Cost-Effectiveness Analysis of the Oncotype DX Breast Recurrence Score® Test in Node-Negative Early Breast Cancer.

Background: The 21-gene assay (the Oncotype DX Breast Recurrence Score® test) is a validated multigene assay which produces the Recurrence Score® result (RS) to inform decisions on the use of adjuvant chemotherapy in human epidermal growth factor receptor 2-negative (HER2-), hormone receptor positive (HR+) early invasive breast cancer. A model-based economic evaluation estimated the cost-effectiveness of the 21-gene assay against the use of clinical risk tools alone based on the latest evidence from prospective studies. Methods: The proportion of patients assigned to chemotherapy conditional on their RS result was obtained from retrospective data from the Clalit registry. The probability of distant recurrence with endocrine and chemo-endocrine therapy conditional on RS result was obtained from TAILORx and NSABP B-20 trials. The cost-effectiveness of the 21-gene assay compared to using clinical risk tools alone was estimated in terms of cost per quality-adjusted life-year (QALY) over a lifetime horizon. Results: The 21-gene assay was more effective (0.17 more quality-adjusted life years) at a lower cost (-£519) over a lifetime compared to clinical risk alone. The model results were sensitive to assumptions around the magnitude of benefit of chemotherapy in the high RS result subgroup. Other assumptions underpinning the model, such as the proportion of patients assigned to chemotherapy in the low and mid-range RS result subgroups and long-term distant recurrence probabilities, had a smaller impact on the results. Conclusion: The analysis showed that the cost-effectiveness of the 21-gene assay is sensitive to assumptions for chemotherapy sparing for patients with RS 0-25 whose outcomes with endocrine therapy are no worse compared to chemotherapy-assigned patients, and a chemotherapy benefit in the RS 26-100 group. Future studies need to incorporate a wider set of tumour profiling tests other than the 21-gene assay to allow a direct comparison of their cost-effectiveness.

Cost-effectiveness analysis of the Oncotype DX Breast Recurrence Score test in node-positive early breast cancer.

AIMS: Given the high rate of adverse events and high cost of adjuvant chemotherapy, it is optimal to avoid its use when endocrine therapy is equally effective at preventing distant recurrence of early breast cancer. The Oncotype DX test is a predictive and prognostic multigene assay used to guide adjuvant chemotherapy decisions in early breast cancer based on a Recurrence Score (RS) result. A model-based cost-effectiveness analysis compared the Oncotype DX test to clinical risk tools alone for HR+/HER2- node-positive (1-3 axillary lymph nodes) early breast cancer patients based on results from the RxPONDER trial. MATERIALS AND METHODS: A decision-tree and Markov model was developed in Microsoft Excel. Distributions of patients and distant recurrence probabilities with endocrine and chemo-endocrine therapy were derived from the RxPONDER trial, TransATAC and SWOG-8814. Chemotherapy assignment data were obtained from the Clalit registry. The cost of adjuvant chemotherapy was based on the distribution of treatments used in the UK combined with published drug unit costs in the UK. The cost of distant recurrence and health state utility values were obtained from literature. RESULTS: The Oncotype DX test was found to be more effective (with an estimated 0.02 additional QALYs) at a lower estimated cost (-£989) compared to clinical risk tools alone. The results did not substantially change with more conservative clinical and cost scenarios. The RxPONDER trial was restricted to RS 0-25, and data synthesis with other studies was required to inform the analysis, which increased uncertainty. CONCLUSIONS: The Oncotype DX test is highly likely to be cost-effective in node-positive early breast cancer. The results were driven by reduction in the use of chemotherapy with consequence avoidance of the costs and harmful effects of chemotherapy. Targeted treatment of a minority (11%) of women with RS 26-100 who benefit from chemotherapy reduced cost and improved survival.

Clinical outcome and predictors of adverse events of an enhanced older adult psychiatric liaison service: Rapid Assessment Interface and Discharge (Newport).

BACKGROUND: Hospitals are currently admitting an increasing number of older people, and more than one-third could have an underlying mental health problem. The existing Older Adult Mental Health (OAMH) liaison service was increasingly unable to meet the escalating needs of older and frail patients. Therefore, the service was modernized and enhanced on an "invest-to-save" principle to provide a prompt holistic assessment for older adults with mental health problems. The objective of this study was a service evaluation to appraise clinical outcome, minimize the length of stay, and measure the predictors of adverse outcomes to streamline this enhanced service. MATERIALS AND METHODS: Patient demographics, social care needs, comorbidity burden (Charlson comorbidity index, CCI), and functional status (Barthel index, BI) were recorded from November 2014 to February 2015. Frailty status (frailty index, FI) was measured by an index (Rockwood index) of accumulated deficits. The outcomes were compared with the previous OAMH liaison service data over the same period a year earlier. RESULTS: The new Rapid Assessment Interface and Discharge service assessed 339 patients compared to 179 by the previous liaison team over the 4-month period. Mean age was 82.18±8.04 years, with 60% women; preadmission BI was 14.96±4.35, and admission BI was 11.38±5.73 (P<0.001, paired t-test); mean CCI was 1.66±1.53, and mean FI was 0.34±0.99, and 80% were on polypharmacy. The direct discharges from front door were increased by 7%. The mean hospital stay reduced from 35 to 20 days in acute site and from 108 to 47 days in long-stay wards. The cost benefits were based on the mean reduction in hospital stay (41.8 days) and admission reduction (2.2 days), leading to a total annualized bed savings of 44 days. FI was the most highly significant factor between patient groups with a good and poor outcome (P=0.00003, independent groups t-test, t=-4.38, df 98). CONCLUSION: Prompt mental health assessments for acutely unwell frail older people are not only cost effective but also improve clinical outcomes.

Elementary school-located influenza vaccine programs: key stakeholder experiences from initiation to continuation.

This study examined the initiation and logistics, funding, perceived barriers and benefits, and disruption of school activities by school-located influenza vaccination (SLIV) programs conducted during the 2008-2009 influenza season. Seventy-two interviews using a structured protocol were conducted with 26 teachers, 16 school administrators, and 30 health care professionals from 34 schools in 8 school districts. SLIV programs used a variety of locations, scheduling and staffing options, and methods for receiving parental consent and screening children. Health care professionals were primarily responsible for implementing SLIV programs, and most administrators and health care professionals considered programs easy to initiate. Health care professionals identified successful programs as requiring adequate planning/coordination, a dedicated program coordinator, and a consistent funding source. Most respondents (96%) reported minimal school-day disruptions. The perception of most stakeholders is that SLIV programs can be relatively easy to initiate, minimally disruptive and can become more efficient with experience, especially with feedback from all stakeholders.

Economic analyses comparing tiotropium with ipratropium or salmeterol in UK patients with COPD.

AIMS: This study presents a cost-effectiveness and budget impact analysis comparing cost and outcomes for UK patients with COPD treated with either tiotropium, ipratropium or salmeterol. METHODS: A previously-published COPD cost-effectiveness model was adapted for the UK, then used to estimate the cost-effectiveness of tiotropium compared to salmeterol and ipratropium. Additional epidemiological data were used to estimate the budget impact of switching patients from ipratropium or salmeterol to tiotropium. RESULTS: In England, the estimated annual cost per patient on tiotropium was pound1350, on salmeterol was pound1404, and on ipratropium was pound1427; in Scotland/Wales/Northern Ireland (S/W/NI) these costs were pound1439, pound1565, and pound1631, respectively. Tiotropium patients experienced better quality-adjusted life-years (QALYs) across all comparisons, and this option was therefore dominant compared to salmeterol and ipratropium. The probability of tiotropium being dominant ranged from 72% to 87% across comparisons. At a willingness to pay threshold of pound20,000 per QALY, tiotropium had at least a 97% chance of being cost-effective. The estimated annual saving per primary care trust (PCT) of switching patients from salmeterol and ipratropium to tiotropium in England was pound230,000 and in S/W/NI was pound160,000. CONCLUSIONS: Tiotropium is a cost-effective alternative to ipratropium and salmeterol, and switching COPD patients from ipratropium and salmeterol to tiotropium could result in considerable cost savings for PCTs along with improvements in quality-of-life.

Continuity in provider and site of care and preventive services receipt in an adult Medicaid population with physical disabilities.

BACKGROUND: This study investigated the relationship between continuity of care (having one's own doctor and a regular site of care), and receipt of preventive services in a population of adult fee-for-service Medicaid enrollees with physical disabilities. METHODS: A random sample of 555 physically disabled Rhode Island Medicaid enrollees aged 18 to 64 years were surveyed by telephone. Respondents were asked about receipt of six preventive services in the previous year. They were also asked whether they had their own doctor and whether they had a regular site of care. Regression analyses with propensity score corrections for selection bias were used to test the associations between care continuity measures and the number of preventive services received, as well as the receipt of each individual service. RESULTS: After adjustment for predisposing, enabling, and need factors, respondents with their own doctor received 0.73 more preventive services than peers without their own doctor, and respondents who had a usual site of care received 0.85 more services than peers who received care at the emergency department or who had no regular site. The influences of having a regular doctor and a usual site of care varied according to type of preventive service, and these influences appear to be largely complementary rather than overlapping. CONCLUSIONS: Study findings suggest that care models for adults with physical disabilities should include mechanisms to ensure both physician and site continuity. A strong primary care component that links individual patients with a personal doctor, as well as care protocols that ensure receipt of preventive services, appear to be optimal for medically needy populations.

Comparison of tiotropium bromide and combined ipratropium/salbutamol for the treatment of COPD: a UK General Practice Research Database 12-month follow-up study.

AIMS: To compare the effectiveness of the long-acting anticholinergic, tiotropium with ipratropium/salbutamol in reducing the risk of exacerbations and COPD-related referrals in patients with COPD. METHODS: Data were obtained from the General Practice Research Database (GPRD). Propensity score matching was used to balance prognostic covariates between treatment groups. Incidence rate ratios and 95% confidence intervals during a 12-month follow-up period were estimated. RESULTS: 4193 patients (3385, tiotropium; 808, ipratropium/salbutamol) in the GPRD met the inclusion/exclusion criteria. Patients treated with tiotropium had more severe COPD than patients treated with ipratropium/salbutamol. Following propensity score matching, 1222 tiotropium-treated patients and 633 ipratropium/salbutamol-treated patients were included in the final analysis. Incidence rate ratios (95% confidence intervals) were 0.74 (0.64-0.85; p=0.0086) for exacerbations and 0.57 (0.46-0.70; p=0.004) for COPD-related referrals/hospitalisations. CONCLUSIONS: Tiotropium is associated with a reduced risk of exacerbations and COPD-related referrals and hospitalisation compared to combined ipratropium/salbutamol in patients with COPD.

Nutrition and health series--6. Exercise and diet for a healthier New Year!

It is widely accepted that physical activity is of paramount importance to general well-being and good health. It can reduce the risk of coronary heart disease, high blood pressure, certain cancers, type 2 diabetes and obesity. Mental functioning and self-esteem can also be greatly improved by regular exercise. This article provides many simple ideas on how to improve diet and incorporate physical activity into daily life.

Nutrition for the lads.

Throughout their lives, men's health compares badly to that of women. This article looks at healthy eating for men, whose energy and nutritional requirements differ from women's. It outlines the changes in food and alcohol intake that some males need to make in order to reduce their risk of ill-health and disease. A healthy diet in adolescence is also important as this is the period of rapid growth when much of the body's bone mass is laid down. Since men attend health centres and visit their general practitioners less often than women, health professionals should consider raising nutritional issues opportunistically.

Pharmacological inhibition and genetic deficiency of plasminogen activator inhibitor-1 attenuates angiotensin II/salt-induced aortic remodeling.

OBJECTIVE: To test the hypothesis that pharmacological plasminogen activator inhibitor (PAI)-1 inhibition protects against renin-angiotensin-aldosterone system-induced cardiovascular injury, the effect of a novel orally active small-molecule PAI-1 inhibitor, PAI-039, was examined in a mouse model of angiotensin (Ang) II-induced vascular remodeling and cardiac fibrosis. METHODS AND RESULTS: Uninephrectomized male C57BL/6J mice were randomized to vehicle subcutaneus, Ang II (1 mug/h) subcutaneous, vehicle+PAI-039 (1 mg/g chow), or Ang II+PAI-039 during high-salt intake for 8 weeks. Ang II caused significant medial, adventitial, and aortic wall thickening compared with vehicle. PAI-039 attenuated Ang II-induced aortic remodeling without altering the pressor response to Ang II. Ang II increased heart/body weight ratio and cardiac fibrosis. PAI-039 did not attenuate the effect of Ang II on cardiac hypertrophy and increased fibrosis. The effect of PAI-039 on Ang II/salt-induced aortic remodeling and cardiac fibrosis was comparable to the effect of genetic PAI-1 deficiency. Ang II increased aortic mRNA expression of PAI-1, collagen I, collagen III, fibronectin, osteopontin, monocyte chemoattractant protein-1, and F4/80; PAI-039 significantly decreased the Ang II-induced increase in aortic osteopontin expression at 8 weeks. CONCLUSIONS: This study demonstrates that pharmacological inhibition of PAI-1 protects against Ang II-induced aortic remodeling. Future studies are needed to determine whether the interactive effect of Ang II/salt and reduced PAI-1 activity on cardiac fibrosis is species-specific. In this study, the effect of pharmacological PAI-1 inhibition in a mouse model of Ang II-induced vascular remodeling and cardiac fibrosis was examined. PAI-1 inhibition significantly attenuated Ang II-induced aortic medial and wall thickening, but not cardiac hypertrophy, and enhanced Ang II/salt-induced cardiac fibrosis.

Weight loss on an energy-restricted, low-fat, sugar-containing diet in overweight sedentary men.

With the increasing prevalence of obesity in the United Kingdom, the search for an effective weight reducing diet is a priority in helping to reverse this trend. A 12-week dietary intervention study was carried out to test the effectiveness of an energy-restricted, low-fat, sugar-containing diet on weight loss in sedentary overweight men. The study also aimed to assess eating behaviour, to measure change in attitude towards sugar-containing foods and to measure the impact of the study on perceived quality of life. Subjects were recruited from three UK cities; Edinburgh, Birmingham and London. Seventy-six men, aged between 25 and 60 years, completed the study. Baseline diets were assessed by a 7-day diet diary. Compliance to the subsequent dietary advice was measured on four occasions post intervention, by 4-day diaries. Measures of body weight status were also monitored. Eating behaviour, attitudes towards sugar-containing foods and quality of life were assessed by questionnaire. Significant reductions in body weight (5.2%), body fat (11.2%) and waist:hip ratio (3%) were observed following reported dietary changes that included a reduction in reported energy intake of 3.2 MJ/day (770 kcal/day), a reduction in the percent energy from fat (from 38.1% to 26.2%), an increase in the percent energy from total carbohydrate (from 44.4% to 54%) and from protein (from 17.3% to 20.6%). Subjects scored relatively highly for dietary restraint and emotional eating, and were strongly influenced by external eating cues. On completion of the 12-week study, subjects had a more positive attitude towards sugar-containing foods and perceived an improved quality of life. It is concluded, therefore, that including sugar-containing foods in a weight-reducing diet may be an effective strategy to achieve a palatable, low-fat, high-carbohydrate diet, which promotes weight loss in overweight individuals.

Health and fitness series--3. Popular dietary fads: how should health professionals respond?

Many magazines and health books for lay people extol the virtues of diets that produce weight loss, often rapidly and using unconventional régimes. In this article a dietitian summarises the basic physiology of weight loss and discusses three such types of diet: food-combining; "detox"; and the Atkins or high-protein, low-carbohydrate diet, including their physiological flaws and possible adverse side-effects.

Rapidly increasing prevalence of penicillin-resistant Streptococcus pneumoniae in middle Tennessee: a 10-year clinical and molecular analysis.

The clinical and molecular epidemiology of penicillin-resistant Streptococcus pneumoniae and the diagnostic accuracy of a six-primer PCR assay in identifying penicillin resistance were analyzed by using clinical isolates recovered over a 10-year period in middle Tennessee. The prevalence of non-penicillin-susceptible S. pneumoniae isolates (MIC, > or =0.1 microg/ml) increased from 10% in 1990 to 70% in 1999 (P < 0.001). Among S. pneumoniae isolates for which the penicillin MIC was > or =2 microg/ml (highly penicillin-resistant S. pneumoniae [PRSP]), 23 and 5% were resistant to at least three and at least five other antimicrobial classes, respectively. Pulsed-field gel electrophoresis identified 13 unique strain types, with type B accounting for 33% of PRSP isolates. The sensitivity, specificity, and negative and positive predictive values of the PCR assay in detecting PRSP were 99, 100, 99, and 100%, respectively. Penicillin resistance is rapidly increasing among S. pneumoniae isolates in Tennessee. The simultaneous detection of S. pneumoniae and high-level penicillin resistance can be accurately performed with the six-primer PCR assay.