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.

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.

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.

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.

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.