Making soft intelligence hard: a multi-site qualitative study of challenges relating to voice about safety concerns.

BACKGROUND: Healthcare organisations often fail to harvest and make use of the 'soft intelligence' about safety and quality concerns held by their own personnel. We aimed to examine the role of formal channels in encouraging or inhibiting employee voice about concerns. METHODS: Qualitative study involving personnel from three academic hospitals in two countries. Interviews were conducted with 165 participants from a wide range of occupational and professional backgrounds, including senior leaders and those from the sharp end of care. Data analysis was based on the constant comparative method. RESULTS: Leaders reported that they valued employee voice; they identified formal organisational channels as a key route for the expression of concerns by employees. Formal channels and processes were designed to ensure fairness, account for all available evidence and achieve appropriate resolution. When processed through these formal systems, concerns were destined to become evidenced, formal and tractable to organisational intervention. But the way these systems operated meant that some concerns were never voiced. Participants were anxious about having to process their suspicions and concerns into hard evidentiary facts, and they feared being drawn into official procedures designed to allocate consequence. Anxiety about evidence and process was particularly relevant when the intelligence was especially 'soft'-feelings or intuitions that were difficult to resolve into a coherent, compelling reconstruction of an incident or concern. Efforts to make soft intelligence hard thus risked creating 'forbidden knowledge': dangerous to know or share. CONCLUSIONS: The legal and bureaucratic considerations that govern formal channels for the voicing of concerns may, perversely, inhibit staff from speaking up. Leaders responsible for quality and safety should consider complementing formal mechanisms with alternative, informal opportunities for listening to concerns

Mechanism of Activation and Inhibition of the HER4/ErbB4 Kinase

SummaryHER4/ErbB4 is a ubiquitously expressed member of the EGF/ErbB family of receptor tyrosine kinases that is essential for normal development of the heart, nervous system, and mammary gland. We report here crystal structures of the ErbB4 kinase domain in active and lapatinib-inhibited forms. Active ErbB4 kinase adopts an asymmetric dimer conformation essentially identical to that observed to be important for activation of the EGF receptor/ErbB1 kinase. Mutagenesis studies of intact ErbB4 in Ba/F3 cells confirm the importance of this asymmetric dimer for activation of intact ErbB4. Lapatinib binds to an inactive form of the ErbB4 kinase in a mode equivalent to its interaction with the EGF receptor. All ErbB4 residues contacted by lapatinib are conserved in the EGF receptor and HER2/ErbB2, which lapatinib also targets. These results demonstrate that key elements of kinase activation and inhibition are conserved among ErbB family members

An exploration of knowledge, attitudes and advice given by health professionals to parents in Ireland about the introduction of solid foods. A pilot study

<p>Abstract</p> <p>Background</p> <p>For the purposes of this paper "weaning is defined as the introduction of the first solid foods to infants". Global recommendations by the World Health Organisation (WHO) recommend that all infants be exclusively breast-fed for the first six months of life. No global recommendations have been made for formula fed infants. In Europe it is recommended that weaning foods should be introduced between 18 weeks and 26 weeks regardless of whether infants are breast or formula fed. In the United Kingdom it is recommended that solids be introduced at around six-months for both breast and formula fed infants. In Ireland official guidelines recommend that breast fed infants should be introduced solids at 6 months of age while for formula fed infants the recommendation is for 4 months. The disparity between these global, European, UK and local recommendations may be a source of confusion for parents and health care professional based in Ireland. Emerging evidence suggests that babies in Ireland are given solid foods before the recommended age but there has been little investigation of the weaning advice provided by health professionals. Since community health professionals have routine parent interactions in the pre-weaning and early-weaning period and hence are in a unique position to positively influence parental weaning decisions, this study aimed to explore their knowledge, attitudes and advice practices about weaning.</p> <p>Methods</p> <p>A mixed-methods approach was used for the research, commencing with a multi-disciplinary focus group to guide and develop a questionnaire. Questionnaires were then distributed in a postal survey to General Practitioners (GPs) (<it>n </it>179), Practice Nurses (PNs) (<it>n </it>121), Public Health Nurses (PHNs) (<it>n </it>107) and Community Dieticians (CDs) (<it>n </it>8).</p> <p>Results</p> <p>The results indicate varying levels of knowledge of official weaning recommendations and a variety of advice practices. CDs and PHNs acknowledged a clear role in providing weaning advice while demonstrating high confidence levels in providing this advice. However, 19% of PNs and 7% of GP respondents did not acknowledge that they have a role in providing weaning advice to parents; even though Health Service Executive (HSE) written literature given to parents states that they should seek information from PNs and GPs.</p> <p>Conclusion</p> <p>Small pockets of misinformation about the introduction of solid foods persist amongst health professionals which may lead to inconsistent advice for parents. Further research is needed.</p

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Explaining Matching Michigan: an ethnographic study of a patient safety program

BACKGROUND: Quality and safety improvement initiatives in healthcare often display two disconcerting effects. The first is a failure to outperform the secular trend. The second is the decline effect, where an initially promising intervention appears not to deliver equally successful results when attempts are made to replicate it in new settings. Matching Michigan, a patient safety program aimed at decreasing central line infections in over 200 intensive care units (ICUs) in England, may be an example of both. We aimed to explain why these apparent effects may have occurred. METHODS: We conducted interviews with 98 staff and non-participant observation on 19 ICUs; 17 of these units were participating in Matching Michigan. We undertook further telephone interviews with 29 staff who attended program training events and we analyzed relevant documents. RESULTS: One Matching Michigan unit transformed its practices and culture in response to the program; five boosted existing efforts, and 11 made little change. Matching Michigan's impact may have been limited by features of program design and execution; it was not an exact replica of the original project. Outer and inner contexts strongly modified the program's effects. The outer context included previous efforts to tackle central line infections superimposed on national infection control policies that were perceived by some as top-down and punitive. This undermined engagement in the program and made it difficult to persuade participants that the program was necessary. Individual ICUs' histories and local context were also highly consequential: their past experience of quality improvement, the extent to which they were able to develop high quality data collection and feedback systems, and the success of local leaders in developing consensus and coalition all influenced the program's impact on local practices. CONCLUSIONS: Improved implementation of procedural good practice may occur through many different routes, of which program participation is only one. The 'phenotype' of compliance may therefore arise through different 'genotypes.' When designing and delivering interventions to improve quality and safety, risks of decline effects and difficulties in demonstrating added value over the secular trend might be averted by improved understanding of program mechanisms and contexts of implementation

Unblinding following trial participation:qualitative study of participants' perspectives

Background: The implications of offering unblinding to trial participants to treatment arm after trial completion have been little explored. Purpose: We sought to explore trial participants’ perspectives on whether they would like to be unblinded as to the treatment arm to which they were allocated following involvement in a large randomised controlled trial (RCT). Methods: We conducted semi-structured interviews with 38 women who had participated in a trial during suspected preterm labour and had received the results of a long-term follow-up study that identified adverse outcomes for children in some of the treatment groups. Participants were sampled purposively. Analysis was based on the constant comparative method. Results: Most women reported that they wanted to know the treatment arm to which they had been allocated. While the primary motive for some was curiosity, many others wanted to know as part of an attempt to understand or explain their child’s current health problems. These women were motivated by a search for a coherent causal narrative, even though unblinding was unlikely to be able to meet their aspirations. Some participants identified potential disadvantages in discovering their treatment allocation, including feeling responsible for their child’s health status, and some women were very clear that they did not want to know their treatment group. Limitations: A purposive sample was used and the extent to which it represents the views of all participants in the study is not established. Conclusions Important challenges arise in offering to unblind trial participants, whatever the trial results. Participants may need help and support to understand the limitations of the knowledge they gain through being unblinded and to decide whether they wish to know to which treatment arm they were allocated