Improving Medicine Use for Children: A Global Imperative.

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.

An International Asset Map of Clinicians, Educators, and Researchers Pursuing Better Medicine Use in Children: Initial Findings.

The world's 1.89 billion children (age 0-14) too frequently receive treatments that have not been validated through clinical pharmacology research, especially in low- and middle-income countries. Initial findings from an international asset map of professionals and clinician scientists available to address the needs for education, research, and treatment support suggest a critical shortage of clinical pharmacologists, clinical pharmacists, and other professionals with advanced training in the evaluation of therapies for childhood conditions and illnesses. A total of 497 individuals responded to a survey conducted between May 2015 and February 2016. An alarming signal is apparent showing that, while the overall resource pool is unquestionably limited, 87% of relevant qualified personnel are located in high-income countries. The data suggest an urgent need for targeted training in pediatric clinical pharmacology, with particular focus on the needs in Africa, Latin America, and most of Asia.

Pediatric clinical drug trials in low-income countries: key ethical issues.

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.

A review of glaucoma treatment in Scotland 1994-2004.

OBJECTIVE: This study evaluated the changing trends in glaucoma management in Scotland between 1994 and 2004. METHODS: A retrospective analysis of national health statistics in Scotland from 1994 to 2004. The Scottish morbidity record was used to collect information on all episodes of trabeculectomy. Data on number of prescriptions were gathered for individual drugs and also for groups of active ingredient. The population likely to have glaucoma (PLG) was calculated from estimates of prevalence in individuals aged 40 years and older, based on published epidemiological studies. The outcome measures were trabeculectomy rates, corrected for population likely to be at risk of glaucoma (PLG), and prescribing volume and cost for glaucoma medications. RESULTS: Trabeculectomy rates have fallen by 67% from 46 per 1,000 PLG in 1994 to 15.4 per 1,000 PLG in 2004. Over the same time period, the population likely to be at risk of glaucoma (PLG) increased by 16.6%. The cost of prescribing has increased by 122% over 11 years compared with an increase in number of items per 1,000 PLG by 27.5%. In 1994, beta-blockers accounted for 65.2% of prescribed drugs but by 2004 this had dropped to 33%. Since their introduction, the prescribing of prostaglandin analogues has increased rapidly and in 2004, they accounted for 39.4% of prescribed drugs. CONCLUSION: The increasing use of prostaglandin analogues has led to an increase in prescribing rates and a rapid increase in cost. At the same time, prescribing of beta-blockers has declined and trabeculectomy rates have fallen.

Impact of antibiotic administrative restrictions on trends in antibiotic resistance.

CONTEXT: In March 2001, in response to concerns about increasing resistance to fluoroquinolone (FQ) antibiotics, the Ontario Drug Benefit (ODB) program limited reimbursement of FQs to ODB beneficiaries defined as high risk or in whom other therapies are not tolerated. OBJECTIVE: To analyze the impact of the limited use (LU) policy changes on antibiotic resistance rates in Ontario, focussing on community-acquired pathogens. DESIGN: Ontario data submitted to the Canadian Bacterial Surveillance Network (CBSN) between January 1, 1998 and June 30, 2002 were analyzed for rates of resistance in various pathogen-antibiotic combinations. The effect of the LU policy on the level and rate of change of antibiotic resistance was estimated using time series models. RESULTS: Resistance rates for S. pneumoniae were 10-12% for penicillin, erythromycin and trimethoprim sulfamethoxazole (TMP/SMX) and less than 3% for amoxicillin and all three FQs tested. There was a statistically significant increasing trend in resistance rates of S. pneumoniae to amoxicillin and levofloxacin throughout the study period. Antibiotic resistance of S. pneumoniae to ciprofloxacin indicated a statistically significant decreasing trend over the study period with a statistically significant increase in the level of antibiotic resistance at the time of the LU policy implementation. No other indication of any statistically significant decrease in resistance rates associated with the LU policy was found. CONCLUSIONS: Although no direct cause and effect can be proven with these observational data, there is no evidence that the limited use policy to restrict fluoroquinolones decreased antibiotic resistance in any of the pathogen-antibiotic combinations tested.

Observations on the adherence of Proteus mirabilis onto polymer surfaces.

AIMS: Infection of the catheterized urinary tract with Proteus mirabilis causes blockage of the catheter by crystalline bacterial biofilms. The aim of this work is to identify a surface-coating for catheters that is not vulnerable to colonization by Pr. mirabilis. METHODS AND RESULTS: A parallel-plate flow-cell and phase contrast microscopy were used to follow bacterial adhesion onto polymer films. Experiments with a urease-negative mutant of Pr. mirabilis suspended in buffer or urine, identified agarose as a polymer on which biofilm did not form. In tests with wild-type urease-producing cells in urine, no adhesion of cells onto agarose was observed for 3 h but then as the pH rose above 8.2, the surface rapidly became colonized by crystalline biofilm. CONCLUSIONS: In urine at pH below 8.0, Pr. mirabilis does not adhere to agarose-coated surfaces. When the pH rises above 8.2, however, aggregates of crystals and bacteria form in the urine and are deposited on such surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: Strategies to prevent the formation of crystalline biofilms on urinary catheters will need to consider both the properties of the surface-coatings and the requirement to prevent the alkaline conditions that induce crystal formation in urine.

Experimental keloid scar models: a review of methodological issues.

BACKGROUND: Keloid scars are benign fibrous proliferations in the dermis that arise after dermal trauma. The scars are raised in appearance and extend beyond the boundaries of the original wound. Scarring in predisposed individuals is out of proportion to the severity of the inciting wound. Current treatments sometimes yield early benefit but scars often resume exuberant growth. The pathophysiology of keloid scars is still poorly understood. In order for new treatments to be developed, the mechanisms leading to the formation of keloid scars must be further elucidated. The search for improved experimental models is of critical importance because such models have an important role to play in both the study of keloid formation and in the development of new therapies. OBJECTIVE: The objective of this article is to introduce the reader to the experimental models available for studying keloid scars and to outline the advantages and limitations of animal and tissue culture models. CONCLUSION: Both models may help to elucidate the pathways of keloid formation and promote development and testing of therapies. Tissue culture is better suited to studies of pathogenesis, whereas the animal models are more suitable for therapeutic testing.

Dry powder versus intravenous and nebulized gentamicin in cystic fibrosis and bronchiectasis. A pilot study.

Aminoglycosides are a mainstay of therapy for patients with cystic fibrosis (CF) or non-CF bronchiectasis who are infected with Pseudomonas aeruginosa (Psa). Traditionally, aerosolized antibiotics are delivered by liquid nebulization. The objective of this study was to determine whether a gentamicin dry powder inhaler (DPI) is as microbiologically active and potentially safe as gentamicin inhaled via a small-volume nebulizer (SVN) or given intravenously. The study was done according to a randomized, single-dose, and triple crossover protocol. Ten patients with CF or non-CF bronchiectasis and chronically infected with Psa were recruited. Patients received a single dose of either gentamicin 160 mg via DPI or SVN, or gentamicin at 5 mg/kg by intravenous infusion. In seven of the 10 patients, the minimum inhibitory concentration (MIC) was achieved in sputum after DPI and SVN, with mean (95% confidence interval) gentamicin concentrations at 2 h after administration of 13.1 microgram/g sputum (range: 2.2 to 23.9 microgram/g) and 97.2 microgram/g sputum (range: 0.3 to 194.2 microgram/g), respectively, whereas gentamicin levels in the sputum after intravenous administration failed to reach the MIC. Gentamicin given by DPI and SVN significantly decreased the sputum Psa density (p < 0.05), by almost one order of magnitude. No significant decline in bacterial counts was observed after intravenous gentamicin. When gentamicin was inhaled, blood concentrations were minimal, and were below concentrations known to cause systemic toxicity. For treatment of Psa infections susceptible to gentamicin, gentamicin administration by DPI appeared to be as efficient as by SVN, despite the delivery of a 7-fold lower dose to the airways.

The role of research evidence in pharmaceutical policy making: evidence when necessary but not necessarily evidence.

The use of research evidence in policy making at the legislative and administrative levels would appear to be very selective. Focusing on pharmaceutical policy, this paper argues that research evidence is only one ingredient leading to a policy decision and that any examination of research transfer into policy must take into account the many other factors which impact on decision making. The paper describes the policy making process, barriers to the uptake of research evidence into policy and ways of improving research uptake into policy making. Examples are given from drug licensing, remuneration policies, post-marketing surveillance and product withdrawal from the market.

Research in medical schools: rationale, priorities, roles and balance.

Although medical schools traditionally rest on the "three-legged stool" of research, education and service, it may often seem to the outsider that research is ascendant. In the past 50 years, medical schools' research success has been abundant; they are often most secure in contemplating their indispensable role in this domain. Recently, however, growing criticism of educational programs and increased competition for service responsibility (and the attendant revenue) from the nonacademic and private sectors have fuelled asymmetry. Research may well be the best bulwark against diminished importance or mediocrity, but it should be fortified by a new balance in which the medical schools' mission in education and service is reinforced. Unipolar concentration on the understanding of disease mechanisms must be eschewed in favour of a blended program of basic, clinical and population health sciences. Medical schools must pay greater attention to their responsibilities for training graduate students in a variety of health-related disciplines; in the future, nonphysician health care professionals will increasingly share the scientific preparation and views of physicians as they work in multiprofessional teams. Research will continue to thrive in the medical school of the future, but success will come from a careful assessment of current realities and a strategic resetting of priorities.

Developing a Canadian prescribing practices network. Network Development Committee of the Canadian Prescribing Practices Network Project.

Expenditure on drug therapy in Canada has been growing at a faster rate than spending on any other aspect of health care. Increasing societal pressure to use scarce resources more efficiently, advances in communication technology and data indicating that there is room for improvement in drug prescribing suggest that the time has come for an organized linkage of the available drug-utilization and health-outcomes data-bases across the country. A national prescribing practices network would assist prescribers, researchers and policymakers to optimize prescribing with respect to both cost effectiveness and health outcomes. The authors outline the main concerns addressed in the 1994 report to the National Pharmaceutical Strategy and present the results of discussions by the Canadian Prescribing Practices Network Project with respect to the potential users and data sources of a national network and the communications technology on which it would rely.