Pooled analysis of the phase 3 REVIVE trials: randomised, double-blind studies to evaluate the safety and efficacy of iclaprim versus vancomycin for treatment of acute bacterial skin and skin-structure infections.

Iclaprim, a diaminopyrimidine antimicrobial, was compared with vancomycin for treatment of patients with acute bacterial skin and skin-structure infections (ABSSSIs) in two studies (REVIVE-1 and REVIVE-2). Here, the efficacy and tolerability of iclaprim in a pooled analysis of results from both studies was explored. REVIVE-1 and REVIVE-2 were phase 3, double-blind, randomised, multicentre, active-controlled, non-inferiority (margin of 10%) trials, each designed to enrol 600 patients with ABSSSI using identical study protocols. Iclaprim 80 mg and vancomycin 15 mg/kg were administered intravenously every 12 h for 5-14 days. The primary endpoint was a ≥20% reduction from baseline in lesion size [early clinical response (ECR)] at the early time point (ETP) (48-72 h after starting study drug) in the intent-to-treat population. In REVIVE-1, ECR at the ETP was 80.9% with iclaprim versus 81.0% with vancomycin (treatment difference -0.13%, 95% CI -6.42% to 6.17%). In REVIVE-2, ECR was 78.3% with iclaprim versus 76.7% with vancomycin (treatment difference 1.58%, 95% CI -5.10% to 8.26%). The pooled ECR was 79.6% with iclaprim versus 78.8% with vancomycin (treatment difference 0.75%, 95% CI -3.84 to 5.35%). Iclaprim and vancomycin were comparable for the incidence of mostly mild adverse events, except for a higher incidence of elevated serum creatinine with vancomycin (n = 7) compared with iclaprim (n = 0). Iclaprim achieved non-inferiority compared with vancomycin for ECR at the ETP and secondary endpoints with a similar safety profile in two phase 3 studies for treatment of ABSSSI suspected or confirmed as caused by Gram-positive pathogens. [Clinical Trials Registration. NCT02600611 and NCT02607618.].

Enablers and determinants of the provision of written action plans to patients with asthma: a stratified survey of Canadian physicians.

Despite national recommendations, most patients with asthma are not given a written action plan . The objectives were to ascertain physicians' endorsement of potential enablers to providing a written action plan, and the determinants and proportion, of physician-reported use of a written action plan. We surveyed 838 family physicians, paediatricians, and emergency physicians in Quebec. The mailed questionnaire comprised 102 questions on asthma management, 11 of which pertained to written action plan and promising enablers. Physicians also selected a case vignette that best corresponded to their practice and reported their management. The survey was completed by 421 (56%) physicians (250 family physicians, 115 paediatricians and 56 emergency physicians); 43 (5.2%) reported providing a written action plan to ≥70% of their asthmatic patients and 126 (30%) would have used a written action plan in the selected vignette. Most (>60%) physicians highly endorsed the following enablers: patients requesting a written action plan, adding a blank written action plan to the chart, receiving a copy of the written action plan completed by a consultant, receiving a monetary compensation for its completion, and having another healthcare professional explain the completed written action plan to patients. Four determinants were significantly associated with providing a written action plan: being a paediatrician (RR:2.1), treating a child (RR:2.0), aiming for long-term asthma control (RR:2.5), and being aware of national recommendations to provide a written action plan to asthmatic patients (RR:2.9). A small minority of Quebec physicians reported providing a written action plan to most of their patients, revealing a huge care gap. Several enablers to improve uptake, highly endorsed by physicians, should be prioritised in future implementation efforts. ASTHMA: ENCOURAGING DOCTORS TO PROVIDE WRITTEN ACTION PLANS: Changes to practice organization and doctors' perceptions should encourage the provision of written action plans for all asthma patients. International guidelines state that effective long-term treatment of asthma requires educated self-management, regular reviews and provision of a written action plan (WAP). However, many patients have poor asthma control and as few as 30 per cent have a WAP. Fabienne Djandji at the Saint-Justine University Central Hospital in Montreal, Canada, and co-workers conducted a survey of 421 doctors to determine their attitudes and provision of WAPs. Only 5.2 per cent of respondents provided WAPs to patients; those treating children or aiming for long-term asthma control were more likely to do so. The doctors said that incentives to provide WAPs would include requests from patients themselves, being paid to complete WAPs and having extra support from specialists or other health care professionals such as pharmacists.

Physician agreement regarding the expansion of pharmacist professional activities in the management of patients with asthma.

BACKGROUND: Asthma control remains suboptimal in Canada. Expansion of pharmacist's professional activities offers the opportunity to improve the interdisciplinary management of patients with asthma. OBJECTIVE: The aim of this study was to determine the level of agreement of physicians regarding the expansion of pharmacists' professional activities in the management of asthma patients. METHODS: We conducted a survey of randomly selected Quebec physicians in family medicine, paediatrics and emergency medicine. A 102-item questionnaire, including 10 questions regarding pharmacist's expanded professional activities, was sent using the Tailored Design Method. Questions were answered on a 6-point Likert-like scale (0 - strong disagreement to 5 - strong agreement). RESULTS: With a 56% response rate, 421 (250 family medicine, 115 paediatric and 56 emergency medicine) physicians participated; the median years of practice (25%, 75%) was 13 (5-21) years and 69% of respondents were women. Physicians were in favour of the expansion of pharmacist's professional activities with strong endorsement rates (rating of ≥4 on a maximum of 5) exceeding 60% for all but three activities: suggesting a written action plan to the physician (55%), adjusting the dose of prescribed asthma medication to achieve a therapeutic target (52%) and offering spirometry testing in pharmacies (45%). Emergency physicians, physicians with fewer years of practice, and those with a favourable perception of an interprofessional approach were associated with higher endorsement of these activities. CONCLUSION: Physicians are favourable to the expansion of pharmacist activities in the management of patients with asthma. More complex activities were less frequently endorsed. The characteristics of strong intenders have been identified.

Enablers of Physician Prescription of a Long-Term Asthma Controller in Patients with Persistent Asthma.

Objective. We aimed to identify key enablers of physician prescription of a long-term controller in patients with persistent asthma. Methods. We conducted a mailed survey of randomly selected Quebec physicians. We sent a 102-item questionnaire, seeking reported management regarding one of 4 clinical vignettes of a poorly controlled adult or child and endorsement of enablers to prescribe long-term controllers. Results. With a 56% participation rate, 421 physicians participated. Most (86%) would prescribe a long-term controller (predominantly inhaled corticosteroids, ICS) to the patient in their clinical vignette. Determinants of intention were the recognition of persistent symptoms (OR 2.67), goal of achieving long-term control (OR 5.31), and high comfort level in initiating long-term ICS (OR 2.33). Decision tools, pharmacy reports, reminders, and specific training were strongly endorsed by ≥60% physicians to support optimal management. Physicians strongly endorsed asthma education, lung function testing, specialist opinion, accessible asthma clinic, and paramedical healthcare professionals to guide patients, as enablers to improve patient adherence to and physicians' comfort with long-term ICS. Interpretation. Tools and training to improve physician knowledge, skills, and perception towards long-term ICS and resources that increase patient adherence and physician comfort to facilitate long-term ICS prescription should be considered as targets for implementation.

Caregiver's functional status during a young child's asthma exacerbation: A validated instrument.

BACKGROUND: Few instruments exist to measure caregivers' functional status during a young child's asthma exacerbation. OBJECTIVE: We sought to develop and validate a measure of caregivers' functional status during a preschooler's asthma exacerbation. METHODS: The psychometric properties of the 21-item questionnaire Effects of a Young Child's Asthma Flare-up on the Parents (ECAP) were tested in a randomized placebo-controlled trial of pre-emptive high-dose fluticasone in preschoolers with virus-induced asthma. Caregivers completed the ECAP questionnaire on the last day their child exhibited symptoms of an upper respiratory tract infection or asthma exacerbation (episode). The mean of each item, scored on a scale of 1 (best) to 7 (worst), provided the ECAP score. RESULTS: Ninety-three preschoolers (2.5 ± 1.0 years old; 62.4% male) experienced 878 episodes. Feasibility (80% questionnaire return rate; 90% completion) and internal consistency (Cronbach α = 0.97) were high. Of 628 episodes with a completed ECAP questionnaire, 621 (98.9%) had data on exacerbations, and 609 (97.0%) had data on health care use. The ECAP score was significantly higher for children experiencing an asthma exacerbation versus those who were not (mean difference, 0.8; 95% CI, 0.6-1.0) and for episodes resulting versus not resulting in an emergency visit (mean difference, 1.2; 95% CI, 1.0-1.4), systemic corticosteroid use (mean difference, 1.4; 95% CI, 1.1-1.7), or hospitalization (mean difference, 1.9; 95% CI, 1.4-2.5). The ECAP score was significantly lower in children treated with fluticasone versus those treated with placebo (mean difference, -0.7; 95% CI, -1.1 to -0.3). CONCLUSIONS: The 21-item ECAP questionnaire, showing high feasibility, internal consistency, discriminative validity, and responsiveness, has the psychometric properties to serve as a validated outcome to measure the burden of preschoolers' asthma exacerbations on their caregivers' functional status.

Asthma Flare-up Diary for Young Children to monitor the severity of exacerbations.

BACKGROUND: Few instruments exist to ascertain the severity of a preschool-aged child's asthma exacerbations managed at home. OBJECTIVE: We sought to develop and validate a functional status instrument to assess asthma exacerbation severity in preschoolers. METHODS: The parent-completed Asthma Flare-up Diary for Young Children (ADYC), which was developed systematically, comprises 17 items, each scored from 1 (best) to 7 (worst). The ADYC was completed daily from the onset of an upper respiratory tract infection (URTI) until asthma symptom resolution; the cumulative daily score was reported. The ADYC was examined for key psychometric properties in a randomized placebo-controlled trial of pre-emptive high-dose fluticasone in preschoolers with URTI-induced asthma. RESULTS: In 121 children aged 2.7 ± 1.1 years (59.5% male), the ADYC's internal consistency (Cronbach α = .97), feasibility (97% completion), and test-retest reliability (r = 0.71; 95% CI, 0.59-0.80) were demonstrated. The ADYC was responsive to change between 2 consecutive days (Guyatt statistic = 0.77) with a minimal important difference of 0.22 (0.17-0.27). Of 871 episodes, the cumulative ADYC score was significantly higher during exacerbations than during URTIs (mean difference [MD], 7.6; 95% CI, 6.4-8.9) and for exacerbations with an acute-care visit (MD, 9.1; 95% CI, 7.6-10.7), systemic corticosteroids (MD, 10.1; 95% CI, 8.3-12.0), and hospitalization (MD, 6.8; 95% CI, 2.9-10.7) versus those without. In children receiving fluticasone, the ADYC score was significantly lower versus that in the placebo group (MD, 5.1; 95% CI, 1.8-8.3). CONCLUSIONS: The 17-item ADYC proved feasible, responsive to day-to-day changes, and discriminative across exacerbations of different severities. In a trial testing effective therapy in preschoolers, it identified a significant reduction in asthma exacerbation severity.

Orthodontics treatments for managing obstructive sleep apnea syndrome in children: A systematic review and meta-analysis.

A small maxilla and/or mandible may predispose children to sleep-disordered breathing, which is a continuum of severity from snoring to obstructive sleep apnea. Preliminary studies have suggested that orthodontic treatments, such as orthopedic mandibular advancement or rapid maxillary expansion, may be effective treatments. The aim is to investigate the efficacy of orthopedic mandibular advancement and/or rapid maxillary expansion in the treatment of pediatric obstructive sleep apnea. Pubmed, Medline, Embase, and Internet were searched for eligible studies published until April 2014. Articles with adequate data were selected for the meta-analysis; other articles were reported in the qualitative assessment. Data extraction was conducted by two independent authors. A total of 58 studies were identified. Only eight studies were included in the review; of these, six were included in the meta-analysis. The research yielded only a small number of studies. Consequently, any conclusions from the pooled diagnostic parameters and their interpretation should be treated carefully. Although the included studies were limited, these orthodontic treatments may be effective in managing pediatric snoring and obstructive sleep apnea. Other related health outcomes, such as neurocognitive and cardiovascular functions have not yet been systematically addressed. More studies are needed with larger sample size, specific inclusion and exclusion criteria and standardized data reporting to help establish guidelines for the orthodontic treatment of pediatric obstructive sleep apnea.

The effect of rapid palatal expansion on sleep bruxism in children.

BACKGROUND: Sleep bruxism (SB) is a movement described as an involuntary mastication movement during sleep, also defined as rhythmic masticatory muscle activity (RMMA). It is observed in 2-40 % of the pediatric population. A link was suggested between respiratory events and RMMA. Rapid palatal expansion (RPE) is an effective orthopedic treatment for correcting maxillary transverse deficiency and sleep-disordered breathing (SDB) in children. The aim was to evaluate the possible reduction of SB after rapid palatal expansion (RPE) therapy. METHODS: A total of 32 patients (8-14 years old; 22 girls and 10 boys) received an orthodontic treatment for transverse maxillary deficiency (5 mm or more) at the orthodontics department of the Université de Montréal. They underwent an ambulatory polysomnography (PSG) before, after expansion with the expander, and at the end of the study without the expander. They were classified into three subgroups based on sleep electromyography (EMG) data. RESULTS: Total sleep time and stage NREM 3 presented significant differences between the types of appliances. Moreover, there was a time effect observed for total sleep time, sleep cycles, stage NREM 2, and stage REM, while only a trend suggested for stage NREM 3. Significant differences were observed between subgroups for both RMMA episodes and burst indexes, similarly, for the oxygen desaturation index (ODI). A total of 50 % of the patients were classified as responders when RMMA episodes index decreased by more than 25 % when comparing treatment efficacy at baseline night. CONCLUSION: Most bruxers (65 %) reduced their RMMA episode index after expansion, but sleep and respiratory variables remained unchanged.