Through the looking glass: understanding non-inferiority

Non-inferiority trials test whether a new product is not unacceptably worse than a product already in use. This paper introduces concepts related to non-inferiority, and discusses the regulatory views of both the European Medicines Agency and the United States Food and Drug Administration

The effect of provider- and workflow-focused strategies for guideline implementation on provider acceptance

<p>Abstract</p> <p>Background</p> <p>The effective implementation of clinical practice guidelines (CPGs) depends critically on the extent to which the strategies that are deployed for implementing the guidelines promote provider acceptance of CPGs. Such implementation strategies can be classified into two types based on whether they primarily target providers (<it>e.g.</it>, academic detailing, grand rounds presentations) or the work context (<it>e.g.</it>, computer reminders, modifications to forms). This study investigated the independent and joint effects of these two types of implementation strategies on provider acceptance of CPGs.</p> <p>Methods</p> <p>Surveys were mailed to a national sample of providers (primary care physicians, physician assistants, nurses, and nurse practitioners) and quality managers selected from Veterans Affairs Medical Centers (VAMCs). A total of 2,438 providers and 242 quality managers from 123 VAMCs participated. Survey items measured implementation strategies and provider acceptance (<it>e.g.</it>, guideline-related knowledge, attitudes, and adherence) for three sets of CPGs--chronic obstructive pulmonary disease, chronic heart failure, and major depressive disorder. The relationships between implementation strategy types and provider acceptance were tested using multi-level analytic models.</p> <p>Results</p> <p>For all three CPGs, provider acceptance increased with the number of implementation strategies of either type. Moreover, the number of workflow-focused strategies compensated (contributing more strongly to provider acceptance) when few provider-focused strategies were used.</p> <p>Conclusion</p> <p>Provider acceptance of CPGs depends on the type of implementation strategies used. Implementation effectiveness can be improved by using both workflow-focused as well as provider-focused strategies.</p

Development and use of a computer program to detect potentially inappropriate prescribing in older adults residing in Canadian long-term care facilities

BACKGROUND: Inappropriate prescribing has been estimated to be as high as 40% in long-term care. The purpose of this study was to develop a computer program that identifies potentially inappropriate drug prescriptions and to test its reliability. METHODS: Potentially inappropriate prescriptions were identified based on modified McLeod guidelines. A database from one pharmacy servicing long-term care facilities in Ontario was utilized for this cross-sectional study. Prescription information was available for the 356 long-term care residents and included: the date the prescription was filled, the quantity of drug prescribed and the eight-digit drug identification number. The pharmacy database was linked to the computer-based program for targeting potential inappropriate prescriptions. The computer program's reliability was assessed by comparing its results to a manual search conducted by two independent research assistants. RESULTS: There was complete agreement between the computer and manual abstraction for the total number of potentially inappropriate prescriptions detected. In total, 83 potentially inappropriate prescriptions were identified. Fifty-three residents (14.9%) received at least one potentially inappropriate prescription. Of those, twenty (37.7%) received two potential inappropriate prescriptions and eight (15.1%) received 3 or more potential inappropriate prescriptions. The most common potential inappropriate prescriptions were identified as long-term use of non-steroidal anti-inflammatory agents and tricyclic antidepressants with active metabolites. CONCLUSION: A computer program can accurately and automatically detect inappropriate prescribing in residents of long-term care facilities. This tool may be used to identify potentially inappropriate drug combinations and educate health care professionals

Developing indicators of pattern identification in patients with stroke using traditional Korean medicine

Abstract Background The traditional Korean medical diagnoses employ pattern identification (PI), a diagnostic system that entails the comprehensive analysis of symptoms and signs. The PI needs to be standardized due to its ambiguity. Therefore, this study was performed to establish standard indicators of the PI for stroke through the traditional Korean medical literature, expert consensus and a clinical field test. Methods We sorted out stroke patterns with an expert committee organized by the Korean Institute of Oriental Medicine. The expert committee composed a document for a standardized pattern of identification for stroke based on the traditional Korean medical literature, and we evaluated the clinical significance of the document through a field test. Results We established five stroke patterns from the traditional Korean medical literature and extracted 117 indicators required for diagnosis. The indicators were evaluated by a field test and verified by the expert committee. Conclusions This study sought to develop indicators of PI based on the traditional Korean medical literature. This process contributed to the standardization of traditional Korean medical diagnoses.</p

Relationship between the population incidence of febrile convulsions in young children in Sydney, Australia and seasonal epidemics of influenza and respiratory syncytial virus, 2003-2010: a time series analysis

<p>Abstract</p> <p>Background</p> <p>In 2010, intense focus was brought to bear on febrile convulsions in Australian children particularly in relation to influenza vaccination. Febrile convulsions are relatively common in infants and can lead to hospital admission and severe outcomes. We aimed to examine the relationships between the population incidence of febrile convulsions and influenza and respiratory syncytial virus (RSV) seasonal epidemics in children less than six years of age in Sydney Australia using routinely collected syndromic surveillance data and to assess the feasibility of using this data to predict increases in population rates of febrile convulsions.</p> <p>Methods</p> <p>Using two readily available sources of routinely collected administrative data; the NSW Emergency Department (ED) patient management database (1 January 2003 - 30 April 2010) and the Ambulance NSW dispatch database (1 July 2006 - 30 April 2010), we used semi-parametric generalized additive models (GAM) to determine the association between the population incidence rate of ED presentations and urgent ambulance dispatches for 'convulsions', and the population incidence rate of ED presentations for 'influenza-like illness' (ILI) and 'bronchiolitis' - proxy measures of influenza and RSV circulation, respectively.</p> <p>Results</p> <p>During the study period, when the weekly all-age population incidence of ED presentations for ILI increased by 1/100,000, the 0 to 6 year-old population incidence of ED presentations for convulsions increased by 6.7/100,000 (P < 0.0001) and that of ambulance calls for convulsions increased by 3.2/100,000 (P < 0.0001). The increase in convulsions occurred one week earlier relative to the ED increase in ILI. The relationship was weaker during the epidemic of pandemic (H1N1) 2009 influenza virus.</p> <p>When the 0 to 3 year-old population incidence of ED presentations for bronchiolitis increased by 1/100,000, the 0 to 6 year-old population incidence of ED presentations for convulsions increased by 0.01/100,000 (P < 0.01). We did not find a meaningful and statistically significant association between bronchiolitis and ambulance calls for convulsions.</p> <p>Conclusions</p> <p>Influenza seasonal epidemics are associated with a substantial and statistically significant increase in the population incidence of hospital attendances and ambulance dispatches for reported febrile convulsions in young children. Monitoring syndromic ED and ambulance data facilitates rapid surveillance of reported febrile convulsions at a population level.</p

Dietary behaviors related to cancer prevention among pre-adolescents and adolescents: the gap between recommendations and reality

<p>Abstract</p> <p>Background</p> <p>Diet is thought to play an important role in cancer risk. This paper summarizes dietary recommendations for cancer prevention and compares these recommendations to the dietary behaviors of U.S. youth ages 8-18.</p> <p>Methods</p> <p>We identified cancer prevention-related dietary recommendations from key health organizations and assessed dietary consumption patterns among youth using published statistics from the National Health and Nutrition Examination Survey, the national Youth Risk Behavior Survey, and other supplemental sources.</p> <p>Results</p> <p>Cancer prevention guidelines recommend a diet rich in fruits, vegetables, and whole grains, recommend limiting sugary foods and beverages, red and processed meats, sodium, and alcohol, and recommend avoiding foods contaminated with carcinogens. However, youth typically do not meet the daily recommendations for fruit, vegetable, or whole grain consumption and are over-consuming energy-dense, sugary and salty foods.</p> <p>Conclusions</p> <p>A large discrepancy exists between expert recommendations about diet and cancer and actual dietary practices among young people and points to the need for more research to better promote the translation of science into practice. Future research should focus on developing and evaluating policies and interventions at the community, state and national levels for aligning the diets of youth with the evolving scientific evidence regarding cancer prevention.</p

Potency analysis of cellular therapies: the emerging role of molecular assays

Potency testing is an important part of the evaluation of cellular therapy products. Potency assays are quantitative measures of a product-specific biological activity that is linked to a relevant biological property and, ideally, a product's in vivo mechanism of action. Both in vivo and in vitro assays can be used for potency testing. Since there is often a limited period of time between the completion of production and the release from the laboratory for administration to the patient, in vitro assays such are flow cytometry, ELISA, and cytotoxicity are typically used. Better potency assays are needed to assess the complex and multiple functions of cellular therapy products, some of which are not well understood. Gene expression profiling using microarray technology has been widely and effectively used to assess changes of cells in response to stimuli and to classify cancers. Preliminary studies have shown that the expression of noncoding microRNA which play an important role in cellular development, differentiation, metabolism and signal transduction can distinguish different types of stem cells and leukocytes. Both gene and microRNA expression profiling have the potential to be important tools for testing the potency of cellular therapies. Potency testing, the complexities associated with potency testing of cellular therapies, and the potential role of gene and microRNA expression microarrays in potency testing of cellular therapies is discussed

A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects

BACKGROUND: Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD). In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention. METHODS: This study was carried out in women aged 19–44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I) Determination of rates of NTDs; II) Dietary assessment; III) Blood analysis; IV) Assessment of knowledge and use of folic acid supplements. RESULTS: The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991–93 and 1994–97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76–1.34). The rates of NTDs fell by 78% (95% CI 65%–86%) after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35). The average dietary intake of folic acid due to fortification was 70 μg/day in women aged 19–44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B(12 )deficiencies, and no evidence of improved folate status masking haematological manifestations of vitamin B(12 )deficiency. The proportion of women aged 19–44 years taking a vitamin supplement containing folic acid increased from 17% to 28%. CONCLUSIONS: Based on these findings, mandatory food fortification in Canada should continue at the current levels. Public education regarding folic acid supplement use by women of childbearing age should also continue