Improving the delivery of brief interventions for heavy drinking in primary health care: outcome results of the Optimizing Delivery of Health Care Intervention (ODHIN) five country cluster randomized factorial trial

Aims: To test if training and support of primary health care providers (PHCP), financial reimbursement to PHCP for screening and brief advice, and option for PHCP to refer screen positive patients to an internet-based method of giving advice (eBI) increases PHCP’s delivery of screening and advice to heavy drinkers, compared to a control group of PHCPs. Design: Cluster randomized factorial trial with 12-week implementation measurement period. Setting: Primary health care units (PHCU) in different locations throughout Catalonia, England, Netherlands, Poland and Sweden. Participants: 120 PHCU, 24 in each of Catalonia, England, Netherlands, Poland and Sweden. Interventions PHCUs were randomized to one of eight groups: care as usual, training and support (TS), financial reimbursement (FR), and eBI; paired combinations of TS, FR and eBI, and all of FR, TS and eBI. Outcome measures Primary outcome measures is proportion of eligible patients screened during a 12-week implementation period. Secondary outcome measures are proportion of screen positive patients advised; and, proportion of consulting adult patients given an intervention (screening and advice to screen positives) during the same 12-week implementation period. Results During a 4-week baseline measurement period, 5.9 (95% CI 3.4 to 8.4)per 100 adult patients consulting per PHCU were screened for their alcohol consumption. Based on the factorial design, PHCU that received TS had a 1.48 (95% CI 1.13 to 1.95)relatively higher proportion of patients screened during the 12-week implementation period than PHCU that did not receive TS; PHCU that received FR had a 2.00 (95% CI 1.56 to 2.56) relatively higher proportion than no FR. The option of referral to eBI did not have a higher proportion. A combination of TS plus FR had a 2.34 (95% CI 1.77 to 3.10) relatively higher proportion of patients screened than no TS plus FR. A combination of TS plus FR plus eBI had a 1.68 (95% CI 1.11 to 2.53) relatively higher proportion of patients screened than no TS plus FR plus eBI. Conclusions Training and support of PHCP, and financial reimbursement to PHCP for screening and brief advice increase the proportion of adult patients screened for their alcohol consumption, at least in the short term

How communication of genetic information within the family is addressed in genetic counselling: a systematic review of research evidence

Supporting consultands to communicate risk information with their relatives is key to obtaining the full benefits of genetic health care. To understand how health-care professionals address this issue in clinical practice and what interventions are used specifically to assist consultands in their communication of genetic information to appropriate relatives, we conducted a systematic review. Four electronic databases and four subject-specific journals were searched for papers published, in English, between January 1997 and May 2014. Of 2926 papers identified initially, 14 papers met the inclusion criteria for the review and were heterogeneous in design, setting and methods. Thematic data analysis has shown that dissemination of information within families is actively encouraged and supported by professionals. Three overarching themes emerged: (1) direct contact from genetic services: sending letters to relatives of mutation carriers; (2) professionals' encouragement of initially reluctant consultands to share relevant information with at-risk relatives and (3) assisting consultands in communicating genetic information to their at-risk relatives, which included as subthemes (i) psychoeducational guidance and (ii) written information aids. Findings suggest that professionals' practice and interventions are predicated on the need to proactively encourage family communication. We discuss this in the context of what guidance of consultands by professionals might be appropriate, as best practices to facilitate family communication, and of the limits to non-directiveness in genetic counselling

Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.

BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.)

Shocks and cold fronts in galaxy clusters

Table of contents (abridged): COLD FRONTS Origin and evolution of merger cold fronts Cold fronts in cluster cool cores . . . Simulations of gas sloshing. Origin of density discontinuity. . . . Effect of sloshing on cluster mass estimates and cooling flows. Zoology of cold fronts COLD FRONTS AS EXPERIMENTAL TOOL Velocities of gas flows Thermal conduction and diffusion across cold fronts Stability of cold fronts . . . Rayleigh-Taylor instability. Kelvin-Helmholtz instability. Possible future measurements using cold fronts . . . Plasma depletion layer and magnetic field. Effective viscosity of ICM. SHOCK FRONTS AS EXPERIMENTAL TOOL Cluster merger shocks Mach number determination Front width Mach cone and reverse shock? Test of electron-ion equilibrium . . . Comparison with other astrophysical plasmas Shocks and cluster cosmic ray population . . . Shock acceleration. Compression of fossil electrons. . . . Yet another method to measure intracluster magnetic field.Comment: 67 pages, 38 figures. v2: minor corrections. An updated version of a review article to appear in Physics Report

The E-ELT first light spectrograph HARMONI: capabilities and modes

Trabajo presentado en SPIE Astronomical Telescopes, celebrado en San Diego (California), del 26 de junio al 1 de julio de 2016HARMONI is the E-ELT's first light visible and near-infrared integral field spectrograph. It will provide four different spatial scales, ranging from coarse spaxels of 60 × 30 mas best suited for seeing limited observations, to 4 mas spaxels that Nyquist sample the diffraction limited point spread function of the E-ELT at near-infrared wavelengths. Each spaxel scale may be combined with eleven spectral settings, that provide a range of spectral resolving powers (R 3500, 7500 and 20000) and instantaneous wavelength coverage spanning the 0.5 - 2.4 ¿m wavelength range of the instrument. In autumn 2015, the HARMONI project started the Preliminary Design Phase, following signature of the contract to design, build, test and commission the instrument, signed between the European Southern Observatory and the UK Science and Technology Facilities Council. Crucially, the contract also includes the preliminary design of the HARMONI Laser Tomographic Adaptive Optics system. The instrument's technical specifications were finalized in the period leading up to contract signature. In this paper, we report on the first activity carried out during preliminary design, defining the baseline architecture for the system, and the trade-off studies leading up to the choice of baseline

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year