Search

Context: Relapses of acute asthma following emergency department (ED) discharge can be reduced with systemic corticosteroid treatment. However, whether inhaled corticosteroids (ICSs) provide additional benefit is not known. Objective To determine whether the addition of ICSs to oral corticosteroid treatment would reduce relapses in patients with acute asthma discharged from the ED.Design and Setting: Placebo-controlled, double-blind, randomized clinical trial conducted in a community teaching hospital ED in Canada between November 1995 and September 1997, with a 21-day follow-up.Participants: A total of 1006 consecutive patients aged 16 to 60 years presented to the ED with acute asthma; after excluding those using oral and/or inhaled corticosteroids as well as those meeting other exclusion criteria, 188 were included in the study.Interventions: Patients were discharged with a nontapering course of oral prednisone (50 mg/d) for 7 days. In a double-blind fashion, patients were randomly assigned to 1600 microg/d of inhaled budesonide (n = 94) or identical placebo (n = 94) for 21 days.Main Outcome Measures: Incidence of relapse, defined as an unscheduled visit for worsening asthma symptoms, in budesonide vs placebo groups. Secondary outcomes included response to the Asthma Quality of Life Questionnaire, beta2-agonist use, symptom score, global asthma improvement assessment, and pulmonary function.Results: Five patients in the budesonide group and 3 in the placebo group either dropped out or were lost to follow-up but were included in primary analyses. After 21 days, 12 (12.8%) of 94 patients in the budesonide group experienced a relapse compared with 23 (24.5%) of 94 in the placebo group, a 48% relapse reduction (P=.049). Asthma Quality of Life Questionnaire scores were higher (better quality) in the budesonide group (P=.001), as well as for all domain scores (P=.001 to .01). Fewer beta2-agonist activations were used at the end of the trial by patients receiving budesonide (2.4/d vs 4.2/d; P=.01). Symptom scores (P=.001 to .004) and self-assessed asthma improvement scores (based on a 7-point Likert scale) (6.2 vs 5.2; P<.001) were higher (indicating fewer symptoms) for budesonide vs placebo. There were no differences in pulmonary function between the groups (peak expiratory flow rate: budesonide, 437 vs placebo, 453 L/min; P= .39) at 21 days. Using this approach, as few as 9 patients would require budesonide to prevent 1 relapse.Conclusions: Patients discharged from the ED following treatment for acute asthma benefit from added treatment with high-dose inhaled budesonide for 21 days compared with oral corticosteroids alone. [ABSTRACT FROM AUTHOR]

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., (© 2015 International Parkinson and Movement Disorder Society.)

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., (© 2013 John Wiley & Sons Ltd.)

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.

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.

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.

Study Design: Articles reflecting the convergent or discriminant validity of the lumbar range of motion tests were reviewed and compared. Mean scores and standard deviations for lumber range of motion from healthy control subjects were plotted against those from patients with low back injuries., Objective: To use published research to analyze the convergent and discriminant validity of lumbar range of motion tests for the characterization of low back pain and injury., Summary of Background Data: Several publications have addressed lumbar range of motion validity. Individual studies suggest that the tests possess convergent validity, but that their discriminant validity is indeterminate., Methods: English-language journals were searched on Medline using "region," "lumbar," "range of motion," "validity of results," "observer variation," and "low back pain" as title and subject search terms. The study methods approximating the specifications of the American Medical Association Guides to the Evaluation of Permanent Impairment were included in the analysis., Results: Convergent validity research showed inconsistent relations between inclinometric and radiographic lumbar range of motion measurements. Some studies showed strong relation, whereas others showed essentially no relation between the two techniques. Correlations between lumbar range of motion scores and spinal disability and function were similarly inconclusive. Studies reporting mean scores and standard deviations for lumbar range of motion measurements showed a high degree of overlap between the scores of participants with low back injuries and those without such injuries., Conclusions: Convergent and discriminant validities of the lumbar range of motion tests currently require further substantiation. Absolute lumbar range of motion scores may not be suitable as the sole determinants of low back pathology diagnosis. Implications for using the lumbar range of motion tests to characterize low back injuries in medicolegal situations are discussed.

Previous studies have found that questions are considerably less sensitive for predicting sensitization to dust mites than to pollens or to household pets. We studied 1160 children with respiratory symptoms to find whether the sensitivity for predicting mite allergy could be increased by asking several rather than single questions. Parents accompanying the children were asked standardized validated questions. Of the four individual questions relevant to mites, the one with the highest sensitivity for predicting a positive skin prick test to this allergen was whether the symptoms were worse when the house was being swept, vacuumed or dusted (29.8%). If an affirmative answer to that question, or to any of the other three questions, was taken as predictive of sensitization, the sensitivity increased to 54.2%. However, requiring only a single affirmative answer to this combination of questions decreased the specificity. The sensitivity of the combination of questions was comparable to that of questions for predicting positive tests to tree pollens (56.4%), cats (56.4%), grass pollens (52.5%) and dogs (51.4%). We conclude that asking a combination of questions is an useful for indicating possible sensitization to dust mite as are questions for detecting sensitization to other common inhalant allergens.

Background: The clinical history is given considerable weight when one decides which allergens are responsible for a patient's symptoms, and in research studies the clinical history has been used as the "gold standard" with which different tests for allergy are compared., Objectives: To determine whether standardized questions accurately predict replies to detailed questions asked by an experienced allergist, and to assess the utility of certain standardized questions for predicting sensitization to individual allergen groups., Methods: Trained interviewers put standardized questions to parents of 1160 children, aged 1 to 17 years, who had respiratory symptoms and had been newly referred to the allergy clinic of a children's hospital. For the first 151 of the subjects the answers were compared with those elicited by questions asked by a pediatric allergist. Skin prick tests and pollen counts were performed by a technologist., Results: The standardized questions had an accuracy for predicting the allergist's history of 93% to 97% for all questions except one. The standardized questions with the highest accuracy for predicting the skin test results to the appropriate allergens were the following: for mite, improvement in symptoms when outdoors (66.8%) and when in dry areas 69.4%), and aggravation during house cleaning (65.9%) and when bed making (70.6%); for dog, symptoms when with dogs (80.6%); for cat, symptoms when with cats (77.3%); for tree pollen, symptoms worse in April (70.8%) and when among trees in March and April (80.8%); and for grass pollen, exacerbation in June (69.2l%) and during lawn mowing (71.2%). Although specificity was generally above 80%, sensitivity was variable, ranging from 11% to 56%., Conclusions: The standardized questions accurately predicted a detailed history obtained by an experienced allergist. Because standardized questions are reproducible they are the preferred method of history taking for research projects. Because several of the standardized questions have a high specificity they are useful for excluding sensitization to individual allergen groups, but because they have only a modest sensitivity, they are less helpful for detecting those who are sensitized to individual allergen groups.

Background: Many allergists, but few otolaryngologists, consider allergic rhinitis to be a common cause of nosebleeds in childhood., Objective: To determine whether the two conditions are related, and whether epistaxis could be due solely to the local effects of nasal symptoms., Methods: We studied 557 children who were referred consecutively to an allergy clinic of a children's hospital. Standardized questions were put to their accompanying parents, and skin prick tests were performed on the children, using common local inhalant allergens., Results: On univariate analysis children who had both nasal symptoms and a positive skin test were found to have recurrent nosebleeds more frequently (20.2%) than had those with nasal symptoms on their own (9.9%), a positive skin test alone (3.4%), or neither (2.1%). Similarly, on logistic regression the odds ratio (OR) of nosebleeds was 3.3, 1.3, 1.65, and 1, respectively. Nosebleeds were more common in those who owned a dog or a cat and had a positive skin test to that species than in the remainder of the children (27.8% vs 10.8%)., Conclusions: Allergic rhinitis is commonly associated with recurrent epistaxis. In many children it appears that nosebleeds are due to nasal symptoms plus some abnormality that is found in the atopic state: a disorder of hemostasis is suspected as the contributing factor.

To determine observer agreement for a clinical score and oximetry in lower respiratory infection in children less than 2 yr of age, a convenience sample of 56 infants hospitalized with bronchiolitis or pneumonia was assessed independently by two observers. A total of 12 infants had chronic lung disease of prematurity or congenital heart disease. Infants in whom oxygen supplementation could not be discontinued for at least 5 min were excluded. A severity score was assigned for each of four categories (respiratory rate, retractions, wheeze, and general appearance). A total for each patient was obtained by summing the score for each category. Oxygen saturation was measured using a Nellcor oximeter. Agreement beyond chance was measured using the kappa statistic. The relationship between observers for total score and oximetry and the mean total score and mean oximetry value for each patient was expressed as a Pearson correlation coefficient. A total of 56 infants and children were studied: 2 had pneumonia, 11 had an exacerbation of pulmonary signs and symptoms with their underlying cardiac or pulmonary disease, and 43 had bronchiolitis. Kappa was 0.48 for general assessment, 0.38 for respiratory rate, 0.31 for wheeze, and 0.25 for retractions. All values were statistically significantly greater than 0 at p less than 0.01. Correlations for total score and for oximetry were 0.68 and 0.88, respectively. The median difference between oximetry readings was 1. The correlation coefficient between total score and oximetry was -0.04. The limited agreement for clinical signs makes comparison of patient illness severity between studies difficult.(ABSTRACT TRUNCATED AT 250 WORDS)

Our objective was to determine the effect of treatment on the likelihood of pregnancy among couples with unexplained infertility. We used a nonrandomized, prospective, multicentered cohort analytic study, with mean follow-up time of 14.5 months (range, 0.5-46 months). The subjects were 470 couples who attended infertility clinics affiliated with medical schools in Canada, in whom no abnormality was found after investigation. They were drawn from a total of 2,106 couples registered from April 1, 1984 to March 31, 1987. Of these, 130 couples were selected for treatment at the discretion of the care givers; 340 couples were not treated. Selection for treatment resulted in imbalance between the groups: the treated couples had a longer mean duration of infertility (48 vs. 36 months), and were more likely to have had a laparoscopy as part of the investigation (72% vs. 48%). No specific protocol of treatment was used. Treatments most commonly used were clomiphene (87); gonadotropins (31); intrauterine insemination (20); IVF or GIFT (16); bromocriptine (12); 43 couples had two treatments, and 11 had three treatments. The only important determinants of treatment (logistic regression) were time under observation and laparoscopy status. Duration of infertility was only a minor determinant of treatment. Crude, unadjusted pregnancy rates were 25% for the treated group and 34% for the untreated group. The early occurrence of pregnancy in the untreated couples accounted for much of this difference. After adjustment for baseline differences between the groups and times to and under treatment with proportional hazards analysis, the cumulative probability of pregnancy is 2.0 (95% CI 1.3 to 3.1) times as high with treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To assess the consistency of an index of the scientific quality of research overviews., Design: Agreement was measured among nine judges, each of whom assessed the scientific quality of 36 published review articles. ITEM SELECTION: An iterative process was used to select ten criteria relative to five key tasks entailed in conducting a research overview., Sample: The review articles were drawn from three sampling frames: articles highly rated by criteria external to the study; meta-analyses; and a broad spectrum of medical journals. JUDGES: Three categories of judges were used: research assistants; clinicians with research training; and experts in research methodology; with three judges in each category., Results: The level of agreement within the three groups of judges was similar for their overall assessment of scientific quality and for six of the nine other items. With four exceptions, agreement among judges within each group and across groups, as measured by the intraclass correlation coefficient (ICC), was greater than 0.5, and 60% (24/40) of the ICCs were greater than 0.7., Conclusions: It was possible to achieve reasonable to excellent agreement for all of the items in the index, including the overall assessment of scientific quality. The implications of these results for practising clinicians and the peer review system are discussed.

Over a 2-year period, 227 couples were evaluated by an extended assessment of the male partner's ejaculate. This extended assessment comprised sperm penetration of denuded hamster oocytes, ability of sperm to penetrate synthetic mucus, and the adenosine triphosphate (ATP) content of whole semen. In proportional hazards analysis adjusting for the contribution of clinical and other seminal variables, the sperm penetration assay (SPA) test was a predictor of pregnancy in the subgroup with normal conventional seminal variables (greater than 40 million motile sperm per ejaculate). When the SPA result was 20% or more the probability of pregnancy was 3.7 times higher; the performance of the SPA as a diagnostic test was better in the couples with treated tubal disease than in other diagnostic categories.

We prospectively measured levels of factors XI and XII in parallel with other coagulation factors in 39 unselected patients with liver disease and in 20 control subjects. Mean levels of factors XI and XII in subjects with liver disease were significantly reduced, being 58% and 61%, respectively, compared with 100% and 94% in controls. Reductions in levels of factors XI and XII were most pronounced in those subjects with low serum albumin. The partial thromboplastin time (APTT) reflected low levels of either factor XI or XII and was most prolonged when both were low, but cause and effect was not demonstrated. Low levels of these factors may explain previous reports of poor response of APTT to infusions of prothrombin complex concentrates. Finally, these low levels strongly suggest that factors XI and XII are produced in the liver.

In order to determine whether children screened 6-12 months previously for vision and hearing had fewer vision and hearing problems than a non-screened cohort, a trained nurse-tester examined 763 screened and 743 non-screened kindergarten children matched for age, sex, and socioeconomic status. The screened cohort had significantly fewer vision problems (10%) than the unscreened (15%). The difference for moderately severe problems (visual activity 20/50 or worse) was also significant. 58% more screened than unscreened children were wearing glasses. The screened cohort had more hearing problems (16.8%) than the non-screened group (14%), but the difference was not statistically significant. There was a marked seasonal variation in prevalence of hearing problems, the frequency in November and December being twice that in April, presumably a result of increased frequency of upper respiratory problems in those months. Preschool hearing screening, unlike vision screening, is not associated with improved end results.

A double-blind randomized trial of vitamin E therapy was conducted in premature infants whose birth weight was less than 1,500 gm. Treated infants received 25 mg of vitamin E daily by mouth for the first six weeks of life. Detailed studies of plasma coagulation factors were performed prior to therapy and at days 7 and 42. None of the factors differed significantly between the treated and control groups. Although vitamin E therapy has been reported to affect the blood levels of vitamin K dependent coagulation factors, no such effect was noted in this group of premature infants.

The effect of hydrocortisone (HC) on the formation of granulocyte-macrophage (GM) colonies was assessed in vitro in cultures of normal human bone marrow. Subphysiological concentrations (less than or equal to 10(-8) mol/l) of HC had no impact on GM colony formation, but at physiological and therapeutic levels (10(-7) mol/l-10(-5) mol/l) the hormone stimulated the production of an increased number of colonies. By contrast, physiological concentrations of progesterone (10(-9) mol/l-10(-7) mol/l) were without effect and even at 10(-6) mol/l there was no influence of progesterone alone on GM colony formation. However, progesterone at 10(-6) mol/l inhibited the stimulant effect of HC to a degree which was related inversely to the concentration of HC and the duration of the culture interval. The data from this study suggest that the neutrophilia which accompanies glucocorticosteroid therapy is matched by an increase in the production of granulocytes and that HC may play a rôle, which is mediated by steroid receptors, in the physiological regulation of human granulopoiesis.