Summary Background Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration ...decreases the rate of microvascular complications in people with type 2 diabetes. Methods ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA1c concentrations (>7·5%), and cardiovascular disease (or ≥2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A1c HbA1c of <6·0%) or standard (7·0–7·9%) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291·7 μmol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov , number NCT00000620. Findings 10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1·00, 95% CI 0·88–1·14; p=1·00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0·96, 0·89–1·02; p=0·19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 HR 0·95, 95% CI 0·85–1·07, p=0·42; and second 1956 of 5119 vs 2046 of 5115, respectively 0·95, 0·89–1·01, p=0·12). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Six secondary measures at study end favoured intensive therapy (p<0·05). Interpretation Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia. Funding US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.
Guidelines of care for acne vulgaris management Strauss, John S., MD; Krowchuk, Daniel P., MD; Leyden, James J., MD ...
Journal of the American Academy of Dermatology,
04/2007, Letnik:
56, Številka:
4
Journal Article
Recenzirano
Disclaimer Adherence to these guidelines will not ensure successful treatment in every situation. Furthermore, these guidelines should not be deemed inclusive of all proper methods of care or ...exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient.
Objectives To assess antenatal and early postnatal antecedents of attention problems identified by the Child Behavior Checklist in extremely preterm children. Study design In a cohort of 826 children ...born between 23 and 27 weeks' gestation, we collected demographic, birth, and postnatal information. We then identified behavior problems by using parent ratings from the Child Behavior Checklist at 2 years' adjusted age. We created time-oriented logistic regression risk models to identify significant risk factors for attention problems and Diagnostic and Statistical Manual of Mental Disorders –compatible attention deficit/hyperactivity problems (ADHPDSM ). Results Children were at increased risk of both attention problems if they were born to a woman who had no formal education beyond high school and/or a woman who was exposed to secondhand smoke. Recovery of a single organism from the placenta was associated with increased risk of an attention problem, and fetal stem vessel thrombosis and recovery of Mycoplasma species were associated with increased risk of ADHPDSM . Infants of multifetal gestations were at reduced risk of both attention problems. The only postnatal risk factor for an attention problem was recovery of bacteria from a tracheal aspirate. Conclusion Among extremely preterm infants, several potentially modifiable antenatal and perinatal antecedents are associated with increased risk for attention problems and ADHPDSM at 2 years adjusted age.
Objectives We tested the hypothesis that exposure to concentrated ambient particles (CAP) and/or ozone (O3 ) would increase dispersion of ventricular repolarization. Background Elevated levels of air ...pollution are associated with cardiac arrhythmias through mechanisms yet to be elucidated. Methods Each of 25 volunteers (18 to 50 years of age) had four 2-h exposures to 150 μg/m3 CAP; 120 parts per billion O3 ; CAP + O3 ; and filtered air (FA). Exposure-induced changes (Δ = 5-min epochs at end-start) in spatial dispersion of repolarization were determined from continuous 12-lead electrocardiographic recording. Results Spatial dispersion of repolarization assessed by corrected ΔT-wave peak to T-wave end interval increased significantly for CAP + O3 (0.17 ± 0.03, p < 0.0001) exposure only, remaining significant when factoring FA (CAP + O3 − FA) as control (0.11 ± 0.04, p = 0.013). The influence on repolarization was further verified by a significant increase in ΔQT dispersion (for CAP + O3 compared with FA (5.7 ± 1.4, p = 0.0002). When the low-frequency to high-frequency ratio of heart rate variability (a conventional representation of sympathetic-parasympathetic balances) was included as a covariate, the effect estimate was positive for both corrected ΔT-wave peak to T-wave end interval (p = 0.002) and ΔQT dispersion (p = 0.038). When the high-frequency component (parasympathetic heart rate modulation) was included as a covariate with corrected ΔT-wave peak to T-wave end interval, the effect estimate for high frequency was inverse (p = 0.02). Conclusions CAP + O3 exposure alters dispersion of ventricular repolarization in part by increasing sympathetic and decreasing parasympathetic heart rate modulation. Detection of changes in repolarization parameters, even in this small cohort of healthy individuals, suggests an underappreciated role for air pollutants in urban arrhythmogenesis.
Abstract Background Several studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk ...prediction. However, to date, no risk score incorporating CAC has been developed. Objectives The goal of this study was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors. Methods Algorithm development was conducted in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective community-based cohort study of 6,814 participants age 45 to 84 years, who were free of clinical heart disease at baseline and followed for 10 years. MESA is sex balanced and included 39% non-Hispanic whites, 12% Chinese Americans, 28% African Americans, and 22% Hispanic Americans. External validation was conducted in the HNR (Heinz Nixdorf Recall Study) and the DHS (Dallas Heart Study). Results Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p < 0.0001). External validation in both the HNR and DHS studies provided evidence of very good discrimination and calibration. Harrell’s C-statistic was 0.779 in HNR and 0.816 in DHS. Additionally, the difference in estimated 10-year risk between events and nonevents was approximately 8% to 9%, indicating excellent discrimination. Mean calibration, or calibration-in-the-large, was excellent for both studies, with average predicted 10-year risk within one-half of a percent of the observed event rate. Conclusions An accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians when communicating risk to patients and when determining risk-based treatment strategies.
Abstract Context Because the Family Evaluation of Treatment at End of Life (FATE) survey was too long for routine use in the Veterans Administration (VA) health care system to measure quality of ...care, a shorter instrument was developed. Objectives To evaluate the short version of the FATE survey for use as a nationwide quality measure in the VA health care system. Methods Fifty-one VA medical centers, including acute and long-term care, participated in this nationwide telephone survey. Family members of the patients were eligible if the patients died in a participating facility. One family member per patient was selected from medical records using predefined eligibility criteria and invited to participate. The survey consists of 14 items describing key aspects of the patient’s care in his or her last month of life, one global rating, and two open-ended questions for additional comments. Results Interviews were completed with 2827 family members. Overall, the survey showed excellent psychometric characteristics, with good homogeneity (e.g., Cronbach’s α = 0.84) and strong evidence of discriminant validity. Two survey items have been targeted for quality improvement efforts in multisite collaboratives. Conclusion Surveys of surrogates offer an important source of quality data that can be used to improve the quality of end-of-life care and promote accountability.
Objective To examine the extent to which weight gain and weight status in the first 2 years of life relate to the risk of neurodevelopmental impairment in extremely preterm infants. Study design In a ...cohort of 1070 infants born between 23 and 27 weeks' gestation, we examined weight gain from 7-28 days of life (in quartiles) and weight z -score at 12 and 24 months corrected age (in 4 categories: <−2; ≥−2, <−1; ≥1, <1; and ≥1) in relation to these adverse neurodevelopmental outcomes: Bayley-II mental development index <55, Bayley-II psychomotor development index <55, cerebral palsy, Gross Motor Function Classification System ≥1 (cannot walk without assistance), microcephaly. We adjusted for confounders in logistic regression, stratified by sex, and performed separate analyses including the entire sample, and excluding children unable to walk without assistance (motor impairment). Results Weight gain in the lowest quartile from 7-28 days was not associated with higher risk of adverse outcomes. Children with a 12-month weight z-score <−2 were at increased risk for all adverse outcomes in girls, and for microcephaly and Gross Motor Function Classification System ≥1 in boys. However, excluding children with motor impairment attenuated all associations except that of weight z-score <−2 with microcephaly in girls. Similarly, most associations of low weight z-score at 24 months with adverse outcomes were attenuated with exclusion of children with motor impairment. Conclusion Excluding children who have gross motor impairment appears to eliminate the association of low weight status with neurodevelopmental impairments at 2 years in extremely preterm infants.
Abstract Background: The addition of hydralazine/isosorbide dinitrate (H-ISDN) to a standard heart failure treatment regimen in the African-American Heart Failure Trial was associated with a 43% ...reduction in mortality. However, the effectiveness of H-ISDN in a community sample of African-American patients and other racial/ethnic groups is unknown. Objective: The aim of this study was to assess the associations between treatment with H-ISDN and mortality or hospitalization for heart failure in veterans with the disease. Methods: For this retrospective cohort study, electronic data on outpatient prescriptions, comorbidity, and other heart failure risk factors were analyzed in veterans with heart failure. Patients were classified based on whether they were prescribed H-ISDN and subclassified based on race/ethnicity (African American, Hispanic, or white). Patients who were prescribed H-ISDN were subclassified based on time of initiation of H-ISDN treatment (0–121, 122–365, or >365 days after diagnosis). Data were analyzed using propensity-adjusted Cox regression analyses, with exposure to H-ISDN modeled as a time-varying covariate. Results: Data from 76,828 veterans were analyzed (98% men, 2% women). H-ISDN prescription was not associated with the risk of death in 5 of the 9 subgroups predefined by race/ethnicity or time of initiation of H-ISDN; however, H-ISDN was associated with an increased risk of death in the 4 subgroups with longer times to initiation. H-ISDN was associated with a significantly increased risk of heart failure hospitalization in all but 1 of the 9 subgroups. The risk of both mortality and hospitalization associated with H-ISDN was significantly lower in African-American patients than in those who were Hispanic or white. Concurrent prescription of other, evidence-based heart failure therapies (eg, angiotensin-converting enzyme inhibitors, β-blockers, and combinations) had strong, statistically significant associations with reduced mortality. Conclusions: In this population of veterans with heart failure, H-ISDN prescription was not associated with significant reductions in mortality or hospitalization in any of the subgroups defined by race/ethnicity and time of initiation of H-ISDN analyzed compared with the group that did not receive H-ISDN. It is possible, or even likely, that unmeasured differences in important risk factors—particularly heart failure severity and left ventricular dysfunction—between the group that received H-ISDN and the one that did not masked a beneficial effect of H-ISDN. Therefore, our conclusions must be regarded as hypothesis generating and need to be tested in subsequent randomized trial(s).
Background Selenium is a central determinant of antioxidative glutathione peroxidase 1 (GPx-1) expression and activity. The relevance of selenium supplementation on GPx-1 in coronary artery disease ...(CAD) needs to be established. We assessed the effect of selenium supplementation on GPx-1 in cell culture and on endothelial function in a prospective clinical trial. Methods Human coronary artery endothelial cells were incubated with 5.78 to 578 nmol/L sodium selenite, Se-methyl-selenocysteine hydrochloride, or seleno- l -methionine. Glutathione peroxidase 1 mRNA and protein expression and activity were measured. Coronary artery disease patients (n = 465) with impaired endothelial function (flow-mediated dilation FMD <8%) were randomly assigned to receive 200 or 500 μg sodium selenite daily or matching placebo during a 12-week period. We tested the effect on red blood cell GPx-1 activity and brachial artery FMD. Furthermore, differences in biomarkers of oxidative stress and inflammation were measured. Results Sodium selenite and Se-methyl-selenocysteine hydrochloride increased GPx-1 protein and activity in a dose-dependent manner ( P < .0001). The intention-to-treat groups comprised 433 CAD patients. Glutathione peroxidase 1 activity increased from 37.0 U/gHb (31.3-41.7) to 41.1 U/gHb (35.2-48.4) ( P < .0001) in the 200 μg and from 38.1 U/gHb (33.2-43.8) to 42.6 U/gHb (35.0-49.1) ( P < .0001) in the 500 μg sodium selenite group treated for 12-weeks. No relevant changes were observed for FMD or biomarkers of oxidative stress and inflammation. Conclusions Sodium selenite supplementation increases GPx-1 activity in endothelial cells and in CAD patients. Future studies have to demonstrate whether long-term CAD outcome can be improved.