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Functional renal outcome in on-pump and off-pump coronary revascularization: a propensity-based analysis.

BACKGROUND: Since the advent of off-pump coronary artery bypass grafting (OPCAB), comparisons have been made between it and on-pump coronary artery bypass grafting. Some observe a lesser incidence of acute renal failure requiring renal replacement therapy with OPCAB whereas others do not. The objective was to compare the occurrence of renal adverse outcome between on-pump coronary artery bypass grafting and OPCAB. Renal adverse outcome was defined as minor (20% increase in serum creatinine from preoperative) or major (composite end point of postoperative serum creatinine >200 mumol/L or postoperative mechanical renal support). METHODS: The study was based on 2,041 patients with no known preoperative renal disease having first-time isolated coronary artery bypass grafting of multiple coronary arteries between January 2001 and November 2003, at St. Mary's Hospital, Harefield Hospital, and Hammersmith Hospital, in West London; 1,224 patients had on-pump coronary artery bypass grafting and 817 patients had OPCAB. Selection bias for surgical technique was addressed by calculating the propensity score for each patient and using it as an independent variable for adjustment in the multivariate analysis. Univariate and multivariate ordered logistic regressions were used to identify factors associated with renal adverse outcome ordered as none, minor, and major. RESULTS: The number of grafts was 3.22 +/- 0.82 for the on-pump coronary artery bypass grafting group and 3.35 +/- 0.95 for the OPCAB group. On-pump coronary artery bypass grafting and increasing age were found to be the strongest independent predictors (p < 0.001) of renal adverse outcome. Other independent predictors included hypertension (p = 0.005), diabetes (p = 0.032), and preoperative serum creatinine (p = 0.001). A left ventricular ejection fraction of 0.30 to 0.49 (p = 0.099) and an ejection fraction of 0.50 or greater (p < 0.001) were associated with decreased risk compared with patients with an ejection fraction of less than 0.30. Interestingly, the use of non-left internal mammary arterial conduits significantly decreased the likelihood of renal adverse outcome (p = 0.034). CONCLUSIONS: The results of this propensity-based study show that the OPCAB technique may reduce the risk for minor and major renal adverse outcome after coronary artery bypass grafting.

Aged↗

Preoperative statin use and in-hospital outcomes following heart surgery in patients with unstable angina.

OBJECTIVE: Unstable angina (UA) is characterized by a state of coronary artery vascular inflammation and endothelial dysfunction. Statins mitigate inflammation and endothelial dysfunction and decrease mortality associated with percutaneous interventions for UA. We determined whether preoperative statin use is associated with decreased mortality and morbidity following coronary artery bypass+/-valve surgery for UA. METHODS: Patients with CCS Class IV angina having CABG+/-valve surgery were identified (n=1706). A logistic regression model determined the association of preoperative statin use with in-hospital mortality (IHM). Propensity score analysis was used to match two sub-groups of patients (GrpI, on statins, n=534; GrpII, not on statins, n=534) on factors known to affect outcomes. Outcomes were IHM, intra-aortic balloon pump (IABP) use, perioperative myocardial infarction (PMI), prolonged (>24 h) ventilation (p-vent), stroke, and a composite outcome (comp) defined as any one or more of the above. RESULTS: Of the 1706 patients, 1075 were on statins and 631 were not. Patients on statins were more likely to have isolated CABG, EF>40%, and be on a beta-blocker (P=0.0001); and less likely to have renal failure, MI<7 days, CHF, and undergoing urgent/emergent surgery (P=0.0001). Unadjusted rates of IHM (9 vs. 5%, P=0.001), stroke (4.4 vs. 2.3%, P=0.015), p-vent (28.4 vs. 19%, P=0.0001), and comp (32.5 vs. 22.8%, P=0.0001) were lower in patients receiving statins. After adjustment, statin use was not associated with a reduction in IHM (OR=1.0, 95% CI=0.6-1.5, P=0.85) or comp (OR=1.1, 95% CI=0.8-1.4, P=0.69). No significant differences were found in any of the propensity-adjusted outcomes for GrpI vs. GrpII: IHM (7.1 vs. 6.4%), PMI (2.8 vs. 1.7%), IABP use (3 vs. 3.8%), stroke (3.8 vs. 3.9%), p-vent (26.4 vs. 23.8%), comp (31.5 vs. 27.5%). CONCLUSIONS: Preoperative statin use is not associated with a reduction in IHM or major morbidity following CABG+/-valve surgery in patients with UA.

Aged↗

Health and economic outcomes of vancomycin-resistant enterococci.

BACKGROUND: The health and economic impact of vancomycin-resistant enterococci has not been quantified. METHODS: A retrospective matched cohort study was conducted comparing the outcomes of patients with vancomycin-resistant enterococci (cases) with those of control subjects matched for length of hospital stay until inclusion in the cohort, hospital location, and calendar date. The propensity to be a vancomycin-resistant enterococci case was modeled based on patient characteristics, and included in multivariable models to adjust for confounding. Analyses included the following: (1) conditional logistic regression for mortality, surgery, intensive care unit admission, and discharge to long-term care; (2) linear regression for the logarithm of cost; and (3) accelerated failure time model for length of stay. RESULTS: A total of 233 cases were compared with 647 controls. Groups were similar in age (mean, 62 years), sex (female, 47%), and length of stay before inclusion in the cohort (mean, 8.1 days), but differed in primary diagnosis and comorbidities, past infection or colonization with methicillin sodium-resistant Staphylococcus aureus or Clostridium difficile, and treatment with cephalosporins or metronidazole. These variables were included in the propensity score, which had good to excellent prediction. Outcomes for cases vs controls and adjusted risks (relative risks [RRs]) were as follows: (1) case fatality rate, 17% vs 6% (RR, 2.13; P =.04); (2) length of stay after inclusion in the cohort, 15.1 vs 8.5 days (RR, 1.73; P<.001); (3) hospital costs, $52 449 vs $31 915 (RR, 1.40; P<.001); (4) surgery after inclusion in the cohort, 18% vs 10% (RR, 2.74; P =.001); (5) intensive care unit admission after inclusion in the cohort, 25% vs 14% (RR, 3.47; P<.001); and (6) transfer to an institution, 51% vs 35% (RR, 2.01; P =.001). CONCLUSION: Compared with a matched hospital population, a population with vancomycin-resistant enterococci was associated with severe adverse outcomes: increased mortality, morbidity, and costs.

Cohort Studies↗

beta-Blocker use in long-term dialysis patients: association with hospitalized heart failure and mortality.

BACKGROUND: beta-Blockers have been shown to be beneficial in the treatment and prevention of heart failure (HF) in the general population, but they have not been assessed for their association with nonfatal HF in a nationally representative population of long-term dialysis patients. METHODS: We conducted a retrospective cohort study of 2550 patients enrolled in the US Renal Data System (USRDS) Wave 2 who were Medicare eligible at the start of the study. Analysis was stratified by the presence or absence of a known diagnosis of HF, and patients followed up until December 31, 2000. Cox regression analysis, including propensity scores, was used to model adjusted hazard ratios for beta-blocker use (assessed separately by cardioselective activity and lipid solubility) with time to the first Medicare institutional claim for HF, cardiovascular-related death, or death from any cause. RESULTS: In patients without a previous history of HF, beta-blocker use was significantly associated with a lower adjusted risk of HF (adjusted hazard ratio, 0.69; 95% confidence interval, 0.52-0.91; P=.008), with a similar reduction in risk of cardiac-related and all-cause death. beta-Blocker use had no statistically significant associations with outcomes in patients with previous HF. CONCLUSIONS: In dialysis patients without a previous documented history of HF, beta-blocker use was associated with a lower risk of new HF, cardiovascular death, and death from any cause. No such associations were seen for dialysis patients with a previous history of HF. These results are hypothesis generating only and should be confirmed in randomized trials.

Adrenergic beta-Antagonists↗

Effectiveness of implantable cardioverter-defibrillators in patients with ischemic heart disease and left ventricular dysfunction.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) have been shown in primary prevention efficacy trials to reduce mortality in patients with ischemic heart disease and left ventricular dysfunction. To investigate the generalizabilty of this mortality reduction, we examined the effectiveness of ICDs in clinical practice. METHODS: We developed a prospective multicenter cohort of 770 patients with ischemic left ventricular dysfunction (ejection fraction < or =35%) and without a history of ventricular arrhythmia, of whom 395 (52%) received ICDs. Mean +/- SD follow-up was 27 +/- 12 months. We assessed the degree to which ICDs decreased mortality risk using Cox proportional hazards analyses that controlled for clinical predictors of death, receipt of ICD (a propensity score analysis), and predictors of arrhythmic death (including electrophysiologic variables). RESULTS: Multivariate Cox analyses showed that those with ICDs had significantly lower all-cause mortality (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.33-0.86). This mortality reduction was mediated through dramatically lower arrhythmia-related mortality (HR, 0.35; 95% CI, 0.17-0.73), with no significant effect on cardiovascular nonarrhythmic (HR, 0.81; 95% CI, 0.34-1.96) and noncardiovascular (HR, 0.76; 95% CI, 0.29-2.05) mortality. No differences were found between the ICD and non-ICD groups for a composite outcome of all-cause mortality, appropriate ICD shocks, or documented symptomatic ventricular arrhythmia, which suggests that the 2 groups had similar baseline risk for life-threatening arrhythmic events (HR, 0.96; 95% CI, 0.63-1.45). CONCLUSION: In clinical practice, ICDs appear to reduce all-cause and arrhythmic rates of mortality at levels similar to those found in primary prevention trials.

Aged↗

Impact and cost-effectiveness of respiratory syncytial virus prophylaxis for Kansas medicaid's high-risk children.

OBJECTIVES: To determine the impact of prophylactic therapy for respiratory syncytial virus (RSV) infections on subsequent hospitalizations and related lengths of stay and costs and to estimate whether prophylactic treatment was cost-effective. DESIGN: Retrospective cohort study of the 1999-2000 RSV season. Propensity scores were used to identify an untreated comparison group to adjust for treatment selection bias. SETTING: State of Kansas Medicaid program. PARTICIPANTS: The study population included children 10 months or younger at the start of the RSV season or born during the season who either were premature or had chronic lung disease. All children were continuously enrolled in Medicaid throughout the season. MAIN OUTCOME MEASURES: Inpatient admission for RSV infections and associated lengths of stay and costs; cost-benefit analysis of drug costs per reduction in hospitalization costs. RESULTS: The RSV-preventive treatments reduced the odds of hospitalizations to 0.47, lengths of stay by 74%, and hospitalization costs by $703. Given an average drug cost of $4687, the cost-benefit ratio was 6.67. CONCLUSIONS: Despite the demonstrated efficacy of intravenous RSV immune globulin and palivizumab in clinical trials, use of these agents in actual practice has not generated expected outcomes in the Kansas Medicaid program. Although their use generated reductions in all 3 hospital-related outcomes, their costs overwhelmed these benefits.

Cost-Benefit Analysis↗

Violent behavior by girls reporting violent victimization: a prospective study.

OBJECTIVE: To assess the relationships between individual victimization and neighborhood-level violence on subsequent violent perpetration by adolescent girls in a community-based sample. DESIGN: Longitudinal, multilevel analysis of data collected by the Project on Human Development in Chicago Neighborhoods. Three in-home interviews were conducted approximately 24 months apart between November 1995 and January 2002 with youth and their caregivers. Community-level data also were collected in 1995 from a random sample of Chicago residents. Hierarchical regression models and propensity scores were used. SETTING: Families and neighborhoods in Chicago. PARTICIPANTS: Population-based sample of 637 girls, ages 9 to 15 years at baseline, and the neighborhoods in which they resided. This sample is diverse in race/ethnicity, socioeconomic status, family structure, and neighborhood characteristics. MAIN OUTCOME MEASURE: Self-reports of violent behavior in the 12 months before the third interview. RESULTS: At baseline, 38% of the girls reported perpetrating at least 1 violent behavior in the prior 12 months, 28% reported past year violent behavior at the first follow-up interview, and 14% reported past year violent behavior at the third interview. The odds of violent behavior were 2.2 times higher among girls who reported prior violent victimization, after prior confounding factors and baseline violent behavior were controlled (95% confidence interval, 1.3- 4.4). Homicides and concentrated poverty in girls' neighborhoods also were associated with aggression by girls. CONCLUSIONS: Improving safety in communities and homes may reduce rates of violent perpetration by adolescent girls. Study results suggest that, to facilitate identification of and healing among adolescent survivors of violence, practitioners should recognize perpetration of violence as potential sequelae of prior violent victimization.

Adolescent↗

Early statin treatment following acute myocardial infarction and 1-year survival.

CONTEXT: Randomized trials have established statin treatment as secondary prevention in coronary artery disease, but it is unclear whether early treatment with statins following acute myocardial infarction (AMI) influences survival. OBJECTIVE: To evaluate the association between statin treatment initiated before or at the time of hospital discharge and 1-year mortality after AMI. DESIGN AND SETTING: Prospective cohort study using data from the Swedish Register of Cardiac Intensive Care on patients admitted to the coronary care units of 58 Swedish hospitals in 1995-1998. One-year mortality data were obtained from the Swedish National Cause of Death Register. PATIENTS: Patients with first registry-recorded AMI who were younger than 80 years and who were discharged alive from the hospital, including 5528 who received statins at or before discharge and 14 071 who did not. MAIN OUTCOME MEASURE: Relative risk of 1-year mortality according to statin treatment. RESULTS: At 1 year, unadjusted mortality was 9.3% (1307 deaths) in the no-statin group and 4.0% (219 deaths) in the statin treatment group. In regression analysis adjusting for confounding factors and propensity score for statin use, early statin treatment was associated with a reduction in 1-year mortality (relative risk, 0.75; 95% confidence interval, 0.63-0.89; P =.001) in hospital survivors of AMI. This reduction in mortality was similar among all subgroups based on age, sex, baseline characteristics, previous disease manifestations, and medications. CONCLUSIONS: Early initiation of statin treatment in patients with AMI is associated with reduced 1-year mortality. These results emphasize the importance of implementing the results of randomized statin trials in unselected AMI patients.

Aged↗

Prognostic value of a normal or nonspecific initial electrocardiogram in acute myocardial infarction.

CONTEXT: Although previous studies have suggested that normal and nonspecific initial electrocardiograms (ECGs) are associated with a favorable prognosis for patients with acute myocardial infarction (AMI), their independent predictive value for mortality has not been examined. OBJECTIVE: To compare in-hospital mortality among patients with AMI who have normal or nonspecific initial ECGs with that of patients who have diagnostic ECGs. DESIGN, SETTING, AND PATIENTS: Multihospital observational study in which 391 208 patients with AMI met the study criteria between June 1994 and June 2000 and had ECGs that were normal (n = 30 759), nonspecific (n = 137 574), or diagnostic (n = 222 875; defined as ST-segment elevation or depression and/or left bundle-branch block). A logistic regression model was constructed using a propensity score for ECG findings and data on demographics, medical history, diagnostic procedures, and therapy to determine the independent prognostic value of a normal or nonspecific initial ECG. MAIN OUTCOME MEASURES: In-hospital mortality; composite outcome of in-hospital death and life-threatening adverse events. RESULTS: In-hospital mortality rates were 5.7%, 8.7%, and 11.5% while the rates of the composite of mortality and life-threatening adverse events were 19.2%, 27.5%, and 34.9% for the normal, nonspecific, and diagnostic ECG groups, respectively. After adjusting for other predictor variables, the odds of mortality for the normal ECG group was 0.59 (95% confidence interval [CI], 0.56-0.63; P<.001) and for the nonspecific group was 0.70 (95% CI, 0.68-0.72; P<.001), compared with the diagnostic ECG group. CONCLUSION: In this large cohort of patients with AMI, patients presenting with normal or nonspecific ECGs did have lower in-hospital mortality rates than those of patients with diagnostic ECGs, yet the absolute rates were still unexpectedly high.

Aged↗

Diuretics, mortality, and nonrecovery of renal function in acute renal failure.

CONTEXT: Acute renal failure is associated with high mortality and morbidity. Diuretic agents continue to be used in this setting despite a lack of evidence supporting their benefit. OBJECTIVE: To determine whether the use of diuretics is associated with adverse or favorable outcomes in critically ill patients with acute renal failure. DESIGN: Cohort study conducted from October 1989 to September 1995. PATIENTS AND SETTING: A total of 552 patients with acute renal failure in intensive care units at 4 academic medical centers affiliated with the University of California. Patients were categorized by the use of diuretics on the day of nephrology consultation and, in companion analyses, by diuretic use at any time during the first week following consultation. MAIN OUTCOME MEASURES: All-cause hospital mortality, nonrecovery of renal function, and the combined outcome of death or nonrecovery. RESULTS: Diuretics were used in 326 patients (59%) at the time of nephrology consultation. Patients treated with diuretics on or before the day of consultation were older and more likely to have a history of congestive heart failure, nephrotoxic (rather than ischemic or multifactorial) origin of acute renal failure, acute respiratory failure, and lower serum urea nitrogen concentrations. With adjustment for relevant covariates and propensity scores, diuretic use was associated with a significant increase in the risk of death or nonrecovery of renal function (odds ratio, 1.77; 95% confidence interval, 1.14-2.76). The risk was magnified (odds ratio, 3.12; 95% confidence interval, 1.73-5.62) when patients who died within the first week following consultation were excluded. The increased risk was borne largely by patients who were relatively unresponsive to diuretics. CONCLUSIONS: The use of diuretics in critically ill patients with acute renal failure was associated with an increased risk of death and nonrecovery of renal function. Although observational data prohibit causal inference, it is unlikely that diuretics afford any material benefit in this clinical setting. In the absence of compelling contradictory data from a randomized, blinded clinical trial, the widespread use of diuretics in critically ill patients with acute renal failure should be discouraged.

Acute Kidney Injury↗

Secular trends in nosocomial infections and mortality associated with noninvasive ventilation in patients with exacerbation of COPD and pulmonary edema.

CONTEXT: Randomized controlled trials have shown that the use of noninvasive ventilation (NIV) reduces the need for endotracheal intubation and invasive mechanical ventilation and reduces complication rates and mortality in selected groups of patients. But whether these benefits translate to a clinical setting is unclear. OBJECTIVE: To evaluate longitudinally the routine implementation of NIV and its effect on patients admitted to the intensive care unit (ICU) with acute exacerbation of chronic obstructive pulmonary disease (COPD) or severe cardiogenic pulmonary edema (CPE). DESIGN: Retrospective, observational cohort study using prospectively collected data from January 1, 1994, through December 31, 2001. SETTING: A 26-bed medical intensive care unit (ICU) of a French university referral hospital. PARTICIPANTS: A cohort of 479 consecutive patients ventilated for acute exacerbation of COPD or CPE. MAIN OUTCOME MEASURES: The ICU mortality and incidence rates of ICU-acquired infections. RESULTS: A significant increase in NIV use and a concomitant decrease in mortality and ICU-acquired infection rates were observed over the study years. With adjustment for relevant covariates and propensity scores, NIV was identified as an independent factor linked with a reduced risk of death in the cohort (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.18-0.78), whereas a high severity score on admission (OR, 1.05; 95% CI, 1.01-1.10) and the occurrence of a nosocomial infection (OR, 3.08; 95% CI, 1.62-5.84) were independently associated with death. Rates of ICU-acquired pneumonia decreased from 20% in 1994 to 8% in 2001 (P =.04). CONCLUSION: Implementing routine use of NIV in critically ill patients with acute exacerbation of COPD or severe CPE was associated with improved survival and reduction of nosocomial infections.

Acute Disease↗

Survival associated with treatment vs observation of localized prostate cancer in elderly men.

CONTEXT: Prostate-specific antigen screening has led to an increase in the diagnosis and treatment of localized prostate cancer. However, the role of active treatment of low- and intermediate-risk disease in elderly men is controversial. OBJECTIVE: To estimate the association between treatment (with radiation therapy or radical prostatectomy) compared with observation and overall survival in men with low- and intermediate-risk prostate cancer. DESIGN AND SETTING: Observational US cohort from Surveillance, Epidemiology, and End Results Medicare data. PATIENTS: At total of 44,630 men aged 65 to 80 years who were diagnosed between 1991 and 1999 with organ-confined, well- or moderately differentiated prostate cancer and who had survived more than a year past diagnosis. Patients were followed up until death or study end (December 31, 2002). Patients were classified as having received treatment (n=32,022) if they had claims for radical prostatectomy or radiation therapy during the first 6 months after diagnosis. They were classified as having received observation (n=12,608) if they did not have claims for radical prostatectomy, radiation, or hormonal therapy. Patients who received only hormonal therapy were excluded. MAIN OUTCOME MEASURE: Overall survival. RESULTS: At the end of the 12-year study period, 4663 men (37%) in the observational group and 7639 men (23.8%) in the treatment group had died. The treatment group had longer 5- and 10-year survival than the observation group. After using propensity scores to adjust for potential confounders (tumor characteristics, demographics, and comorbidities), there was a statistically significant survival advantage associated with treatment (hazard ratio, 0.69; 95% confidence interval, 0.66-0.72). A benefit associated with treatment was seen in all subgroups examined, including older men (aged 75-80 years at diagnosis), black men, and men with low-risk disease. CONCLUSIONS: This study suggests a survival advantage is associated with active treatment for low- and intermediate-risk prostate cancer in elderly men aged 65 to 80 years. Because observational data cannot completely adjust for potential selection bias and confounding, these results must be validated in randomized controlled trials of alternative management strategies in elderly men with localized prostate cancer.

Aged↗

Infections in patients with rheumatoid arthritis treated with biologic agents.

OBJECTIVE: To estimate the incidence rates of serious and nonserious infections in patients with rheumatoid arthritis (RA) who start treatment with a biologic agent, and to compare these rates with those in patients with RA who receive conventional treatment. METHODS: Patients enrolled in the German biologics register between May 2001 and September 2003 were included. Treating rheumatologists assessed adverse events and serious adverse events. All adverse events and serious adverse events experienced within 12 months after study entry were analyzed. Propensity score methods were applied to estimate which part of a rate increase was likely to be attributable to differences in patient characteristics. RESULTS: Data were available for 512 patients receiving etanercept, 346 patients receiving infliximab, 70 patients receiving anakinra, and 601 control patients treated with disease-modifying antirheumatic drugs. The total number of adverse events per 100 patient-years was 22.6 (95% confidence interval [95% CI] 18.7-27.2) among patients receiving etanercept, 28.3 (95% CI 23.1-34.7) among patients receiving infliximab, and 6.8 (95% CI 5.0-9.4) among controls (P < 0.0001). Significant differences in the rate of serious adverse events were also observed. For patients receiving etanercept, those receiving infliximab, and controls, the total numbers of serious adverse events per 100 patient-years were 6.4 (95% CI 4.5-9.1), 6.2 (95% CI 4.0-9.5), and 2.3 (95% CI 1.3-3.9), respectively (P = 0.0016). After adjusting for differences in the case patient mix, the relative risks of serious adverse events were 2.2 (95% CI 0.9-5.4) for patients receiving etanercept and 2.1 (95% CI 0.8-5.5) for patients receiving infliximab, compared with controls. CONCLUSION: Patients treated with biologic agents have a higher a priori risk of infection. However, our data suggest that this risk is increased by treatment with tumor necrosis factor inhibitors.

Adalimumab↗

Improving follow-up to abnormal breast cancer screening in an urban population. A patient navigation intervention.

Delays in follow-up after cancer screening contribute to racial/ethnic disparities in cancer outcomes. We evaluated a patient navigator intervention among inner-city women with breast abnormalities. A full-time patient navigator supported patients using the care management model. Female patients 18 years and above, referred to an urban, hospital-based, diagnostic breast health practice from January to June 2000 (preintervention) and November 2001 to February 2003 (intervention), were studied. Timely follow-up was defined as arrival to diagnostic evaluation within 120 days from the date the original appointment was scheduled. Data were collected via computerized registration, medical records, and patient interview. Bivariate and multivariate logistic regression analyses were conducted, comparing preintervention and intervention groups, with propensity score analysis and time trend analysis to address the limitations of the pre-post design. 314 patients were scheduled preintervention; 1018, during the intervention. Overall, mean age was 44 years; 40% black, 36% non-Hispanic white, 14% Hispanic, 4% Asian, 5% other; 15% required an interpreter; 68% had no or only public insurance. Forty-four percent of referrals originated from a community health center, 34% from a hospital-based practice. During the intervention, 78% had timely follow-up versus 64% preintervention (P < .0001). In adjusted analyses, women in the intervention group had 39% greater odds of having timely follow-up (95% CI, 1.01-1.9). Timely follow-up in the adjusted model was associated with older age (P = .0003), having private insurance (P = .006), having an abnormal mammogram (P = .0001), and being referred from a hospital-based practice, as compared to a community health center (P = .003). Our data suggest a benefit of patient navigators in reducing delay in breast cancer care for poor and minority populations. Cancer 2007. (c) 2006 American Cancer Society.

Adolescent↗

Mortality in type 2 diabetic subjects prescribed metformin and sulphonylurea drugs in combination: cohort study.

BACKGROUND: In the UK Prospective Diabetes Study, treatment with sulphonylurea and metformin in combination was associated with increased mortality. We compared mortality in subjects treated either with metformin or sulphonylurea drugs alone, or in combination. METHODS: Cohort study in 263 general practices in the United Kingdom. Subjects were aged >/=30 years. Outcome was survival from first prescription of oral hypoglycaemic drugs till death from any cause. Transfer to metformin and sulphonylurea in combination was modelled as a time-dependent covariate. Hazard ratios were adjusted for age, sex, year of treatment, presence of coronary heart disease or prescription of cardiovascular drugs. Analyses were also stratified by propensity score. RESULTS: There were 8488 subjects who were initially prescribed sulphonylureas with a total of 20 783 person years of follow-up and 1157 deaths. The crude mortality rate was 58.56 per 1000 person years during suphonlyurea as sole treatment. In 1868 subjects who were prescribed additional metformin, the mortality rate was 39.75 per 1000. The adjusted hazard ratio was 1.06 (95% confidence interval 0.85 to 1.31, P = 0.616). There were 3099 subjects initially treated with metformin with a total of 7306 person years of follow-up and 176 deaths. During metformin-only treatment, the mortality rate was 25.48 per 1000. After addition of sulphonylurea in 867 subjects, mortality was 19.35 per 1000. The adjusted hazard ratio was 0.95 (0.64 to 1.40, P = 0.801). CONCLUSIONS: In this large non-randomized study, there was no evidence of increased mortality risk following prescription of sulphonylurea and metformin in combination, as compared to either drug prescribed singly.

Adult↗

Summary report: Missing data and pedigree and genotyping errors.

Genetic epidemiology is faced with mapping complex traits to genes with relatively small effects whose phenotypes may be modulated by temporal factors. To do this, detailed and accurate data must be available on families, perhaps collected over time. The Framingham Heart Study data supplied to Genetic Analysis Workshop 13 (GAW13), along with its simulated counterpart, contain longitudinal measurements and genomic scan data on 2,885 individuals in 330 families, and offer an opportunity to examine data quality and completeness issues as they affect analytical conclusions. Six GAW13 contributions applied methods to deal with missing data, both phenotypic and genotypic, at a single time point and longitudinally, and with possible errors in pedigree structure and genotypes. The methods included missing phenotypic data imputation by Markov chain Monte Carlo sampling, propensity scoring, regression, and adjusted mean values, as well as the assessment of transmission-disequilibrium tests when missing marker data may be allele-specific. Pedigree structural errors were found by genome-wide allele-sharing probabilities, while Mendelian consistent genotype errors were evaluated through likelihoods of double-recombination events. Each of the methods reviewed here offered insights into how to better take advantage of large, time-dependent, familial data sets. However, no one of them dealt with the longitudinal and familial aspects simultaneously. Overall, more consideration needs to be given to the effects that missing data and data errors have on our ability to map complex traits efficiently and accurately.

Cardiovascular Diseases↗

Linkage mapping methods applied to the COGA data set: presentation Group 4 of Genetic Analysis Workshop 14.

Presentation Group 4 participants analyzed the Collaborative Study on the Genetics of Alcoholism data provided for Genetic Analysis Workshop 14. This group examined various aspects of linkage analysis and related issues. Seven papers included linkage analyses, while the eighth calculated identity-by-descent (IBD) probabilities. Six papers analyzed linkage to an alcoholism phenotype: ALDX1 (four papers), ALDX2 (one paper), or a combination both (one paper). Methods used included Bayesian variable selection coupled with Haseman-Elston regression, recursive partitioning to identify phenotype and covariate groupings that interact with evidence for linkage, nonparametric linkage regression modeling, affected sib-pair linkage analysis with discordant sib-pair controls, simulation-based homozygosity mapping in a single pedigree, and application of a propensity score to collapse covariates in a general conditional logistic model. Alcoholism linkage was found with > or =2 of these approaches on chromosomes 2, 4, 6, 7, 9, 14, and 21. The remaining linkage paper compared the utility of several single-nucleotide polymorphism (SNP) and microsatellite marker maps for Monte Carlo Markov chain combined oligogenic segregation and linkage analysis, and analyzed one of the electrophysiological endophenotypes, ttth1, on chromosome 7. Linkage was found with all marker sets. The last paper compared the multipoint IBD information content of several SNP sets and the microsatellite set, and found that while all SNP sets examined contained more information than the microsatellite set, most of the information contained in the SNP sets was captured by a subset of the SNP markers with approximately 1-cM marker spacing. From these papers, we highlight three points: a 1-cM SNP map seems to capture most of the linkage information, so denser maps do not appear necessary; careful and appropriate use of covariates can aid linkage analysis; and sources of increased gene-sharing between relatives should be accounted for in analyses.

Alcoholism↗

Road injuries and long-run effects on income and employment.

This paper investigates whether unexpected shocks in terms of road injuries 'cause' a permanent change in disposable income, earnings, employment, and public transfer income. We use 'propensity score matching' and apply a difference-in-difference matching method to estimate the counterfactual of what the disposable income, earnings, employment, and the amount of public transfer income would have been of a particular group of persons injured by road accidents if they had not in fact been injured. We find that road injuries have important consequences. Older injured persons and injured persons in the lower part of the income distribution have significantly lower disposable incomes than older and low-income non-injured persons. In both the short and the long run the employment rates for the injured men are significantly lower than for non-injured persons. No effects on the employment rate are found for women. Besides, earnings are reduced in the long run for men where significant effects are only found for older women. The analysis shows that both injured men and women are compensated in terms of a significant increase in public transfer incomes in both the short and the long run.

Accidents, Traffic↗