Predictors of survival in sporadic Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies.

A collaborative study of human transmissible spongiform encephalopathies has been carried out from 1993 to 2000 and includes data from 10 national registries, the majority in Western Europe. In this study, we present analyses of predictors of survival in sporadic (n = 2304), iatrogenic (n = 106) and variant Creutzfeldt-Jakob disease (n = 86) and in cases associated with mutations of the prion protein gene (n = 278), including Gerstmann-Sträussler-Scheinker syndrome (n = 24) and fatal familial insomnia (n = 41). Overall survival for each disease type was assessed by the Kaplan-Meier method and the multivariate analyses by the Cox proportional hazards model. In sporadic disease, longer survival was correlated with younger age at onset of illness, female gender, codon 129 heterozygosity, presence of CSF 14-3-3 protein and type 2a prion protein type. The ability to predict survival based on patient covariates is important for diagnosis and counselling, and the characterization of the survival distributions, in the absence of therapy, will be an important starting point for the assessment of potential therapeutic agents in the future.

The efficacy of nebulized budesonide in dexamethasone-treated outpatients with croup.

OBJECTIVE: To determine the added clinical benefit of nebulized budesonide in children with mild to moderate croup treated with 0.6 mg/kg oral dexamethasone. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Emergency department of a tertiary-care pediatric hospital with 47,000 visits per year. PARTICIPANTS: Children 3 months to 5 years of age with a syndrome consisting of hoarseness, inspiratory stridor, and barking cough and a croup score of 3 or greater after at least 15 minutes of mist therapy. Patients were excluded from the study if they had diagnoses of epiglottitis, chronic upper or lower airway disease (not including asthma), or severe croup or had received corticosteroids within the preceding 2 weeks. INTERVENTION: All patients received 0.6 mg/kg oral dexamethasone and were randomly assigned to receive 4 mL (2 mg) of budesonide solution (n=25) or 4 mL of 0.9% saline solution (n=25) by updraft nebulizer with a continuous flow of oxygen at 5 to 6 L/min. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of patients in each group who had clinically important changes (two points) in the croup score during the 4 hours after treatment. RESULTS: Eighty-four percent (n=21) of the patients who received budesonide had clinically important responses, compared with 56% (n=14) in the placebo group. The number of patients who would need to be treated with nebulized budesonide for one patient to have a clinically important response is four patients. CONCLUSIONS: Despite receiving simultaneous oral dexamethasone, pediatric outpatients with mild to moderate croup have added, clinically important improvement in respiratory symptoms after treatment with budesonide.

Blepharophimosis, minor facial anomalies, genital anomalies, and mental retardation: report of two sibs with a unique syndrome.

We report on two sibs, a 2.5-year-old girl and a 10-month-old boy, with a hitherto unreported combination of congenital anomalies: blepharophimosis, ptosis, midface hypoplasia, abnormal palate, low anterior and posterior hairlines, displaced hair whorl, apparently low-set and abnormally shaped ears, trigonocephaly, dental anomalies, laryngomalacia, sensorineural hearing loss, genital anomalies, hypotonia, and mental retardation. The occurrence of a similar pattern of anomalies in two sibs of opposite sex suggests autosomal recessive inheritance. To our knowledge, this combination of anomalies has not been reported previously, and thus we propose it to be a formal genesis syndrome.

Levator injury during blepharoplasty.

Upper eyelid blepharoplasty has been increasing in popularity and complexity. New techniques involve deep dissection into the upper eyelid, with increased surgical risk to the levator complex. The resulting forms of trauma and subsequent ptosis commonly include direct injury, edema, hematoma, supratarsal fixation, and septal adhesion. Ptosis after blepharoplasty is common and, while spontaneous resolution occurs in some cases, other may require one of the suggested methods for treatment.

Agreement in the interpretation of extremity radiographs of injured children and adolescents.

OBJECTIVES: To measure agreement beyond chance (kappa) for comparison interpretations of extremity radiographs by pediatric radiologists and emergency physicians (EPs) and to identify factors associated with disagreement. METHODS: A random sample of 205 radiographs was selected from 1,016 patients having x-rays of their extremities in the emergency and radiology departments of a tertiary care pediatric hospital. Interpretations by the "official" reporting pediatric radiologist (ORPR), the treating EP, and a pediatric radiologist blinded to all clinical information (BPR) were compared for three categories: "abnormal" (one or more of fracture, dislocation, or effusion); "possibly abnormal"; and "normal." RESULTS: The overall weighted kappa (Kw) for the ORPRs and the EPs was 0.55. For fractures alone, the Kw for the ORPRs vs the EPs was 0.77; and for effusions alone, the value was 0.34. The Kw for the ORPRs vs the BPR was 0.63 (range 0.43-0.83 for individual ORPRs). The main areas of disagreement were in the identification of joint effusions and of nondisplaced fractures of the phalanges, elbow joint, tarsals, or metatarsals. CONCLUSIONS: There is good agreement between EPs and pediatric radiologists in interpreting extremity radiographs of injured children and adolescents. Disagreement occurs mainly for effusions or minor fractures and for the elbow region. Because of the importance of recognizing abnormalities in this region, an educational intervention to improve this area of deficiency is recommended.

A randomized, clinical trial comparing butylcyanoacrylate with octylcyanoacrylate in the management of selected pediatric facial lacerations.

OBJECTIVE: To compare two tissue adhesives, butylcyanoacrylate and octylcyanoacrylate, in the treatment of small (<4 cm) superficial linear traumatic facial lacerations in children. METHODS: This was a randomized, clinical trial with parallel design. 94 children <18 years of age seen in the ED of a tertiary care pediatric hospital with a facial laceration suitable for tissue adhesive closure underwent laceration closure using either butylcyanoacrylate or octylcyanoacrylate. The primary outcome was the cosmetic result at three months rated from photographs by a plastic surgeon on a visual analog scale (VAS). Secondary outcomes included the time to perform the procedure, the perceived difficulty of the procedure, the pain perceived by the patient, and a wound evaluation score at ten to 14 days and three months. RESULTS: Ninety-four patients were randomized with 47 in each group. The two groups were similar for baseline demographic and clinical characteristics. There was no difference in the three-month cosmesis VAS (median, 70.0 mm for n-butyl-2-cyanoacrylate vs 67.5 mm for octylcyanocrylate, p = 0.84). There was no difference between the groups for time to complete the procedure (p = 0.88), parent/patient-perceived pain of the procedure (p = 0.37), or physician-perceived difficulty of the procedure (p = 0.33). Similarly, there was no difference between the groups for the percentage of early (p = 0.58) or late (p = 0.71) optimal wound evaluation scores. CONCLUSIONS: In the closure of small linear pediatric facial lacerations, octylcyanoacrylate is similar to butylcyanoacrylate in ease of use and early and late cosmetic outcomes. The superior physical properties of octylcyanoacrylate appear to add little benefit to the management of these selected lacerations. Physician preference and differing costs may dictate use for these small selected lacerations.

Variation in utilization of computed tomography scanning for the investigation of minor head trauma in children: a Canadian experience.

OBJECTIVES: To compare the utilization rates of CT scans in investigating minor head trauma in children in Canada, to identify the injuries determined by these scans, and to identify clinical findings that are highly associated with its diagnosis and the injury itself. METHODS: A retrospective cohort study involving nine pediatric hospitals in Canada was conducted. A structured data collection method was used. Inclusion criteria included age 16 years or less, history of blunt head trauma, and a Glasgow Coma Scale score (GCS) greater than or equal to 13. Data collected included demographic information, type of injury, relevant clinical information, computed tomography (CT) scan data, and clinical outcome. Clinical findings associated with CT scan and positive CT scan were identified using logistic regression. RESULTS: One thousand one hundred sixty-four children were included in the study. One hundred seventy-one (15%) had a CT scan, of which 60 (35%) were abnormal. There was a significant difference in the rate of ordering of CT scans among the participating hospitals, but no significant difference in the rate of abnormal CT scans. Mechanism of injury, GCS, and loss of consciousness were significantly related to the presence of an abnormal CT scan. CONCLUSIONS: Although there is a significant difference in the utilization of CT scans to investigate minor head trauma in children across Canada, there is no significant difference in the frequency of head injuries in these patients. This suggests that it may be possible to determine clinical criteria that are predictive of a head injury in these patients.

Beyond terminology: the policy impact of a grassroots movement.

This article discusses the history of the grassroots movement led by self-advocates and their families to replace the stigmatizing term "mental retardation" with "intellectual disability" in federal statute. It also describes recent and pending changes in federal regulations and policy to adopt the new terminology for Social Security and Medicaid.

Can magnetic resonance spectroscopy predict neurodevelopmental outcome in very low birth weight preterm infants?

OBJECTIVE: To determine if metabolite ratios at near-term age predict outcome in very low birth weight preterm infants at 18 to 24 months adjusted age. STUDY DESIGN: Thirty-six infants (birth weight

Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada.

BACKGROUND: An international study of the epidemiologic characteristics of Creutzfeldt-Jakob disease (CJD) was established in 1993 and included national registries in France, Germany, Italy, the Netherlands, Slovakia, and the United Kingdom. In 1997, the study was extended to Australia, Austria, Canada, Spain, and Switzerland. METHODS: Data were pooled from all participating countries for the years 1993 to 2002 and included deaths from definite or probable CJD of all etiologic subtypes. RESULTS: Four thousand four hundred forty-one cases were available for analysis and included 3,720 cases of sporadic CJD, 455 genetic cases, 138 iatrogenic cases, and 128 variant cases. The overall annual mortality rate between 1999 and 2002 was 1.67 per million for all cases and 1.39 per million for sporadic CJD. Mortality rates were similar in all countries. There was heterogeneity in the distribution of cases by etiologic subtype with an excess of genetic cases in Italy and Slovakia, of iatrogenic cases in France and the UK, and of variant CJD in the UK. CONCLUSIONS: This study has established overall epidemiologic characteristics for Creutzfeldt-Jakob disease (CJD) of all types in a multinational population-based study. Intercountry comparisons did not suggest any relative change in the characteristics of sporadic CJD in the United Kingdom, and the evidence in this study does not suggest the occurrence of a novel form of human bovine spongiform encephalopathy infection other than variant CJD. However, this remains a possibility, and countries currently unaffected by variant CJD may yet have cases.

Twice-daily antibiotics in the treatment of acute otitis media: trimethoprim-sulfamethoxazole versus amoxicillin-clavulanate.

Twice-daily trimethoprim-sulfamethoxazole has been shown to be effective in the treatment of acute otitis media except that caused by group A beta-streptococci. Amoxicillin-clavulanate potassium is effective in vitro against all bacterial pathogens causing acute otitis media and has been reported to be effective when given twice daily for urinary tract infections, acute otitis media and respiratory tract infections. To determine whether the in-vitro efficacy of amoxicillin-clavulanate carries over clinically, we conducted a prospective randomized double-blind trial in 219 children presenting at a pediatric walk-in clinic. Diagnosis and follow-up assessments were made by means of examination of the tympanic membrane and acoustic otoscopy. Of the 219 children 202 (101 in either group) were assessed by a specially trained nurse at a follow-up visit 12 to 16 (mean 14) days after treatment was begun. Cure was defined as absence of symptoms and normal results of both visual inspection of the tympanic membrane and acoustic reflectometry; improvement was defined as absence of symptoms and either normal appearance of the tympanic membrane or normal results of acoustic reflectometry; treatment failure was defined as abnormal appearance of the tympanic membrane along with an acoustic reflectometry reading of 5 units or more. There were no differences in age (mean 60 months), sex or proportion of subjects with unilateral versus bilateral disease between the two groups. The combined rate of cure an improvement was significantly higher with trimethoprim-sulfamethoxazole (93%) than with amoxicillin-clavulanate (82%) (p = 0.03). The rate of compliance (more than 80% of the drug taken) did not differ significantly between the two groups. Gastrointestinal side effects were more common with amoxicillin-clavulanate (p less than 0.0001). Our results suggest that for acute otitis media twice-daily trimethoprim-sulfamethoxazole is more effective clinically and produces fewer side effects than twice-daily amoxicillin-clavulanate.

Bleeding in cosmetic blepharoplasty: an anatomical approach.

The complication of bleeding associated with cosmetic blepharoplasty was investigated by dissection of two fresh-frozen cadaver heads. The arteries were injected with Neoprene latex and dissection of the tissues encountered in blepharoplasty surgery was performed. From the study, three major components of the orbital and eyelid vascular system were felt to be important. These consisted of the individual tissue vascularity, the major arterial trunks in the region, and the connective tissue support of the arteries. Conclusions are reached regarding the prevention of bleeding associated with cosmetic blepharoplasty.

A randomized trial comparing the efficacy of epinephrine with salbutamol in the treatment of acute bronchiolitis.

This randomized, double-blind trial compared the efficacy of nebulized epinephrine with salbutamol in the treatment of infants with acute bronchiolitis. The mean percent oxygen saturation at 60 minutes was significantly higher in the epinephrine group. Thirty-three percent of the patients in epinephrine group were admitted to the hospital compared with 81% of the salbutamol group (p = 0.003). We conclude that nebulized epinephrine is more efficacious than salbutamol for infants with acute bronchiolitis seen in an emergency department.

A randomized trial comparing octylcyanoacrylate tissue adhesive and sutures in the management of lacerations.

OBJECTIVE: To assess the effectiveness of a new tissue adhesive for laceration closure. DESIGN: A prospective, randomized controlled trial. SETTING: An adult teaching hospital. PARTICIPANTS: One hundred thirty patients with 136 lacerations who consented to enrollment during a 5-month period. The lacerations included all eligible nonmucosal facial lacerations, as well as selected extremity and torso lacerations (not on hands, feet, or joints). One hundred six lacerations were available for early follow-up, and 98 were available for 3-month evaluation. INTERVENTIONS: Lacerations were randomly allocated to have skin closure with octylcyanoacrylate adhesive or monofilament suture. MAIN OUTCOME MEASURE: A 3-month photograph of the wound was assigned a cosmesis score on a previously validated 100-mm visual analog cosmesis scale by a plastic surgeon who was unaware of the method of wound closure. RESULTS: There were no differences in the mean visual analog cosmesis scores (67 mm for octylcyanoacrylate vs 68 mm for sutures; P=.65). Similarly, there was no difference in the percentage of early (80% vs 82%; P=.80) or late (72% vs 75%; P=.74) optimal wound evaluation scores. The tissue adhesive was a faster method of wound repair (3.6 vs 12.4 minutes; P<.001) as well as being less painful (visual analog pain scores, 7.2 vs 18.0 mm; P<.001). CONCLUSIONS: Octylcyanoacrylate tissue adhesive effectively closes selected lacerations. This relatively painless and fast method of wound repair can replace the need for suturing several million lacerations each year.

Computerisation of diabetic clinic records.

A simple system for putting diabetic records on a computer file is achieved by using stationery that combines the usual handwritten records (not computerised) with the minimum of essential data suitable for punching on to computer tape. The record may be brought up to date at a selected time time interval. This simple, cheap system has been in use in a busy clinic for six years. The information on about 8000 diabetics now held in the computer file is used chiefly to help research by creating registers of patients with specified characteristics, such as treatment, heredity complications, and pregnancy. A complete up-to-date index of the entire clinic population is always available, and routine clinic statistics are returned every six months.

Children Presenting to Emergency with Chest Pain: Long-term follow-up study.

This study examines the long-term outcome of a cohort of 317 pediatric patients who presented to an emergency department with chest pain. There were no deaths and few hospital stays. Patients were all perceived as "well" (self-assessment or parental assessment) at follow-up contact. This study supports the belief that chest pain in children is benign.

Tissue adhesive versus suture wound repair at 1 year: randomized clinical trial correlating early, 3-month, and 1-year cosmetic outcome.

STUDY OBJECTIVE: To compare the 1-year cosmetic outcome of wounds treated with octylcyanoacrylate tissue adhesive and monofilament sutures and to correlate the early, 3-month, and 1-year cosmetic outcomes. METHODS: We prospectively randomized 136 cases of traumatic laceration to repair with octylcyanoacrylate tissue adhesive or 5-0 or smaller monofilament suture. A wound score was assigned by a research nurse, and validated by a second nurse blinded to the treatment, at 5 to 10 days after injury (early), 3 months, and 1 year. Standardized photographs were taken at 3 months and 1 year and shown to a cosmetic surgeon blinded to the method of closure, who rated the wounds on a validated cosmesis scale. RESULTS: We were able to examine 77 lacerations at 1 year for follow-up. No differences were found in the demographic or clinical characteristics between groups. Likewise, at 1 year no difference was found in the optimal wound scores (73% versus 68%, P =.60) or in visual analog scale cosmesis scores (69 versus 69 mm, P =.95) for octylcyanoacrylate and sutures, respectively. Agreement was poor between early and 3-month wound scores (kappa=.34; 95% confidence interval [CI],.10 to.58) but a strong association existed between 3-month and 1-year wound scores (kappa=.71; 95% CI,.52 to.90). We noted a moderate correlation between 3-month and 1-year results on the visual analog cosmesis scale (intraclass correlation,.48; 95% CI, .30 to.63). CONCLUSION: One year after wound repair, no difference is noted in the cosmetic outcomes of traumatic lacerations treated with octylcyanoacrylate tissue adhesive and sutures. The assessment of wounds 3 months after injury and wound repair provides a good measure of long-term cosmetic outcome.

Nebulized budesonide for children with mild-to-moderate croup.

BACKGROUND: Although recent evidence has strongly supported the use of glucocorticoid therapy in children hospitalized with croup, the benefit of this therapy in children with less severe croup has not been documented. This randomized, double-blind trial compared a nebulized glucocorticoid, budesonide, with placebo in outpatients with mild-to-moderate croup. METHODS: Children three months to five years of age were eligible for the study if their croup scores fell in the mild-to-moderate range (scores of 2 to 7 out of a possible 17). The patients were randomly assigned to receive either 2 mg (4 ml) of nebulized budesonide (27 children) or 4 ml of nebulized normal saline (27 children); they were then assessed hourly for up to four hours by investigators who were unaware of the assigned treatments. RESULTS: The median croup score at entry into the study was 4 in both groups. At the final study assessment, the median score was significantly lower in the budesonide group than in the placebo group (1 vs. 3, P = 0.005). The patients in the budesonide group were discharged from the emergency department significantly earlier than those in the placebo group (P = 0.002). One week after enrollment, 21 patients assigned to placebo had received dexamethasone, as compared with 15 patients assigned to budesonide (P = 0.10), and 7 patients assigned to placebo had been admitted to the hospital, as compared with 1 patient assigned to budesonide (P = 0.05). CONCLUSIONS: We conclude that nebulized budesonide leads to a prompt and important clinical improvement in children with mild-to-moderate croup who come to the emergency department.