A substantial increase in the knowledge of the genetic basis of cardiomyopathy has occurred, and noninvasive phenotypic characterization has become significantly more sophisticated. ...the American ...Heart Association (AHA) (7) and the European Society of Cardiology (ESC) (8) in the last decade have proposed revisions to the classification of cardiomyopathic disorders. In the ESC 2008 classification, the cardiomyopathy was defined as familial when present in more than 1 member of the family.\n Disease MIM# Phenotype Inheritance Age of Onset Disease Gene Cardiac Phenotype Extracardiac Markers/Involvement of Other Organs Treatment Multiple acyl-CoA dehydrogenase deficiency Glutaric acidemia IIA 231680 AR Neonatal ETFA DCM, neonatal Nervous, skeletal, muscle, liver, kidney (often polycystic), metabolic acidosis, hypoglycemia  Glutaric acidemia IIB 231680 AR Neonatal, childhood ETFB Sudden neonatal death Nervous, skeletal, muscle, liver  Glutaric acidemia IIC 231680 AR Childhood to adult ETFDH DCM Nervous, skeletal, muscle, liver, kidney (often polycystic), lung, metabolic acidosis, hypoglycemia  Primary, systemic, carnitine transporter deficiency 212140 AR Childhood to adult SLC22A5 DCM, HCM < Total plasma carnitine, hypoketotic hypoglycemia, hepatomegaly, elevated transaminases, and hyperammonemia in infants; skeletal myopathy, > creatine kinase, in childhood; cardiomyopathy, arrhythmias, or fatigability in adulthood Carnitine supplementation Chanarin-Dorfman syndrome (NLSD-I) 275630 AR Childhood to adult ABHD5 DCM Skin (ichthyosiform erythroderma), liver, muscle, nervous (with possible MR), ocular Suggested: diet low in long-chain fatty acids; retinoids for skin in patients w/o liver dysfunction Neutral lipid storage disease with myopathy (NLSD-M) 610717 AR Childhood to adult PNPLA2low * DCM Myopathy  Table 5 Major Lipid Storage Disorders With Possible Myocardial Involvement MR = mental retardation; other abbreviations as in Table 1.
Autism Spectrum Symptoms in a Tourette's Disorder Sample Darrow, Sabrina M; Grados, Marco; Sandor, Paul ...
Journal of the American Academy of Child and Adolescent Psychiatry,
07/2017, Letnik:
56, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Tourette's disorder (TD) and autism spectrum disorder (ASD) share clinical features and possibly an overlapping etiology. The aims of this study were to examine ASD symptom rates in participants with ...TD, and to characterize the relationships between ASD symptom patterns and TD, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD).
Participants with TD (n = 535) and their family members (n =234) recruited for genetic studies reported TD, OCD, and ADHD symptoms and completed the Social Responsiveness Scale Second Edition (SRS), which was used to characterize ASD symptoms.
SRS scores in participants with TD were similar to those observed in other clinical samples but lower than in ASD samples (mean SRS total raw score = 51; SD = 32.4). More children with TD met cut-off criteria for ASD (22.8%) than adults with TD (8.7%). The elevated rate in children was primarily due to high scores on the SRS Repetitive and Restricted Behaviors (RRB) subscale. Total SRS scores were correlated with TD (r = 0.27), OCD (r = 0.37), and ADHD (r = 0.44) and were higher among individuals with OCD symptom-based phenotypes than for those with tics alone.
Higher observed rates of ASD among children affected by TD may in part be due to difficulty in discriminating complex tics and OCD symptoms from ASD symptoms. Careful examination of ASD-specific symptom patterns (social communication vs. repetitive behaviors) is essential. Independent of ASD, the SRS may be a useful tool for identifying patients with TD with impairments in social communication that potentially place them at risk for bullying and other negative sequelae.
Purpose Randomized controlled trials (RCTs) have demonstrated the efficacy of biologic agents in the treatment of rheumatic diseases. However, results from RCTs may not be generalizable to clinical ...practice because of their strict inclusion and exclusion criteria. Assessment of safety using RCT data also is limited by short duration of follow-up and relatively small sample sizes, which generally preclude analysis of longer term outcomes and rare adverse events. In rheumatology, various observational cohorts and registries have been created to complement information obtained from RCTs, some with the primary purpose of monitoring effectiveness and safety of biologic agents. Most registries are either drug based or disease based. These registries include patients with a variety of rheumatic diseases including RA. Methods To provide a qualitative comparison of selected U.S. and European rheumatoid arthritis (RA) biologics registries and cohorts including ARTIS, BIOBADASER, BSRBR, BRASS, CLEAR, CORRONA, NDB, RABBIT, SCQM, and VARA. Results A careful comparison of these registries, as provided in this article, can provide a basis for understanding the many similarities and differences inherent in their design, as well as societal context and content, all of which can significantly impact their results and comparisons across registers. Summary The increasing use of biologic agents for treatment of rheumatic diseases has raised important questions about cost, safety, and effectiveness of these agents. The unique and variable features of patient populations and registry designs in Europe and the U.S. provide valuable and complementary data on comparative effectiveness and safety of biologic agents to what can be derived from RCTs.
Background Patients with heart failure (HF) are at high risk for mortality and rehospitalization in the early period after hospital discharge. We developed clinical models predictive of short-term ...clinical outcomes in a broad patient population discharged after hospitalization for HF. Methods The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry is a comprehensive hospital-based registry and performance-improvement program for patients hospitalized with HF. Follow-up data were scheduled to be prospectively collected at 60 to 90 days postdischarge in a prespecified 10% sample. For the 4,402 patients included in this analysis, 19 prespecified potential predictor variables were used in a stepwise Cox proportional hazards model for all-cause mortality. Logistic regression including 45 potential variables was used to model mortality or rehospitalization. Results The 60- to 90-day postdischarge mortality rate was 8.6% (n = 481), and 29.6% (n = 1,715) were rehospitalized. Factors predicting early postdischarge mortality include age, serum creatinine, reactive airway disease, liver disease, lower systolic blood pressure, lower serum sodium, lower admission weight, and depression. Use of statins and β-blockers at discharge was associated with significantly decreased mortality. The C -index of the model was 0.74. The most important predictors for the combined end point of death or rehospitalization were admission serum creatinine, systolic blood pressure, admission hemoglobin, discharge use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and pulmonary disease. From this analysis, 8 factors identified to carry significant risk were selected for use in a point scoring system to predict the risk of mortality within 60 days after discharge, with a C -index of 0.72. Conclusions A substantial risk of mortality and mortality or rehospitalization is present in the first 60 to 90 days after discharge from a hospitalization for HF. Several factors were identified that signal high-risk patients. Application of these findings with a simple algorithm can distinguish patients who are low risk from those at high risk who may benefit from closer monitoring and aggressive evidence-based treatment.
Summary Background Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton-pump inhibitor plus amoxicillin and clarithromycin are significantly less ...effective for eradication of Helicobacter pylori infection than are 5-day concomitant and 10-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses than do three-drug regimens and thus could be suitable for eradication programmes in low-resource settings. Few studies in Latin America have been done, where the burden of H pylori -associated diseases is high. We therefore did a randomised trial in Latin America comparing the effectiveness of four-drug regimens given concomitantly or sequentially with that of a standard 14-day regimen of triple therapy. Methods Between September, 2009, and June, 2010, we did a randomised trial of empiric 14-day triple, 5-day concomitant, and 10-day sequential therapies for H pylori in seven Latin American sites: Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites). Participants aged 21–65 years who tested positive for H pylori by a urea breath test were randomly assigned by a central computer using a dynamic balancing procedure to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); 5 days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by urea breath test 6–8 weeks after randomisation. The trial was not masked. Our primary outcome was probablity of H pylori eradication. Our analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , registration number NCT01061437. Findings 1463 participants aged 21–65 years were randomly allocated a treatment: 488 were treated with 14-day standard therapy, 489 with 5-day concomitant therapy, and 486 with 10-day sequential therapy. The probability of eradication with standard therapy was 82·2% (401 of 488), which was 8·6% higher (95% adjusted CI 2·6–14·5) than with concomitant therapy (73·6% 360 of 489) and 5·6% higher (–0·04% to 11·6) than with sequential therapy (76·5% 372 of 486). Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites. Interpretation Standard 14-day triple-drug therapy is preferable to 5-day concomitant or 10-day sequential four-drug regimens as empiric therapy for H pylori infection in diverse Latin American populations. Funding Bill & Melinda Gates Foundation, US National Institutes of Health.
Previous studies have suggested that female and elderly patients with heart failure (HF) are less likely to receive guideline-recommended therapies, but these studies have involved select patient ...populations. We evaluated the differences in medical care and patient outcomes by age and gender among a broad cohort of hospitalized patients with HF. The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) is a registry and performance-improvement program involving 48,612 patients with HF from 259 hospitals. The data were analyzed by gender, age <75 years, and age ≥75 years. Appropriate angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and β-blocker use were similar between women and men (p = 0.244 and p = 0.237, respectively). However, compared with men, fewer women received hospital discharge instructions (p <0.001) and the length of stay was longer (p <0.001). Risk-adjusted in-hospital and postdischarge mortality were similar. All guideline-recommended cardiac medications were prescribed less frequently at discharge to eligible patients ≥75 than to those <75 years (all p <0.001). Older age was independently associated with in-hospital and postdischarge mortality risk increases (76% and 62%, respectively; p <0.001 for both). In conclusion, among the OPTIMIZE-HF hospitals, female patients with HF generally received similar medical care and had similar risks of adverse clinical outcomes compared with male patients. Older patients with HF were less likely to receive guideline-recommended therapies and remained at greater risk of adverse outcomes.
Abstract Background Depression is a risk factor of excessive morbidity and mortality in heart failure. We examined in-hospital treatment and postdischarge outcomes in hospitalized heart failure ...patients with a documented history of depression from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure. Methods We identified patient factors associated with depression history and evaluated the association of depression with hospital treatments and mortality, and early postdischarge mortality, emergency care, and rehospitalization. Results In 48,612 patients from 259 hospitals, depression history was present in 10.6% and occurred more often in females, whites, and those with common heart failure comorbidities, including chronic pulmonary obstructive disease (36% vs 27%), anemia (27% vs 16.5%), insulin-dependent diabetes mellitus (20% vs 16%), and hyperlipidemia (38% vs 31%), all P <.001. Patients with depression history were less likely to receive coronary interventions and cardiac devices, all P <.01; or be referred to outpatient disease management programs, P <.001. Length of hospital stay was longer with depression history (7.0 vs 6.4 days, P <.001). In 5791 patients followed-up at 60-90 days postdischarge, those with depression history had higher mortality (8.8% vs 6.4%; P = .025). After multivariable modeling, depression history remained a predictor of length of hospital stay, P <.001 and postdischarge mortality, P = .02. Conclusions Depression history at heart failure hospitalization may be a predictor of prolonged length of hospital stay, less use of cardiac procedures and postdischarge disease management, and increased 60-90 day mortality. Patients with depression might represent a vulnerable group in which improved use of evidence-based treatment should be considered.
Background Major depressive disorder (MDD) is a global health concern. This study examined the efficacy, safety and tolerability of an extended-release (ER) formulation of levomilnacipran, an ...antidepressant approved for the treatment of MDD in adults. Methods This 10- week (1-week placebo run-in period, 8-week double-blind treatment, 1-week down-taper), multicentre, double-blind, placebo-controlled, parallel-group, fixed-dose study was conducted between June 2011 and March 2012. Adult outpatients (age 18-75 yr) with MDD were randomly assigned (1:1:1) to placebo or to levomilnacipran ER 40 mg/day or 80 mg/day. For primary efficacy, we analyzed the Montgomery-Asberg Depression Rating Scale (MADRS) change from baseline to week 8 using a mixed-effects model for repeated- measures approach on the intent-to-treat (ITT) population. For secondary efficacy, we used the Sheehan Disability Scale (SDS), and for safety, we examined adverse events and laboratory, vital sign/physical and electrocardiography findings. Results The ITT population consisted of 185 patients in the placebo group, 185 in the levomilnacipran ER 40 mg/day group and 187 in the levomilnacipran ER 80 mg/ day group. Study completion rates were similar among the groups (76%–83%). On MADRS change from baseline the least squares mean difference (LSMD) and 95% confidence interval (CI) versus placebo was significant for levomilnacipran ER 40 mg/day (–3.3 –5.5 to –1.1, p = 0.003) and 80 mg/day (–3.1, –5.3 to –1.0, p = 0.004). On SDS change from baseline the LSMD (and 95% CI) versus placebo was also significant for levomilnacipran ER 40 mg/day (–1.8, 95% –3.6 to 0, p = 0.046) and 80 mg/day (–2.7 –4.5 to –0.9, p = 0.003). More patients in the levomilnacipran ER than the placebo group prematurely exited the study owing to adverse events; common adverse events (> 5% and > double the rate of placebo) were nausea, dry mouth, increased heart rate, constipation, dizziness, hyperhidrosis, urinary hesitation and erectile dysfunction. Limitations Limitations to our study included short treatment duration and lack of an active control arm. Conclusion Levomilnacipran ER at doses of 40 mg/day and 80 mg/day demonstrated efficacy on symptomatic and functional measures of MDD and was generally well tolerated in this patient population. Clinical trial registration NCT01377194.
Influence of Beta-Blocker Continuation or Withdrawal on Outcomes in Patients Hospitalized With Heart Failure: Findings From the OPTIMIZE-HF Program Gregg C. Fonarow, William T. Abraham, Nancy M. ...Albert, Wendy Gattis Stough, Mihai Gheorghiade, Barry H. Greenberg, Christopher M. O'Connor, Jie Lena Sun, Clyde W. Yancy, James B. Young, on behalf of the OPTIMIZE-HF Investigators and Coordinators Whether beta-blocker therapy should be continued or withdrawn during hospitalization for heart failure has not been well studied. The OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) data were analyzed according to whether beta-blocker therapy was continued, withdrawn, or not started. Among beta-blocker–eligible patients, there were 1,350 (57.1%) who were continued on beta-blocker therapy, 79 (3.3%) in whom therapy was withdrawn, and 303 (12.8%) who were eligible but not treated. Continuation of beta-blocker therapy was associated with a significantly lower adjusted risk of post-discharge death and death/rehospitalization compared with no beta-blocker therapy. In contrast, withdrawal of beta-blocker therapy was associated with higher adjusted post-discharge mortality risk compared with continuation.
Anemia in heart failure (HF) is increasingly recognized and treated, but little is known about the prevalence and its relation to outcomes in patients hospitalized for decompensated HF in a situation ...of both reduced and preserved systolic function. We hypothesized that lower hemoglobin is correlated with death during hospitalization and 60 to 90 days postdischarge in patients with HF. The Organized Program to Initiate Lifesaving Treatment in Patients with Heart Failure is a registry and performance improvement program for hospitalized patients with HF. Study cohorts were defined by admission hemoglobin quartile. Data from 48,612 patients at 259 hospitals showed that half of the total cohort had low hemoglobin (<12.1 g/dl) and that 25% were moderately to severely anemic (lowest hemoglobin quartile, 5 to 10.7 g/dl). Patients with low hemoglobin were older, were more often women and Caucasian, and had preserved systolic function and elevated creatinine. They were also less likely to receive angiotensin-converting enzyme inhibitors and β blockers at discharge. Anemic patients had higher in-hospital mortality (4.8% vs 3.0%, lowest vs highest quartile), longer hospital length of stay (6.5 vs 5.3 days), and more readmissions by 90 days (33.1% vs 24.2%) (all p <0.0001). In conclusion, these data reveal a higher prevalence of low hemoglobin in hospitalized patients than noted in randomized HF trials and outpatient registries. Lower hemoglobin is associated with higher morbidity and mortality in hospitalized patients with HF.
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