The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2.

BACKGROUND: Our study aimed to establish 'real-world' performance and cost-effectiveness of ovarian cancer (OC) surveillance in women with pathogenic germline BRCA1/2 variants who defer risk-reducing bilateral salpingo-oophorectomy (RRSO). METHODS: Our study recruited 875 female BRCA1/2-heterozygotes at 13 UK centres and via an online media campaign, with 767 undergoing at least one 4-monthly surveillance test with the Risk of Ovarian Cancer Algorithm (ROCA) test. Surveillance performance was calculated with modelling of occult cancers detected at RRSO. The incremental cost-effectiveness ratio (ICER) was calculated using Markov population cohort simulation. RESULTS: Our study identified 8 OCs during 1277 women screen years: 2 occult OCs at RRSO (both stage 1a), and 6 screen-detected; 3 of 6 (50%) were ≤stage 3a and 5 of 6 (83%) were completely surgically cytoreduced. Modelled sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for OC were 87.5% (95% CI, 47.3 to 99.7), 99.9% (99.9-100), 75% (34.9-96.8) and 99.9% (99.9-100), respectively. The predicted number of quality-adjusted life years (QALY) gained by surveillance was 0.179 with an ICER cost-saving of -£102,496/QALY. CONCLUSION: OC surveillance for women deferring RRSO in a 'real-world' setting is feasible and demonstrates similar performance to research trials; it down-stages OC, leading to a high complete cytoreduction rate and is cost-saving in the UK National Health Service (NHS) setting. While RRSO remains recommended management, ROCA-based surveillance may be considered for female BRCA-heterozygotes who are deferring such surgery.

Factors Influencing Motivation and Work Engagement of Healthcare Professionals.

Background: Low level of health professionals' work motivation is a critical challenge for countries' health care system. A survey of ministries of health in many countries showed that low motivation was seen as the second most important health workforce problem after staff shortages. Objective: The aim of the study was to examine in detail the factors which can affect motivation and work engagement, to assess the motivation levels of personnel working in public hospitals and to identify any differences between the various categories of healthcare professionals employed at the 1st Regional Health Authority of Attica. Methods: Frederick Herzberg's motivation-hygiene theory was used as the theoretical framework. Twelve phrases were used that correspond to intrinsic and extrinsic motivating factors, namely achievement, recognition, nature of work, responsibility, advancement, growth, organizational policies, supervision, interpersonal relationships, working conditions, salary and job security. Phrases 1-6 covered the internal motivators and 7-12 correspond to the external. Additional questions were added covering the socio-demographic characteristics of respondents. Results: The response rate was 81.95% and 3,278 questionnaires were collected. Findings suggest that extrinsic motivation factors have slightly higher mean scores (MS=8.30) than intrinsic motivation factors (7.81). The role of factors like salary (9.31), organizational policies (8.91), growth (8.89) and job security (8.86) was significant. However, every category of hospital staff is affected in a different way and degree by each factor. In periods of crisis, the need of extrinsic factors of motivation increased. Conclusions: Providing a motivating environment for employees becomes more fundamental in the healthcare system. Motivation of healthcare employees was affected by factors related to supervision, financial benefits, job training and growth. Efforts should be made to provide such benefits to health employees as appropriate especially, to those who did not get any such benefits. Officially recognizing best performance is suggested.

Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial.

BACKGROUND: Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS. METHODS: In this randomised controlled trial, postmenopausal women aged 50-74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032. FINDINGS: Between April 17, 2001, and Sept 29, 2005, of 1 243 282 women invited, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group. At a median follow-up of 16·3 years (IQR 15·1-17·3), 2055 women were diagnosed with tubal or ovarian cancer: 522 (1·0%) of 50 625 in the MMS group, 517 (1·0%) of 50 623 in the USS group, and 1016 (1·0%) of 101 314 in the no screening group. Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (-41·8 to -2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (-21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group. INTERPRETATION: The reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended. FUNDING: National Institute for Health Research, Cancer Research UK, and The Eve Appeal.

Hospital coordination and integration with social care in England: The effect on post-operative length of stay.

In spite of significant policy interest in improving the integration of health and social care services, little is known about the economics of coordination across the two sectors. We specify a Markov queuing model and use data collected from administrative records to estimate the link between two proxy indicators of across-sector complexity of discharge arrangements and post-operative length of stay in hospital for older people undergoing hip replacements. The results suggest that the number of local authorities involved in care planning and commissioning of social care services for discharges from a given hospital is significantly positively correlated with longer post-operative lengths of stay. A particularly strong effect is found between variability through time in the number of authorities involved in discharges from a given hospital and lengths of stay. The results suggest that improving information systems and joint assessment processes used during the discharge of patients with social care needs is likely to achieve significant efficiency gains in the health care system as a whole.

The cost-effectiveness of screening for ovarian cancer: results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

BACKGROUND: To assess the within-trial cost-effectiveness of an NHS ovarian cancer screening (OCS) programme using data from UKCTOCS and extrapolate results based on average life expectancy. METHODS: Within-trial economic evaluation of no screening (C) vs either (1) an annual OCS programme using transvaginal ultrasound (USS) or (2) an annual ovarian cancer multimodal screening programme with serum CA125 interpreted using a risk algorithm (ROCA) and transvaginal ultrasound as a second-line test (MMS), plus comparison of lifetime extrapolation of the no screening arm and the MMS programme using both a predictive and a Markov model. RESULTS: Using a CA125-ROCA cost of £20, the within-trial results show USS to be strictly dominated by MMS, with the MMS vs C comparison returning an incremental cost-effectiveness ratio (ICER) of £91 452 per life year gained (LYG). If the CA125-ROCA unit cost is reduced to £15, the ICER becomes £77 818 per LYG. Predictive extrapolation over the expected lifetime of the UKCTOCS women returns an ICER of £30 033 per LYG, while Markov modelling produces an ICER of £46 922 per QALY. CONCLUSION: Analysis suggests that, after accounting for the lead time required to establish full mortality benefits, a national OCS programme based on the MMS strategy quickly approaches the current NICE thresholds for cost-effectiveness when extrapolated out to lifetime as compared with the within-trial ICER estimates. Whether MMS could be recommended on economic grounds would depend on the confirmation and size of the mortality benefit at the end of an ongoing follow-up of the UKCTOCS cohort.

Cluster-randomised non-inferiority trial comparing DVD-assisted and traditional genetic counselling in systematic population testing for BRCA1/2 mutations.

BACKGROUND: Newer approaches to genetic counselling are required for population-based testing. We compare traditional face-to-face genetic counselling with a DVD-assisted approach for population-based BRCA1/2 testing. METHODS: A cluster-randomised non-inferiority trial in the London Ashkenazi Jewish population. INCLUSION CRITERIA: Ashkenazi Jewish men/women >18 years; exclusion criteria: (a) known BRCA1/2 mutation, (b) previous BRCA1/2 testing and (c) first-degree relative of BRCA1/2 carrier. Ashkenazi Jewish men/women underwent pre-test genetic counselling prior to BRCA1/2 testing in the Genetic Cancer Prediction through Population Screening trial (ISRCTN73338115). Genetic counselling clinics (clusters) were randomised to traditional counselling (TC) and DVD-based counselling (DVD-C) approaches. DVD-C involved a DVD presentation followed by shorter face-to-face genetic counselling. Outcome measures included genetic testing uptake, cancer risk perception, increase in knowledge, counselling time and satisfaction (Genetic Counselling Satisfaction Scale). Random-effects models adjusted for covariates compared outcomes between TC and DVD-C groups. One-sided 97.5% CI was used to determine non-inferiority. SECONDARY OUTCOMES: relevance, satisfaction, adequacy, emotional impact and improved understanding with the DVD; cost-minimisation analysis for TC and DVD-C approaches. RESULTS: 936 individuals (clusters=256, mean-size=3.6) were randomised to TC (n=527, clusters=134) and DVD-C (n=409, clusters=122) approaches. Groups were similar at baseline, mean age=53.9 (SD=15) years, women=66.8%, men=33.2%. DVD-C was non-inferior to TC for increase in knowledge (d=-0.07; lower 97.5% CI=-0.41), counselling satisfaction (d=-0.38, 97.5% CI=1.2) and risk perception (d=0.08; upper 97.5% CI=3.1). Group differences and CIs did not cross non-inferiority margins. DVD-C was equivalent to TC for uptake of genetic testing (d=-3%; lower/upper 97.5% CI -7.9%/1.7%) and superior for counselling time (20.4 (CI 18.7 to 22.2) min reduction (p<0.005)). 98% people found the DVD length and information satisfactory. 85-89% felt it improved their understanding of risks/benefits/implications/purpose of genetic testing. 95% would recommend it to others. The cost of genetic counselling for DVD-C=£7787 and TC=£17 307. DVD-C resulted in cost savings=£9520 (£14/volunteer). CONCLUSIONS: DVD-C is an effective, acceptable, non-inferior, time-saving and cost-efficient alternative to TC. TRIAL REGISTRATION NUMBER: ISRCTN 73338115.

Cost-effectiveness of population screening for BRCA mutations in Ashkenazi jewish women compared with family history-based testing.

BACKGROUND: Population-based testing for BRCA1/2 mutations detects the high proportion of carriers not identified by cancer family history (FH)-based testing. We compared the cost-effectiveness of population-based BRCA testing with the standard FH-based approach in Ashkenazi Jewish (AJ) women. METHODS: A decision-analytic model was developed to compare lifetime costs and effects amongst AJ women in the UK of BRCA founder-mutation testing amongst: 1) all women in the population age 30 years or older and 2) just those with a strong FH (≥10% mutation risk). The model assumes that BRCA carriers are offered risk-reducing salpingo-oophorectomy and annual MRI/mammography screening or risk-reducing mastectomy. Model probabilities utilize the Genetic Cancer Prediction through Population Screening trial/published literature to estimate total costs, effects in terms of quality-adjusted life-years (QALYs), cancer incidence, incremental cost-effectiveness ratio (ICER), and population impact. Costs are reported at 2010 prices. Costs/outcomes were discounted at 3.5%. We used deterministic/probabilistic sensitivity analysis (PSA) to evaluate model uncertainty. RESULTS: Compared with FH-based testing, population-screening saved 0.090 more life-years and 0.101 more QALYs resulting in 33 days' gain in life expectancy. Population screening was found to be cost saving with a baseline-discounted ICER of -£2079/QALY. Population-based screening lowered ovarian and breast cancer incidence by 0.34% and 0.62%. Assuming 71% testing uptake, this leads to 276 fewer ovarian and 508 fewer breast cancer cases. Overall, reduction in treatment costs led to a discounted cost savings of £3.7 million. Deterministic sensitivity analysis and 94% of simulations on PSA (threshold £20000) indicated that population screening is cost-effective, compared with current NHS policy. CONCLUSION: Population-based screening for BRCA mutations is highly cost-effective compared with an FH-based approach in AJ women age 30 years and older.

Assessment of health-related quality of life in a greek symptomatic population with atrial fibrillation: correlation with functional status and echocardiographic indices.

INTRODUCTION: Atrial fibrillation (AF) is known to have an unfavorable impact on quality of life. The purpose of this study was to assess the health-related quality of life (HRQOL) in a symptomatic population with AF seeking medical advice in a tertiary hospital, as well as to explore the relationship between HRQOL, functional status, and echocardiographic indices of left ventricular (LV) systolic and diastolic function. METHODS: The study sample consisted of 108 symptomatic patients suffering from AF who presented in the emergency department or were admitted to the cardiology department in an urban Greek tertiary hospital between January 1 and May 31, 2012. HRQOL was assessed using the SF-36 and EQ-5D instruments. RESULTS: In the study sample, AF was newly diagnosed in 16.5% of the patients, paroxysmal/persistent in 43.6% and permanent in 39.9%. The mean levels of physical and mental summary components of the SF-36 were 40.28 and 40.89, respectively. The EQ-VAS mean score was 59.63%, while the EQ-5D Europe VAS index and the York A1 Tariff index were 0.586 and 0.547, respectively. Reliability analysis found Cronbach's to be 0.890 for the SF-36 and 0.701 for the EQ-5D. Convergent validity was proved to be at satisfactory levels. Impaired HRQOL was associated with worse NYHA class and echocardiographic indices of impaired LV systolic and diastolic function. Apart from higher NYHA class, other predisposing factors for lower HRQOL were female sex, advanced age, low physical activity, and higher levels of brain natriuretic peptide. CONCLUSIONS: Symptomatic AF patients report impaired HRQOL. Functional status and echocardiographic indices of LV systolic and diastolic function appear to affect HRQOL significantly in these patients. The SF-36 and the EQ-5D are shown to be reliable and valid instruments in assessing HRQOL in patients with AF.

An assessment of health related quality of life in a male prison population in Greece associations with health related characteristics and characteristics of detention.

BACKGROUND: Prisoners constitute a group with increased health and social care needs. Although implementing policies that aim at improving outcomes within this population should be a priority area, studies that attempt to assess health outcomes and health related quality of life (HRQoL) in this population are limited. AIM: To assess HRQoL in a prison population in Greece and to explore the relationship between HRQoL and a set of individual sociodemographic and health related characteristics and characteristics of detention. METHODS: A cross-sectional study involving 100 male prisoners was conducted in the prison of Corinth in Greece. HRQoL was assessed through the use of the SF-36 and the EQ-5D. RESULTS: The mean physical and mental summary scores of the SF-36 were 55.33 and 46.82, respectively. The EQ-VAS mean score was 76.41%, while the EQ-5D index was 0.72. Multivariate analysis identified a statistical relationship between HRQoL and the conditions of detention, controlling for the effect of sociodemographic characteristics, morbidity, and mental problems. The use of narcotics in particular is significantly associated with lower HRQoL. CONCLUSIONS: Implementation of policies that aim at preventing the use of narcotics within the prison environment is expected to contribute to improved HRQoL in this population.

An assessment of the cost of percutaneous pulmonary valve implantation (PPVI) versus surgical pulmonary valve replacement (PVR) in patients with right ventricular outflow tract dysfunction.

BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) using the Melody * transcatheter pulmonary valve is a new procedure introduced in 2000 as a less invasive treatment for right ventricular outflow tract (RVOT) dysfunction. The aim of this new procedure is to restore pulmonary valve competence without the need of open-chest operation. By prolonging the conduit lifespan, it delays surgical pulmonary valve replacement (PVR) and it can therefore potentially reduce the number of open-chest interventions over a patient's lifetime. PPVI has been shown to be feasible and safe and can be performed with a low complication rate. OBJECTIVES AND METHODS: The aim of this study is to assess the cost of PPVI and the cost of surgical pulmonary valve replacement (PVR) in patients with right ventricular outflow tract dysfunction using a cohort simulation model applied to the UK population. RESULTS: The model resulted in an estimate of mean cost per patient of £5,791 when PPVI is unavailable as a treatment option and in an estimate of mean cost per patient of £8,734 when PPVI is available over the 25-year period of analysis. After sensitivity analysis was undertaken the results showed that the mean per patient cost difference in implementing PPVI over 25 years as compared to surgical PVR lies somewhere between £2,041 and £3,913. LIMITATIONS: Given the lack of long-term data on treatment progression, the cost estimates derived here are subject to considerable uncertainty, and extensive sensitivity analysis has been used to counter this. Consequently this study is merely indicative of the levels of cost which can be expected in a cohort of 1,000 patients faced with a choice of treatment with PPVI or surgery. It is not a cost-effectiveness study but it helps place current knowledge on short-term benefits into context. CONCLUSIONS: As this analysis shows PPVI is associated with a relatively small increase in treatment management costs over a long time period. It is left entirely to the reader to value whether this inferred increase in long-term cost is worthwhile given the known short-term benefits and any personal judgement formed over long-term benefit.

Estimating the cost related to surveillance of colorectal cancer in a French population.

Little is known about costs related to the surveillance of patients that have undergone curative resection of colorectal cancer. The aim of this study was to calculate the observed surveillance costs for 385 patients followed-up over a 3-year period, to estimate surveillance costs if French guidelines are respected, and to identify the determinants related to surveillance costs to derive a global estimation for France, using a linear mixed model. The observed mean surveillance cost was 713. If French recommendations were strictly applied, the estimated mean cost would vary between 680 and 1,069 according to the frequency of abdominal ultrasound. The predicted determinants of cost were: age, recurrence, duration of surveillance since diagnosis, and adjuvant treatments. For France, the surveillance cost represented 4.4% of the cost of colorectal cancer management. The cost of surveillance should now be balanced with its effectiveness and compared with surveillance alternatives.

Cost-effectiveness analysis of oxaliplatin compared with 5-fluorouracil/leucovorin in adjuvant treatment of stage III colon cancer in the US.

BACKGROUND: The MOSAIC trial demonstrated that oxaliplatin/5-fluorouracil/leucovorin (FU/LV) (FOLFOX4) as adjuvant treatment of TNM stage II and III colon cancer significantly improves disease-free survival compared with 5-FU/LV alone. For stage III patients the 4-year disease-free survival (DFS) was 69% in the FOLFOX4 arm vs 61% in the LV5FU2 arm, P = .002). The cost-effectiveness of FOLFOX4 in stage III patients was evaluated from a US Medicare perspective. METHODS: By using individual patient-level data from the MOSAIC trial (median follow-up: 44.2 months), DFS and overall survival (OS) were estimated up to 4 years from randomization. DFS was extrapolated from 4 to 5 years by fitting a Weibull model and subsequent survival was estimated from life tables. OS beyond 4 years was predicted from the extrapolated DFS estimates and observed survival after recurrence. Costs were calculated from trial data and external estimates of resources to manage recurrence. RESULTS: Patients on FOLFOX4 were predicted to gain 2.00 (95% confidence interval [CI]: 0.63, 3.37) years of DFS over those on 5-FU/LV. The predicted life expectancy of stage III patients on FOLFOX4 and 5-FU/LV was 17.61 and 16.26 years, respectively. Mean total lifetime disease-related costs were $56,300 with oxaliplatin and $39,300 with 5-FU/LV. Compared with 5-FU/LV, FOLFOX4 was estimated to cost $20,600 per life-year gained and $22,800 per quality-adjusted life-year (QALY) gained, discounting costs and outcomes at 3% per annum. CONCLUSIONS: FOLFOX4 is likely to be cost-effective compared with 5-FU/LV in the adjuvant treatment of stage III colon cancer. The incremental cost-effectiveness ratio compares favorably with other funded interventions in oncology.

Long-term mortality, morbidity and hospital care following intracerebral hemorrhage: an 11-year cohort study.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) represents the severest form of stroke, yet examinations of long-term prognosis and associated health care use are rare. This study assessed survival, morbidity and cost of hospital care over 11 years following a first-ever ICH in the UK. METHODS: We used a population-based retrospective inception cohort design using data from the Hospital Record Linkage System in Scotland. Long-term survival, morbidity and treatment provided in hospitals were evaluated in all patients with a first diagnosis of ICH in 1995. A cohort of ischemic stroke (IS) patients was also examined for comparison. RESULTS: A total of 705 patients with ICH and 8,893 with IS were identified. The mean age was 65 years (SD = 17.2) for ICH and 73 years (SD = 11.8) for IS at stroke onset. The acute in-hospital mortality was 45.7 and 30.1% for ICH and IS, 51.2 and 39.9% at 1 year, while 76.0 and 80.4% were dead 11 years later. The cumulative risk of nonfatal or fatal ICH was 8.0, 12.7 and 13.7% at 1, 5 and 10 years, and 7.0, 11.1 and 12.9% for IS in the ICH cohort. The mean cost of initial hospital care was GBP 10,332 (SD = 19,919) for ICH and GBP 9,937 (SD = 15,777) for IS. The mean total costs over 11 years were GBP 18,629 (SD = 29,943) for ICH and GBP 21,505 (SD = 27,190) for IS. CONCLUSION: Following a first ICH, individuals have a poorer short-term prognosis than individuals with IS, yet both ICH and IS imply significant follow-up care.

The economics of screening and treatment in type 2 diabetes mellitus.

A systematic review of the literature was conducted to identify articles on the economics of type 2 diabetes mellitus. Articles were classified into two main categories: cost/burden-of-illness studies of type 2 diabetes and economic evaluations of type 2 diabetes interventions. This systematic review was supplemented by an overview of the findings relating to economic evaluations of associated diabetic complications. A number of conclusions emerge from this review, the most important of which is that intensive treatment of patients with type 2 diabetes appears to be relatively cost effective compared with more conservative strategies. This finding reflects the cost offsets that arise from the range and degree of complications attributable to diabetes. Primary prevention of type 2 diabetes also appears to be cost effective, particularly in high-risk groups. The evidence on screening for type 2 diabetes is less conclusive and further economic analysis is required.