172 research outputs found

    Regulating Medicines in a Globalized World With Increased Recognition and Reliance Among Regulators: A National Academies Report

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    Research and development of pharmaceuticals are now complex global endeavors, with drug companies operating worldwide using global supply chains. Pharmaceutical companies source their products from many countries, conduct trials in multiple sites, and market essential drugs and vaccines globally. Yet oversight of drug safety and effectiveness is primarily the responsibility of national regulators of variable capacities. National agencies often undertake product reviews without recognizing that similar reviews are occurring elsewhere, sometimes simultaneously. The result is duplication and redundancy, which benefits neither national nor global public health. Supported by the US Food and Drug Administration (FDA), the National Academies of Sciences, Engineering, and Medicine convened an expert committee to explore the benefits of mutual recognition and other reliance activities among regulators. Even well-resourced regulators (for example, the FDA, the European Medicines Agency, the Pharmaceutical and Medical Devices Agency Japan, and Health Canada) find it difficult to ensure the safety, efficacy, and quality of medicines in a globalized world. Regulatory failures cause harm to the population and undermine public trust in government. In 2008, following discovery of contaminated heparin originating from China, the Bush administration authorized the FDA to coordinate certain product manufacturing inspections with Australian and European regulators in China and India—setting the stage for “third country” inspections (ie, inspections conducted outside the jurisdiction of either regulator). Yet concerns about the quality of active pharmaceutical ingredients and finished pharmaceutical products persist. For example, in 2018, the FDA recalled generic medications used to treat hypertension and cardiovascular disease because of contamination

    Altruistic bet-hedging and the evolution of cooperation in a Kalahari bird

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    Altruism is globally associated with unpredictable environments, but we do not understand why. New theory has highlighted that unpredictable environments could favor the evolution of altruism if altruistic acts reduce environmentally induced variance in the reproductive success of relatives (“altruistic bet-hedging”). Here, we show that altruism does indeed reduce environmentally induced reproductive variance in a wild cooperative bird. Our decade-long field study reveals that altruistic helping actually has no overall effect on the mean reproductive success of relatives but instead reduces their reproductive variance. This remarkable pattern arises because helpers improve reproductive performance in dry conditions but reduce it in wet conditions. Helpers thereby specifically reduce rainfall-induced reproductive variance, the very mechanism required for altruistic bet-hedging to explain the enigmatic global association between avian altruism and unpredictable rainfall

    Otto coupling to a transverse-electric-polarized mode on a metamaterial surface

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    publication-status: Publishedtypes: ArticleAlastair P. Hibbins, Matthew J. Lockyear and J. Roy Sambles, Physical Review B, Vol. 84, article 115130 (2011). Copyright © 2011 by the American Physical Society.Using the Otto geometry, prism coupling of microwave radiation to a metamaterial surface that supports a bound transverse-electric-polarized surface mode is demonstrated. The dispersion of this surface mode is characterised experimentally for incident radiation beyond the critical angle of the prism, and its resonant fields are explored using a numerical model

    A Patient-Centered Prescription Drug Label to Promote Appropriate Medication Use and Adherence

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    BACKGROUND: Patient misunderstanding of prescription drug label instructions is a common cause of unintentional misuse of medication and adverse health outcomes. Those with limited literacy and English proficiency are at greater risk. OBJECTIVE: To test the effectiveness of a patient-centered drug label strategy, including a Universal Medication Schedule (UMS), to improve proper regimen use and adherence compared to a current standard. DESIGN: Two-arm, multi-site patient-randomized pragmatic trial. PARTICIPANTS: English- and Spanish-speaking patients from eight community health centers in northern Virginia who received prescriptions from a central-fill pharmacy and who were 1) ≥30 years of age, 2) diagnosed with type 2 diabetes and/or hypertension, and 3) taking ≥2 oral medications. INTERVENTION: A patient-centered label (PCL) strategy that incorporated evidence-based practices for format and content, including prioritized information, larger font size, and increased white space. Most notably, instructions were conveyed with the UMS, which uses standard intervals for expressing when to take medicine (morning, noon, evening, bedtime). MAIN MEASURES: Demonstrated proper use of a multi-drug regimen; medication adherence measured by self-report and pill count at 3 and 9 months. KEY RESULTS: A total of 845 patients participated in the study (85.6 % cooperation rate). Patients receiving the PCL demonstrated slightly better proper use of their drug regimens at first exposure (76.9 % vs. 70.1 %, p = 0.06) and at 9 months (85.9 % vs. 77.4 %, p = 0.03). The effect of the PCL was significant for English-speaking patients (OR 2.21, 95 % CI 1.13-4.31) but not for Spanish speakers (OR 1.19, 95 % CI 0.63-2.24). Overall, the intervention did not improve medication adherence. However, significant benefits from the PCL were found among patients with limited literacy (OR 5.08, 95 % CI 1.15-22.37) and for those with medications to be taken ≥2 times a day (OR 2.77, 95 % CI 1.17-6.53). CONCLUSIONS: A simple modification to pharmacy-generated labeling, with minimal investment required, can offer modest improvements to regimen use and adherence, mostly among patients with limited literacy and more complex regimens. Trial Registration (ClinicalTrials.gov): NCT00973180, NCT01200849

    Electrophysiologic actions of high plasma concentrations of propranolol in human subjects

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    The authors have previously shown that 40% of patients whose ventricular arrhythmias respond to propranolol require plasma concentrations in excess of those producing substantial beta-receptor blockade (> 150 ng/ml). However, the electrophysiologic actions of propranolol have only been examined in human beings after small intravenous doses achieving concentrations of less than 100 ng/ml. In this study, the electrophysiologic effects of a wider concentration range of propranolol was examined in nine patients. Using a series of loading and maintenance infusions, measurements were made at baseline, at low mean plasma propranolol concentrations (104 ± 17 ng/ml) and at high concentrations (472 ± 68 ng/ml). Significant (p < 0.05) increases in AH interval and sinus cycle length were seen at low concentrations of propranolol, with no further prolongation at the high concentrations; these effects are typical of those produced by beta-blockade. However, progressive shortening of the endocardial monophasic action potential duration and QTc interval were seen over the entire concentration range tested (p < 0.05). At high concentrations, there was significant (p < 0.05) further shortening of both the QTc and monophasic action potential duration beyond that seen at low propranolol concentrations, along with a progressive increase in the ratio of the ventricular effective refractory period to monophasic action potential duration. No significant changes were seen in HV interval, QRS duration or ventricular effective refractory period.In summary, the concentration-response relations for atrioventricular conductivity and sinus node automat-icity were flat above concentrations of 150 ng/ml. On the other hand, the durations of the monophasic action potential and the QTc interval shortened at high concentrations. It is concluded that propranolol, in addition to blocking beta-receptors, produces other beta-receptor independent electrophysiologic effects in human beings

    Surface plasmons on zig-zag gratings

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    publication-status: Publishedtypes: ArticleThis paper was published in Optics Express and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://dx.doi.org/10.1364/OE.20.023921 Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law.© Copyright 2012 Optical Society of Americ
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