449 research outputs found
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Are providers prepared for genomic medicine: interpretation of Direct-to-Consumer genetic testing (DTC-GT) results and genetic self-efficacy by medical professionals.
BACKGROUND:Precision medicine is set to deliver a rich new data set of genomic information. However, the number of certified specialists in the United States is small, with only 4244 genetic counselors and 1302 clinical geneticists. We conducted a national survey of 264 medical professionals to evaluate how they interpret genetic test results, determine their confidence and self-efficacy of interpreting genetic test results with patients, and capture their opinions and experiences with direct-to-consumer genetic tests (DTC-GT). METHODS:Participants were grouped into two categories, genetic specialists (genetic counselors and clinical geneticists) and medical providers (primary care, internists, physicians assistants, advanced nurse practitioners, etc.). The survey (full instrument can be found in the Additional file 1) presented three genetic test report scenarios for interpretation: a genetic risk for diabetes, genomic sequencing for symptoms report implicating a potential HMN7B: distal hereditary motor neuropathy VIIB diagnosis, and a statin-induced myopathy risk. Participants were also asked about their opinions on DTC-GT results and rank their own perceived level of preparedness to review genetic test results with patients. RESULTS:The rates of correctly interpreting results were relatively high (74.4% for the providers compared to the specialist's 83.4%) and age, prior genetic test consultation experience, and level of trust assigned to the reports were associated with higher correct interpretation rates. The self-selected efficacy and the level of preparedness to consult on a patient's genetic results were higher for the specialists than the provider group. CONCLUSION:Specialists remain the best group to assist patients with DTC-GT, however, primary care providers may still provide accurate interpretation of test results when specialists are unavailable
Are providers prepared for genomic medicine: interpretation of Direct-to-Consumer genetic testing (DTC-GT) results and genetic self-efficacy by medical professionals
Background: Precision medicine is set to deliver a rich new data set of genomic information. However, the number of certified specialists in the United States is small, with only 4244 genetic counselors and 1302 clinical geneticists. We conducted a national survey of 264 medical professionals to evaluate how they interpret genetic test results, determine their confidence and self-efficacy of interpreting genetic test results with patients, and capture their opinions and experiences with direct-to-consumer genetic tests (DTC-GT). Methods: Participants were grouped into two categories, genetic specialists (genetic counselors and clinical geneticists) and medical providers (primary care, internists, physicians assistants, advanced nurse practitioners, etc.). The survey (full instrument can be found in the Additional file 1) presented three genetic test report scenarios for interpretation: a genetic risk for diabetes, genomic sequencing for symptoms report implicating a potential HMN7B: distal hereditary motor neuropathy VIIB diagnosis, and a statin-induced myopathy risk. Participants were also asked about their opinions on DTC-GT results and rank their own perceived level of preparedness to review genetic test results with patients. Results: The rates of correctly interpreting results were relatively high (74.4% for the providers compared to the specialistâs 83.4%) and age, prior genetic test consultation experience, and level of trust assigned to the reports were associated with higher correct interpretation rates. The self-selected efficacy and the level of preparedness to consult on a patientâs genetic results were higher for the specialists than the provider group. Conclusion: Specialists remain the best group to assist patients with DTC-GT, however, primary care providers may still provide accurate interpretation of test results when specialists are unavailable
Structures of mixed manganese ruthenium oxides crystallised under acidic hydrothermal conditions
A synthesis method for the preparation of mixed manganeseâruthenium oxides is presented along with a detailed characterisation of the solids produced. The use of 1 M aqueous sulfuric acid mediates the redox reaction between KRuO, KMnO and Mn to form ternary oxides. At reaction temperature of 100°C the products are mixtures of α-MnO (hollandite-type) and ÎČ-MnO (rutile-type), with some evidence of Ru incorporation in each from their expanded unit cell volumes. At reaction temperature of 200°C solid-solutions ÎČ-MnRuO are formed and materials with x †0.6 have been studied. The amount of Ru included in the oxide is greater than expected from the ratio of metals used in the synthesis, as determined by elemental analysis, implying that some Mn remains unreacted in solution. Powder X-ray diffraction (XRD) shows that while the unit cell volume expands in a linear manner, following Vegard's law, the tetragonal lattice parameters, and the a/c ratio, do not follow the extrapolated trends: this anisotropic behaviour is consistent with the different local coordination of the metals in the end members. Powder XRD patterns show increased peak broadening with increasing ruthenium content, which is corroborated by electron microscopy that shows nanocrystalline material. X-ray absorption near-edge spectra show that the average oxidation state of Mn in the solid solutions is reduced below +4 while that of Ru is increased above +4, suggesting some redistribution of charge. Analysis of the extended X-ray absorption fine structure provides complementary local structural information, confirming the formation of a solid solution, while X-ray photoelectron spectroscopy shows that the surface oxidation states of both Ru and Mn are on average lower than +4, suggesting a disordered surface layer may be present in the materials
Dating Violence: Outcomes Following a Brief Motivational Interviewing Intervention Among Atârisk Adolescents in an Urban Emergency Department
Objectives A recent study demonstrated the efficacy of the SafERteens intervention in reducing peer violence among adolescents presenting to the emergency department (ED). The objective of this study was to determine the efficacy of this EDâbased brief intervention (BI) on dating violence 1 year following the ED visit among the subsample of adolescents in the original randomized controlled trial reporting pastâyear dating violence. Methods Patients (aged 14 to 18 years) at an ED were eligible for inclusion if they had pastâyear violence and alcohol use. Participants were randomized to one of three conditions (BI delivered by a computer [CBI], BI delivered by a therapist and a computer (T+CBI), or control) and completed followâups at 3, 6, and 12 months. In addition to content on alcohol misuse and peer violence, adolescents reporting dating violence received a tailored module on dating violence. The outcome of interest was frequency of moderate and severe dating violence victimization and aggression (baseline and 3, 6, and 12 months after ED visit). Results Among eligible adolescents, 55% ( n  = 397) reported dating violence and were included in these analyses. Compared to the control group (who received a resource brochure only), participants in the CBI showed reductions in moderate dating victimization at 3 months (interârater reliability [IRR] = 0.71; 95% confidence interval [CI] = 0.51 to 0.99; p < 0.05) and 6 months (IRR = 0.56; 95% CI = 0.38 to 0.83; p < 0.01). Models examining interaction effects were significant for the CBI on moderate dating victimization at 3 months (IRR = 0.81; 95% CI = 0.67 to 0.98; p < 0.05) and 6 months (IRR = 0.81; 95% CI = 0.66 to 0.99; p < 0.05). Significant interaction effects were found for the T+CBI on moderate dating violence victimization at 6 months (IRR = 0.81; 95% CI = 0.69 to 0.96; p < 0.01) and 12 months (IRR = 0.76; 95% CI = 0.63 to 0.90; p < 0.001) and severe dating violence victimization at 3 months (IRR = 0.76; 95% CI = 0.59 to 0.96; p < 0.05). Conclusions EDâbased BIs tailored to address multiple risk behaviors (i.e., peer violence, alcohol use, and dating violence) show promise for reducing moderate and severe dating victimization for up to 1 year following an ED visit. Resumen La Violencia de Pareja: Resultados tras una IntervenciĂłn mediante una Entrevista Breve Motivacional entre los Adolescentes en Riesgo en un Servicio de Urgencias Urbano Objetivos Un estudio reciente demostrĂł la eficacia de la intervenciĂłn SafERteens en reducir la violencia entre los adolescentes que acuden al servicio de urgencias (SU). El objetivo de este estudio fue determinar la eficacia de esta intervenciĂłn breve (IB) en los SU en la violencia de pareja al año tras la visita al SU en una muestra de adolescentes del ensayo clĂnico original controlado y aleatorizado que documentĂł la violencia de pareja del pasado año. MetodologĂa Se incluyeron los pacientes entre 14 y 18 años de edad del SU que tenĂan antecedentes de violencia o consumo de alcohol en el pasado año. Los participantes fueron aleatorizados a una de las tres situaciones: IB realizada por un ordenador (IBO), IB realizada por un terapeuta y un ordenador (IBO + T), o control; y completaron 3, 6, y 12 meses de seguimiento. AdemĂĄs de contener abuso de alcohol y violencia entre iguales, los adolescentes que documentaron la violencia de pareja recibieron un mĂłdulo adaptado en violencia de pareja. El resultado de interĂ©s fue la frecuencia de violencia de pareja moderada o grave como vĂctima y agresor (basal, 3, 6 y 12 meses tras la visita). Resultados Entre los adolescentes elegibles, el 55% (n=397) documentĂł datos de violencia de pareja y fueron incluidos en estos anĂĄlisis. En comparaciĂłn con el grupo control (que recibieron sĂłlo el recurso de un folleto informativo), los participantes en la IBO mostraron una reducciĂłn en la violencia de pareja moderada como vĂctima a los 3 meses (concordancia entre evaluadores [K] 0,71; IC 95% = 0,51 a 0,99; p < 0,05) y a los 6 meses (K 0,56; IC 95%= 0,38 a 0,83; p < 0,01); los modelos que examinaron los efectos de interacciĂłn fueron significativos para la IBO en la violencia de pareja moderada como vĂctima a los 3 meses (K 0,81; IC 95% = 0,67 a 0,98; p < 0,05) y a los 6 meses (K 0,81; IC 95% = 0,66 a 0,99; p < 0,05). Se hallaron efectos de interacciĂłn significativos para la IBO+T en la violencia de pareja moderada como vĂctima a los 6 meses (K 0,81; IC 95% = 0,69 a 0,96; p < 0,01) y a los 12 meses (K 0,76; IC 95% = 0,63 a 0,90; p < 0,001), y en la violencia de pareja grave como vĂctima a los 3 meses (K 0.76; IC 95% = 0,59 a 0,96; p < 0,05). Conclusiones Las IB en el SU adaptadas para valorar mĂșltiples comportamientos de riesgo (ej: violencia entre iguales, consumo de alcohol y violencia de pareja) son prometedores para reducir la violencia de pareja moderada y grave como vĂctima hasta un año tras la visita al SU.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98214/1/acem12151.pd
Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction
Background: Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF). Objectives: This study sought to describe AF burden and its clinical impact among individuals with HFpEF and HFmrEF who participated in a randomized clinical trial of atrial shunt therapy (REDUCE LAP-HF II [A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]) and to evaluate the effect of atrial shunt therapy on AF burden. Methods: Study investigators characterized AF burden among patients in the REDUCE LAP-HF II trial by using ambulatory cardiac patch monitoring at baseline (median patch wear time, 6 days) and over a 12-month follow-up (median patch wear time, 125 days). The investigators determined the association of baseline AF burden with long-term clinical events and examined the effect of atrial shunt therapy on AF burden over time. Results: Among 367 patients with cardiac monitoring data at baseline and follow-up, 194 (53%) had a history of AF or atrial flutter (AFL), and median baseline AF burden was 0.012% (IQR: 0%-1.3%). After multivariable adjustment, baseline AF burden â„0.012% was significantly associated with heart failure (HF) events (HR: 2.00; 95% CI: 1.17-3.44; P = 0.01) both with and without a history of AF or AFL (P for interaction = 0.68). Adjustment for left atrial reservoir strain attenuated the baseline AF burden-HF event association (HR: 1.71; 95% CI: 0.93-3.14; P = 0.08). Of the 367 patients, 141 (38%) had patch-detected AF during follow-up without a history of AF or AFL. Atrial shunt therapy did not change AF incidence or burden during follow-up. Conclusions: In HFpEF and HFmrEF, nearly 40% of patients have subclinical AF by 1 year. Baseline AF burden, even at low levels, is associated with HF events. Atrial shunt therapy does not affect AF incidence or burden.</p
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The adaptive designs CONSORT extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design
Abstract: Adaptive designs (ADs) allow pre-planned changes to an ongoing trial without compromising the validity of conclusions and it is essential to distinguish pre-planned from unplanned changes that may also occur. The reporting of ADs in randomised trials is inconsistent and needs improving. Incompletely reported AD randomised trials are difficult to reproduce and are hard to interpret and synthesise. This consequently hampers their ability to inform practice as well as future research and contributes to research waste. Better transparency and adequate reporting will enable the potential benefits of ADs to be realised. This extension to the Consolidated Standards Of Reporting Trials (CONSORT) 2010 statement was developed to enhance the reporting of randomised AD clinical trials. We developed an Adaptive designs CONSORT Extension (ACE) guideline through a two-stage Delphi process with input from multidisciplinary key stakeholders in clinical trials research in the public and private sectors from 21 countries, followed by a consensus meeting. Members of the CONSORT Group were involved during the development process. The paper presents the ACE checklists for AD randomised trial reports and abstracts, as well as an explanation with examples to aid the application of the guideline. The ACE checklist comprises seven new items, nine modified items, six unchanged items for which additional explanatory text clarifies further considerations for ADs, and 20 unchanged items not requiring further explanatory text. The ACE abstract checklist has one new item, one modified item, one unchanged item with additional explanatory text for ADs, and 15 unchanged items not requiring further explanatory text. The intention is to enhance transparency and improve reporting of AD randomised trials to improve the interpretability of their results and reproducibility of their methods, results and inference. We also hope indirectly to facilitate the much-needed knowledge transfer of innovative trial designs to maximise their potential benefits. In order to encourage its wide dissemination this article is freely accessible on the BMJ and Trials journal websites.âTo maximise the benefit to society, you need to not just do research but do it wellâ Douglas G Altma
The insecticide resistance status of malaria vectors in the Mekong region
<p>Abstract</p> <p>Background</p> <p>Knowledge on insecticide resistance in target species is a basic requirement to guide insecticide use in malaria control programmes. Malaria transmission in the Mekong region is mainly concentrated in forested areas along the country borders, so that decisions on insecticide use should ideally be made at regional level. Consequently, cross-country monitoring of insecticide resistance is indispensable to acquire comparable baseline data on insecticide resistance.</p> <p>Methods</p> <p>A network for the monitoring of insecticide resistance, MALVECASIA, was set up in the Mekong region in order to assess the insecticide resistance status of the major malaria vectors in Cambodia, Laos, Thailand, and Vietnam. From 2003 till 2005, bioassays were performed on adult mosquitoes using the standard WHO susceptibility test with diagnostic concentrations of permethrin 0.75% and DDT 4%. Additional tests were done with pyrethroid insecticides applied by the different national malaria control programmes.</p> <p>Results</p> <p><it>Anopheles dirus s.s</it>., the main vector in forested malaria foci, was susceptible to permethrin. However, in central Vietnam, it showed possible resistance to type II pyrethroids. In the Mekong delta, <it>Anopheles epiroticus </it>was highly resistant to all pyrethroid insecticides tested. It was susceptible to DDT, except near Ho Chi Minh City where it showed possible DDT resistance. In Vietnam, pyrethroid susceptible and tolerant <it>Anopheles minimus s.l</it>. populations were found, whereas <it>An. minimus s.l</it>. from Cambodia, Laos and Thailand were susceptible. Only two <it>An. minimus s.l</it>. populations showed DDT tolerance. <it>Anopheles vagus </it>was found resistant to DDT and to several pyrethroids in Vietnam and Cambodia.</p> <p>Conclusion</p> <p>This is the first large scale, cross-country survey of insecticide resistance in <it>Anopheles </it>species in the Mekong Region. A unique baseline data on insecticide resistance for the Mekong region is now available, which enables the follow-up of trends in susceptibility status in the region and which will serve as the basis for further resistance management. Large differences in insecticide resistance status were observed among species and countries. In Vietnam, insecticide resistance was mainly observed in low or transmission-free areas, hence an immediate change of malaria vector control strategy is not required. Though, resistance management is important because the risk of migration of mosquitoes carrying resistance genes from non-endemic to endemic areas. Moreover, trends in resistance status should be carefully monitored and the impact of existing vector control tools on resistant populations should be assessed.</p
A research agenda to support the development and implementation of genomics-based clinical informatics tools and resources.
OBJECTIVE: The Genomic Medicine Working Group of the National Advisory Council for Human Genome Research virtually hosted its 13th genomic medicine meeting titled Developing a Clinical Genomic Informatics Research Agenda . The meeting\u27s goal was to articulate a research strategy to develop Genomics-based Clinical Informatics Tools and Resources (GCIT) to improve the detection, treatment, and reporting of genetic disorders in clinical settings.
MATERIALS AND METHODS: Experts from government agencies, the private sector, and academia in genomic medicine and clinical informatics were invited to address the meeting\u27s goals. Invitees were also asked to complete a survey to assess important considerations needed to develop a genomic-based clinical informatics research strategy.
RESULTS: Outcomes from the meeting included identifying short-term research needs, such as designing and implementing standards-based interfaces between laboratory information systems and electronic health records, as well as long-term projects, such as identifying and addressing barriers related to the establishment and implementation of genomic data exchange systems that, in turn, the research community could help address.
DISCUSSION: Discussions centered on identifying gaps and barriers that impede the use of GCIT in genomic medicine. Emergent themes from the meeting included developing an implementation science framework, defining a value proposition for all stakeholders, fostering engagement with patients and partners to develop applications under patient control, promoting the use of relevant clinical workflows in research, and lowering related barriers to regulatory processes. Another key theme was recognizing pervasive biases in data and information systems, algorithms, access, value, and knowledge repositories and identifying ways to resolve them
Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.Peer reviewe
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