Challenges in implementing a pediatric cardiovascular home telehealth project.

OBJECTIVE: Infants with "single ventricle" congenital heart disease are at high risk for sudden death following palliative surgical management. We developed a pilot telemedicine project to evaluate the feasibility of using Web-based daily reporting of clinical data with the goal of reducing unexpected admissions and sudden death. SUBJECTS AND METHODS: We enrolled 9 subjects (enrolled subjects [ES]) following surgical palliation over 12 months. Parents electronically transmitted ES daily weight and oxygen saturation and then completed an automated 10-point phone questionnaire on nutrition, activity, and distress. Subject enrollment continued until a second surgical palliative procedure (n=5), sudden death (n=2), or disenrollment (n=2). We collected clinical data on all ES and 9 historical controls (HC) from the preceding 18 months and analyzed clinical management, including outpatient telephone surveillance success, scheduled and unscheduled office and emergency department visits, hospitalizations, procedures, and adverse events, including death. RESULTS: Subject recruitment was more difficult than expected. Weight transmission success was high, but there was poor correlation between telemedicine system-measured oxygen saturation and a commercial monitor. The outpatient clinical telephone surveillance success rate for HC and ES was approximately 30%. After technical adjustments, parents of all ES (100%) were able to transmit questionnaire data. There were 9 emergency room visits for ES versus 11 unscheduled emergency room visits for HC. Sudden death occurred in 1 of 9 HC and 2 of 9 ES. CONCLUSIONS: Telemedicine monitoring for high-risk congenital heart disease patients is feasible but challenging, may reduce unscheduled visits, but may not impact the primary end point of preventing sudden death in this high-risk pediatric population.

The competency index for clinical research professionals: a potential tool for competency-based clinical research academic program evaluation.

Background: Accreditation of graduate academic programs in clinical research requires demonstration of program achievement of Joint Task Force for Clinical Trial Competence-based standards. Evaluation of graduate programs include enrollment, student grades, skills-based outcomes, and completion rates, in addition to other measures. Standardized measures of competence would be useful. Methods: We used the Competency Index for Clinical Research Professionals (CICRP), in a separate-sample pretest-posttest study to measure self-confidence or self-efficacy in clinical research competency comparing cohorts of students entering and completing a master's degree program in clinical research across three semesters (summer 2021 - spring 2022). CICRP is a 20-item Likert scale questionnaire (0 = Not at all confident; 10 = extremely confident). Results: The study sample of 110 students (54 in the entry course, 56 in the exit course) showed overall 80.9% entered the program with only a baccalaureate degree and 55.5% had no prior experience in managing clinical trial research. Cronbach alpha for the instrument showed a high level of content validity (range 0.93-0.98). Median CICRP item rating range at entry was [1, 6] and at exit [7, 10]. Mean CICRP total score (sum of 20 items) at entry was 72.7 (SD 41.9) vs. 167.0 (SD 21.1) at exit (p < 0.001). Mean total score at program entry increased with increasing years of clinical trial management experience but attenuated at program exit. Conclusion: This is the first use of the CICRP for academic program evaluation. The CICRP may be a useful tool for competency-based academic program evaluation, in addition to other measures of program excellence.

The Competency of Clinical Research Coordinators: The Importance of Education and Experience.

BACKGROUND: The organization and operation of clinical trials have become increasingly complex requiring the coordination of a well-trained workforce to ensure that complicated protocols yield valid results that will advance human health. We hypothesized that formal education in clinical research is equivalent to a number of years of work experience as a clinical research professional in terms of self-perceived clinical research competence. METHODS: Using REDCap, we conducted a survey of students and recent graduates from academic programs in clinical research in the USA using the CICRP index that consists of 20 clinical research core competencies. We compared the responses of recent graduates to CRCs wording in the USA and Canada in various research settings who responded to a similar survey conducted by the Joint Task Force and to experienced CRCs working at research-intensive CTSA hubs and their affiliated hospitals who were surveyed as part of the NIH funded DIAMOND project. RESULTS: We found that the degree of self-perceived competence to perform advanced core competencies such as those related to regulatory affairs among new graduates of formal academic programs without research experience to be equivalent to as many as five years of on-the-job-training in a research-intensive CTSA setting and more than ten years of experience in less research-intensive community settings. CONCLUSIONS: These findings suggest that scores on both forms of the CICRP differentiate CRCs according to formal education in clinical research, years of experience as a CRC and type of research setting in which they work. Further, the self-perceived competency assessed by CICRP acquired by completing an academic program in clinical research is equivalent to years of work experience.

Meta-analysis: sequential therapy appears superior to standard therapy for Helicobacter pylori infection in patients naive to treatment.

BACKGROUND: Standard proton-pump inhibitor-based therapy for Helicobacter pylori infection fails in up to one quarter of patients. Sequential therapy may be more efficacious. PURPOSE: To compare sequential therapy with standard triple therapy for H. pylori infection. DATA SOURCES: MEDLINE, EMBASE (1981 to October 2007), the Cochrane Central Register of Controlled Trials, and Google Scholar. PubMed and Ovid were the search engines used. STUDY SELECTION: Randomized, controlled trials (RCTs) comparing sequential and standard triple therapies in treatment-naive patients with documented H. pylori infection. DATA EXTRACTION: 3 reviewers independently assessed trial eligibility and quality and extracted data on eradication. DATA SYNTHESIS: The crude rates of H. pylori eradication in 10 RCTs involving 2747 patients were 93.4% (95% CI, 91.3% to 95.5%) for sequential therapy (n = 1363) and 76.9% (CI, 71.0% to 82.8%) for standard triple therapy (n = 1384) (relative risk reduction, 71% [CI, 64% to 77%]; absolute risk reduction, 16 percentage points [CI, 14 to 19 percentage points]). The median rates of adherence were 97.4% (range, 90.0% to 98.9%) for sequential therapy and 96.8% (range, 93.0% to 100%) for standard therapy. Sequential therapy appeared superior in prespecified sensitivity (subgroup) analyses stratified by trial quality; smoking status; diagnosis (ulcer disease or nonulcer dyspepsia); resistance to clarithromycin, imidazoles, or both; duration of triple therapy; and method of diagnosis. Both treatments had similar side effect profiles. LIMITATIONS: Only 1 study was double-blinded. Most patients were from Italy. There was clear evidence of publication bias. CONCLUSION: Sequential therapy appears superior to standard triple therapy for eradication of H. pylori infection. If RCTs in other countries confirm these findings, 10-day sequential therapy could become a standard treatment for H. pylori infection in treatment-naive patients.

Another duel in the sun: weighing the balances between sun protection, tanning beds, and malignant melanoma.

OBJECTIVE: The purpose of this report is to put the dueling factors of risk and prevention for melanoma in perspective for the thoughtful pediatric specialist to facilitate preteen preventive health counseling. STUDY DESIGN: We examined the rate of malignant melanoma among Kentucky residents and compared this rate with indicators of tanning bed prevalence in a large metropolitan area and sunscreen sales from a major distributor. We obtained malignant melanoma annual incidence data from the Kentucky Cancer Registry, which recorded Kentucky population incidence rates over the years 1995 to 2004. The rates reflected 2 malignant melanoma classifications: pre-invasive cancer only, or both invasive and noninvasive cancers combined. RESULTS: The age-adjusted incidence rate per hundred thousand for combined invasive and pre-invasive malignant melanoma swelled from 21.9 in 1995 to 31.3 in 2004. The respective invasive-only malignant melanoma incidence rates increased less dramatically, from 17.3 to 20.7, during this same 10-year time period. Since 1983, the number of separate tanning bed businesses increased from 1 in 1983 to 119 by the mid-1990s, and then declined to about 74 separate businesses by 2003. Sunscreen sales data is uneven between states and is currently inconclusive. CONCLUSIONS: Although current data cannot draw a precise link between melanoma and the use of tanning beds, the associated risk is implicit, as the ultraviolet A (UVA) and ultraviolet B (UVB) radiation in tanning bed usage is a well-established melanoma risk factor. In advising patients, the pediatric specialist should consider that melanoma rates are poised as a balance of some known risk factors and a few potential preventive factors.

Indices of Clinical Research Coordinators' Competence.

INTRODUCTION: There is a clear need to educate and train the clinical research workforce to conduct scientifically sound clinical research. Meeting this need requires the creation of tools to assess both an individual's preparedness to function efficiently in the clinical research enterprise as well as tools to evaluate the quality and effectiveness of programs that are designed to educate and train clinical research professionals. Here we report the development and validation of a competency self-assessment entitled the Competency Index for Clinical Research Professionals, version II (CICRP-II). METHODS: CICRP-II was developed using data collected from clinical research coordinators (CRCs) participating in the "Development, Implementation and Assessment of Novel Training In Domain-Based Competencies" project at four clinical and translational science award (CTSA) hubs and partnering institutions. RESULTS: An exploratory factor analysis identified a two-factor structure: the first factor measures self-reported competence to perform routine clinical research functions while the second factor measures competence to perform advanced clinical functions. We demonstrate the between groups validity by comparing CRCs working in different research settings. DISCUSSION: The excellent psychometric properties of CICRP-II, its ability to distinguish between experienced CRCs at research intensive CTSA hubs and CRCs working in less intensive community-based sites coupled with the simplicity of alternative methods for scoring respondents make it a valuable tool for gauging an individual's perceived preparedness to function in the role of CRC as well as an equally valuable tool to evaluate the value and effectiveness of clinical research education and training programs.

Granulocyte colony-stimulating factor therapy for cardiac repair after acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Small clinical studies of granulocyte colony-stimulating factor (G-CSF) therapy for cardiac repair after acute myocardial infarction (MI) have yielded divergent results. The effect of G-CSF therapy on left ventricular (LV) function and structure in these patients remains unclear. METHODS: We searched MEDLINE, EMBASE, Science Citation Index, CINAHL, and the Cochrane CENTRAL database of controlled clinical trials (July 2007) for randomized controlled trials of G-CSF therapy in patients with acute MI. We conducted a fixed-effects meta-analysis across 8 eligible studies (n = 385 patients). RESULTS: Compared with controls, G-CSF therapy increased LV ejection fraction (EF) by 1.09%, increased LV scar size by 0.22%, decreased LV end-diastolic volume by 4.26 mL, and decreased LV end-systolic volume by 2.50 mL. None of these effects were statistically significant. The risk of death, recurrent MI, and in-stent restenosis was similar in G-CSF-treated patients and controls. Subgroup analysis revealed a modest but statistically significant increase in EF (4.73%, P < .0001) with G-CSF therapy in studies that enrolled patients with mean EF <50% at baseline. Subgroup analysis also showed a significant increase in EF (4.65%, P < .0001) when G-CSF was administered relatively early (< or =37 hours) after the acute event. CONCLUSIONS: Granulocyte colony-stimulating factor therapy in unselected patients with acute MI appears safe but does not provide an overall benefit. Subgroup analyses suggest that G-CSF therapy may be salutary in acute MI patients with LV dysfunction and when started early. Larger randomized studies may be conducted to evaluate the potential benefits of early G-CSF therapy in acute MI patients with LV dysfunction.

Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis.

BACKGROUND: The results from small clinical studies suggest that therapy with adult bone marrow (BM)-derived cells (BMCs) reduces infarct size and improves left ventricular function and perfusion. However, the effects of BMC transplantation in patients with ischemic heart disease remains unclear. METHODS: We searched MEDLINE, EMBASE, Science Citation Index, CINAHL (Cumulative Index to Nursing and Allied Health), and the Cochrane Central Register of Controlled Trials (CENTRAL) (through July 2006) for randomized controlled trials and cohort studies of BMC transplantation to treat ischemic heart disease. We conducted a random-effects meta-analysis across eligible studies measuring the same outcomes. RESULTS: Eighteen studies (N = 999 patients) were eligible. The adult BMCs included BM mononuclear cells, BM mesenchymal stem cells, and BM-derived circulating progenitor cells. Compared with controls, BMC transplantation improved left ventricular ejection fraction (pooled difference, 3.66%; 95% confidence interval [CI], 1.93% to 5.40%; P<.001); reduced infarct scar size (-5.49%; 95% CI, -9.10% to -1.88%; P = .003); and reduced left ventricular end-systolic volume (-4.80 mL; 95% CI, -8.20 to -1.41 mL; P = .006). CONCLUSIONS: The available evidence suggests that BMC transplantation is associated with modest improvements in physiologic and anatomic parameters in patients with both acute myocardial infarction and chronic ischemic heart disease, above and beyond conventional therapy. Therapy with BMCs seems safe. These results support conducting large randomized trials to evaluate the impact of BMC therapy vs the standard of care on patient-important outcomes.

Caveat emptor: the need for evidence, regulation, and certification of home telehealth systems for the management of chronic conditions.

The home telehealth market is rapidly expanding. The technology and capabilities currently available have the potential to significantly affect the clinical management of an aging population, particularly, the large number with multiple coexisting disease processes. Potential benefits of home-monitoring systems for patients with heart failure range from decreased rates of mortality and improved quality of life to providing third party payers, including the federal government (ie, Centers for Medicare and Medicaid Services), with significant long-term cost savings. The current regulatory process does not provide adequate oversight and standards for these systems that transmit and process data (telehealth systems) critical for patient management. Home telehealth vendors must address the possibility that increased utilization increases their risk of liability due to patient safety issues. In all, 5 major areas need to be addressed to maximize the benefits and safety of this technology: effectiveness of patient management; evidence-based outcomes; regulation; cost, including cost effectiveness and reimbursement; and certification to ensure reliability.

Delayed preconditioning-mimetic actions of nitroglycerin in patients undergoing exercise tolerance tests.

BACKGROUND: Nitroglycerin (NTG) induces delayed preconditioning (PC)-mimetic effects in animal models and in humans during coronary angioplasty. We tested the hypothesis that NTG mitigates ischemia and enhances functional capacity during an exercise tolerance test (ETT) in patients with coronary artery disease. METHODS AND RESULTS: Twenty-eight patients with stable angina and ischemia documented by a stress test were randomized in a double-masked, crossover design to receive a titrated intravenous infusion of NTG or normal saline over 4 hours. At 24 to 28 hours after study medication infusion, each patient underwent 2 ETTs separated by a 1-week washout period. Compared with control patients, pretreatment with NTG was associated with a dose-dependent increase in exercise duration averaging 40 seconds (412+/-19 versus 372+/-24 seconds, P=0.014) and an improvement in ECG manifestations of ischemia, as shown by a decrease in maximal ST-segment depression (1.84+/-0.14 versus 1.63+/-0.13 mm, P=0.011), sum of ST-segment depressions in 12 leads (7.64+/-1.01 versus 6.61+/-0.83 mm, P=0.027), and time to resolution of ST-segment depression (229+/-30 versus 207+/-28 s, P=0.018). These benefits occurred despite an increase in myocardial workload after NTG, as indicated by a higher peak rate-pressure product (24 492+/-1054 versus 22 536+/-1019 mm Hg/min, P=0.015). CONCLUSIONS: NTG produces a late PC-mimetic effect that mitigates the ECG manifestations of ischemia during exercise and improves exercise capacity. To our knowledge, this is the first study to demonstrate that NTG can alleviate exercise-induced ischemia 24 hours after its administration, long after the hemodynamic effects have subsided. The finding that nitrate-induced late PC ameliorates a common manifestation of coronary artery disease has potentially significant implications for the management of this disorder and for the design of clinical trials.

Smoking and inflammatory bowel disease: a meta-analysis.

OBJECTIVE: To assess whether there is a true effect of smoking on the 2 most prevalent forms of inflammatory bowel disease (IBD): Crohn disease (CD) and ulcerative colitis (UC). METHODS: For this meta-analysis, we searched multiple health care databases, including MEDLINE and EMBASE (January 1980 to January 2006), to examine the relationship between smoking and IBD. Keywords searched included smoking, Inflammatory bowel disease, Crohn's disease, and ulcerative colitis. Data were abstracted using predefined inclusion and exclusion criteria. An odds ratio (OR) was recalculated for each study using the random-effects model, and a combined OR was calculated. RESULTS: A total of 245 articles were obtained through an electronic search of health care databases. Thirteen studies examined the relationship between UC and smoking, whereas 9 examined the relationship between CD and smoking. We found evidence of an association between current smoking and CD (OR, 1.76; 95% confidence interval [CI], 1.40-2.22) and former smoking and UC (OR, 1.79; 95% CI, 1.37-2.34). Current smoking had a protective effect on the development of UC when compared with controls (OR, 0.58; 95% CI, 0.45-0.75). CONCLUSION: This is the first meta-analysis, to our knowledge, to evaluate the relationship between smoking and IBD using accepted quality standards for meta-analysis reporting. Our meta-analyses confirm that smoking is an important environmental factor in IBD with differing effects in UC and CD. By using predefined inclusion criteria and testing for homogeneity, the current analysis provides an estimate of the effect of smoking on both these forms of IBD.

Methamphetamine laboratory explosions: a new and emerging burn injury.

The proliferation of clandestine methamphetamine laboratories (meth labs) as a result of the growing popularity of the drug has resulted in an increasing incidence of burn injuries associated with laboratory accidents. We undertook this study to characterize these injuries. Fifteen consecutive patients were identified and case-matched by age and TBSA to 45 control subjects. Most meth lab patients were men, Caucasian, unemployed, and positive for polysubstance abuse. Resuscitation requirements were 1.8 times greater in these patients. There was a higher incidence of inhalational injury corresponding to higher intubation and tracheostomy rate and longer ventilator days among meth lab patients. The rate of nosocomial pneumonia, skin graft loss, and mortality were not different between the two groups. Meth lab injury is unique and requires more critical care resources. It also is associated with lack of insurance coverage and poor follow-up after injury. This injury has a significant impact not only on patients but also on the healthcare system.

Does this patient have influenza?

CONTEXT: Influenza vaccination lowers, but does not eliminate, the risk of influenza. Making a reliable, rapid clinical diagnosis is essential to appropriate patient management that may be especially important during shortages of antiviral agents caused by high demand. OBJECTIVES: To systematically review the precision and accuracy of symptoms and signs of influenza. A secondary objective was to review the operating characteristics of rapid diagnostic tests for influenza (results available in <30 min). DATA SOURCES: Structured search strategy using MEDLINE (January 1966-September 2004) and subsequent searches of bibliographies of retrieved articles to identify articles describing primary studies dealing with the diagnosis of influenza based on clinical signs and symptoms. The MEDLINE search used the Medical Subject Headings EXP influenza or EXP influenza A virus or EXP influenza A virus human or EXP influenza B virus and the Medical Subject Headings or terms EXP sensitivity and specificity or EXP medical history taking or EXP physical examination or EXP reproducibility of results or EXP observer variation or symptoms.mp or clinical signs.mp or sensitivity.mp or specificity.mp. STUDY SELECTION: Of 915 identified articles on clinical assessment of influenza-related illness, 17 contained data on the operating characteristics of symptoms and signs using an independent criterion standard. Of these, 11 were eliminated based on 4 inclusion criteria and availability of nonduplicative primary data. DATA EXTRACTION: Two authors independently reviewed and abstracted data for estimating the likelihood ratios (LRs) of clinical diagnostic findings. Differences were resolved by discussion and consensus. DATA SYNTHESIS: No symptom or sign had a summary LR greater than 2 in studies that enrolled patients without regard to age. For decreasing the likelihood of influenza, the absence of fever (LR, 0.40; 95% confidence interval [CI], 0.25-0.66), cough (LR, 0.42; 95% CI, 0.31-0.57), or nasal congestion (LR, 0.49; 95% CI, 0.42-0.59) were the only findings that had summary LRs less than 0.5. In studies limited to patients aged 60 years or older, the combination of fever, cough, and acute onset (LR, 5.4; 95% CI, 3.8-7.7), fever and cough (LR, 5.0; 95% CI, 3.5-6.9), fever alone (LR, 3.8; 95% CI, 2.8-5.0), malaise (LR, 2.6; 95% CI, 2.2-3.1), and chills (LR, 2.6; 95% CI, 2.0-3.2) increased the likelihood of influenza to the greatest degree. The presence of sneezing among older patients made influenza less likely (LR, 0.47; 95% CI, 0.24-0.92). CONCLUSIONS: Clinical findings identify patients with influenza-like illness but are not particularly useful for confirming or excluding the diagnosis of influenza. Clinicians should use timely epidemiologic data to ascertain if influenza is circulating in their communities, then either treat patients with influenza-like illness empirically or obtain a rapid influenza test to assist with management decisions.

Androgens, Bilateral Oophorectomy, and Cardiovascular Disease Mortality in Postmenopausal Women With and Without Diabetes: The Study of Osteoporotic Fractures.

OBJECTIVE: Diabetes elevates cardiovascular disease (CVD) risk more markedly in women than in men. Because the high risk of CVD among women with type 2 diabetes (DM2) may be partly due to increased ovarian androgen production, we investigated whether a history of bilateral salpingo oophorectomy (BSO) is inversely associated with CVD mortality among women with DM2. RESEARCH DESIGN AND METHODS: Data were obtained from 7,977 women (a random subset of 564 had measurements of sex-steroid hormones) enrolled in the Study of Osteoporotic Fractures (SOF), a community-based, multicenter study that monitored women aged ≥65 years for a mean of 15.1 years. Adjusted hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards regression. RESULTS: The average age at baseline was 71.5 years, with 6.3% and 18% of participants reporting a history of diabetes or BSO, respectively. In the subset of the SOF cohort with sex-steroid hormone measurements, those with DM2 had 43.6% significantly higher levels of free testosterone that were partly explained by age and adiposity, whereas total and free testosterone levels were lower in women with BSO than in those with intact ovaries. CVD mortality was elevated in women with DM2 without BSO (HR 1.95, 95% CI 1.62-2.35) as well as in women with DM2 and BSO (HR 2.56, 95% CI 1.79-3.65; P = 0.190 for interaction). Overall, BSO was not associated with CVD mortality (HR 1.05, 95% CI 0.89-1.23). CONCLUSIONS: The association of diabetes with CVD was not reduced by BSO, suggesting that ovarian hyperandrogenemia may not be a primary mechanism to explain the high risk for CVD among women with DM2.

Cardiovascular disease among women with and without diabetes mellitus and bilateral oophorectomy.

AIMS: Women with type-2 diabetes (DM2) are at high risk of cardiovascular disease (CVD) which may be partly due to increased ovarian androgen production. Since the association of bilateral oophorectomy (BSO) with CVD remains controversial, we evaluated whether BSO is inversely associated with CVD among DM2. METHODS: Data were obtained from a national sample of 9599 postmenopausal women. Adjusted estimates and 95% confidence intervals (CIs) were calculated using logistic and Cox regression. RESULTS: At baseline 2426 women had type-2 diabetes, of whom 580 had BSO. DM2 had adverse CVD risk profiles compared to women without diabetes, as did women with BSO with or without diabetes compared to those with intact ovaries. In DM2, BSO was positively associated with prevalent CVD (odds ratio: 1.63, 95%CI: 1.16-2.30). However, the higher odds were limited to women who had BSO before age 45 years (OR: 2.11, CI: 1.45-3.08). During a mean follow-up of 12.7 years, BSO in DM2 was positively associated with CVD mortality (hazard ratio: 2.23, CI: 1.25-3.99). Among women with BSO, those with family members who had MI before age 50 had elevated odds of CVD (OR: 2.29, CI: 1.56-3.37) compared to those without such family history (OR: 0.90, CI: 0.67-1.20), Pinteraction=0.04. CONCLUSIONS: The risk of CVD is increased not decreased with BSO in DM2. Further, we propose that the association of BSO and CVD in young women with diabetes may partly reflect genetic susceptibility to CVD rather than an effect of ovarian hormones.

Charting a future for epidemiologic training.

PURPOSE: To identify macro-level trends that are changing the needs of epidemiologic research and practice and to develop and disseminate a set of competencies and recommendations for epidemiologic training that will be responsive to these changing needs. METHODS: There were three stages to the project: (1) assembling of a working group of senior epidemiologists from multiple sectors, (2) identifying relevant literature, and (3) conducting key informant interviews with 15 experienced epidemiologists. RESULTS: Twelve macro trends were identified along with associated actions for the field and educational competencies. The macro trends include the following: (1) "Big Data" or informatics, (2) the changing health communication environment, (3) the Affordable Care Act or health care system reform, (4) shifting demographics, (5) globalization, (6) emerging high-throughput technologies (omics), (7) a greater focus on accountability, (8) privacy changes, (9) a greater focus on "upstream" causes of disease, (10) the emergence of translational sciences, (11) the growing centrality of team and transdisciplinary science, and (12) the evolving funding environment. CONCLUSIONS: Addressing these issues through curricular change is needed to allow the field of epidemiology to more fully reach and sustain its full potential to benefit population health and remain a scientific discipline that makes critical contributions toward ensuring clinical, social, and population health.

Risk of heart failure among postmenopausal women: a secondary analysis of the randomized trial of vitamin D plus calcium of the women's health initiative.

BACKGROUND: Vitamin D supplementation may be an inexpensive intervention to reduce heart failure (HF) incidence. However, there are insufficient data to support this hypothesis. This study evaluates whether vitamin D plus calcium (CaD) supplementation is associated with lower rates of HF in postmenopausal women and whether the effects differ between those at high versus low risk for HF. METHODS AND RESULTS: Analyses were restricted to 35 983 (of original 36 282) women aged 50 to 79 years old in the Women's Health Initiative randomized trial of CaD supplementation who were randomized 1:1 in a double-blinded fashion to receive 1000 mg/d of calcium plus 400 IU/d of vitamin D3 or placebo. Overall, 744 adjudicated incident HF cases (intervention, 363; control, 381) occurred during a median follow-up of 7.1 (interquartile range, 1.6) years. CaD supplementation, compared with placebo, was not associated with reduced HF risk in the overall population, hazard ratio, 0.95; P=0.46. However, CaD supplementation had differential effects (P interaction=0.005) in subgroups stratified by baseline risk status of HF defined by the presence (high risk=17 449) or absence (low risk=18 534) of pre-existing HF precursors including coronary heart diseases, diabetes mellitus, or hypertension: 37% (hazard ratio, 0.63 [95% confidence interval, 0.46-0.87]) lower risk of HF in the low-risk versus hazard ratio, 1.06; P=0.51, in the high-risk subgroups. CONCLUSIONS: CaD supplementation did not significantly reduce HF incidence in the overall cohort, however, it was beneficial among postmenopausal women without major HF precursors while of little value in high-risk subgroups. Additional studies are warranted to confirm these findings and investigate the underlying mechanism. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Normokinesia adjacent to left ventricular aneurysm: a differential risk for sudden cardiac death.

BACKGROUND: Following myocardial infarction, the ejection fraction (EF) is an indiscriminate predictor of both non-sudden cardiac death (NSCD) and sudden cardiac death (SCD). However, development of a left ventricular aneurysm (LVA) confers independent risk only for SCD. Thus, we tested the hypothesis that mechanical factors, other than the global left ventricular performance, are causally related to SCD in the presence of LVA. METHODS: A secondary analysis was conducted from a longitudinal, prospective, long-term follow-up cohort study of 66 patients with LVA (diastolic eccentricity and systolic dyskinesia) diagnosed by ventriculography. The left ventricular contour was divided into five segments and contractility scores for the residual myocardium and the segments adjacent to the aneurysm were allocated along with assessment of the EF. A normal adjacent segment was considered present when at least one segment adjacent to the aneurysm exhibited normokinesia. Presence of ventricular tachycardia was documented by Holter recording. RESULTS: At a 5.2-year median follow-up, there were 12 NSCD and 8 SCD. The EF was lower among patients who died vs. survivors (31.5% vs. 39.7%, P=0.01). Patients with NSCD and SCD, exhibited similar EF but disparate residual contractility scores (3.0 vs. 4.1, P<0.004). Among cardiac deaths, a decreasing residual contractility score differentially predicted NSCD (odds ratio=17.06, P<0.03), while a normokinetic adjacent segment differentially predicted SCD (odds ratio=21, P<0.02). Albeit a predictor of both NSCD and SCD, ventricular tachycardia increased markedly the model significance (P<0.004) only when tested with a normokinetic adjacent segment vis-a'-vis SCD. CONCLUSIONS: In the presence of LVA, the contractility of the non-aneurysmal myocardium is a differential predictor of death from pump failure. In contrast, a normal segment adjacent to LVA constitutes an independent and discriminate predictor of SCD, possibly through an arrhythmic substrate linked to the motion discordance between the expanding aneurysm and a normokinetic adjacent myocardium.

Frequency and severity of systemic disease in patients with subacute cutaneous lupus erythematosus.

OBJECTIVE: To compare the frequency and severity of systemic disease in patients with subacute cutaneous lupus erythematosus (SCLE) followed up in a dermatology practice vs patients with systemic lupus erythematosus (SLE) followed up in a rheumatology practice. DESIGN: Case-control comparison of patients matched for age, sex, and ethnicity. SETTING: University-affiliated dermatology and rheumatology practices. PATIENTS: Seventy-six patients with SCLE were compared with 24 patients with SLE. INTERVENTION: All medical records were reviewed and the patients were interviewed. MAIN OUTCOME MEASURES: Systemic and serologic findings were compared between patients with SCLE and those with SLE. RESULTS: Hematologic disorders were present in 6 patients (8%) with SCLE and in 13 patients (54%) with SLE (P<.001). Serositis was present in 1 patient (1%) with SCLE and in 3 patients (12%) with SLE (P =.04). Renal involvement was present in 12 patients (16%) with SCLE and in 6 patients (25%) with SLE (P =.36). Antinuclear antibodies were found in 52 patients (68%) with SCLE compared with 23 patients (96%) with SLE (P =.006). Anti-Ro antibodies were found in 37 patients (49%) with SCLE compared with 10 patients (42%) with SLE (P =.64). Other serologic abnormalities (anti-native DNA, anti-Sm antibody, or anti-U(1)RNP) were present in 6 patients (8%) with SCLE compared with 15 patients (62%) with SLE (P<.001). Photosensitivity was present in 65 patients (86%) with SCLE, compared with 11 patients (46%) with SLE (P<.001). CONCLUSIONS: This analysis reveals a dissimilar frequency of internal organ involvement between patients with SCLE and SLE. Renal disease was similar in frequency and severity, and documented central nervous system involvement was rare in both groups.

Bilateral oophorectomy and the risk of incident diabetes in postmenopausal women.

OBJECTIVE: Ovarian hormones regulate glucose uptake and insulin sensitivity. Despite the high frequency of surgical menopause, its relationship with diabetes has not been extensively investigated. We assessed the association between hysterectomy with or without bilateral oophorectomy (BSO) status, menopausal age, and reproductive life span with incident diabetes. RESEARCH DESIGN AND METHODS: Data were from a cohort of 2,597 postmenopausal women enrolled in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study without diabetes mellitus at baseline. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% CIs. RESULTS: After a median follow-up time of 9.2 years, the incidence of diabetes (in cases per 1,000 person-years) was 7.4 for women with no hysterectomy or BSO, 8.2 for hysterectomy alone, and 8.5 for hysterectomy with BSO. Hysterectomy status was associated positively with diabetes (HR 1.66, 95% CI 1.23-2.23). However, the elevated risk was restricted to women with both hysterectomy and BSO after adjustment for relevant confounders (HR 1.57, 95% CI 1.03-2.41). An earlier age at menopause and a shorter reproductive life span also exhibited a linear relationship with the development of diabetes irrespective of type of menopause (P for trend = 0.001). CONCLUSIONS: Women with hysterectomy concomitant with BSO may represent a unique population with elevated risk for diabetes and other chronic diseases. Therefore, the decision to remove the ovaries at the time of hysterectomy for benign conditions during the premenopausal years should be balanced with the risk of diabetes and its potential complications. Furthermore, the mechanism linking BSO to diabetes mellitus needs to be clarified.