The effects of medications on the outcome of aortic dissection remain poorly understood. We sought to address this by analyzing the International Registry of Acute Aortic Dissection (IRAD) global ...registry database. A total of 1,301 patients with acute aortic dissection (722 with type A and 579 with type B) with information on their medications at discharge and followed for ≤5 years were analyzed for the effects of the medications on mortality. The initial univariate analysis showed that use of β blockers was associated with improved survival in all patients (p = 0.03), in patients with type A overall (p = 0.02), and in patients with type A who received surgery (p = 0.006). The analysis also showed that use of calcium channel blockers was associated with improved survival in patients with type B overall (p = 0.02) and in patients with type B receiving medical management (p = 0.03). Multivariate models also showed that the use of β blockers was associated with improved survival in those with type A undergoing surgery (odds ratio 0.47, 95% confidence interval 0.25 to 0.90, p = 0.02) and the use of calcium channel blockers was associated with improved survival in patients with type B medically treated patients (odds ratio 0.55, 95% confidence interval 0.35 to 0.88, p = 0.01). In conclusion, the present study showed that use of β blockers was associated with improved outcome in all patients and in type A patients (overall as well as in those managed surgically). In contrast, use of calcium channel blockers was associated with improved survival selectively in those with type B (overall and in those treated medically). The use of angiotensin-converting enzyme inhibitors did not show association with mortality.
Summary Background HLA-DRB1*15 genotype, previous infection with Epstein-Barr virus, and vitamin D insufficiency are susceptibility factors for multiple sclerosis, but whether they act ...synergistically to increase risk is unknown. We aimed to assess the contributions of these risk factors and the effect of established precursors of multiple sclerosis, such as brain lesions on MRI and oligoclonal bands in CSF at the time of incident demyelination, on development of multiple sclerosis in children. Methods In our prospective national cohort study, we assessed children who presented with incident CNS demyelination to any of the 16 paediatric health-care facilities or seven regional health-care facilities in Canada. We did univariate and multivariable analyses to assess contributions of HLA-DRB1*15 , Epstein-Barr virus, vitamin D status, MRI evidence of brain lesions, and CSF oligoclonal bands as determinants of multiple sclerosis. We used classification and regression tree analyses to generate a risk stratification algorithm for clinical use. Findings Between Sept 1, 2004, and June 30, 2010, we screened 332 children of whom 302 (91%) were eligible and followed-up for a median of 3·14 years (IQR 1·61–4·51). 63 (21%) children were diagnosed with multiple sclerosis after a median of 127 days (99–222). Although the risk of multiple sclerosis was increased with presence of one or more HLA-DRB1*15 alleles (hazard ratio HR 2·32, 95% CI 1·25–4·30), reduced serum 25-hydroxyvitamin D concentration (HR per 10 nmol/L decrease 1·11, 1·00–1·25), and previous Epstein-Barr-virus infection (HR 2·04, 0·99–4·20), no interactions between these variables were detected on multivariate analysis. Multiple sclerosis was strongly associated with baseline MRI evidence of one or more brain lesion (HR 37·9, 5·26–273·85) or CSF oligoclonal bands (6·33, 3·35–11·96), suggesting established disease. One patient diagnosed with multiple sclerosis had a normal MRI scan, and therefore sensitivity of an abnormal MRI scan for multiple sclerosis diagnosis was 98·4%. Interpretation Risk of multiple sclerosis in children can be stratified by presence of HLA-DRB1*15 alleles, remote Epstein-Barr virus infection, and low serum 25-hydroxyvitamin D concentrations. Similar to previous studies in adults, brain lesions detected on MRI and CSF oligoclonal bands in children are probable precursors to the clinical onset of multiple sclerosis. Children with a normal MRI are very likely to have a monophasic illness. Funding Canadian Multiple Sclerosis Scientific Research Foundation.
...considerations are influenced by the morphological diversity of HCM and the unpredictable instability of the myocardial substrate, as well as the additive risk created by intense training and ...competition in susceptible patients with HCM (3). ...in HCM, the most common cause of sudden death in young athletes (1-3), engagement in intense competitive sports is itself an acknowledged modifiable risk factor (1-3). At present, the risk for sudden death in gene-positive-phenotype-negative family members appears to be extremely low and likely no different from the risk in the general population of the same age without heart disease (5,20).\n Cooper, Jr Mayo Clinic None None None None None None None N.A. Mark Estes III Tufts Medical Center None None None None None Medtroniclow *; St. Jude Medicaldagger; Boston Scientificdagger None Mark S. Link Tufts Medical Center None None None None None None None Martin S. Maron Tufts Medical Center None None None None None None None Rick A. Nishimura Mayo Clinic None None None None None None None James E. Udelson Tufts Medical Center Gilead (DSMB member for a clinical trial)low * None None None None None None low * Writing Group Disclosures This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit.
Background Previous studies have shown that patients with chronic kidney disease, including those with diabetic nephropathy, are more likely to die of cardiovascular disease than reach end-stage ...renal disease (ESRD). This analysis was conducted to determine whether ESRD is a more common outcome than cardiovascular death in patients with type 2 diabetic nephropathy, significant proteinuria, and decreased kidney function who were selected for participation in a clinical trial. Study Design Retrospective analysis of the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) database derived from 2 prospective randomized controlled clinical trials (IDNT Irbesartan Diabetic Nephropathy Trial and RENAAL Reduction of Endpoints in Non–Insulin-dependent Diabetes With the Angiotensin II Antagonist Losartan). Setting & Participants 3,228 adult patients with type 2 diabetic nephropathy from IDNT and RENAAL were combined to establish the DIAMETRIC database. This is the largest global source of clinical information for patients with type 2 diabetic nephropathy who have decreased kidney function and significant proteinuria. Intervention Angiotensin receptor blocker versus non–angiotensin receptor blocker therapy to slow the progression of type 2 diabetic nephropathy (in the prospective trials). Outcomes & Measurements Incidence rates of ESRD, cardiovascular death, and all-cause mortality. Results Mean follow-up was 2.8 years; 19.5% of patients developed ESRD, approximately 2.5 times the incidence of cardiovascular death and 1.5 times the incidence of all-cause mortality. ESRD was more common than cardiovascular death in all subgroups analyzed with the exception of participants with low levels of albuminuria (albumin excretion <1.0 g/g) and well-preserved levels of kidney function (estimated glomerular filtration rate >45 mL/min/1.73 m2 ) at baseline. Limitations All participants were included in a prospective clinical trial. Conclusions Patients with type 2 diabetic nephropathy, characterized by decreased kidney function and significant proteinuria, are more likely to reach ESRD than die during 3 years' mean follow-up. Given the rapidly increasing number of cases of type 2 diabetes worldwide, this has implications for predicting future renal replacement therapy requirements.
Background An urgent need exists in the United States to establish treatment goals in psoriasis. Objective We aim to establish defined treatment targets toward which clinicians and patients with ...psoriasis can strive to inform treatment decisions, reduce disease burden, and improve outcomes in practice. Methods The National Psoriasis Foundation conducted a consensus-building study among psoriasis experts using the Delphi method. The process consisted of: (1) literature review, (2) pre-Delphi question selection and input from general dermatologists and patients, and (3) 4 Delphi rounds. Results A total of 25 psoriasis experts participated in the Delphi process. The most preferred instrument was body surface area (BSA). The most preferred time for evaluating patient response after starting new therapies was at 3 months. The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline. The target response at 3 months postinitiation was BSA 1% or less. During the maintenance period, evaluation every 6 months was most preferred. The target response at every 6 months maintenance evaluation is BSA 1% or less. Limitations Although BSA is feasible in practice, it does not encompass health-related quality of life, costs, and risks of side effects. Conclusion With defined treatment targets, clinicians and patients can regularly evaluate treatment responses and perform benefit-risk assessments of therapeutic options individualized to the patient.
Objective This study compared the performance of the Aorfix endograft (Lombard Medical, Oxfordshire, United Kingdom) in standard (<60°), highly angled (60°-90°), and severely angled (>90°) aortic ...necks in the PYTHAGORAS study and evaluated changes in neck morphology over time. Methods PYTHAGORAS is a prospective nonrandomized clinical trial of the Aorfix endograft. We divided the endovascular aneurysm repair (EVAR) cohort into groups by standard, high, and severe neck angle. The primary control group was patients concurrently undergoing open repair. Mortality at 30 days, 1 year, and 2 years and 30-day freedom from Society for Vascular Surgery major adverse events for the EVAR groups was compared with the open control. Aneurysm sac change, type I and III endoleaks, graft migration, and the reintervention rate at 1 and 2 years was compared between the standard, highly, and severely angled populations. The relative risk of graft complications with a neck diameter increase >10% was also calculated. At predetermined anatomic points, the effect of oversizing on aortic diameter was evaluated by calculating oversize percentage (1 − outer aortic diameter measured at a given time/stent graft diameter × 100%) preoperatively and at 3 years. In addition, the average oversizing percentage at 30 days and annually at 1 to 5 years was compared with the preoperative oversizing percentage. Finally, complication rates with ≥30% vs <30% planned oversizing were compared. Results The adverse event rate was lower for every EVAR group than the open control. In addition, the mortality rates at 30 days, 1 year, and 2 years were similar between the standard-angle (1.5%, 3.0%, 4.5%), high-angle (0.9%, 7.3%, 13.8%), and severe-angle (4.8%, 9.5%, 14.3%) EVAR groups and the open control groups (1.3, 6.6%, 10.5%). At 1 and 2 years, there was no difference in graft complications among the EVAR groups. However, with neck dilatation of >10% at 5 mm above the proximal renal and 1 mm below the distal renal, there was an increased risk of graft migration (relative risk, 4.38 P = .01 and 4.33 P = .002, respectively). For all predetermined anatomic points, the oversizing percentage decreased over time. The rate of oversize percentage decrease was faster at more distal aortic locations, reaching <10% at 30 days 15 mm below the renal, at 2 years 7 mm below the renal, and at 5 years 1 mm below the renal ( P < .001 for all). Half the oversize percentage achieved at the index procedure remained at 3 years (Pearson correlation coefficient = 0.5). However, there was no difference in complications between the ≥30% and <30% planned oversize groups. Conclusions The Aorfix endograft has performed well in excluding aneurysms with standard and highly angled aortic neck anatomy.
Abstract Background Whether myocardial recovery occurs more frequently in peripartum cardiomyopathy (PPCM) than in recent onset cardiomyopathies in men and nonperipartum women has not been ...prospectively evaluated. This was examined through an analysis of outcomes in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) registry. Methods and Results IMAC2 enrolled 373 subjects with recent onset nonischemic dilated cardiomyopathy. Left ventricular ejection fraction (LVEF) was assessed at entry and 6 months, and subjects followed for up to 4 years. Myocardial recovery was compared between men (group 1), nonperipartum women (group 2) and subjects with PPCM (group 3). The cohort included 230 subjects in group 1, 104 in group 2, and 39 in group 3. The mean LVEF at baseline in groups 1, 2, and 3 was 0.23 ± 0.08, 0.24 ± 0.08, and 0.27 ± 0.07 ( P = .04), and at 6 months was 0.39 ± 0.12, 0.42 ± 0.11, and 0.45 ± 0.14 ( P = .007). Subjects in group 3 had a much greater likelihood of achieving an LVEF >0.50 at 6 months than groups 1 or 2 (19 %, 34%, and 48% respectively, P = .002). Conclusions Prospective evaluation confirms myocardial recovery is greatest in women with PPCM, poorest in men, and intermediate in nonperipartum women. On contemporary therapy, nearly half of women with PPCM normalize cardiac function by 6 months.
Summary Background To reduce lipid abnormalities and other side-effects associated with antiretroviral regimens containing lopinavir-ritonavir, patients might want to switch one or more components of ...their regimen. We compared substitution of raltegravir for lopinavir-ritonavir with continuation of lopinavir-ritonavir in HIV-infected patients with stable viral suppression on lopinavir-ritonavir-based combination therapy. Methods The SWITCHMRK 1 and 2 studies were multicentre, double-blind, double-dummy, phase 3, randomised controlled trials. HIV-infected patients aged 18 years or older were eligible if they had documented viral RNA (vRNA) concentration below the limit of assay quantification for at least 3 months while on a lopinavir-ritonavir-based regimen. 707 eligible patients were randomly allocated by interactive voice response system in a 1:1 ratio to switch from lopinavir-ritonavir to raltegravir (400 mg twice daily; n=353) or to remain on lopinavir-ritonavir (two 200 mg/50 mg tablets twice daily; n=354), while continuing background therapy consisting of at least two nucleoside or nucleotide reverse transcriptase inhibitors. Primary endpoints were the mean percentage change in serum lipid concentrations from baseline to week 12; the proportion of patients with vRNA concentration less than 50 copies per mL at week 24 (with all treated patients who did not complete the study counted as failures) with a prespecified non-inferiority margin of −12% for each study; and the frequency of adverse events up to 24 weeks. Analyses were done according to protocol. These trials are registered with ClinicalTrials.gov , numbers NCT00443703 and NCT00443729. Findings 702 patients received at least one dose of study drug and were included in the efficacy and safety analyses for the combined trials (raltegravir, n=350; lopinavir-ritonavir, n=352). Percentage changes in lipid concentrations from baseline to week 12 were significantly greater (p<0·0001) in the raltegravir group than in the lopinavir-ritonavir group in each study, yielding combined results for total cholesterol −12·6% vs 1·0%, non-HDL cholesterol −15·0% vs 2·6%, and triglycerides −42·2% vs 6·2%. At week 24, 293 (84·4%, 95% CI 80·2–88·1) of 347 patients in the raltegravir group had vRNA concentration less than 50 copies per mL compared with 319 (90·6%, 87·1–93·5) of 352 patients in the lopinavir-ritonavir group (treatment difference −6·2%, −11·2 to −1·3). Clinical and laboratory adverse events occurred at similar frequencies in the treatment groups. There were no serious drug-related adverse events or deaths. The only drug-related clinical adverse event of moderate to severe intensity reported in 1% or more of either treatment group was diarrhoea, which occurred in ten patients in the lopinavir-ritonavir group (3%) and no patients in the raltegravir group. The studies were terminated at week 24 because of lower than expected virological efficacy in the raltegravir group compared with the lopinavir-ritonavir group. Interpretation Although switching to raltegravir was associated with greater reductions in serum lipid concentrations than was continuation of lopinavir-ritonavir, efficacy results did not establish non-inferiority of raltegravir to lopinavir-ritonavir. Funding Merck.
Abstract Purpose To describe factors associated with racial disparities in HIV (human immunodeficiency virus) incidence among men who have sex with men (MSM) in the United States. Methods In a ...longitudinal cohort of black and white HIV-negative MSM in Atlanta, HIV incidence rates were compared by race. Incidence hazard ratios (HRs) between black and white MSM were estimated with an age-scaled Cox proportional hazards model. A change-in-estimate approach was used to understand mediating time-independent and -dependent factors that accounted for the elevated HR. Results Thirty-two incident HIV infections occurred among 260 black and 302 white MSM during 843 person-years (PY) of follow-up. HIV incidence was higher among black MSM (6.5/100 PY; 95% confidence interval CI: 4.2–9.7) than white MSM (1.7/100 PY; CI: 0.7–3.3) and highest among young (18–24 years) black MSM (10.9/100 PY; CI: 6.2–17.6). The unadjusted hazard of HIV infection for black MSM was 2.9 (CI: 1.3–6.4) times that of white MSM; adjustment for health insurance status and partner race explained effectively all of the racial disparity. Conclusions Relative to white MSM in Atlanta, black MSM, particularly young black MSM, experienced higher HIV incidence that was not attributable to individual risk behaviors. In a setting where partner pool risk is a driver of disparities, it is also important to maximize care and treatment for HIV-positive MSM.
Objectives To test the hypothesis that heavy metal toxicity and consumption of thiaminase-containing foods predispose to symptomatic thiamine deficiency. Study design In a case-control study, ...thiamine diphosphate (TDP) blood concentrations were measured in 27 infants diagnosed with beriberi at a rural clinic, as well as their mothers and healthy Cambodian and American controls. Blood and urine levels of lead, arsenic, cadmium, mercury, and thallium were measured. Local food samples were analyzed for thiaminase activity. Results Mean TDP level among cases and Cambodian controls was 48 and 56 nmol/L, respectively ( P = .08) and was 132 nmol/L in American controls ( P < .0001 compared with both Cambodian groups). Mean TDP level of mothers of cases and Cambodian controls was 57 and 57 nmol/L ( P = .92), and was 126 nmol/L in American mothers ( P < .0001 compared with both Cambodian groups). Cases (but not controls) had lower blood TDP levels than their mothers ( P = .02). Infant TDP level decreased with infant age and was positively associated with maternal TDP level. Specific diagnostic criteria for beriberi did not correlate with TDP level. There was no correlation between heavy metal levels and either TDP level or case/control status. No thiaminase activity was observed in food samples. Conclusions Thiamine deficiency is endemic among infants and nursing mothers in rural southeastern Cambodia and is often clinically inapparent. Neither heavy metal toxicity nor consumption of thiaminase-containing foods account for thiamine deficiency in this region.
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