A cost-effectiveness analysis of intrauterine spacers used to prevent the formation of intrauterine adhesions following endometrial cavity surgery.

AIM: To assess, from a United States (US) payer's perspective, the cost-effectiveness of gels designed to separate the endometrial surfaces (intrauterine spacers) placed following intrauterine surgery. MATERIALS AND METHODS: A decision tree model was developed to estimate the cost-effectiveness of intrauterine spacers used to facilitate endometrial repair and prevent the formation (primary prevention) and reformation (secondary prevention) of intrauterine adhesions (IUAs) and associated pregnancy- and birth-related adverse outcomes. Event rates and costs were extrapolated from data available in the existing literature. Sensitivity analyses were conducted to corroborate the base case results. RESULTS: In this model, using intrauterine spacers for adhesion prevention led to net cost savings for US payers of $2,905 per patient over a 3.5-year time horizon. These savings were driven by the direct benefit of preventing procedures associated with IUA formation ($2,162 net savings) and the indirect benefit of preventing pregnancy-related complications often associated with IUA formation ($3,002). These factors offset the incremental cost of intrauterine spacer use of $1,539 based on an assumed price of $1,800 and the related increase in normal deliveries of $931. Model outcomes were sensitive to the probability of preterm and normal deliveries. Budget impact analyses show overall cost savings of $19.96 per initial member within a US healthcare plan, translating to $20 million over a 5-year time horizon for a one-million-member plan. LIMITATIONS: There are no available data on the effects of intrauterine spacers or IUAs on patients' quality of life. Resultingly, the model could not evaluate patients' utility related to treatment with or without intrauterine spacers and instead focused on costs and events avoided. CONCLUSION: This analysis robustly demonstrated that intrauterine spacers would be cost-saving to healthcare payers, including both per-patient and per-plan member, through a reduction in IUAs and improvements to patients' pregnancy-related outcomes.

Every year, women in the United States (US) undergo surgery to treat intrauterine abnormalities to maintain or improve the uterus' ability to support fetal development and result in a term delivery. Despite the benefits of these procedures, damage caused to the endometrium (uterine lining) is associated with a risk of adherence of the endometrial cavity surfaces with scar tissue known as intrauterine adhesions (IUAs).Damage to the endometrium and the resulting IUAs may be associated with infertility, light or absent menstruation, pregnancy loss, and other pregnancy-related complications. Treating these conditions within the US healthcare system consumes resources and adds costs for healthcare payers (public and private insurance providers).To facilitate endometrial repair and to reduce or prevent IUAs, researchers have developed materials to place within the endometrial cavity following surgery to separate the endometrial surfaces during the early healing period. These intrauterine "spacers" are intended to improve patients' subsequent clinical outcomes and save money for healthcare payers. It is unknown whether these improved clinical outcomes offset the cost of the routine use of spacers following "at-risk" procedures that involve the endometrial cavity.We developed a model designed to determine the cost-effectiveness of an intrauterine spacer by quantifying improvements in clinical outcomes and the resultant cost savings for patients undergoing uterine surgeries with or without spacers. Our model predicted that routinely using such spacers following at-risk procedures would improve patient outcomes and reduce costs to US payers.

Quality of Life in Primary Open-Angle Glaucoma and Cataract: An Analysis of VFQ-25 and OSDI From the iStent inject® Pivotal Trial.

OBJECTIVE: To assess quality of life (QOL) as measured by patient-reported outcomes (PRO) within the iStent inject® pivotal trial. DESIGN: Randomized controlled trial analysis of secondary outcomes. METHODS: The Vision Function Questionnaire (VFQ-25) and Ocular Surface Disease Index (OSDI) questionnaire were administered at baseline and at months 1, 6, 12, and 24. PRO responders were defined as patients reaching improvement based on minimally important differences. RESULTS: A total of 505 patients were randomized (386 iStent inject® [Glaukos], 119 surgery alone). The iStent inject® group exhibited a greater percentage of PRO responders across all follow-up visits over 24 months, averaging 58.0% vs 45.8%; P < .05 for VFQ-25 composite scores and 56.7% vs 48.9%; P < .05 for OSDI composite scores. Odds of being a responder in the iStent inject® group was 60% (P < .05) higher for the VFQ-25 and 32% (P > .05) higher for the ODSI. Driving (49.0% vs 28.8%; P < .05), ocular pain (59.3% vs 47.2%; P < .05), and general vision (71.8% vs 60.0%; P < .05) were the VFQ-25 subscales responsible for differences between treatment groups. At month 24, 76.5% of VFQ-25 responders and 62.5% of nonresponders were medication free regardless of treatment group (P < .05). CONCLUSIONS: Exploratory analysis suggests that by reducing medication dependence, implantation with the micro-scale iStent inject® device with cataract surgery may improve QOL vs cataract surgery alone over 24 months, with improvements influenced by ocular symptoms and vision-related activities.

"Real-World" Comparison of Prasugrel With Ticagrelor in Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention in the United States.

OBJECTIVES: The 30-day clinical outcomes with prasugrel or ticagrelor were compared using a US payer database in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). BACKGROUND: Prasugrel and ticagrelor demonstrated superior efficacy with increased non-coronary artery bypass graft major bleeding compared with clopidogrel in randomized clinical trials. No direct randomized or observational studies have compared clinical outcomes between prasugrel and ticagrelor. METHODS: Patients hospitalized for ACS-PCI between August 1, 2011 and April 30, 2013 and prescribed prasugrel or ticagrelor were selected. Drug treatment cohorts were propensity matched based upon demographic and clinical characteristics. The primary objective compared 30-day net adverse clinical events (NACE) in prasugrel- and ticagrelor-treated patients using a prespecified 20% noninferiority margin. Secondary objectives included comparisons of major adverse cardiovascular events (MACE) and major bleeding. RESULTS: Data were available for 16,098 patients (prasugrel, n = 13,134; ticagrelor, n = 2,964). In unmatched cohorts, prasugrel-treated patients were younger with fewer comorbidities than ticagrelor-treated patients, and 30-day NACE rates were 5.6 and 9.3%, respectively (P < 0.001). Following propensity matching, NACE was noninferior (P < 0.001) and 22% lower in prasugrel-treated than in ticagrelor-treated patients (RR, 0.78; 95% CI, 0.64-0.94). A 30-day adjusted MACE (RR, 0.80; 95% CI, 0.64-0.98) and major bleeding (RR, 0.65; 95% CI, 0.45-0.95) were also lower in prasugrel-treated patients compared with ticagrelor-treated patients. CONCLUSIONS: In this "real-world," retrospective, observational study, physicians appear to preferentially use prasugrel in younger patients with lower risk of bleeding or comorbidities compared with ticagrelor. Following adjustment, clinical outcomes associated with prasugrel use appear as good, if not better, than those associated with ticagrelor in ACS-PCI patients. © 2015 Wiley Periodicals, Inc.

Management of cystic or predominantly cystic thyroid nodules: role of simple aspiration of internal fluid.

PURPOSE: The purpose of this study is to evaluate the efficacy of simple aspiration of cystic thyroid nodules by comparing with control groups to exclude the occurrence of spontaneous regression by the definition of current guidelines of American Thyroid Association. MATERIALS AND METHODS: 217 nodules from 210 patients with cystic thyroid nodules (cystic portion >50%) were included. Nodules were classified into three groups as follows: Group 1, observation only; Group 2, fine needle aspiration (FNA) without aspiration of internal fluid; and Group 3, FNA after aspiration of internal fluid. Significant nodule size change was defined as a difference in the largest diameter of 20%, as seen on the last follow-up ultrasound (US) compared to the initial US. RESULTS: Demographic characteristics did not show significant differences among the three groups except for the patient age (p = 0.039). Mean nodule size significantly decreased only in group 3 (p = 0.005). Significant nodule size reductions were observed in 22.0% (13/59) in group 1, 25.7% (28/109) in group 2, and 40.8% (20/49) in group 3, respectively. CONCLUSIONS: Aspiration of internal fluid should be considered as the first-line procedure for both the diagnosis and treatment of cystic or predominantly cystic thyroid nodules.

Persistent organochlorines in 13 shark species from offshore and coastal waters of Korea: Species-specific accumulation and contributing factors.

Data on persistent organochlorines (OCs) in sharks are scarce. Concentrations of OCs such as polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were determined in the muscle tissue of 13 shark species (n=105) collected from offshore (Indian and Pacific Oceans) and coastal waters of Korea, to investigate species-specific accumulation of OCs and to assess the potential health risks associated with consumption of shark meat. Overall OC concentrations were highly variable not only among species but also within the same species of shark. The concentrations of PCBs, DDTs, chlordanes, hexachlorobenzene, and heptachlor in all shark species ranged from

Real-world cost-effectiveness: lower cost of treating patients to glycemic goal with liraglutide versus exenatide.

INTRODUCTION: While the liraglutide effect and action in diabetes (LEAD-6) clinical trial compared the efficacy and safety of liraglutide once daily (LIRA) to exenatide twice daily (EXEN) in adult patients with type 2 diabetes, few studies have explored the associated per-patient costs of glycemic goal achievement of their use in a real-world clinical setting. METHODS: This retrospective cohort study used integrated medical and pharmacy claims linked with glycated hemoglobin A1C (A1C) results from the IMS Patient-Centric Integrated Data Warehouse. Patients' ≥18 years and naïve to incretin therapies during a 6-month pre-index period, with ≥1 prescription for LIRA or EXEN between January 2010 and December 2010, were included. Patients with evidence of insulin use (pre- or post-index) were excluded. Only patients who were persistent on their index treatment during a 180-day post-index period were included. Follow-up A1C assessments were based on available laboratory data within 45 days before or after the 6-month post-index point in time. Diabetes-related pharmacy costs over the 6-month post-index period were captured and included costs for both the index drugs and concomitant diabetes medications. RESULTS: 234 LIRA and 182 EXEN patients were identified for the analysis. The adjusted predicted diabetes-related pharmacy costs per patient over the 6-month post-index period were higher for LIRA compared to EXEN ($2,002 [95% confidence interval (CI): $1,981, $2,023] vs. $1,799 [95% CI: $1,778, $1,820]; P < 0.001). However, a higher adjusted predicted percentage of patients on LIRA reached A1C < 7% goal (64.4% [95% CI: 63.5, 65.3] vs. 53.6% [95% CI: 52.6, 54.6]; P < 0.05), translating into lower average diabetes-related pharmacy costs per successfully treated patient for LIRA as compared to EXEN ($3,108 vs. $3,354; P < 0.0001). CONCLUSIONS: Although predicted diabetes-related pharmacy costs were greater with LIRA vs. EXEN, a higher proportion of patients on LIRA achieved A1C < 7%, resulting in a lower per-patient cost of A1C goal achievement with LIRA compared to EXEN.

Frequency of blood glucose testing among insulin-treated diabetes mellitus patients in the United Kingdom.

BACKGROUND: Through a retrospective database analysis, this study seeks to provide an understanding of the utilization of SMBG by insulin therapy and diabetes type and to estimate healthcare costs of blood glucose monitoring in the UK diabetes population. METHODS: Data were obtained from the IMS LifeLink Electronic Medical Record-Europe (EMR-EU) Database, a longitudinal database containing anonymized patient records from physician-practice data systems of office-based physicians in the UK. Depending on the insulin types used for type 1 and type 2 diabetes, patients were sub-categorized into one of four insulin regimen groups (basal, bolus, pre-mixed, or basal-bolus). Frequency of blood glucose testing was assessed descriptively throughout the 12-month post-index period, and generalized linear models were used to evaluate the effect of baseline characteristics, including insulin type, on the likelihood of blood glucose test utilization. Healthcare resource utilization and costs for all-cause services were assessed by insulin type. RESULTS: This study identified 8322 type 1 and type 2 diabetes patients with two insulin pharmacy records between January 1, 2009 and December 31, 2010. After applying study inclusion and exclusion criteria, a total of 2676 (32.2%) insulin-treated diabetes mellitus patients in the UK were identified, with the number of pharmacy blood glucose test strips averaging 771.1 (median 600). The glucose testing frequency was lowest among basal-only insulin patients and pre-mixed insulin patients (mean=576.2 [median=450] and mean=599.5 [median=500], respectively; non-significantly different) compared to other insulin types. CONCLUSION: Although the data did not capture the glucose frequency comprehensively, it varied significantly by insulin types, and was higher than what is recommended in the guidelines for patients with type 2 diabetes.

Safety assessment of an anti-obesity drug (sibutramine): a retrospective cohort study.

BACKGROUND: Obesity is a serious and rapidly growing health problem worldwide. Few therapies are available beyond diet, exercise and bariatric surgery. A previously approved medication, sibutramine, has been withdrawn from the market due to concerns over the potential of increased risk of cardiovascular (CV) events, based on a phase IV clinical trial that included only individuals at high risk for CV events. OBJECTIVE: The aim of the study was to compare sibutramine users and matched non-users on rates of CV events, both overall and stratified by whether the patient qualified for on-label sibutramine use, using data from real-life clinical practice. METHODS: A retrospective cohort was constructed from electronic medical record data from physician office practices (mostly primary care) in the UK and Germany, using the LifeLink™ database from IMS Health Incorporated. For patients with at least one physician visit in which sibutramine was prescribed between 1 April 1999 and 31 October 2008, the date of their first such prescription was their index date. Users and non-users were matched 1 : 1 on index date (within 30 days), sex, age group (six categories), Charlson Comorbidity Index and evidence of obesity (high body mass index [BMI] or, if BMI was missing, diagnosis of obesity or very high weight relative to height). The resultant total samples analysed were 6186 in Germany and 7264 in the UK. User and non-user cohorts in the samples were compared according to the ratio of their crude incidence rates of acute myocardial infarction (AMI), stroke and either AMI or stroke per 1000 patient-years of follow-up. Cox regression analysis was used to compare the risk of CV events as a hazard ratio (HR) with 95% confidence intervals (CIs) between sibutramine user and non-user cohorts, controlling for label status and/or history of prior CV disease at baseline. RESULTS: The risk of AMI, stroke and either AMI or stroke was not higher among sibutramine users than comparable non-users of sibutramine in both Germany and the UK [Germany: HR 0.47 (95% CI 0.17, 1.26), 0.43 (0.23, 0.81) and 0.44 (0.26, 0.75), respectively; UK: HR 0.44 (0.15, 1.31), 0.63 (0.25, 1.60) and 0.54 (0.27, 1.10), respectively]. Regardless of whether or not the model controlled for prior CV disease (CVD), the direction and statistical significance of the differences did not change. In the sensitivity analyses including only those without a history of CVD in the 365 days prior to the index date there was no increased risk of CV events in either Germany or the UK. CONCLUSION: This study offers a framework for the safety assessment of anti-obesity drugs using an observational epidemiological study design. Large electronic health databases were used to construct retrospective cohorts to examine the risk in a population using one specific anti-obesity drug. Use of sibutramine in general practice settings was not found to increase the risk of acute CV events.

Treatment pattern by hormone receptors and HER2 status in patients with metastatic breast cancer in the UK, Germany, France, Spain and Italy (EU-5): results from a physician survey.

BACKGROUND: The differences in country-specific treatment patterns across Europe for metastatic breast cancer (mBC) patients have not been extensively studied. This study compared the treatment choices in aggregate, as well as by biomarker status, between various lines of therapy in clinical practice in the EU-5 countries among newly diagnosed mBC patients. MATERIALS & METHODS: The IMS LifeLink™ Oncology Analyzer database, based on surveys of practicing oncologists, was used to identify mBC patients aged ≥21 years. In this database, sample-level data are projected to national-level estimates for each country using a sample projection technique. RESULTS: The prevalence of hormone receptors (71-74%) is quite similar across different countries, while HER2 overexpression varies from 22 (France) to 34% (Italy); chemotherapy combined with HER2-targeted medicine was the mainstay of treatment for HER2(+) patients. The use of HER2-targeted medicine and bevacizumab greatly varied: while they were most frequently used in France, they were least frequently used in the UK. Fewer treatment options existed for triple-negative patients and patients with HER2(+) disease following trastuzumab treatment. Chemotherapy was the treatment choice for triple-negative patients, as these patients do not respond to hormonal therapy and HER2-targeted medicine. CONCLUSION: This study found that, while a trastuzumab-based regimen is the preferred option for treating HER2(+) mBC patients in the EU-5, variations in this personalized medicine approach exist between different EU-5 countries. However, fewer treatment options exist for triple-negative and HER2(+) patients after trastuzumab treatment, highlighting the unmet need for these patient subgroups.

Imaging features of benign solid testicular and paratesticular lesions.

OBJECTIVE: The presence of an intratesticular solid lesion is usually highly suspicious for malignancy. Conversely, most extratesticular solid lesions including paratesticular lesions are benign. The characteristic imaging features of malignant solid testicular lesions are well known, but various unusual causes and imaging features of benign solid testicular lesions can be particularly misleading. Therefore, a careful assessment of solid testicular and paratesticular lesions is warranted. The purpose of this article is to present the clinical and imaging features of the spectrum of benign solid testicular and paratesticular lesions. METHODS: We demonstrate a variety of benign solid testicular and paratesticular lesions and correlate them with pathologic results. RESULTS: Specific the clinical and imaging features of the spectrum of benign solid testicular and paratesticular lesions have been described. CONCLUSIONS: Familiarity with the clinical setting and imaging features of benign solid testicular and paratesticular lesions should facilitate prompt, accurate diagnosis and treatment.

Thoracic splenosis: a case report and the importance of clinical history.

We present a case of thoracic splenosis in a 42-yr-old man with a medical history of abdominal surgery for a penetration injury with an iron bar of the left abdomen and back. He had been in good condition, but a chest radiograph taken during a regular checkup showed a multinodular left pleura-based mass. Computed tomography (CT) showed that the mass was well-enhanced and homogeneous, indicating a sclerosing hemangioma. Following its removal by video-assisted thoracoscopic surgery, the mass appeared similar to a hemangioma, with marked adhesion to the left side diaphragmatic pleura and lung parenchyma. Frozen section showed that the lesion was a solid mass consisted with abundant lymphoid cells, suggesting a low grade lymphoma. On permanent section, however, the mass was found to be composed of white pulp, red pulp, a thick capsule and trabeculae and was diagnosed as ectopic splenic tissue, or thoracic splenosis. Review of the patient's history and chest CT at admission revealed that the patient had undergone a splenectomy for the penetration injury 20 yr previously.

Results of a model analysis of the cost-effectiveness of liraglutide versus exenatide added to metformin, glimepiride, or both for the treatment of type 2 diabetes in the United States.

BACKGROUND: Nearly half of all US patients with type 2 diabetes mellitus (T2DM) are unable to maintain adequate glycosylated hemoglobin (HbA1(c)) control (ie, <7.0%). OBJECTIVE: The aim of this work was to determine the long-term cost-effectiveness of incretin-based therapy with once-daily liraglutide (vs twice-daily exenatide) combined with metformin, glimepiride, or both for the treatment of T2DM. METHODS: Patient data were obtained from the Liraglutide Effect and Action in Diabetes 6 (LEAD 6) trial. Baseline data included mean HbA1(c) (8.15%), age (56.7 years), disease duration (8 years), sex, body mass index, blood pressure, lipid levels, cardiovascular and renal risk factors, and other complications. The IMS Center for Outcomes Research Diabetes Model was used to project and compare lifetime (ie, 35-year) clinical and economic outcomes for once-daily liraglutide 1.8 mg compared with twice-daily exenatide 10 (ig, each used as add-on therapy with maximum-dose metformin and/or glimepiride. Treatment-effect assumptions were also derived from the LEAD 6 trial. Transition probabilities, utilities, and complication costs were obtained from published sources. All outcomes were discounted at 3% per annum, and the analysis was conducted from the perspective of a third-party payer in the United States. RESULTS: The base-case analysis indicated that, compared with exenatide, liraglutide add-on therapy was associated with a mean (SD) increase in life expectancy of 0.187 (0.250) years and an increase in qualityadjusted life-years of 0.322 (0.164) years. Compared with exenatide, total lifetime treatment costs for liraglutide were $12,956 higher, yielding an incremental costeffectiveness ratio (ICER) of $40,282. However, the costs of diabetes-related complications were lower with liraglutide than with exenatide ($49,784 vs $52,429, respectively). Sensitivity analysis indicated that setting patient HbA(1c) levels at the 95% upper limit reduced the ICER for liraglutide compared with exenatide to $33,086. CONCLUSION: In this model analysis using published clinical data and current medication acquisition price assumptions, liraglutide (in combination with metformin and/or glimepiride) appeared to be cost-effective in the US payer setting over a 35-year time horizon.

Value of intra-adnexal and extra-adnexal computed tomographic imaging features diagnosing torsion of adnexal tumor.

OBJECTIVE: The objective of this study was to evaluate the usefulness of the intra-adnexal and extra-adnexal computed tomographic (CT) features in identifying adnexal torsion. PATIENTS AND METHODS: We retrospectively analyzed CT examinations of 38 adnexal masses with torsion and 270 without torsion, which has been surgicopathologically confirmed. The CT features were evaluated according to 2 categorized groups. The first group included the intra-adnexal features dealing with the ovary and uterine tube, whereas the other included the extra-adnexal features dealing with changes of adjacent anatomical structures such as the uterus, gonadal vein, and peritumoral zone. We acquired statistical proportions for the frequencies of these 2 groups of CT features in ovarian tumors with adnexal torsion versus those without adnexal torsion. RESULTS: When there were intra-adnexal CT features of adnexal torsion, peculiar uterine tube thickening was identified in 74% of the lesions, eccentric or concentric wall thickening in 54% (of only cystic lesions), eccentric septal thickening in 50% (of only cystic lesions except mature cystic teratoma), and eccentric or diffuse decreased or poor contrast enhancement of the internal solid component or thickened wall in 50%. In extra-adnexal CT features of adnexal torsion, uterine deviation to the twisted side was identified in 61% of the lesions, peritumoral infiltration in 40%, nonvisualized anatomic continuity of the ipsilateral gonadal vein with the twisted adnexal mass in 71%, and ascites in 13%. There were significant differences in all of the intra-adnexal and extra-adnexal CT findings, except for ascites, between twisted and nontwisted adnexal tumors. CONCLUSIONS: The intra-adnexal and extra-adnexal groups of CT features are valuable in identifying torsion of adnexal mass.

Sonographic findings in a case of scrotal lymphangioma in a 68-year-old male.

Lymphangiomas are benign tumors resulting from a congenital lymphatic malformation in infant and children. Most common sites are head, neck and axilla, and scrotal lymphangioma is very rare. Lymphangiomas are classified as capillary, cavernous, and cystic type and cystic type is most common. Complete surgical excision is definitive treatment and incomplete excision leads to local recurrence. We report a case of scrotal lymphangioma in 68-year-old male patient. Gray-scale sonography revealed multiseptated, hypoechoic mass abutting the upper pole of the normal right testis. Color Doppler sonography showed no remarkable blood flow in the mass. MRI demonstrated multispetated extratesticular and extraepididymal mass in the right scrotum. Surgical excision was performed and the histopathologic diagnosis was a cystic lymphangioma. In conclusion when multiseptated cystic scrotal mass was discovered in an elderly patient, scrotal lymphangioma should be included in differential diagnosis.

A retrospective managed care claims data analysis of medication adherence to vaginal estrogen therapy: implications for clinical practice.

OBJECTIVES: This study sought to assess refill-based treatment duration and adherence to vaginal estrogen therapy (VET) in clinical practice and to compare treatment duration in women prescribed vaginal tablets (VT) or vaginal creams (VC) in clinical trials with that in clinical practice. METHODS: Adults initiating VET between January and June 2004 were identified in 57 commercial health plans in the United States and followed for up to 10 months after treatment initiation. Treatment duration (Kaplan-Meier analysis) and adherence (medication possession ratio [MPR]) were examined for VC and VT cohorts and compared with a weighted average of treatment duration calculated for seven clinical trials identified in the literature. RESULTS: Of 13,074 women (mean age 54 +/- 9.1 years) identified, patients on VT had significantly longer treatment duration compared with patients on VC (149.1 +/- 101.1 days vs. 91.6 +/- 30.0 days, p < 0.01). Among 5,599 patients receiving multiple prescriptions, higher treatment durations were observed for both VT-treated and VC-treated patients (198.5 +/- 82.4 days vs. 177.1 +/- 86.7 days, p < 0.01) compared with 165 days observed in clinical trials. Medication adherence (MPR > or = 80%) was significantly higher among VT users compared with VC users (74% +/- 27% vs. 52% +/- 32%], p < 0.01); OR, 3.24, 95% CI 2.84-3.70). CONCLUSIONS: Duration of VET among patients receiving multiple prescriptions was longer in real-world clinical practice than in clinical trials. Newly treated patients initiating VT were more likely to continue treatment for longer periods and exhibited greater medication adherence than did those on VC.

Perioperative myocardial ischemic injury in high-risk vascular surgery patients: incidence and clinical significance in a prospective clinical trial.

OBJECTIVE: The purpose of this study was to assess prospectively the incidence, health care resource utilization, and economic burden associated with perioperative myocardial ischemic injury (PMII) in high-risk patients undergoing noncardiac vascular surgery. METHODS: Two hundred thirty-six patients consented to participate in a pharmacoeconomic substudy as part of a randomized, multicenter clinical trial. Patients were assessed for myocardial ischemic injury by using clinical, biochemical, and electrocardiographic criteria. PMII was defined as fatal or nonfatal myocardial infarction, new or worsened congestive heart failure, or new arrhythmias. Resource utilization parameters were compared for patients with and without PMII. Patients underwent the following index procedures: open abdominal aortic aneurysm repair (n = 44), bypass for aortoiliac disease (n = 29), bypass for femoropopliteal disease (n = 62), bypass for femorotibial disease (n = 71), extra-anatomic bypass (n = 23), and miscellaneous (n = 7). Patients undergoing carotid endarterectomy or only endovascular interventions were excluded. The incremental cost of PMII was estimated by applying the average costs (adjusted to 2004 US dollars) of the hospital ward (dollar 700.00/d) or intensive care unit (dollar 2500.00/d) to the length of stay differences for patients with and without PMII. RESULTS: The overall mortality was 3.4% (8/236), and 7 of 8 deaths were related to PMII. PMII occurred in 42 (17.8%) of 236 patients: 22 myocardial infarctions, 11 congestive heart failures, and 12 new arrhythmias (3 patients had 2 PMII events). There was no evidence of differences in the incidence of PMII among the various index procedures. PMII was associated with a dramatic increase in resource utilization. The mean length of stay was 16.8 and 10.0 days for patients with and without PMII, respectively (P < .001). Intensive care unit care was required by 35 (83.3%) of 42 patients with and 121 (62.4%) of 194 patients without PMII (P < .009). The mean intensive care unit length of stay was 6.6 and 3.7 days for patients with and without PMII, respectively (P < .009). Ten (23.8%) of 42 patients with and 20 (10.3%) of 194 patients without PMII returned to the emergency department for care after discharge (P < .02). CONCLUSIONS: In modern vascular surgery practice, PMII remains common despite the availability of beta-blockers and other preventative strategies. PMII is associated with dramatic increases in resource utilization and cost. The increase in resource utilization associated with PMII resulted in an estimated incremental cost per patient of dollar 9980.00. If 250,000 high-risk open vascular operations are performed annually in the United States, the economic burden of PMII in these procedures alone approximates dollar 444 million. Strategies to decrease PMII incidence and severity should be evaluated in large-scale prospective trials.

Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer.

PURPOSE: Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density, a surrogate for fracture risk, in men with prostate cancer. We conducted a claims-based cohort study to characterize the relationship between GnRH agonists and risk for clinical fractures in men with nonmetastatic prostate cancer. PATIENTS AND METHODS: Using medical claims data from a 5% national random sample of Medicare beneficiaries, we identified a study group of men with nonmetastatic prostate cancer who initiated GnRH agonist treatment from 1992 to 1994 (n = 3,887). A comparison group of men with nonmetastatic prostate cancer who did not receive GnRH agonist treatment during the study period (n = 7,774) was matched for age, race, geographic location, and comorbidity. Clinical fractures were identified using inpatient, outpatient, and physician claims during 7 years of follow-up. RESULTS: In men with nonmetastatic prostate cancer, GnRH agonists significantly increased fracture risk. The rate of any clinical fracture was 7.88 per 100 person-years at risk in men receiving a GnRH agonist compared with 6.51 per 100 person-years in matched controls (relative risk, 1.21; 95% CI, 1.14 to 1.29; P < .001). Rates of vertebral fractures (relative risk, 1.45; 95% CI, 1.19 to 1.75; P < .001) and hip/femur fractures (relative risk, 1.30; 95% CI, 1.10 to 1.53; P = .002) were also significantly higher in men who received a GnRH agonist. GnRH agonist treatment independently predicted fracture risk in multivariate analyses. Longer duration of treatment conferred greater fracture risk. CONCLUSION: GnRH agonists significantly increase risk for any clinical fracture, hip fractures, and vertebral fractures in men with prostate cancer.

Natural history of bone complications in men with prostate carcinoma initiating androgen deprivation therapy.

BACKGROUND: As evidence accumulates in favor of androgen deprivation therapy (ADT) in patients with recurrent or metastatic prostate carcinoma, concern has increased regarding bone loss associated with therapeutic hypogonadism. The current study described the natural history of bone complications in men with prostate carcinoma who have initiated ADT. METHODS: Using 1992-2001 claims data from a 5% national random sample of Medicare beneficiaries, the authors identified men with prostate carcinoma who initiated ADT between 1992 and 1994. They analyzed inpatient, outpatient, and physician claims for bone complications over 7 subsequent years. They stratified the quartile of patients who survived longest into 2 cohorts: those who had received ADT for longer than and those who had received ADT for shorter than the median of 697 days. They evaluated the cumulative proportions of patients in each cohort with claims for pathologic fractures, osteoporosis/osteopenia, and nonpathologic fractures. RESULTS: In the 1992-1994 sample, 4494 men with prostate carcinoma initiated ADT. Of these, 1126 survived > 2028 days (5.5 years). During the first 3 years of evaluation, the proportion of bone events was similar for men with shorter durations of ADT and men with longer durations of ADT. However, by 7 years, more men in the longer ADT cohort (45%) had sustained at least 1 pathologic or nonpathologic fracture compared with men in the shorter ADT cohort (40%). CONCLUSIONS: In the current study, men with prostate carcinoma were found to be at risk for adverse bone effects from both the disease and the treatment. These longitudinal data revealed that fractures are common in this patient population and appear to be linked to the duration of ADT.

Blood pressure lowering and life expectancy based on a Markov model of cardiovascular events.

The life expectancy benefits of antihypertensive treatment, based on both systolic and diastolic blood pressure reduction, was estimated with a cardiovascular disease event Markov model with prospective data from 57 573 men and women. Seven patient states were defined, including (1) no cardiovascular disease, (2) stroke, (3) myocardial infarction, (4) revascularization, (5) history of cardiovascular disease, (6) noncardiovascular disease death, and (7) cardiovascular death. Risk functions were developed from gender-specific multivariate Cox proportional hazards models for primary events and age-, smoking-, and diabetes-adjusted models for secondary events. At baseline we assumed (1) hypothetical pretreatment blood pressures of 160/95 or 150/90 mm Hg; (2) strategies A and B lower blood pressure by 20/13 and 13/8 mm Hg, respectively; and (3) baseline age of 35 years. For subjects initially at 160/95 mm Hg, those with antihypertensive treatment, antihypertensive treatment and diabetes, or antihypertensive treatment, diabetes, and currently smoking had corresponding gains in life expectancy of 2.43, 2.80, and 2.43 years for Strategy A. An initial blood pressure of 150/90 mm Hg resulted in similar gains. Compared with Strategy B, with blood pressure reductions of 13/8 mm Hg, Strategy A provided additional gains in life expectancy of 0.84, 0.99, and 0.87 years for those with antihypertensive treatment, antihypertensive treatment and diabetes, or antihypertensive treatment, diabetes, and currently smoking. The initial blood pressure level did not affect the magnitude of life expectancy gains for equivalent blood pressure reductions. Greater gains in life expectancy among hypertensive and diabetic women suggest that blood pressure lowering may yield greater benefits in selected subgroups.