11-[3-(Dimethyl­amino)prop­yl]-6,11-dihydro­dibenzo[b,e]thiepin-11-ol

There are two independent mol­ecules (A and B) in the asymmetric unit of the title compound, C19H23NOS. In each mol­ecule, the seven-membered thiepine ring is bent into a slightly twisted V-shape. The dihedral angles between the mean planes of the two benzene rings fused to the thiepine ring are 75.7 (5) in mol­ecule A and 73.8 (4)° in mol­ecule B. In both mol­ecules, an intra­molecular O—H⋯N hydrogen bond occurs. In the crystal, weak inter­molecular C—H⋯O and C—H⋯π-ring inter­actions are observed

Emerging Infectious Diseases: a 10-Year Perspective from the National Institute of Allergy and Infectious Diseases

Advances in infectious disease research over the past 10 years have allowed breakthroughs in th

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

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

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

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. 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. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

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

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

Spirituality, Religion and Psychiatry in New Zealand: A survey of psychiatrists in New Zealand

The literature on spirituality, religion and health identifies spirituality and religious belief as being important components in the recovery from mental illness (May, Muir-Cochrane, & Clare, 2005; Swinton, 2001; Turbott, 1996). This project attempted to identify by use of a questionnaire New Zealand psychiatrists’ attitudes and practice with regard to religious and spiritual issues in mental health. This study drew on and modified previous work on the topic (Curlin et al., 2007). Three questions were asked: 1. What are the opinions and attitudes of New Zealand psychiatrists regarding religion/spirituality and mental health? 2. What factors determine a clinician’s attitude and practice, with respect to spiritual matters? 3. What factors determine a clinician’s attitude and practice, with regard to spiritual and culturally-based mental health care providers? (i.e. Chaplains and kaumatua/tohunga) An online survey was used, and advertised in the Royal Australian and New Zealand College of Psychiatrists on-line newsletter. The response rate was 18% of the total number of psychiatrists in New Zealand. Respondents self-selected to complete the survey, and, as such, the sample may not be representative of psychiatrists in New Zealand. The opinions and attitudes of respondents regarding religion/spirituality and mental health were found to be mixed. A number, however, whilst not necessarily professing religious and spiritual beliefs, acknowledged their importance to patients and therefore to psychiatric assessment and treatment. The findings suggest that in New Zealand ethnicity is the single most significant factor that determines clinicians’ opinions and practices with respect to religion and spirituality. Those psychiatrists in this sample who identified as New Zealanders were less likely to believe in God, less likely to see value in religious involvement and less likely to refer patients to spiritual and cultural advisors or carers. On the other hand, psychiatrists identifying as New Zealanders, particularly those still in training, were more likely to see value in marae involvement but were not more likely to refer Maori patients to Maori spiritual leaders. The findings suggest further research is needed in this area of psychiatry in New Zealand using a more representative sample. This could help provide a basis for better training of psychiatrists in the religious/spiritual domain and therefore better understanding. As a result mental health consumers could receive more effective treatment modalities and outcomes

Spirituality, Religion and Psychiatry in New Zealand: A survey of psychiatrists in New Zealand

The literature on spirituality, religion and health identifies spirituality and religious belief as being important components in the recovery from mental illness (May, Muir-Cochrane, & Clare, 2005; Swinton, 2001; Turbott, 1996). This project attempted to identify by use of a questionnaire New Zealand psychiatrists’ attitudes and practice with regard to religious and spiritual issues in mental health. This study drew on and modified previous work on the topic (Curlin et al., 2007). Three questions were asked: 1. What are the opinions and attitudes of New Zealand psychiatrists regarding religion/spirituality and mental health? 2. What factors determine a clinician’s attitude and practice, with respect to spiritual matters? 3. What factors determine a clinician’s attitude and practice, with regard to spiritual and culturally-based mental health care providers? (i.e. Chaplains and kaumatua/tohunga) An online survey was used, and advertised in the Royal Australian and New Zealand College of Psychiatrists on-line newsletter. The response rate was 18% of the total number of psychiatrists in New Zealand. Respondents self-selected to complete the survey, and, as such, the sample may not be representative of psychiatrists in New Zealand. The opinions and attitudes of respondents regarding religion/spirituality and mental health were found to be mixed. A number, however, whilst not necessarily professing religious and spiritual beliefs, acknowledged their importance to patients and therefore to psychiatric assessment and treatment. The findings suggest that in New Zealand ethnicity is the single most significant factor that determines clinicians’ opinions and practices with respect to religion and spirituality. Those psychiatrists in this sample who identified as New Zealanders were less likely to believe in God, less likely to see value in religious involvement and less likely to refer patients to spiritual and cultural advisors or carers. On the other hand, psychiatrists identifying as New Zealanders, particularly those still in training, were more likely to see value in marae involvement but were not more likely to refer Maori patients to Maori spiritual leaders. The findings suggest further research is needed in this area of psychiatry in New Zealand using a more representative sample. This could help provide a basis for better training of psychiatrists in the religious/spiritual domain and therefore better understanding. As a result mental health consumers could receive more effective treatment modalities and outcomes