Effect of Tocilizumab on Fatigue and Bone Mineral Density in Patients with Rheumatoid Arthritis.

BACKGROUND: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients. OBJECTIVES: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. METHODS: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. RESULTS: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data. CONCLUSIONS: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported.

The impact of the 21-gene Recurrence Score assay on clinical decision-making in node-positive (up to 3 positive nodes) estrogen receptor-positive breast cancer patients.

Oncotype DX testing is reimbursed in Israel for node-negative and node-positive (N1+; up to 3 positive nodes including micrometastases), estrogen receptor positive (ER+), breast cancer patients. This retrospective study evaluated the impact of Oncotype DX testing on treatment decisions in N1+/ER+ breast cancer patients. To this end, we compared treatments for all N+ patients for whom testing had been ordered with treatments for patients with similar characteristics where the test had not been available. The retrospective analysis included 951 patients (282 Oncotype DX, 669 controls), all of whom received endocrine therapy with or without chemotherapy. In Oncotype DX patients, 7.1, 37.0, and 100 % of those with low, intermediate, and high Recurrence Score results (Oncotype DX summary score) received chemotherapy, respectively (P < 0.0001, all comparisons). Chemotherapy use was lower in Oncotype DX patients versus controls (24.5 vs. 70.1 %). In a multivariate logistic regression analysis in which the probability of receiving chemotherapy was modeled as a function of Oncotype DX testing, age, tumor size, tumor grade, nodal status, and the interactions between Oncotype DX testing and the other covariates, Oncotype DX testing was associated with significantly lower odds of receiving chemotherapy (odds ratio 0.16; 95 % CI 0.11-0.24; P < 0.0001). In summary, our findings suggest that Oncotype DX testing has a significant impact on reducing chemotherapy use in N1+/ER+ breast cancer patients in Israel.

Twelve-year follow-up of a population-based primary care diabetes program in Israel.

OBJECTIVE: To describe the effects of a long-term intervention including 72% of Israeli diabetes patients, aimed at improving diabetes care in a primary care setting. DESIGN: A retrospective periodic population-based cross-sectional study. SETTING: Two health maintenance organizations (HMOs) in Israel-intervention and control. PARTICIPANTS: All diagnosed diabetes patients enrolled in both HMOs. INTERVENTION: Multifaceted interventions directed toward primary care providers, including educational strategies, registries, clinical pathways, care quality indicators, computerized reminders and feedback. MAIN OUTCOME MEASURES: Performance in quality indicators, compared with an HMO that did not implement an intervention program. RESULTS: The prevalence of diabetes increased from 20.2/1000 in 1995 to 63.7/1000 in 2007. Annual testing of hemoglobin A1c (HbA1c) rose from 22% in 1995 to 88% in 2007. The corresponding figures for low-density lipoprotein (LDL) were 23 and 89%, and for microalbumin 10 and 69%, respectively (P< 0.0001 for all comparisons). The proportion of HbA1c ≤7% increased from 10 to 53%, while HbA1c >9% decreased from 40 to 13% (P< 0.0001). Good control of LDL ≤100 mg/dl increased from 26 to 59% (P< 0.0001). In the comparison HMO, subtle increases in the performance of HbA1c (55.8-63.4%), LDL (59.7-67.0%) and microalbumin (55.1-67.6%) were noted between 2005 and 2007, respectively. HbA1c ≤7 and >9% remained stable (36 and 13%, respectively), while LDL ≤100 mg/dl rose from 38 to 44% in the control HMO. CONCLUSION: A community-oriented program for diabetes care led to improvements in performance of tests, as well as control of HbA1c and LDL among 72% of diabetes patients in Israel.

[The effect of the introduction of pneumococcal vaccination for adults as a quality measure on vaccination rates in Clalit Health Services].

BACKGROUND: The incidence of invasive pneumococcal infections in industrialized countries is above 50/100,000 annuaty in adults over the age of 65 years. The Israel Ministry of Health recommends 23-valent polysaccharide anti-pneumococcaL vaccination for patients with immune suppression or chronic diseases and citizens above the age of 65 years. METHODS: in 1.1.2008 pneumococcal vaccination for adults was introduced as a quality measure in CLalit Health Services (CHS). At the time of the introduction of pneumococcaL vaccination as a new quality measure in CHS, as one of 70 quality measures in community medicine, the target population included all CHS enrollees over 65 years of age and patients with specific chronic diseases. The relative weight of this quality measure within the set of CHS quality measures was set at 3.19%. The goal for the measure was set at 75%. Pneumococcal vaccination was paired with the influenza vaccination campaign. Mandatory copayment was reduced from NIS 57 to NIS 25 for enroLLees without supplementary medical insurance, and from NIS 11 to NIS 5 for enrollees with supplementary insurance. An alert for performing pneumococcaL vaccination for the target population was introduced into the medical software used by all CHS physicians. RESULTS: During a period of two years foLLowing the introduction of pneumococcaL vaccination as a quality measure in CHS, approximately 400,000 CHS enrollees within the target population received pneumococcaL vaccination, and the rate of immunization increased 10-fold (with respect to August 2007). CONCLUSION: The introduction of pneumococcal vaccination as a quality measure in CHS, coupled by other managerial and service-related actions, substantially increased the vaccination rates.

[The quality indigators program in Clalit Health Services: the first decade].

The quality indicators program in the community has existed in Clalit Health Services for over a decade. As a part of this program, approximately 70 evidence-based quality indicators have been defined, in 11 different domains. The indicators relate to preventive medicine (immunizations, early detection of diseases, e.g. colorectal cancer, breast cancer, hypertension, chronic renal failure), chronic disease management (diabetes, hyperlipidemia, ischemic heart disease, asthma, congestive heart failure), care of the elderly (prevention of repeated hospitalizations) and child care (obesity detection, anemia detection and treatment). The indicators program is founded on one of the worldwide leading information systems, based on a common data warehouse with data regarding sociodemographic factors, purchase of medications, health services utilization, laboratory and imaging data, as well as a unique, validated registry of chronic diseases. The program has led to progress in several domains, including control of diabetes and hyperlipidemia, pneumococcal vaccination and early detection of colorectal cancer. The program narrowed the gaps and reduced inequalities between the Arab and Jewish populations, and between socioeconomic levels. The improvement in quality indicators is based on teamwork of physicians, nurses, other health professionals and administrative staff. The day-to-day work and the major effort invested in Clalit's enrollees are reflected in the continuing improvement in clinical quality.

Sensitivity, but not specificity, of a quantitative immunochemical fecal occult blood test for neoplasia is slightly increased by the use of low-dose aspirin, NSAIDs, and anticoagulants.

OBJECTIVES: We evaluated the effect of the use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), and anticoagulants on the performance of immunochemical fecal occult blood test (I-FOBT). METHODS: A prospective, cross-sectional study of 1,221 ambulatory patients having total colonoscopy after preparing three I-FOBTs. Information regarding the use of medications was collected from the health medical organization (HMO) database. I-FOBT was analyzed with the OC-MICRO instrument using both >or=75 and 100 ngHb/ml of buffer thresholds to determine positivity. RESULTS: Colorectal cancer (CRC) was found in 17 and advanced adenomatous polyp (AAP) in 97 patients. A total of 212 patients were using aspirin/NSAIDS at the time of I-FOBT testing. Qualitative analysis for the detection of AAP/CRC reveals a trend for an increased sensitivity with aspirin/NSAIDS use. At the threshold 75 ng/ml for positivity, the sensitivity for the detection of AAP/CRC was 66.7% for aspirin/NSAIDS use vs. 51.2% for nondrug takers (P=0.20), and at the threshold of 100 ng/ml, the sensitivity was 66.7 vs. 46.5% (P=0.09). The specificity, however, was not affected by the use of aspirin/NSAIDS. At the threshold of 75 ng/ml for positivity, the specificity for the detection of AAP/CRC was 89.5% for aspirin/NSAIDS use vs. 91.2% for nondrug takers (P=0.47), and at the threshold of 100 ng/ml, the specificity was 92.17 vs. 93.0% (P=0.69). A total of 33 patients were using antithrombotics/coagulants at the time of I-FOBT testing. This group was small; however, it appears that their use was also associated with a trend for increased sensitivity and no change in specificity. CONCLUSIONS: The use of aspirin/NSAIDS and anticoagulants was associated with a trend for increased sensitivity with no change in specificity for the detection of AAP/CRC. This study suggests that there is no need to stop these agents before I-FOBT testing.

Effectiveness of dasabuvir/ombitasvir/paritaprevir/ritonavir for hepatitis C virus in clinical practice: A population-based observational study.

BACKGROUND: Direct acting antivirals for hepatitis C virus have shown dramatic results in clinical trials. However, their effectiveness has yet to be demonstrated within observational cohorts which lack exclusion criteria found in randomized control trials. AIM: To determine the effectiveness of dasabuvir/ombitasvir/paritaprevir/ritonavir in achieving sustained virological response. METHODS: Retrospective observational cohort study of all Clalit Health Services members with hepatitis C virus genotype 1 who were dispensed dasabuvir/ombitasvir/paritaprevir/ritonavir from January 1, 2015 to-November 31, 2015. RESULTS: There were 564 participants during the study period. The average age was 61.9 years, 52.0% were male, and 61.5% were born Eastern/Central Europe or Central Asia. The prevalence of diabetes was 31.7% and 70.3% were overweight/obese. Cirrhosis was present in 41.0% of participants, of whom 52.8% had stage 4 fibrosis. Of the cohort, 416 (74.8%) had follow-up viral load testing at 10 or more weeks after the end of treatment. We report a sustained virological response of 98.8% among those tested. CONCLUSIONS: Treatment with dasabuvir/ombitasvir/paritaprevir/ritonavir demonstrated a near universal effectiveness in achieving a sustained virological response among HCV patients in a large cohort.

The use of focus groups as a basis for planning and implementing culturally appropriate health promotion among people with diabetes in the Arab community.

OBJECTIVE: The main study objective was to identify perceived barriers to achieving glycemic control among the Arab population in Israel, by both members of the Arab community with type 2 diabetes and by primary care teams working with the Arab community. METHODS: A series of six focus groups using qualitative research methodology were conducted in two phases among people with diabetes and primary care professionals treating them. RESULTS: The perception of the disease among people with diabetes was one of low severity. Barriers to adopting a healthy lifestyle and to self-management included awareness of the need, financial considerations regarding medication, and traditional gender roles. Food preparation in family life was identified as a strong cultural determinant. The health literacy needs for more in-depth and accessible educational programs were identified. Primary care staff viewed the needs similarly, with the exception of the need for in-depth instructional materials. CONCLUSION AND PRACTICE IMPLICATIONS: The understanding of the significance of healthy lifestyles and self-management was essential for developing culturally appropriate implementation programs and policy. Consultation with, and involvement of patient groups in needs assessment and planning is essential and should be established in policy that promotes best practice and health promotion in chronic illness.

Clinical experience with repaglinide in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND: Repaglinide, a new insulin secretagogue, is purported to be as effective as sulphonylurea but is less hypoglycemic-prone. OBJECTIVES: To assess the efficacy of repaglinide and its proclivity for hypoglycemia in a post-marketing study. METHODS: The study group comprised 688 patients, aged 26-95 years, clinically diagnosed with non-insulin-dependent type 2 diabetes. The patients were divided into three groups based on previous therapy: a) sulphonylurea-treated (group 1, n = 132); b) metformin with or without sulphonylurea where sulphonylurea was replaced with repaglinide (group 2, n = 302); and c) lifestyle modification alone (drug-naive) (group 3, n = 254). At initiation of the study, all patients were transferred from their current treatment to repaglinide. Only patients in group 2, with combined sulphonylurea plus metformin, continued with metformin plus repaglinide. Fasting blood sugar, hemoglobin A1c and weight were measured at study entry and 4-8 weeks following repaglinide therapy. A questionnaire documented the number of meals daily and the presence of eating from fear of hypoglycemia. RESULTS: The fasting blood sugar level of the entire cohort dropped from 191 +/- 2.4 to 155 +/- 2.0 mg/dl (P < 0.0001); HbA1c from 8.8 +/- 0.1 to 7.7 +/- 0.1% (P < 0.0001). The drop of HbA1c in groups 1, 2 and 3 respectively were: 1.04 +/- 0.22% (P < 0.0001), 1.14 +/- 0.24% (P < 0.0001), and 1.51 +/- 0.31% (P = 0.0137). Weight dropped from 81 +/- 0.7 to 80.2 +/- 0.7 kg (P < 0.0001), and eating from fear of hypoglycemia from 157 to 97 (P < 0.001). The daily number of meals decreased from 2.9 +/- 0.4 to 2.4 +/- 0.4 (P < 0.001). No serious adverse reactions occurred during the study. CONCLUSIONS: Repaglinide is an effective oral hypoglycemic agent taken either as monotherapy or combination therapy. There is less eating to avoid hypoglycemia, fewer meals consumed, and weight loss.

Maternal-fetal medicine--how can we practically connect the "M" to the "F"?

Maternal-fetal medicine (MFM) is a multidisciplinary subspecialty dedicated to optimization of pregnancy and perinatal outcomes. MFM utilizes novel technologies for diagnostics and treatments in order to optimize obstetrical care and pregnancy outcome. Although defined as maternal and fetal medicine, originally aiming to equally address fetal and/or maternal issues, in reality the main focus of MFM has been shifted from improving maternal outcome and preventing maternal short- and long-term complications to improving fetal and neonatal outcome. In this article, we address the lack of communication between the two subspecialties and propose a resolution that will bridge the discrepancies by proposing to connect the leading hypotheses in MFM and in fetal medicine to those in maternal medicine.

Pregnancy and neonatal outcome after bariatric surgery.

The global obesity epidemic is changing the face of maternal-fetal medicine. One in five women is obese at time of conception, and increasing numbers of parturients have undergone bariatric surgery. Recent publication of large, population-based studies and comparison studies of preoperative and post-operative pregnancies have highlighted new risks and benefits to the mother and child. Pregnancy after bariatric surgery appears to effectively reduce the risk of complications such as fetal macrosomia, gestational diabetes mellitus, and hypertensive disorders of pregnancy; however, women who become pregnant after bariatric surgery may constitute a unique obstetric population with an increased risk for preterm and small-for-gestational-age infants. In this article, we provide an overview of the current knowledge of the impact of maternal bariatric surgery on neonatal and pregnancy outcomes.

Clinical Assessment of Individualized Glycemic Goals in Patients With Type 2 Diabetes: Formulation of an Algorithm Based on a Survey Among Leading Worldwide Diabetologists.

OBJECTIVE: Observations over the past few years have demonstrated the need to adjust glycemic targets based on parameters pertaining to individual patient characteristics and comorbidities. However, the weight and value given to each parameter will clearly vary depending on the experience of the provider, the characteristics of the patient, and the specific clinical situation. RESEARCH DESIGN AND METHODS: To determine if there is current consensus on a global level with regard to identifying these parameters and their relative importance, we conducted a survey among 244 key worldwide opinion-leading diabetologists. Initially, the physicians were to rank the factors they take into consideration when setting their patients' glycemic target according to their relative importance. Subsequently, six clinical vignettes were presented, and the experts were requested to suggest an appropriate glycemic target. The survey results were used to formulate an algorithm according to which an estimate of the patient's glycemic target based on individualized parameters can be computed. Three additional clinical cases were submitted to a new set of experts for validation of the algorithm. RESULTS: A total of 151 (61.9%) experts responded to the survey. The parameters "life expectancy" and "risk of hypoglycemia from treatment" were considered to be the most important. "Resources" and "disease duration" ranked the lowest. An algorithm was constructed based on survey results. It was validated by presenting three new cases to 57 leading diabetologists who suggested glycemic targets that were similar to those calculated by the algorithm. CONCLUSIONS: The resultant suggested algorithm is an additional decision-making tool offered to the clinician to supplement clinical decision making when considering a glycemic target for the individual patient with diabetes.

Sustained Reduction in Health Disparities Achieved through Targeted Quality Improvement: One-Year Follow-up on a Three-Year Intervention.

OBJECTIVE: To assess a quality improvement disparity reduction intervention and its sustainability. DATA SOURCES/STUDY SETTING: Electronic health records and Quality Index database of Clalit Health Services in Israel (2008-2012). STUDY DESIGN: Interrupted time-series with pre-, during, and postintervention disparities measurement between 55 target clinics (serving approximately 400,000 mostly low socioeconomic, minority populations) and all other (126) clinics. DATA COLLECTION/EXTRACTION METHODS: Data on a Quality Indicator Disparity Scale (QUIDS-7) of 7 indicators, and on a 61-indicator scale (QUIDS-61). PRINCIPAL FINDINGS: The gap between intervention and nonintervention clinics for QUIDS-7 decreased by 66.7 percent and by 70.4 percent for QUIDS-61. Disparity reduction continued (18.2 percent) during the follow-up period. CONCLUSIONS: Quality improvement can achieve significant reduction in disparities in a wide range of clinical domains, which can be sustained over time.

Defining the role of medication adherence in poor glycemic control among a general adult population with diabetes.

AIMS: This study assesses the attributable impact of adherence to oral glucose medications as a risk factor for poor glycemic control in population subgroups of a large general population, using an objective medication adherence measure. METHODS: Using electronic health records data, adherence to diabetes medications over a two-year period was calculated by prescription-based Medication Possession Ratios for adults with diabetes diagnosed before January 1, 2010. Glycemic control was determined by the HbA1c test closest to the last drug prescription during 2010-2012. Poor control was defined as HbA1c>75 mmol/mol (9.0%). Medication adherence was categorized as "good" (>80%), "moderate" (50-80%), or "poor" (<50%). Logistic regression models assessed the role medication adherence plays in the association between disease duration, age, and poor glycemic control. We calculated the change in the attributable fraction of glucose control if the non-adherent diabetic medication population would become adherent by age-groups. RESULTS: Among 228,846 diabetes patients treated by oral antiglycemic medication, 46.4% had good, 28.8% had moderate, and 24.8% had poor adherence. Good adherence rates increased with increasing disease duration, while glycemic control became worse. There was a strong inverse association between adherence level and poor control (OR = 2.50; CI = 2.43-2.58), and adherence was a significant mediator between age and poor control. CONCLUSIONS: A large portion of the diabetes population is reported to have poor adherence to oral diabetes medications, which is strongly associated with poor glycemic control in all disease durations. While poor adherence does not mediate the poorer glycemic control seen in patients with longer-standing disease, it is a significant mediator of poor glycemic control among younger diabetes patients. A greater fraction of poorly controlled younger patients, compared to older patients, could be prevented if at least 80% adherence to their medications was achieved. Therefore, our results suggest that interventions to improve adherence should focus on this younger sub-group.

The cost-effectiveness of gestational diabetes screening including prevention of type 2 diabetes: application of a new model in India and Israel.

OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with elevated risks of perinatal complications and type 2 diabetes mellitus, and screening and intervention can reduce these risks. We quantified the cost, health impact and cost-effectiveness of GDM screening and intervention in India and Israel, settings with contrasting epidemiologic and cost environments. METHODS: We developed a decision-analysis tool (the GeDiForCE™) to assess cost-effectiveness. Using both local data and published estimates, we applied the model for a general medical facility in Chennai, India and for the largest HMO in Israel. We computed costs (discounted international dollars), averted disability-adjusted life years (DALYs) and net cost per DALY averted, compared with no GDM screening. RESULTS: The programme costs per 1000 pregnant women are $259,139 in India and $259,929 in Israel. Net costs, adjusted for averted disease, are $194,358 and $76,102, respectively. The cost per DALY averted is $1626 in India and $1830 in Israel. Sensitivity analysis findings range from $628 to $3681 per DALY averted in India and net savings of $72,420-8432 per DALY averted in Israel. CONCLUSION: GDM interventions are highly cost-effective in both Indian and Israeli settings, by World Health Organization standards. Noting large differences between these countries in GDM prevalence and costs, GDM intervention may be cost-effective in diverse settings.

Global adaptation of IADPSG recommendations: a national approach.

The current practice for diagnosing gestational diabetes mellitus (GDM) in Israel employs a two-step screening approach using a 50 g glucose challenge test (GCT) followed by a 3-hour 100 g oral glucose tolerance test (OGTT). The overall adherence to this process is more than 90%. Recently, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommended changing this practice to a single-step GDM screening, employing a 75 g OGTT. New plasma glucose cutoffs were recommended. To make recommendations for a new screening and diagnosis policy for GDM in Israel, a committee was assembled, including representatives of professional medical organizations, health maintenance organizations (HMOs), health policy makers, epidemiologists and biostatisticians. There was agreement that a consensus can be achieved only by clinical evidence and that consensus is a key factor for changing health policy. It was also realized that the availability of local data on the annual rates of GDM, its complications, and cost-effectiveness of screening and treatment are suboptimal. This generated two studies: the first provided additional analyses of data concerning Israeli women participating in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, and the second was a cost-effectiveness analysis based on Clalit Health Service's (the largest HMO in the country) database. We found that the prevalence of GDM in Israel is approximately 6% and is expected to increase to 9% by adopting the new IADPSG recommendations. The conclusion was that a one-step approach is presumed to be not only cost-effective but cost-saving, even under conservative estimates. We recommend such a process for other countries debating whether to change their GDM screening and diagnostic approach.

Reducing health disparities: strategy planning and implementation in Israel's largest health care organization.

OBJECTIVE: To describe an organization-wide disparity reduction strategy and to assess its success in quality improvement and reduction of gaps in health and health care. STUDY SETTING: Clalit Health Services, Israel's largest non-for-profit insurer and provider serving 3.8 million persons. STUDY DESIGN: Before and after design: quality assessment before and 12-month postinitiation of the strategic plan. A composite weighted score of seven quality indicators, measuring attainment of diabetes, blood pressure, and lipid control, lack of anemia in infants, and performance of mammography, occult blood tests, and influenza vaccinations. DATA EXTRACTION METHODS: Quality indicator scores, derived from Clalit's central data warehouse, based on data from electronic medical records. PRINCIPAL FINDINGS: Low-performing clinics, of low-socioeconomic and minority populations, were targeted for intervention. Twelve months after the initiation of the project continuous improvement was observed coupled with a reduction of 40 percent of the gap between disadvantaged clinics, serving ~10 percent of enrollees, and all other medium-large clinics. CONCLUSION: The comprehensive strategy, following a quality improvement framework, with a top-down top-management incentives and monitoring, and a bottom-up locally tailored interventions, approach, is showing promising results of overall quality improvement coupled with disparity reduction in key health and health care indicators.

Reduction in sex-based mortality difference with implementation of new cardiology guidelines.

BACKGROUND: Mortality from acute coronary syndrome has historically been higher in women as compared with men. We hypothesized that adoption of a more sensitive definition for the diagnosis of acute myocardial infarction and managing patients according to the 2000 European Society of Cardiology and American College of Cardiology guidelines would reduce this difference. METHODS: A retrospective cohort study was conducted of all acute coronary syndrome admissions to 7 regional tertiary hospitals in Israel during 1999-2004. The primary end point was all-cause 1-year mortality. Differences in risk between men and women were assessed using Cox proportional hazards regression. RESULTS: The number of patients admitted with acute coronary syndrome was 20,206 and 15,583 before and after adoption of the guidelines, respectively. An invasive strategy during the index hospitalization was more frequent in men in both the pre- (47.6% vs 33.6, P <.001) and post- (55.7% vs 40.9%, P <.001) transition periods. Secondary prevention was intensified in the post-transition period in both sexes. Multivariate analysis adjusting for differences in baseline clinical characteristics between men and women and invasive strategy demonstrated that female sex was associated with increased 1-year mortality during the pretransition period (hazard ratio 1.34, 95% confidence interval, 1.24-1.45), but was not a significant factor in the post-transition period (hazard ratio 1.04, 95% confidence interval, 0.94-1.14). CONCLUSIONS: The transition to the 2000 European Society of Cardiology and American College of Cardiology guidelines was associated with a reduction in the sex-based mortality difference in patients with acute coronary syndrome despite the fact that an early invasive strategy and secondary prevention continued to be underutilized in female patients in both periods.