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Background: Securing a diagnosis of ovarian cancer and establishing means to predict outcomes to therapeutics remain formidable clinical challenges. Early diagnosis is particularly important since survival rates are markedly improved if tumour is detected early. Methods: Comprehensive miRNA profiles were generated on presurgical plasma samples from 42 women with confirmed serous epithelial ovarian cancer, 36 women diagnosed with a benign neoplasm, and 23 comparably age-matched women with no known pelvic mass. Results: Twenty-two miRNAs were differentially expressed between healthy controls and the ovarian cancer group ( P <0.05), while a six miRNA profile subset distinguished presurgical plasma from benign and ovarian cancer patients. There were also significant differences in miRNA profiles in presurgical plasma from women diagnosed with ovarian cancer who had short overall survival when compared to women with long overall survival ( P <0.05). Conclusion: Our preliminary data support the utility of circulating plasma miRNAs to distinguish women with ovarian cancer from those with a benign mass and identify women likely to benefit from currently available treatment for serous epithelial ovarian cancer from those who may not.

Background Researchers and policy makers have determined that accounting for productivity costs, or “indirect costs,” may be as important as including direct medical expenditures when evaluating the societal value of health interventions. These costs are also important when estimating the global burden of disease. The estimation of indirect costs is commonly done on a country-specific basis. However, there are few studies that evaluate indirect costs across countries using a consistent methodology. Methods Using the human capital approach, we developed a model that estimates productivity costs as the present value of lifetime earnings (PVLE) lost due to premature mortality. Applying this methodology, the model estimates productivity costs for 29 selected countries, both developed and emerging. We also provide an illustration of how the inclusion of productivity costs contributes to an analysis of the societal burden of smoking. A sensitivity analysis is undertaken to assess productivity costs on the basis of the friction cost approach. Results PVLE estimates were higher for certain subpopulations, such as men, younger people, and people in developed countries. In the case study, productivity cost estimates from our model showed that productivity loss was a substantial share of the total cost burden of premature mortality due to smoking, accounting for over 75 % of total lifetime costs in the United States and 67 % of total lifetime costs in Brazil. Productivity costs were much lower using the friction cost approach among those of working age. Conclusions Our PVLE model is a novel tool allowing researchers to incorporate the value of lost productivity due to premature mortality into economic analyses of treatments for diseases or health interventions. We provide PVLE estimates for a number of emerging and developed countries. Including productivity costs in a health economics study allows for a more comprehensive analysis, and, as demonstrated by our illustration, can have important effects on the results and conclusions.

IntroductionUterine serous carcinoma (USC) accounts for 40% of endometrial cancer-related deaths. The standard of care for stages III and IV USC yields a 20%–30% survival at 2 years and a 10%–20% survival at 3–5 years. Recent advances in the second-line treatment of advanced or recurrent USC are rapidly evolving. Targeted therapeutic approaches with the use of lenvatinib plus pembrolizumab, as well as the use of trastuzumab deruxtecan, offer new hope for successful second-line therapies for patients. However, further investigation into novel targeted therapeutic approaches is warranted, given the high burden of disease associated with this aggressive histological subtype. USC shares clinical and genomic similarities with epithelial ovarian cancer, suggesting a correlation with ‘BRCAness’. Niraparib, a potent PARP1 and PARP2 inhibitor, was shown to have a positive impact on platinum-sensitive recurrent ovarian cancer, regardless of the presence or absence of BRCA status. Our hypothesis is that patients with stage III, stage IV and platinum-sensitive recurrent USC receiving niraparib maintenance in addition to standard therapy for USC may have an improved progression-free survival.Methods and analysisParticipating sites include the primary site, Northwell Health Zucker Cancer Centre, and secondary site, Rutgers Cancer Institute of NJ. Females over the age of 18 with stage III, stage IV or platinum-sensitive recurrent USC will be recruited and enrolled based on inclusion/exclusion criteria. 24 subjects will be enrolled during phase 1 and 21 subjects will be enrolled during phase 2, over a total of 3 years. Patients will receive an individualised dose of niraparib daily every 28 days per cycle for 1 year or until progression of disease. Follow-up of disease status will continue for 5 years poststudy treatment. This phase II clinical trial will employ a Simon two-stage minimax design to test the null hypothesis that the 1 year response rate is <20% versus the alternative hypothesis that the 1 year response rate is ≥40%, with alpha=0.05 and power=0.90.Ethics and disseminationEthical approval was granted by Northwell Health Cancer Institute institutional review board (reference number: 19–0380) and PRMS. Alongside journal publications, results will be available publicly on completion of the study as approved by the sponsor investigator.Trial registration numberNCTN04080284

Background Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics. Methods De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple subgroup analyses were conducted across patient demographic and clinical characteristics to examine any heterogeneity in treatment effects. Results Following matching, 440,599 new users of SGLT-2i and oGLDs were included in each group. Mean follow-up time was 396 days for SGLT-2i initiation and 406 days for oGLDs initiation. SGLT-2i initiation was associated with a lower risk of HHF (HR: 0.66, 95%CI 0.58–0.75; p < 0.001), ACD (HR: 0.52, 95%CI 0.45–0.60; p < 0.001), the composite of HHF or ACD (HR: 0.60, 95%CI 0.53–0.68; p < 0.001), MI (HR: 0.85, 95%CI 0.78–0.92; p < 0.001), and stroke (HR: 0.78, 95%CI 0.72–0.85; p < 0.001); regardless of patient characteristics, including established cardiovascular disease, or geographic region. Conclusions This CVD-REAL study extends the findings from the SGLT-2i clinical trials to the broader setting of an ethnically and geographically diverse population, and across multiple subgroups. Trial registration NCT02993614

The clinical and histological findings are described of a patient who presented with the nephrotic syndrome and was found at necropsy to have a bronchial carcinoma. Amyloidosis, renal vein thrombosis, and neoplastic infiltration of the kidneys were excluded. The kidneys showed a diffuse glomerulonephritis of mesangiocapillary type. The possible aetiological association between these two conditions is discussed.

The Pediatrician’s LamentWith U.S. politics threatening to erase the gains of science, reduce access to vaccines, and undermine their vast public health benefit, what is a conscientious pediatrician to do?

The members of the E Street Band have changed in the last five decades. Perhaps we would find ease by viewing loss as the price paid for the privilege of patient care, rather than a system failure. Brooks D. Bruce Springsteen and the Art of Aging Well.

Several fourth-year medical students had gathered in a classroom to learn more about the pediatric residency program he represented. Determined to return to my home city, where the pearl-less residency program was located, I was deliberately unoffended. Inappropriate, however, is in the eye of the beholder. Because wardrobe, unlike gender and race, are choices, we feel entitled to lean into our biases. Someday, I tell her, she will be in a position of power and no longer need to consider these issues.