An unusual case of alpha-1-antitrypsin deficiency: SZ/Z.

A female patient was first seen at age 65 due to a diagnosis of alpha-1-antitrypsin deficiency (AATD). She was a lifelong non-smoker, with no significant history of second hand smoke exposure. There was no prior family history of AATD or liver disease. Her serum AAT concentration was measured on two occasions and in both cases, concentration was <0.21 g/L. The patient was referred for genetic testing to determine her SERPINA1 (the gene responsible for AATD) genotype. Three deficiency alleles were identified: she was heterozygous for S, a mild deficiency allele, and homozygous for Z, a severe deficiency allele. This case represents unusual convergence of three pathogenic SERPINA1 variants in a single individual. We report the investigations used to clarify her unusual genotype and propose non-crossover gene conversion as the likely mechanism.

A systematic review of the vitamin B12, folate and homocysteine triad across body mass index.

OBJECTIVE: Multiple studies have explored the association between serum or plasma vitamin B12 status and obesity, in part because of the relationship between elevated homocysteine concentrations and atherosclerosis. This review will address the inconsistent finding of these studies with the objective of determining whether vitamin B12 concentrations are lower in people with higher body mass indices. DESIGN: MEDLINE and EMBASE were searched to February 2017. Observational studies in general and clinical populations comparing serum/plasma B12 concentrations across groups of different body mass indices were selected. We did network and pairwise meta-analyses of serum/plasma B12, folate and homocysteine using frequentist techniques. Evidence-based items potentially indicating risk of bias were assessed. RESULTS: Of 844 citations, we identified 19 eligible observational studies with 7,055 participants. The overall network, while showing no significant inconsistency between indirect and direct comparisons (P = 0.34), was qualitatively inconsistent. Based on the results of the meta-regression, in an exploratory sub-network meta-analysis where obesity groups were combined, we excluded disease-specific populations and studies with inadequate description of populations. The direction of the indirect and direct evidence was consistent. The pairwise results from this sub-network showed lower levels of B12 in people with higher body mass indices: obesity versus control difference in means (MD) -56 pmol L-1 (95% CI -90, -23), obesity versus overweight MD -21 pmol L-1 (95% CI -37, -5) and overweight versus control MD -51 pmol L-1 (95% CI -51, -24). Heterogeneity remained very large for most comparisons, and all the studies carried a high risk for bias. CONCLUSIONS: This review did not establish an inverse association (or J-curve) between serum or plasma B12 concentrations and body mass index, but the direct pairwise evidence is consistent with an inverse association and supports further investigation.

Experimental Bayesian Quantum Phase Estimation on a Silicon Photonic Chip.

Quantum phase estimation is a fundamental subroutine in many quantum algorithms, including Shor's factorization algorithm and quantum simulation. However, so far results have cast doubt on its practicability for near-term, nonfault tolerant, quantum devices. Here we report experimental results demonstrating that this intuition need not be true. We implement a recently proposed adaptive Bayesian approach to quantum phase estimation and use it to simulate molecular energies on a silicon quantum photonic device. The approach is verified to be well suited for prethreshold quantum processors by investigating its superior robustness to noise and decoherence compared to the iterative phase estimation algorithm. This shows a promising route to unlock the power of quantum phase estimation much sooner than previously believed.

Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes.

Individual studies indicate that kidney transplantation is associated with lower mortality and improved quality of life compared with chronic dialysis treatment. We did a systematic review to summarize the benefits of transplantation, aiming to identify characteristics associated with especially large or small relative benefit. Results were not pooled because of expected diversity inherent to observational studies. Risk of bias was assessed using the Downs and Black checklist and items related to time-to-event analysis techniques. MEDLINE and EMBASE were searched up to February 2010. Cohort studies comparing adult chronic dialysis patients with kidney transplantation recipients for clinical outcomes were selected. We identified 110 eligible studies with a total of 1 922 300 participants. Most studies found significantly lower mortality associated with transplantation, and the relative magnitude of the benefit seemed to increase over time (p < 0.001). Most studies also found that the risk of cardiovascular events was significantly reduced among transplant recipients. Quality of life was significantly and substantially better among transplant recipients. Despite increases in the age and comorbidity of contemporary transplant recipients, the relative benefits of transplantation seem to be increasing over time. These findings validate current attempts to increase the number of people worldwide that benefit from kidney transplantation.

Bariatric surgery: a systematic review and network meta-analysis of randomized trials.

The clinical efficacy and safety of bariatric surgery trials were systematically reviewed. MEDLINE, EMBASE, CENTRAL were searched to February 2009. A basic PubCrawler alert was run until March 2010. Trial registries, HTA websites and systematic reviews were searched. Manufacturers were contacted. Randomized trials comparing bariatric surgeries and/or standard care were selected. Evidence-based items potentially indicating risk of bias were assessed. Network meta-analysis was performed using Bayesian techniques. Of 1838 citations, 31 RCTs involving 2619 patients (mean age 30-48 y; mean BMI levels 42-58 kg/m(2) ) met eligibility criteria. As compared with standard care, differences in BMI levels from baseline at year 1 (15 trials; 1103 participants) were as follows: jejunoileal bypass [MD: -11.4 kg/m(2) ], mini-gastric bypass [-11.3 kg/m(2) ], biliopancreatic diversion [-11.2 kg/m(2) ], sleeve gastrectomy [-10.1 kg/m(2) ], Roux-en-Y gastric bypass [-9.0 kg/m(2) ], horizontal gastroplasty [-5.0 kg/m(2) ], vertical banded gastroplasty [-6.4 kg/m(2) ], and adjustable gastric banding [-2.4 kg/m(2) ]. Bariatric surgery appears efficacious compared to standard care in reducing BMI. Weight losses are greatest with diversionary procedures, intermediate with diversionary/restrictive procedures, and lowest with those that are purely restrictive. Compared with Roux-en-Y gastric bypass, adjustable gastric banding has lower weight loss efficacy, but also leads to fewer serious adverse effects.

The effects of angiotensin-receptor blockers on mortality and morbidity in heart failure: a systematic review.

BACKGROUND: Trials evaluating angiotensin-receptor blockers in heart failure (HF) have shown inconsistent results. OBJECTIVE: To evaluate the effect of angiotensin II (AII) receptor blockers in HF patients on total mortality and HF hospitalisations. METHODS: Systematic search of the literature through MEDLINE (1980-2007) and abstracts of major cardiovascular congresses from 2002 to 2007. ELIGIBILITY CRITERIA: (i) randomised controlled trials with more than 500 patients and follow up > 6 months, (ii) availability of total mortality and/or (iii) availability of hospital admission because of worsening HF. Data retrieved by two independent reviewers. DerSimonian random effects model was used. RESULTS: Mortality data were available from 27,495 patients. When AII receptor blockers plus angiotensin-converting enzyme inhibitors (ACE-I) were compared with ACE-I in chronic HF trials, the relative risk (RR) for death was 0.98 (95% CI: 0.84-1.15). When AII receptor blockers were compared with ACE-I the RR for death was 1.06 (95% CI: 0.56-1.62). Similar results were found for postmyocardial infarction trials. The effects on hospital admission revealed a RR of 0.83 (95% CI: 0.71-0.97) and 1.09 (95% CI: 0.74-1.60) respectively. CONCLUSION: Angiotensin II receptor blockers did not show any beneficial effect on mortality when used in combination with ACE-I or when compared with ACE-I alone. A 17% reduction in hospital admissions was observed.

Mortality of Canadians treated by peritoneal dialysis in remote locations.

Patients residing in remote locations may be more likely to initiate peritoneal dialysis when starting renal replacement therapy to avoid relocation. These patients may have reduced access to medical care, however. To examine the hypothesis that patients residing some distance from their nephrologists would be more likely to select peritoneal dialysis but have an increased risk of mortality, we used prospectively collected data in a random sample of 26,775 patients initiating dialysis in Canada between 1990 and 2000. The distance between the patient's residence at dialysis inception and the practice location of their nephrologists was calculated. We used Cox proportional hazard models to determine the adjusted relation between this distance and clinical outcomes over a mean follow-up period of 2.5 years up to 14 years. Remote-dwelling patients were more likely than urban dwellers to commence peritoneal dialysis in distances ranging from 50 to greater than 300 km than those residing within 50 km. The adjusted rates of death and the adjusted hazard ratio among patients initiating peritoneal dialysis was significantly higher in those living further from the nephrologists than those living within 50 km. Further study into the quality of care delivered to remote-dwelling patients on peritoneal dialysis is needed.

Patient and allograft survival of Indo Asian and East Asian dialysis patients treated in Canada.

Kidney failure is relatively common among Canadians of Asian origin. However, little is known about the health outcomes after initiation of renal replacement therapy in this population. Our study evaluates differences in the likelihood of renal transplantation and graft loss among Asian and white patients. We studied 21 523 adults of East Asian, Indo Asian or white ethnicity who had initiated dialysis in Canada from 1990-2000. Subjects were followed until death, loss to follow-up or end of study (2004). The proportion of the eligible subjects who were East Asian, Indo Asian, or white was 6, 3, and 91%, respectively. Compared to white patients, East Asian and Indo Asian patients were significantly less likely to receive a renal transplant after adjusting for potential confounding factors. This disparity is greater for transplants from living donors as compared to those from deceased donors. The adjusted death censored graft loss in transplant recipients was not significantly different between ethnic groups. The adjusted risk of death following transplantation, however, was significantly lower in Indo Asian than in white patients. Our findings show that in a Canadian population, patients of East Asian or Indo Asian origin had lower rates of renal transplantation than white patients, especially for living donor transplantation. These findings warrant further study, especially given the good graft outcomes in these individuals.

Oral versus intravenous rehydration for treating dehydration due to gastroenteritis in children.

BACKGROUND: Dehydration associated with gastroenteritis is a serious complication. Oral rehydration is an effective and inexpensive treatment, but some physicians prefer intravenous methods. OBJECTIVES: To compare oral with intravenous therapy for treating dehydration due to acute gastroenteritis in children. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (March 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to March 2006), EMBASE (1974 to March 2006), LILACS (1982 to March 2006), and reference lists. We also contacted researchers, pharmaceutical companies, and relevant organizations. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing intravenous rehydration therapy (IVT) with oral rehydration therapy (ORT) in children up to 18 years of age with acute gastroenteritis. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed quality using the Jadad score. We expressed dichotomous data as a risk difference (RD) and number needed to treat (NNT), and continuous data as a weighted mean difference (WMD). We used meta-regression for subgroup analyses. MAIN RESULTS: Seventeen trials (1811 participants), of poor to moderate quality, were included. There were more treatment failures with ORT (RD 4%, 95% confidence interval (CI) 1 to 7, random-effects model; 1811 participants, 18 trials; NNT = 25). Six deaths occurred in the IVT group and two in the ORT groups (4 trials). There were no significant differences in weight gain (369 participants, 6 trials), hyponatremia (248 participants, 2 trials) or hypernatremia (1062 participants, 10 trials), duration of diarrhea (960 participants, 8 trials), or total fluid intake at six hours (985 participants, 8 trials) and 24 hours (835 participants, 7 trials). Shorter hospital stays were reported for the ORT group (WMD -1.20 days, 95% CI -2.38 to -0.02 days; 526 participants, 6 trials). Phlebitis occurred more often in the IVT group (NNT 50, 95% CI 25 to 100) and paralytic ileus more often in the ORT group (NNT 33, 95% CI 20 to 100, fixed-effect model), but there was no significant difference between ORT using the low osmolarity solutions recommended by the World Health Organization and IVT (729 participants, 6 trials). AUTHORS' CONCLUSIONS: Although no clinically important differences between ORT and IVT, the ORT group did have a higher risk of paralytic ileus, and the IVT group was exposed to risks of intravenous therapy. For every 25 children (95% CI 14 to 100) treated with ORT one would fail and require IVT.

Association between residence location and likelihood of kidney transplantation in Aboriginal patients treated with dialysis in Canada.

For reasons that are not well understood, Aboriginal people with end-stage renal disease (ESRD) have lower rates of kidney transplantation. We hypothesized that distance between residence location and the closest transplant center was greater in Aboriginal dialysis patients and would partially explain the lower rate of transplantation in this population. We studied a random sample of 9905 patients initiating dialysis in Canada between 1990 and 2000. We calculated the distance between residence location at dialysis inception and the closest transplant center. Cox proportional hazards models were used to examine the relation between residence location and the likelihood of transplantation over a median period of 2.3 years. The proportion of Aboriginal participants living 300 km from the closest transplant center was 25, 18, 18, and 39% respectively, compared with 55, 19, 11, and 15% among white subjects. The relative likelihood of transplantation was significantly lower for Aboriginal compared to white participants across all four distance strata, with no apparent effect of residence location. For example, the relative likelihood of transplantation was hazard ratio (HR) 0.47, 95% confidence interval (CI) (0.31-0.72) in Aboriginal participants residing 300 km from the closest transplant center. Results were similar for transplants from deceased donors and living donors, and in all seven regions studied. In conclusion, remote location of residence does not explain the lower rate of kidney transplantation among Aboriginal people treated for ESRD in Canada.

Acyclovir for treating varicella in otherwise healthy children and adolescents.

BACKGROUND: Acyclovir has the potential to shorten the course of illness which may result in reduced costs and morbidity associated with chickenpox. OBJECTIVES: 1) To examine the evidence evaluating the efficacy of acyclovir in alleviating symptoms of chickenpox and shortening the duration of illness. 2) To examine complications of chickenpox and adverse effects associated with acyclovir as reported in the relevant trials. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2005), MEDLINE (January 1966 to June 2005), and EMBASE (1988 to June 2005). The reference lists of all relevant articles were reviewed. The primary author of relevant studies and the pharmaceutical company that manufactures acyclovir were contacted. SELECTION CRITERIA: Randomized controlled trials that evaluated otherwise healthy children zero to 18 years of age, with chickenpox. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the studies for eligibility. Two authors independently assessed methodological quality of the relevant studies using the Jadad scale and allocation concealment. Differences were resolved by consensus. Data were extracted by one author using a structured form and checked by a second. Continuous data were converted to the weighted mean difference (WMD). Weighted mean differences were combined into an overall estimate using random effects. There were too few studies to consider exploring statistical heterogeneity between studies (i.e., differences in reported effects), formally, or to assess for publication bias. MAIN RESULTS: Three studies were included. Study quality was three (n = 2) and four (n = 1) on the Jadad scale. Acyclovir was associated with a reduction in the number of days with fever (-1.1 days, 95% CI -1.3 to -0.9) and in reducing the maximum number of lesions (-76 lesions, -145 to -8). Results were less supportive with respect to the number of days to no new lesions and the number of days to the relief of itching. There were no clinically important differences between acyclovir and placebo with respect to complications associated with chickenpox or adverse effects associated with the treatment. AUTHORS' CONCLUSIONS: Acyclovir appears to be effective in reducing the number of days with fever and the maximum number of lesions among otherwise healthy children with chickenpox. The results were less convincing with respect to the number of days to no new lesions and relief of itchiness. The clinical importance of acyclovir treatment in otherwise healthy children remains uncertain.

Pain relief for neonatal circumcision.

BACKGROUND: Circumcision is a painful procedure that many newborn males undergo in the first few days after birth. Interventions are available to reduce pain at circumcision; however, many newborns are circumcised without pain management. OBJECTIVES: The objective of this review was to assess the effectiveness and safety of interventions for reducing pain at neonatal circumcision. SEARCH STRATEGY: We searched Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), MEDLINE (1966 - April 2004), EMBASE (1988 - 2004 week 19), CINAHL (1982 - May week 1 2004), Dissertation Abstracts (1986 - May 2004), Proceedings of the World Congress on Pain (1993 - 1999), and reference lists of articles. Language restrictions were not imposed. SELECTION CRITERIA: Randomised controlled trials comparing pain interventions with placebo or no treatment or comparing two active pain interventions in male term or preterm infants undergoing circumcision. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed trial quality and extracted data. Ten authors were contacted for additional information. Adverse effects information was obtained from the trial reports. For meta-analysis, data on a continuous scale were reported as weighted mean difference (WMD) or, when the units were not compatible, as standardized mean difference. MAIN RESULTS: Thirty-five trials involving 1,984 newborns were included. Thirty-three trials enrolled healthy, full term neonates, and two enrolled infants born preterm. Fourteen trials involving 592 newborns compared dorsal penile nerve block (DPNB) with placebo or no treatment. Compared to placebo/no treatment, DPNB demonstrated significantly lower heart rate [WMD -35 bpm, 95% CI -41 to -30], decreased time crying [WMD -54 %, 95% CI -64 to -44], and increased oxygen saturation [WMD 3.2 %, 95% CI 2.7 to 3.7]. Six trials involving 190 newborns compared eutectic mixture of analgesics (EMLA) with placebo. EMLA demonstrated significantly lower facial action scores [WMD -46.5, 95% CI -80.4 to -12.6], decreased time crying [WMD - 15.8 %, 95% CI -20.8 to -6.8] and lower heart rate [WMD -15 bpm, 95% CI -19 to -10]. DPNB, compared with EMLA in four trials involving 164 newborns, demonstrated significantly lower heart rate [WMD -17 bpm, 95% CI -23 to -11] and pain scores. When compared with sucrose in two trials involving 126 newborns, DPNB demonstrated less time crying [MD -166 s, 95% CI -211 to -121], and lower heart rate [WMD -27 bpm, 95% CI -33 to -20]. Results obtained for trials comparing oral sucrose and oral analgesics to placebo, and trials of environmental modification were either inconsistent or were not significantly different. Adverse effects included gagging, choking, and emesis in placebo/untreated groups. Minor bleeding, swelling and hematoma were reported with DPNB. Erythema and mild skin pallor were observed with the use of EMLA. Methaemoglobin levels were evaluated in two trials of EMLA, and results were within normal limits. REVIEWERS' CONCLUSIONS: DPNB was the most frequently studied intervention and was the most effective for circumcision pain. Compared to placebo, EMLA was also effective, but was not as effective as DPNB. Both interventions appear to be safe for use in newborns. None of the studied interventions completely eliminated the pain response to circumcision.

Acyclovir for treating varicella in otherwise healthy children and adolescents.

BACKGROUND: Acyclovir has the potential to shorten the course of illness which may result in reduced costs and morbidity associated with chickenpox. OBJECTIVES: 1) To examine the evidence evaluating the efficacy of acyclovir in alleviating symptoms of chickenpox and shortening the duration of illness. 2) To examine complications of chickenpox and adverse effects associated with acyclovir as reported in the relevant trials. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2003), MEDLINE (January 1966 to May 2003), and EMBASE (1988 to April 2003). The reference lists of all relevant articles were reviewed. The primary author of relevant studies and the pharmaceutical company that manufactures acyclovir were contacted. SELECTION CRITERIA: Randomized controlled trials that evaluated otherwise healthy children zero to 18 years of age, with chickenpox. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed the studies for eligibility. Two reviewers independently assessed methodological quality of the relevant studies using the Jadad scale and allocation concealment. Differences were resolved by consensus. Data were extracted by one reviewer using a structured form and checked by a second.Continuous data were converted to the weighted mean difference (WMD). Weighted mean differences were combined into an overall estimate using random effects. There were too few studies to consider exploring statistical heterogeneity between studies (i.e., differences in reported effects), formally, or to assess for publication bias. MAIN RESULTS: Three studies were included. Study quality was three (n = 2) and four (n = 1) on the Jadad scale. Acyclovir was associated with a reduction in the number of days with fever (-1.1 days, 95% CI -1.3 to -0.9) and in reducing the maximum number of lesions (-76 lesions, -145 to -8). Results were less supportive with respect to the number of days to no new lesions and the number of days to the relief of itching. There were no clinically important differences between acyclovir and placebo with respect to complications associated with chickenpox or adverse effects associated with the treatment. REVIEWERS' CONCLUSIONS: Acyclovir appears to be effective in reducing the number of days with fever and the maximum number of lesions among otherwise healthy children with chickenpox. The results were less convincing with respect to the number of days to no new lesions and relief of itchiness. The clinical importance of acyclovir treatment in otherwise healthy children remains controversial.

Graduated driver licensing for reducing motor vehicle crashes among young drivers.

BACKGROUND: Graduated driver licensing (GDL) has been proposed as a means of reducing crash rates among novice drivers by gradually introducing them to higher risk driving situations. OBJECTIVES: To examine the effectiveness of GDL systems in reducing crash rates of young drivers. SEARCH STRATEGY: Studies were identified through searches of MEDLINE, EMBASE, CINAHL, Healthstar, Web of Science, NTIS Bibliographic Database, TRIS Online, SIGLE, the World Wide Web, relevant conference proceedings, consultation with experts and authors, and reference lists. The search was not restricted by language or publication status. SELECTION CRITERIA: Studies were included if: 1) they compared outcomes pre- and post-implementation of a GDL program within the same jurisdiction, 2) comparisons were made between jurisdictions with and without GDL, or 3) both. Studies had to report at least one objective, quantified outcome. Two reviewers independently screened searches and assessed the full text of potentially relevant studies for inclusion using a standard form. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and checked by a second. Additional data were requested from authors. Results were not pooled due to substantial heterogeneity between studies. Percentage change was calculated for each year after the intervention, using one year prior to the intervention as the baseline rate. Results were adjusted by internal controls. Analyses were stratified by different denominators (population, licensed drivers). Results were calculated for the different crash types (overall, injury, fatal, night-time, alcohol, and those resulting in hospitalization). Results were presented for 16 year-olds alone and all teenage drivers combined. MAIN RESULTS: We included 13 studies evaluating 12 GDL programs that were implemented between 1979 and 1998 in the US (n=7), Canada (3), New Zealand (1), and Australia (1). Programs varied in their restrictions during the intermediate stage: e.g. night curfews (8); limitations of extra passengers (2); roadway restrictions (1). Based on the Insurance Institute for Highway Safety classification scheme, no programs were good, six were acceptable, five were marginal, and one was poor. Reductions in crash rates were seen in all jurisdictions and for all crash types. Among 16 year-old drivers, the median decrease in per population overall crash rates during the first year was 31% (range 26-41%). Per population injury crash rates were similar (median 28%, range 4-43%). Results for all teenage drivers, rates per licensed driver, and rates adjusting for internal controls were generally reduced when comparing within jurisdictions. REVIEWERS' CONCLUSIONS: The existing evidence shows that GDL is effective in reducing the crash rates of young drivers, although the magnitude of the effect is unclear. The conclusions are supported by consistent direction of the findings, and the temporal relationship and plausibility of the association. The reviewers have made recommendations for primary research on GDL (e.g. study methods, standardized reporting of outcomes and results, long-term follow-up). The project has also shown what is needed to carry out systematic reviews of observational studies (e.g. quality assessment instruments).

Glucocorticoids for croup.

BACKGROUND: Since the initial version of this systematic review in 1997, a number of randomised trials examining the benefit of glucocorticoids have been published, reflecting a continued interest in the use of glucocorticoids to treat patients with croup. The objective of this review was to provide evidence to guide clinicians in their treatment of patients with croup by determining the effectiveness of glucocorticoids and to identify areas of uncertainty for future research. OBJECTIVES: To determine the effect of glucocorticoids for children with croup. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1, 2003), MEDLINE (January 1966 to April 2003) and Excerpta Medica/EMBASE (January 1974 to August 2003). We also contacted authors of identified croup trials published in the last ten years to inquire about additional published or unpublished trials. SELECTION CRITERIA: Randomised controlled trials that examine children with croup and objectively measure the effectiveness of glucocorticoid treatment. DATA COLLECTION AND ANALYSIS: Based on review of the title and abstract (when available), two researchers identified studies for potential relevance. The complete text was retrieved and using a priori inclusion criteria, the studies were independently reviewed for relevance by two reviewers. Two observers independently assessed quality. Differences with respect to inclusion status and quality assessment were resolved by consensus. Data were extracted using a structured form by one reviewer and checked for accuracy by a second reviewer. Standard statistical analyses were performed. MAIN RESULTS: Thirty-one studies were deemed relevant for inclusion (N = 3736). Glucocorticoid treatment was associated with an improvement in the Westley score at six hours with a weighted mean difference of -1.2 (95% confidence interval -1.6 to -0.8) and at 12 hours -1.9 (-2.4 to -1.3); at 24 hours this improvement was no longer significant (-1.3, -2.7 to 0.2). Fewer return visits and/or (re)admissions occurred in patients treated with glucocorticoids (relative risk 0.50; 0.36 to 0.70). Length of time spent in accident and emergency or hospital (weighted mean difference 12 hours, five to 19 hours) was significantly decreased for patients treated with glucocorticoids. Use of epinephrine decreased for children treated with a glucocorticoid (risk difference 10%; 1 to 20). No other decreases in additional treatments were found in the primary analysis. Publication bias does not impact results importantly. No between-trial significant differences were found between populations with mild and moderate croup. Oral dexamethasone may be superior to intramuscular dexamethasone. REVIEWER'S CONCLUSIONS: Dexamethasone and budesonide are effective in relieving the symptoms of croup as early as six hours after treatment. Fewer return visits and/or (re)admissions are required and the length of time spent in hospital is decreased in inpatients. Dexamethasone is also effective in mild croup populations. Research is required to examine the most beneficial method for disseminating croup practice guidelines and to increase the uptake of evidence to improve outcomes.

Epinephrine for bronchiolitis.

BACKGROUND: Bronchodilators are commonly used in the management of bronchiolitis. A recent systematic review showed that bronchodilators produce modest short-term benefit among patients with mild or moderate bronchiolitis. OBJECTIVES: To compare epinephrine versus placebo and other bronchodilators in infants less than 2 years of age with bronchiolitis. SEARCH STRATEGY: Electronic searches were conducted on the following bibliographic databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1, 2003), MEDLINE (January 1966 to May 2003), and EMBASE (January 1988 to May 2003). The reference lists of all selected articles were examined for relevant studies. Primary authors were contacted for information on additional trials. SELECTION CRITERIA: Studies were included if they: 1) were RCTs comparing epinephrine with placebo or other bronchodilator; 2) involved children less than two years with bronchiolitis; 3) presented at least one quantitative outcome. DATA COLLECTION AND ANALYSIS: Searches were screened and inclusion criteria applied independently by two reviewers. Quality was assessed by two reviewers using the Jadad scale and allocation concealment. Data were extracted by one reviewer using a structured form and checked by a second. Separate analyses were conducted for the two types of control groups (placebo, non-epinephrine bronchodilators) and for patient status (inpatient, outpatient). MAIN RESULTS: Fourteen studies were included. Quality ranged from one to five (Jadad scale) with a median of three (inter-quartile range: two to three). Allocation concealment was adequate in six trials and unclear in eight. Among inpatient studies comparing epinephrine and placebo (n = five), there was one significant outcome favouring epinephrine: change in clinical score at 60 minutes post-treatment (SMD -0.52; 95% CI -1.00,-0.03). For outpatient studies (n = three), change in clinical score at 60 minutes (SMD -0.81; -1.56,-0.07), change in oxygen saturation at 30 minutes (WMD 2.79;1.50,4.08), respiratory rate at 30 minutes (WMD -4.54;-8.89-0.19), and "improvement" (OR 25.06; 4.95,126.91) favoured epinephrine. Heart rate at 60 minutes post-treatment favoured placebo (WMD 11.80; 5.20,18.40). Admission rates and change in oxygen saturation at 60 minutes post-treatment were not significantly different. For inpatient studies comparing epinephrine and salbutamol (n = four), only one of the seven outcomes was statistically significant: respiratory rate at 30 minutes favoured epinephrine (WMD -5.12; -6.83;-3.41). Among outpatient studies (n = four), change in oxygen saturation at 60 minutes (WMD 1.91; 0.38,3.44), heart rate at 90 minutes (WMD -14.00; -22.95;-5.05), respiratory rate at 60 minutes (WMD -7.76; -11.35,-4.17) post-treatment and "improvement" (OR 4.51; 1.93,10.53) favoured epinephrine. Admission rates were not significantly different (OR 0.40; 0.12,1.33). Pallor at 30 minutes post-treatment was significantly higher in the epinephrine group (OR 6.00; 1.33,27.00). REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the use of epinephrine for the treatment of bronchiolitis among inpatients. There is some evidence to suggest that epinephrine may be favourable to salbutamol and placebo among outpatients. A number of large, multi-centered trials are required to examine the effectiveness of epinephrine compared to placebo and salbutamol for infants presenting to outpatient settings. There is a need to develop a validated, reliable scoring system that is sensitive to important clinical changes in patients with bronchiolitis.

Tissue adhesives for traumatic lacerations in children and adults.

BACKGROUND: Tissue adhesives have been used for many years to close simple lacerations as an alternative to standard wound closure (sutures, staples, adhesive strips). They offer many potential advantages over standard wound closure, including ease of use, decrease in pain and time to apply, as well as not requiring a follow-up visit for removal. Many studies have compared tissue adhesives and standard wound closure to determine the cosmetic outcome as well as these other secondary outcomes in their respective study populations. However, due to the wide variation in study parameters, there are no generalisable, definitive answers about the effectiveness of tissue adhesives. No study has been adequately powered to assess differences in complications, which are rare. OBJECTIVES: To summarize the best available evidence for the effect of tissue adhesives in the management of traumatic lacerations in children and adults. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (CD ROM 2001 Issue 4), the Cochrane Wounds Group Specialized Trials Register (Nov 2001), MEDLINE (1966 to Oct 1, 2001), and EMBASE (1988 to Sept 1, 2001) for relevant randomised controlled trials (RCTs). We also searched the citations of selected studies, and we contacted relevant authors and manufacturers of tissue adhesives to inquire about other published and unpublished trials. SELECTION CRITERIA: We included RCTs comparing tissue adhesives versus standard wound closure or tissue adhesive versus tissue adhesive for acute, linear, low tension, traumatic lacerations in an emergency or primary care setting. Trials evaluating tissue adhesives for surgical incisions or other types of wounds were not considered. DATA COLLECTION AND ANALYSIS: Data from eligible studies were extracted by one reviewer and checked for accuracy by a second reviewer. Two reviewers independently assessed masked copies for quality. Outcomes of cosmesis (subgroups of age, wound location and need for deep sutures), pain, procedure time, ease of use and complications were analysed separately for two comparisons: 1) tissue adhesive versus standard wound care; and 2) tissue adhesive versus tissue adhesive. MAIN RESULTS: Eight studies compared a tissue adhesive with standard wound care. No significant difference was found for cosmesis at any of the time points examined, using either Cosmetic Visual Analogue Scale (CVAS) or Wound Evaluation Score (WES). Data were only available for subgroup analysis for age; no significant differences were found. Pain scores (Parent VAS WMD -15.7 mm; 95% CI -21.9, -9.5) and procedure time (WMD -5.6 minutes; 95% CI -8.2, -3.1) significantly favoured tissue adhesives. No studies reported on ease of use. Small but statistically significant risk differences were found for dehiscence (favouring standard wound care NNH 25 95% CI 14, 100) and erythema (favouring tissue adhesive NNH 8 95% CI 4, 100). Other complications were not significantly different between treatment groups. Only one study was identified that compared two tissue adhesives (butylcyanoacrylate (Histoacryl TM) versus octylcyanoacrylate (Dermabond TM)) for pediatric facial lacerations. No significant difference was found for cosmesis using CVAS at 1-3 months, or using WES at 5-14 days and 1-3 months. Similarly, no significant difference was found in pain, procedure time or complications. Results for ease of use were incomplete as reported. REVIEWER'S CONCLUSIONS: Tissue adhesives are an acceptable alternative to standard wound closure for repairing simple traumatic lacerations. There is no significant difference in cosmetic outcome between tissue adhesives and standard wound closure, or between different tissue adhesives. They offer the benefit of decreased procedure time and less pain, compared to standard wound closure. A small but statistically significant increased rate of dehiscence with tissue adhesives must be considered when choosing the closure method (NNH 25).

Acyclovir for treating varicella in otherwise healthy children and adolescents.

BACKGROUND: Acyclovir has the potential to shorten the course of illness which may result in reduced costs and morbidity. OBJECTIVES: 1) To examine the evidence evaluating the efficacy of acyclovir in alleviating symptoms and shortening the duration of illness. 2) To examine complications of chickenpox and adverse effects associated with acyclovir as reported in the relevant trials. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (2002, Issue 2), MEDLINE (January 1966 to October 2001), EMBASE (1988 to September 2001). The reference lists of all relevant articles were reviewed. The primary author of relevant studies and the pharmaceutical company that manufactures acyclovir were contacted. SELECTION CRITERIA: Randomized controlled trials that evaluated otherwise healthy children 0-18 years of age with chickenpox. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed the studies for eligibility. Two reviewers independently assessed methodological quality of the relevant studies using the Jadad scale and allocation concealment. Differences were resolved by consensus. Data were extracted by one reviewer using a structured form and checked by a second. Continuous data were converted to the weighted mean difference (WMD). Weighted mean differences were not combined into an overall estimate due to the varied age groups between studies. There were too few studies to consider statistical heterogeneity between studies (i.e., differences in reported effects), to perform subgroup or sensitivity analyses, or to assess for publication bias. MAIN RESULTS: Three studies were included. Study quality was three (n=2) and four (n=1) on the Jadad scale. Acyclovir was associated with a reduction in the number of days with fever, from -1.0 (95% CI -1.5,-0.5) to -1.3 (95% CI -2.0,-0.6). Results were inconsistent with respect to the number of days to no new lesions, the maximum number of lesions and the number of days to the relief of itching. There were no clinically important differences between acyclovir and placebo with respect to complications associated with chickenpox or adverse effects associated with the drug. REVIEWER'S CONCLUSIONS: Acyclovir appears to be effective in reducing the number of days with fever among otherwise healthy children with chickenpox. The results were inconsistent with respect to the number of days to no new lesions, relief of itchiness and maximum number of lesions. The clinical importance of acyclovir treatment in otherwise healthy children remains controversial.