Thiazide Diuretics and Risk of Colorectal Cancer: A Population-Based Cohort Study.

Evidence from clinical trials and observational studies on the association between thiazide diuretics and colorectal cancer risk is conflicting. We aimed to determine whether thiazide diuretics are associated with an increased colorectal cancer risk compared with dihydropyridine calcium channel blockers (dCCBs). A population-based, new-user cohort was assembled using the UK Clinical Practice Research Datalink. Between 1990-2018, we compared thiazide diuretic initiators with dCCB initiators and estimated hazard ratios (HR) with 95% confidence intervals (CIs) of colorectal cancer using Cox proportional hazard models. Models were weighted using standardized morbidity ratio weights generated from calendar time-specific propensity scores. The cohort included 377,760 thiazide diuretic initiators and 364,300 dCCB initiators, generating 3,619,883 person-years of follow-up. Compared with dCCBs, thiazide diuretics were not associated with colorectal cancer (weighted HR = 0.97, 95% CI: 0.90, 1.04). Secondary analyses yielded similar results, although an increased risk was observed among patients with inflammatory bowel disease (weighted HR = 2.45, 95% CI: 1.13, 5.35) and potentially polyps (weighted HR = 1.46, 95% CI: 0.93, 2.30). Compared with dCCBs, thiazide diuretics were not associated with an overall increased colorectal cancer risk. While these findings provide some reassurance, research is needed to corroborate the elevated risks observed among patients with inflammatory bowel disease and history of polyps.

Invited Commentary: Cross-Sectional Studies and Causal Inference-It's Complicated.

In this issue of the Journal, Savitz and Wellenius (Am J Epidemiol. 2023;192(4):514-516) discuss the contribution of cross-sectional studies to causal inference when the data are used to address etiological research questions. We elaborate on their thoughts with a discussion of the conditions needed for addressing etiology with the cross-sectional design, using a modern causal inference lens.

Applying behaviour change models to policy-making: development and validation of the Policymakers' Information Use Questionnaire (POLIQ).

BACKGROUND: The purpose of this study was to develop and validate the Policymakers' Information Use Questionnaire (POLIQ) to capture the intention of individuals in decision-making positions, such as health policy-makers, to act on research-based evidence in order to inform theory and the application of behaviour change models to decision-making spheres. METHODS: The development and validation comprised three steps: item generation, qualitative face validation with cognitive debriefing and factorial construct validation. Confirmatory factor analysis was applied to estimate item-domain correlations for five predefined constructs relating to content, beliefs, behaviour, control and intent. Cronbach's alpha coefficient was calculated to assess the overall consistency of questionnaire items with the predefined constructs. Participants in the item generation and face validation were health and policy researchers and two former decision-makers (former assistant deputy ministers) from the Canadian provincial level. Participants in the construct validation were 39 Canadian decision-makers at various positions of municipal, provincial and federal jurisdiction who participated in a series of policy dialogues focused on childhood disability. RESULTS: Cognitive debriefing allowed for small adjustments in language for clarity, including simultaneous validation of the English and French questionnaires. Participants found that the questions were clear and addressed the domains being targeted. Internal consistency of items belonging to the respective questionnaire domains was moderate to high, with estimated Cronbach's alpha values ranging from 0.67 to 0.84. Estimated item-domain correlations indicated moderate to high measurement performance for the domains norm, control and beliefs, whereas weak to moderate correlations resulted for the constructs content and intent. Estimated imprecision of factor loadings (95% confidence interval widths) was considerable for the questionnaire domains content and intent. CONCLUSION: Measuring decision-makers' behaviour in relation to research evidence use is challenging. We provide initial evidence on face validity and appropriate measurement properties of the POLIQ based on a convenience sample of decision-makers in social and health policy. Larger validation studies and further psychometric property testing will support further utility of the POLIQ.

Feasibility of a Platform Trial Design for the Development of Mobile Health Applications: A Review.

Background: A novel adaptive trial design called platform trials (PTs) may offer an effective, efficient, and unbiased approach to evaluate different developer versions of mobile health (m-health) apps. However, the feasibility of their use for this purpose is yet to be explored. Objective: This literature review aims to explore the reported challenges associated with the adaptive PT design to assess its feasibility for the development of m-health apps. Methods: A descriptive literature review using two databases (MEDLINE and Embase) was conducted. Documents published in English between 1947 and September 20, 2020, were eligible for inclusion. Results: The titles and abstracts of 758 records were screened after which 179 full-text articles were assessed for eligibility. A total of 41 articles were included in the synthesis, all published after the year 2000. The synthesis yielded eight distinct categories of challenging issues with PTs relevant to their application in m-health app development, along with potential solutions. These categories are ethical issues (e.g., related to informed consent, equipoise, justice) (with 19 articles contributing content), biases (7 articles), temporal drift (4 articles), miscellaneous statistical issues (3 articles), logistical issues (e.g., cost and human resources, frequent amendments; 6 articles), sample size and power conflict (2 articles), generalizability of the results (2 articles), and operational challenges (1 article). Conclusion: Although PT designs are relatively new, they have promising feasibility for the seamless evaluation of interventions that undergo continuous development, including m-health apps; however, various challenges may hinder their successful implementation.

Interprofessional Primary Care and Acute Care Hospital Use by People With Dementia: A Population-Based Study.

PURPOSE: Interprofessional primary care has the potential to optimize hospital use for acute care among people with dementia. We compared 1-year emergency department (ED) visits and hospitalizations among people with dementia enrolled in a practice having an interprofessional primary care team with those enrolled in a physician-only group practice. METHODS: A population-based, repeated cohort study design was used to extract yearly cohorts of 95,323 community-dwelling people in Ontario, Canada, newly identified in administrative data with dementia between April 1, 2005 and March 31, 2015. Patient enrollment in an interprofessional practice or a physician-only practice was determined at the time of dementia diagnosis. We used propensity score-based inverse probability weighting to compare study groups on overall and nonurgent ED visits as well as on overall and potentially avoidable hospitalizations in the 1 year following dementia diagnosis. RESULTS: People with dementia enrolled in a practice having an interprofessional primary care team were more likely to have ED visits (relative risk = 1.03; 95% CI, 1.01-1.05) and nonurgent ED visits (relative risk = 1.22; 95% CI, 1.18-1.28) compared with those enrolled in a physician-only primary care practice. There was no evidence of an association between interprofessional primary care and hospitalization outcomes. CONCLUSIONS: Interprofessional primary care was associated with increased ED use but not hospitalizations among people newly identified as having dementia. Although interprofessional primary care may be well suited to manage the growing and complex dementia population, a better understanding of the optimal characteristics of team-based care and the reasons leading to acute care hospital use by people with dementia is needed.

Exploring social determinants of health in a Saudi Arabian primary health care setting: the need for a multidisciplinary approach.

BACKGROUND: Action on social determinants of health (SDH) in primary health care settings is constrained by practitioners, organizational, and contextual factors. The aim of this study is to identify barriers and enablers for addressing SDH in clinical settings in Saudi Arabia, taking into consideration the influence of local cultural and social norms, to improve care and support for marginalized and underserved patients. METHODS: We conducted a qualitative study involving individual in-depth interviews with a sample of 17 primary health care physicians purposefully selected based on the inclusion criteria, as well as a focus group with four social workers, all recruited from King Khalid University Hospital (KKUH) in Riyadh, Saudi Arabia. All interviews were audio-recorded, translated from Arabic to English, transcribed verbatim, and analyzed using thematic analysis following a deductive-inductive approach. RESULTS: According to study participants, financial burdens, challenges in familial dynamics, mental health issues and aging population difficulties were common social problems in Saudi primary health care. Action on SDH in primary care was hindered by 1) lack of physician knowledge or training; 2) organizational barriers including time constraints, patient referral/follow up; 3) patient cultural norms and 4) lack of awareness of physician's role in managing SDH. Enablers to more socially accountable care suggested by participants includes: 1) more education and training on addressing SDH in clinical care; 2) organizational innovations to streamline identification of SDH during patient encounters (e.g. case finding questionnaire completed in waiting room); 3) better interprofessional coordination and clarification of roles (e.g. when to refer to social work, what support is provided by physicians); 4) identifying opportunities for broader advocacy to improve living conditions for marginalized groups. CONCLUSION: Enabling more socially accountable care requires a multipronged approach including leadership from the Ministry of Health, hospital administrations and medical schools. In particular, there is a need for: 1) training physicians to help patients in navigating social challenges; 2) improving clinical/administrative interprofessional teams, 3) mobilizing local communities in addressing social challenges; and 4) advocating for intersectoral action to prevent health inequities before they become more complex issues presenting to clinical care.

Community control strategies for scabies: A cluster randomised noninferiority trial.

BACKGROUND: Scabies is a neglected tropical disease hyperendemic to many low- and middle-income countries. Scabies can be successfully controlled using mass drug administration (MDA) using 2 doses of ivermectin-based treatment. If effective, a strategy of 1-dose ivermectin-based MDA would have substantial advantages for implementing MDA for scabies at large scale. METHODS AND FINDINGS: We did a cluster randomised, noninferiority, open-label, 3-group unblinded study comparing the effectiveness of control strategies on community prevalence of scabies at 12 months. All residents from 35 villages on 2 Fijian islands were eligible to participate. Villages were randomised 1:1:1 to 2-dose ivermectin-based MDA (IVM-2), 1-dose ivermectin-based MDA (IVM-1), or screen and treat with topical permethrin 5% for individuals with scabies and their household contacts (SAT). All groups also received diethylcarbamazine and albendazole for lymphatic filariasis control. For IVM-2 and IVM-1, oral ivermectin was dosed at 200 µg/kg and when contraindicated substituted with permethrin. We designated a noninferiority margin of 5%. We enrolled 3,812 participants at baseline (July to November 2017) from the 35 villages with median village size of 108 (range 18 to 298). Age and sex of participants were representative of the population with 51.6% male and median age of 25 years (interquartile range 10 to 47). We enrolled 3,898 at 12 months (July to November 2018). At baseline, scabies prevalence was similar in all groups: IVM-2: 11.7% (95% confidence interval (CI) 8.5 to 16.0); IVM-1: 15.2% (95% CI 9.4 to 23.8); SAT: 13.6% (95% CI 7.9 to 22.4). At 12 months, scabies decreased substantially in all groups: IVM-2: 1.3% (95% CI 0.6 to 2.5); IVM-1: 2.7% (95% CI 1.1 to 6.5); SAT: 1.1% (95% CI 0.6 to 2.0). The risk difference in scabies prevalence at 12 months between the IVM-1 and IVM-2 groups was 1.2% (95% CI -0.2 to 2.7, p = 0.10). Limitations of the study included the method of scabies diagnosis by nonexperts, a lower baseline prevalence than anticipated, and the addition of diethylcarbamazine and albendazole to scabies treatment. CONCLUSIONS: All 3 strategies substantially reduced prevalence. One-dose was noninferior to 2-dose ivermectin-based MDA, as was a screen and treat approach, for community control of scabies. Further trials comparing these approaches in varied settings are warranted to inform global scabies control strategies. TRIAL REGISTRATION: Clinitrials.gov NCT03177993 and ANZCTR N12617000738325.

Spline-based accelerated failure time model.

The accelerated failure time (AFT) model has been suggested as an alternative to the Cox proportional hazards model. However, a parametric AFT model requires the specification of an appropriate distribution for the event time, which is often difficult to identify in real-life studies and may limit applications. A semiparametric AFT model was developed by Komárek et al based on smoothed error distribution that does not require such specification. In this article, we develop a spline-based AFT model that also does not require specification of the parametric family of event time distribution. The baseline hazard function is modeled by regression B-splines, allowing for the estimation of a variety of smooth and flexible shapes. In comprehensive simulations, we validate the performance of our approach and compare with the results from parametric AFT models and the approach of Komárek. Both the proposed spline-based AFT model and the approach of Komárek provided unbiased estimates of covariate effects and survival curves for a variety of scenarios in which the event time followed different distributions, including both simple and complex cases. Spline-based estimates of the baseline hazard showed also a satisfactory numerical stability. As expected, the baseline hazard and survival probabilities estimated by the misspecified parametric AFT models deviated from the truth. We illustrated the application of the proposed model in a study of colon cancer.

Does spaced education improve clinical knowledge among Family Medicine residents? A cluster randomized controlled trial.

Spaced education is a learning strategy to improve knowledge acquisition and retention. To date, no robust evidence exists to support the utility of spaced education in the Family Medicine residency. We aimed to test whether alerts to encourage spaced education can improve clinical knowledge as measured by scores on the Canadian Family Medicine certification examination. METHOD: We conducted a cluster randomized controlled trial to empirically and pragmatically test spaced education using two versions of the Family Medicine Study Guide mobile app. 12 residency training programs in Canada agreed to participate. At six intervention sites, we consented 335 of the 654 (51%) eligible residents. Residents in the intervention group were sent alerts through the app to encourage the answering of questions linked to clinical cases. At six control sites, 299 of 586 (51%) residents consented. Residents in the control group received the same app but with no alerts. Incidence rates of case completion between trial arms were compared using repeated measures analysis. We linked residents in both trial arms to their knowledge scores on the certification examination of the College of Family Physicians of Canada. RESULTS: Over 67 weeks, there was no statistically significant difference in the completion of clinical cases by participants. The difference in mean exam scores and the associated confidence interval did not exceed the pre-defined limit of 4 percentage points. CONCLUSION: Further research is recommended before deploying spaced educational interventions in the Family Medicine residency to improve knowledge.

Weight status and nonadherence to asthma maintenance therapy among children enrolled in a public drug insurance plan.

Objective: The pediatric obese-asthma phenotype is associated with poor control, perhaps because of medication nonadherence. This study aimed to assess whether weight status is associated with nonadherence in children prescribed new asthma maintenance therapies.Methods: A historical cohort was constructed from a clinical database linking individual patient and prescription data to Quebec's prescription claims registry. Children aged 2-18 years with specialist-diagnosed asthma who were newly prescribed one of the following maintenance controllers: leukotriene receptor antagonists (LTRA); low-dose inhaled corticosteroids (ICS); medium/high-dose ICS; or combination therapy (ICS with long-acting beta-2 agonists and/or LTRA), at the Asthma Center of the Montreal Children's Hospital from 2000-2007 were included. Primary nonadherence was defined as not claiming any prescriptions, whereas secondary nonadherence was measured with the proportion of prescribed days covered (PPDC ≤ 50%) among primary adherers over a 6-month follow-up period. A modified Poisson regression model served to estimate the effect of excess weight (BMI > 85th percentile) on primary and secondary nonadherence.Results: Approximately one third of patients were primary nonadherers and 60% took less than 50% of prescribed therapy. Excess weight was associated with a trend toward increased risk of primary nonadherence in children newly prescribed low-dose ICS (RR 1.53, 95%CI 0.94-2.49), and of secondary nonadherence in children initiating medium/high-dose ICS (RR 1.24; 95%CI 0.98-1.59).Conclusions: Excess weight status is a possible determinant of primary nonadherence in children initiating low-dose ICS and secondary nonadherence to higher-dose ICS regimens. This hypothesis-generating study suggests that nonadherence may be a potential contributor to higher morbidity in children with obese-asthma.

Predictors of patient satisfaction and outpatient health services in China: evidence from the WHO SAGE survey.

BACKGROUND: Patient satisfaction is an essential indicator in medical practise and research. To monitor the health and well-being of adult populations and the ageing process, the World Health Organization (WHO) has initiated the Study on Global AGEing and Adult Health (SAGE), compiling longitudinal information in six countries including China as one major data source. OBJECTIVE: The objective of this study was to identify potential predictors for patient satisfaction based on the 2007-10 WHO SAGE China survey. METHODS: Data were analysed using random forests (RFs) and ordinal logistic regression models based on 5774 responses to predict overall patient satisfaction on their most recent outpatient health services visit over the last 12 months. Potential predictor variables included access to care, costs of care, quality of care, socio-demographic and health care characteristics and health service features. Increase of the mean-squared error (incMSE) due to variable removal was used to assess relative importance of the model variables for accurately predicting patient satisfaction. RESULTS: The survey data suggest low frequency of dissatisfaction with outpatient services in China (1.8%). Self-reported treatment outcome of the respective visit of a care facility demonstrated to be the strongest predictor for patient satisfaction (incMSE +15%), followed by patient-rated communication (incMSE +2.0%), and then income, waiting time, residency and patient age. Individual patient satisfaction in the survey population was predicted with 74% accuracy using either logistic regression or RF. CONCLUSIONS: Patients' perceived outcomes of health care visits and patient communication with health care professionals are the most important variables associated with patient satisfaction in outpatient health services settings in China.

Outcomes of Equity-Oriented, Web-Based Parenting Information in Mothers of Low Socioeconomic Status Compared to Other Mothers: Participatory Mixed Methods Study.

BACKGROUND: Typically, web-based consumer health information is considered more beneficial for people with high levels of education and income. No evidence shows that equity-oriented information offers equal benefits to all. This is important for parents of low socioeconomic status (SES; low levels of education and income and usually a low level of literacy). OBJECTIVE: This study is based on a conceptual framework of information outcomes. In light of this, it aims to compare the perception of the outcomes of web-based parenting information in low-SES mothers with that of other mothers and explore the perspective of low-SES mothers on contextual factors and information needs and behavior associated with these outcomes. METHODS: A participatory mixed methods research was conducted in partnership with academic researchers and Naître et grandir (N&G) editors. N&G is a magazine, website, and newsletter that offers trustworthy parenting information on child development, education, health, and well-being in a format that is easy to read, listen, or watch. Quantitative component (QUAN) included a 3-year longitudinal observational web survey; participants were mothers of 0- to 8-year-old children. For each N&G newsletter, the participants' perception regarding the outcomes of specific N&G webpages was gathered using a content-validated Information Assessment Method (IAM) questionnaire. Differences between participants of low SES versus others were estimated. Qualitative component (QUAL) was interpretive; participants were low-SES mothers. The thematic analysis of interview transcripts identified participants' characteristics and different sources of information depending on information needs. Findings from the two components were integrated (QUAN+QUAL integration) through the conceptual framework and assimilated into the description of an ideal-typical mother of low SES (Kate). A narrative describes Kate's perception of the outcomes of web-based parenting information and her perspective on contextual factors, information needs, and behavior associated with these outcomes. RESULTS: QUAN-a total of 1889 participants completed 2447 IAM responses (50 from mothers of low SES and 2397 from other mothers). N&G information was more likely to help low-SES participants to better understand something, decrease worries, and increase self-confidence in decision making. QUAL-the 40 participants (21 N&G users and 19 nonusers) used 4 information sources in an iterative manner: websites, forums, relatives, and professionals. The integration of QUAN and QUAL findings provides a short narrative, Kate, which summarizes the main findings. CONCLUSIONS: This is the first study comparing perceptions of information outcomes in low-SES mothers with those of other mothers. Findings suggest that equity-oriented, web-based parenting information can offer equal benefits to all, including low-SES mothers. The short narrative, Kate, can be quickly read by decision policy makers, for example, web editors, and might encourage them to reach the underserved and provide and assess trustworthy web-based consumer health information in a format that is easy to read, listen, or watch.

Development and Validation of the McGill Empowerment Assessment-Diabetes (MEA-D).

BACKGROUND: Diabetes is a prevalent chronic condition that poses a major burden for patients and the health care system. Evidence suggests that patient engagement in self-care improves diabetes control and reduces the risk of complications. To provide effective interventions that aim to improve empowerment processes relating to diabetes, a comprehensive and valid measure of empowerment is needed. This article details the development and validation of the McGill Empowerment Assessment-Diabetes (MEA-D). METHODS: The development and validation of the MEA-D questionnaire comprised three steps: item generation, qualitative face validation, and factorial content validation. An initial version was created by combining existing items and inductively generated items. Items were mapped to an empowerment framework with four domains: attitude, knowledge, behavior, and relatedness. Semi-structured interviews were conducted with 21 adults living with diabetes to assess face validity. The questionnaire was revised by a team of clinicians, researchers, and patient-partners. Factorial content validation was then performed using responses from 300 adult Canadians living with type 1 or type 2 diabetes. RESULTS: The final version of the MEA-D contained 28 items. A moderately good item-domain correlation was found between the individual items within the four domains. Cronbach's α was 0.81 (95% CI 0.78-0.85) for attitude, 0.73 (95% CI 0.67-0.79) for knowledge, 0.84 (95% CI 0.81-0.87) for behavior, and 0.81 (95% CI 0.77-0.84) for relatedness. CONCLUSION: The evaluation of diabetes programs demands a validated measure of empowerment. We developed the MEA-D to address this need. The MEA-D may be adapted to measure patients' empowerment regarding other chronic health conditions.

Long-Term Outcomes of Hypertrophic Cardiomyopathy Diagnosed During Childhood: Results From a National Population-Based Study.

BACKGROUND: Late survival and symptomatic status of children with hypertrophic cardiomyopathy have not been well defined. We examined long-term outcomes for pediatric hypertrophic cardiomyopathy. METHODS: The National Australian Childhood Cardiomyopathy Study is a longitudinal population-based cohort study of children (0-10 years of age) diagnosed with cardiomyopathy between 1987 and 1996. The primary study end point was time to death or cardiac transplantation. RESULTS: There were 80 patients with hypertrophic cardiomyopathy, with a median age at diagnosis of 0.48 (interquartile range, 0.1, 2.5) years. Freedom from death/transplantation was 86% (95% confidence interval [CI], 77.0-92.0) 1 year after presentation, 80% (95% CI, 69.0-87.0) at 10 years, and 78% (95% CI, 67.0-86.0) at 20 years. From multivariable analyses, risk factors for death/transplantation included symmetrical left ventricular hypertrophy at the time of diagnosis (hazard ratio, 4.20; 95% CI, 1.60-11.05; P=0.004), Noonan syndrome (hazard ratio, 2.88; 95% CI, 1.02-8.08; P=0.045), higher posterior wall thickness z score (hazard ratio, 1.45; 95% CI, 1.22-1.73; P<0.001), and lower fractional shortening z score (hazard ratio, 0.84; 95% CI, 0.74-0.95; P=0.005) during follow-up. Nineteen (23%) subjects underwent left ventricular myectomy. At a median of 15.7 years of follow-up, 27 (42%) of 63 survivors were treated with ß-blocker, and 13 (21%) had an implantable cardioverter-defibrillator. CONCLUSIONS: The highest risk of death or transplantation for children with hypertrophic cardiomyopathy is within 1 year after diagnosis, with low attrition rates thereafter. Many subjects receive medical, surgical, or device therapy.

Impact of a behavioral intervention, delivered by pediatricians or psychologists, on sleep problems in children with ADHD: a cluster-randomized, translational trial.

BACKGROUND: We have demonstrated the efficacy of a brief behavioral intervention for sleep in children with ADHD in a previous randomized controlled trial and now aim to examine whether this intervention is effective and cost-effective when delivered by pediatricians or psychologists in community settings. METHODS: Translational, cluster-randomized trial of a behavioral intervention versus usual care from 19th January, 2015 to 30th June, 2017. Participants (n = 361) were children aged 5-13 years with ADHD and parent report of a moderate/severe sleep problem who met criteria for American Academy of Sleep Medicine criteria for chronic insomnia disorder, delayed sleep-wake phase disorder, or were experiencing sleep-related anxiety. Participants were randomized at the level of the pediatrician (n = 61) to intervention (n = 183) or usual care (n = 178). Families in the intervention group received two consultations with a pediatrician or a psychologist covering sleep hygiene and tailored behavioral strategies. RESULTS: In an intention-to-treat analysis, at 3 and 6 months respectively, the proportion of children with moderate to severe sleep problems was lower in the intervention (28.0%, 35.8%) compared with usual care group (55.4%, 60.1%; 3 month: risk ratio (RR): 0.51, 95% CI 0.37, 0.70, p < .001; 6 month: RR: 0.58; 95% CI 0.45, 0.76, p < .001). Intervention children had improvements across multiple Children's Sleep Habits Questionnaire subscales at 3 and 6 months. No benefits of the intervention were observed in other domains. Cost-effectiveness of the intervention was AUD 13 per percentage point reduction in child sleep problem at 3 months. CONCLUSIONS: A low-cost brief behavioral sleep intervention is effective in improving sleep problems when delivered by community clinicians. Greater sample comorbidity, lower intervention dose or insufficient clinician supervisions may have contributed to the lack benefits seen in our previous trial.

The obese-asthma phenotype in children: An exacerbating situation?

BACKGROUND: Current evidence regarding the relationship between childhood obesity, decreased response to inhaled corticosteroids (ICSs), and poor asthma control is conflicting. OBJECTIVES: We assessed whether obesity (1) is associated with time to first exacerbation among children with asthma initiating step 3 maintenance therapies and (2) modifies the effectiveness of step 3 therapies. METHODS: A retrospective cohort study was conducted from clinical data linked to health and drug administrative databases. The cohort consisted of children aged 2 to 18 years with specialist-confirmed asthma who initiated medium/high-dose ICS monotherapy or low/medium-dose ICS with leukotriene receptor antagonist/long-acting ß-agonist (combination therapy) at the Montreal Children's Hospital Asthma Center from 2000 to 2007. Children were classified as exposed to step 3 therapies when they were dispensed a corresponding drug claim during follow-up, whereas those without claims were classified as nonadherers. Marginal structural Cox models were used to estimate the effect of obesity (body mass index > 97th percentile) and treatment on time to exacerbation, which was defined as any emergency department visit, hospitalization, or use of oral corticosteroids for asthma. RESULTS: Of the 4621 cohort patients, 231 initiated ICS monotherapy, and 97 initiated combination therapy. The hazard ratio (HR) for obesity was 1.67 (95% CI, 1.41-1.98). Compared with nonobese nonadherers, the HR for obese nonadherers was 1.54 (95% CI, 0.97-2.45); the HR for ICS monotherapy in obese and nonobese children was 0.85 (95% CI, 0.47-1.52) and 0.58 (95% CI, 0.37-0.91), respectively; and the HR for combination therapy in obese and nonobese children was 0.50 (95% CI, 0.13-1.89) and 0.46 (95% CI, 0.23-0.92), respectively. CONCLUSION: Obesity might be a determinant of shorter exacerbation-free time in children with asthma; however, we could not rule out a differential response to step 3 therapies by obesity status, potentially because of a lack of precision.

Implementing evidence-based practices in the care of infants with bronchiolitis in Australasian acute care settings: study protocol for a cluster randomised controlled study.

BACKGROUND: Bronchiolitis is the most common reason for admission to hospital for infants less than one year of age. Although management is well defined, there is substantial variation in practice, with infants receiving ineffective therapies or management. This study will test the effectiveness of tailored, theory informed knowledge translation (KT) interventions to decrease the use of five clinical therapies or management processes known to be of no benefit, compared to usual dissemination practices in infants with bronchiolitis. The primary objective is to establish whether the KT interventions are effective in increasing compliance to five evidence based recommendations in the first 24 h following presentation to hospital. The five recommendations are that infants do not receive; salbutamol, antibiotics, glucocorticoids, adrenaline, or a chest x-ray. METHODS/DESIGN: This study is designed as a cluster randomised controlled trial. We will recruit 24 hospitals in Australia and New Zealand, stratified by country and provision of tertiary or secondary paediatric care. Hospitals will be randomised to either control or intervention groups. Control hospitals will receive a copy of the recent Australasian Bronchiolitis Guideline. Intervention hospitals will receive KT interventions informed by a qualitative analysis of factors influencing clinician care of infants with bronchiolitis. Key interventions include, local stakeholder meetings, identifying medical and nursing clinical leads in both emergency departments and paediatric inpatient areas who will attend a single education train-the-trainer day to then deliver standardised staff education with the training materials provided and coordinate audit and feedback reports locally over the study period. Data will be extracted retrospectively for three years prior to the study intervention year, and for seven months of the study intervention year bronchiolitis season following intervention delivery to determine compliance with the five evidence-based recommendations. Data will be collected to assess fidelity to the implementation strategies and to facilitate an economic evaluation. DISCUSSION: This study will contribute to the body of knowledge to determine the effectiveness of tailored, theory informed interventions in acute care paediatric settings, with the aim of reducing the evidence to practice gaps in the care of infants with bronchiolitis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616001567415 (retrospectively registered on 14 November 2016).

Parental Immunisation Needs and Attitudes Survey in paediatric hospital clinics and community maternal and child health centres in Melbourne, Australia.

AIM: Despite Australia's high vaccination rates, an estimated 3.3% of children are under-vaccinated due to vaccine refusal and the proportion of parents with concerns is unclear. Amongst Australian parents, we aimed to determine the prevalence of vaccine concerns, resources and health-care providers (HCPs) accessed and satisfaction with these resources in two different settings. We also aimed to identify relationships between the level of vaccine concern, socio-economic status and vaccine uptake. METHODS: Parents of children under 5 years attending general paediatric clinics in a tertiary paediatric hospital (n = 301/398, 76%) and children under 19 months attending community maternal child health centres (n = 311/391, 81%) completed the survey. Vaccination status was obtained from the Australian Childhood Immunisation Register. RESULTS: Despite high support for vaccination (98%, confidence interval (CI) 97-99), 43% of parents reported vaccine concerns (CI 40-47) including the number of vaccines given in the first 2 years (25%, CI 22 to 29), vaccine ingredients (22%, CI 19-25), allergies (18%, CI 15-21), weakening of the immune system (17%, CI 14-20) and autism (11%, CI 8-13). HCPs were the most commonly accessed and trusted information source. In all, 23% of parents reported insufficient knowledge to make good vaccination decisions (CI 20-26). There was little evidence of an association between parental vaccine acceptance or socio-economic status and vaccination status. CONCLUSIONS: Despite high support for vaccines, nearly half of Australian parents have some concerns and a quarter lack vaccine decision-making confidence regarding childhood vaccines. Parents frequently access and report high trust in HCPs, who are best placed to address parental vaccine concerns through provision of clear information, using effective communication strategies. Further research in more highly hesitant populations is required to determine the relationship between the level and nature of vaccination concerns and vaccine uptake.

PREDICT prioritisation study: establishing the research priorities of paediatric emergency medicine physicians in Australia and New Zealand.

BACKGROUND: The Paediatric Research in Emergency Departments International Collaborative (PREDICT) performs multicentre research in Australia and New Zealand. Research priorities are difficult to determine, often relying on individual interests or prior work. OBJECTIVE: To identify the research priorities of paediatric emergency medicine (PEM) specialists working in Australia and New Zealand. METHODS: Online surveys were administered in a two-stage, modified Delphi study. Eligible participants were PEM specialists (consultants and senior advanced trainees in PEM from 14 PREDICT sites). Participants submitted up to 3 of their most important research questions (survey 1). Responses were collated and refined, then a shortlist of refined questions was returned to participants for prioritisation (survey 2). A further prioritisation exercise was carried out at a PREDICT meeting using the Hanlon Process of Prioritisation. This determined the priorities of active researchers in PEM including an emphasis on the feasibility of a research question. RESULTS: One hundred and six of 254 (42%) eligible participants responded to survey 1 and 142/245 (58%) to survey 2. One hundred and sixty-eight (66%) took part in either or both surveys. Two hundred forty-six individual research questions were submitted in survey 1. Survey 2 established a prioritised list of 35 research questions. Priority topics from both the Delphi and Hanlon process included high flow oxygenation in intubation, fluid volume resuscitation in sepsis, imaging in cervical spine injury, intravenous therapy for asthma and vasopressor use in sepsis. CONCLUSION: This prioritisation process has established a list of research questions, which will inform multicentre PEM research in Australia and New Zealand. It has also emphasised the importance of the translation of new knowledge.

Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial.

BACKGROUND: Preclinical data suggest that general anaesthetics affect brain development. There is mixed evidence from cohort studies that young children exposed to anaesthesia can have an increased risk of poor neurodevelopmental outcome. We aimed to establish whether general anaesthesia in infancy has any effect on neurodevelopmental outcome. Here we report the secondary outcome of neurodevelopmental outcome at 2 years of age in the General Anaesthesia compared to Spinal anaesthesia (GAS) trial. METHODS: In this international assessor-masked randomised controlled equivalence trial, we recruited infants younger than 60 weeks postmenstrual age, born at greater than 26 weeks' gestation, and who had inguinal herniorrhaphy, from 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand. Infants were randomly assigned (1:1) to receive either awake-regional anaesthesia or sevoflurane-based general anaesthesia. Web-based randomisation was done in blocks of two or four and stratified by site and gestational age at birth. Infants were excluded if they had existing risk factors for neurological injury. The primary outcome of the trial will be the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI-III) Full Scale Intelligence Quotient score at age 5 years. The secondary outcome, reported here, is the composite cognitive score of the Bayley Scales of Infant and Toddler Development III, assessed at 2 years. The analysis was as per protocol adjusted for gestational age at birth. A difference in means of five points (1/3 SD) was predefined as the clinical equivalence margin. This trial is registered with ANZCTR, number ACTRN12606000441516 and ClinicalTrials.gov, number NCT00756600. FINDINGS: Between Feb 9, 2007, and Jan 31, 2013, 363 infants were randomly assigned to receive awake-regional anaesthesia and 359 to general anaesthesia. Outcome data were available for 238 children in the awake-regional group and 294 in the general anaesthesia group. In the as-per-protocol analysis, the cognitive composite score (mean [SD]) was 98.6 (14.2) in the awake-regional group and 98.2 (14.7) in the general anaesthesia group. There was equivalence in mean between groups (awake-regional minus general anaesthesia 0.169, 95% CI -2.30 to 2.64). The median duration of anaesthesia in the general anaesthesia group was 54 min. INTERPRETATION: For this secondary outcome, we found no evidence that just less than 1 h of sevoflurane anaesthesia in infancy increases the risk of adverse neurodevelopmental outcome at 2 years of age compared with awake-regional anaesthesia. FUNDING: Australia National Health and Medical Research Council (NHMRC), Health Technologies Assessment-National Institute for Health Research UK, National Institutes of Health, Food and Drug Administration, Australian and New Zealand College of Anaesthetists, Murdoch Childrens Research Institute, Canadian Institute of Health Research, Canadian Anesthesiologists' Society, Pfizer Canada, Italian Ministry of Heath, Fonds NutsOhra, and UK Clinical Research Network (UKCRN).