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Introduction The prevalence of ethanol use in many Sub-Saharan African countries is high, but little research exists on use during pregnancy. The objective of this study was to assess the prevalence and predictors of ethanol use among pregnant women in Southwestern Uganda. Methods This descriptive, cross-sectional study was conducted in the maternity ward at Mbarara Regional Referral Hospital (MRRH). All pregnant women giving birth at MRRH between September 23, 2013 and November 23, 2013 were eligible for enrollment. The primary outcome was the proportion of women with ethanol use during pregnancy as determined by self-report. Secondary outcomes included the proportion with positive fatty acid ethyl ester (FAEE) results (indicating ethanol use) and positive TWEAK questionnaire results (indicating possible problem drinking). Predictors of ethanol use were assessed and stratified by patterns of ethanol intake. Results Overall, 505 mother–child dyads enrolled in the study. The proportion of women who reported any ethanol use during pregnancy was 16 % (n = 81, 95 % CI 13–19 %) and the prevalence of heavy drinking 6.3 % (n = 32, 95 % CI 3.8–7.9 %). The strongest predictor of use during pregnancy was pre-pregnancy use, with maternal education as a protective factor. Few neonates (n = 11, 2 %) tested positive for FAEE > 2.00 nmol/g in meconium. The TWEAK questionnaire captured 75 % of women who reported moderate/heavy drinking and aligned more with self-reported ethanol use than meconium results. Conclusions The substantial prevalence and clear predictors of ethanol use suggest that legislative action and educational interventions to increase awareness of potential harms could assist in efforts to decrease use during pregnancy in Southwestern Uganda.

Professionals committed to optimal medical care of children recognize the need to increase future availability of thoroughly validated medicinal treatments. This will only be achieved through expanded efforts of pediatric clinical pharmacologists and clinical pharmacists equipped with the necessary skills in relevant research and educational methods. Recent research has demonstrated a shortfall in the human resource pool, particularly in low- and lower-middle-income countries where a majority of children under 14 years of age reside.

The explosion of knowledge concerning the interplay of genetic and environmental factors determining pathophysiology and guiding therapeutic choice has altered the landscape in pediatric clinical pharmacology and pharmacy. The need for innovative research methods and design expertise for small clinical trials to be undertaken in sparse populations has been accentuated. At the same time, shortfalls in critical human resources represent a key challenge, especially in low- and middle-income countries where the need for new research and education directions is greatest. Unless a specific action plan is urgently developed, there will be a continuing gap in availability of the essential expertise needed to address treatment challenges in special patient populations such as neonates, patients suffering from rare or neglected diseases, and children of all ages.

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.

Think back; think wayyy back: before laptops, internet and smartphones. Bank machines didn’t exist, tele-phones were permanently plugged into the wall, airport security meant only checking that you paid for your ticket and medical journals came in the mail (as did the bills for the journals). As it turned out, the 1970s was not a kind decade for medical journals, and several were struggling financially. Even the New England Journal of Medicine (NEJM), desperate for cash, was forced to offer a lifetime subscription to anyone who could pay the princely sum of $350! (A colleague of ours, now retired, still receives the weekly NEJM by mail, 45 years later!)

For more than 50 years, the importance of studying new medicines in childhood has been widely recognized. Nonetheless, Health Canada has eschewed policies requiring such evaluation, despite effective reforms elsewhere. In 2012, the Council of Canadian Academies convened an expert panel to assess Canada’s research base for labelling of pediatric therapies. The September 2014 report has not yet resulted in action, but it deserves consideration by the new government with timely recognition of the high priority that evidence-based treatment of children deserves.

Globally there are numerous impediments, both logistical, regulatory and more recently global drug shortages, hindering pediatric access to therapeutic drugs of all types. Efforts to reduce barriers are ongoing and are especially important in low and middle income countries and for children requiring treatment of conditions such as those encountered in pediatric oncology characterized by the risk of life threatening treatment failures. Progress has been made through the efforts of the World Health Organization and regulators in the US and Europe to encourage the development of therapeutic agents for use in pediatrics and measures taken have fostered the availability of stronger pediatric data to guide therapeutic decisions. Nonetheless, pharmaceuticals remain a global commodity, subject to regulation by the World Trade Organization and this has often had detrimental effects in low and middle income countries. This article emphasizes the need for closer international collaboration to address the barriers currently impeding access to antineoplastic and supportive care medicines for children. Pediatr Blood Cancer 2014; 61:1513–1517. © 2014 Wiley Periodicals, Inc.

A point has been reached in the pursuit of op- timal 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. From the International Alliance for Better Medici- nes for Children The IABMC has initiated the development of an asset map that will include as broad a cross-section as possible of researchers, educators and clinicians committed to the optimization of pediatric drug therapy.

Most bioequivalence (BE) studies are conducted in males with the assumption that variability in pharmacokinetics is similar between the sexes. The purpose of this single-center, reference replicate study was to determine the effect of sex on the pharmacokinetics and BE of doxylamine-pyridoxine 10 mg-10 mg delayed-release tablets. Healthy males (n = 12) and non-pregnant females (n = 12) were administered two tablets, and blood sampling was conducted from 1 hour pre-dose until 72 hours post-dose. After 21 days, dose administration and blood sampling were re-conducted. All analytes were measured using liquid chromatography-tandem mass-spectrometry. Pharmacokinetic parameters were calculated for each study period using standard, non-compartmental methods, and differences were assessed using ANOVA. BE testing was conducted using the relative 90% confidence interval for the AUC0-t for each analyte. Females had significantly larger AUC0-t for doxylamine, 1,550 ng h/mL (coefficient of variance [CV = 19%]) versus 1,272 ng h/mL (CV = 21%; P ≤ .05), and pyridoxine, 35 ng h/mL, (CV = 43%) versus 25 ng h/mL (CV = 31%; P ≤ .05) compared to males. A higher Cmax for doxylamine was observed in females, 107 ng/mL (CV = 16%), compared to males, 86 ng/mL (CV = 15%) (P ≤ .05). BE testing did not demonstrate bioequivalence between males and females. Pharmacokinetic differences observed between the sexes have implications for future BE studies using doxylamine-pyridoxine.

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.

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.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.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.Half of the BC population18 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.

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.

Until now, there has been no standardized method of performing and presenting budget impact analyses (BIAs) in Canada. Nevertheless, most drug plan managers have been requiring this economic data to inform drug reimbursement decisions. This paper describes the process used to develop the Canadian BIA Guidelines; describes the Guidelines themselves, including the model template; and compares this guidance with other guidance on BIAs. The intended audience includes those who develop, submit or use BIA models, and drug plan managers who evaluate BIA submissions. The Patented Medicine Prices Review Board (PMPRB) initiated the development of the Canadian BIA Guidelines on behalf of the National Prescription Drug Utilisation Information System (NPDUIS). The findings and recommendations from a needs assessment with respect to BIA submissions were reviewed to inform guideline development. In addition, a literature review was performed to identify existing BIA guidance. The detailed guidance was developed on this basis, and with the input of the NPDUIS Advisory Committee, including drug plan managers from multiple provinces in Canada and a representative from the Canadian Agency for Drugs and Technologies in Health. A Microsoft® Excel-based interactive model template was designed to support BIA model development. Input regarding the guidelines and model template was sought from each NPDUIS Advisory Committee member to ensure compatibility with existing drug plan needs. Decisions were made by consensus through multiple rounds of review and discussion. Finally, BIA guidance in Canadian provinces and other countries were compared on the basis of multiple criteria. The BIA guidelines consist of three major sections: Analytic Framework, Inputs and Data Sources, and Reporting Format. The Analytic Framework section contains a discussion of nine general issues surrounding BIAs (model design, analytic perspective, time horizon, target population, costing, scenarios to be compared, the characterisation of uncertainty, discounting, and validation methods). The Inputs and Data Sources section addresses methods for market size estimation, comparator selection, scenario forecasting and drug price estimation. The Reporting Format section describes methods for BIA reporting. The new Canadian BIA Guidelines represent a significant departure from the limited guidance that was previously available from some of the provinces, because they include specific details of the methods of performing BIAs. The Canadian BIA Guidelines differ from the Principles of Good Research Practice for BIAs developed by the International Society for Pharmacoeconomic and Outcomes Research (ISPOR), which provide more general guidance. The Canadian BIA Guidelines and template build upon existing guidance to address the specific requirements of each of the participating drug plans in Canada. Both have been endorsed by the NPDUIS Steering Committee and the PMPRB for the standardization of BIA submissions.

RationaleAccurate 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.ObjectiveTo 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.DesignWeight, 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.ResultsMean (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 ConclusionThe 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.

Naturally occurring retirement communities (NORCs) are broadly defined as communities where individuals either remain or move when they retire. Using the determinants of health model as a base, we hypothesize that some environmental determinants have a different impact on people at different ages. Health benefits to living within NORCs have been observed and likely vary depending upon where the specific NORC exists on the NORC to healthy-NORC spectrum. Some NORC environments are healthier than others for seniors, because the NORC environment has characteristics associated with better health for seniors. Health benefits within healthy NORCs are higher where physical and social environments facilitate greater activity and promote feelings of well-being. Compared to the provision of additional medical or social services, healthy NORCs are a low-cost community-level approach to facilitating healthy aging. Municipal governments should pursue policies that stimulate and support the development of healthy NORCs.

Objective: In a potential attempt to guide antibiotic prescribing based on current clinical evidence and mitigate the spread of antibiotic resistance, in March 2001 the Ontario Drug Benefit programme restricted reimbursement of two fluoroquinolone antibiotics – ciprofloxacin and ofloxacin – to its beneficiaries. Our objective was to determine the impact of this policy on the volume and cost of antibiotic prescribing. Method: Weekly administrative data on antibiotic prescribing volumes and expenditures were analysed between January 1999 and September 2002 to estimate the effect of the policy changes using time series analysis. Results: The policy changes were associated with a statistically significant shift downwards for the fluoroquinolones as a category (1905 fewer prescriptions each week, representing a saving of Can$105,707 a week), driven by a decrease in prescriptions for ciprofloxacin (2084 fewer prescriptions a week, saving Can$129,421 a week). Nitrofurantoin (200 more prescriptions a week, costing an extra Can$2082 a week) and trimethoprim-sulphamethoxazole (532 more prescriptions a week, costing an extra Can$1473 a week) demonstrated a statistically significant shift upwards. The latter also showed a decrease in trend and nitrofurantoin an increase in trend during the time period. There was no statistically significant change in either the total number of antibiotic prescriptions or expenditures associated with the policy of limiting their use. Conclusions: Although no direct cause and effect can be shown with these observational data, the results suggest that the change in reimbursement policy to restrict prescribing of fluoroquinolones decreased their use and associated expenditures. These decreases were offset by increases in the use of other antibiotics. The balance of consequent benefit and harm of these shifts in prescribing patterns needs to be examined carefully. Alternative solutions to encourage appropriate use of antibiotics deserve exploration.

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.

Currently, bioequivalence (BE) studies are carried out exclusively in males, assuming that intrasubject variabilities are similar between the sexes. This article challenges this hypothesis on the basis of available evidence and urges that studies of BE of sufficient power be undertaken in women also for all generic drugs aimed at women.

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.

This chapter addresses ways in which progress made in developed countries can be extended to benefit the much greater number of children resident in low- and middle-income countries (LMIC). According to the World Bank (2013), out of a total child population (0–14 years) of 2.5 billion, approximately 331 million are in low-income countries, with 1,342 million in middle-income countries. In sub-Saharan Africa, 43 % of 936 million people are under the age of 14 and most of these children live in circumstances where system performance and delivery of essential care are compromised by low availability of fiscal resources required. Perhaps most alarmingly, the number of children living in low-income countries continues to escalate rapidly with no expectation that current trends will suddenly change. We must now give priority consideration to how best to prioritize and encourage research activity that will serve the worldwide needs of newborns, infants, children, and youth.

Background: Pediatrics must adopt its own set of practices for assessing the pharmacoeconomics of therapeutics to help those who care for children to provide high-quality, efficient care and allocate resources appropriately. Objective: This article reviews the use of pharmacoeconomic analysis in pediatric research. Discussion: The major components of pharmacoeconomic analysis in pediatrics include health economics; burden of illness; health-technology assessment; disease models; and research on health outcomes, delivery, and policy. In pharmacoeconomic assessments of pediatric health care, impact on health status and impact on health costs must be carefully balanced. Among the issues in pediatric pharmacoeconomics that remain unresolved are the value of such analysis, its use as an aid to decision making (rather than a substitute for judgment), and the need to appraise the quality of pharmacoeconomic studies. Conclusions: Pharmacoeconomic analysis and outcomes research are still experimental tools, especially in the field of pediatrics. However, when properly applied, pharmacoeconomic analysis is a useful addition to technical and value judgments for health care providers and policymakers.

Background: Legislation such as the FDA Modernization Act of 1997 and the Pediatric Rule of 1998 in the United States has fueled pediatric pharmacologic research in developed countries; however, this change has not yet reached developing countries. Objective: This article reviews the obstacles to and priorities for improving pediatric health care in developing countries. Discussion: Information provided by the social and behavioral sciences is now included with that afforded by the basic and clinical sciences in decisions about optimal pharmacologic therapy for adults. This change must also occur in pediatric health care and policy, especially in developing countries, where poverty and illiteracy are key factors in the development and treatment of disease in childhood, and where often at least 50% of the population is younger than 18 years. Maternal illness and illiteracy have also been linked to illness and mortality among children in these countries. Pediatric pharmacologic research should consider the most common communicable diseases as well as those for which there are currently no satisfactory treatments, and should investigate the use of herbal and other natural health products often used to treat children in developing countries. Nutrition, dissemination of drug information, and management of supplies must also be taken into account. Conclusions: The international pediatric community must come together in pursuit of better health outcomes for all children through improved pharmacotherapy.

The pursuit of better drug therapy for children and youth is a public health issue of worldwide concern. Health care practitioners treating children have long appreciated the limitations of research data supporting optimal therapy for their patients. It is a lamentable fact, true even in 2011, that most drugs used in paediatrics have not been adequately studied, although the level of relevant research has recently increased dramatically. International attention became focused on this issue as early as 1968, when Dr Harry Shirkey coined the term ‘therapeutic orphans’ to describe the situation of infants, toddlers and children who, in his view, were being deprived of access to properly validated modern drug therapy (1). Clearly, there are some exceptions to this alarming broad view: adequate studies have been conducted in some drug categories including antibiotics, respiratory therapies, anti seizure treatments, analgesics and vitamins. It is also true that considerable emphasis has sometimes been placed on the study of drugs intended for use in conditions relatively prevalent in childhood including, among others, infections, attention-deficit disorder, autism, asthma and seizures. Canada has been a leader in paediatric therapeutics since a ground-breaking research program started at McGill University (Montreal, Quebec) in the 1970s, which focused on neonatology, drug safety, and the development of drug biotransformation capacity in utero and in infancy. In the 1980s, the University of Toronto (Toronto, Ontario) devoted substantial resources to the fostering of paediatric clinical pharmacology at The Hospital for Sick Children (Toronto), resulting in a world-leading program with important research findings in toxicology, pharmacogenetics, anti-infective therapy, anesthesia, analgesia, oncology, respirology, neonatology and obstetrical pharmacology. In spite of Canada’s international leadership in such therapeutic areas, there has been only limited success in changing the national drug regulatory environment and in securing adequate labelling for most products used in paediatrics. Drug evaluation and regulation evolved steadily throughout the past century as a more sophisticated process of drug discovery resulted in an ever-increasing number of therapeutic entities with potential for use in younger patients. An influence of equal importance has been the recognition of unanticipated toxicities affecting children, in particular, sulfanilamide in the 1930s, chloramphenicol in the 1950s and thalidomide in 1960 (2–4). In 1962, the drug regulatory framework in the United States was overhauled by the amendments to the Food, Drug and Cosmetic Act. In spite of such progress, relatively little parallel attention was paid to drug therapy for children (5–10). Until the early 1990s, paediatric prescribers were usually left without adequate product labelling, but this situation has begun to change through efforts made in the United States and Europe to better serve children through regulatory and policy reform (11,12). Recent data in the United States suggest that most drugs likely to be commonly used in paediatric practice are now receiving appropriate research attention before licensure (13). In 2007, the European community introduced legislation requiring companies filing for licensure of new products to submit a paediatric investigation plan if there was any likelihood of use in children (14). These legislative initiatives are beginning to bear fruit in the form of appropriate product labelling of new products for therapeutic use in infants, toddlers, children and youth, although some would argue that recent progress is still insufficient to the enormity of gaps in evidence-based paediatric treatment. Because of earlier inadequacies in drug evaluation and the lack of a legislative structure to encourage drug investigation in the paediatric population, many older therapies continue to be used without being acceptably studied. This knowledge gap is likely to remain challenging for government decision makers and practitioners as well as for children and families.

Potential child participants in clinical research trials in low-income countries are often vulnerable because of poverty, high morbidity and mortality, inadequate education, and varied local cultural norms. However, vulnerability by itself must not be accepted as an obstacle blocking children from the health benefits that may accrue as an outcome of sound clinical research. As greater emphasis is placed on evidence-based treatment of children, it should be anticipated that there will be a growing call for agreement on principles to guide clinical investigations in low-income countries. There is now general acceptance of the view that children must be protected from non-evidence-based interventions and from substandard treatments. The questions remaining relate to how best to stimulate clinical research activity that will serve the needs of infants, children, and youth in developing countries and how best to assign priority to ethically sound research that will meet their clinical requirements. In low-income countries, 39 % of citizens are 13 years of age or younger, and consequently it is certain that clinical investigations of some new therapeutic products will be conducted there more frequently. This review offers some suggestions for approaches that will help to achieve more effective ethical consideration, including (1) improving the quality of research ethics boards; (2) fostering collaborative partnerships among important stakeholders; (3) making concerted efforts to build capacity; (4) improving the quality of the consent and waiver process; and (5) developing improved governance for harmonized ethics platforms. Continuing support by international organizations is required to sustain the establishment and maintenance of stronger research ethics boards to protect children enrolled in clinical trials. This review underscores the importance of developing a culture of solidarity and true partnership between developed and low-income country organizations, which will allow all those involved, and especially child patients, to benefit from the advancement of therapeutics.

Background A substantial literature suggests that mobile phones have great potential to improve management and survival of acutely ill children in rural Africa. The national strategy of the Ugandan Ministry of Health calls for employment of volunteer community health workers (CHWs) in implementation of Integrated Community Case Management (iCCM) of common illnesses (diarrhea, acute respiratory infection, pneumonia, fever/malaria) affecting children under five years of age. A mobile phone enabled system was developed within iCCM aiming to improve access by CHWs to medical advice and to strengthen reporting of data on danger signs and symptoms for acutely ill children under five years of age. Herein critical steps in development, implementation, and integration of mobile phone technology within iCCM are described. Methods Mechanisms to improve diagnosis, treatment and referral of sick children under five were defined. Treatment algorithms were developed by the project technical team and mounted and piloted on the mobile phones, using an iterative process involving technical support personnel, health care providers, and academic support. Using a purposefully developed mobile phone training manual, CHWs were trained over an intensive five-day course to make timely diagnoses, recognize clinical danger signs, communicate about referrals and initiate treatment with appropriate essential drugs. Performance by CHWs and the accuracy and completeness of their submitted data was closely monitored post training test period and during the subsequent nine month community trial. In the full trial, the number of referrals and correctly treated children, based on the agreed treatment algorithms, was recorded. Births, deaths, and medication stocks were also tracked. Results and Discussion Seven distinct phases were required to develop a robust mobile phone enabled system in support of the iCCM program. Over a nine month period, 96 CHWs were trained to use mobile phones and their competence to initiate a community trial was established through performance monitoring. Conclusion Local information/communication consultants, working in concert with a university based department of pediatrics, can design and implement a robust mobile phone based system that may be anticipated to contribute to efficient delivery of iCCM by trained volunteer CHWs in rural settings in Uganda.

The development of an orphan drug policy with the focus on essential research that may be undertaken in Canada's universities.

It is considered axiomatic by those pursuing better health outcomes that well defined goals and clear timelines are essential to orderly progress. Many attribute to Florence Nightingale (1820–1910) leadership in creating the beginnings of management science by calling for accurate measurement applied to healthcare decision making in the 19th century. This guiding principle recognized in the earlier quotation from Galileo finds a modern counterpart in the Millennium Development Goals (MDG), the focus of this editorial [1]. With important implications for child health, the United Nations Millennium Summit, in 2000, advanced a set of eight development goals and targets intended to create a partnership between developed and developing countries with the aim of eliminating poverty and encouraging economic and social development [1]. Specific reductions in infant/child and maternal mortality were also targeted. The resulting campaign that began at the turn of the century has been endorsed by UN member states presently numbering 193 and by at least 23 international organizations representing civil society [2]. Why is this important to the readers of Pediatric Drugs? The achievement of optimal drug therapy, while not explicitly described, is clearly an element central to the main thrust of the Millennium Campaign. Goal 4, reduce child mortality; Goal 5, improve maternal health; and Goal 6, combat HIV/AIDS, malaria and other diseases [2, 3] are all reliant to some extent on achievement of consistent therapeutic excellence if ambitious targets for reduced morbidity and mortality are to be met. MDG 4 targets a reduction by two-thirds in the 1990 under-5 mortality rate (U5MR) by July 1, 2015. In addition, Goal 8 calls for new partnerships in development, including Target 8e, establishment of cooperative programs with pharmaceutical companies to provide access to affordable drugs in developing countries [3]. Evidence-informed therapy provides an essential foundation for the entire range of preventive and curative interventions in maternal and child health. Reductions in infant and child morbidity and mortality rely on improved nutrition and sanitation coupled with effectively deployed and equitably accessible therapies, including especially those targeting common conditions: micronutrients including trace minerals such as zinc, vitamins, vaccines, antimalarials and antimicrobials. The extent of shortfalls globally in provision of priority medicines for maternal and child health has recently been highlighted [4]. As a key component of the Millennium Campaign, more research about effects and disposition of medicines in the maturing infant and child is also needed. This has partly been accomplished in recent years by facilitation of pediatric clinical trials thanks to regulatory measures in the United States and in the European Union, but also as a result of a more positive attitude to research in children. Children have the same rights as adults to have access to therapies with drugs that are well documented in their own age groups. Although most progress in pediatric pharmacology has been made in developed countries, the clinical results will be applied in future for the benefit of children S. MacLeod (&) Child & Family Research Institute, BC Children’s Hospital, 950 West 28th Ave, Vancouver, BC V5Z 4H4, Canada e-mail: smacleod@cfri.ca

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.

In 2007 the World Health Assembly (WHA) passed WHA resolution 60.20 calling for better medicines for children. This step, long overdue, recognised the need for a coordinated approach to improved prescribing for children with special emphasis on those living in remote and low resource settings. Following the adoption of the WHA resolution, rapid progress has been made in the development of an essential medicines list for children (EMLc) now in its fourth edition. A central issue in the ensuing discussions has been a call for the development of easily adaptable child-friendly formulations. It is generally accepted as axiomatic that improved availability of syrups will not constitute an acceptable answer to this problem because of bulk, weight and problems in transportation. From the earliest days of EMLc development the need has been recognised for easily and reliably dispersible formulations of commonly used therapies, such as amoxicillin. Fortunately, suitable …

The prevalence of general alcohol use in many countries of sub-Saharan Africa (SSA) is high. However, research examining alcohol use in among pregnant women within this population is limited. A review of the current status of research examining the prevalence of alcohol exposed pregnancies (AEP) is required to inform future research aiming to decrease this occurrence and its subsequent socio-economic complications.The primary objective was to identify all published papers estimating prevalence and risk-factors of alcohol use among pregnant women in SSA. A secondary objective was to determine changes in alcohol use following pregnancy recognition.PubMed/Medline, Embase, IPA, CINAHL were systematically searched using MeSH terms and keywords from inception date to March 2013. Studies from SSA reporting prevalence of alcohol use among pregnant women were included.Twelve studies were identified. Studies varied significantly according to design and study population. Prevalence of alcohol use during pregnancy ranged from 2.2%-87%. The most important risk-factors for alcohol use included tobacco use, partner violence, urban living, and having a male partner who drank alcohol. Only three studies examined changes in alcohol use prior to and following pregnancy recognition with absolute reductions of between 9% and 15%.Although the burden of alcohol use during pregnancy is likely a significant problem, limited data currently exist for the majority of SSA countries. Furthermore, significant variation likely exists within various populations. Further research is required to explore alcohol use in pregnancy. Strategies to decrease AEP must be developed and implemented in standard pre-natal care.

The impact of genetic factors on the risk of adverse drug reactions (ADRs) is being increasingly recognized as clinically important. ADR Prioritization Tool (APT) was developed to facilitate the prioritization of drugs and their associated ADRs for future pharmacogenomic studies.To describe a novel tool developed for the prioritization of pharmacogenomic investigation of ADRs and discuss the impact of specific scoring criteria.APT scores were based on 25 key scientific and feasibility criteria relevant for clinical research evaluating the genetic basis of ADRs, with a maximum possible score of 60 points. The tool was independently applied to five ADRs (warfarin-induced bleeding/thrombosis, cisplatin-induced ototoxicity, methotrexate-induced neutropenia, carbamazepine-induced Stevens-Johnson syndrome, and abacavir-induced hypersensitivity) by two researchers. Scores were compared using the intraclass correlation coefficient (ICC) to determine level of agreement.Overall scores for target ADRs ranged from 19.5 to 44 points (33-73% of maximum possible score). Cisplatin-induced ototoxicity, a frequent and severe ADR, received the highest score (44). Lower scores were obtained for abacavir-induced hypersensitivity (19.5) and methotrexate-induced neutropenia (28). High agreement was observed between the scientific, feasibility, and total scores from two reviewers (ICC values = 0.895, 0.980, and 0.983, respectively).Application of APT enables simple and direct comparison of potential study targets for research groups embarking on pharmacogenomic investigation of ADRs. Research teams will be able to identify which study targets are best suited for their research environment and discern how to optimize resource allocation for successful discovery and replication of clinically relevant biomarkers.