A longitudinal study of magnetic resonance spectroscopy Huntington's disease biomarkers.

Putaminal metabolites examined using cross-sectional magnetic resonance spectroscopy (MRS) can distinguish pre-manifest and early Huntington's Disease (HD) individuals from controls. An ideal biomarker, however, will demonstrate longitudinal change over short durations. The objective here was to evaluate longitudinal in vivo brain metabolite profiles in HD over 24 months. Eighty-four participants (30 controls, 25 pre-manifest HD, 29 early HD) recruited as part of TRACK-HD were imaged at baseline, 12 months, and 24 months using 3T MRS of left putamen. Automated putaminal volume measurement was performed simultaneously. To quantify partial volume effects, spectroscopy was performed in a second, white matter voxel adjacent to putamen in six subjects. Subjects underwent TRACK-HD motor assessment. Statistical analyses included linear regression and one-way analysis of variance (ANOVA). At all time-points N-acetyl aspartate and total N-acetyl aspartate (NAA), neuronal integrity markers, were lower in early HD than in controls. Total NAA was lower in pre-manifest HD than in controls, whereas the gliosis marker myo-inositol (MI) was robustly elevated in early HD. Metabolites were stable over 24 months with no longitudinal change. Total NAA was not markedly different in adjacent white matter than putamen, arguing against partial volume confounding effects in cross-sectional group differences. Total NAA correlations with disease burden score suggest that this metabolite may be useful in identifying neurochemical responses to therapeutic agents. We demonstrate almost consistent group differences in putaminal metabolites in HD-affected individuals compared with controls over 24 months. Future work establishing spectroscopy as an HD biomarker should include multi-site assessments in large, pathologically diverse cohorts.

Paroxysmal nocturnal haemoglobinuria phenotype cells and leucocyte subset telomere length in childhood acquired aplastic anaemia.

The significance of paroxysmal nocturnal haemoglobinuria (PNH(pos) ) cells and leucocyte subset telomere lengths in paediatric aplastic anaemia (AA) is unknown. Among 22 children receiving immunosuppressive therapy (IST) for AA, 73% (16/22) were PNH(pos) , of whom 94% achieved at least a partial response (PR) to IST; 11/16 (69%) achieved complete response (CR). Only 2/6 (33%) PNH(neg) patients achieved PR. PNH(pos) patients were less likely to fail IST compared to PNH(neg) patients (odds ratio 0·033; 95% confidence interval 0·002-0·468; P = 0·012). Children with AA had short granulocyte (P = 7·8 × 10(-9) ), natural killer cell (P = 6·0 × 10(-4) ), naïve T lymphocyte (P = 0·002) and B lymphocyte (P = 0·005) telomeres compared to age-matched normative data.

Short-term late-generation antibiotics versus longer term penicillin for acute streptococcal pharyngitis in children.

BACKGROUND: The standard duration of treatment for children with acute group A beta hemolytic streptococcus (GABHS) pharyngitis with oral penicillin is 10 days. Shorter duration antibiotics may have comparable efficacy. OBJECTIVES: To summarize the evidence regarding the efficacy of two to six days of newer oral antibiotics (short duration) compared to 10 days of oral penicillin (standard duration) in treating children with acute GABHS pharyngitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 3) which contains the Cochrane Acute Respiratory Infections Group's Specialized Register, MEDLINE (January 1966 to March week 3, 2012) and EMBASE (January 1990 to April 2012). SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing short duration oral antibiotics to standard duration oral penicillin in children aged 1 to 18 years with acute GABHS pharyngitis. DATA COLLECTION AND ANALYSIS: Two review authors scanned the titles and abstracts of retrieved citations and applied the inclusion criteria. We retrieved included studies in full, and extracted data. Two review authors independently assessed trial quality. MAIN RESULTS: We included 20 studies with 13,102 cases of acute GABHS pharyngitis. The updated search did not identify any new eligible studies; the majority of studies were at high risk of bias. However, the majority of the results were consistent. Compared to standard duration treatment, the short duration treatment studies had shorter periods of fever (mean difference (MD) -0.30 days, 95% confidence interval (CI) -0.45 to -0.14) and throat soreness (MD -0.50 days, 95% CI -0.78 to -0.22); lower risk of early clinical treatment failure (odds ratio (OR) 0.80, 95% CI 0.67 to 0.94); no significant difference in early bacteriological treatment failure (OR 1.08, 95% CI 0.97 to 1.20) or late clinical recurrence (OR 0.95, 95% CI 0.83 to 1.08). However, the overall risk of late bacteriological recurrence was worse in the short duration treatment studies (OR 1.31, 95% CI 1.16 to 1.48), although no significant differences were found when studies of low dose azithromycin (10 mg/kg) were eliminated (OR 1.06, 95% CI 0.92 to 1.22). Three studies reported long duration complications. Out of 8135 cases of acute GABHS pharyngitis, only six cases in the short duration treatment versus eight in the standard duration treatment developed long-term complications in the form of glomerulonephritis and acute rheumatic fever, with no statistically significant difference (OR 0.53, 95% CI 0.17 to 1.64). AUTHORS' CONCLUSIONS: Three to six days of oral antibiotics had comparable efficacy compared to the standard duration 10-day course of oral penicillin in treating children with acute GABHS pharyngitis. . In areas where the prevalence of rheumatic heart disease is still high, our results must be interpreted with caution.

Does adjuvant steroid therapy post-Kasai portoenterostomy improve outcome of biliary atresia? Systematic review and meta-analysis.

BACKGROUND: The role of adjuvant steroid therapy in the postoperative management of patients with biliary atresia (BA) is unclear. OBJECTIVE: To systematically review the literature and perform a meta-analysis to determine the efficacy of adjuvant steroid therapy post-Kasai portoenterostomy (KP) on BA outcome. METHODS: A systematic review and meta-analysis of randomized trials and/or observational studies that examined the role of steroids on BA outcomes published between January 1969 and June 2010 was conducted. Studies were identified using the Medline, PubMed, EMBASE and Cochrane databases. RESULTS: Sixteen observational studies and one randomized controlled trial (RCT) were found. Four of the 16 observational studies (160 participants) and the RCT (73 participants) met the entry criteria and were eligible to be included in the analysis. There was no statistically significant difference in the effect of steroids either on normalizing serum bilirubin levels at six months (pooled OR 1.48 [95% CI 0.67 to 3.28]) or in delaying the need for early liver transplantation (within the first year post-KP (pooled OR 0.59 [95% CI 0.21 to 1.72]). CONCLUSION: The present meta-analysis did not find a significant effect of steroid over standard therapy, either in normalizing serum bilirubin levels at six months or at delaying the need for early liver transplantation post-KP. RCT studies of sufficient size and comprehensive design using high-dose steroids are needed to determine the effectiveness of steroids on the short and intermediate post-KP outcomes for BA patients.

Immunosuppressive therapy without hematopoietic growth factor exposure in pediatric acquired aplastic anemia.

Immunosuppressive therapy (IST) is recommended for children with acquired aplastic anemia (AA) who lack a human leukocyte antigen (HLA)-matched sibling donor for hematopoietic cell transplantation (HCT). Hematopoietic growth factors have often been included in IST supportive care, but prolonged exposure may increase the risk of secondary clonal evolution. The authors evaluated response, survival, and the incidence of clonal evolution following cyclosporine-based IST without hematopoietic growth factor exposure in a population-based pediatric cohort, identified retrospectively. Forty-five patients with a median age of 7.3 years (range 1.2-17.0 years) were included. Partial (PR) and complete (CR) response was achieved in 82% and 64%, at a median of 55 days (range 11-414 days) and 7.6 months (range 2.8-82.2 months), respectively. Patients with associated seronegative hepatitis had an increased likelihood of PR and CR on multivariate analyses (PR: hazard ratio [HR] 3.15, 95% confidence interval [CI] 1.40, 7.11; CR: HR 2.99, 95% CI 1.35, 6.62), whereas older children were less likely to achieve IST response than children younger than 5 years at diagnosis. Five- and 10-year overall survival was 96% ± 4% and 90% ± 7%, respectively, and 5-year failure-free survival was 63% ± 8%. There was no infection-related mortality, although 16.4% of patients had at least 1 episode of documented bacteremia. The 5-year cumulative incidence of relapse was 12.9% and of clonal evolution was 3.2%. The authors conclude that children with AA who receive IST without hematopoietic growth factor support have excellent response and survival outcomes and a low incidence of clonal evolution.

Aminophylline in bradyasystolic cardiac arrest: a randomised placebo-controlled trial.

BACKGROUND: Endogenous adenosine might cause or perpetuate bradyasystole. Our aim was to determine whether aminophylline, an adenosine antagonist, increases the rate of return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest. METHODS: In a double-blind trial, we randomly assigned 971 patients older than 16 years with asystole or pulseless electrical activity at fewer than 60 beats per minute, and who were unresponsive to initial treatment with epinephrine and atropine, to receive intravenous aminophylline (250 mg, and an additional 250 mg if necessary) (n=486) or placebo (n=485). The patients were enrolled between January, 2001 and September, 2003, from 1886 people who had had cardiac arrests. Standard resuscitation measures were used for at least 10 mins after the study drug was administered. Analysis was by intention-to-treat. This trial is registered with the ClinicalTrials.gov registry with the number NCT00312273. FINDINGS: Baseline characteristics and survival predictors were similar in both groups. The median time from the arrival of the advanced life-support paramedic team to study drug administration was 13 min. The proportion of patients who had an ROSC was 24.5% in the aminophylline group and 23.7% in the placebo group (difference 0.8%; 95% CI -4.6% to 6.2%; p=0.778). The proportion of patients with non-sinus tachyarrhythmias after study drug administration was 34.6% in the aminophylline group and 26.2% in the placebo group (p=0.004). Survival to hospital admission and survival to hospital discharge were not significantly different between the groups. A multivariate logistic regression analysis showed no evidence of a significant subgroup or interactive effect from aminophylline. INTERPRETATION: Although aminophylline increases non-sinus tachyarrhythmias, we noted no evidence that it significantly increases the proportion of patients who achieve ROSC after bradyasystolic cardiac arrest.

Are components of a comprehensive medical assessment predictive of work disability after an episode of occupational low back trouble?

STUDY DESIGN: One hundred fifty-nine subacute low back work-injured patients completed a full medical assessment at baseline. A full repeat examination was performed 3 months later, when return-to-work status was determined. OBJECTIVE: To determine the prognostic value of a comprehensive medical assessment for the prediction of return-to-work status. SUMMARY OF BACKGROUND DATA: A systematic review of the work disability prediction literature of low back trouble prognosis revealed that no high-quality studies included a full medical history and physical examination in the design. The results of studies included in the systematic review were equivocal with respect to predictive usefulness of medical variables. METHODS: Participants completed medical history questionnaires and then were clinically examined by one of six experienced examiners (three physicians and three physiotherapists). Return-to-work status was measured 3 months later, and predictive validity was evaluated using logistic regression modeling. RESULTS: Medical variables (, medical history subscales, physical examination subscales, and lumbar range-of-motion tests) showed modest correct classification rates varying between 61.6% and 69.1% for participants. CONCLUSIONS: Comprehensive medical assessments play a crucial role in the early identification of serious pathology after low back trouble. We were unable to identify, however, any medical evaluation variables that would account for significant proportions of variance in return to work. The weight of evidence obtained in this study suggests that injured workers' subjective interpretations and appraisals may be more powerful predictors of the course of postinjury recovery than exclusively medical assessments.