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1.  Off-label prescribing for allergic diseases in children 
The majority of drugs prescribed have not been tested in children and safety and efficacy of children’s medicines are frequently supported by low quality of evidence. Therefore, a large percentage of prescriptions for children in the clinical daily practice are used off label. Despite the several recent legislation and regulatory efforts performed worldwide, they have not been successful in increasing availability of medicines adapted to children. Moreover, if we consider that 30% of the prescribed drugs for children are for the respiratory field and only 4% of new investigation projects for children research were proposed to access drugs for respiratory and allergy treatment, there is a clear imbalance of the children needs in this therapeutic area. This narrative review aimed to describe and discuss the off-label use of medicines in the treatment and control of respiratory and allergic diseases in children. It was recognized that a large percentage of prescriptions performed for allergy treatment in daily clinical practice are off label. The clinicians struggle on a daily basis with the responsibility to balance risk-benefits of an off-label prescription while involving the patients and their families in this decision. It is crucial to increase awareness of this reality not only for the clinician, but also to the global organizations and competent authorities. New measures for surveillance of off-label use should be established, namely through population databases implementation. There is a need for new proposal to correct the inconsistency between the priorities for pediatric drug research, frequently dependent on commercial motivations, in order to comply to the true needs of the children, especially on the respiratory and allergy fields.
doi:10.1186/1939-4551-7-4
PMCID: PMC3928583  PMID: 24528848
Child; Preschool child; Off-label use; Unlicensed; Asthma; Urticaria; Atopic dermatitis; Rhinitis; Anti-asthmatic agents; Drugs
2.  Pharmaceutical research in paediatric populations and the new EU Paediatric Legislation: an industry perspective 
A large proportion of medicines used in children are prescribed off-label, and children have often been denied access to new or innovative medications. Because such situation is unethical, the need to obtain paediatric information for medicines used in children seems nowadays a matter of consensus on a global basis. Based on this, it was clear in EU, like what has happened in the US, that there was a need for a legal obligation for Pharmaceutical Companies to perform studies. This new European Paediatric Regulation that entered into force in 2007 opens a new era of European drug regulatory history and will offer a major opportunity to improve children's health through advancements in research by providing a new framework for evaluating the efficacy and safety of medicines for children. But, paediatric development remains challenging and the hurdles of conducting research in paediatric population are numerous. The article presents the new European Paediatric Regulation, illustrates its rationale through paediatric psychopharmacology, and discusses some of its consequences on paediatric research from an industry perspective. Recommendations for further international collaboration are also suggested to make global paediatric development plans.
doi:10.1186/1753-2000-2-38
PMCID: PMC2629463  PMID: 19063723
3.  BCG Vaccination in HIV-Infected Children 
Despite the use of Bacillus Calmette-Guérin (BCG) vaccination for many years, infants and young children exposed to adults with infectious forms of tuberculosis (TB) are at high risk of developing complicated TB disease. This risk is much higher among HIV-infected children, and data on BCG protective efficacy in HIV-infected children is lacking. Recent research on BCG safety in HIV-infected infants has resulted in policy shifts, but implementation is challenging. New approaches to preventing TB among infants and children, particularly HIV-infected infants, are needed. This paper briefly reviews BCG safety and efficacy considerations in HIV-infected infants and discusses other approaches to preventing TB, including new TB vaccines and vaccination strategies.
doi:10.1155/2011/712736
PMCID: PMC3335547  PMID: 22567268
4.  Considering statins for cholesterol-reduction in children if lifestyle and diet changes do not improve their health: a review of the risks and benefits 
Children who appear healthy, even if they have one or more recognized cardiovascular risk factors, do not generally have outcomes of cardiovascular or other vascular disease during childhood. Historically, pediatric medicine has not aggressively screened for or treated cardiovascular risk factors in otherwise healthy children. However, studies such as the P-Day Study (Pathobiological Determinants of Atherosclerosis in Youth), and the Bogalusa Heart Study, indicate that healthy children at remarkably young ages can have evidence of significant atherosclerosis. With the increasing prevalence of pediatric obesity, can we expect more health problems related to the consequences of pediatric dyslipidemia, hypertriglyceridemia, and atherosclerosis in the future? For many years, medications have been available and used in adult populations to treat dyslipidemia. In recent years, reports of short-term safety of some of these medications in children have been published. However, none of these studies have detailed long-term follow-up, and therefore none have described potential late side-effects of early cholesterol-lowering therapy, or potential benefits in terms of reduction of or delay in cardiovascular or other vascular end-points. In 2007, the American Heart Association published a scientific statement on the use of cholesterol-lowering therapy in pediatric patients. In this review paper, we discuss some of the current literature on cholesterol-lowering therapy in children, including the statins that are currently available for use in children, and some of the cautions with using these and other cholesterol-lowering medications. A central tenet of this review is that medications are not a substitute for dietary and lifestyle interventions, and that even in children on cholesterol-lowering medications, physicians should take every opportunity to encourage children and their parents to make healthy diet and lifestyle choices.
doi:10.2147/VHRM.S7356
PMCID: PMC3037084  PMID: 21339908
cholesterol; statins; children; adolescents; vascular risk
5.  Safety of a New Chewable Formulation of Mebendazole for Preventive Chemotherapy Interventions to Treat Young Children in Countries with Moderate-to-High Prevalence of Soil Transmitted Helminth Infections 
Journal of Tropical Medicine  2012;2012:590463.
The primary objective was to evaluate the safety and tolerability of the new chewable formulation of mebendazole to treat soil-transmitted helminth (STH) infections in children ≤10 years old with the goal of using this formulation in preventive chemotherapy programs and expand treatment to young children who are unable to swallow solid tablets. In this open-label, single-arm, phase 3 study conducted at Pemba Island, Zanzibar, Tanzania, children aged 2 to 10 years (median age: 4 years) were administered a single dose of the mebendazole 500 mg chewable tablet. Safety was assessed 30 minutes after dose and 3 days later. Of the 390 (98%) children who completed the study, 195 (55%) had ≥1 STH infection and 157 (45%) had no infection at baseline. The most common STH infections were Trichuris trichiura (51%), hookworm (16%), and Ascaris lumbricoides (7%). Treatment-emergent adverse events (TEAEs) were experienced by 11% of children. There was no difference in the percentage of children experiencing TEAEs between the age strata of 2–5 years and 6–10 years. Diarrhea was reported only in children aged 2–5 years. No correlation was observed between the type or percentage of AEs and presence or severity of infection. A single dose of mebendazole 500 mg chewable tablet was safe and well tolerated in children aged 2 to 10 years.
doi:10.1155/2012/590463
PMCID: PMC3540782  PMID: 23319961
6.  Dispersible formulation of artemether/lumefantrine: specifically developed for infants and young children 
Malaria Journal  2009;8(Suppl 1):S7.
Infants and children under five years of age are the most vulnerable to malaria with over 1,700 deaths per day from malaria in this group. However, until recently, there were no WHO-endorsed paediatric anti-malarial formulations available.
Artemisinin-based combination therapy is the current standard of care for patients with uncomplicated falciparum malaria in Africa. Artemether/lumefantrine (AL) meets WHO pre-qualification criteria for efficacy, safety and quality. Coartem®, a fixed dose combination of artemether and lumefantrine, has consistently achieved cure rates of >95% in clinical trials. However, AL tablets are inconvenient for caregivers to administer as they need to be crushed and mixed with water or food for infants and young children. Further, in common with other anti-malarials, they have a bitter taste, which may result in children spitting the medicine out and not receiving the full therapeutic dose. There was a clear unmet medical need for a formulation of AL specifically designed for children.
Ahead of a call from WHO for child-friendly medicines, Novartis, working in partnership with Medicines for Malaria Venture (MMV), started the development of a new formulation of AL for infants and young children: Coartem® Dispersible. The excellent efficacy, safety and tolerability already demonstrated by AL tablets were confirmed with dispersible AL in a large trial comparing the crushed tablets with dispersible tablets in 899 African children with falciparum malaria. In the evaluable population, 28-day PCR-corrected cure rates of >96% were achieved. Further, its sweet taste means that it is palatable for children, and the dispersible formulation makes it easier for caregivers to administer than bitter crushed tablets. Easing administration may foster compliance, hence improving therapeutic outcomes in infants and young children and helping to preserve the efficacy of ACT.
doi:10.1186/1475-2875-8-S1-S7
PMCID: PMC2760242  PMID: 19818174
7.  Web-Based eHealth to Support Counseling in Routine Well-Child Care: Pilot Study of E-health4Uth Home Safety 
JMIR Research Protocols  2013;2(1):e9.
Background
Providing safety education to parents of young children is important in the prevention of unintentional injuries in or around the home. We developed a Web-based, tailored safety advice module to support face-to-face counseling in the setting of preventive youth health care (E-health4Uth home safety) in order to improve the provision of safety information for parents of young children.
Objective
This pilot study evaluated a Web-based, tailored safety advice module (E-health4Uth home safety) and evaluated the use of E-health4Uth home safety to support counseling in routine well-child care visits.
Methods
From a preventive youth health care center, 312 parents with a child aged 10-31 months were assigned to the E-health4Uth home safety condition or to the care-as-usual condition (provision of a generic safety information leaflet). All parents completed a questionnaire either via the Internet or paper-and-pencil, and parents in the E-health4Uth condition received tailored home safety advice either online or by a print that was mailed to their home. This tailored home safety advice was used to discuss the safety of their home during the next scheduled well-child visit. Parents in the care-as-usual condition received a generic safety information leaflet during the well-child visit.
Results
Mean age of the parents was 32.5 years (SD 5.4), 87.8% (274/312) of participants were mothers; mean age of the children was 16.9 months (SD 5.1). In the E-health4Uth condition, 38.4% (61/159) completed the online version of the questionnaire (allowing Web-based tailored safety advice), 61.6% (98/159) preferred to complete the questionnaire via paper (allowing only a hardcopy of the advice to be sent by regular mail). Parents in the E-health4Uth condition evaluated the Web-based, tailored safety advice (n=61) as easy to use (mean 4.5, SD 0.7), pleasant (mean 4.0, SD 0.9), reliable (mean 4.6, SD 0.6), understandable (mean 4.6, SD 0.5), relevant (mean 4.2, SD 0.9), and useful (mean 4.3, SD 0.8). After the well-child visit, no significant differences were found between the E-health4Uth condition and care-as-usual condition with regard to the satisfaction with the information received (n=61, P=.51). Health care professionals (n=43) rated the tailored safety advice as adequate (mean 4.0, SD 0.4) and useful (mean 3.9, SD 0.4).
Conclusions
Less than half of the parents accepted the invitation to complete a Web-based questionnaire to receive online tailored safety advice prior to a face-to-face consultation. Despite wide access to the Internet, most parents preferred to complete questionnaires using paper-and-pencil. In the subgroup that completed E-health4Uth home safety online, evaluations of E-health4Uth home safety were positive. However, satisfaction scores with regard to tailored safety advice were not different from those with regard to generic safety information leaflets.
doi:10.2196/resprot.1862
PMCID: PMC3628163  PMID: 23611794
child health services; eHealth; counseling; health care evaluation mechanisms; health promotion; Internet
8.  'BeSAFE', effect-evaluation of internet-based, tailored safety information combined with personal counselling on parents' child safety behaviours: study design of a randomized controlled trial 
BMC Public Health  2010;10:466.
Background
Injuries in or around the home are the most important cause of death among children aged 0-4 years old. It is also a major source of morbidity and loss of quality of life. In order to reduce the number of injuries, the Consumer Safety Institute introduced the use of Safety Information Leaflets in the Netherlands to provide safety education to parents of children aged 0-4 years. Despite current safety education, necessary safety behaviours are still not taken by a large number of parents, causing unnecessary risk of injury among young children. In an earlier study an E-health module with internet-based, tailored safety information was developed and applied. It concerns an advice for parents on safety behaviours in their homes regarding their child. The aim of this study is to evaluate the effect of this safety information combined with personal counselling on parents' child safety behaviours.
Methods/Design
Parents who are eligible for the regular well-child visit with their child at child age 5-8 months are invited to participate in this study. Participating parents are randomized into one of two groups: 1) internet-based, tailored safety information combined with personal counselling (intervention group), or 2) personal counselling using the Safety Information Leaflets of the Consumer Safety Institute in the Netherlands for children aged 12 to 24 months (control group). All parents receive safety information on safety topics regarding the prevention of falling, poisoning, drowning and burning. Parents of the intervention group will access the internet-based, tailored safety information module when their child is approximately 10 months old. After completion of the assessment questions, the program compiles a tailored safety advice. The parents are asked to devise and inscribe a personal implementation intention. During the next well-child visit, the Child Health Clinic professional will discuss this tailored safety information and the implementation intention with the parents. The control group will receive usual care, i.e. the provision of Safety Information Leaflets during their well-child visit at the child's age of 11 months.
Discussion
It is hypothesized that the intervention, internet-based, tailored safety information combined with personal counselling results in more parents' child safety behaviours.
Trial registration
Current Controlled Trials NTR1836
doi:10.1186/1471-2458-10-466
PMCID: PMC2924290  PMID: 20696070
9.  Number of Patients Studied Prior to Approval of New Medicines: A Database Analysis 
PLoS Medicine  2013;10(3):e1001407.
In an evaluation of medicines approved by the European Medicines Agency 2000 to 2010, Ruben Duijnhoven and colleagues find that the number of patients evaluated for medicines approved for chronic use are inadequate for evaluation of safety or long-term efficacy.
Background
At the time of approval of a new medicine, there are few long-term data on the medicine's benefit–risk balance. Clinical trials are designed to demonstrate efficacy, but have major limitations with regard to safety in terms of patient exposure and length of follow-up. This study of the number of patients who had been administered medicines at the time of medicine approval by the European Medicines Agency aimed to determine the total number of patients studied, as well as the number of patients studied long term for chronic medication use, compared with the International Conference on Harmonisation's E1 guideline recommendations.
Methods and Findings
All medicines containing new molecular entities approved between 2000 and 2010 were included in the study, including orphan medicines as a separate category. The total number of patients studied before approval was extracted (main outcome). In addition, the number of patients with long-term use (6 or 12 mo) was determined for chronic medication. 200 unique new medicines were identified: 161 standard and 39 orphan medicines. The median total number of patients studied before approval was 1,708 (interquartile range [IQR] 968–3,195) for standard medicines and 438 (IQR 132–915) for orphan medicines. On average, chronic medication was studied in a larger number of patients (median 2,338, IQR 1,462–4,135) than medication for intermediate (878, IQR 513–1,559) or short-term use (1,315, IQR 609–2,420). Safety and efficacy of chronic use was studied in fewer than 1,000 patients for at least 6 and 12 mo in 46.4% and 58.3% of new medicines, respectively. Among the 84 medicines intended for chronic use, 68 (82.1%) met the guideline recommendations for 6-mo use (at least 300 participants studied for 6 mo and at least 1,000 participants studied for any length of time), whereas 67 (79.8%) of the medicines met the criteria for 12-mo patient exposure (at least 100 participants studied for 12 mo).
Conclusions
For medicines intended for chronic use, the number of patients studied before marketing is insufficient to evaluate safety and long-term efficacy. Both safety and efficacy require continued study after approval. New epidemiologic tools and legislative actions necessitate a review of the requirements for the number of patients studied prior to approval, particularly for chronic use, and adequate use of post-marketing studies.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Before any new medicine is marketed for the treatment of a human disease, it has to go through extensive laboratory and clinical research. In the laboratory, scientists investigate the causes of diseases, identify potential new treatments, and test these interventions in disease models, some of which involve animals. The safety and efficacy of potential new interventions is then investigated in a series of clinical trials—studies in which the new treatment is tested in selected groups of patients under strictly controlled conditions, first to determine whether the drug is tolerated by humans and then to assess its efficacy. Finally, the results of these trials are reviewed by the government body responsible for drug approval; in the US, this body is the Food and Drug Administration, and in the European Union, the European Medicines Agency (EMA) is responsible for the scientific evaluation and approval of new medicines.
Why Was This Study Done?
Clinical trials are primarily designed to test the efficacy—the ability to produce the desired therapeutic effect—of new medicines. The number of patients needed to establish efficacy determines the size of a clinical trial, and the indications for which efficacy must be shown determine the trial's duration. However, identifying adverse effects of drugs generally requires the drug to be taken by more patients than are required to show efficacy, so the information about adverse effects is often relatively limited at the end of clinical testing. Consequently, when new medicines are approved, their benefit–risk ratios are often poorly defined, even though physicians need this information to decide which treatment to recommend to their patients. For the evaluation of risk or adverse effects of medicines being developed for chronic (long-term) treatment of non-life-threatening diseases, current guidelines recommend that at least 1,000–1,500 patients are exposed to the new drug and that 300 and 100 patients use the drug for six and twelve months, respectively, before approval. But are these guidelines being followed? In this database analysis, the researchers use data collected by the EMA to determine how many patients are exposed to new medicines before approval in the European Union and how many are exposed for extended periods of time to medicines intended for chronic use.
What Did the Researchers Do and Find?
Using the European Commission's Community Register of Medicinal Products, the researchers identified 161 standard medicines and 39 orphan medicines (medicines to treat or prevent rare life-threatening diseases) that contained new active substances and that were approved in the European Union between 2000 and 2010. They extracted information on the total number of patients studied and on the number exposed to the medicines for six months and twelve months before approval of each medicine from EMA's European public assessment reports. The average number of patients studied before approval was 1,708 for standard medicines and 438 for orphan medicines (marketing approval is easier to obtain for orphan medicines than for standard medicines to encourage drug companies to develop medicines that might otherwise be unprofitable). On average, medicines for chronic use (for example, asthma medications) were studied in more patients (2,338) than those for intermediate use such as anticancer drugs (878), or short-term use such as antibiotics (1,315). The safety and efficacy of chronic use was studied in fewer than 1,000 patients for at least six and twelve months in 46.4% and 58.4% of new medicines, respectively. Finally, among the 84 medicines intended for chronic use, 72 were studied in at least 300 patients for six months, and 70 were studied in at least 100 patients for twelve months.
What Do These Findings Mean?
These findings suggest that although the number of patients studied before approval is sufficient to determine the short-term efficacy of new medicines, it is insufficient to determine safety or long-term efficacy. Any move by drug approval bodies to require pharmaceutical companies to increase the total number of patients exposed to a drug, or the number exposed for extended periods of time to drugs intended for chronic use, would inevitably delay the entry of new products into the market, which likely would be unacceptable to patients and healthcare providers. Nevertheless, the researchers suggest that a reevaluation of the study size and long-term data requirements that need to be met for the approval of new medicines, particularly those designed for long-term use, is merited. They also stress the need for continued study of both the safety and efficacy of new medicines after approval and the importance of post-marketing studies that actively examine safety issues.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001407.
The European Medicines Agency (EMA) provides information about all aspects of the scientific evaluation and approval of new medicines in the European Union; its European public assessment reports are publicly available
The European Commission's Community Register of Medicinal Products is a publicly searchable database of medicinal products approved for human use in the European Union
The US Food and Drug Administration provides information about drug approval in the US for consumers and for health professionals
The US National Institutes of Health provides information (including personal stories) about clinical trials
doi:10.1371/journal.pmed.1001407
PMCID: PMC3601954  PMID: 23526887
10.  A novel scheme for the reporting of adverse drug reactions 
Archives of Disease in Childhood  2001;84(4):337-339.
BACKGROUND—The safety of medicines used in children is of considerable public interest, yet available data to monitor the safety of medicines in children is limited.
AIMS—To raise awareness and stimulate reporting of adverse drug reactions (ADRs) in children in the Trent region.
METHODS—A pilot Paediatric Regional Monitoring Centre (PRMC) has been established in the Trent region. The scheme operates as an extension of the UK's spontaneous reporting scheme, the Yellow Card Scheme run by the Medicines Control Agency and the Committee on Safety of Medicines. Proactive interventions including a monthly reminder letter and presentations to staff in the identified hospitals have been made.
RESULTS—During the first year of the PRMC, 95 reports were received from the Trent region compared to 40 for the previous year. Twenty four of these reports were for medicines used "off label". The 95 reports involved 105 drugs and 171 suspected ADRs. Twenty six of the ADRs (15%) were considered medically significant.
CONCLUSIONS—The number of ADR reports from the Trent region has increased considerably in the first year of the scheme. The results show that intensive education and promotion of ADR reporting can result in a major increase in reporting. This initiative will increase our knowledge about the safety of medicines used to treat children and so help protect public health.


doi:10.1136/adc.84.4.337
PMCID: PMC1718721  PMID: 11259235
11.  Implementing the 2009 Institute of Medicine recommendations on resident physician work hours, supervision, and safety 
Long working hours and sleep deprivation have been a facet of physician training in the US since the advent of the modern residency system. However, the scientific evidence linking fatigue with deficits in human performance, accidents and errors in industries from aeronautics to medicine, nuclear power, and transportation has mounted over the last 40 years. This evidence has also spawned regulations to help ensure public safety across safety-sensitive industries, with the notable exception of medicine.
In late 2007, at the behest of the US Congress, the Institute of Medicine embarked on a year-long examination of the scientific evidence linking resident physician sleep deprivation with clinical performance deficits and medical errors. The Institute of Medicine’s report, entitled “Resident duty hours: Enhancing sleep, supervision and safety”, published in January 2009, recommended new limits on resident physician work hours and workload, increased supervision, a heightened focus on resident physician safety, training in structured handovers and quality improvement, more rigorous external oversight of work hours and other aspects of residency training, and the identification of expanded funding sources necessary to implement the recommended reforms successfully and protect the public and resident physicians themselves from preventable harm.
Given that resident physicians comprise almost a quarter of all physicians who work in hospitals, and that taxpayers, through Medicare and Medicaid, fund graduate medical education, the public has a deep investment in physician training. Patients expect to receive safe, high-quality care in the nation’s teaching hospitals. Because it is their safety that is at issue, their voices should be central in policy decisions affecting patient safety. It is likewise important to integrate the perspectives of resident physicians, policy makers, and other constituencies in designing new policies. However, since its release, discussion of the Institute of Medicine report has been largely confined to the medical education community, led by the Accreditation Council for Graduate Medical Education (ACGME).
To begin gathering these perspectives and developing a plan to implement safer work hours for resident physicians, a conference entitled “Enhancing sleep, supervision and safety: What will it take to implement the Institute of Medicine recommendations?” was held at Harvard Medical School on June 17–18, 2010. This White Paper is a product of a diverse group of 26 representative stakeholders bringing relevant new information and innovative practices to bear on a critical patient safety problem. Given that our conference included experts from across disciplines with diverse perspectives and interests, not every recommendation was endorsed by each invited conference participant. However, every recommendation made here was endorsed by the majority of the group, and many were endorsed unanimously. Conference members participated in the process, reviewed the final product, and provided input before publication. Participants provided their individual perspectives, which do not necessarily represent the formal views of any organization.
In September 2010 the ACGME issued new rules to go into effect on July 1, 2011. Unfortunately, they stop considerably short of the Institute of Medicine’s recommendations and those endorsed by this conference. In particular, the ACGME only applied the limitation of 16 hours to first-year resident physicans. Thus, it is clear that policymakers, hospital administrators, and residency program directors who wish to implement safer health care systems must go far beyond what the ACGME will require. We hope this White Paper will serve as a guide and provide encouragement for that effort.
Resident physician workload and supervision
By the end of training, a resident physician should be able to practice independently. Yet much of resident physicians’ time is dominated by tasks with little educational value. The caseload can be so great that inadequate reflective time is left for learning based on clinical experiences. In addition, supervision is often vaguely defined and discontinuous. Medical malpractice data indicate that resident physicians are frequently named in lawsuits, most often for lack of supervision. The recommendations are: The ACGME should adjust resident physicians workload requirements to optimize educational value. Resident physicians as well as faculty should be involved in work redesign that eliminates nonessential and noneducational activity from resident physician dutiesMechanisms should be developed for identifying in real time when a resident physician’s workload is excessive, and processes developed to activate additional providersTeamwork should be actively encouraged in delivery of patient care. Historically, much of medical training has focused on individual knowledge, skills, and responsibility. As health care delivery has become more complex, it will be essential to train resident and attending physicians in effective teamwork that emphasizes collective responsibility for patient care and recognizes the signs, both individual and systemic, of a schedule and working conditions that are too demanding to be safeHospitals should embrace the opportunities that resident physician training redesign offers. Hospitals should recognize and act on the potential benefits of work redesign, eg, increased efficiency, reduced costs, improved quality of care, and resident physician and attending job satisfactionAttending physicians should supervise all hospital admissions. Resident physicians should directly discuss all admissions with attending physicians. Attending physicians should be both cognizant of and have input into the care patients are to receive upon admission to the hospitalInhouse supervision should be required for all critical care services, including emergency rooms, intensive care units, and trauma services. Resident physicians should not be left unsupervised to care for critically ill patients. In settings in which the acuity is high, physicians who have completed residency should provide direct supervision for resident physicians. Supervising physicians should always be physically in the hospital for supervision of resident physicians who care for critically ill patientsThe ACGME should explicitly define “good” supervision by specialty and by year of training. Explicit requirements for intensity and level of training for supervision of specific clinical scenarios should be providedCenters for Medicare and Medicaid Services (CMS) should use graduate medical education funding to provide incentives to programs with proven, effective levels of supervision. Although this action would require federal legislation, reimbursement rules would help to ensure that hospitals pay attention to the importance of good supervision and require it from their training programs
Resident physician work hours
Although the IOM “Sleep, supervision and safety” report provides a comprehensive review and discussion of all aspects of graduate medical education training, the report’s focal point is its recommendations regarding the hours that resident physicians are currently required to work. A considerable body of scientific evidence, much of it cited by the Institute of Medicine report, describes deteriorating performance in fatigued humans, as well as specific studies on resident physician fatigue and preventable medical errors.
The question before this conference was what work redesign and cultural changes are needed to reform work hours as recommended by the Institute of Medicine’s evidence-based report? Extensive scientific data demonstrate that shifts exceeding 12–16 hours without sleep are unsafe. Several principles should be followed in efforts to reduce consecutive hours below this level and achieve safer work schedules. The recommendations are: Limit resident physician work hours to 12–16 hour maximum shiftsA minimum of 10 hours off duty should be scheduled between shiftsResident physician input into work redesign should be actively solicitedSchedules should be designed that adhere to principles of sleep and circadian science; this includes careful consideration of the effects of multiple consecutive night shifts, and provision of adequate time off after night work, as specified in the IOM reportResident physicians should not be scheduled up to the maximum permissible limits; emergencies frequently occur that require resident physicians to stay longer than their scheduled shifts, and this should be anticipated in scheduling resident physicians’ work shiftsHospitals should anticipate the need for iterative improvement as new schedules are initiated; be prepared to learn from the initial phase-in, and change the plan as neededAs resident physician work hours are redesigned, attending physicians should also be considered; a potential consequence of resident physician work hour reduction and increased supervisory requirements may be an increase in work for attending physicians; this should be carefully monitored, and adjustments to attending physician work schedules made as needed to prevent unsafe work hours or working conditions for this group“Home call” should be brought under the overall limits of working hours; work load and hours should be monitored in each residency program to ensure that resident physicians and fellows on home call are getting sufficient sleepMedicare funding for graduate medical education in each hospital should be linked with adherence to the Institute of Medicine limits on resident physician work hours
Moonlighting by resident physicians
The Institute of Medicine report recommended including external as well as internal moonlighting in working hour limits. The recommendation is: All moonlighting work hours should be included in the ACGME working hour limits and actively monitored. Hospitals should formalize a moonlighting policy and establish systems for actively monitoring resident physician moonlighting
Safety of resident physicians
The “Sleep, supervision and safety” report also addresses fatigue-related harm done to resident physicians themselves. The report focuses on two main sources of physical injury to resident physicians impaired by fatigue, ie, needle-stick exposure to blood-borne pathogens and motor vehicle crashes. Providing safe transportation home for resident physicians is a logistical and financial challenge for hospitals. Educating physicians at all levels on the dangers of fatigue is clearly required to change driving behavior so that safe hospital-funded transport home is used effectively. Fatigue-related injury prevention (including not driving while drowsy) should be taught in medical school and during residency, and reinforced with attending physicians; hospitals and residency programs must be informed that resident physicians’ ability to judge their own level of impairment is impaired when they are sleep deprived; hence, leaving decisions about the capacity to drive to impaired resident physicians is not recommendedHospitals should provide transportation to all resident physicians who report feeling too tired to drive safely; in addition, although consecutive work should not exceed 16 hours, hospitals should provide transportation for all resident physicians who, because of unforeseen reasons or emergencies, work for longer than consecutive 24 hours; transportation under these circumstances should be automatically provided to house staff, and should not rely on self-identification or request
Training in effective handovers and quality improvement
Handover practice for resident physicians, attendings, and other health care providers has long been identified as a weak link in patient safety throughout health care settings. Policies to improve handovers of care must be tailored to fit the appropriate clinical scenario, recognizing that information overload can also be a problem. At the heart of improving handovers is the organizational effort to improve quality, an effort in which resident physicians have typically been insufficiently engaged. The recommendations are: Hospitals should train attending and resident physicians in effective handovers of careHospitals should create uniform processes for handovers that are tailored to meet each clinical setting; all handovers should be done verbally and face-to-face, but should also utilize written toolsWhen possible, hospitals should integrate hand-over tools into their electronic medical records (EMR) systems; these systems should be standardized to the extent possible across residency programs in a hospital, but may be tailored to the needs of specific programs and services; federal government should help subsidize adoption of electronic medical records by hospitals to improve signoutWhen feasible, handovers should be a team effort including nurses, patients, and familiesHospitals should include residents in their quality improvement and patient safety efforts; the ACGME should specify in their core competency requirements that resident physicians work on quality improvement projects; likewise, the Joint Commission should require that resident physicians be included in quality improvement and patient safety programs at teaching hospitals; hospital administrators and residency program directors should create opportunities for resident physicians to become involved in ongoing quality improvement projects and root cause analysis teams; feedback on successful quality improvement interventions should be shared with resident physicians and broadly disseminatedQuality improvement/patient safety concepts should be integral to the medical school curriculum; medical school deans should elevate the topics of patient safety, quality improvement, and teamwork; these concepts should be integrated throughout the medical school curriculum and reinforced throughout residency; mastery of these concepts by medical students should be tested on the United States Medical Licensing Examination (USMLE) stepsFederal government should support involvement of resident physicians in quality improvement efforts; initiatives to improve quality by including resident physicians in quality improvement projects should be financially supported by the Department of Health and Human Services
Monitoring and oversight of the ACGME
While the ACGME is a key stakeholder in residency training, external voices are essential to ensure that public interests are heard in the development and monitoring of standards. Consequently, the Institute of Medicine report recommended external oversight and monitoring through the Joint Commission and Centers for Medicare and Medicaid Services (CMS). The recommendations are: Make comprehensive fatigue management a Joint Commission National Patient Safety Goal; fatigue is a safety concern not only for resident physicians, but also for nurses, attending physicians, and other health care workers; the Joint Commission should seek to ensure that all health care workers, not just resident physicians, are working as safely as possibleFederal government, including the Centers for Medicare and Medicaid Services and the Agency for Healthcare Research and Quality, should encourage development of comprehensive fatigue management programs which all health systems would eventually be required to implementMake ACGME compliance with working hours a “ condition of participation” for reimbursement of direct and indirect graduate medical education costs; financial incentives will greatly increase the adoption of and compliance with ACGME standards
Future financial support for implementation
The Institute of Medicine’s report estimates that $1.7 billion (in 2008 dollars) would be needed to implement its recommendations. Twenty-five percent of that amount ($376 million) will be required just to bring hospitals into compliance with the existing 2003 ACGME rules. Downstream savings to the health care system could potentially result from safer care, but these benefits typically do not accrue to hospitals and residency programs, who have been asked historically to bear the burden of residency reform costs. The recommendations are: The Institute of Medicine should convene a panel of stakeholders, including private and public funders of health care and graduate medical education, to lay down the concrete steps necessary to identify and allocate the resources needed to implement the recommendations contained in the IOM “Resident duty hours: Enhancing sleep, supervision and safety” report. Conference participants suggested several approaches to engage public and private support for this initiativeEfforts to find additional funding to implement the Institute of Medicine recommendations should focus more broadly on patient safety and health care delivery reform; policy efforts focused narrowly upon resident physician work hours are less likely to succeed than broad patient safety initiatives that include residency redesign as a key componentHospitals should view the Institute of Medicine recommendations as an opportunity to begin resident physician work redesign projects as the core of a business model that embraces safety and ultimately saves resourcesBoth the Secretary of Health and Human Services and the Director of the Centers for Medicare and Medicaid Services should take the Institute of Medicine recommendations into consideration when promulgating rules for innovation grantsThe National Health Care Workforce Commission should consider the Institute of Medicine recommendations when analyzing the nation’s physician workforce needs
Recommendations for future research
Conference participants concurred that convening the stakeholders and agreeing on a research agenda was key. Some observed that some sectors within the medical education community have been reluctant to act on the data. Several logical funders for future research were identified. But above all agencies, Centers for Medicare and Medicaid Services is the only stakeholder that funds graduate medical education upstream and will reap savings downstream if preventable medical errors are reduced as a result of reform of resident physician work hours.
doi:10.2147/NSS.S19649
PMCID: PMC3630963  PMID: 23616719
resident; hospital; working hours; safety
12.  Safety, Immunogenicity and Duration of Protection of the RTS,S/AS02D Malaria Vaccine: One Year Follow-Up of a Randomized Controlled Phase I/IIb Trial 
PLoS ONE  2010;5(11):e13838.
Background
The RTS,S/AS02D vaccine has been shown to have a promising safety profile, to be immunogenic and to confer protection against malaria in children and infants.
Methods and Findings
We did a randomized, controlled, phase I/IIb trial of RTS,S/AS02D given at 10, 14 and 18 weeks of age staggered with routine immunization vaccines in 214 Mozambican infants. The study was double-blind until the young child completed 6 months of follow-up over which period vaccine efficacy against new Plasmodium falciparum infections was estimated at 65.9% (95% CI 42.6–79.8, p<0.0001). We now report safety, immunogenicity and estimated efficacy against clinical malaria up to 14 months after study start. Vaccine efficacy was assessed using Cox regression models. The frequency of serious adverse events was 32.7% in the RTS,S/AS02D and 31.8% in the control group. The geometric mean titers of anti-circumsporozoite antibodies declined from 199.9 to 7.3 EU/mL from one to 12 months post dose three of RTS,S/AS02D, remaining 15-fold higher than in the control group. Vaccine efficacy against clinical malaria was 33% (95% CI: −4.3–56.9, p = 0.076) over 14 months of follow-up. The hazard rate of disease per 2-fold increase in anti-CS titters was reduced by 84% (95% CI 35.1–88.2, p = 0.003).
Conclusion
The RTS,S/AS02D malaria vaccine administered to young infants has a good safety profile and remains efficacious over 14 months. A strong association between anti-CS antibodies and risk of clinical malaria has been described for the first time. The results also suggest a decrease of both anti-CS antibodies and vaccine efficacy over time.
Trial Registration
ClinicalTrials.gov NCT00197028
doi:10.1371/journal.pone.0013838
PMCID: PMC2973956  PMID: 21079803
13.  Pharmacokinetic research in children: an analysis of registered records of clinical trials 
BMJ Open  2011;1(1):e000221.
Background
Reported off-label/unlicensed prescribing rates in children range from 11% to 80%. Research into pharmacokinetic profiles of children's medicines is essential in the creation of more knowledge on the safety and efficacy of medicines in children. This study investigated how often pharmacokinetic data are collected in clinical trials of medicines in children by analysing registered records of clinical trials.
Methods
The registered records of all clinical trials in children that were recruiting on 22 May 2009 were identified on the International Clinical Trials Registry Platform using a Clinical Trials in Children search filter. The records of trials in children below 12 years of age, in which the intervention was one or more medicines, were assessed for evidence that pharmacokinetic data would be collected.
Results
Of 1081 eligible trial records, 257 (24%) declared that pharmacokinetic data would be collected. Of these trials, 199 (77%) recruited in Northern America; recruitment in all other regions was below 20%. Trials recruited most often in children over 2 years of age (74%), and least often in newborn infants (32%). Most trials researched medicines in the field of cancer (29%). Trials investigated one-third of the medicines that were indicated as a priority for pharmacokinetic research by the European Medicines Agency.
Conclusions
There is a need for increased knowledge of the pharmacokinetic profiles of children's medicines. The amount of currently ongoing pharmacokinetic research does not seem to address adequately the lack of knowledge in this area. This study sets a baseline for monitoring of future progress on the amount of ongoing pharmacokinetic research in children.
Article summary
Article focus
The main aim of this study was to assess how many registered records of clinical trials of medicines that were recruiting children and were identifiable on the International Clinical Trials Registry Platform Search Portal contained evidence that pharmacokinetic data would be collected.
Secondary aims were to assess which pharmacokinetic data were collected and what types of trials were reporting pharmacokinetic data.
Key messages
This study quantifies, for the first time, the amount of currently ongoing research into pharmacokinetic profiles of medicines in children.
It shows how much and what kind of pharmacokinetic research is being carried out worldwide as registered at clinical trial registries and analyses the types of trials that perform this research.
It sets a baseline for future studies, to monitor progress in the amount of pharmacokinetic research that is performed in children.
Strengths and limitations of this study
Our study is one of the first studies of its kind, in that it has created a comprehensive oversight of the amount of ongoing research in one particular research area, by analysing information in registered records of clinical trials. Using information in clinical trial databases as such offers a unique, and currently underused, method for informing future research prioritisation efforts at a policy level (in our case of paediatric off-patent medicines by the European Medicines Agency).
This study is limited by the quality of information in the included registered records. Studying registered records of clinical trials is not the same as studying how clinical trials were in fact conducted. However, in the absence of open access to complete trial protocols we have no other choice than to use the information entered into a trial registry for this type of analysis.
doi:10.1136/bmjopen-2011-000221
PMCID: PMC3191584  PMID: 22021789
Public health; statistics &research methods; pharmacokinetics; clinical trials registration; paediatrics; pharmacology; clinical trial
14.  Current and emerging therapies in multiple sclerosis: a systematic review 
Multiple sclerosis (MS) is a potentially disabling chronic autoimmune neurological disease that mainly affects young adults. Our understanding of the pathophysiology of MS has significantly advanced in the past quarter of a century. This has led to the development of many disease-modifying therapies (DMTs) that prevent exacerbations and new lesions in patients with relapsing remitting MS (RRMS). So far there is no drug available that can completely halt the neurodegenerative changes associated with the disease. It is the purpose of this review to provide concise information regarding mechanism of action, indications, side effects and safety of Food and Drug Administration and European Medicines Agency approved agents for MS, emerging therapies, and drugs that can be considered for off-label use in MS.
doi:10.1177/1756285612450936
PMCID: PMC3388530  PMID: 22783370
disease-modifying therapies; emerging therapies; fingolimod; glatiramer acetate; interferon β; multiple sclerosis; natalizumab
15.  Group interventions for the prevention of injuries in young children: a systematic review 
Injury Prevention  2005;11(3):143-147.
Objective: This systematic review examined group based injury prevention interventions that targeted young children to determine the effectiveness of such strategies in enhancing children's safety behaviors.
Methods: A comprehensive (manual and electronic) search of the literature was performed using the following study selection criteria: (1) intervention engaged children under the age of 6 years; (2) included a control group; (3) used a group intervention approach; (4) study written in English language; (5) addressed unintentional injuries; and (6) outcomes included injuries, knowledge, or safety behaviors. Data abstraction was performed independently by two researchers using a standardized approach.
Results: Nine studies met the criteria that included safety interventions of road crossing (4), car restraint (2), spinal cord safety (1), poison safety (1), and 911/stranger danger/street crossing (1). The types of interventions included videos, interactive activities, cartoons, stories, puppets, singing, coloring, games, simulation games, demonstrations, modeling/role playing, and rehearsal practice using seat belts, models, and real street crossing. The intensity and duration of interventions varied substantially and only two studies randomly assigned participants. The review revealed a positive effect (knowledge, behaviour, and/or attitude) for five of the studies, three had mixed effect, and one reported no effect.
Conclusions: Although no clear conclusions can be drawn from the limited number of studies of diverse design and rigor, researchers should attempt to minimize shortcomings occurring in community based research. Engaging community partners including teachers and parents who influence relationships and outcomes could provide opportunity for more rigorous, comprehensive, and integrated approach to longitudinal research that could identify key factors of successful strategies.
doi:10.1136/ip.2004.007971
PMCID: PMC1730222  PMID: 15933404
16.  Effectiveness of Web-Based Tailored Advice on Parents’ Child Safety Behaviors: Randomized Controlled Trial 
Background
Injuries at home are a major cause of death, disability, and loss of quality of life among young children. Despite current safety education, required safety behavior of parents is often lacking. To prevent various childhood disorders, the application of Web-based tools has increased the effectiveness of health promotion efforts. Therefore, an intervention with Web-based, tailored, safety advice combined with personal counseling (E-Health4Uth home safety) was developed and applied.
Objective
To evaluate the effect of E-Health4Uth home safety on parents’ safety behaviors with regard to the prevention of falls, poisoning, drowning, and burns.
Methods
A randomized controlled trial was conducted (2009-2011) among parents visiting well-baby clinics in the Netherlands. Parents were randomly assigned to the intervention group (E-Health4Uth home safety intervention) or to the control condition consisting of usual care. Parents in the intervention condition completed a Web-based safety behavior assessment questionnaire; the resulting tailored safety advice was discussed with their child health care professional at a well-baby visit (age approximately 11 months). Parents in the control condition received counseling using generic safety information leaflets at this well-baby visit. Parents’ child safety behaviors were derived from self-report questionnaires at baseline (age 7 months) and at follow-up (age 17 months). Each specific safety behavior was classified as safe/unsafe and a total risk score was calculated. Logistic and linear regression analyses were used to reveal differences in safety behavior between the intervention and the control condition at follow-up.
Results
A total of 1292 parents (response rate 44.79%) were analyzed. At follow-up, parents in the intervention condition (n=643) showed significantly less unsafe behavior compared to parents in the control condition (n=649): top of staircase (23.91% vs 32.19%; OR 0.65, 95% CI 0.50-0.85); bottom of staircase (63.53% vs 71.94%; OR 0.69, 95% CI 0.53-0.88); top and bottom of staircase (68.94% vs 78.28%; OR 0.62, 95% CI 0.48-0.81); storage of cleaning products (30.33% vs 39.91%; OR 0.67, 95% CI 0.53-0.85); bathing of the child (23.46% vs 32.25%; OR 0.65, 95% CI 0.51-0.84); drinking hot fluids (34.84% vs 41.73%; OR 0.76, 95% CI 0.61-0.96); using rear hotplates (79.34% vs 85.27%; OR 0.67, 95% CI 0.50-0.90); and the total risk score in which a higher score indicates more unsafe behavior (mean 13.63, SD 6.12 vs mean 15.34, SD 6.07; beta –1.59, 95% CI –2.26 to –0.93). There were no significant differences for other specific behaviors between the two study conditions.
Conclusions
Compared to generic written materials, the E-Health4Uth home safety intervention seems more effective in promoting parents’ safety behavior for safe staircases, storage of cleaning products, bathing, drinking hot fluids, and cooking. This study supports the application of Web-based, tailored, safety advice for the prevention of unintentional injuries in the youth health care setting.
Trial Registration
Nederlands Trial Register: NTR1836; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1836 (Archived by WebCite at http://www.webcitation.org/6MPIGQxpx).
doi:10.2196/jmir.2521
PMCID: PMC3913924  PMID: 24463421
child; eHealth; injury; parent; prevention; primary care; RCT; safety
17.  Behavioral Vaccines and Evidence Based Kernels: Non-Pharmaceutical Approaches for the Prevention of Mental, Emotional and Behavioral Disorders 1 
In March of 2009, the Institute of Medicine issued a new report on the Prevention of Mental, Emotional and Behavioral Disorders Among Young People.1 Fundamentally, the report calls for ending the rationing of prevention of mental, emotional and behavioral disorders (MEBs) among America’s children, youth and young adults. Continued rationing of access to scientifically proven prevention causes a serious threat to the country’s national security2 and to our economic competitiveness compared to 22 other rich countries.3 Such MEBs are also the leading preventable cost center for local, state and the federal governments.1, 4 These preventable MEBs cause health-care costs to continue to spiral up.
The IOM Report calls for a public-health approach to MEBs—basically like how America and Canada dealt with the polio epidemic, measles, mumps, car passenger injuries to children, and accidental poisoning from medications and toxic chemicals. Why is this necessary? America’s rates of some of these mental, emotional and behavioral problems are worse than other developed countries,5, 6 and rates of some of these problems have objectively increased over the past 20-50 years in America.7 The attributes of a public-health approach for MEBs are defined in the article.
The article discusses multiple examples of how public health approaches might reduce or prevent MEBs using low-cost evidence based kernels, which are fundamental units of behavior. Such kernels can be used repeatedly, which then act as “behavioral vaccines” to reduce morbidity or mortality and/or improve human wellbeing. This document calls for six key policy actions to improve mental, emotional and behavioral health in young people—with resulting wellbeing and economic competiveness of North America and reducing health-care costs.
doi:10.1016/j.psc.2010.11.003
PMCID: PMC3064963  PMID: 21333837
evidence-based kernels; behavioral vaccines; prevention; public-health
18.  Promoting automobile safety belt use by young children. 
A program using behavioral practice, assertiveness training, and social and contrived reinforcers was developed to establish and maintain automobile safety belt use by young children. Sixteen children (ages 4.8 to 7 years) who never used their safety belts during a 5-day preexperimental observation period were randomly assigned to two groups of eight each. A multiple baseline design across groups was used to evaluate the effectiveness of the training program. During the 8-day baseline period for Group 1, no children used their safety belts when unobtrusively observed while being driven from school. During the 26-day intervention period, the children were buckled up on 96% of the observations. Follow-up probes conducted 2-3 months after program discontinuance found safety belt use to range from 86% to 100%. For Group 2, the 14-day baseline safety belt use averaged 6% and increased to a mean of 81% during the 20-day training and maintenance program. Follow-up probes 2-3 months later found safety belt use to occur during 75% to 96% of the observations. Parent questionnaires indicated the generalizability and social validity of the program.
doi:10.1901/jaba.1987.20-133
PMCID: PMC1285963  PMID: 3610893
19.  The safety netting behaviour of first contact clinicians: a qualitative study 
BMC Family Practice  2013;14:140.
Background
Acute illness is common in childhood, and it is difficult for healthcare professionals to distinguish seriously ill children from the vast majority with minor or self-limiting illnesses. Safety netting provides parents with advice on when and where to return if their child deteriorates, and it is widely recommended that parents of acutely sick young children should be given safety netting advice. Yet little is known about how and when this is given. We aimed to understand what safety netting advice first contact clinicians give parents of acutely sick young children, how, when, and why.
Methods
This was a qualitative study. Interviews and focus groups were held with doctors and nurses in a general practice surgery, a District General Hospital emergency department, a paediatric emergency department, and an out-of-hours service. Data were analysed using the method of constant comparison.
Results
Sixteen clinicians participated. They described that safety netting advice includes advising parents what to look for, when and where to seek help. How safety netting was delivered and whether it was verbal or written was inconsistent, and no participants described being trained in this area. Safety netting appeared to be rarely documented, and was left to individual preference. Limitations of written materials, and structural barriers to the provision of safety netting, were perceived. Participants described that safety netting was influenced by clinicians’ experience, confidence, time and knowledge; and perceived parental anxiety, experience, and competence. Participants noted several limitations to safety netting including not knowing if it has been understood by parents or been effective; parental difficulty interpreting information and desire for face-to-face reassurance; and potential over-reassurance.
Conclusion
First contact clinicians employ a range of safety netting techniques, with inconsistencies within and between organisations. Structural changes, clinician training, and documentation in patient notes may improve safety netting provision. Research is needed into the optimal components of safety netting advice so that clinicians can consistently deliver the most effective advice for parents.
doi:10.1186/1471-2296-14-140
PMCID: PMC3849506  PMID: 24066842
Primary health care; Safety netting; Parents; Qualitative research; Acute disease
20.  Pediatric procedural sedation and analgesia 
Procedural sedation and analgesia (PSA) is an evolving field in pediatric emergency medicine. As new drugs breach the boundaries of anesthesia in the Pediatric Emergency Department, parents, patients, and physicians are finding new and more satisfactory methods of sedation. Short acting, rapid onset agents with little or no lingering effects and improved safety profiles are replacing archaic regimens. This article discusses the warning signs and areas of a patient's medical history that are particularly pertinent to procedural sedation and the drugs used. The necessary equipment is detailed to provide the groundwork for implementing safe sedation in children. It is important for practitioners to familiarize themselves with a select few of the PSA drugs, rather than the entire list of sedatives. Those agents most relevant to PSA in the pediatric emergency department are presented.
doi:10.4103/0974-2700.43189
PMCID: PMC2700614  PMID: 19561987
Analgesia; pediatric; sedation
21.  Setting an Agenda for Advancing Young Worker Safety in the U.S. and Canada 
Public Health Reports  2012;127(3):246-252.
Scholars and practitioners from multiple perspectives, including developmental science, sociology, business, medicine, and public health, have considered the implications of employment for young people. We summarize a series of meetings designed to synthesize information from these perspectives and derive recommendations to guide research, practice, and policy with a focus on young worker safety and health. During the first three meetings, participants from the United States and Canada considered invited white papers addressing developmental issues, public health data and findings, as well as programmatic advances and evaluation needs. At the final meeting, the participants recommended both research and policy directions to advance understanding and improve young worker safety.
PMCID: PMC3314067  PMID: 22547854
22.  Medication administered to children from 0 to 7.5 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) 
Objective
To present data on the parentally-reported use of all types of medicinal products in children from 0 to 7.5 years, in a large cohort in south-west England.
Methods
Participants in the population-based Avon Longitudinal Study of Parents and Children (ALSPAC) have been sent self-completion postal questionnaires since they were enrolled during pregnancy. The use of medicinal products has been obtained from questionnaires sent out when the study children were 4 weeks, 54, 78 and 91 months old.
Results
The data included prescription, over-the-counter and complementary and alternative medicines. Around three-quarters of study children were exposed to some form of medicinal product before 8 weeks of age. Dermatological preparations were the most commonly used products in young babies. Activated dimeticone, for treatment of colic and flatulence, was given to 16% of babies and gripe water was used by 13%. Other commonly reported products included oral and topical antifungals and ophthalmic antibiotics. Several OTC products, not licensed for use in this age group, were reported. At each of the older ages surveyed, over 95% of children had used some form of medicinal product within the previous 12–18 months. Use of several product categories was higher at 54 months than at 78 or 91 months, such as topical steroids, analgesics (mostly paracetamol) and systemic antibiotics (mainly amoxicillin). Conversely, use of other categories, such as asthma medication, throat preparations (sprays and lozenges) and anti-inflammatory products, increased with increasing age.
Conclusion
Parentally-reported use of medicinal products in the ALSPAC study children appears to be consistent with data from other sources. The use of medicinal products by young children is high and does not always conform to the product labelling.
doi:10.1007/s00228-006-0231-y
PMCID: PMC1779627  PMID: 17200835
Children; Paediatric drug use; Medication; ALSPAC
23.  Engagement in safety practices to prevent home injuries in preschool children among white and non-white ethnic minority families 
Injury Prevention  2004;10(6):375-378.
Objective: To examine engagement in home safety practices to prevent injuries in preschool children among white and non-white ethnic minority families.
Design: A self completion postal questionnaire assessed sociodemographic characteristics and engagement in home safety practices.
Setting: Deprived areas in the city of Nottingham, United Kingdom.
Subjects: 3906 caregivers of children aged under 5 years.
Main outcome measures: Use of fireguards, stair gates, smoke alarms, window locks and safe storage of medicines, sharp objects, and cleaning products.
Results: Of the 3906 families, 3805 gave their ethnic origin of which 16.5% classed themselves as from a non-white ethnic minority. The safety practices most commonly adopted by respondents were safe storage of medicines (87.9%) and use of smoke alarms (72.3%). Respondents from non-white ethnic minorities were significantly less likely to adopt all safety practices except they were less likely than whites to store sharp objects unsafely (odds ratio (OR) 0.68, 95% confidence interval (CI) 0.56 to 0.84). Those from non-white ethnic minorities were significantly more likely to indicate that they "did not know they could get" fireguards (adjusted OR 6.01, 95% CI 2.64 to 13.65), stair gates (adjusted OR 4.47, 95% CI 1.53 to 13.05), and cupboard locks (adjusted OR 3.96, 95% CI 2.77 to 5.66) than whites. They were also significantly more likely to say they would need help fitting fireguards (adjusted OR 1.98, 95% CI 1.03 to 3.81), stair gates (adjusted OR 3.61, 95% CI 2.11 to 6.17), and cupboard locks (adjusted OR 1.88, 95% CI 1.39 to 2.54).
Conclusions: Our results support the hypothesis that families from non-white ethnic minorities are less likely to engage in some safety practices and illustrate inequalities in access to information regarding the availability and fitting of safety equipment. Further work is required to examine the association between adoption of safety practices and injury rates in children from non-white ethnic minorities.
doi:10.1136/ip.2004.005397
PMCID: PMC1730154  PMID: 15583260
24.  Current guidelines for the management of asthma in young children 
The diagnosis and management of asthma in young children is difficult, since there are many different wheezy phenotypes with varying underlying aetiologies and outcomes. This review discusses the different approaches to managing young children with wheezy illnesses presented in recently published global guidelines. Four major guidelines published since 2007 are considered. Helpful approaches are presented to assist the clinician to decide whether a clinical diagnosis of asthma can, or should be made in a young child with a recurrent wheezy illness and which treatments would be appropriate, dependent on risk factors, age of presentation, response to initial treatment and safety considerations. Each of the guidelines provide useful information for clinicians assessing young children with recurrent wheezy illnesses. There are differences in classification of the disease and treatment protocols. Although a firm diagnosis of asthma may only be made retrospectively in some cases and there are several effective guidelines to initiating treatment. Consistent review of the need for ongoing treatment with a particular pharmacological modality is essential, since many children with recurrent wheezing in infancy go into spontaneous remission. It is probable that newer biomarkers of airway inflammation will assist the clinician as to when to initiate and when to continue pharmacological treatment in the future.
doi:10.4168/aair.2010.2.1.1
PMCID: PMC2831604  PMID: 20224672
Asthma; preschool child; guideline
25.  Surveillance for fatal suspected adverse drug reactions in the UK 
Archives of Disease in Childhood  2002;87(6):462-466.
Aim: To determine the nature and number of suspected adverse drug reactions (ADRs) associated with fatal outcomes in children reported through the yellow card scheme.
Methods: All reports of suspected ADRs with a fatal outcome in children received by the UK Committee on Safety of Medicines through its Yellow Card Scheme from 1964 until December 2000 were reviewed. Reports associated with vaccines and overdose were excluded. The medicine, date of the report, diagnosis, ADR, and the age of the child were analysed. No formal causality assessment was performed.
Results: There were 331 deaths with 390 suspected medicines reported for children aged 16 years or less. Medicines most frequently mentioned were anticonvulsants (65 deaths), cytotoxics (34 deaths), anaesthetic agents (30 deaths), and antibiotics (29 deaths). The individual drug most frequently mentioned was sodium valproate (31 deaths). The nature of the reported ADRs were diverse, with hepatic failure the most frequent. In the past decade, there has been an increase in both the total number of suspected ADRs reported in children and the number of reports with a fatal outcome.
Conclusions: A wide range of suspected ADRs are associated with fatalities in children. Anticonvulsants were associated with the greatest number of reports of fatalities and hepatotoxicity in particular.
doi:10.1136/adc.87.6.462
PMCID: PMC1755830  PMID: 12456539

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