Validation of Acute Myocardial Infarction (AMI) in the FDA’s Mini-Sentinel Distributed Database

The Food and Drug Administration’s (FDA) Mini-Sentinel is a pilot program that aims to conduct active surveillance to detect and refine safety signals that emerge for marketed medical products. The purpose of this Mini-Sentinel AMI Validation project was to: (a) develop and design an abstraction and adjudication process to use when full text medical record review is required to confirm a coded diagnosis; and (b) to test this approach by validating a code algorithm for acute myocardial infarction (AMI)

Research shapes policy: but the dynamics are subtle

Major policy initiatives such as the Quality and Outcomes Framework (QOF) in the national contract for UK general practitioners might variably be informed by evidence at their inception, implementation and subsequent evolution. But what evidence gets admitted into these policy debates—and what is left out? Using QOF as an example, this article demonstrates what an analysis of the relationship between policy and the associated research can tell us about the underlying policy assumptions and about the role of evidence in policy debates

Knowledge of and perceived need for evidence-based educational materials about antipsychotic medication safety by nursing home staff

Background: Given the widespread overuse of antipsychotic medications among US nursing home (NH) residents, we sought to identify knowledge of and perceived need for the AHRQ Comparative Effectiveness Research Summary Guide (CERSG) “Off-Label Use of Atypical Antipsychotic Drugs”. Methods: We conducted a baseline needs assessment with 12 NHs participating in a randomized controlled trail evaluating evidence dissemination strategies. Using a mixed method approach, we conducted in-depth assessments of knowledge, attitudes, and practice behavior using telephone interviews with NH leadership (administrators, directors of nursing [DON], and medical directors), and questionnaires with NH leadership, consultant pharmacists and direct care staff. Interviews were transcribed, verbatim responses were coded independently by 2 project staff. The coding scheme was revised after each round until substantial agreement (85%) was reached. Results: Interviews revealed that 70% of medical directors and 46% of DON and administrators believed that antipsychotics decreased agitation and controlled harmful behavior; 50% of medical directors and 7% of DONs & administrators reported knowledge of the increased risk of morbidity and mortality due to atypical antipsychotics. Half of administrators and DONs expressed interest in receiving information for NH staff pertaining to understanding dementia and dementia-related behaviors, 42% believed families would benefit from information about antipsychotic use for dementia-related behaviors. Questionnaire results were similar. When leaders were asked to list any risks associated with antipsychotic use for residents with dementia, only 17% reported death as a possible adverse event; licensed nursing staff (RN and LPNs) reported death 5% of the time. Over half of consultant pharmacists identified that their biggest barrier to improving medication use in challenging NHs was physician resistance to accepting recommendations. Conclusions: The responses of the NH leaders, staff and consultant pharmacists suggest widespread knowledge gaps regarding antipsychotic benefits and risks, and suggest a need for increase evidence dissemination and broad organizational change

A Mixed-Methods Study To Characterize Pharmaceutical Marketing in the Nursing Home Setting: Off-Label Use of Atypical Antipsychotics

Background: Despite FDA warnings that atypical antipsychotic medications are associated with an increased risk of death when used to treat behavioral disorders in older adults with dementia, they are prescribed to nearly one-third of older U.S. nursing home (NH) residents. Reasons for their high use in NHs are poorly understood, but may include pharmaceutical marketing efforts in the NH setting. Methods: This study is nested within an ongoing cluster randomized trial to improve the use of atypical antipsychotics in NHs. We analyzed semistructured interviews (n = 36) and surveys (n = 139) of administrators, directors of nursing and medical directors from 62 NHs in Connecticut. Using prescription drug claims from a national long-term care pharmacy, we arrayed study NHs into lowest to highest tertile of atypical antipsychotic use. We tested for differences in the receipt of information or clinical tools from pharmaceutical company representatives (PCRs) to manage dementia-related behaviors by medication use tertiles, adjusting for NH profit status, size, quality (overall, health inspections, staffing) and staffing measures (daily nurse hours per resident). Results: Average baseline use of atypical antipsychotics ranged from 6.6 to 44.3 percent of all residents in the facility. Approximately one-quarter of NH leaders presently receive information on dementia-related behavioral management strategies from PCRs through detailing, in-service training, written or Web-based material or sponsorship as speakers. However, we did not detect statistically significant differences in the receipt of information by level of atypical antipsychotic use, NH characteristics, quality and staffing measures. Conclusions: This first attempt to characterize pharmaceutical marketing within the NH setting did not find differences among reports of marketing efforts with respect to medication use and facility-level characteristics. However, studies across a wider geographic area should continue investigating the possible role of marketing efforts on overall use and choice of atypical antipsychotics in the NH setting

Target product profiles for protecting against outdoor malaria transmission.

BACKGROUND\ud \ud Long-lasting insecticidal nets (LLINs) and indoor residual sprays (IRS) have decimated malaria transmission by killing indoor-feeding mosquitoes. However, complete elimination of malaria transmission with these proven methods is confounded by vectors that evade pesticide contact by feeding outdoors.\ud \ud METHODS\ud \ud For any assumed level of indoor coverage and personal protective efficacy with insecticidal products, process-explicit malaria transmission models suggest that insecticides that repel mosquitoes will achieve less impact upon transmission than those that kill them outright. Here such models are extended to explore how outdoor use of products containing either contact toxins or spatial repellents might augment or attenuate impact of high indoor coverage of LLINs relying primarily upon contact toxicity.\ud \ud RESULTS\ud \ud LLIN impact could be dramatically enhanced by high coverage with spatial repellents conferring near-complete personal protection, but only if combined indoor use of both measures can be avoided where vectors persist that prefer feeding indoors upon humans. While very high levels of coverage and efficacy will be required for spatial repellents to substantially augment the impact of LLINs or IRS, these ambitious targets may well be at least as practically achievable as the lower requirements for equivalent impact using contact insecticides.\ud \ud CONCLUSIONS\ud \ud Vapour-phase repellents may be more acceptable, practical and effective than contact insecticides for preventing outdoor malaria transmission because they need not be applied to skin or clothing and may protect multiple occupants of spaces outside of treatable structures such as nets or houses

An adaptable implementation package targeting evidence-based indicators in primary care: a pragmatic cluster-randomised evaluation

Background In primary care, multiple priorities and system pressures make closing the gap between evidence and practice challenging. Most implementation studies focus on single conditions, limiting generalisability. We compared an adaptable implementation package against an implementation control and assessed effects on adherence to four different evidence-based quality indicators. Methods and findings We undertook two parallel, pragmatic cluster-randomised trials using balanced incomplete block designs in general practices in West Yorkshire, England. We used ‘opt-out’ recruitment, and we randomly assigned practices that did not opt out to an implementation package targeting either diabetes control or risky prescribing (Trial 1); or blood pressure (BP) control or anticoagulation in atrial fibrillation (AF) (Trial 2). Within trials, each arm acted as the implementation control comparison for the other targeted indicator. For example, practices assigned to the diabetes control package acted as the comparison for practices assigned to the risky prescribing package. The implementation package embedded behaviour change techniques within audit and feedback, educational outreach, and computerised support, with content tailored to each indicator. Respective patient-level primary endpoints at 11 months comprised the following: achievement of all recommended levels of haemoglobin A1c (HbA1c), BP, and cholesterol; risky prescribing levels; achievement of recommended BP; and anticoagulation prescribing. Between February and March 2015, we recruited 144 general practices collectively serving over 1 million patients. We stratified computer-generated randomisation by area, list size, and pre-intervention outcome achievement. In April 2015, we randomised 80 practices to Trial 1 (40 per arm) and 64 to Trial 2 (32 per arm). Practices and trial personnel were not blind to allocation. Two practices were lost to follow-up but provided some outcome data. We analysed the intention-to-treat (ITT) population, adjusted for potential confounders at patient level (sex, age) and practice level (list size, locality, pre-intervention achievement against primary outcomes, total quality scores, and levels of patient co-morbidity), and analysed cost-effectiveness. The implementation package reduced risky prescribing (odds ratio [OR] 0.82; 97.5% confidence interval [CI] 0.67–0.99, p = 0.017) with an incremental cost-effectiveness ratio of £1,359 per quality-adjusted life year (QALY), but there was insufficient evidence of effect on other primary endpoints (diabetes control OR 1.03, 97.5% CI 0.89–1.18, p = 0.693; BP control OR 1.05, 97.5% CI 0.96–1.16, p = 0.215; anticoagulation prescribing OR 0.90, 97.5% CI 0.75–1.09, p = 0.214). No statistically significant effects were observed in any secondary outcome except for reduced co-prescription of aspirin and clopidogrel without gastro-protection in patients aged 65 and over (adjusted OR 0.62; 97.5% CI 0.39–0.99; p = 0.021). Main study limitations concern our inability to make any inferences about the relative effects of individual intervention components, given the multifaceted nature of the implementation package, and that the composite endpoint for diabetes control may have been too challenging to achieve. Conclusions In this study, we observed that a multifaceted implementation package was clinically and cost-effective for targeting prescribing behaviours within the control of clinicians but not for more complex behaviours that also required patient engagement. Trial registration The study is registered with the ISRCTN registry (ISRCTN91989345)