Factors influencing receipt and time to treatment of immunotherapy relative to chemotherapy in stage III and stage IV melanoma.

BACKGROUND: Immunotherapies have changed the landscape of late-stage melanoma; however, data evaluating timely access to immunotherapy are lacking. METHODS: A retrospective cohort study utilizing the National Cancer Database was conducted. Stage III and IV melanoma cases diagnosed between 2011 and 2018 that received systemic treatment with either immunotherapy or chemotherapy were included. Chemotherapy included BRAF/MEK inhibitors. Multivariable logistic regression models were utilized to evaluate factors associated with the likelihood of receiving immunotherapy as primary systemic treatment relative to chemotherapy; additionally, Cox proportional hazards models were utilized to incorporate time from diagnosis to primary systemic therapy into the analysis. RESULTS: The study population was comprised of 14,446 cases. The cohort included 12,053 (83.4%) immunotherapy and 2393 (16.6%) chemotherapy cases. In multivariable logistic regression analysis, factors significantly associated with immunotherapy receipt included population density, circle distance, year of diagnosis, Breslow thickness, and cancer stage. Immunotherapy timing was evaluated using multivariable Cox regression analysis. Minorities were less likely to receive timely immunotherapy than non-Hispanic Whites (HR 0.83, CI 0.74-0.93, p = 0.001). Patients at circle distances of 10-49 miles (HR 0.94, CI 0.89-0.99, p = 0.02) and ≥50 miles (HR 0.83, CI 0.77-0.90, p < 0.001) were less likely to receive timely immunotherapy. CONCLUSION: Patients traveling ≥10 miles and minorities have a decreased likelihood of receiving timely immunotherapy administration for primary systemic treatment. Future research is needed to identify what barriers and approaches can be leveraged to address these inequities.

Evidence for a maintenance cost for birds maintaining highly flexible basal, but not summit, metabolic rates.

Reversible phenotypic flexibility allows organisms to better match phenotypes to prevailing environmental conditions and may produce fitness benefits. Costs and constraints of phenotypic flexibility may limit the capacity for flexible responses but are not well understood nor documented. Costs could include expenses associated with maintaining the flexible system or with generating the flexible response. One potential cost of maintaining a flexible system is an energetic cost reflected in the basal metabolic rate (BMR), with elevated BMR in individuals with more flexible metabolic responses. We accessed data from thermal acclimation studies of birds where BMR and/or Msum (maximum cold-induced metabolic rate) were measured before and after acclimation, as a measure of metabolic flexibility, to test the hypothesis that flexibility in BMR (ΔBMR), Msum (ΔMsum), or metabolic scope (Msum - BMR; ΔScope) is positively correlated with BMR. When temperature treatments lasted at least three weeks, three of six species showed significant positive correlations between ΔBMR and BMR, one species showed a significant negative correlation, and two species showed no significant correlation. ΔMsum and BMR were not significantly correlated for any species and ΔScope and BMR were significantly positively correlated for only one species. These data suggest that support costs exist for maintaining high BMR flexibility for some bird species, but high flexibility in Msum or metabolic scope does not generally incur elevated maintenance costs.

A cross-sectional analysis of trends in dermatology practice size in the United States from 2012 to 2020.

Physicians are trending towards practice consolidation nationally; however, changes in dermatology practice size remain to be assessed. The objective of this study was to analyze trends in dermatology practice size from 2012 to 2020 using a large-scale Medicare physician database. We performed a retrospective cross-sectional analysis using 2012 and 2020 data obtained from the Physician Compare Database. Responses from dermatologists were analyzed for trends in practice size, with a sub-analysis to examine differences among different regions, gender, and years of experience. The proportion of dermatologists in solo practice decreased from 26.1% in 2012 to 15.6% in 2020 (p < 0.001). Dermatologists were 40% less likely to be practicing in solo practice and 36% more likely to be in a practice with 10 or more members in 2020 (p < 0.001). These findings were consistent among all regions and genders examined. Additionally, in 2020, dermatologists with 30 or more years in practice were 7.5 times more likely to be in solo practice compared to dermatologists with 0-9 years in practice (p < 0.001). There is a trend of dermatologists working for larger practices, which is consistent with a larger nationwide trend of expanding physician practices. This shift in practice settings should be closely monitored to analyze the effect on healthcare efficiency, cost, and delivery.

A Proposed Blueprint for Operative Performance Training, Assessment, and Certification.

OBJECTIVE: The aim of this study was to propose an evidence-based blueprint for training, assessment, and certification of operative performance for surgical trainees. SUMMARY BACKGROUND DATA: Operative skill is a critical aspect of surgical performance. High-quality assessment of operative skill therefore has profound implications for training, accreditation, certification, and the public trust of the profession. Current methods of operative skill assessment for surgeons rely heavily on global assessment strategies across a very broad domain of procedures. There is no mechanism to assure technical competence for individual procedures. The science and scalability of operative skill assessment has progressed significantly in recent decades, and can inform a much more meaningful strategy for competency-based assessment of operative skill than has been previously achieved. METHODS: The present article reviews the current status and science of operative skill assessment and proposes a template for competency-based assessment which could be used to update training, accreditation, and certification processes. The proposal is made in reference to general surgery but is more generally applicable to other procedural specialties. RESULTS: Streamlined, routine assessment of every procedure performed by surgical trainees is feasible and would enable a more competency-based educational paradigm. In light of the constraints imposed by both clinical volume and assessment bias, trainees should be expected to become proficient and be measured against a mastery learning standard only for the most important and highest-frequency procedures. For less frequently observed procedures, performance can be compared to a norm-referenced standard and, to provide an overall trajectory of performance, analyzed in aggregate. Key factors in implementing this approach are the number of evaluations, the number of raters, the timeliness of evaluation, and evaluation items. CONCLUSIONS: A competency-based operative skill assessment can be incorporated into surgical training, assessment, and certification. The time has come to develop a systematic approach to this issue as a means of demonstrating professional standards worthy of the public trust.

Including ultrasound scans in antenatal care in low-resource settings: Considering the complementarity of obstetric ultrasound screening and maternity waiting homes in strengthening referral systems in low-resource, rural settings.

Recent World Health Organization (WHO) antenatal care recommendations include an ultrasound scan as a part of routine antenatal care. The First Look Study, referenced in the WHO recommendation, subsequently shows that the routine use of ultrasound during antenatal care in rural, low-income settings did not improve maternal, fetal or neonatal mortality, nor did it increase women's use of antenatal care or the rate of hospital births. This article reviews the First Look Study, reconsidering the assumptions upon which it was built in light of these results, a supplemental descriptive study of interviews with patients and sonographers that participated in the First Look study intervention, and a review of the literature. Two themes surface from this review. The first is that focused emphasis on building the pregnancy risk screening skills of rural primary health care personnel may not lead to adaptations in referral hospital processes that could benefit the patient accordingly. The second is that agency to improve the quality of patient reception at referral hospitals may need to be manufactured for obstetric ultrasound screening, or remote pregnancy risk screening more generally, to have the desired impact. Stemming from the literature, this article goes on to examine the potential for complementarity between obstetric ultrasound screening and another approach encouraged by the WHO, the maternity waiting home. Each approach may address existing shortcomings in how the other is currently understood. This paper concludes by proposing a path toward developing and testing such a hybrid approach.

Use of ultrasound and mHealth to improve perinatal outcomes in low and middle income countries.

The explosion of mobile health and portable obstetric ultrasound interventions in low- and middle-income countries (LMIC) reflects the optimism that technology can help reduce persistently high rates of maternal and neonatal mortality and morbidity in these settings. While these technology-driven interventions have had success in improving aspects of antenatal and perinatal care, they have not clearly demonstrated reductions in mortality. The expanding synergy between mobile health (mHealth) and ultrasound technology shows promise to enhance care, but it will likely take combining these technological advances with system-wide approaches that also address referral patterns and infrastructure barriers to improve outcomes.

2018 Consensus framework for good assessment.

Introduction: In 2010, the Ottawa Conference produced a set of consensus criteria for good assessment. These were well received and since then the working group monitored their use. As part of the 2010 report, it was recommended that consideration be given in the future to preparing similar criteria for systems of assessment. Recent developments in the field suggest that it would be timely to undertake that task and so the working group was reconvened, with changes in membership to reflect broad global representation.Methods: Consideration was given to whether the initially proposed criteria continued to be appropriate for single assessments and the group believed that they were. Consequently, we reiterate the criteria that apply to individual assessments and duplicate relevant portions of the 2010 report.Results and discussion: This paper also presents a new set of criteria that apply to systems of assessment and, recognizing the challenges of implementation, offers several issues for further consideration. Among these issues are the increasing diversity of candidates and programs, the importance of legal defensibility in high stakes assessments, globalization and the interest in portable recognition of medical training, and the interest among employers and patients in how medical education is delivered and how progression decisions are made.

Experimental Increases in Foraging Costs Affect Pectoralis Muscle Mass and Myostatin Expression in Female, but Not Male, Zebra Finches (Taeniopygia guttata).

Skeletal muscle remodeling is an important component of phenotypic flexibility in birds and impacts organismal metabolism and performance, which could potentially influence fitness. One regulator of skeletal muscle remodeling is myostatin, an autocrine/paracrine muscle growth inhibitor that may be down-regulated under conditions promoting heavier muscle masses. In this study, we employed protocols requiring hovering while foraging to increase foraging costs and modify phenotypes of zebra finches (Taeniopygia guttata). We examined the effects of high-cost foraging (HF) on skeletal muscle masses and used real-time reverse-transcription polymerase chain reaction and Western blots to measure gene and protein expression of myostatin and its metalloproteinase activators tolloid-like proteases TLL-1 and TLL-2 in pectoralis muscle. Female finches average shorter wings and higher wing loading than males, so increased flight costs might be expected to disproportionately affect females. Indeed, HF female finches exhibited reduced total fat masses, increased pectoralis muscle masses, and lower myostatin protein levels than controls. Male finches showed no significant differences in pectoralis muscle masses or myostatin protein levels between HF and control birds. Myostatin, TLL-1, and TLL-2 messenger RNA (mRNA) expression remained stable between treatments for both female and male finches. Myostatin mRNA and protein levels showed variable directions of correlations with pectoralis mass residuals among treatments. Thus, these data offer only mixed support for a regulatory role for myostatin in mediating the flexibility of pectoralis muscle phenotypes of small birds.

Patient-reported health-related quality of life for men treated with low-dose-rate prostate brachytherapy as monotherapy with 125-iodine, 103-palladium, or 131-cesium: Results of a prospective phase II study.

PURPOSE: To compare quality of life (QoL) after brachytherapy with one of the three approved radioactive isotopes. METHODS AND MATERIALS: Patients with mostly favorable intermediate-risk prostate cancer were treated on this prospective phase II trial with brachytherapy as monotherapy, without hormonal therapy. QoL was recorded at baseline and each follow-up by using the Expanded Prostate Cancer Index Composite instrument. The minimal clinically important difference was defined as half the standard deviation of the baseline score for each domain. Mixed effect models were used to compare the different isotopes, and time-driven activity-based costing was used to compute costs. RESULTS: From 2006 to 2013, 300 patients were treated with iodine-125 (I-125, n = 98, prescribed dose [PD] = 145 Gy), palladium-103 (Pd-103, n = 102, PD = 125 Gy), or cesium-131 (Cs-131, n = 100, PD = 115 Gy). Median age was 64.9 years. Median follow-up time was 5.1 years for the entire cohort, and 7.1, 4.8 and 3.3 years for I-125, Pd-103, and Cs-131 groups, respectively. All three isotope groups showed an initial drop in QoL at first follow-up, which gradually improved over the first 2 years for urinary and bowel domains. QoL profiles were similar between I-125 and Pd-103, whereas Cs-131 showed a statistically significant decrease in QoL regarding bowel and sexual function at 12 months compared with Pd-103. However, these differences did not reach the minimal clinically important difference. Compared with I-125, the use of Pd-103 or Cs-131 resulted in cost increases of 18% and 34% respectively. CONCLUSIONS: The three different isotopes produced a similar QoL profile. Statistically significant differences favored Pd-103/I-125 over Cs-131 for bowel and sexual QoL, but this did not reach clinical significance.

Challenges of Implementing Antenatal Ultrasound Screening in a Rural Study Site: A Case Study From the Democratic Republic of the Congo.

Persistent global disparities in maternal and neonatal outcomes and the emergence of compact ultrasound technology as an increasingly viable technology for low-resource settings provided the genesis of the First Look Ultrasound study. Initiated in 2014 in 5 low- and middle-income countries and completed in June 2016, the study's intervention included the training of health personnel to perform antenatal ultrasound screening and to refer women identified with high-risk pregnancies to hospitals for appropriate care. This article examines the challenges that arose in implementing the study, with a particular focus on the site in Equateur Province of the Democratic Republic of the Congo (DRC) where the challenges were greatest and the efforts to meet these challenges most illuminating. During the study period, we determined that with resources and dedicated staff, it was possible to leverage the infrastructure and implement ultrasound at antenatal care across a variety of remote sites, including rural DRC. However, numerous technical and logistical challenges had to be addressed including security of the equipment, electricity requirements, and integration of the intervention into the health system. To address security concerns, in most of the countries field sonographers were hired and dispatched each day with the equipment to the health centers. At the end of each day, the equipment was locked in a secure, central location. To obtain the required power source, the DRC health centers installed solar panels bolted on adjacent poles since the thatch roofs of the centers prohibited secure roof-top installation. To realize the full value of the ultrasound intervention, women screened with high-risk pregnancies had to seek a higher level of care at the referral hospital for a definitive diagnosis and appropriate care. While the study did provide guidance on referral and systems management to health center and hospital administration, the extent to which this resulted in the necessary structural changes varied depending on the motivation of the stakeholders. In order for such an intervention to be scaled up and sustained as part of a health system's general services, it would require considerable effort, political will, and financial and human resources. Preliminary results from the study indicate that taking routine antenatal ultrasound screening to scale is not warranted. Lessons learned in implementing the study, however, can help inform future studies or programs that are considering use of ultrasound or other imaging technology for other applications in low-resource settings.

Defining the value framework for prostate brachytherapy using patient-centered outcome metrics and time-driven activity-based costing.

PURPOSE: Value, defined as outcomes over costs, has been proposed as a measure to evaluate prostate cancer (PCa) treatments. We analyzed standardized outcomes and time-driven activity-based costing (TDABC) for prostate brachytherapy (PBT) to define a value framework. METHODS AND MATERIALS: Patients with low-risk PCa treated with low-dose-rate PBT between 1998 and 2009 were included. Outcomes were recorded according to the International Consortium for Health Outcomes Measurement standard set, which includes acute toxicity, patient-reported outcomes, and recurrence and survival outcomes. Patient-level costs to 1 year after PBT were collected using TDABC. Process mapping and radar chart analyses were conducted to visualize this value framework. RESULTS: A total of 238 men were eligible for analysis. Median age was 64 (range, 46-81). Median followup was 5 years (0.5-12.1). There were no acute Grade 3-5 complications. Expanded Prostate Cancer Index Composite 50 scores were favorable, with no clinically significant changes from baseline to last followup at 48 months for urinary incontinence/bother, bowel bother, sexual function, and vitality. Ten-year outcomes were favorable, including biochemical failure-free survival of 84.1%, metastasis-free survival 99.6%, PCa-specific survival 100%, and overall survival 88.6%. TDABC analysis demonstrated low resource utilization for PBT, with 41% and 10% of costs occurring in the operating room and with the MRI scan, respectively. The radar chart allowed direct visualization of outcomes and costs. CONCLUSIONS: We successfully created a visual framework to define the value of PBT using the International Consortium for Health Outcomes Measurement standard set and TDABC costs. PBT is associated with excellent outcomes and low costs. Widespread adoption of this methodology will enable value comparisons across providers, institutions, and treatment modalities.

Defining a standard set of patient-centered outcomes for men with localized prostate cancer.

BACKGROUND: Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment. OBJECTIVE: To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value. DESIGN, SETTING, AND PARTICIPANTS: We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set. RESULTS AND LIMITATIONS: We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons. CONCLUSIONS: We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care. PATIENT SUMMARY: Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer.

Declining use of brachytherapy for the treatment of prostate cancer.

PURPOSE: To analyze the recent trends in the utilization of external beam radiation therapy (EBRT) and brachytherapy (BT) for the treatment of prostate cancer. METHODS AND MATERIALS: Using the Surveillance, Epidemiology, and End Results (SEER) database, information was obtained for all patients diagnosed with localized prostate adenocarcinoma between 2004 and 2009 who were treated with radiation as local therapy. We evaluated the utilization of BT, EBRT, and combination BT+EBRT by the year of diagnosis and performed a multivariable analysis to determine the predictors of BT as treatment choice. RESULTS: Between 2004 and 2009, EBRT monotherapy use increased from 55.8% to 62.0%, whereas all BT use correspondingly decreased from 44.2% to 38.0% (BT-only use decreased from 30.4% to 25.6%, whereas BT+EBRT use decreased from 13.8% to 12.3%). The decline of BT utilization differed by patient race, SEER registry, median county income, and National Comprehensive Cancer Network risk categorization (all p<0.001), but not by patient age (p=0.763) or marital status (p=0.193). Multivariable analysis found that age, race, marital status, SEER registry, median county income, and National Comprehensive Cancer Network risk category were independent predictors of BT as treatment choice (all p<0.001). Moreover, after controlling for all available patient and tumor characteristics, there was decreasing utilization of BT with increasing year of diagnosis (odds ratio for BT=0.920, 95% confidence interval: 0.911-0.929, p<0.001). CONCLUSIONS: Our analysis reveals decreasing utilization of BT for prostate cancer. This finding has significant implications in terms of national health care expenditure.

Activation of the immune system incurs energetic costs but has no effect on the thermogenic performance of house sparrows during acute cold challenge.

Trade-offs between the immune system and other condition-dependent life-history traits (reproduction, predator avoidance and somatic growth) have been well documented in both birds and mammals. However, no studies have examined the impact of immune activation on thermoregulatory performance during acute cold exposure. Because of their high surface-area-to-volume ratios, small birds incur high energetic costs associated with thermoregulation during cold exposure. Consequently, we predicted that the immune system and the thermoregulatory system would compete for energetic resources. To test this, we immunologically challenged adult house sparrows (Passer domesticus) with 5 mg kg(-1) of lipopolysaccharide (LPS) to induce an acute phase response and measured both resting (RMR; minimum metabolic rate) and summit ( ; maximal metabolic rate during cold exposure) metabolic rates. We found that birds injected with LPS had significantly higher RMR and than birds injected with phosphate-buffered saline, indicating that LPS-treated birds were able to support the cost of both immune activation and thermoregulation under conditions eliciting maximal thermogenic performance. These results suggest that, in the absence of a pathogen, birds that experience short-term activation of the immune system have higher energetic costs during cold exposure, but immune activation does not compromise maximum thermoregulatory performance.

Research in assessment: consensus statement and recommendations from the Ottawa 2010 Conference.

Medical education research in general is a young scientific discipline which is still finding its own position in the scientific range. It is rooted in both the biomedical sciences and the social sciences, each with their own scientific language. A more unique feature of medical education (and assessment) research is that it has to be both locally and internationally relevant. This is not always easy and sometimes leads to purely ideographic descriptions of an assessment procedure with insufficient general lessons or generalised scientific knowledge being generated or vice versa. For medical educational research, a plethora of methodologies is available to cater to many different research questions. This article contains consensus positions and suggestions on various elements of medical education (assessment) research. Overarching is the position that without a good theoretical underpinning and good knowledge of the existing literature, good research and sound conclusions are impossible to produce, and that there is no inherently superior methodology, but that the best methodology is the one most suited to answer the research question unambiguously. Although the positions should not be perceived as dogmas, they should be taken as very serious recommendations. Topics covered are: types of research, theoretical frameworks, designs and methodologies, instrument properties or psychometrics, costs/acceptability, ethics, infrastructure and support.