Trends in Clinical Breast Density Assessment From the Breast Cancer Surveillance Consortium.

Changes to mammography practice, including revised Breast Imaging Reporting and Data System (BI-RADS) density classification guidelines and implementation of digital breast tomosynthesis (DBT), may impact clinical breast density assessment. We investigated temporal trends in clinical breast density assessment among 2 990 291 digital mammography (DM) screens and 221 063 DBT screens interpreted by 722 radiologists from 144 facilities in the Breast Cancer Surveillance Consortium. After age-standardization, 46.3% (95% CI = 44.1% to 48.6%) of DM screens were assessed as dense (heterogeneously/extremely dense) during the BI-RADS 4th edition era (2005-2013), compared to 46.5% (95% CI = 43.8% to 49.1%) during the 5th edition era (2014-2016) (P = .93 from two-sided generalized score test). Among DBT screens in the BI-RADS 5th edition era, 45.8% (95% CI = 42.0% to 49.7%) were assessed as dense (P = .77 from two-sided generalized score test) compared to 46.5% (95% CI = 43.8% to 49.1%) dense on DM in BI-RADS 5th edition era. Results were similar when examining all four density categories and age subgroups. Clinicians, researchers, and policymakers may reasonably expect stable density distributions across screened populations despite changes to the BI-RADS guidelines and implementation of DBT.

Recommendations for the conduct of economic evaluations in osteoporosis: outcomes of an experts' consensus meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the US branch of the International Osteoporosis Foundation.

Economic evaluations are increasingly used to assess the value of health interventions, but variable quality and heterogeneity limit the use of these evaluations by decision-makers. These recommendations provide guidance for the design, conduct, and reporting of economic evaluations in osteoporosis to improve their transparency, comparability, and methodologic standards. INTRODUCTION: This paper aims to provide recommendations for the conduct of economic evaluations in osteoporosis in order to improve their transparency, comparability, and methodologic standards. METHODS: A working group was convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis to make recommendations for the design, conduct, and reporting of economic evaluations in osteoporosis, to define an osteoporosis-specific reference case to serve a minimum standard for all economic analyses in osteoporosis, to discuss methodologic challenges and initiate a call for research. A literature review, a face-to-face meeting in New York City (including 11 experts), and a review/approval by a larger group of experts worldwide (including 23 experts in total) were conducted. RESULTS: Recommendations on the type of economic evaluation, methods for economic evaluation, modeling aspects, base-case analysis and population, excess mortality, fracture costs and disutility, treatment characteristics, and model validation were provided. Recommendations for reporting economic evaluations in osteoporosis were also made and an osteoporosis-specific checklist was designed that includes items to report when performing an economic evaluation in osteoporosis. Further, 12 minimum criteria for economic evaluations in osteoporosis were identified and 12 methodologic challenges and need for further research were discussed. CONCLUSION: While the working group acknowledges challenges and the need for further research, these recommendations are intended to supplement general and national guidelines for economic evaluations, improve transparency, quality, and comparability of economic evaluations in osteoporosis, and maintain methodologic standards to increase their use by decision-makers.

Impact of prescription drugs on second fragility fractures among US Medicare patients.

Drugs that increase the risk of fracture are commonly prescribed to survivors of a fragility fracture. This study shows that starting new high-risk medications after fracture increases the risk of a second, potentially preventable fracture. For most drug classes, however, it is safe to continue medications taken before the fracture. INTRODUCTION: Most patients who survive a fragility fracture are subsequently exposed to prescription drugs that have been linked to increased fracture risk. This study was designed to quantify the extent to which current prescribing practices result in potentially preventable second fractures. METHODS: We analyzed a cohort of 138,526 Medicare beneficiaries who returned to the community after a fragility fracture. Post-fracture drug use was defined using retail pharmacy fills. The risk of second fracture associated with individual drug classes was analyzed using Cox proportional hazard models. Data were further analyzed to determine whether there is a difference in risk between continuing previous therapy and initiating new therapy after fracture. RESULTS: Many drug classes previously identified as increasing fracture risk were not associated with increased fracture risk in this cohort. Discontinuing therapy at the time of fracture was only beneficial for patients taking selective serotonin reuptake inhibitors; however, initiating therapy in previous non-users increased second fracture risk for five classes of drugs (selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, proton pump inhibitors, and non-benzodiazepine hypnotics). CONCLUSION: Discontinuing high-risk drugs after fracture was not generally protective against subsequent fractures. Preventing the addition of new medications may result in greater improvements in post-fracture care.

Preoperative breast MRI and mortality in older women with breast cancer.

PURPOSE: The survival benefit from detecting additional breast cancers by preoperative magnetic resonance imaging (MRI) continues to be controversial. METHODS: We followed a cohort of 4454 women diagnosed with non-metastatic breast cancer (stage I-III) from 2/2005-6/2010 in five registries of the breast cancer surveillance consortium (BCSC). BCSC clinical and registry data were linked to Medicare claims and enrollment data. We estimated the cumulative probability of breast cancer-specific and all-cause mortality. We tested the association of preoperative MRI with all-cause mortality using a Cox proportional hazards model. RESULTS: 917 (20.6%) women underwent preoperative MRI. No significant difference in the cumulative probability of breast cancer-specific mortality was found. We observed no significant difference in the hazard of all-cause mortality during the follow-up period after adjusting for sociodemographic and clinical factors among women with MRI (HR 0.90; 95% CI 0.72-1.12) compared to those without MRI. CONCLUSION: Our findings of no breast cancer-specific or all-cause mortality benefit supplement prior results that indicate a lack of improvement in surgical outcomes associated with use of preoperative MRI. In combination with other reports, the results of this analysis highlight the importance of exploring the benefit of preoperative MRI in patient-reported outcomes such as women's decision quality and confidence levels with decisions involving treatment choices.

Temporal trends in healthcare utilization following primary melanoma diagnosis among Medicare beneficiaries.

BACKGROUND: Little is known about the impact of primary melanoma diagnosis on healthcare utilization and changes in utilization over time. OBJECTIVES: To evaluate population-based temporal trends in healthcare utilization following primary melanoma diagnosis. METHODS: We conducted a before-and-after multiple time series study of Medicare beneficiaries aged ≥ 66 years with primary melanoma diagnoses between 2000 and 2009 using the Surveillance, Epidemiology, and End Results Medicare database. Primary exposure was time from primary melanoma diagnosis at 3-6 months and 6-24 months postdiagnosis. Covariates included tumour-, patient- and geographical-level characteristics and healthcare utilization in the 6 months before diagnosis. Poisson regression was used to estimate population-based risk-adjusted utilization rates for skin biopsies, benign skin excisions, internal medicine office visits and dermatology office visits. RESULTS: The study population included 56 254 patients with first diagnoses of primary melanoma. Most patients were ≥ 75 years old (56·8%), male (62·1%), and had in situ melanoma (42·4%) or localized invasive melanoma (45·9%). From 2000 to 2009, risk-adjusted skin biopsy rates 24 months postdiagnosis increased from 358·3 to 541·3 per 1000 person-years (P < 0·001), and dermatology visits increased from 989·0 to 1535·6 per 1000 person-years (P < 0·001). Benign excisions and internal medicine visits remained stable. In 2000, risk-adjusted skin biopsy rates 6 months postdiagnosis increased by 208·5 relative to the 6 months before diagnosis (148·7 vs. 357·2) compared with an observed absolute increase of 272·5 (290·9 vs. 563·1) in 2009. Trends in dermatology visits were similar. CONCLUSIONS: Utilization of skin biopsies and dermatology office visits following primary melanoma diagnosis has increased substantially over time. These results may inform optimization of care delivery for melanoma within the Medicare population.

Skin biopsy utilization and melanoma incidence among Medicare beneficiaries.

BACKGROUND: Melanoma incidence has increased in recent decades in the U.S.A. Uncertainty remains regarding how much of this increase is attributable to greater melanoma screening activities, potential detection bias and overdiagnosis. OBJECTIVES: To use a cross-sectional ecological analysis to evaluate the relationship between skin biopsy and melanoma incidence rates over a more recent time period than prior reports. METHODS: Examination of the association of biopsy rates and melanoma incidence (invasive and in situ) in SEER-Medicare data (including 10 states) for 2002-2009. RESULTS: The skin biopsy rate increased by approximately 50% (6% per year) throughout this 8-year period, from 7012 biopsies per 100 000 persons in 2002 to 10 528 biopsies per 100 000 persons in 2009. The overall melanoma incidence rate increased approximately 4% (< 1% per year) over the same time period. The incidence of melanoma in situ increased approximately 10% (1% per year), while the incidence of invasive melanoma increased from 2002 to 2005 then decreased from 2006 to 2009. Regression models estimated that, on average, for every 1000 skin biopsies performed, an additional 5·2 (95% confidence interval 4·1-6·3) cases of melanoma in situ were diagnosed and 8·1 (95% confidence interval 6·7-9·5) cases of invasive melanoma were diagnosed. When considering individual states, some demonstrated a positive association between biopsy rate and invasive melanoma incidence, others an inverse association, and still others a more complex pattern. CONCLUSIONS: Increased skin biopsies over time are associated with increased diagnosis of in situ melanoma, but the association with invasive melanoma is more complex.

Second fractures among older adults in the year following hip, shoulder, or wrist fracture.

UNLABELLED: We report on second fracture occurrence in the year following a hip, shoulder or wrist fracture using insurance claims. Among 273,330 people, 4.3 % had a second fracture; risk did not differ by first fracture type. Estimated adjusted second fracture probabilities may facilitate population-based evaluation of secondary fracture prevention strategies. INTRODUCTION: The purpose of this study was estimate second fracture risk for the older US population in the year following a hip, shoulder, or wrist fracture. METHODS: Observational cohort study of Medicare fee-for-service beneficiaries with an index hip, shoulder, or wrist fragility fracture in 2009. Time-to-event analyses using Cox proportional hazards models to characterize the relationship between index fracture type (hip, shoulder, wrist) and patient factors (age, gender, and comorbidity) on second fracture risk in the year following the index fracture. RESULTS: Among 273,330 individuals with fracture, 11,885 (4.3 %) sustained a second hip, shoulder or wrist fracture within one year. Hip fracture was most common, regardless of the index fracture type. Comparing adjusted second fracture risks across index fracture types reveals that the magnitude of second fracture risk within each age-comorbidity group is similar regardless of the index fracture. Men and women face similar risks with frequently overlapping confidence intervals, except among women aged 85 years or older who are at greater risk. CONCLUSIONS: Regardless of index fracture type, second fractures are common in the year following hip, shoulder or wrist fracture. Secondary fracture prevention strategies that take a population perspective should be informed by these estimates which take competing mortality risks into account.

The International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS)--quality of life during the first 4 months after fracture.

UNLABELLED: The quality of life during the first 4 months after fracture was estimated in 2,808 fractured patients from 11 countries. Analysis showed that there were significant differences in the quality of life (QoL) loss between countries. Other factors such as QoL prior fracture and hospitalisation also had a significant impact on the QoL loss. INTRODUCTION: The International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS) was initiated in 2007 with the objective of estimating costs and quality of life related to fractures in several countries worldwide. The ICUROS is ongoing and enrols patients in 11 countries (Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, UK and the USA). The objective of this paper is to outline the study design of ICUROS and present results regarding the QoL (measured using the EQ-5D) during the first 4 months after fracture based on the patients that have been thus far enrolled ICUROS. METHODS: ICUROS uses a prospective study design where data (costs and quality of life) are collected in four phases over 18 months after fracture. All countries use the same core case report forms. Quality of life was collected using the EQ-5D instrument and a time trade-off questionnaire. RESULTS: The total sample for the analysis was 2,808 patients (1,273 hip, 987 distal forearm and 548 vertebral fracture). For all fracture types and countries, the QoL was reduced significantly after fracture compared to pre-fracture QoL. A regression analysis showed that there were significant differences in the QoL loss between countries. Also, a higher level of QoL prior to the fracture significantly increased the QoL loss and patients who were hospitalised for their fracture also had a significantly higher loss compared to those who were not. CONCLUSIONS: The findings in this study indicate that there appear to be important variations in the QoL decrements related to fracture between countries.

Predicting EQ-5D-US and SF-6D societal health state values from the Osteoporosis Assessment Questionnaire.

SUMMARY: Linear regression was applied to data from 275 persons with osteoporosis-related fracture to estimate EQ-5D-US and SF-6D health state values from the Osteoporosis Assessment Questionnaire. The models explained 56% and 58% of the variance in scores, respectively, and root mean square error values (0.096 and 0.085) indicated adequate prediction for use when actual values are unavailable. INTRODUCTION: This study was conducted to provide models that predict EQ-5D-US and SF-6D societal health state values from the Osteoporosis Assessment Questionnaire (OPAQ). METHODS: OPAQ, EQ-5D, and SF-6D data from individuals at two centers with prior osteoporosis-related fracture were used. Fractures were classified by type as hip/hip-like, spine/spine-like, or wrist/wrist-like. Spearman rank correlations between preference-based system (EQ-5D and SF-6D) dimensions and OPAQ subscales were estimated. Linear regression was used to estimate preference-based system health state values based on OPAQ subscales. We assessed models including age, sex, and fracture type and chose the model with the best performance based on the root mean square error (RMSE) estimate. RESULTS: Among the 275 participants (198 women), with mean age of 68 years (range 50-94), the distribution of fracture types included 10% hip/5% hip-like, 18% spine/11% spine-like, and 24% wrist/18% wrist-like. The final regression model for EQ-5D-US included three OPAQ attributes (physical function, emotional status, and symptoms), predicted 56% of the variance in EQ-5D-US scores, and had a RMSE of 0.096. The final model for SF-6D, which included all four OPAQ dimensions, predicted 58% of the variance in SF-6D scores and had a RMSE of 0.085. CONCLUSIONS: Two models were developed to estimate EQ-5D-US and SF-6D health state values from OPAQ and demonstrated adequate prediction for use when actual values are not available.

Cost-effectiveness of Denosumab for the treatment of postmenopausal osteoporosis.

UNLABELLED: Denosumab is an injectable drug that reduces the risk of fractures. The objective was to estimate the cost-effectiveness of denosumab in a Swedish setting, also accounting for poor adherence to treatment. Denosumab is cost-effective, particularly for patients at high risk of fracture and low adherence to oral treatments. INTRODUCTION: Denosumab is a novel biologic agent developed for the treatment of osteoporosis and osteoporotic fractures that has been shown to reduce the risk of fractures in a phase III trial. The objective of this study was to estimate the cost-effectiveness of denosumab from a societal perspective compared with generic alendronate, branded risedronate, strontium ranelate, and no treatment in a Swedish setting. METHODS: A Markov cohort model was used to estimate the cost-effectiveness of denosumab given for up to 5 years to a typical Swedish patient population (women aged 71 years, T-score ≤ -2.5 SD and a prevalence of morphometric vertebral fractures of 34%). The model included treatment persistence and residual effect after discontinuation assumed to be equal to the time on treatment. Persistence with the comparator treatments and with denosumab was derived from prescription data and a persistence study, respectively. RESULTS: The base-case incremental cost-effectiveness ratios were estimated at €27,000, €12,000, €5,000, and €14,000, for denosumab compared with generic alendronate, risedronate, strontium ranelate, and no treatment, respectively. Sub-optimal persistence had the greatest impact in the comparison with generic alendronate, where the difference in drug cost was large. CONCLUSION: Improving persistence with osteoporosis treatment impacts positively on cost-effectiveness with a larger number of fractures avoided in the population targeted for treatment. Denosumab is a cost-effective alternative to oral osteoporosis treatments, particularly for patients at high risk of fracture and low expected adherence to oral treatments.

Identifying cost-effective treatment with raloxifene in postmenopausal women using risk algorithms for fractures and invasive breast cancer.

INTRODUCTION: The National Osteoporosis Foundation (NOF) recommends considering treatment in women with a 20% or higher 10-year probability of a major fracture. However, raloxifene reduces both the risk of vertebral fractures and invasive breast cancer so that raloxifene treatment may be clinically appropriate and cost-effective in women who do not meet a 20% threshold risk. The aim of this study was to identify cost-effective scenarios of raloxifene treatment compared to no treatment in younger postmenopausal women at increased risk of invasive breast cancer and fracture risks below 20%. METHOD: A micro-simulation model populated with data specific to American Caucasian women was used to quantify the costs and benefits of 5-year raloxifene treatment. The population evaluated was selected based on 10-year major fracture probability as estimated with FRAX® being below 20% and 5-year invasive breast cancer risk as estimated with the Gail risk model ranging from 1% to 5%. RESULTS: The cost per QALY gained ranged from US $22,000 in women age 55 with 5% invasive breast cancer risk and 15-19.9% fracture probability, to $110,000 in women age 55 with 1% invasive breast cancer risk and 5-9.9% fracture probability. Raloxifene was progressively cost-effective with increasing fracture risk and invasive breast cancer risk for a given age cohort. At lower fracture risk in combination with lower invasive breast cancer risk or when no preventive raloxifene effect on invasive breast cancer was assumed, the cost-effectiveness of raloxifene worsened markedly and was not cost-effective given a willingness-to-pay of US $50,000. At fracture risk of 15-19.9% raloxifene was cost-effective also in women at lower invasive breast cancer risk. CONCLUSIONS: Raloxifene is potentially cost-effective in cohorts of young postmenopausal women, who do not meet the suggested NOF 10-year fracture risk threshold. The cost-effectiveness is contingent on their 5-year invasive breast cancer risk. The result highlights the importance of considering a woman's full risk profile when considering anti-osteoporosis treatment.

Implications of absolute fracture risk assessment for osteoporosis practice guidelines in the USA.

UNLABELLED: Application of the WHO fracture prediction algorithm in conjunction with an updated US economic analysis indicates that osteoporosis treatment is cost-effective in patients with fragility fractures or osteoporosis, in older individuals at average risk and in younger persons with additional clinical risk factors for fracture, supporting existing practice recommendations. INTRODUCTION: The new WHO fracture prediction algorithm was combined with an updated economic analysis to evaluate existing NOF guidance for osteoporosis prevention and treatment. METHODS: The WHO fracture prediction algorithm was calibrated to the US population using national age-, sex- and race-specific death rates and age- and sex-specific hip fracture incidence rates from the largely white population of Olmsted County, MN. Fracture incidence for other races was estimated by ratios to white women and men. The WHO algorithm estimated the probability (%) of a hip fracture (or a major osteoporotic fracture) over 10 years, given specific age, gender, race and clinical profiles. The updated economic model suggested that osteoporosis treatment was cost-effective when the 10-year probability of hip fracture reached 3%. RESULTS: It is cost-effective to treat patients with a fragility fracture and those with osteoporosis by WHO criteria, as well as older individuals at average risk and osteopenic patients with additional risk factors. However, the estimated 10-year fracture probability was lower in men and nonwhite women compared to postmenopausal white women. CONCLUSIONS: This analysis generally endorsed existing clinical practice recommendations, but specific treatment decisions must be individualized. An estimate of the patient's 10-year fracture risk should facilitate shared decision-making.

Cost-effective osteoporosis treatment thresholds: the United States perspective.

UNLABELLED: A United States-specific cost-effectiveness analysis, which incorporated the cost and health consequences of clinical fractures of the hip, spine, forearm, shoulder, rib, pelvis and lower leg, was undertaken to identify the 10-year hip fracture probability required for osteoporosis treatment to be cost-effective for cohorts defined by age, sex, and race/ethnicity. A 3% 10-year risk of hip fracture was generally required for osteoporosis treatment to cost less than $60,000 per QALY gained. INTRODUCTION: Rapid growth of the elderly United States population will result in so many at risk of osteoporosis that economically efficient approaches to osteoporosis care warrant consideration. METHODS: A Markov-cohort model of annual United States age-specific incidence of clinical hip, spine, forearm, shoulder, rib, pelvis and lower leg fractures, costs (2005 US dollars), and quality-adjusted life years (QALYs) was used to assess the cost-effectiveness of osteoporosis treatment ($600/yr drug cost for 5 years with 35% fracture reduction) by gender and race/ethnicity groups. To determine the 10-year hip fracture probability at which treatment became cost-effective, average annual age-specific probabilities for all fractures were multiplied by a relative risk (RR) that was systematically varied from 0 to 10 until a cost of $60,000 per QALY gained was observed for treatment relative to no intervention. RESULTS: Osteoporosis treatment was cost-effective when the 10-year hip fracture probability reached approximately 3%. Although the RR at which treatment became cost-effective varied markedly between genders and by race/ethnicity, the absolute 10-year hip fracture probability at which intervention became cost-effective was similar across race/ethnicity groups, but tended to be slightly higher for men than for women. CONCLUSIONS: Application of the WHO risk prediction algorithm to identify individuals with a 3% 10-year hip fracture probability may facilitate efficient osteoporosis treatment.

Excess mortality following hip fracture: the role of underlying health status.

UNLABELLED: We evaluated the long-term excess mortality associated with hip fracture, using prospectively collected data on pre-fracture health and function from a nationally representative sample of U.S. elders. Although mortality was elevated for the first six months following hip fracture, we found no evidence of long-term excess mortality. INTRODUCTION: The long-term excess mortality associated with hip fracture remains controversial. METHODS: To assess the association between hip fracture and mortality, we used prospectively collected data on pre-fracture health and function from a representative sample of U.S. elders in the Medicare Current Beneficiary Survey (MCBS) to perform survival analyses with time-varying covariates. RESULTS: Among 25,178 MCBS participants followed for a median duration of 3.8 years, 730 sustained a hip fracture during follow-up. Both early (within 6 months) and subsequent mortality showed significant elevations in models adjusted only for age, sex and race. With additional adjustment for pre-fracture health status, functional impairments, comorbid conditions and socioeconomic status, however, increased mortality was limited to the first six months after fracture (hazard ratio [HR]: 6.28, 95% CI: 4.82, 8.19). No increased mortality was evident during subsequent follow-up (HR: 1.04, 95% CI: 0.88, 1.23). Hip-fracture-attributable population mortality ranged from 0.5% at age 65 among men to 6% at age 85 among women. CONCLUSIONS: Hip fracture was associated with substantially increased mortality, but much of the short-term risk and all of the long-term risk was explained by the greater frailty of those experiencing hip fracture.

Cost-equivalence of different osteoporotic fractures.

METHODS: Among 985 Olmsted County, Minnesota, residents who experienced an osteoporotic fracture (distal forearm, humerus, clavicle/scapula/sternum, ribs, vertebrae, pelvis, hip, other femur or tibia/fibula [the latter in women only]), we estimated the incremental cost of direct medical care in the following year compared with age- and sex-matched controls without a fracture randomly sampled from the same community. RESULTS: The overall median incremental (case minus control) cost in the succeeding year was $2,390, with a particularly high incremental cost for hip fractures ($11,241). There was fair concordance between the incremental cost of the different fractures, relative to hip fracture alone, and the previously published disutility associated with each fracture type relative to hip fracture. Overall, the incremental cost for all osteoporotic fractures combined was 46% greater than that for hip fractures alone in women and 47% greater in men. This is consistent with the earlier report that overall morbidity from all osteoporotic fractures combined is 47% and 39% greater in women and men, respectively, than the morbidity attributable solely to hip fractures. CONCLUSION: These data lend support to the notion that other osteoporotic fractures can be quantified relative to hip fracture on the basis of their cost, as well as their morbidity and mortality. This may simplify health economic analyses by allowing all fracture outcomes to be modeled relative to hip fractures (i.e., hip fracture 'equivalents') and will provide a more comprehensive assessment of osteoporosis outcomes than is possible by focusing only on hip fractures.

A cost-effectiveness analysis of universal versus selective immunization with Mycobacterium bovis bacille Calmette-Guérin in Finland.

SETTING: Mycobacterium bovis bacille Calmette-Guerin (BCG) is provided to all infants born in Finland. OBJECTIVE: To analyze the cost-effectiveness of universal versus selective BCG immunization. DESIGN: A Markov model was developed to simulate rates of tuberculosis (TB) and non-tuberculous mycobacterial disease (NTM), and to examine the cost-effectiveness in terms of cost per case averted of three different strategies: universal BCG, selective BCG (10% of infants at higher TB risk than other infants) or no BCG immunization. RESULTS: In a cohort of 60,000 infants over 15 years, the model predicts five cases each of TB and NTM disease with universal immunization, 8-21 TB and 31 NTM cases with various strategies of selective immunization, and 25 TB and 34 NTM cases with no BCG immunization. BCG side-effects are predicted in 5, 0.5 and 0 infants, respectively. The cost per case averted for immunization strategies ranges from a cost of 38,311 US dollars to a savings of 323 dollars as selective immunization becomes more efficient at targeting infants at highest risk of TB. CONCLUSIONS: In a country with a low incidence of pediatric tuberculosis, selective BCG immunization is a more cost-effective strategy than universal BCG immunization for the prevention of tuberculosis, but results in an increase in NTM cases.

Direct medical costs attributable to osteoporotic fractures.

Osteoporotic fractures are a major cause of morbidity in the elderly, the most rapidly growing segment of our population. We characterized the incremental direct medical costs following such fractures in a population-based cohort of men and women in Olmsted County, Minnesota. Cases included all County residents 50 years of age and older with an incident fracture due to minimal or moderate trauma between January 1, 1989 and January 1, 1992. For each case, a control of the same age (+/- 1 year) and sex who was attended in the local medical system in the same year was identified. Total incremental costs (cases - controls) in the year after fracture were estimated. Unit costs for each health service/procedure were obtained through the Mayo Cost Data Warehouse, which provides a standardized, inflation-adjusted estimate reflecting the national average cost of providing the service. Regression analysis was used to identify factors associated with incremental costs. There were 1263 case/control pairs; their average age was 73.8 years and 78% were female. Median total direct medical costs were $761 and $625, respectively, for cases and nonfracture controls in the year prior to fracture, and $3884 and $712, respectively, in the year following fracture. The highest median incremental costs were for distal femur ($11756) and hip fractures ($11241), whereas the lowest were for rib fractures ($213). Although hip fractures resulted in more incremental cost than any other fracture type, this amounted to only 37% of the total incremental cost of all moderate-trauma fractures combined. Regression analyses revealed that age, prior year costs and type of fracture were significant predictors of incremental costs (p<0.03 for all comparisons). The incremental costs of osteoporotic fractures are therefore substantial. Whereas hip fractures contributed disproportionately, they accounted for only one-third of the total incremental cost of fractures in our cohort. The use of incremental costs in economic analyses will provide a more accurate reflection of the true cost-effectiveness of osteoporosis prevention.

Challenges for model-based economic evaluations of postmenopausal osteoporosis interventions.

Assessing the cost-effectiveness of long-term treatment for osteoporosis requires use of mathematical models to estimate health effects and costs for competing interventions. The primary motivations for model-based analyses include the lack of long-term clinical trial outcome data and the lack of data comparing all relevant treatments within randomized clinical trials. We report on specific modeling challenges that arose in the development of a model of the natural history of postmenopausal osteoporosis that is suitable for assessing the cost-effectiveness of osteoporosis interventions among various population subgroups in diverse countries. These include choice of modeling changes in bone mineral density (BMD) or in fracture rate, definition of health states, modeling mortality and costs of long-term care following fracture, incorporation of health utility, and model validation. This report should facilitate future postmenopausal osteoporosis model development and provide insight for decision-makers who must evaluate model-based economic analyses of postmenopausal osteoporosis interventions.

A comparison of treatment strategies for hypoplastic left heart syndrome using decision analysis.

OBJECTIVES: We sought to identify the optimal treatment strategy for hypoplastic left heart syndrome (HLHS). BACKGROUND: Surgical treatment of HLHS involves either transplantation (Tx) or staged palliation of the native heart. Identifying the best treatment for HLHS requires integrating individual patient risk factors and center-specific data. METHODS: Decision analysis is a modeling technique used to compare six strategies: staged surgery; Tx; stage 1 surgery as an interim to Tx; and listing for transplant for one, two, or three months before performing staged surgery if a donor is unavailable. Probabilities were derived from current literature and a dataset of 231 patients with HLHS born between 1989 and 1994. The goal was to maximize first-year survival. RESULTS: If a donor is available within one month, Tx is the optimal choice, given baseline probabilities; if no donor is found by the end of one month, stage 1 surgery should be performed. When survival and organ donation probabilities were varied, staged surgery was the optimal choice for centers with organ donation rates < 10% in three months and with stage 1 mortality <20%. Waiting one month on the transplant list optimized survival when the three-month organ donation rate was > or =30%. Performing stage 1 surgery before listing, or performing stage 1 surgery after an unsuccessful two- or three-month wait for transplant, were almost never optimal choices. CONCLUSIONS: The best strategy for centers that treat patients with HLHS should be guided by local organ availability, stage 1 surgical mortality and patient risk factors.