Economic evaluation of adjuvant trastuzumab emtansine in patients with HER2-positive early breast cancer and residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment in Canada.

Background: In the katherine trial, adjuvant trastuzumab emtansine [T-DM1, Kadcyla (Genentech, South San Francisco, CA, U.S.A.)], compared with trastuzumab, significantly reduced the risk of recurrence or death by 50% (unstratified hazard ratio: 0.50; 95% confidence interval: 0.39 to 0.64; p < 0.0001) in patients with her2-positive early breast cancer (ebc) and residual invasive disease after neoadjuvant systemic treatment. A cost-utility evaluation, with probabilistic analyses, was conducted to examine the incremental cost per quality-adjusted life-year (qaly) gained associated with T-DM1 relative to trastuzumab, given the higher per-cycle cost of T-DM1. Methods: A Markov model comprising a number of health states was used to examine clinical and economic outcomes over a lifetime horizon from the Canadian public payer perspective. Patients entered the model in the invasive disease-free survival (idfs) state, where they received either T-DM1 or trastuzumab. Transition probabilities between the health states were derived from the katherine trial, Canadian life tables, and published literature from other relevant clinical trials (emilia, cleopatra, and M77001). Resource use, costs, and utilities were derived from katherine, other clinical trials, published literature, provincial fee schedules, and clinical expert opinion. Sensitivity analyses were conducted for key assumptions and model parameters. Results: Compared with trastuzumab, adjuvant T-DM1 was associated with a cost savings of $8,300 per patient and a 2.16 incremental qaly gain; thus T-DM1 dominated trastuzumab. Scenario analyses yielded similar results, with T-DM1 dominating trastuzumab or producing highly favourable incremental cost-utility ratios of less than $10,000 per qaly. Conclusions: Adjuvant T-DM1 monotherapy is a cost-effective strategy compared with trastuzumab alone in the treatment of patients with her2-positive ebc and residual invasive disease after neoadjuvant systemic treatment.

The effects of state-level expenditures for home- and community-based services on the risk of becoming a long-stay nursing home resident after hip fracture.

SUMMARY: This study measures the effect of spending policies for long-term care services on the risk of becoming a long-stay nursing home resident after a hip fracture. Relative spending on community-based services may reduce the risk of long-term nursing home residence. Policies favoring alternative sources of care may provide opportunities for older adults to remain community-bound. INTRODUCTION: This study aims to understand how long-term care policies affect outcomes by investigating the effect of state-level spending for home- and community-based services (HCBSs) on the likelihood of an individual's nursing home placement following hip fracture. METHODS: This study uses data from the 5% sample of Medicare beneficiaries from 2005 to 2010 to identify incident hip fractures among dual-eligibility, community-dwelling adults aged at least 65 years. A multilevel generalized estimating equation (GEE) model estimated the association between an individual's risk of nursing home residence within 1 year and the percent of states' Medicaid long-term support service (LTSS) budget allocated to HCBS. Other covariates included expenditures for Title III services and individual demographic and health status characteristics. RESULTS: States vary considerably in HCBS spending, ranging from 17.7 to 83.8% of the Medicaid LTSS budget in 2009. Hip fractures were observed from claims among 7778 beneficiaries; 34% were admitted to a nursing home and 25% died within 1 year. HCBS spending was associated with a decreased risk of nursing home residence by 0.17 percentage points (p 0.056). CONCLUSIONS: Consistent with other studies, our findings suggest that state policies favoring an emphasis on HCBS may reduce nursing home residence among low-income older adults with hip fracture who are at high risk for institutionalization.

Prediction of antidepressant response to venlafaxine by a combination of early response assessment and therapeutic drug monitoring.

INTRODUCTION: Early assessment of a therapeutic response is a central goal in antidepressant treatment. The present study examined the potential for therapeutic drug monitoring and symptom rating to predict venlafaxine treatment efficacy (measured by overall patient response and remission). METHODS: 88 patients were uptitrated homogenously to 225 mg/day venlafaxine. Serum concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODV) were measured at week 2. Continuous psychopathometric ratings were measured for up to 6 weeks by independent study raters. RESULTS: An early improvement was significantly more common in venlafaxine responders than non-responders (χ(2); p=0.007). While ODV serum levels were significantly higher in responders (t test; p=0.006), VEN serum levels, sum level of VEN+ODV and the ratio of ODV/VEN levels were not. Moreover, patients who showed an early response combined with an ODV serum level above the median of 222 ng/mL were significantly more likely to achieve full response (binary logistic model; p<0.01). Sensitivity (84% for early response) and specificity (81% for combination of early response and therapeutic drug monitoring) were sufficient to qualify as a reasonable screening instrument. CONCLUSION: Our results indicate that early improvement and ODV serum concentration are predictive of therapeutic outcome and can thus be used to guide use of the antidepressant venlafaxine.

Cost-effectiveness of denosumab in the treatment of postmenopausal osteoporosis in Canada.

OBJECTIVE: Denosumab is a novel biologic agent approved in Canada for treatment of post-menopausal osteoporosis (PMO) in women at high risk for fracture or who have failed or are intolerant to other osteoporosis therapies. This study estimated cost-effectiveness of denosumab vs usual care from the perspective of the Ontario public payer. METHODS: A previously published PMO Markov cohort model was adapted for Canada to estimate cost-effectiveness of denosumab. The primary analysis included women with demographic characteristics similar to those from the pivotal phase III denosumab PMO trial (FREEDOM; age 72 years, femoral neck BMD T-score -2.16 SD, vertebral fracture prevalence 23.6%). Three additional scenario sub-groups were examined including women: (1) at high fracture risk, defined in FREEDOM as having at least two of three risk factors (age 70+; T-score ≤ -3.0 SD at lumbar spine, total hip, or femoral neck; prevalent vertebral fracture); (2) age 75+; and (3) intolerant or contraindicated to oral bisphosphonates (BPs). Analyses were conducted over a lifetime horizon comparing denosumab to usual care ('no therapy', alendronate, risedronate, or raloxifene [sub-group 3 only]). The analysis considered treatment-specific persistence and post-discontinuation residual efficacy, as well as treatment-specific adverse events. Both deterministic and probabilistic sensitivity analyses were conducted. RESULTS: The multi-therapy comparisons resulted in incremental cost-effectiveness ratios for denosumab vs alendronate of $60,266 (2010 CDN$) (primary analysis) and $27,287 per quality-adjusted life year gained for scenario sub-group 1. Denosumab dominated all therapies in the remaining scenarios. LIMITATIONS: Key limitations include a lack of long-term, real-world, Canadian data on persistence with denosumab as well as an absence of head-to-head clinical data, leaving one to rely on meta-analyses based on trials comparing treatment to placebo. CONCLUSIONS: Denosumab may be cost-effective compared to oral PMO treatments for women at high risk of fractures and those who are intolerant and/or contraindicated to oral BPs.

[Assessment of the capability of performance of patients with psychic and psychosomatic diseases--a diagnostic model]. / Begutachtung der Leistungsfähigkeit bei Personen mit psychischen und psychosomatischen Störungen--ein diagnostisches Modell.

The limited availability of appropriate methods and criteria makes the assessment of capability by psychic and psychosomatic disorders difficult. This article displays and discusses the standards relating to content and method in capability assessments. The underlying diagnostic model of assessment capability has been conceptualised and tested empirically by a multicentric and interdisciplinary work-group. Different diagnostic levels of the manual are outlined as well as the procedures of operationalisation of the diagnostic categories. Furthermore, first results of empirical analysis are described and important conditions of the application of the diagnostic model are discussed.

Clinical and demographic factors associated with fractures among older Americans.

UNLABELLED: Medicare claims data were used to investigate associations between history of previous fractures, chronic conditions, and demographic characteristics and occurrence of fractures at six anatomic sites. The study confirmed previously established associations for hip and spine fractures and identified several new associations of interest for nonhip, nonspine fractures. INTRODUCTION: This study investigates the associations of a history of fracture, comorbid chronic conditions, and demographic characteristics with incident fractures among Medicare beneficiaries. The majority of fracture incidence studies have focused on the hip and on white females. This study examines a greater variety of fracture sites and more population subgroups than prior studies. METHODS: We used Medicare claims data to examine the incidence of fracture at six anatomic sites in a random 5% sample of Medicare beneficiaries during the time period 2000 through 2005. RESULTS: For each type of incident fracture, women had a higher rate than men, and there was a positive association with age and an inverse association with income. Whites had a higher rate than nonwhites. Rates were lowest among African-Americans for all sites except ankle and tibia/fibula, which were lowest among Asian-Americans. Rates of hip and spine fracture were highest in the South, and fractures of other sites were highest in the Northeast. Fall-related conditions and depressive illnesses were associated with each type of incident fracture, conditions treated with glucocorticoids with hip and spine fractures and diabetes with ankle and humerus fractures. Histories of hip and spine fractures were associated positively with each site of incident fracture except ankle; histories of nonhip, nonspine fractures were associated with most types of incident fracture. CONCLUSIONS: This study confirmed previously established associations for hip and spine fractures and identified several new associations of interest for nonhip, nonspine fractures.

"Pathologic" fractures: should these be included in epidemiologic studies of osteoporotic fractures?

UNLABELLED: Pathologic fractures are often excluded in epidemiologic studies of osteoporosis. Using Medicare administrative data, we identified persons with vertebral and hip fractures. Among these, 48% (vertebral) and 3% (hip) of the fractures were coded as pathologic. Only 25% and 66% of persons with these pathologic fractures had evidence for malignancy. INTRODUCTION: Analyses of osteoporosis-related fractures that use administrative data often exclude pathologic fractures (ICD-9 733.1x) due to concern that these are caused by cancer. We examined "pathologic" fractures of the vertebrae and hip to evaluate their contribution to fracture incidence and assessed the evidence for a malignancy. METHODS: We studied US Medicare beneficiaries age > or =65 with new fractures identified using ICD-9 diagnosis codes 733.13 (pathologic vert), 805.0, 805.2, 805.4, 805.8 (nonpathologic vert); and 733.14 (pathologic hip), 820.0, 820.2, 820.8 (nonpathologic hip). We further examined the proportion of cases with a diagnosis of a malignancy proximate to the fracture. RESULTS: We identified 44,120 individuals with a vertebral fracture and 60,354 with a hip fracture. Approximately 48% of vertebral fractures and 3% of hip fractures were coded as pathologic. For only approximately 25% of persons with a "pathologic" vertebral fracture ICD-9 code, but 66% of persons with a "pathologic" hip fracture, there was evidence of a possible cancer diagnosis. CONCLUSION: Among US Medicare beneficiaries, one fourth of pathologic vertebral fracture and two thirds of pathologic hip fracture cases had evidence for a malignancy. Particularly for vertebral fractures, excluding persons with pathologic fractures in epidemiologic analyses that utilize administrative claims data substantially underestimates the burden of fractures due to osteoporosis.

The geographic availability and associated utilization of dual-energy X-ray absorptiometry (DXA) testing among older persons in the United States.

UNLABELLED: Using national Medicare data from 1999-2006, we evaluated the relationship between travel distance and receipt of dual-energy X-ray absorptiometry (DXA). After adjusting for potentially confounding factors, travel distance was strongly associated with DXA testing. Rural residents were most strongly dependent on the availability of DXAs performed in physician offices. INTRODUCTION: Medicare reimbursement for DXAs performed in non-facility settings (e.g., physician offices) decreased in 2007. With declining reimbursement, some DXA providers may cease providing this service, which would increase travel distance for some people. The impact of travel distance on access to DXA is unclear. METHODS: Using national Medicare data, we identified claims for DXA to evaluate trends in the number and locations of DXAs performed. Travel distance was the distance from beneficiaries' residence and the nearest DXA provider. Binomial regression evaluated the relationship between travel distance and receipt of DXA. RESULTS: In 2006, 2.9 million DXAs were performed, a 103% increase since 1999. In 2005-2006, 8.0% of persons were tested at non-facility sites versus 4.2% at facility sites. The remainder (88%) had no DXA. Persons traveling 5-9, 10-24, 25-39, and 40-54, and > or = 55 miles were less likely to receive DXA (adjusted risk ratios = 0.92, 0.79, 0.43, 0.32, and 0.26, respectively, < 5 miles referent). Rural residents were more dependent than urban residents on the availability of DXA from non-facility providers. CONCLUSION: Approximately two-thirds of DXAs in 2005-2006 were performed in non-facility settings (e.g., physician offices). Rural residents would have preferentially reduced access to DXA if there were fewer non-facility sites.

Implementing supported employment as an evidence-based practice.

Supported employment for people with severe mental illness is an evidence-based practice, based on converging findings from eight randomized controlled trials and three quasi-experimental studies. The critical ingredients of supported employment have been well described, and a fidelity scale differentiates supported employment programs from other types of vocational services. The effectiveness of supported employment appears to be generalizable across a broad range of client characteristics and community settings. More research is needed on long-term outcomes and on cost-effectiveness. Access to supported employment programs remains a problem, despite their increasing use throughout the United States. The authors discuss barriers to implementation and strategies for overcoming them based on successful experiences in several states.

When she was bad: borderline personality disorder in a posttraumatic age.

The advent of the posttraumatic stress disorder diagnosis has been welcomed by many as a recognition of the circumstances and needs of victimized women. This paper argues that the increasing application of the PTSD label to women formerly diagnosed with borderline personality disorder, rather than resolving the dilemmas inherent in use of the borderline diagnosis, has succeeded instead in further medicalizing women's problems and reproducing the previously existing caste system of diagnosis and treatment.

Research on the individual placement and support model of supported employment.

This paper reviews research on the Individual Placement and Support (IPS) model of supported employment for people with severe mental illness. Current evidence indicates that IPS supported employment is a more effective approach for helping people with psychiatric disabilities to find and maintain competitive employment than rehabilitative day programs or than traditional, stepwise approaches to vocational rehabilitation. There is no evidence that the rapid-job-search, high-expectations approach of IPS produces untoward side effects. IPS positively affects satisfaction with finances and vocational services, but probably has minimal impact on clinical adjustment. The cost of IPS is similar to the costs of other vocational services, and cost reductions may occur when IPS displaces traditional day treatment programs. Future research should be directed at efforts to enhance job tenure and long-term vocational careers.

Body image preferences among urban African Americans and whites from low income communities.

OBJECTIVE: The purpose of this study was to determine (1) how African-American and white men and women from similar low income communities perceive their body mass relative to others in the population; and (2) whether ethnic and gender differences exist in the selection of ideal body image sizes for the same and opposite sex. DESIGN: A street survey of African-American and white men and women was conducted using a census tract sampling schema. Participants (N = 927) were interviewed and asked to provide their height and weight and to select body size images from a standardized ethnic-specific Figure Rating Scale to represent their current self, ideal self, and their estimation of ideals for the opposite sex. Sociodemographics and co-morbidity were assessed by self-report. RESULTS: All ethnic and gender groups showed a significant correlation between their body mass index and selected body image size, r = .63 to .74, all P<.001. Average ideal body image size for self was the same for African-American and white men, while African-American women had a significantly greater ideal image size compared with white women (P = .004). Ideal body image size preferences for members of the opposite sex were greater for African-Americans. White women had a notable preference for the smallest body image sizes. Multiple linear regression analyses showed that, independent of sociodemographic variables and co-morbidity, body image sizes for current self, ideal self, and ideal for the opposite sex were all significantly greater in African-Americans. CONCLUSION: Strategies to ameliorate overweight and its attendant diseases may require a shift in social norms, particularly among African-American women in low socioeconomic communities. This has implications for the design of community-based interventions and suggests a need for ethnic-specific interventions.

Reducing cigarette sales to minors in an urban setting: issues and opportunities for merchant intervention.

INTRODUCTION: Intervention studies to reduce cigarette sales to minors have been conducted primarily in suburban settings. Little is known about sociocultural factors influencing cigarette sales to minors in urban settings. This study sought to determine sociodemographic and cultural factors that may play a role in cigarette sales and in efforts to reduce sales to minors in urban areas. METHODS: Merchant education and follow-up surveys were conducted in small local stores in predominantly African-American urban census tracts in Baltimore. The stores had prior evidence of cigarette sales to minors. RESULTS: Merchants reported hostility (66%) and foul language (64%) when they requested youth identification. Youthful-oriented advertising of cigarettes was highly prevalent in all stores and moreso in stores owned and staffed by Asian merchants. Advertising with specific youthful content was predictive (OR = 3.97; 95% CI = 1.70, 9.23; P = .0014) of higher requests for cigarettes from minors. CONCLUSIONS: Youth-oriented cigarette advertising is a prevalent environmental risk for urban youth. Differences between Asian and African-American merchants suggest socioethnic factors may be an influential component of illegal sales and educational campaigns to reduce smoking among minors.

Benefits and costs of supported employment from three perspectives.

Administrators, consumers, and policy makers are increasingly interested in supported employment as a way of helping persons with severe mental illness get and keep competitive jobs. However, in an atmosphere of increased expectations for performance and declining public financing, administrators want to know the costs and benefits of different approaches before they reallocate scarce treatment or rehabilitative dollars. This article discusses the net benefits of two approaches to supported employment that were compared in a randomized trial: Individual Placement and Support (IPS) and Group Skills Training (GST). The authors analyze costs and benefits from societal, government, and consumer perspectives. Although a previous analysis showed that IPS participants were significantly more likely to find work, worked more hours, and had higher earnings, net benefits of the two programs were not significantly different. The authors also discuss some of the strengths and weaknesses of cost-benefit analysis in mental health care and suggest future directions for policy and research.

Cigarette sales to African-American and white minors in low-income areas of Baltimore.

OBJECTIVES: This study documented illegal sales of cigarettes to minors in low-income African-American and White urban areas in East Baltimore. METHODS: Six youths, aged 14 through 16 years, were sent to a random sample of 83 corner stores to attempt to purchase cigarettes. The youths provided the investigators with data on merchant, store, and purchase characteristics. RESULTS: The youths successfully purchased cigarettes in 85.5% of the stores; 58% of the stores displayed five or more cigarette advertisements outside their premises. CONCLUSIONS: Cigarette sales to minors and associated advertising remain prevalent in this urban community.

The feasibility of a street-intercept survey method in an African-American community.

OBJECTIVES: This study evaluates the feasibility of a nonquota, street-intercept survey method that utilized random selection of interview sites. METHODS: The street-intercept survey was compared with a random digit-dial telephone survey conducted in the same catchment area among African-American adults aged 18 or older. RESULTS: The street-intercept survey's response rate was 80.2%; residence rate, 85.3%; interview completion rate, 97.9%; interference rate, 4.0%; and yield rate, 2.5 interviews per interviewer per hour. The street-intercept method produced more representative distributions of age and sex than the random-digit-dial survey. CONCLUSIONS: The street-intercept method is a feasible alternative to traditional population survey methods and may provide better access to harder-to-reach segments of the urban population in a safe manner.

Health insurance and the financial impact of IDDM in families with a child with IDDM.

OBJECTIVE: To examine the health insurance experience and out-of-pocket health care costs of families with a child with IDDM. RESEARCH DESIGN AND METHODS: A case-control study of 197 families with a child with IDDM and 142 control families with no diabetic children was conducted. IDDM-affected families were identified from the Allegheny County IDDM Registry. Brothers and sisters of the parents in the IDDM-affected families were asked to participate as control subjects. Health insurance coverage and the money that families spent on health care services and supplies not reimbursed by insurance (out-of-pocket costs) were assessed by questionnaire. RESULTS: No difference was found between the IDDM-affected and control families in the percentages with or without insurance. Families with low household incomes ($10,000-$19,999) were at the greatest risk for having no insurance. While coverage provided by private plans was similar between the IDDM-affected and control families, many families had no reimbursement for insulin (10%), syringes (10%), or blood testing strips (30%). Out-of-pocket expenses were 56% higher in the IDDM-affected families than in the control families. Seventeen percent of the IDDM-affected families had expenses over 10% of their household income. This particularly affected families with low household incomes. Pre-existing illness clauses and insurance denial affected only a small proportion of the case families. CONCLUSIONS: These data illustrate that most families with a child with IDDM have health insurance, yet still incur larger out-of-pocket health care costs than do families without the presence of diabetes. IDDM-affected families likely face a number of economic decisions regarding health insurance and the use of health care.

Follow-up of University of Virginia experience with the modified Lothrop procedure.

Current surgical treatment of the frontal sinus disease include external approaches to obliterate or ablate the sinus and both external and transnasal methods to restore drainage into the nasal cavity. The original Lothrop procedure resects the medial frontal sinus floor, superior nasal septum, and intersinus septum, creating a large frontonasal communication. However, as described, the external approach used in this procedure often allowed medial collapse of soft tissue and the stenosis of the nasofrontal communication. This report further relates our experience with the modified transnasal endoscopic Lothrop procedure using suction drills for cases in which frontal recess exploration had failed to relieve obstruction of the frontal sinus. We present an update of the University of Virginia experience in performing the modified Lothrop procedure in 20 patients from 10/93 to 4/95. Our findings over the follow-up period (average 12 months) have verified that this procedure is effective, with a 95% patency rate for the surgically enlarged frontal sinus ostium. When compared to osteoplastic flap with fat obliteration, the modified transnasal Lothrop procedure offers the advantages of a less invasive procedure with a shorter and usually no hospitalization, less morbidity, and the increased ability to evaluate post-operatively for recurrent disease. A patient charge analysis was also performed comparing patients undergoing frontal sinus obliteration during the same time period, revealing an additional benefit of decreased patient costs for the modified transnasal Lothrop procedure. None of our patients experienced complications, and all showed significant improvement, if not complete resolution of their symptoms. Although this procedure has produced favorable results, it should be noted that this procedure is technically demanding and will require further long term follow-up to verify its efficacy and proper role in the spectrum of surgical approaches for the treatment of chronic sinusitis.

Comparison of the costs associated with medical and surgical treatment of obesity.

BACKGROUND: We compared the long-term costs and outcomes of gastric bypass versus medical therapy (very low-calorie diet plus weekly behavioral modification) for obese patients. METHODS: A successful outcome was defined as the loss of at least one third of excess weight that was maintained for the duration of the study. A minimal cost was assigned: $3000 for medical and $24,000 for surgical treatment. A cost per pound of weight lost for all patients successfully monitored was calculated. The Federal Trade Commission recently asked all weight loss programs to report this cost for patients at least 2 years after therapy. RESULTS: A total of 201 patients entered surgical and 161 entered medical therapy. The surgical group was initially heavier (mean body mass index [kg/m2] +/- SE = 49.3 +/- 0.6 versus 41.2 +/- 0.7, p < 0.01), but each group's lowest mean body mass index was similar (31.8 versus 32.1, respectively). A significantly higher percentage of patients in the surgical versus the medical group were still successful at year 5: 89% versus 21%. The cost per pound lost for medical therapy exceeded the cost of surgical therapy in the sixth posttreatment year (both more than $250/pound). CONCLUSIONS: Surgical treatment appears to be more cost-effective at producing and maintaining weight loss. It is imperative that long-term follow-up studies be funded to definitely establish this finding.

Tuberculosis screening in adults who have received bacille Calmette-Guérin vaccine.

The incidence of tuberculosis among immigrants to the United States is 12 times that in the native-born population. Screening immigrants for tuberculosis is complicated by the widespread use of bacille Calmette-Guérin (BCG) vaccination. To determine the utility of tuberculin testing in adults who have been vaccinated with BCG vaccine, we studied the tuberculin reactions of 80 adults who came to us for naturalization physical examinations. No adverse effects were reported from tuberculin testing. Subjects from regions with a low prevalence of tuberculosis who had received BCG vaccine were significantly more likely to have a positive reaction than subjects who had not received BCG vaccine. However, among subjects from regions with a high prevalence of tuberculosis, there was no difference in the prevalence of positive reactions between those who reported having BCG vaccinations and those who said they had not. Interpretation of tuberculin reactions in immigrants who receive BCG vaccinations depends on the prevalence of tuberculosis in the country of origin. Adults receiving BCG vaccination who have a positive reaction and no evidence of active tuberculosis should receive prophylactic therapy or be observed carefully.