Radiation Therapy Expenditures Through the First 8 Performance Periods of the Oncology Care Model at a Statewide Multispecialty Health System.

PURPOSE: Our purpose was to use real world data to assess trends in radiation therapy (RT) treatment fractionation and cost under the Oncology Care Model (OCM) through the first 8 performance periods (PPs). METHODS: We identified 17,157 episodes of care from 9898 patients treated at a statewide multispecialty health system through the first 8 6-month PPs (PP1-8: July 1, 2016, to June 30, 2020) of the OCM. Spending was stratified by 10 expenditure domains (eg, Part B/D drugs, radiation oncology [RO], etc), and 21 disease sites were extracted from claims data, from which an analysis of RO expenditures was performed on 2219 episodes from 2033 patients treated with RT. Expenses are expressed in per-beneficiary, per-episode terms. RESULTS: RO expenditures comprised 3% ($14.7M) of total spending over the 8 periods. By primary cancer, the largest RO expenses were for breast ($2.9M; 20%), prostate ($2.9M; 19%), and lung cancer ($2.8M; 13%). For RO, total per-episode average spending remained roughly constant between PP1 ($6314) and PP8 ($6664; Ptrend > .05) and decreased ($6314-$6215) when indexed to the Consumer Price Index for July 2016. Average number of RT fractions per episode decreased from 19.2 in PP1 to 18.6 in PP8; this decrease was most notably seen for breast (-2.1), lung (-2.8), and female genitourinary (-3.5) cancers. Intensity-modulated RT (IMRT) charges accounted for $7.6M (51%) of RT spending and increased 5% from PP1 to 8, whereas conventional external beam RT made up $3.0M (21%) and decreased 8%. Expenses for image guidance ($2.5M; 17%; +2% from PP1-8) and stereotactic RT ($1.3M; 9%; +1%) increased. CONCLUSIONS: In inflation-adjusted terms, total RO expenditures have declined despite greater use of IMRT, stereotactic RT, and image guidance. Conversely, oncology costs have risen because of drug spending. Successful payment models must prioritize high-cost spending areas-including novel drug therapies-while accounting for high-value care and patient outcomes.

Missed opportunities: misconceptions and lack of knowledge about vulval skin care in women attending a sexual health clinic.

Vulval skin care is an important part of women's health, and this evaluation aimed to explore vulval care among women attending our sexual health clinic. A questionnaire was completed by 135 women over a five-week period. Forty-three women (32%) washed their vulva two to three times a day, with 93 (69%) using a detergent-containing product. Thirty-eight women (28%) used sanitary products when not menstruating. Ninety-five women (70%) reported at least one previous vulvo-vaginal condition. One hundred and two women (76%) reported being confident in vulval care; however, 60 women (44%) wished to receive more information. The mismatch between women's confidence and knowledge may reflect mixed sources of education used by women. We recommend that sexual health clinics review the information they provide to patients on vulval care.

Gastrulation occurs in multiple phases at two distinct sites in Latrodectus and Cheiracanthium spiders.

BACKGROUND: The longstanding canonical model of spider gastrulation posits that cell internalization occurs only at a unitary central blastopore; and that the cumulus (dorsal organizer) arises from within the early deep layer by cell-cell interaction. Recent work has begun to challenge the canonical model by demonstrating cell internalization at extra-blastoporal sites in two species (Parasteatoda tepidariorum and Zygiella x-notata); and showing in Zygiella that the prospective cumulus internalizes first, before other cells are present in the deep layer. The cell behaviors making up spider gastrulation thus appear to show considerable variation, and a wider sampling of taxa is indicated. RESULTS: We evaluated the model in three species from two families by direct observation of living embryos. Movements of individual cells were traced from timelapse recordings and the origin and fate of the cumulus determined by CM-DiI labeling. We show that there are two distinct regions of internalization: most cells enter the deep layer via the central blastopore but many additional cells ingress via an extra-blastoporal ring, either at the periphery of the germ disc (Latrodectus spp.) or nearer the central field (Cheiracanthium mildei). In all species, the cumulus cells internalize first; this is shown by tracing cells in timelapse, histology, and by CM-DiI injection into the deep layer. Injection very early in gastrulation labels only cumulus mesenchyme cells whereas injections at later stages label non-cumulus mesoderm and endoderm. CONCLUSIONS: We propose a revised model to accommodate the new data. Our working model has the prospective cumulus cells internalizing first, at the central blastopore. The cumulus cells begin migration before other cells enter the deep layer. This is consistent with early specification of the cumulus and suggests that cell-cell interaction with other deep layer cells is not required for its function. As the cumulus migrates, additional mesendoderm internalizes at two distinct locations: through the central blastopore and at an extra-blastoporal ring. Our work thus demonstrates early, cell-autonomous behavior of the cumulus and variation in subsequent location and timing of cell internalization during gastrulation in spiders.

Prolonged exposure to a Mer ligand in leukemia: Gas6 favors expression of a partial Mer glycoform and reveals a novel role for Mer in the nucleus.

Mer tyrosine kinase is ectopically expressed in acute lymphoblastic leukemia and associated with enhanced chemoresistance and disease progression. While such effects are generally ascribed to increased engagement of oncogenic pathways downstream of Mer stimulation by its ligand, Gas6, Mer has not been characterized beyond the scope of its signaling activity. The present study explores Mer behavior following prolonged exposure to Gas6, a context similar to the Gas6-enriched microenvironment of the bone marrow, where a steady supply of ligand facilitates continuous engagement of Mer and likely sustains the presence of leukemic cells. Long-term Gas6 exposure induced production of a partially N-glycosylated form of Mer from newly synthesized stores of protein. Preferential expression of the partial Mer glycoform was associated with diminished levels of Mer on the cell surface and altered Mer localization within the nuclear-soluble and chromatin-bound fractions. The presence of Mer in the nucleus is a novel finding for this receptor, and the glycoform-specific preferences observed in each nuclear compartment suggest that glycosylation may influence Mer function within particular subcellular locales. Previous studies have established Mer as an attractive cancer biologic target, and understanding the complexity of its activity has important implications for potential strategies of Mer inhibition in leukemia therapy. Our results identify several novel features of Mer that expand the breadth of its functions and impact the development of therapeutic modalities designed to target Mer.

Outbreaks of Serratia marcescens in neonatal and pediatric intensive care units: clinical aspects, risk factors and management.

The following recommendations are derived from a systematic analysis of 34 Serratia marcescens outbreaks described in 27 publications from neonatal and pediatric intensive care units (NICU, PICU), in which genotyping methods were used to confirm or exclude clonality. The clinical observation of two or more temporally related cases of nosocomial S. marcescens infection should raise the suspicion of an outbreak, particularly in the NICU or PICU setting. Since colonized or infected patients represent the most important reservoir for cross transmission, hygienic barrier precautions (contact isolation/cohortation, the use of gloves and gowns in addition to strictly performed hand disinfection, enhanced environmental disinfection) should immediately be implemented and staff education given. Well-planned sampling of potential environmental sources should only be performed when these supervised barrier precautions do not result in containment of the outbreak. The current strategy of empiric antibiotic treatment should be reevaluated by a medical microbiologist or an infectious disease specialist. Empiric treatment of colonized children should use combination therapy informed by in vitro susceptibility data; in this context the high propensity of S. marcescens to cause meningitis and intracerebral abscess formation should be considered. In vitro susceptibility patterns do not reliably prove or exclude the clonality of the outbreak isolate. Genotyping of the isolates by pulse-field gel electrophoresis or PCR-based methods should be performed, but any interventions to interrupt further nosocomial spread should be carried out without waiting for the results.

Group G streptococcal bacteraemia: an opportunistic infection associated with immune senescence.

The number of cases of group G streptococcal bacteraemia reported worldwide is increasing. Twenty-six cases of group G streptococcal bacteraemia were identified during a 70-month period at a single university teaching hospital in Sheffield, UK. These cases represented 20% of all bacteraemias due to beta-hemolytic Streptococci, a higher proportion than previously reported. The median age of these cases was 72 y and although medical comorbidities were common only cutaneous ulceration was clearly linked to the presenting syndromes. The skin was the source of infection in 16 cases (62%) and the most frequent clinical presentations were cellulitis in 13 cases (50%) and endovascular infection in 5 (19%). Eight (31%) of the cases died during the period of follow-up but only 2 deaths were related to the streptococcal infection. Immunosenescence represents the major risk factor for group G streptococcal infection in this population and comorbidities, including carcinoma, may be markers of the senescent immune system rather than direct contributing factors to group G streptococcal bacteraemia.