35 research outputs found

    Effect of a care transition intervention by pharmacists: an RCT

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    Abstract Background Pharmacists may improve medication-related outcomes during transitions of care. The aim of the Iowa Continuity of Care Study was to determine if a pharmacist case manager (PCM) providing a faxed discharge medication care plan from a tertiary care institution to primary care could improve medication appropriateness and reduce adverse events, rehospitalization and emergency department visits. Methods Design. Randomized, controlled trial of 945 participants assigned to enhanced, minimal and usual care groups conducted 2007 to 2012. Subjects. Participants with cardiovascular-related conditions and/or asthma or chronic obstructive pulmonary disease were recruited from the University of Iowa Hospital and Clinics following admission to general medicine, family medicine, cardiology or orthopedics. Intervention. The minimal group received admission history, medication reconciliation, patient education, discharge medication list and medication recommendations to inpatient team. The enhanced group also received a faxed medication care plan to their community physician and pharmacy and telephone call 3–5 days post-discharge. Participants were followed for 90 days post-discharge. Main Outcomes and Measures. Medication appropriateness index (MAI), adverse events, adverse drug events and post-discharge healthcare utilization were compared by study group using linear and logistic regression, as models accommodating random effects due to pharmacists indicated little clustering. Results Study groups were similar at baseline and the intervention fidelity was high. There were no statistically significant differences by study group in medication appropriateness, adverse events or adverse drug events at discharge, 30-day and 90-day post-discharge. The average MAI per medication as 0.53 at discharge and increased to 0.75 at 90 days, and this was true across all study groups. Post-discharge, about 16% of all participants experienced an adverse event, and this did not differ by study group (p > 0.05). Almost one-third of all participants had any type of healthcare utilization within 30 days post-discharge, where 15% of all participants had a 30-day readmission. Healthcare utilization post-discharge was not statistically significant different at 30 or 90 days by study group. Conclusion The pharmacist case manager did not affect medication use outcomes post-discharge perhaps because quality of care measures were high in all study groups. Trial registration Clinicaltrials.gov registration: NCT00513903 , August 7, 2007.http://deepblue.lib.umich.edu/bitstream/2027.42/109686/1/12913_2014_Article_3640.pd

    The last bastion? X-chromosome genotyping of Anopheles gambiae species-pair males from a hybrid zone reveals complex recombination within the major candidate ‘genomic island of speciation’

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    Speciation with gene flow may be aided by reduced recombination helping to build linkage between genes involved in the early stages of reproductive isolation. Reduced recombination on chromosome-X has been implicated in speciation within the Anopheles gambiae complex, species of which represent the major Afrotropical malaria vectors. The most recently diverged, morphologically-indistinguishable, species-pair, An. gambiae and An. coluzzii, ubiquitously display a ‘genomic island of divergence’ spanning over 4Mb from chromosome-X centromere, which represents a particularly promising candidate region for reproductive isolation genes, in addition to containing the diagnostic markers used to distinguish the species. Very low recombination makes the island intractable for experimental recombination studies, but an extreme hybrid zone in Guinea Bissau offers the opportunity for natural investigation of X-island recombination. SNP-analysis of chromosome-X hemizygous males revealed: (i) strong divergence in the X-island despite a lack of autosomal divergence; (ii) individuals with multiple-recombinant genotypes, including likely double crossovers and localized gene conversion; (iii) recombination-driven discontinuity both within and between the molecular species markers, suggesting that the utility of the diagnostics is undermined under high hybridization. The largely-, but incompletely-protected nature of the X-centromeric genomic island is consistent with a primary candidate area for accumulation of adaptive variants driving speciation with gene flow, whilst permitting some selective shuffling and removal of genetic variation

    Management of insecticide resistance in the major Aedes vectors of arboviruses Advances and challenges

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    Background The landscape of mosquito-borne disease risk has changed dramatically in recent decades, due to the emergence and reemergence of urban transmission cycles driven by invasive Aedes aegypti and Ae. albopictus. Insecticide resistance is already widespread in the yellow fever mosquito, Ae. Aegypti; is emerging in the Asian tiger mosquito Ae. Albopictus; and is now threatening the global fight against human arboviral diseases such as dengue, yellow fever, chikungunya, and Zika. Because the panel of insecticides available for public health is limited, it is of primary importance to preserve the efficacy of existing and upcoming active ingredients. Timely implementation of insecticide resistance management (IRM) is crucial to maintain the arsenal of effective public health insecticides and sustain arbovirus vector control. Methodology and principal findings This Review is one of a series being generated by the Worldwide Insecticide resistance Network (WIN) and aims at defining the principles and concepts underlying IRM, identifying the main factors affecting the evolution of resistance, and evaluating the value of existing tools for resistance monitoring. Based on the lessons taken from resistance strategies used for other vector species and agricultural pests, we propose a framework for the implementation of IRM strategies for Aedes mosquito vectors. Conclusions and significance Although IRM should be a fixture of all vector control programs, it is currently often absent from the strategic plans to control mosquito-borne diseases, especially arboviruses. Experiences from other public health disease vectors and agricultural pests underscore the need for urgent action in implementing IRM for invasive Aedes mosquitoes. Based on a plan developed for malaria vectors, here we propose some key activities to establish a global plan for IRM in Aedes spp. Author summary Arthropod-borne viruses transmitted by Aedes aegypti and Ae. albopictus represent a major public health concern at a global scale. The insecticidal treatments exerted on both species have selected for various resistance mechanisms within wild populations. Although the impact of insecticide resistance on the efficacy of vector control operations remains broadly unknown, it is of primary importance to implement strategies for preserving the efficacy of treatments and reducing the pathogen transmission during epidemics. For this purpose, there are urgent needs for new tools for vector control and insecticide resistance monitoring to improve the management of insecticide resistance in Aedes species

    High Genetic Diversity and Fine-Scale Spatial Structure in the Marine Flagellate Oxyrrhis marina (Dinophyceae) Uncovered by Microsatellite Loci

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    Free-living marine protists are often assumed to be broadly distributed and genetically homogeneous on large spatial scales. However, an increasing application of highly polymorphic genetic markers (e.g., microsatellites) has provided evidence for high genetic diversity and population structuring on small spatial scales in many free-living protists. Here we characterise a panel of new microsatellite markers for the common marine flagellate Oxyrrhis marina. Nine microsatellite loci were used to assess genotypic diversity at two spatial scales by genotyping 200 isolates of O. marina from 6 broad geographic regions around Great Britain and Ireland; in one region, a single 2 km shore line was sampled intensively to assess fine-scale genetic diversity. Microsatellite loci resolved between 1–6 and 7–23 distinct alleles per region in the least and most variable loci respectively, with corresponding variation in expected heterozygosities (He) of 0.00–0.30 and 0.81–0.93. Across the dataset, genotypic diversity was high with 183 genotypes detected from 200 isolates. Bayesian analysis of population structure supported two model populations. One population was distributed across all sampled regions; the other was confined to the intensively sampled shore, and thus two distinct populations co-occurred at this site. Whilst model-based analysis inferred a single UK-wide population, pairwise regional FST values indicated weak to moderate population sub-division (0.01–0.12), but no clear correlation between spatial and genetic distance was evident. Data presented in this study highlight extensive genetic diversity for O. marina; however, it remains a substantial challenge to uncover the mechanisms that drive genetic diversity in free-living microorganisms

    Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

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    Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes1, with epidemiological association with other autoimmune diseases2. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment

    Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

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    Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

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    Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research
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