Public health training in internal medicine residency programs: a national survey

BACKGROUND: The IOM recommends public health training for all physicians. Data characterizing such training of internal medicine (IM) residents are lacking. PURPOSE: To describe the current state of public health education at IM residency programs, characterize programs offering public health education, and quantify interest in expanding training opportunities. METHODS: IM residency program directors from the 380 Accreditation Council for Graduate Medical Education-accredited residency programs in the U.S were invited to participate in a cross-sectional survey. Responses were received from 127 programs (33%). Data were collected July-December 2012 and analyzed in January 2013. Participants were queried on domestic public health training offered, perceived resident interest in and satisfaction with this training, and interest in expanding training. RESULTS: Eighty-four respondents (66%) provide some form of public health training, but structure and content vary widely. In many programs offering public health training, few residents (\u3c10%) receive it. Although 93 programs (73%) integrate public health into core curricula, only three topics were common to a majority of these programs. Sixty-six respondents (52%) offer clinical training at community-based health centers. Most residency program directors (90%) are very or somewhat interested in expanding their public health training. CONCLUSIONS: This study characterizes the structures and content of public health training across IM residency programs. The wide range highlights the diverse definition of public health training used by IM residency program directors and lack of universal public health competencies required for IM physicians. Opportunities exist for collaboration among residency programs and between IM and public health educators to share best practices

‘Sustaining the Ambition’: The contribution of GTCS-registered teachers as part of the Early Learning and Childcare Workforce in Scotland

This report is about young children and the hopes and ambitions Scotland has for them. Scottish Government policy aspires to make Scotland the best place in the world to grow up. Part of this ambition is to tackle child poverty in Scotland and narrow the gap that disadvantage brings to educational outcomes. At the same time as increasing the free entitlement to early learning and childcare (ELC) with the aim of this rising to 1,140 hours per year by 2020, there has been, over the last 10 years in Scotland, a 29% reduction in the numbers of GTCS-registered teachers employed in such services, but only a 4% drop in child numbers, which gives a ratio of 1 teacher to 84 children at this important stage. The numbers of GTCS-registered teachers in pre-school services face further reductions: if Scotland is to achieve its aspiration of changing child outcomes, no further attrition in teacher employment can be tolerated and serious consideration needs to be given to the future composition of the ELC workforce: a task that is underway following the Scottish Government’s Response to the Independent Review of the Workforce (Siraj & Kingston, 2015)

Pharmacological analysis and structure determination of 7-methylcyanopindolol–bound b1-adrenergic receptor

Comparisons between structures of the b1-adrenergic receptor (AR) bound to either agonists, partial agonists, or weak partial agonists led to the proposal that rotamer changes of Ser5.46, coupled to a contraction of the binding pocket, are sufficient to increase the probability of receptor activation. (RS)-4-[3 (tertbutylamino)-2-hydroxypropoxy]-1H-indole-2 carbonitrile (cyanopindolol) is a weak partial agonist of b1AR and, based on the hypothesis above, we predicted that the addition of a methyl group to form 4-[(2S)-3 (tert-butylamino)-2-hydroxypropoxy]-7-methyl-1H-indole-2 carbonitrile (7-methylcyanopindolol) would dramatically reduce its efficacy. An eight-step synthesis of 7- methylcyanopindolol was developed and its pharmacology was analyzed. 7-Methylcyanopindolol bound with similar affinity to cyanopindolol to both b1AR and b2AR. As predicted, the efficacy of 7-methylcyanopindolol was reduced significantly compared with cyanopindolol, acting as a very weak partial agonist of turkey b1AR and an inverse agonist of human b2AR. The structure of 7-methylcyanopindolol–bound b1AR was determined to 2.4-Å resolution and found to be virtually identical to the structure of cyanopindolol-bound b1AR. The major differences in the orthosteric binding pocket are that it has expanded by 0.3 Å in 7-methylcyanopindolol–bound b1AR and the hydroxyl group of Ser5.46 is positioned 0.8 Å further from the ligand, with respect to the position of the Ser5.46 side chain in cyanopindololbound b1AR. Thus, the molecular basis for the reduction in efficacy of 7 methylcyanopindolol compared with cyanopindolol may be regarded as the opposite of the mechanism proposed for the increase in efficacy of agonists compared with antagonists

Novel associations in disorders of sex development: findings from the I-DSD registry

Context: The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases.<p></p> Objective: To report the range of associated conditions identified in the international DSD (I-DSD) Registry.<p></p> Design, Setting, and Patients: Anonymized data were extracted from the I-DSD Registry for diagnosis, karyotype, sex of rearing, genetic investigations, and associated anomalies. If necessary, clarification was sought from the reporting clinician.<p></p> Results: Of 649 accessible cases, associated conditions occurred in 168 (26%); 103 (61%) cases had one condition, 31 (18%) had two conditions, 20 (12%) had three conditions, and 14 (8%) had four or more conditions. Karyotypes with most frequently reported associations included 45,X with 6 of 8 affected cases (75%), 45,X/46,XY with 19 of 42 cases (45%), 46,XY with 112 of 460 cases (24%), and 46,XX with 27 of 121 cases (22%). In the 112 cases of 46,XY DSD, the commonest conditions included small for gestational age in 26 (23%), cardiac anomalies in 22 (20%), and central nervous system disorders in 22 (20%), whereas in the 27 cases of 46,XX DSD, skeletal and renal anomalies were commonest at 12 (44%) and 8 (30%), respectively. Of 170 cases of suspected androgen insensitivity syndrome, 19 (11%) had reported anomalies and 9 of these had confirmed androgen receptor mutations.<p></p> Conclusions: Over a quarter of the cases in the I-DSD Registry have an additional condition. These associations can direct investigators toward novel genetic etiology and also highlight the need for more holistic care of the affected person.<p></p&gt

Comparison of whole-body MRI, CT, and bone scintigraphy for response evaluation of cancer therapeutics in metastatic breast cancer to bone

In participants receiving systemic anticancer therapy for bone-only metastatic breast cancer, whole-body MRI enabled identification of progressive disease earlier than whole-body CT and bone scintigraphy. Background CT and bone scintigraphy have limitations in evaluating systemic anticancer therapy (SACT) response in bone metastases from metastatic breast cancer (MBC). Purpose To evaluate whether whole-body MRI enables identification of progressive disease (PD) earlier than CT and bone scintigraphy in bone-only MBC. Materials and Methods This prospective study evaluated participants with bone-only MBC between May 2016 and January 2019 (ClinicalTrials.gov identifier: NCT03266744). Participants were enrolled at initiation of first or subsequent SACT based on standard CT and bone scintigraphy imaging. Baseline whole-body MRI was performed within 2 weeks of entry; those with extraosseous disease were excluded. CT and whole-body MRI were performed every 12 weeks until definitive PD was evident with one or both modalities. In case of PD, bone scintigraphy was used to assess for bone disease progression. Radiologists independently interpreted images from CT, whole-body MRI, or bone scintigraphy and were blinded to results with the other modalities. Systematic differences in performance between modalities were analyzed by using the McNemar test. Results Forty-five participants (mean age, 60 years ± 13 [standard deviation]; all women) were evaluated. Median time on study was 36 weeks (range, 1–120 weeks). Two participants were excluded because of unequivocal evidence of liver metastases at baseline whole-body MRI, two participants were excluded because they had clinical progression before imaging showed PD, and one participant was lost to follow-up. Of the 33 participants with PD at imaging, 67% (22 participants) had PD evident at whole-body MRI only and 33% (11 participants) had PD at CT and whole-body MRI concurrently; none had PD at CT only (P < .001, McNemar test). There was only slight agreement between whole-body MRI and CT (Cohen κ, 0.15). PD at bone scintigraphy was reported in 50% of participants (13 of 26) with bone progression at CT and/or whole-body MRI (P < .001, McNemar test). Conclusion Whole-body MRI enabled identification of progressive disease before CT in most participants with bone-only metastatic breast cancer. Progressive disease at bone scintigraphy was evident in only half of participants with bone progression at whole-body MRI

Framing access to medicines in developing countries: an analysis of media coverage of Canada's Access to Medicines Regime

<p>Abstract</p> <p>Background</p> <p>In September 2003, the Canadian government committed to developing legislation that would facilitate greater access to affordable medicines for developing countries. Over the course of eight months, the legislation, now known as Canada's Access to Medicines Regime (CAMR), went through a controversial policy development process and the newspaper media was one of the major venues in which the policy debates took place. The purpose of this study was to examine how the media framed CAMR to determine how policy goals were conceptualized, which stakeholder interests controlled the public debate and how these variables related to the public policy process.</p> <p>Methods</p> <p>We conducted a qualitative content analysis of newspaper coverage of the CAMR policy and implementation process from 2003-2008. The primary theoretical framework for this study was framing theory. A total of 90 articles from 11 Canadian newspapers were selected for inclusion in our analysis. A team of four researchers coded the articles for themes relating to access to medicines and which stakeholders' voice figured more prominently on each issue. Stakeholders examined included: the research-based industry, the generic industry, civil society, the Canadian government, and developing country representatives.</p> <p>Results</p> <p>The most frequently mentioned themes across all documents were the issues of drug affordability, intellectual property, trade agreements and obligations, and development. Issues such as human rights, pharmaceutical innovation, and economic competitiveness got little media representation. Civil society dominated the media contents, followed far behind by the Canadian government, the research-based and generic pharmaceutical industries. Developing country representatives were hardly represented in the media.</p> <p>Conclusions</p> <p>Media framing obscured the discussion of some of the underlying policy goals in this case and failed to highlight issues which are now significant barriers to the use of the legislation. Using the media to engage the public in more in-depth exploration of the policy issues at stake may contribute to a more informed policy development process. The media can be an effective channel for those stakeholders with a weaker voice in policy deliberations to raise public attention to particular issues; however, the political and institutional context must be taken into account as it may outweigh media framing effects.</p

ACCORD: A Multicentre, Seamless, Phase 2 Adaptive Randomisation Platform Study to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalised Patients: A structured summary of a study protocol for a randomised controlled trial

Funder: UKRIAbstract: Objectives: Stage 1: To evaluate the safety and efficacy of candidate agents as add-on therapies to standard of care (SoC) in patients hospitalised with COVID-19 in a screening stage. Stage 2: To confirm the efficacy of candidate agents selected on the basis of evidence from Stage 1 in patients hospitalised with COVID-19 in an expansion stage. Trial design: ACCORD is a seamless, Phase 2, adaptive, randomised controlled platform study, designed to rapidly test candidate agents in the treatment of COVID-19. Designed as a master protocol with each candidate agent being included via its own sub-protocol, initially randomising equally between each candidate and a single contemporaneous SoC arm (which can adapt into 2:1). Candidate agents currently include bemcentinib, MEDI3506, acalabrutinib, zilucoplan and nebulised heparin. For each candidate a total of 60 patients will be recruited in Stage 1. If Stage 1 provides evidence of efficacy and acceptable safety the candidate will enter Stage 2 where a total of approximately 126 patients will be recruited into each study arm sub-protocol. Enrollees and outcomes will not be shared across the Stages; the endpoint, analysis and sample size for Stage 2 may be adjusted based on evidence from Stage 1. Additional arms may be added as new potential candidate agents are identified via candidate agent specific sub-protocols. Participants: The study will include hospitalised adult patients (≥18 years) with confirmed SARS-CoV-2 infection, the virus that causes COVID-19, that clinically meet Grades 3 (hospitalised – mild disease, no oxygen therapy), Grades 4 (hospitalised, oxygen by mask or nasal prongs) and 5 (hospitalised, non-invasive ventilation or high flow oxygen) of the WHO Working Group on the Clinical Characteristics of COVID-19 9-point category ordinal scale. Participants will be recruited from England, Northern Ireland, Wales and Scotland. Intervention and comparator: Comparator is current standard of care (SoC) for the treatment of COVID-19. Current candidate experimental arms include bemcentinib, MEDI3506, acalabrutinib, zilucoplan and nebulised heparin with others to be added over time. Bemcentinib could potentially reduce viral infection and blocks SARS-CoV-2 spike protein; MEDI3506 is a clinic-ready anti-IL-33 monoclonal antibody with the potential to treat respiratory failure caused by COVID; acalabrutinib is a BTK inhibitor which is anti-viral and anti-inflammatory; zilucoplan is a complement C5 inhibitor which may block the severe inflammatory response in COVID-19 and; nebulised heparin has been shown to bind with the spike protein. ACCORD is linked with the UK national COVID therapeutics task force to help prioritise candidate agents. Main outcomes: Time to sustained clinical improvement of at least 2 points (from randomisation) on the WHO 9-point category ordinal scale, live discharge from the hospital, or considered fit for discharge (a score of 0, 1, or 2 on the ordinal scale), whichever comes first, by Day 29 (this will also define the “responder” for the response rate analyses). Randomisation: An electronic randomization will be performed by Cenduit using Interactive Response Technology (IRT). Randomisation will be stratified by baseline severity grade. Randomisation will proceed with an equal allocation to each arm and a contemporaneous SoC arm (e.g. 1:1 if control and 1 experimental arm; 1:1:1 if two experimental candidate arms etc) but will be reviewed as the trial progresses and may be changed to 2:1 in favour of the candidate agents. Blinding (masking): The trial is open label and no blinding is currently planned in the study. Numbers to be randomised (sample size): This will be in the order of 60 patients per candidate agent for Stage 1, and 126 patients for Stage 2. However, sample size re-estimation may be considered after Stage 1. It is estimated that up to 1800 patients will participate in the overall study. Trial Status: Master protocol version ACCORD-2-001 - Master Protocol (Amendment 1) 22nd April 2020, the trial has full regulatory approval and recruitment is ongoing in the bemcentinib (first patient recruited 6/5/2020), MEDI3506 (first patient recruited 19/5/2020), acalabrutinib (first patient recruited 20/5/2020) and zilucoplan (first patient recruited 19/5/2020) candidates (and SoC). The recruitment dates of each arm will vary between candidate agents as they are added or dropped from the trial, but will have recruited and reported within a year. Trial registration: EudraCT 2020-001736-95, registered 28th April 2020. Full protocol: The full protocol (Master Protocol with each of the candidate sub-protocols) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Environmental Source of Candida dubliniensis

We isolated Candida dubliniensis from a nonhuman source, namely, tick samples from an Irish seabird colony. The species was unambiguously identified by phenotypic and genotypic means. Analysis of the 5.8S rRNA gene showed that the environmental isolates belong to C. dubliniensis genotype 1