Senicapoc treatment in COVID-19 Patients with Severe Respiratory Insufficiency - A Randomized, Open-Label, Phase II Trial

BACKGROUND: The aim of the current study was to determine if treatment with senicapoc, improves the PaO(2)/FiO(2) ratio in patients with COVID‐19 and severe respiratory insufficiency. METHODS: Investigator‐initiated, randomized, open‐label, phase II trial in four intensive care units (ICU) in Denmark. We included patients aged ≥18 years and admitted to an ICU with severe respiratory insufficiency due to COVID‐19. The intervention consisted of 50 mg enteral senicapoc administered as soon as possible after randomization and again after 24 h. Patients in the control group received standard care only. The primary outcome was the PaO(2)/FiO(2) ratio at 72 h. RESULTS: Twenty patients were randomized to senicapoc and 26 patients to standard care. Important differences existed in patient characteristics at baseline, including more patients being on non‐invasive/invasive ventilation in the control group (54% vs. 35%). The median senicapoc concentration at 72 h was 62.1 ng/ml (IQR 46.7–71.2). The primary outcome, PaO(2)/FiO(2) ratio at 72 h, was significantly lower in the senicapoc group (mean 19.5 kPa, SD 6.6) than in the control group (mean 24.4 kPa, SD 9.2) (mean difference −5.1 kPa [95% CI −10.2, −0.04] p = .05). The 28‐day mortality in the senicapoc group was 2/20 (10%) compared with 6/26 (23%) in the control group (OR 0.36 95% CI 0.06–2.07, p = .26). CONCLUSIONS: Treatment with senicapoc resulted in a significantly lower PaO(2)/FiO(2) ratio at 72 h with no differences for other outcomes

Policy assessment and policy development for physical activity promotion: results of an exploratory intervention study in 15 European Nations

<p>Abstract</p> <p>Background</p> <p>Purpose of the study was to test a theoretical model to assess and develop policies for the promotion of physical activity among older people as part of an international intervention study.</p> <p>Methods</p> <p>248 semi-standardized interviews with policy-makers were conducted in 15 European nations. The questionnaire assessed policy-makers' perceptions of organizational goals, resources, obligations, as well as organizational, political and public opportunities in the area of physical activity promotion among older people. In order to develop policies, workshops with policy-makers were conducted. Workshop outputs and outcomes were assessed for four nations nine months after the workshops.</p> <p>Results</p> <p>Policy assessment: Results of the policy assessment were diverse across nations and policy sectors. For example, organizational goals regarding actions for physical activity promotion were perceived as being most favorably by the sports sector. Organizational obligations for the development of such policies were perceived as being most favorably by the health sector.</p> <p>Policy development: The workshops resulted in different outputs: a national intersectoral action plan (United Kingdom), a national alliance (Sweden), an integrated policy (the Netherlands), and a continuing dialogue (Germany).</p> <p>Conclusions</p> <p>Theory-driven policy assessment and policy-maker workshops might be an important means of scientific engagement in policy development for health promotion.</p

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

Studie av potensialet for verdiskaping og sysselsetting av sirkulærøkonomiske tiltak.Utvalgte tiltak og case.

Sirkulærøkonomi handler om å utnytte ressursene våre best mulig. Det sikrer bærekraft og verdiskaping på både kort og lang sikt. Sirkulærøkonomien prøver å lukke materialsløyfene for å hindre at mulige ressurser går tapt. Vi ønsker at ressursene skal vare lenger, og derfor at ressursenes verdi og kvalitet forblir så høy som mulig så lenge som mulig. I dette studiet vil vi undersøke hvilke verdiskapings- og sysselsettingspotensialer sirkulærøkonomi kan utløse i ulike sektorer og regioner i Norge frem til 2030. Vi benytter makroøkonomisk kryssløpsanalyse for å utføre disse analysene. EU la i mars 2020 fram sin nye handlingsplan for sirkulærøkonomi, som er en høyt prioritert leveranse under The European Green Deal, EUs grønne vekststrategi. Handlingsplanen inneholder 35 initiativer og tiltak som skal fremme en sirkulærøkonomi, og som vil legges fram de neste tre årene. Mye av dette arbeidet får gjennom EØS-avtalen betydning for Norge, og regjeringen planlegger å legge fram en nasjonal strategi om sirkulærøkonomi i 2020. Med bakgrunn i de overnevnte handlingsplanene, reguleringer og mål ser vi i dette studiet nærmere på følgende sektorer og produkter: • Elektronikk og elektronisk utstyr • Tekstiler • Møbler • Batterier • Byggevarer • Plastemballasje • Gjenvinning Økt næringsaktivitet, i form av sysselsatte og verdiskaping, er basert på nåværende økonomiske struktur. Å fremskrive disse resultatene frem til 2030 vil ikke nødvendigvis fange hele bildet, men det gir et godt utgangspunkt for å gjøre vurderinger knyttet til den sirkulærøkonomiske omstillingen, samt hvilke tiltak som bør iverksettes for å oppnå ønsket utvikling. Tiltak knyttet til etablering av ny industri bør derfor ta hensyn til både historisk sammensetting og fremtidsbehovene. Resultatene fra de ulike casene og scenarioene beskrevet i denne rapporten viser at verdiskapingspotensialet er betydelig for en omstilling til et mer sirkulærøkonomisk samfunn. Dette vil også kunne medføre et betraktelig behov for nye sysselsatte. Både verdiskaping og behovet for nye sysselsatte er estimert å bre seg utover hele landet, og det er gjort anslag på hvor store virkninger omstillingen kan gi per fylke. En sirkulærøkonomisk omstilling vil også kunne kreve en del endringer for arbeidsplassene, blant annet knyttet til endrede kompetansebehov i nye og eksisterende næringer. Ut ifra analyseresultatene anslår vi at det kommer til å stilles krav til høy domenekunnskap og/eller fagbrev for mange av disse fremvoksende arbeidsplassene. Analysen i denne rapporten viser en tydelig positiv effekt av en sirkulærøkonomisk omstilling. Likevel eksisterer det flere systemiske barrierer, og avgifts- og reguleringssystemer i dagens samfunn som er mer tilrettelagt for lineær produksjon og forbruk. Overgangen til sirkulærøkonomi er ekstremt avhengig av innovativ politikkimplementering, som også beskrevet i "kunnskapsgrunnlag for nasjonal strategi for sirkulærøkonomi".publishedVersio

Semiautomated improvement of RNA alignments

We have developed a semiautomated RNA sequence editor (SARSE) that integrates tools for analyzing RNA alignments. The editor highlights different properties of the alignment by color, and its integrated analysis tools prevent the introduction of errors when doing alignment editing. SARSE readily connects to external tools to provide a flexible semiautomatic editing environment. A new method, Pcluster, is introduced for dividing the sequences of an RNA alignment into subgroups with secondary structure differences. Pcluster was used to evaluate 574 seed alignments obtained from the Rfam database and we identified 71 alignments with significant prediction of inconsistent base pairs and 102 alignments with significant prediction of novel base pairs. Four RNA families were used to illustrate how SARSE can be used to manually or automatically correct the inconsistent base pairs detected by Pcluster: the mir-399 RNA, vertebrate telomase RNA (vert-TR), bacterial transfer-messenger RNA (tmRNA), and the signal recognition particle (SRP) RNA. The general use of the method is illustrated by the ability to accommodate pseudoknots and handle even large and divergent RNA families. The open architecture of the SARSE editor makes it a flexible tool to improve all RNA alignments with relatively little human intervention. Online documentation and software are available at http://sarse.ku.dk

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Running title: Semi-automated RNA sequence editin