development of appropriately designed business skill training opportunities to increase competencies in this critical domain.

Microvessel area as a predictor of sorafenib response in metastatic renal cell carcinoma.

BACKGROUND: Sorafenib was the first Food and Drug Administration approved anti-angiogenic therapy for renal cell carcinoma (RCC). Currently, there are no validated predictive biomarkers for sorafenib. Our purpose was to determine if sorafenib target expression is predictive of sorafenib sensitivity. METHODS: We used an automated, quantitative immunofluorescence-based method to determine expression levels of sorafenib targets VEGF, VEGF-R1, VEGF-R2, VEGF-R3, c-RAF, B-RAF, c-Kit, and PDGFR-ß in a cohort of 96 patients treated with sorafenib. To measure vasculature in the tumor samples, we measured microvessel area (MVA) by CD-34 staining. RESULTS: Of the markers studied, only high MVA was predictive of response (p = 0.005). High MVA was associated with smaller primary tumors (p = 0.005). None of the biomarkers studied was predictive of overall or progression-free survival. Using the Bonferroni adjustment correcting for 9 variables with an alpha of 0.05, MVA remained significantly associated with sorafenib response. CONCLUSIONS: Our results suggest that high MVA in tumor specimens might be associated with a greater likelihood of response to therapy. Further studies are needed to confirm these results in additional patients and in patients receiving other VEGF-R2 inhibitors, as MVA might be useful to improve patient selection for VEGF-R2 inhibitors.

Expression of drug targets in primary and matched metastatic renal cell carcinoma tumors.

BACKGROUND: Targeted therapies in renal cell carcinoma can have different effects on primary and metastatic tumors. To pave the way for predictive biomarker development, we assessed differences in expression of targets of currently approved drugs in matched primary and metastatic specimens from 34 patients. METHODS: Four cores from each site were embedded in tissue microarray blocks. Expression of B-Raf, C-Raf, cKIT, FGF-R1, HIF-2α, mTOR, PDGF-Rß, VEGF-R1, VEGF-R2, VEGF-R3, VEGF, VEGF-B, VEGF-C, VEGF-D, MEK1, and ERK1/2 was studied using a quantitative immunofluorescence method. RESULTS: No significant differences were observed in global expression levels in primary and metastatic renal cell carcinoma tumors, with the exception of MEK, which had higher expression in metastatic than primary specimens. Similarly, more ki67 positive cells were seen in metastatic specimens. Correlations between marker expression in primary and metastatic specimens were variable, with the lowest correlation seen for FGF-R1 and VEGF-D. There were no significant differences in the degree of heterogeneity in primary versus metastatic tumors. CONCLUSIONS: Expression of most of the studied markers was similar in primary and metastatic renal cell carcinoma tumors, suggesting that predictive biomarker testing for these markers can be conducted on either the primary or metastatic tumors for most markers.

Vascularity of primary and metastatic renal cell carcinoma specimens.

PURPOSE: Anti-angiogenic therapies are among the most commonly used drugs in renal cell carcinoma. Tumor vascularity, defined by microvessel area, may be associated with response to these drugs. Clinical studies suggest that metastatic sites are more responsive than primary tumors. Our purpose was to characterize microvessel area (MVA) in matched primary and metastatic samples and in samples of different histologies. METHODS: We employed a method of automated, quantitative analysis of in situ tumor components to identify the area of CD-34 staining endothelial cells within renal cell carcinoma tumors. MVA was assessed in corresponding primary and metastatic samples from 34 patients, as well as in 334 primary nephrectomy specimens with variable histologies. RESULTS: MVA measurements from different parts of the same tumor correlated well (R = 0.75), indicating that MVA was fairly uniform within a tumor. While MVA was slightly higher in primary tumors than corresponding metastatic sites, the difference was not statistically significant (P = 0.1). MVA in paired primary and metastatic samples correlated moderately well (R = 0.36). MVA was higher in clear cell than papillary histology and oncocytomas (P < 0.0001 and P = 0.018, respectively). CONCLUSIONS: Lack of significant differences MVA in matched primary and metastatic samples suggests that both types of tumors should respond to anti-angiogenic drugs. This should be confirmed on additional cohorts. Given the small cohort, future predictive biomarker studies entailing MVA measurements should include specimens from both sites. Clear cell carcinomas are more vascular than other histologic subtypes, which may explain the higher response rates to anti-angiogenic therapies in clear cell tumors.

Studies of NVP-BEZ235 in melanoma.

The PI3k pathway represents an attractive target for drug development in melanoma, as numerous studies have shown that this pathway is active in malignant melanocytes. In addition, previous work has shown that multi-level targeting of this pathway might be more effective than targeting the pathway at a single level. In this review, we discuss targeting different members of this pathway, potential escape mechanisms, classes of specific molecular inhibitors, and development of NVP-BEZ235, a novel dual PI3k/mTOR inhibitor.

Vertical pathway targeting in cancer therapy.

Malignant cells arise from particular mutations in genes controlling cell proliferation, invasion, and survival. Older antineoplastic drugs were designed to target vital cellular processes, such as DNA maintenance and repair and cell division. As a result, these drugs can affect all proliferating cells and are associated with unavoidable toxicities. Recent discoveries in cancer research have identified "driver" mutations in some types of cancer, and efforts have been undertaken to develop drugs targeting these oncogenes. In most cases, due to escape mechanisms and adaptive responses, single oncogene targeting is insufficient to induce prolonged responses in solid tumors. Drug combinations are therefore used to enhance the growth inhibitory and cytotoxic effects of the targeted therapies. Depending on the position of additional targets within the signaling network, drug combinations may target either different signaling pathways (parallel targeting) or the same pathway at several fragile nodes (vertical targeting). In this review, we discuss strategies of multitarget inhibition with a focus on vertical signaling pathway targeting.

CD70 expression patterns in renal cell carcinoma.

CD70 is up-regulated in several malignancies, where it induces cytotoxic effects on B and T lymphocytes, leading to immune escape. Novel therapeutic agents targeting CD70 have entered clinical trials. We characterized expression of CD70 protein in renal cell carcinoma specimens of various histologic subtypes and assessed their prognostic value and association with clinical/pathologic variables. We used tissue microarrays containing 330 cases using a novel fluorescent immunohistochemistry-based method of Automated Quantitative Analysis of in situ protein expression. The mean expression of CD70 was almost twice as high in tumors relative to normal tissue (P < .0001). When broken into subsets, CD70 was higher in sarcomatoid and clear cell tumors (P < .0001) and was variably elevated in oncocytomas and some papillary tumors. No association was found between CD70 expression and stage or grade. High CD70 expression was associated with decreased survival on univariate analysis in the clear cell subset of renal cell carcinoma; however, it did not retain significance on multivariate analysis. Given the elevated expression of CD70 in clear cell, sarcomatoid, and some papillary tumors, our findings suggest that CD70 might be a good drug target in renal cell carcinoma. Additional studies are warranted to assess the association between expression of CD70 and response to therapy with CD70-targeting drugs in renal cell carcinoma.