CSCI and the future of clinical health science research in Canada.

In 2003, Dr. MacLeod became Professor (emeritus since 2014) in the Department of Pediatrics, University of British Columbia and Director of the BC Children's Hospital Research Institute. Previously, he had spent 14 years as a clinical pharmacologist at the University of Toronto and The Hospital for Sick Children and was Dean of the Faculty of Health Sciences, McMaster University 1987-1992. His research interests include pediatric clinical pharmacology, treatments for rare disorders, global health and medical education. From 1984-85, he was President of the Canadian Society for Clinical Investigation.

Prescription drug dispensing profiles for one million children: a population-based analysis.

BACKGROUND: Population-based drug utilization databases that comprehensively capture an entire population's drug dispensing are scarce resources for epidemiological studies. This study aimed to examine the prescription-dispensing rates in children in British Columbia (BC) and describe the differences in the dispensing of medications in BC versus children in the United States (US) and Europe. METHODS: The study population was children aged 0-17 years in BC (n = 855,541). Children with at least one prescription dispensed in 2007 were identified using the provincial outpatient prescription dispensing database. All prescriptions were grouped on the basis of the Anatomical Therapeutic Chemical (ATC) classification system. Prevalence of drug dispensing was calculated in each age group, gender, and therapeutic class. RESULTS: Fifty-five percent of BC children were dispensed at least one prescription in 2007. Antibacterials for systemic use, dermatological corticosteroids, and drugs for obstructive airway diseases were commonly dispensed in each age group. The percentage of children who received psychoanaleptics was two to five times higher than rates reported in European countries, but 30% lower than rates reported in the US. CONCLUSIONS: Half of the BC population <18 years received at least one prescription in 2007. Significant variations in drug dispensing were highlighted between BC, the US, and Europe. Future studies are needed to examine the outcomes of the prescribing in terms of benefit and harm. A variety of factors (e.g., disease prevalence rates, drug prescribing preferences) are likely to contribute to disparate dispensing of specific drug classes and should be principal factors in the investigation.

Twisting the lion's tail: Collaborative health policy making in British Columbia.

The respective roles of government, academia and health authorities in supporting health systems and service delivery research in the context of health policy making have often been unclear. A new strategy is necessary, one that encompasses the interdependence of research and practice and respects different kinds of knowledge and the needs and capacity of all stakeholders. Reform efforts to date have focused mainly on structural change and genuine collaboration has been pushed to the back seat. A major challenge in the health policy making process is expressing not just what we think but how we think, which requires us to be self-aware and critically reflective on how we make sense of our day-to-day realities. Using an analogy with philosophical roots, this essay explores health services research in the context of the BC health system and examines how such research and related activities can be contextualized, understood and applied in health policy making.

Improving drug treatment for children: are we making an impact?

At the beginning of 2009, we are on the threshold of mobilizing expertise in child health care and pediatric pharmacy and pharmacology in pursuit of worldwide major improvements in drug therapy for children. Momentum is built on progressive legislation on pediatric drug therapy from the US and Europe and on recent advances promoted by the WHO, including publication of an essential medicines list for children. Opportunities abound for research, educational initiatives, and practice improvements likely to bear early fruit in the form of better pharmacotherapy for children and youth. The most pressing challenge remaining is mobilization of a critical mass of caregivers, pharmacologists, pharmacists, and other child health professionals prepared to address their skills to this critically important task.

The global alliance for pediatric pharmacology: the future is here and now.

The vast majority of drugs prescribed for children have not been approved by regulatory agencies for the pediatric age group and, in many cases, have not been studied appropriately. In July 2008, at a meeting of pediatric pharmacologists from over 30 countries and 5 continents in Toronto, ON, Canada, it became apparent that numerous pediatric drug studies are being conducted, often duplicating studies done elsewhere. This is also true for pharmacokinetic and pharmacodynamic studies, as well as for the development of pediatric formulations. Finding simple ways to inform the world about existing data may save time and facilitate efforts.

Do women spend longer on wait lists for coronary bypass surgery? Analysis of a population-based registry in British Columbia, Canada.

BACKGROUND: Studies have shown patients who are delayed for surgical cardiac revascularization are faced with increased risks of symptom deterioration and death. This could explain the observation that operative mortality among persons undergoing coronary artery bypass surgery (CABG) is higher among women than men. However, in jurisdictions that employ priority wait lists to manage access to elective cardiac surgery, there is little information on whether women wait longer than men for CABG. It is therefore difficult to ascertain whether higher operative mortality among women is due to biological differences or to delayed access to elective CABG. METHODS: Using records from a population-based registry, we compared the wait-list time between women and men in British Columbia (BC) between 1990 and 2000. We compared the number of weeks from registration to surgery for equal proportions of women and men, after adjusting for priority, comorbidity and age. RESULTS: In BC in the 1990 s, 9,167 patients aged 40 years and over were registered on wait lists for CABG and spent a total of 136,071 person-weeks waiting. At the time of registration for CABG, women were more likely to have a comorbid condition than men. We found little evidence to suggest that women waited longer than men for CABG after registration, after adjusting for comorbidity and age, either overall or within three priority groups. CONCLUSION: Our findings support the hypothesis that higher operative mortality during elective CABG operations observed among women is not due to longer delays for the procedure.

Anthropometric measures are simple and accurate paediatric weight-prediction proxies in resource-poor settings with a high HIV prevalence.

RATIONALE: Accurate weight measurements are essential for both growth monitoring and drug dose calculations in children. Weight can be accurately measured using calibrated scales in resource-rich settings; however, reliable scales are often not available in resource-poor regions or emergency situations. Current age and/or length/height-based weight-prediction equations tend to overestimate weight because they were developed from Western children's measures. OBJECTIVE: To determine the accuracy of several proxy measures for children's weight among a predominately HIV-positive group of children aged 18 months to 12 years in Botswana. DESIGN: Weight, length/height, ulna and tibia lengths, mid-upper arm circumference (MUAC) and triceps skinfold were measured on 775 children recruited from Gaborone, Botswana, between 6 July and 24 August 2011. RESULTS: Mean (95% CI) age and weight were 7.8 years (7.5 to 8.4) and 21.7 kg (21.2 to 22.2), respectively. The majority of children were HIV-positive (n=625, 81%) and on antiretroviral treatment (n=594, 95%). The sample was randomly divided; a general linear model was used to develop weight-prediction equations for one half of the sample (n=387), which were then used to predict the weight of the other half (n=388). MUAC and length/height, MUAC and tibia length and MUAC and ulna length most accurately predicted weight, with an adjusted R2 of 0.96, 0.95 and 0.93, respectively. Using MUAC and length/height, MUAC and tibia length and MUAC and ulna length equations, ≥92% of predicted weight fell within 15% of actual weight, compared with <55% using current equations. CONCLUSION: The development of nomograms using these equations is warranted to allow for rapid and accurate weight prediction from these simple anthropometric measures in HIV-endemic, resource-constrained settings.

Pharmacological treatment of ankylosing spondylitis: a systematic review.

The purpose of this study was to review the evidence regarding the efficacy and safety of pharmacological therapies currently available for the treatment of ankylosing spondylitis (AS).A literature search using MEDLINE from 1966 through to April 2005 and a hand search of abstracts from the American College of Rheumatology (ACR) meetings for 2001 through to 2004 were performed. References of articles retrieved were also searched. The MEDLINE search yielded 570 citations and 157 abstracts from ACR were identified. Eighty-four studies were randomised controlled trials (RCTs); 53 fulfilled the inclusion criteria (pharmacological treatment of AS and RCT) and were included in this review. Statistical pooling of data was not performed because of the disparate outcome measures used. Eight RCTs found nonselective NSAIDs and two RCTs found cyclo-oxygenase (COX)-2-selective NSAIDs to be superior to placebo for relief of pain and improvement in physical function. Twenty-nine RCTs showed comparable efficacy and safety between nonselective NSAIDs. One RCT showed no difference between methylprednisolone 1g and 375 mg. Seven RCTs assessing the efficacy of sulfasalazine (sulphasalazine) and two RCTs of methotrexate provided contradictory evidence as to their benefit for treatment of AS. One RCT showed intravenous pamidronate 60 mg to be more effective than 10mg intravenously for the treatment of axial pain. All six RCTs of anti-tumour necrosis factor (TNF)-alpha agents demonstrated superiority to placebo for the treatment of axial and peripheral symptoms. Nonselective as well as COX-2-selective NSAIDs can be used for pain control in patients with AS. Other proven treatment options include sulfasalazine for the treatment of peripheral joint symptoms, while limited evidence supports the use of pamidronate or methotrexate, which require further studies. Anti-TNFalpha agents have been found very effective for the treatment of both peripheral and axial symptoms in patients with AS, but their use is limited by cost and uncertainty over long-term efficacy and safety.

Better therapies for children: a worldwide search for needed human resources.

A point has been reached in the pursuit of optimal prescribing for infants, children and youth where global deficiencies in inter-professional communication are presenting a substantial barrier to progress. In an effort to remedy this situation, the International Alliance for Better Medicines for Children (IABMC) is seeking to create an international registry of engaged essential personnel. An open invitation is extended to all those who wish to partner with others in actively addressing the pressing global health challenge represented by gaps in the evidence base supporting safe and effective drug therapy for children of all ages. Respondents are invited to complete a brief survey at: https://www.surveymonkey.com/s/H3GKSHP .

A cohort study of morbidity, mortality and health seeking behavior following rural health center visits by children under 12 in southwestern Uganda.

BACKGROUND: Children discharged from hospitals in developing countries are at high risk of morbidity and mortality. However, few data describe these outcomes among children seen and discharged from rural outpatient centers. OBJECTIVE: The objective of this exploratory study was to identify predictors of immediate and follow-up morbidity and mortality among children visiting a rural health center in Uganda. METHODS: Subjects 0-12 years of age seeking care with a caregiver were consecutively enrolled from a single rural health center in Southwestern Uganda. Baseline variables were collected by research nurses and outcomes of referral, admission or death were recorded (immediate events). Death, hospital admission and health seeking occurring during the 30 days following the clinic visit were also determined (follow-up events). Univariate logistic regression was performed to identify baseline variables associated with immediate outcome and follow-up outcomes. RESULTS: Over the four-month recruitment period 717 subjects were enrolled. There were 85 (11.9%) immediate events (10.1% were admitted, 2.2% were referred, none died). Forty-seven (7.8%) events occurred within 30 days after the visit (7.3% sought care from a health provider, 1.5% were admitted and 0.5% died). Variables associated with immediate events included living more than 30 minutes from the health center, age older than 5 years, having received an antimalarial prior to the visit, having seen a community health worker prior to the visit, elevated respiratory rate or temperature, and depressed weight-for-age z score or decreased oxygen saturation. These variables were not associated with follow-up events. CONCLUSIONS: Sick-child visits at a rural health center in South Western Uganda were associated with rates of mortality and subsequent admission of less than 2% in the period following the sick child visits. Other types of health seeking behavior occurred in approximately 7% of subjects during this same period. Several variables were associated with immediate events but there were no reliable predictors of follow-up events, possibly due to low statistical power.

Hospitals and academic health sciences centres: leaders or followers in health globalization?

The overall impact of globalization on health outcomes is contentious, but there is no doubt that knowledge transfer and the extension of specific health interventions to developing countries promise extraordinary benefits. It has been suggested that improved information/communications technology and the creation of distributed hospital systems leading a virtual healthcare web will permit realization of the promise of globalization. It is argued in this commentary that such evolution will require a new model of shared governance in the healthcare system. The leading vision is most likely to come from academic institutions, researchers, health professionals and governments. The "super-hospital" of the future should be expected to play a key role as service provider and partner.

Resistance to antibiotics: administrative response to the challenge.

The authors discuss antibiotic resistance within a conceptual framework that illustrates the dynamic relationships among antibiotic, patient, and population factors. The complexity of these interactions makes it unlikely that any single intervention or approach will adequately address the problem of increasing rates of antibiotic resistance. A case study focused on Streptococcus pneumoniae in the context of community-acquired pneumonia provides a detailed examination of the manner in which antibiotic use, expenditures, and microbial resistance are affected by an administrative reimbursement restriction implemented by a single government payer.

Canadian demand for highly qualified personnel for therapeutic evaluation: an opportunity for academic institutions.

Achievement of optimal therapeutics requires individuals with analytic skills appropriate to the balancing of enterprise, innovation and the need for rigorous scientific validation. A synergistic convergence of discovery research, clinical investigation, evaluative, regulatory and implementation sciences will be essential. None of the needed research capacities are likely to prove obtainable on demand. On the contrary, they require accurate projection of future needs and careful planning of post-secondary training programs. A survey conducted for Health Canada in 2010 revealed significant shortfalls in research skills available outside government and industry. This commentary argues that such an environment represents an outstanding opportunity for the academic community to demonstrate that it is eager to meet the needs of the Canadian public. University leaders should be assertive about their commitment to the ideals of patient oriented research and all governments should be clear about deliverables anticipated in return for consistent post-secondary funding.

Post-market drug evaluation research training capacity in Canada: an environmental scan of Canadian educational institutions.

BACKGROUND: Ongoing efforts by Health Canada intended to modernize the legislation and regulation of pharmaceuticals will help improve the safety and effectiveness of drug products. It will be imperative to ensure that comprehensive and specialized training sites are available to train researchers to support the regulation of therapeutic products. OBJECTIVES: The objective of this educational institution inventory was to conduct an environmental scan of educational institutions in Canada able to train students in areas of post-market drug evaluation research. METHODS: A systematic web-based environmental scan of Canadian institutions was conducted. The website of each university was examined for potential academic programs. Six core programmatic areas were determined a priori as necessary to train competent post-market drug evaluation researchers. These included biostatistics, epidemiology, pharmacoepidemiology, health economics or pharmacoeconomics, pharmacogenetics or pharmacogenomics and patient safety/pharmacovigilance. RESULTS: Twenty-three academic institutions were identified that had the potential to train students in post-market drug evaluation research. Overall, 23 institutions taught courses in epidemiology, 22 in biostatistics, 17 in health economics/pharmacoeconomics, 5 in pharmacoepidemiology, 5 in pharmacogenetics/pharmacogenomics, and 3 in patient safety/pharmacovigilance. Of the 23 institutions, only the University of Ottawa offered six core courses. Two institutions offered five, seven offered four and the remaining 14 offered three or fewer. It is clear that some institutions may offer programs not entirely reflected in the nomenclature used for this review. CONCLUSIONS: As Heath Canada moves towards a more progressive licensing framework, augmented training to increase research capacity and expertise in drug safety and effectiveness is timely and necessary.

Screening and referral to identify children at risk for FASD: Search for new methods 2006-2013.

As part of the Canadian Association of Paediatric Health Centres Taskforce on FASD Screening commitment to further pilot, validate and evaluate the multiple components of the Canadian FASD Screening Tool Kit, it was deemed necessary that recent developments and/or improvements in FASD screening were identified and considered. In 2008 a literature review of methods for screening for FASD was published until 2006 and identified five tools which met pre-set criteria. A review of all new papers was published from the period January 2006 until July 1, 2013. Out of 1392 papers, two new screening methods met the inclusion criteria: Clarren et al's new norms for palpebral fissure length by age in Canada; and Breiner et al's extension of the Neurobehavioral Screening Test (NST) to age 4 years. Further work is needed to validate these methods in other settings. 

Better drug therapy for the children of Africa: current impediments to success and potential strategies for improvement.

A commentary is presented on the urgent need for a comprehensive effort to improve the practice of pediatric therapeutics in Africa. A call for action is addressed to a variety of practitioners internationally, many of whom possess skills that could be fruitfully applied to the improvement of health outcomes for African children. Successful engagement with the many challenges requires the complementary effort of researchers in basic and clinical pharmacology and toxicology, nurses, pharmacists, physicians, clinical pharmacologists, clinical pharmacists, and political leaders and civil servants. While a comprehensive or systematic review of the relevant literature has not been attempted, the authors have highlighted promising initiatives driven by international agencies and academic networks. Two African perspectives are presented to reinforce the prospect of child health gains that can be achieved through consistent pursuit of optimal therapy for conditions such as respiratory infection, diarrhea, malaria, and HIV/AIDS. There is an imperative for development of north-south and south-south partnerships that will amplify current research efforts and mobilize existing knowledge concerning pediatric drugs. The overall goal is a multidisciplinary commitment to making essential medicines available at the right time, the right place, and in the right formulation for African children from infancy to adolescence.