Real-World Treatment Patterns, Survival, and Costs for Ovarian Cancer in Canada: A Retrospective Cohort Study Using Provincial Administrative Data

Background: In 2020, approximately 3100 Canadian women were diagnosed with ovarian cancer (OC), with 1950 women dying of this disease. Prognosis for OC remains poor, with 70% to 75% of cases diagnosed at an advanced stage and an overall 5-year survival of 46%. Current standard of care in Canada involves a combination of cytoreductive surgery and platinum-based chemotherapy. Objective: There are few studies reporting current OC costs. This study sought to determine patient characteristics and costs to the health system for OC in Ontario, Canada. Methods: Women diagnosed with OC in Ontario between 2010 and 2017 were identified. The cohort was linked to provincial administrative databases to capture treatment patterns, survival, and costs. Overall total and mean cost per patient (unadjusted) were reported in 2017 Canadian dollars, using a macro-based costing methodology called GETCOST. It is programmed to determine the costs of short-term and long-term episodes of health-care resources utilized. Results: Of the 2539 OC patients included in the study, the mean age at diagnosis was 60.4±11.35 years. The majority were diagnosed with stage III disease (n=1247). The only treatment required for 74% of stage I patients and 54% of stage II patients was first-line (1L) platinum chemotherapy; in advanced stages (III/IV) 24% and 20%, respectively, did not receive further treatment after 1L therapy. The median overall survival (mOS) for the whole cohort was 5.13 years. Survival was highest in earlier stage disease (mOS not reached in stage I/II), and dropped significantly in advanced stage patients (stage III: mOS=4.09 years; stage IV: mOS=3.47 years). Overall mean costs in patients stage I were CAD $58 099 compared to CAD$124 202 in stage IV. Discussion: The majority of OC patients continue to be diagnosed with advanced disease, which is associated with poor survival and increased treatment costs. Increased awareness and screening could facilitate diagnosis of earlier stage disease and reduce high downstream costs for advanced disease. Conclusion: Advanced OC is associated with poor survival and increased costs, mainly driven by hospitalizations or cancer clinic visits. The introduction of new targeted therapies such as olaparib could impact health system costs, by offsetting higher downstream costs while also improving survival

Genetic and epigenetic profiling of BRCA1/2 in ovarian tumors reveals additive diagnostic yield and evidence of a genomic BRCA1/2 DNA methylation signature

Poly-ADP-ribose-polymerase inhibitor (PARPi) treatment is indicated for advanced-stage ovarian tumors with BRCA1/2 deficiency. The “BRCAness” status is thought to be attributed to a tumor phenotype associated with a specific epigenomic DNA methylation profile. Here, we examined the diagnostic impact of combined BRCA1/2 sequence, copy number, and promoter DNA methylation analysis, and evaluated whether genomic DNA methylation patterns can predict the BRCAness in ovarian tumors. DNA sequencing of 172 human tissue samples of advanced-stage ovarian adenocarcinoma identified 36 samples with a clinically significant tier 1/2 sequence variants (point mutations and in/dels) and 9 samples with a CNV causing a loss of function in BRCA1/2. DNA methylation analysis of the promoter of BRCA1/2 identified promoter hypermethylation of BRCA1 in two mutation-negative samples. Computational modeling of genome-wide methylation markers, measured using Infinium EPIC arrays, resulted in a total accuracy of 0.75, sensitivity: 0.83, specificity: 0.64, positive predictive value: 0.76, negative predictive value: 0.74, and area under the receiver’s operating curve (AUC): 0.77, in classifying tumors harboring a BRCA1/2 defect from the rest. These findings indicate that the assessment of CNV and promoter DNA methylation in BRCA1/2 increases the cumulative diagnostic yield by 10%, compared with the 20% yield achieved by sequence variant analysis alone. Genomic DNA methylation data can partially predict BRCAness in ovarian tumors; however, further investigation in expanded BRCA1/2 cohorts is needed, and the effect of other double strand DNA repair gene defects in these tumors warrants further investigations

Covariant description of inelastic electron--deuteron scattering:predictions of the relativistic impulse approximation

Using the covariant spectator theory and the transversity formalism, the unpolarized, coincidence cross section for deuteron electrodisintegration, $d(e,e'p)n$, is studied. The relativistic kinematics are reviewed, and simple theoretical formulae for the relativistic impulse approximation (RIA) are derived and discussed. Numerical predictions for the scattering in the high $Q^2$ region obtained from the RIA and five other approximations are presented and compared. We conclude that measurements of the unpolarized coincidence cross section and the asymmetry $A_\phi$, to an accuracy that will distinguish between different theoretical models, is feasible over most of the wide kinematic range accessible at Jefferson Lab.Comment: 54 pages and 24 figure

Validation of Aura Microwave Limb Sounder O-3 and CO observations in the upper troposphere and lower stratosphere

International audienceGlobal satellite observations of ozone and carbon monoxide from the Microwave Limb Sounder (MLS) on the EOS Aura spacecraft are discussed with emphasis on those observations in the 215–100 hPa region (the upper troposphere and lower stratosphere). The precision, resolution and accuracy of the data produced by the MLS “version 2.2” processing algorithms are discussed and quantified. O3 accuracy is estimated at ~40 ppbv +5% (~20 ppbv +20% at 215 hPa) while the CO accuracy is estimated at ~30 ppbv +30% for pressures of 147 hPa and less. Comparisons with expectations and other observations show good agreements for the O3 product, generally consistent with the systematic errors quoted above. In the case of CO, a persistent factor of ~2 high bias is seen at 215 hPa. However, the morphology is shown to be realistic, consistent with raw MLS radiance data, and useful for scientific study. The MLS CO data at higher altitudes are shown to be consistent with other observations

The protocols for the 10/66 dementia research group population-based research programme

BACKGROUND: Latin America, China and India are experiencing unprecedentedly rapid demographic ageing with an increasing number of people with dementia. The 10/66 Dementia Research Group's title refers to the 66% of people with dementia that live in developing countries and the less than one tenth of population-based research carried out in those settings. This paper describes the protocols for the 10/66 population-based and intervention studies that aim to redress this imbalance. METHODS/DESIGN: Cross-sectional comprehensive one phase surveys have been conducted of all residents aged 65 and over of geographically defined catchment areas in ten low and middle income countries (India, China, Nigeria, Cuba, Dominican Republic, Brazil, Venezuela, Mexico, Peru and Argentina), with a sample size of between 1000 and 3000 (generally 2000). Each of the studies uses the same core minimum data set with cross-culturally validated assessments (dementia diagnosis and subtypes, mental disorders, physical health, anthropometry, demographics, extensive non communicable disease risk factor questionnaires, disability/functioning, health service utilisation, care arrangements and caregiver strain). Nested within the population based studies is a randomised controlled trial of a caregiver intervention for people with dementia and their families (ISRCTN41039907; ISRCTN41062011; ISRCTN95135433; ISRCTN66355402; ISRCTN93378627; ISRCTN94921815). A follow up of 2.5 to 3.5 years will be conducted in 7 countries (China, Cuba, Dominican Republic, Venezuela, Mexico, Peru and Argentina) to assess risk factors for incident dementia, stroke and all cause and cause-specific mortality; verbal autopsy will be used to identify causes of death. DISCUSSION: The 10/66 DRG baseline population-based studies are nearly complete. The incidence phase will be completed in 2009. All investigators are committed to establish an anonymised file sharing archive with monitored public access. Our aim is to create an evidence base to empower advocacy, raise awareness about dementia, and ensure that the health and social care needs of older people are anticipated and met

Monsoons: global energetics and local physics as drivers of past, present and future monsoons

Global constraints on momentum and energy govern the structure of the zonal mean tropical circulation and rainfall. The continental-scale monsoon systems are also facets of a momentum- and energy-constrained global circulation, but their modern and paleo variability deviates substantially from that of the longitudinal mean through mechanisms neither fully understood nor well simulated. A framework grounded in global constraints yet encompassing the complexities of monsoon dynamics is needed to identify the causes of mismatch between theory, models, and observations and, ultimately, improve regional climate projection. In a first step towards this goal, disparate regional processes must be distilled into gross measures of energy flow in and out of continents and from the surface to the tropopause, so that monsoon dynamics may be coherently diagnosed across modern and paleo observations and across idealized and comprehensive simulations. Accounting for zonal asymmetries in the circulation, land/ocean differences in surface fluxes, and the character of convective systems, such a monsoon framework would integrate our understanding at all relevant scales: from the fine details of how moisture and energy are lifted in the updrafts of thunderclouds, up to the global circulations

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study

Background No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. Findings 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. Funding UK Research and Innovation and National Institute for Health Research