Predictive accuracy of risk prediction models for recurrence, metastasis and survival for early-stage cutaneous melanoma: a systematic review.

OBJECTIVES: To identify prognostic models for melanoma survival, recurrence and metastasis among American Joint Committee on Cancer stage I and II patients postsurgery; and evaluate model performance, including overall survival (OS) prediction. DESIGN: Systematic review and narrative synthesis. DATA SOURCES: Searched MEDLINE, Embase, CINAHL, Cochrane Library, Science Citation Index and grey literature sources including cancer and guideline websites from 2000 to September 2021. ELIGIBILITY CRITERIA: Included studies on risk prediction models for stage I and II melanoma in adults ≥18 years. Outcomes included OS, recurrence, metastases and model performance. No language or country of publication restrictions were applied. DATA EXTRACTION AND SYNTHESIS: Two pairs of reviewers independently screened studies, extracted data and assessed the risk of bias using the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies checklist and the Prediction study Risk of Bias Assessment Tool. Heterogeneous predictors prevented statistical synthesis. RESULTS: From 28 967 records, 15 studies reporting 20 models were included; 8 (stage I), 2 (stage II), 7 (stages I-II) and 7 (stages not reported), but were clearly applicable to early stages. Clinicopathological predictors per model ranged from 3-10. The most common were: ulceration, Breslow thickness/depth, sociodemographic status and site. Where reported, discriminatory values were ≥0.7. Calibration measures showed good matches between predicted and observed rates. None of the studies assessed clinical usefulness of the models. Risk of bias was high in eight models, unclear in nine and low in three. Seven models were internally and externally cross-validated, six models were externally validated and eight models were internally validated. CONCLUSIONS: All models are effective in their predictive performance, however the low quality of the evidence raises concern as to whether current follow-up recommendations following surgical treatment is adequate. Future models should incorporate biomarkers for improved accuracy. PROSPERO REGISTRATION NUMBER: CRD42018086784.

Evaluating high-cost technologies - no need to throw the baby out with the bathwater.

INTRODUCTION: Evidence generation for the health technology assessment (HTA) of a new technology is a long and expensive process with no guarantees that the health technology will be adopted and implemented into a health-care system. This would suggest that there is a greater risk of failure for a company developing a high-cost technology and therefore incentives (such as increasing the funding available for research or additional market exclusivity) may be needed to encourage development of such technologies as has been seen with many high-cost orphan drugs. AREAS COVERED: This paper discusses some of the key issues relating to the evaluation of high-cost technologies through the use of existing HTA processes and what the challenges will be going forward. EXPERT OPINION: We propose that while the current HTA process is robust, its evolution into accommodating the incorporation of real-world data and evidence alongside a life-cycle HTA approach should better enable developers to produce the evidence required on effectiveness and cost-effectiveness. This should lead to reduced decision uncertainty for HTA agencies to make adoption decisions in a more timely and efficient manner. Furthermore, budget impact analysis remains important in understanding the actual financial impact on health-care systems and budgets outside of the cost-effectiveness framework used to aid decision-making.

Systematic review of economic evaluations of aromatase inhibitors in estrogen receptor-positive breast cancer: quality evaluation.

BACKGROUND: Breast cancer (BC) is a leading cause of premature death in women and the most expensive malignancy to treat. Since the introduction of targeted therapies has resulted in changes to BC therapy practices, health economic evaluations have become more important in this area. Taking generic medications, Aromatase Inhibitors (AIs), as a case study, we conducted a systematic review of the recent economic evaluations of AIs for estrogen receptor-positive breast cancer patients and evaluated the quality of these health economic studies. OBJECTIVE: To systematically review and examine the quality of the available economic studies of AIs in estrogen receptor-positive breast cancer. METHODS: A literature search was performed using six relevant databases (MEDLINE, Embase, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, NHS Economic Evaluation Database, and SCOPUS) from January 2010 to July 2021. All economic studies were independently assessed by two reviewers using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist to evaluate the quality of the economic evaluations. This systematic review is registered in the PROSPERO database. To compare the different currencies used in these studies, all costs were converted to international dollars (2021). RESULTS: A total of eight studies were included in the review; six (75%) were performed from the healthcare providers' perspective. They were conducted in seven different countries, and all were model-based analyses using Markov models. Six (75%) considered both Quality Adjusted Life Years (QALYs) and Life Years (LY) outcomes, and all costs were derived from national databases. When compared to tamoxifen, AIs were generally cost-effective in postmenopausal women. Only half of the studies addressed the increased mortality following adverse events, and none mentioned medication adherence. For the quality assessment, six studies fulfilled 85% of the CHEERS checklist requirements and are deemed good quality. CONCLUSION: AIs are generally considered cost-effective compared to tamoxifen in estrogen receptor-positive breast cancer. The overall quality of the included studies was between high and average but characterizing heterogeneity, and distributional effects should be considered in any future economic evaluation studies of AIs. Studies should include adherence and adverse effects profiles to provide evidence to facilitate decision-making among policymakers.

Abemaciclib in Combination with Endocrine Therapy for Adjuvant Treatment of Hormone Receptor-Positive, HER2-Negative, Node-Positive Early Breast Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Eli Lilly) of abemaciclib (Verzenios) to submit evidence for the clinical and cost effectiveness of this drug in combination with endocrine therapy (ET) for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive early breast cancer at high risk of recurrence, as part of the Institute's Single Technology Appraisal (STA) process. Kleijnen Systematic Reviews Ltd, in combination with Newcastle University, was commissioned to act as the independent Evidence Review Group (ERG). This paper summarised the Company Submission (CS), presents the ERG's critical review of the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations, and describes the development of the NICE guidance by the Appraisal Committee. The ERG produced a critical review of the evidence for the clinical and cost-effectiveness evidence in the CS and also independently searched for relevant evidence and modified the manufacturer decision analytic model to examine the impact of altering some of the key assumptions. A systematic literature review identified the MonarchE trial, an ongoing, open-label, randomised, double blind trial involving 5637 people comparing abemaciclib in combination with ET versus ET alone. The trial included two cohorts that used different inclusion criteria to define high risk of recurrence. The ERG considered Cohort 1 as an adequate representation of this population and the AC concluded that Cohort 1 was generalisable to National Health Service clinical practice. Trial results showed improvements in invasive disease-free survival for the abemaciclib arm, which was considered an appropriate surrogate outcome. The ERG believed that the modelling structure presented in the de novo economic model by the company was appropriate but highlighted several areas of uncertainty that had the potential to have a significant impact on the resulting incremental cost-effectiveness ratio (ICER). Areas of uncertainty included the extrapolation of long-term survival curves, the duration of treatment effect and treatment waning, and the proportion of patients who receive other CDK4/6 treatments for metastatic disease after receiving abemaciclib. ICER estimates were £9164 per quality-adjusted life-year gained for the company's base-case and £17,810 for the ERG's base-case. NICE recommended abemaciclib with ET as an option for the adjuvant treatment of HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence.

Time for consensus on "high-risk" - Sentinel lymph node biopsy for cutaneous squamous cell carcinoma: An international survey of skin cancer specialists and a literature update.

There is an urgent need for evidence-based management of cutaneous squamous cell carcinoma (cSCC), particularly "high-risk" tumours. We performed an online survey of skin cancer specialists to assess cSCC research priorities. Respondents were targeted via the international Skin Cancer OUTcomes consortium (SCOUT) and the UK regional Skin Cancer Outcomes North-East (SCONE) research interest group. Thirty-three respondents completed the survey ([46%; 16/33] were non-UK based). 'Defining a role for sentinel lymph node biopsy (SLNB) in high-risk cSCC' was most commonly ranked either 1st or 2nd research priority by respondents (55%; 18/33), with near-total consensus that SLNB could be useful for the early identification of nodal metastasis in high-risk cSCC (97%; 30/31). On this specific research priority, 24 studies with longitudinal follow-up data were identified. Cumulatively, SLNB for cSCC had positivity and false omission rates of 7.0% and 3.1%, respectively, with false negative rates of 29.0%. Given the lack of consensus on a definition of "high-risk" cSCC, it was unsurprising that only two studies of SLNB for head & neck cSCC utilised comparable selection criteria; reporting the highest positivity rates (8.0%) and lowest false-omission rates (2.4%) and false-negative rates (21.4%) overall. There is multi-disciplinary interest in the role of SLNB for "high-risk" cSCC. It appears to perform best in head and neck cases. A consensus definition of "high-risk" cSCC is urgently required to refine the utility of SLNB and guide risk-directed management.

Optimal Surveillance Strategies for Early-Stage Cutaneous Melanoma Post Primary Tumor Excision: An Economic Evaluation.

Background. Consensus on standardized active surveillance or follow-up care by clinicians is lacking leading to considerable variation in practice across countries. An important structural modelling consideration is that self-examination by patients and their partners can detect melanoma recurrence outside of active surveillance regimes. Objectives. To identify candidate melanoma surveillance strategies for American Joint Committee on Cancer (AJCC) stage I disease and compare them with the current recommended practice in a cost-utility analysis framework. Methods. In consultation with UK clinical experts, a microsimulation model was built in TreeAge Pro 2019 R1.0 (Williamstown, MA, USA) to evaluate surveillance strategies for AJCC stage IA and IB melanoma patients separately. The model incorporated patient behaviors such as self-detection and emergency visits to examine suspicious lesions. A National Health Service (NHS) perspective was taken. Model input parameters were taken from the literature and where data were not available, local expert opinion was sought. Probabilistic sensitivity analysis, one-way sensitivity analysis on pertinent parameters and value of information was performed. Results. In the base-case probabilistic sensitivity analysis, less intensive surveillance strategies for AJCC stage IA and IB had lower total lifetime costs than the current National Institute for Health and Care Excellence (NICE) recommended strategy with similar effectiveness in terms of quality-adjusted life years and thereby likely to be cost-effective. Many strategies had similar effectiveness due to the relatively low chance of recurrence and the high rate of self-detection. Sensitivity and scenario analyses did not change these findings. Conclusions. Our model findings suggest that less resource intensive surveillance may be cost-effective compared with the current NICE surveillance guidelines. However, to advocate convincingly for changes, better evidence is required.

Combination therapies for COVID-19: An overview of the clinical trials landscape.

The COVID-19 pandemic has driven an unprecedented level of global activity in drug discovery and clinical development for effective therapeutics targeting the coronavirus disease. There are currently 744 therapeutics being tested in 2879 clinical trials globally. Almost 90% of these clinical trials are focused on monotherapies. Combination therapies are the mainstay of antiviral therapeutics to increase the potency of the individual compounds and to combat the rapid evolution of resistance, although combination therapies have inherently complex clinical and regulatory development challenges. Increased understanding of the SARS-CoV-2 lifecycle and COVID-19 pathology provides a scientific rationale for evaluating the effectiveness of different combinations. In this paper, we provide an overview of the current clinical trial landscape for combination therapeutics targeting COVID-19 through weekly scanning of national and international clinical trial registries. Our analysis delves specifically into dual combination therapies in what can be defined as "pivotal clinical trials" (active, randomised, controlled and at least phase II), with a focus on new and repurposed therapeutic candidates that have shown positive signals and/or been granted authorisation for emergency use based on positive efficacy and safety data.

Optimal surveillance strategies for patients with stage 1 cutaneous melanoma post primary tumour excision: three systematic reviews and an economic model.

BACKGROUND: Malignant melanoma is the fifth most common cancer in the UK, with rates continuing to rise, resulting in considerable burden to patients and the NHS. OBJECTIVES: The objectives were to evaluate the effectiveness and cost-effectiveness of current and alternative follow-up strategies for stage IA and IB melanoma. REVIEW METHODS: Three systematic reviews were conducted. (1) The effectiveness of surveillance strategies. Outcomes were detection of new primaries, recurrences, metastases and survival. Risk of bias was assessed using the Cochrane Collaboration's Risk-of-Bias 2.0 tool. (2) Prediction models to stratify by risk of recurrence, metastases and survival. Model performance was assessed by study-reported measures of discrimination (e.g. D-statistic, Harrel's c-statistic), calibration (e.g. the Hosmer-Lemeshow 'goodness-of-fit' test) or overall performance (e.g. Brier score, R2). Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). (3) Diagnostic test accuracy of fine-needle biopsy and ultrasonography. Outcomes were detection of new primaries, recurrences, metastases and overall survival. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Review data and data from elsewhere were used to model the cost-effectiveness of alternative surveillance strategies and the value of further research. RESULTS: (1) The surveillance review included one randomised controlled trial. There was no evidence of a difference in new primary or recurrence detected (risk ratio 0.75, 95% confidence interval 0.43 to 1.31). Risk of bias was considered to be of some concern. Certainty of the evidence was low. (2) Eleven risk prediction models were identified. Discrimination measures were reported for six models, with the area under the operating curve ranging from 0.59 to 0.88. Three models reported calibration measures, with coefficients of ≥ 0.88. Overall performance was reported by two models. In one, the Brier score was slightly better than the American Joint Committee on Cancer scheme score. The other reported an R2 of 0.47 (95% confidence interval 0.45 to 0.49). All studies were judged to have a high risk of bias. (3) The diagnostic test accuracy review identified two studies. One study considered fine-needle biopsy and the other considered ultrasonography. The sensitivity and specificity for fine-needle biopsy were 0.94 (95% confidence interval 0.90 to 0.97) and 0.95 (95% confidence interval 0.90 to 0.97), respectively. For ultrasonography, sensitivity and specificity were 1.00 (95% confidence interval 0.03 to 1.00) and 0.99 (95% confidence interval 0.96 to 0.99), respectively. For the reference standards and flow and timing domains, the risk of bias was rated as being high for both studies. The cost-effectiveness results suggest that, over a lifetime, less intensive surveillance than recommended by the National Institute for Health and Care Excellence might be worthwhile. There was considerable uncertainty. Improving the diagnostic performance of cancer nurse specialists and introducing a risk prediction tool could be promising. Further research on transition probabilities between different stages of melanoma and on improving diagnostic accuracy would be of most value. LIMITATIONS: Overall, few data of limited quality were available, and these related to earlier versions of the American Joint Committee on Cancer staging. Consequently, there was considerable uncertainty in the economic evaluation. CONCLUSIONS: Despite adoption of rigorous methods, too few data are available to justify changes to the National Institute for Health and Care Excellence recommendations on surveillance. However, alternative strategies warrant further research, specifically on improving estimates of incidence, progression of recurrent disease; diagnostic accuracy and health-related quality of life; developing and evaluating risk stratification tools; and understanding patient preferences. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018086784. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol 25, No. 64. See the NIHR Journals Library website for further project information.

Malignant melanoma is the deadliest of skin cancers; in the UK, > 2500 people die from it every year. Initially, the cancer is removed surgically, which cures it for most people, but, for some, the cancer returns. For this reason, after a melanoma is removed, patients are followed up to see if the melanoma reoccurs or if new melanomas have developed. It is felt that early cancer detection improves the chance of future treatment working. A key question is how best to follow up patients after initial melanoma surgery. This study concentrates on the earliest stage of melanoma (American Joint Committee on Cancer stage I), which accounts for more than 7 out of 10 of all melanoma diagnoses. The study also investigates if new ways of follow-up could be at least as good as current practice and a better use of NHS money. We systematically reviewed studies comparing different ways of organising follow-up, and then methods to identify those patients at high risk of developing a further melanoma and how good different tests are at detecting this cancer. We then compared different possible follow-up strategies. For each strategy, we considered its impact on quality and length of life, and how well it used NHS resources. We found little evidence to support a change in how follow-up should be organised currently. There were some ways of organising follow-up that might be better than current care, but further research is needed. We found that new research on whether or not follow-up should be performed by a cancer nurse specialist, rather than a dermatologist or surgeon, would be worthwhile. We also found that more research could be worthwhile on how frequently melanoma recurs and spreads, as well as how accurately a diagnosis of further cancer is made and how to identify those most at risk of further melanoma spread.

Leisure time physical activity throughout adulthood is associated with lower medicare costs: evidence from the linked NIH-AARP diet and health study cohort.

BACKGROUND: There is limited information about the association between long-term leisure time physical activity (LTPA) participation and healthcare costs. The purpose of this study was to investigate the association between LTPA over adulthood with later life healthcare costs in the USA. METHODS: Using Medicare claims data (between 1999 and 2008) linked to the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, we examined associations between nine trajectories of physical activity participation throughout adulthood with Medicare costs. RESULTS: Compared with adults who were consistently inactive from adolescence into middle age, average annual healthcare costs were significantly lower for maintainers, adults who maintained moderate (-US$1350 (95% CI: -US$2009 to -US$690) or -15.9% (95% CI: -23.6% to -8.1%)) or high physical activity levels (-US$1200 (95% CI: -US$1777 to -US$622) or -14.1% (95% CI: -20.9% to -7.3%)) and increasers, adults who increased physical activity levels in early adulthood (-US$1874 (95% CI: US$2691 to -US$1057) or -22.0% (95% CI: -31.6% to -12.4%)) or in middle age (-US$824 (95% CI: -US$1580 to -US$69 or -9.7% (95% CI -18.6% to -0.8%)). For the four trajectories where physical activity decreased, the only significant difference was for adults who increased physical activity levels during early adulthood with a decline in middle age (-US$861 (95% CI:-US$1678 to -US$45) or -10.1% (95% CI: -19.7% to -0.5%)). CONCLUSION: Our analyses suggest the healthcare cost burden in later life could be reduced through promotion efforts supporting physical activity participation throughout adulthood.

Effects of Primary Biliary Cholangitis on Quality of Life and Health Care Costs in the United Kingdom.

BACKGROUND & AIMS: There have been few high-quality studies of the costs, preference-based health-related quality of life (HRQoL) and cost effectiveness of treatments for primary biliary cholangitis (PBC). We aimed to estimate the marginal effects of PBC complications and symptoms, accounting for treatment, on HRQoL and the annual cost of health care in the United Kingdom (UK). These are essential components for evaluation of cost effectiveness and this information will aid in evaluation of new treatments. METHODS: Questionnaires were mailed to 4583 participants in the UK-PBC research cohort and data were collected on HRQoL and use of the National Health Service (NHS) in the UK from 2015 through 2016. HRQoL was measured using the EQ-5D-5L instrument. The annual cost of resource use was calculated using unit costs obtained from NHS sources. We performed econometric analyses to determine the effects of treatment, symptoms, complications, liver transplantation status, and patient characteristics on HRQoL and annual costs. RESULTS: In an analysis of data from 2240 participants (over 10% of all UK PBC patients), we found that PBC symptoms have a considerable effect on HRQoL. Ursodeoxycholic acid therapy was associated with significantly higher HRQoL regardless of response status. Having had a liver transplant and ascites were also independently associated with reduced HRQoL. Having had a liver transplant (US$4294) and esophageal varices (US$3401) were the factors with the two greatest mean annual costs to the NHS. Symptoms were not independently associated with cost but were associated with reduction in HRQoL for patients, indicating the lack of effective treatments for PBC symptoms. CONCLUSIONS: In an analysis of data from 2240 participants in the UK PBC, we found that HRQoL and cost estimates provide greater insight into the relative importance of PBC-related symptoms and complications. These findings provide estimates for health technology assessments of new treatments for PBC.

Secondary transfer of emergency stroke patients eligible for mechanical thrombectomy by air in rural England: economic evaluation and considerations.

BACKGROUND: Mechanical thrombectomy (MT) is a time-sensitive emergency procedure for patients who had ischaemic stroke leading to improved health outcomes. Health systems need to ensure that MT is delivered to as many patients as quickly as possible. Using decision modelling, we aimed to evaluate the cost-effectiveness of secondary transfer by helicopter emergency medical services (HEMS) compared with ground emergency medical services (GEMS) of rural patients eligible for MT in England. METHODS: The model consisted of (1) a short-run decision tree with two branches, representing secondary transfer transportation strategies and (2) a long-run Markov model for a theoretical population of rural patients with a confirmed ischaemic stroke. Strategies were compared by lifetime costs: quality-adjusted life years (QALYs), incremental cost per QALY gained and net monetary benefit. Sensitivity and scenario analyses explored uncertainty around parameter values. RESULTS: We used the base case of early-presenting (<6 hours to arterial puncture) patient aged 75 years who had stroke to compare HEMS and GEMS. This produced an incremental cost-effectiveness ratio (ICER) of £28 027 when a 60 min reduction in travel time was assumed. Scenario analyses showed the importance of the reduction in travel time and futile transfers in lowering ICERs. For late presenting (>6 hours to arterial puncture), ground transportation is the dominant strategy. CONCLUSION: Our model indicates that using HEMS to transfer patients who had stroke eligible for MT from remote hospitals in England may be cost-effective when: travel time is reduced by at least 60 min compared with GEMS, and a £30 000/QALY threshold is used for decision-making. However, several other logistic considerations may impact on the use of air transportation.

The COVID-19 pandemic in Ireland: An overview of the health service and economic policy response.

OBJECTIVES: To outline the situation in Ireland with regard to the COVID-19 pandemic. METHODS: Analyse the evolution of the COVID-19 pandemic in Ireland. Review the key public health and health system responses. RESULTS: Over 1700 people have died with COVID-19 by July 19th while almost 3000 people had been admitted to hospital with COVID-19. A high proportion of the deaths occurred in nursing homes and other residential centres who did not receive sufficient attention during the early phase of the pandemic. CONCLUSIONS: Ireland's response to the COVID-19 crisis has been comprehensive and timely. Transparency, a commitment to a relatively open data policy, the use of traditional and social media to inform the population, and the frequency of updates from the Department of Health and the Health Services Executive are all commendable and have led to a high level of compliance among the general public with the various non-medical measures introduced by the government.

Cancer-Attributable Medical Costs for Colorectal Cancer Patients by Phases of Care: What Is the Effect of a Prior Cancer History?

Medical care costing studies have excluded patients with a prior cancer history. This study aims to update methods for estimating medical care costs attributable to cancer and to evaluate the effect of a prior history of cancer on costs for colorectal cancer (CRC) patients. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data and matched cancer patients to controls without cancer to estimate cancer-attributable costs by phases of care using Medicare 2007-2013 claims. CRC annualized average cancer-attributable costs were $56.0 K, $5.3 K, $92.5 K, and $24.3 K in the initial, continuing, and end-of-life cancer and noncancer death phases, respectively, in 2014 dollars. Costs were higher for patients diagnosed with more advanced stage, younger ages, and nonwhite races. Costs for patients with prior cancers were consistently higher than patients without prior cancers, especially in the continuing (4.9 K vs 7.2 K) and end-of-life noncancer death (22.7 K vs 30.0 K). Our CRC costs improve previous estimates by using more recent data and updated methods.

Patterns of Care and Costs for Older Patients With Colorectal Cancer at the End of Life: Descriptive Study of the United States and Canada.

PURPOSE: End-of-life (EOL) cancer care is costly, with challenges regarding intensity and place of care. We described EOL care and costs for patients with colorectal cancer (CRC) in the United States and the province of Ontario, Canada, to inform better care delivery. METHODS: Patients diagnosed with CRC from 2007 to 2013, who died of any cancer from 2007 to 2013 at age ≥ 66 years, were selected from the US SEER cancer registries linked to Medicare claims (n = 16,565) and the Ontario Cancer Registry linked to administrative health data (n = 6,587). We estimated total and resource-specific costs (2015 US dollars) from public payer perspectives over the last 360 days of life by 30-day periods, by stage at diagnosis (0-II, III, IV). RESULTS: In all months, especially 30 days before death, higher percentages of SEER-Medicare than Ontario patients received chemotherapy (15.7% v 8.0%), and imaging tests (39.4% v 31.1%). A higher percentage of Ontario patients were hospitalized (62.5% v 51.0%), but 43.2% of hospitalized SEER-Medicare patients had intensive care unit (ICU) admissions versus 17.9% of hospitalized Ontario patients. Cost differences between cohorts were greater for patients with stage IV disease. In the last 30 days, mean total costs for patients with stage IV disease were $15,881 (SEER-Medicare) and $12,034 (Ontario) versus $19,354 and $17,312 for stage 0-II. Hospitalization costs were higher for SEER-Medicare patients ($11,180 v $9,434), with lower daily hospital costs in Ontario ($1,067 v $2,004). CONCLUSION: These findings suggest opportunities for reducing chemotherapy and ICU use in the United States and hospitalizations in Ontario.

Estimating the effectiveness and cost-effectiveness of establishing additional endovascular Thrombectomy stroke Centres in England: a discrete event simulation.

BACKGROUND: We have previously modelled that the optimal number of comprehensive stroke centres (CSC) providing endovascular thrombectomy (EVT) in England would be 30 (net 6 new centres). We now estimate the relative effectiveness and cost-effectiveness of increasing the number of centres from 24 to 30. METHODS: We constructed a discrete event simulation (DES) to estimate the effectiveness and lifetime cost-effectiveness (from a payer perspective) using 1 year's incidence of stroke in England. 2000 iterations of the simulation were performed comparing baseline 24 centres to 30. RESULTS: Of 80,800 patients admitted to hospital with acute stroke/year, 21,740 would be affected by the service reconfiguration. The median time to treatment for eligible early presenters (< 270 min since onset) would reduce from 195 (IQR 155-249) to 165 (IQR 105-224) minutes. Our model predicts reconfiguration would mean an additional 33 independent patients (modified Rankin scale [mRS] 0-1) and 30 fewer dependent/dead patients (mRS 3-6) per year. The net addition of 6 centres generates 190 QALYs (95%CI - 6 to 399) and results in net savings to the healthcare system of £1,864,000/year (95% CI -1,204,000 to £5,017,000). The estimated budget impact was a saving of £980,000 in year 1 and £7.07 million in years 2 to 5. CONCLUSION: Changes in acute stroke service configuration will produce clinical and cost benefits when the time taken for patients to receive treatment is reduced. Benefits are highly likely to be cost saving over 5 years before any capital investment above £8 million is required.

Association of Leisure-Time Physical Activity Across the Adult Life Course With All-Cause and Cause-Specific Mortality.

Importance: Although the benefits of leisure-time physical activity (LTPA) in middle age are established, the health effects of long-term participation and changes in LTPA between adolescence and middle age have not been documented. Objective: To determine whether an association exists between LTPA life course patterns and mortality. Design, Setting, and Participants: This prospective cohort study used data from the National Institutes of Health-AARP (formerly American Association of Retired Persons) Diet and Health Study established in 1995 to 1996. Data analysis was conducted from March 2017 through February 2018. Data were analyzed for 315 059 adult AARP members living in 6 states, namely, California, Florida, Louisiana, New Jersey, North Carolina, or Pennsylvania, or 2 metropolitan areas, Atlanta, Georgia, or Detroit, Michigan. Exposures: Self-reported LTPA (hours per week) at the baseline interview for ages grouped as 15 to 18, 19 to 29, 35 to 39, and 40 to 61 years. Main Outcomes and Measures: All-cause, cardiovascular disease (CVD)-related, and cancer-related mortality records available through December 31, 2011. Results: Of 315 059 participants, 183 451 (58.2%) were men, and the participants were 50 to 71 years of age at enrollment. Ten LTPA trajectories (categorized as maintaining, increasing, and decreasing LTPA across time) were identified, and 71 377 deaths due to all causes, 22 219 deaths due to CVD, and 16 388 deaths due to cancer occurred. Compared with participants who were consistently inactive throughout adulthood, participants who maintained the highest amount of LTPA in each age period were at lower risks for all-cause, CVD-related, and cancer-related mortality. For example, compared with participants who were consistently inactive, maintaining higher amounts of LTPA was associated with lower all-cause (hazard ratio [HR], 0.64; 95% CI, 0.60-0.68), CVD-related (HR, 0.58; 95% CI, 0.53-0.64), and cancer-related (HR, 0.86; 95% CI, 0.77-0.97) mortality. Adults who were less active throughout most of the adult life course but increased LTPA in later adulthood (40-61 years of age) also had lower risk for all-cause (HR, 0.65; 95% CI, 0.62-0.68), CVD-related (HR, 0.57; 95% CI, 0.53-0.61), and cancer-related (HR, 0.84; 95% CI, 0.77-0.92) mortality. Conclusions and Relevance: Maintaining higher LTPA levels and increasing LTPA in later adulthood were associated with comparable low risk of mortality, suggesting that midlife is not too late to start physical activity. Inactive adults may be encouraged to be more active, whereas young adults who are already active may strive to maintain their activity level as they get older.

Recommendations for Research and Practice to Improve Work Outcomes Among Cancer Survivors.

Major knowledge gaps limit the development and implementation of interventions to improve employment outcomes among people with cancer. To identify research priorities to improve employment outcomes after cancer, the National Cancer Institute sponsored the meeting "Evidence-Based Approaches for Optimizing Employment Outcomes among Cancer Survivors." This article describes research recommendations stemming from the meeting. At the patient level, longitudinal studies are needed to better understand how patient sociodemographic and clinical characteristics and their experiences at work shape employment outcomes. Interventions that mitigate the impact of cancer and its treatment on employment are critical. At the provider-level, future research is needed to characterize the extent to which physicians and other healthcare providers talk to their patients about employment concerns and how that information is used to inform care. Additionally, there is a need to test models of care delivery that support routine screening of employment concerns, the capture of employment outcomes in electronic health records, and the effective use of this information to improve care. At the employer level, evidence-based training programs are needed to prepare supervisors, managers, human resources staff, and occupational health professionals to address health issues in the workplace; and future interventions are needed to improve patient -employer communication and facilitate workplace accommodations. Importantly, research is needed that reflects the perspectives and priorities of patients and their families, providers and healthcare systems, and employers. Transdisciplinary partnerships and stakeholder engagement are essential to ensure that employment-focused interventions and policies are developed, implemented, and sustained in real-world healthcare delivery and workplace settings.

Impact of sociodemographic characteristics on underemployment in a longitudinal, nationally representative study of cancer survivors: Evidence for the importance of gender and marital status.

BACKGROUND: We examined the longitudinal association between sociodemographic factors and an expanded definition of underemployment among those with and without cancer history in the United States. METHODS: Medical Expenditure Panel Survey data (2007-2013) were used in multivariable regression analyses to compare employment status between baseline and two-year follow-up among adults aged 25-62 years at baseline (n = 1,614 with and n = 39,324 without cancer). Underemployment was defined as becoming/staying unemployed, changing from full to part-time, or reducing part-time work significantly. Interaction effects between cancer history/time since diagnosis and predictors known to be associated with employment patterns, including age, gender/marital status, education, and health insurance status at baseline were modeled. RESULTS: Approximately 25% of cancer survivors and 21% of individuals without cancer reported underemployment at follow-up (p = 0.002). Multivariable analyses indicated that those with a cancer history report underemployment more frequently (24.7%) than those without cancer (21.4%, p = 0.002) with underemployment rates increasing with time since cancer diagnosis. A significant interaction between gender/marital status and cancer history and underemployment was found (p = 0.0004). There were no other significant interactions. Married female survivors diagnosed >10 years ago reported underemployment most commonly (38.7%), and married men without cancer reported underemployment most infrequently (14.0%). A wider absolute difference in underemployment reports for married versus unmarried women as compared to married versus unmarried men was evident, with the widest difference apparent for unmarried versus married women diagnosed >10 years ago (18.1% vs. 38.7%). CONCLUSION: Cancer survivors are more likely to experience underemployment than those without cancer. Longer time since cancer diagnosis and gender/marital status are critical factors in predicting those at greatest risk of underemployment. The impact of cancer on work should be systematically studied across sociodemographic groups and recognized as a component of comprehensive survivorship care.