The Importance of Consistent Global Forest Aboveground Biomass Product Validation.

Several upcoming satellite missions have core science requirements to produce data for accurate forest aboveground biomass mapping. Largely because of these mission datasets, the number of available biomass products is expected to greatly increase over the coming decade. Despite the recognized importance of biomass mapping for a wide range of science, policy and management applications, there remains no community accepted standard for satellite-based biomass map validation. The Committee on Earth Observing Satellites (CEOS) is developing a protocol to fill this need in advance of the next generation of biomass-relevant satellites, and this paper presents a review of biomass validation practices from a CEOS perspective. We outline the wide range of anticipated user requirements for product accuracy assessment and provide recommendations for the validation of biomass products. These recommendations include the collection of new, high-quality in situ data and the use of airborne lidar biomass maps as tools toward transparent multi-resolution validation. Adoption of community-vetted validation standards and practices will facilitate the uptake of the next generation of biomass products.

First nations people's perspectives on barriers and supports for enhancing HPV vaccination: Foundations for sustainable, community-driven strategies.

OBJECTIVE: In Canada, Indigenous people have higher human papillomavirus (HPV) infection rates, lower screening rates for cervical cancer, and higher rates of invasive cancer, leading to worse cervical cancer-related outcomes than observed in non-Indigenous Canadian women. Lingering harms from European colonization drive these health inequities and create public health challenges. Policy guidance is needed to optimize HPV vaccination rates and, thereby, decrease the burden of HPV-related illness, including high-morbidity surgical procedures and chemo-radiotherapy. The Enhancing HPV Vaccination In First Nations Populations in Alberta (EHVINA) project focuses on First Nations, a diverse subset of recognized Indigenous people in Canada, and seeks to increase HPV vaccination among girls and boys living in First Nation communities. METHODS: Developing an effective strategy requires partnership with affected communities to better understand knowledge and perceptions about cancer, healthcare, and the HPV vaccine. A 2017 community gathering was convened to engage First Nations community members, health directors, and health services researchers in dialogue around unique barriers and supports to HPV vaccination in Alberta. Voices of community Elders, parents, health directors, and cancer survivors (n=24) are presented as qualitative evidence to help inform intervention design. RESULTS: Key findings from discussions indicate barriers to HPV vaccination include resource constraints and service infrastructure gaps, historical mistrust in healthcare systems, impacts of changing modes of communication, and community sensitivities regarding sexual health promotion. Supports were identified as strengthened inter-generational relationships in communities. CONCLUSIONS AND FUTURE DIRECTION: Ongoing dialogue and co-development of community-based strategies to increase HPV vaccine uptake are required. The identification of possible barriers to HPV vaccination in a Canadian Indigenous population contributes to limited global literature on this subject and may inform researchers and policy makers who work with Indigenous populations in other regions.

Objective structured clinical examination "Death Certificate" station - Computer-based versus conventional exam format.

One option for improving the quality of medical post mortem examinations is through intensified training of medical students, especially in countries where such a requirement exists regardless of the area of specialisation. For this reason, new teaching and learning methods on this topic have recently been introduced. These new approaches include e-learning modules or SkillsLab stations; one way to objectify the resultant learning outcomes is by means of the OSCE process. However, despite offering several advantages, this examination format also requires considerable resources, in particular in regards to medical examiners. For this reason, many clinical disciplines have already implemented computer-based OSCE examination formats. This study investigates whether the conventional exam format for the OSCE forensic "Death Certificate" station could be replaced with a computer-based approach in future. For this study, 123 students completed the OSCE "Death Certificate" station, using both a computer-based and conventional format, half starting with the Computer the other starting with the conventional approach in their OSCE rotation. Assignment of examination cases was random. The examination results for the two stations were compared and both overall results and the individual items of the exam checklist were analysed by means of inferential statistics. Following statistical analysis of examination cases of varying difficulty levels and correction of the repeated measures effect, the results of both examination formats appear to be comparable. Thus, in the descriptive item analysis, while there were some significant differences between the computer-based and conventional OSCE stations, these differences were not reflected in the overall results after a correction factor was applied (e.g. point deductions for assistance from the medical examiner was possible only at the conventional station). Thus, we demonstrate that the computer-based OSCE "Death Certificate" station is a cost-efficient and standardised format for examination that yields results comparable to those from a conventional format exam. Moreover, the examination results also indicate the need to optimize both the test itself (adjusting the degree of difficulty of the case vignettes) and the corresponding instructional and learning methods (including, for example, the use of computer programmes to complete the death certificate in small group formats in the SkillsLab).

Establishment of two forensic medicine OSCE stations on the subject of external post-mortem examination.

An improvement in quality of medical external post-mortem examinations among others can be achieved by more intensive training of medical students. Modern learning and teaching methods such as e-learning modules and SkillsLab stations should be used for this. The introduction of corresponding methods of assessment such as the OSCE procedure is necessary to test the success of learning. In Halle (Germany), two OSCE stations on the subject of external post-mortem examinations were introduced in 2016. The 'practical external post-mortem examination' station test skills and abilities students have learned during practical external post-mortem examination in small group classes on a simulation doll. At the 'death certificate' station, an original death certificate must be filled in, testing the knowledge, skills and abilities learned in the SkillsLab station and during e-learning. A total of 148 students took part in the test. At both stations, at least two thirds of the students (69.5 and 81.7%) were able to show good or very good test results. In addition to the strengths, a detailed evaluation of the test results showed that there were still deficits in terms of the corresponding courses (e.g. inspection of the neck region in the small group classes), which will have to be remedied in the future. When analysing the test concept and the test implementation, objectivity was nearly perfect. There was a satisfactory internal consistency and stability over 8 months. Ultimately, in addition to several strengths (such as good understanding and transparency of the checklists) the evaluation of the examiners also showed further potential areas for improvement (e.g. harmonisation of the degree of difficulty for the individual rotations) when designing the OSCE stations. Overall, it was possible to determine that the OSCE testing format is a suitable tool to test external post-mortem examination skills and that conclusions about improvements in teaching can also be drawn from this.

Successful methodology for large-scale surveillance of severe events following influenza vaccination in Canada, 2011 and 2012.

In 2011 and 2012, a nationwide Canadian vaccine safety surveillance network rapidly collected safety data from healthcare workers (HCW) during the first weeks of the annual influenza vaccination campaign. This network provided the first available post-marketing safety data on seasonal influenza vaccines with information on background rates as a comparator. In 2012, these data were used to investigate a possible safety concern regarding a particular vaccine. An online questionnaire was provided to participating HCW two weeks before the annual influenza vaccination campaign for controls, and eight days after influenza vaccination for vaccinees. Control and vaccinees were requested to report health events occurring in the seven days prior to receiving the questionnaire. Control data were used to calculate background rates. HCW reporting a severe event were followed-up by telephone within 48 hours of the online report to validate the report and check on their health status. More than 22,000 vaccinated HCW were enrolled and surveyed over two seasons and > 90% reported no severe event following vaccination. Validated severe event rates were similar in vaccinated HCW and unvaccinated HCW (2.2% vs 2.3%; p < 0.70). The questionnaire was accurately completed for most reported symptoms, matched the validated report and was able to detect events of interest. Prior to the safety concern, the implicated vaccine was in use at one centre. Reassuring safety data were provided to public health authorities 48 hours after the vaccine was temporarily suspended. Data from this and similar networks can be used for rapid evaluation of vaccine safety and for safety assessment as required by the European Medicines Agency in 2015.

Umbilical cord blood graft engineering: challenges and opportunities.

We are entering a very exciting era in umbilical cord blood transplantation (UCBT), where many of the associated formidable challenges may become treatable by ex vivo graft manipulation and/or adoptive immunotherapy utilizing specific cellular products. We envisage the use of double UCBT rather than single UCBT for most patients; this allows for greater ability to treat larger patients as well as to manipulate the graft. Ex vivo expansion and/or fucosylation of one cord will achieve more rapid engraftment, minimize the period of neutropenia and also give certainty that the other cord will provide long-term engraftment/immune reconstitution. The non-expanded (and future dominant) cord could be chosen for characteristics such as better HLA matching to minimize GvHD, or larger cell counts to enable part of the unit to be utilized for the development of specific cellular therapies such as the production of virus-specific T-cells or chimeric-antigen receptor T-cells which are reviewed in this study.

Increased risk of invasive pneumococcal disease in haematological and solid-organ malignancies.

Large-scale population-based studies have reported a significant increase in invasive pneumococcal disease (IPD) in those with underlying haematological or solid-organ malignancy, but limited condition-specific data are available on rates of IPD in the adult population. A retrospective chart review of all patients with IPD (identified prospectively) in the province of Alberta, Canada (population ~3·3 million) was conducted from 2000 to 2004 to study the epidemiology of IPD. Rates of IPD in patients with various haematological and solid-organ malignancies were determined by obtaining the number of these patients at risk from the provincial cancer registry. Compared to the attack rate of IPD in the adult population aged ≥18 years (11·0 cases/100,000 per year, 95% CI 10·44-11·65), there were significantly increased rates of IPD in those with lung cancer (143·6 cases/100,000 per year, OR 13·4, 95% CI 9·3-19·4, P<0·001) and multiple myeloma (673·9 cases/100,000 per year, OR 62·8, 95% CI 39·6-99·8, P<0·001). More modestly increased rates of IPD were found in those with chronic lymphocytic leukaemia, acute myeloid leukaemia, acute lymphoblastic leukaemia, and Hodgkin's and non-Hodgkin's lymphoma. There was an increased prevalence of serotype 6A in those with these underlying malignancies, but no other serotypes predominated. Fifty-three percent (48/83) of cases were caused by serotypes in the investigational 13-valent pneumococcal conjugate vaccine (PCV13), and 57/83 (69%) of the cases were caused by serotypes in the 23-valent pneumococcal polysaccharide vaccine (PPV23). The incidence of IPD in adults with certain haematological and solid-organ malignancies is significantly greater than the overall adult population. Such patients should be routinely given pneumococcal polysaccharide vaccine; this population could also be targeted for an expanded valency conjugate vaccine.

[Ca2+-signaling in smooth muscles cells of the airways in T-bet knock-out mice]. / Ca2+-signaling in glatten Muskelzellen der Luftwege in T-bet Knock-Out Mäusen.

BACKGROUND: Airway smooth muscle cells (ASMC) play a key role in bronchial hyperresponsiveness (BHR). A major component of the signalling cascade leading to ASMC contraction is calcium. T-bet knock-out (KO) mice show the key features of allergic asthma such as a shift towards T (H2)-lymphocytes and display a broad spectrum of asthma-like histological and functional characteristics. In this study, we aimed at investigating whether Ca (2+)-homeostasis of ASMC is altered in T-bet KO-mice as an experimental model of asthma. METHODS: Lung slices of 100 to 200 microm thickness were obtained from T-bet KO- and wild-type mice. Airway contractions in response to acetylcholine (ACH) were measured by video-microscopy and Ca (2+)-signaling in single ASMC of lung slices was assessed using two-photon microscopy. RESULTS: Airways from T-bet KO-mice showed increased baseline airway tone (BAT) and BHR compared to those of wild-type mice. The increased BAT was correlated with an increased incidence of spontaneous changes in intracellular Ca (2+)-concentrations, whereas BHR correlated with higher ACH-induced Ca (2+)-transients and an increased proportion of ASMC showing Ca (2+)-oscillations. Emptying intracellular Ca (2+)-stores using caffeine or cyclopiazonic acid induced higher Ca (2+)-elevations in ASMC from T-bet KO compared to wild-type mice. CONCLUSIONS: Altered Ca (2+)-homeostasis of ASMC contributes to increased BAT and BHR in lung slices from T-bet KO mice as a murine asthma model. We propose that a higher Ca (2+)-content of the intracellular Ca (2+)-stores is involved in the pathophysiology of these changes.

Ex vivo expansion of mafosfamide-purged PBPC products.

BACKGROUND: Multiple studies have demonstrated that 'purging' of autografts with 4-hydroperoxycyclophosphamide (4HC) or the related compound mafosfamide (Mf), to eradicate residual leukemia, produces the best results associated with autologous blood and marrow transplantation for AML. However, 4HC purging results in prolonged aplasia. Therefore, we evaluated the potential of ex vivo expansion of Mf-treated CD34+ cells from mobilized PBPC. METHODS: CD34+ cells were isolated from PBPC products and treated with 30 microg/mL Mf. The Mf-treated CD34+ cells were washed and cultured for 14 days in StemLine II-defined media containing recombinant human (rh) SCF, G-CSF and thrombopoietin (Tpo). RESULTS: Treatment with Mf resulted in 90% killing of progenitor cells (GM-CFC) but maintenance of SCID-repopulating cells (SRC). Ex vivo culture of the Mf-treated CD34+ cells resulted in decreased cell numbers (10-20% of the starting cell dose) during the first week. Nevertheless, in the second week of culture the total cell numbers expanded to approximately 20-fold above starting cell numbers and progenitor cells returned to approximately pre-treatment levels. DISCUSSION: These studies demonstrate the potential of ex vivo culture to expand both total cell numbers and progenitor cells following treatment of PBPC CD34+ cells with Mf. Clinical studies are currently being initiated to evaluate the engraftment potential of these purged and expanded products.

Bronchial hyperreactivity is correlated with increased baseline airway tone.

Physiologically, airways are not completely relaxed but maintain a baseline airway tone (BAT). Although not fulfilling the criteria for obstructive airway disease, increased BAT may nevertheless be important because the same amount of airway narrowing can be well tolerated or can cause severe airway obstruction depending on the starting point of the narrowing. In this study, we aimed at studying if BAT is correlated with bronchial hyperreactivity (BHR). For in vitro studies, airways in murine lung slices were digitally recorded and the change in cross-sectional area with time was quantified. BAT was measured by the amount of relaxation induced by permeabilization of the cell membrane with beta-escin in zero external calcium. BHR was induced by incubation of lung slices with interleukin-13 (IL-13). T-bet knock-out mice served as an additional model for BHR. T-bet knock-out mice show a shift towards TH2-lymphocytes and display histological as well as functional characteristics of asthma. In vivo, the specific airway resistance of healthy non-smoking volunteers was assessed before and after inhalation of formoterol and bronchial challenge was performed using methacholin. In murine lung slices that had been cultivated without serum, only a minimal BAT could be observed. But, after cultivation with 10 % new born calve serum, airways showed a BAT of approximately 13 % that could be reduced by incubation with an IL-13 receptor antagonist. Atropine, isoproterenol and indomethacin failed to relax airways regardless of cultivation with serum. Incubation of lung slices without serum but with IL-13 increased BAT as well as airway responsiveness to acetylcholine and both effects were more pronounced in small compared to large airways. In lung slices from T-bet knock-out mice, airways were hyperreactive compared to airways in slices from wild type mice and BAT was found to be increased. Again, both effects were more pronounced in small compared to large airways. In human non-smokers without airway obstruction, increased BAT was correlated with bronchial hyperreactivity. We therefore conclude that although not fulfilling the criteria for obstructive airway disease, increased airway tone may yet be relevant in asthma.

Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture.

BACKGROUND: Human mesenchymal stem cells (hMSC) have been isolated and characterized extensively for a variety of clinical applications. Yet it is unclear how the phenomenon of hMSC plasticity can be safely and reasonably exploited for therapeutic use. METHODS: We have generated mesenchymal stem cells (MSC) from normal human BM and identified a novel cell population with a transformed phenotype. This cell population was characterized by morphologic, immunophenotypic, cytogenetic analyzes and telomerase expression. Its tumorigenicity in NOD/SCID mice was also studied. RESULTS: A subpopulation of cells in hMSC culture was noted to appear morphologically distinct from typical MSC. The cells were spherical, cuboidal to short spindle in shape, adherent and exhibited contact independent growth. Phenotypically the cells were CD133(+), CD34(-), CD45(-), CD90(low), CD105(-), VEGFR2(+). Cytogenetic analysis showed chromosome aneuploidy and translocations. These cells also showed a high level of telemerase activity compared with typical MSC. Upon transplantation into NOD/SCID mice, multiple macroscopic solid tumors formed in multiple organs or tissues. Histologically, these tumors were very poorly differentiated and showed aggressive growth with large areas of necrosis. DISCUSSION: The possible explanations for the origin of this cell population are: (1) the cells represent a transformed population of MSC that developed in culture; (2) abnormal cells existed in the donor BM at rare frequency and subsequently expanded in culture. In either case, the MSC culture may provide a suitable environment for transformed cells to expand or propagate in vitro. In summary, our data demonstrate the potential of transformed cells in hMSC culture and highlight the need for karyotyping as a release criteria for clinical use of MSC.

Ex vivo expansion of cord blood mononuclear cells on mesenchymal stem cells.

BACKGROUND: Cord blood (CB) cells are being used increasingly as a source of hematopoietic cells to support high dose chemotherapy. However, CB units contain low numbers of cells, including CD34+ cells, and thus their use is associated with significant delays in engraftment of neutrophils and platelets. Exvivo expansion of CB has been proposed to increase the numbers of cells available. We and others have reported the requirement of CD34 selection for optimal expansion of CB products'; however, the selection of frozen CB products in clinical trials results in significant loss of CD34+ cells, with a median recovery of 50, but less than 40% recovery in more than one-third of products. In the present studies we evaluated the potential of mesenchymal stem cells (MSC) to support ex vivo expansion of unselected CB products. METHODS: Mononuclear cells (MNC) from CB products were isolated and cultured on preformed MSC layers in T150 flasks containing 50 mL Stemline II media plus hematopoietic growth factors. Various culture conditions were compared for optimal expansion of the CB MNC. RESULTS: Ex vivo expansion of CB MNC on MSC resulted in 10- to 20-fold expansion of total nucleated cells, seven- to 18-fold expansion of committed progenitor cells, two- to five-fold expansion of primitive progenitor cells and 16- to 37-fold expansion of CD34+ cells. DISCUSSION: These studies demonstrated significant expansion of CB products without CD34 cell selection using culture conditions that are clinically applicable. Our current focus is to initiate clinical trials to evaluate the in vivo potential of CB cells expanded with these conditions.

Drug-resistant Streptococcus pneumoniae infections: clinical importance, drug treatment, and prevention.

Drug-resistant Streptococcus pneumoniae (DRSP) have complicated the management of pneumococcal infections throughout the world in recent years. Important risk factors for the development of a DRSP infection include recent antibiotic use, young age, immunosuppression, daycare center attendance, and recent hospitalizations. Although intermediate resistance to beta-lactam antibodies does not appear to have an impact on the mortality of S. pneumoniae infections, evidence is accumulating to suggest that more highly resistant isolates may increase mortality. Clinical and bacteriologic failures are more common in DRSP meningitis and otitis media. To select appropriate therapy, one must consider whether a patient has risk factors for resistance, the site and severity of the infection, and antibiotic susceptibility data. Reducing the impact of DRSP may be achieved through reducing antibiotic use in communities and increased understanding of other factors that contribute to the development and transmission of resistance. The most important way to reduce all S. pneumoniae infections is to increase the use of existing polysaccharide vaccines and to begin to use new polysaccharide-protein conjugate vaccines in young children.

Beliefs and behaviours of parents regarding antibiotic use by children.

OBJECTIVE: To determine parents' beliefs and behaviours about antibiotic use by their children in the ambulatory setting. DESIGN: Cross-sectional survey, where a self-administered questionnaire was completed by adult caregivers of children before the medical assessment of the child. SETTING: Three paediatric acute care settings (paediatric emergency department [PED], group paediatric practice and after hours walk-in medical clinic). POPULATION STUDIED: Adult caregivers (n=114; 76% mothers, 19% fathers and 4% other caregivers) of children brought for acute care were surveyed. MAIN RESULTS: Forty-one caregivers completed the survey in the PED, 37 in the paediatric office and 36 in the walk-in clinic. They believed that antibiotics were appropriate for ear infections (86%), pharyngitis (77%), bronchitis (49%), sinus colds (20%), cough (12%), colds (8%) and influenza (8%). Sixty-eight per cent of children had received antibiotics in the previous year. Thirteen per cent of caregivers reported previously requesting an antibiotic for their child, 18% believed a previous antibiotic prescription had been unnecessary and 19% had not complied with prescriptions in the past. Concerns about antibiotic use included antibiotic resistance (50%), harm to the immune system (40%), adverse effects (28%) and lack of efficacy (19%). CONCLUSIONS: In this population, parental knowledge and understanding of indications for antibiotics and their adverse effects were good; however, incorrect beliefs and disagreements with physicians did occur. To improve patterns of antibiotic use by children, it will be necessary to understand parents' beliefs, behaviours and information sources better so that misconceptions and disagreements with caregivers can be addressed appropriately.

Acute infectious conjunctivitis in childhood.

OBJECTIVE: To review the etiology, clinical features and management of acute infectious conjunctivitis in children after the newborn period. DATA SOURCES: Articles obtained from MEDLINE published before March 2000. DATA SELECTION AND EXTRACTION: Representative articles on the etiology and clinical features were selected. Twenty-four clinical trials were also selected. From these articles, the main findings from three placebo controlled trials and two comparative clinical trials involving children are summarized in detail. The main findings from 19 comparative clinical trials in adults are briefly summarized. DATA SYNTHESIS AND CONCLUSIONS: Acute infectious conjunctivitis caused by bacteria or viruses is a very common problem in children after the neonatal period. The most common bacterial pathogens are nontypable Haemophilus influenzae and Streptococcus pneumoniae. Diagnostic microbiology tests are not indicated for uncomplicated cases but may be useful for very young or very ill children if there is no response to initial therapy; for nosocomial cases; for cases suspected to be caused by sexually transmitted pathogens; and for outbreaks. Conjunctivitis is usually a mild, self-limited disease, but topical antibiotics are superior to placebo in reducing the duration and severity of symptoms. Most topical agents have equivalent efficacy; therefore, the selection of first-line agents should include inexpensive drugs with few adverse effects. Good choices include polymyxin/gramicidin, polymyxin/trimethoprim or sulfacetamide. Referral to an ophthalmologist should be considered in situations in which the diagnosis of uncomplicated conjunctivitis is in doubt or if there is no prompt response to therapy.

Disseminated bacille Calmette-Guérin infection in an infant with a novel deletion in the interferon-gamma receptor gene.

Six weeks after receiving BCG vaccination, a Canadian aboriginal infant presented with suspected sepsis, lymphadenopathy and hepatosplenomegaly. Lymph node biopsy revealed macrophages filled with acid-fast bacilli. Mycobacterium bovis was cultured from tissue specimens and there was evidence of concomitant cytomegalovirus disease. The infant died of disseminated BCG infection. A novel deletion at nucleotide 165 in the interferon-gamma receptor (IFN-gammaR1) was identified. The incidence of this mutation in the aboriginal population and the impact on the heterozygous state are unknown.

Bronchodilators for bronchiolitis.

OBJECTIVES: Bronchiolitis is an acute, highly communicable lower respiratory tract infection. Bronchodilators are commonly used in the management of bronchiolitis in North America, but not in the United Kingdom. The objective of this review was to assess the effects of bronchodilators for bronchiolitis. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Reference Update, reference lists of articles, and the files of two of the authors up to June 1998. SELECTION CRITERIA: Randomised trials comparing bronchodilators with placebo in the treatment of bronchiolitis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Unpublished data were requested from authors when necessary. MAIN RESULTS: In eight trials with 394 children, 46% demonstrated an improved clinical score with bronchodilators compared to 75% with placebo (odds ratio for no improvement 0.29, 95% confidence interval 0.19 to 0.45). However, the inclusion of studies that enrolled people with recurrent wheezes may have biased these results in favour of bronchodilators. Bronchodilator recipients did not show improvement in measures of oxygenation, the rate of hospitalisation (18% versus 26%, odds ratio 0.70, 95% confidence interval 0.36 to 1.35) or duration of hospitalisation (weighted mean difference 0.12, 95% confidence interval -0.3 to 0.5). REVIEWER'S CONCLUSIONS: Bronchodilators produce modest short-term improvement in clinical scores. This small benefit must be weighed against the costs of these agents.

Glucocorticoids for croup.

BACKGROUND: Since the last meta-analysis in 1989, a number of randomised trials on the benefit of glucocorticoids have been published, resulting in an increasing interest in the use of glucocorticoids to treat outpatients with croup. The objective of this review was to provide evidence to guide clinicians in their treatment of patients with croup, to examine the effectiveness of glucocorticoids in these patients, 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 Controlled Trials Register, MEDLINE (January 1966 to August 1997) and Excerpta Medica/EMBASE (January 1974 to August 1997). We also contacted (by mail) authors of identified croup trials published in the last five years to inquire about other trials, published or unpublished. SELECTION CRITERIA: Meta-analysis of randomised controlled trials that examine the effectiveness of glucocorticoid treatment in children with croup. DATA COLLECTION AND ANALYSIS: Data were extracted using a structured form, which captured patient status (inpatient or outpatient), intervention and control, with the name of the drug, route of administration and dose. Data were also collected on the primary outcome measures comprised of a clinical croup score at baseline (as well as any other subsequent assessment times), length of stay (hours), patients status improved (yes/no), and use of co-interventions. The quality of the trials was assessed using empirically derived items that involved scales and components. Two researchers (TPK, MA) then selected studies as being potentially relevant based on a review of the titles and abstracts, if available. The complete text of these studies was then retrieved. All studies that had been retrieved were reviewed independently by two reviewers (AS, TPK). Data were extracted by one reviewer (MA) and checked for accuracy by a second reviewer (TPK). Two observers independently assessed quality (MA, JK), and inter rater agreement was measured by the intra class correlation. Differences were resolved by consensus. MAIN RESULTS: Twenty-four studies were deemed relevant for inclusion (N=2221). Glucocorticoid treatment was associated with an improvement in the croup severity score at 6 hours with an effect size of -1.0 (95% confidence interval -1.5 to -0.6) and at 12 hours -1.0 (-1.6 to -0. 4); at 24 hours this improvement was no longer significant (-1.0, -2. 0 to 0.1). There was a decrease in the number of adrenaline treatments needed in children treated with glucocorticoids: a decrease of 9% (95% confidence interval 2 to 16%) among those treated with budesonide and of 12% (4 to 20%) among those treated with dexamethasone. There was also a decrease in the length of time spent in accident and emergency (-11 hours, 95% confidence interval -18 to 4 hours), and for inpatients hospital stay was reduced by 16 hours (-31 to 1 hour). Publication bias seems to play a part in these results. REVIEWER'S CONCLUSIONS: Dexamethasone and budesonide are effective in relieving the symptoms of croup as early as 6 hours after treatment. Fewer co-interventions are used and the length of time spent in hospital is decreased in patients treated with glucocorticoids.

A novel multiresistant Streptococcus pneumoniae serogroup 19 clone from Washington State identified by pulsed-field gel electrophoresis and restriction fragment length patterns.

In 1997, a cluster of multiresistant invasive serogroup 19 pneumococcus infections, including two fatalities, was reported in Washington State. Further investigation identified other cases. Fourteen Washington Streptococcus pneumoniae isolates, four from Alaska, and eight isolates from eastern Canada with reduced penicillin susceptibility (MIC of > or =1 microg/ml) were included in the study. Pulsed-field gel electrophoresis (PFGE) with ApaI, SacII, and SmaI restriction enzymes and IS1167 and mef restriction fragment length polymorphism (RFLP) pattern analysis were performed. Twenty of the 26 isolates had identical or related PFGE patterns, with two or all three enzymes, and identical or related IS1167 RFLP patterns, indicating that they were genetically related. These 20 isolates contained the mef gene conferring erythromycin resistance and had identical mef RFLP patterns. The PFGE and RFLP patterns were distinct from those of six multiresistant clones previously described and suggest that a new multiresistant clone has appeared in Washington, Alaska, and eastern Canada. This newly characterized clone should be included in the Pneumococcal Molecular Epidemiology Network.