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)

The atypical CDK activator RingoA/Spy1 regulates exit from quiescence in neural stem cells

In the adult mammalian brain, most neural stem cells (NSCs) are held in a reversible state of quiescence, which is essential to avoid NSC exhaustion and determine the appropriate neurogenesis rate. NSCs of the mouse adult subependymal niche provide neurons for olfactory circuits and can be found at different depths of quiescence, but very little is known on how their quiescence-to-activation transition is controlled. Here, we identify the atypical cyclin-dependent kinase (CDK) activator RingoA as a regulator of this process. We show that the expression of RingoA increases the levels of CDK activity and facilitates cell cycle entry of a subset of NSCs that divide slowly. Accordingly, RingoA-deficient mice exhibit reduced olfactory neurogenesis with an accumulation of quiescent NSCs. Our results indicate that RingoA plays an important role in setting the threshold of CDK activity required for adult NSCs to exit quiescence and may represent a dormancy regulator in adult mammalian tissues.© 2023 The Author(s)

Effects of pedunculopontine nucleus stimulation on human bladder function

AIMS: The pedunculopontine nucleus (PPN) is a deep brain stimulation target for Parkinson's disease (PD). Unilateral PPN stimulation has been described in a previous case report to provoke urinary frequency, urgency and detrusor overactivity, due to probable activation of the pontine micturition center. Our aim was to evaluate the effect of bilateral PPN DBS on urodynamic parameters and to investigate the likely mechanisms using probabilistic tractography. METHODS: Six male PD subjects with bilateral PPN deep brain stimulators were recruited. Urodynamic bladder filling assessments were carried out with the stimulators ON and OFF. Two subjects also had diffusion-weighted and T1-weighted MRI scans performed and probabilistic tractography was carried out to describe white matter connections with the stimulated area. RESULTS: Five subjects completed urodynamic testing. PPN DBS did not give rise to detrusor overactivity or lower sensory thresholds during bladder filling. However, there was a significant increase in maximal bladder capacity with stimulation: mean bladder volume at maximal capacity was 199 mL (range 103-440) ON stimulation compared with 131 mL (range 39-230) OFF stimulation. Tractography demonstrated extensive connectivity to cortical and subcortical regions, some of which have been implicated in bladder control. Fiber pathways also passed close to the vicinity of the pontine micturition center. CONCLUSIONS: Bilateral PPN DBS did not have a detrimental effect on urodynamic filling parameters or produce detrusor overactivity, but did slightly increase maximal capacity. Possible mechanisms include long-range connectivity or local effects at the pontine micturition center

Family physicians' perceptions of academic detailing: a quantitative and qualitative study

<p>Abstract</p> <p>Background</p> <p>The efficacy of academic detailing in changing physicians' knowledge and practice has been the subject of many primary research publications and systematic reviews. However, there is little written about the features of academic detailing that physicians find valuable or that affect their use of it. The goal of our project was to explore family physicians' (FPs) perceptions of academic detailing and the factors that affect their use of it.</p> <p>Methods</p> <p>We used 2 methods to collect data, a questionnaire and semi-structured telephone interviews. We mailed questionnaires to all FPs in the Dalhousie Office of Continuing Medical Education database and analyzed responses of non-users and users of academic detailing. After a preliminary analysis of questionnaire data, we conducted semi-structured interviews with 7 FPs who did not use academic detailing and 17 who did use it.</p> <p>Results</p> <p>Overall response rate to the questionnaire was 33% (289/869). Response rate of non-users of academic detailing was 15% (60/393), of users was 48% (229/476). The 3 factors that most encouraged use of academic detailing were the topics selected, the evidence-based approach adopted, and the handout material. The 3 factors that most discouraged the use of academic detailing were spending office time doing CME, scheduling time to see the academic detailer, and having CME provided by a non-physician. Users of academic detailing rated it as being more valuable than other forms of CME. Generally, interview data confirmed questionnaire data with the exception that interview informants did not view having CME provided by a non-physician as a barrier. Interview informants mentioned that the evidence-based approach adopted by academic detailing had led them to more critically evaluate information from other CME programs, pharmaceutical representatives, and journal articles, but not advice from specialists.</p> <p>Conclusion</p> <p>Users of academic detailing highly value its educational value and tend to view information from other sources more critically because of its evidence-based approach. Non-users are unlikely to adopt academic detailing despite its high educational value because they find using office time for CME too much of a barrier. To reach these physicians with academic detailing messages, we will have to find other CME formats.</p

Can postponement of an adverse outcome be used to present risk reductions to a lay audience? A population survey

BACKGROUND: For shared decision making doctors need to communicate the effectiveness of therapies such that patients can understand it and discriminate between small and large effects. Previous research indicates that patients have difficulties in understanding risk measures. This study aimed to test the hypothesis that lay people may be able to discriminate between therapies when their effectiveness is expressed in terms of postponement of an adverse disease event. METHODS: In 2004 a random sample of 1,367 non-institutionalized Danes aged 40+ was interviewed in person. The participants were asked for demographic information and asked to consider a hypothetical preventive drug treatment. The respondents were randomized to the magnitude of treatment effectiveness (heart attack postponement of 1 month, 6 months, 12 months, 2 years, 4 years and 8 years) and subsequently asked whether they would take such a therapy. They were also asked whether they had hypercholesterolemia or had experienced a heart attack. RESULTS: In total 58% of the respondents consented to the hypothetical treatment. The proportions accepting treatment were 39%, 52%, 56%, 64%, 67% and 73% when postponement was 1 month, 6 months, 12 months, 2 years, 4 years and 8 years respectively. Participants who thought that the effectiveness information was difficult to understand, were less likely to consent to therapy (p = 0.004). CONCLUSION: Lay people can discriminate between levels of treatment effectiveness when they are presented in terms of postponement of an adverse event. The results indicate that such postponement is a comprehensible measure of effectiveness

Abstracts in high profile journals often fail to report harm

<p>Abstract</p> <p>Background</p> <p>To describe how frequently harm is reported in the abstract of high impact factor medical journals.</p> <p>Methods</p> <p><it>Design and population</it>: We carried out a blinded structured review of a random sample of 363 Randomised Controlled Trials (RCTs) carried out on human beings, and published in high impact factor medical journals in 2003. <it>Main endpoint</it>: 1) Proportion of articles reporting harm in the abstract; and 2) Proportion of articles that reported harm in the abstract when harm was reported in the main body of the article. <it>Analysis</it>: Corrected Prevalence Ratio (cPR) and its exact confidence interval were calculated. Non-conditional logistic regression was used.</p> <p>Results</p> <p>363 articles and 407 possible comparisons were studied. Overall, harm was reported in 135 abstracts [37.2% (CI95%:32.2 to 42.4)]. Harm was reported in the main text of 243 articles [66.9% (CI95%: 61.8 to 71.8)] and was statistically significant in 54 articles [14.9% (CI95%: 11.4 to 19.0)]. Among the 243 articles that mentioned harm in the text, 130 articles [53.5% (CI95% 47.0 to 59.9)] reported harm in the abstract; a figure that rose to 75.9% (CI95%: 62.4 to 86.5) when the harm reported in the text was statistically significant. Harm in the abstract was more likely to be reported when statistically significant harm was reported in the main body of the article [cPR = 1.70 (CI95% 1.47 to 1.92)] and when drug companies (not public institutions) funded the RCTs [cPR = 1.29 (CI95% 1.03 to 1.67)].</p> <p>Conclusion</p> <p>Abstracts published in high impact factor medical journals underreport harm, even when harm is reported in the main body of the article.</p

Educating public health physicians for the future: a current perspective from Aotearoa New Zealand

Persisting, and in some cases widening, inequalities in health within and between countries present significant challenges to the focus and practice of contemporary public health, and by association, to public health education. As public health physicians and academic educators of medically- and non-medically trained public health practitioners, we call for a radical re-think of current approaches to public health medicine education and training in order to address these challenges. The public health physicians of the future, we argue, require not merely technical knowledge and skills but also a set of values that underpin a commitment to ethical principles, social equity, human rights, compassionate action, advocacy and leadership. Furthermore, while they will need to have their action firmly grounded in local realities they should think, if not speak and act, from an informed awareness of global issues. Drawing from our experience in Aotearoa New Zealand, as well as with marginalised communities overseas, we proffer our suggestions for the process and content of public health physician education and training for the future, with the intention of stimulating debate

Laypersons' understanding of relative risk reductions: Randomised cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Despite increasing recognition of the importance of involving patients in decisions on preventive healthcare interventions, little is known about how well patients understand and utilise information provided on the relative benefits from these interventions. The aim of this study was to explore whether lay people can discriminate between preventive interventions when effectiveness is presented in terms of relative risk reduction (RRR), and whether such discrimination is influenced by presentation of baseline risk.</p> <p>Methods</p> <p>The study was a randomised cross-sectional interview survey of a representative sample (n = 1,519) of lay people with mean age 59 (range 40–98) years in Denmark. In addition to demographic information, respondents were asked to consider a hypothetical drug treatment to prevent heart attack. Its effectiveness was randomly presented as RRR of 10, 20, 30, 40, 50 or 60 percent, and half of the respondents were presented with quantitative information on the baseline risk of heart attack. The respondents had also been asked whether they were diagnosed with hypercholesterolemia or had experienced a heart attack.</p> <p>Results</p> <p>In total, 873 (58%) of the respondents consented to the hypothetical treatment. While 49% accepted the treatment when RRR = 10%, the acceptance rate was 58–60% for RRR>10. There was no significant difference in acceptance rates across respondents irrespective of whether they had been presented with quantitative information on baseline risk or not.</p> <p>Conclusion</p> <p>In this study, lay people's decisions about therapy were only slightly influenced by the magnitude of the effect when it was presented in terms of RRR. The results may indicate that lay people have difficulties in discriminating between levels of effectiveness when they are presented in terms of RRR.</p

Health and Human Rights Education in U.S. Schools of Medicine and Public Health: Current Status and Future Challenges

BACKGROUND: Despite increasing recognition of the importance of human rights in the protection and promotion of health, formal human rights education has been lacking in schools of medicine and public health. Our objectives were: 1) to determine the nature and extent of health and human rights (HHR) education among schools of medicine (SOMs) and public health (SPHs); 2) to identify perceived barriers to implementing HHR curricula; 3) to learn about deans' interests and attitudes toward HHR education, and; 4) to identify factors associated with offering HHR education. METHODS AND PRINCIPAL FINDINGS: We conducted a cross-sectional survey among deans of all accredited allopathic SOMs and SPHs in the United States and Puerto Rico. Seventy-one percent of U.S. SOMs and SPHs responded. Thirty-seven percent of respondents indicated that their schools offered some form of HHR education. Main barriers to offering HHR education included competition for time, lack of qualified instructors and lack of funding. Among schools not offering HHR education, 35% of deans were interested in offering HHR education. Seventy-six percent of all deans believed that it was very important or important to offer HHR education. Multiple regression analysis revealed that deans' attitudes were the most important factor associated with offering any HHR education. CONCLUSION: Findings indicate that though a majority of deans of SOMs and SPHs believe that knowledge about human rights is important in health practice and support the inclusion of HHR studies in their schools, HHR education is lacking at most of their institutions. These results and the growing recognition of the critical interdependence between health and human rights indicate a need for SOMs and SPHs to work towards formal inclusion of HHR studies in their curricula, and that HHR competency requirements be considered to overcome barriers to its inclusion