Hospital for Sick Children

About: Hospital for Sick Children is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Medicine. The organization has 4097 authors who have published 3746 publications receiving 129066 citations. The organization is also known as: Sick Kids Hospital & SickKids.

An international consensus approach to the management of atypical hemolytic uremic syndrome in children.

Abstract: Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a disease largely of complement dysregulation. This advance facilitated the development of novel, rational treatment options targeting terminal complement activation, e.g., using an anti-C5 antibody (eculizumab). We review treatment and patient management issues related to this therapeutic approach. We present consensus clinical practice recommendations generated by HUS International, an international expert group of clinicians and basic scientists with a focused interest in HUS. We aim to address the following questions of high relevance to daily clinical practice: Which complement investigations should be done and when? What is the importance of anti-factor H antibody detection? Who should be treated with eculizumab? Is plasma exchange therapy still needed? When should eculizumab therapy be initiated? How and when should complement blockade be monitored? Can the approved treatment schedule be modified? What approach should be taken to kidney and/or combined liver-kidney transplantation? How should we limit the risk of meningococcal infection under complement blockade therapy? A pressing question today regards the treatment duration. We discuss the need for prospective studies to establish evidence-based criteria for the continuation or cessation of anticomplement therapy in patients with and without identified complement mutations.

Drug Therapy of High-Risk Lipid Abnormalities in Children and Adolescents A Scientific Statement From the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, With the Council on Cardiovascular Nursing

Abstract: Despite compliance with lifestyle recommendations, some children and adolescents with high-risk hyperlipidemia will require lipid-lowering drug therapy, particularly those with familial hypercholesterolemia. The purpose of this statement is to examine new evidence on the association of lipid abnormalities with early atherosclerosis, discuss challenges with previous guidelines, and highlight results of clinical trials with statin therapy in children and adolescents with familial hypercholesterolemia or severe hypercholesterolemia. Recommendations are provided to guide decision-making with regard to patient selection, initiation, monitoring, and maintenance of drug therapy.

Enteral nutritional therapy for induction of remission in Crohn's disease

Abstract: Background The role of enteral nutrition in Crohn's disease is controversial. Increasing research on the mechanisms by which nutritional therapy improves the clinical well being of patients with Crohn's disease has led to novel formula design and trials comparing two different forms of enteral nutrition. This meta-analysis aims to provide an update on the existing effectiveness data for both corticosteroids versus enteral nutrition and for one form of enteral nutrition versus another for inducing remission of active Crohn's disease. Objectives To evaluate the effectiveness of exclusive enteral nutrition (EN) as primary therapy to induce remission in Crohn's disease and to examine the importance of formula composition on effectiveness. Search methods Studies were selected using a computer-assisted search of the on-line bibliographic databases MEDLINE (1966-2006) and EMBASE (1984-2006), as well as the Science Citation Index on Web of Science. Additional citations were sought by manual search of references of articles retrieved from the computerized search, abstracts submitted to major gastroenterologic meetings and published in the journals: American Journal of Gastroenterology, Gut, Gastroenterology, Journal of Pediatric Gastroenterology and Nutrition, and Journal of Parenteral and Enteral Nutrition, and from the reviewers' personal files or contact with leaders in the field. Selection criteria All randomized and quasi-randomized controlled trials involving patients with active Crohn's disease defined by a clinical disease activity index were considered for review. Studies evaluating the administration of one type of enteral nutrition to one group of patients and another type of enteral nutrition or conventional corticosteroids to the other group were selected for review. Data collection and analysis Data were extracted independently by two authors and any discrepancies were resolved by rereading and discussion. For the dichotomous variable, achievement of remission, individual and pooled trial statistics were calculated as odds ratios (OR) with 95% confidence intervals (CI); both fixed and random effect models were used. The results for each analysis were tested for heterogeneity using the chi square statistic. The studies were separated into two groups: A. one form of enteral nutrition compared with another form of enteral nutrition and B. one form of enteral nutrition compared with corticosteroids. Subgroup analyses were conducted on the basis of clinical or disease criteria and formula composition. Sensitivity analyses were conducted on the basis of the inclusion of abstract publications, methodologic quality and by random or fixed effects models. Main results In part A, of the 15 included eligible trials (one abstract) comparing different formulations of EN for the treatment of active CD, 11 compared one (or more) elemental formula to a non-elemental one, three compared enteral diets of similar protein composition but different fat composition, and one compared non-elemental diets differing only in glutamine enrichment. Meta-analysis of ten trials comprising 334 patients demonstrated no difference in the efficacy of elemental versus non-elemental formulas (OR 1.10; 95% CI 0.69 to 1.75). Subgroup analyses performed to evaluate the different types of elemental and non-elemental diets (elemental, semi-elemental and polymeric) showed no statistically significant differences. Further analysis of seven trials including 209 patients treated with EN formulas of differing fat content (low fat: 20 g/1000 kCal) demonstrated no statistically significant difference in efficacy (OR 1.13; 95% CI 0.63 to 2.01). Similarly, the effect of very low fat content (< 3 g/1000 kCal) or type of fat (long chain triglycerides) were investigated, but did not demonstrate a difference in efficacy in the treatment of active CD, although a non significant trend was demonstrated favoring very low fat and very low long chain triglyceride content. This result should be interpreted with caution due to statistically significant heterogeneity and small sample size. Sensitivity analyses had no significant effects on the results. The role of specific fatty acids or disease characteristics on response to therapy could not be evaluated. In part B, eight trials (including two abstracts) comparing enteral nutrition to steroid therapy met the inclusion criteria for review. Meta-analysis of six trials that included 192 patients treated with enteral nutrition and 160 treated with steroids yielded a pooled OR of 0.33 favouring steroid therapy (95% CI 0.21 to 0.53). A sensitivity analysis including the abstracts resulted in an increase in the number of participants to 212 in the enteral nutrition group and 179 in the steroid group but the meta-analysis yielded a similar result (OR 0.36; 95% CI 0.23 to 0.56). There were inadequate data from full publications to perform further subgroup analyses by age, disease duration and disease location. Authors' conclusions Corticosteroid therapy is more effective than enteral nutrition for inducing remission of active Crohn's disease as was found in previous systematic reviews. Protein composition does not influence the effectiveness of EN in the treatment of active CD. A non significant trend favouring very low fat and/or very low long chain triglyceride content exists but larger trials are required to explore the significance of this finding.

Primary structure of dystrophin-related protein.

Abstract: DYSTROPHIN-RELATED protein (DRP or 'utrophin'1) is localized in normal adult muscle primarily at the neuromuscular junction2–4. In the absence of dystrophin in Duchenne muscular dystrophy (DMD) patients, DRP is also present in the sarcolemma3–7. DRP is expressed in fetal and regenerating muscle and may play a similar role to dystrophin in early development3,7–9, although it remains to be determined whether DRP can functionally replace dystrophin in adult tissue. Previously we described a 3.5-kilobase complementary DNA clone that exhibits 80 per cent homology to the C-terminal domain of dystrophin10. This sequence identifies a 13-kilobase transcript that maps to human chromosome 6 (refs 2, 11). Antibodies raised against the gene product identify a polypeptide with a relative molecular mass of about 400K in all tissues examined7,8,12. To investigate the relationship between DRP and dystrophin in more detail, we have cloned and sequenced the whole DRP cDNA. Homology between DRP and dystrophin extends over their entire length, suggesting that they derive from a common ancestral gene. Comparative analysis of primary sequences highlights regions of functional importance, including those that may mediate the localization of DRP and dystrophin in the muscle cell.

Neuropsychological profiles of adolescents with ADHD: effects of reading difficulties and gender

Abstract: Background: Executive function, particularly behavioral inhibition, has been implicated as a core deficit specific to Attention-Deficit/Hyperactivity Disorder (ADHD) whereas rapid naming has been implicated as a core deficit specific to reading disabilities (RD). Females may be less impaired in executive function although adolescent females with ADHD have yet to be studied. Method: Neuropsychological profiles of four adolescent groups aged 13–16 with equal female representation were investigated: 35 ADHD, 12 RD, 24 ADHD+RD, and 37 normal controls. A semi-structured interview (K-SADS-PL), the Conners Rating Scales and the Ontario Child Health Study Scales were used to diagnose ADHD. RD was defined as a standard score below 90 on at least one of the following: Reading or Spelling of the WRAT3 or Word Attack or Word Identification of the WRMT-R. The WISC-III, Rapid Automatized Naming, Stroop and Stop tasks were used as measures of cognitive and executive function. Results: The two ADHD groups (ADHD, ADHD+RD) showed deficits in processing speed, naming of objects, poor behavioral inhibition and greater variability in reaction times whereas the two RD groups (RD, RD+ADHD) showed verbal working memory deficits and slower verbal retrieval speed. Only the comorbid group was slower with naming of numbers and colors and had slower reaction times. Regression analyses indicated that incongruent color naming (Stroop) and variability in go reaction time were the best predictors of hyperactive/impulsive ADHD symptoms whereas variability in go reaction time and processing speed were the best predictors of inattentive ADHD symptoms. Speed of letter naming and verbal working memory accounted for the most variability in composite achievement scores. No gender differences were found on any of the cognitive tests. Conclusions: This study challenges the importance of behavioral inhibition deficits in ADHD and that naming deficits are specific to RD. Further investigation into cognitive deficits in these groups is required. ADHD: Attention-Deficit/Hyperactivity Disorder; RD: Reading Difficulties; SES: socio-economic status; CTRS: Conners' Teacher Rating Scale; OCHSS: Ontario Child Health Study Scales; WRAT: Wide Range Achievement Test; WRMT: Woodcock Reading Mastery Test; MDD: Major Depressive Disorder; SAD: Separation Anxiety Disorder; GAD: Generalized Anxiety Disorder; OCD: Obsessive Compulsive Disorder; WISC: Wechsler Intelligence Scale for Children; RAN: Rapid Automatized Naming; SSRT: Stop Signal Reaction Time;