Prophylactic radiotherapy for the prevention of procedure-tract metastases after surgical and large-bore pleural procedures in malignant pleural mesothelioma (SMART): a multicentre, open-label, phase 3, randomised controlled trial.

The use of prophylactic radiotherapy to prevent procedure-tract metastases (PTMs) in malignant pleural mesothelioma remains controversial, and clinical practice varies worldwide. We aimed to compare prophylactic radiotherapy with deferred radiotherapy (given only when a PTM developed) in a suitably powered trial.This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.Published (Open Access

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Gymnasielärare, kön och skolprestationer : Gymnasielärares attityder till kön och skolprestationer, deras kunskaper om genus och deras bemötande av elever

Det har under flera år påtalats att pojkar presterar sämre än flickor i skolan, både i Sverige och i utlandet. Syftet med denna uppsats var att med hjälp av en enkät och några intervjuer ta reda några svenska gymnasielärares uppfattning om könsskillnader i skolprestationer. Syftet var också att ta reda på om lärarna har någon utbildning i frågor som rör genus och jämställdhet, samt att ta reda på om lärarna uppfattar att de bemöter elever lika, oavsett kön. Resultatet visade att det finns kunskaper om orsaker till könsskillnader i skolprestationer bland lärarna. Dock visade även resultatet att det finns brister i kunskaperna hos lärare, samt att en del lärare saknar utbildning i frågor om genus och jämställdhet, vilket riskerar att bidra till att könsstereotyper reproduceras och att könsskillnaderna i skolprestationer kvarstår

Fackförbunden och livslångt lärande : Kritisk analys av livslångt lärande ur ett fackligt perspektiv

Lifelong learning (LLL), a concept dating back to the 1920s, is much used both by the OECD, UNESCO and the EU. But while intergovernmental think-tanks and supranational organisations often use the term in a positive sense, many (not least scholars) are critical of the term. The critique either deals with the lack of a universal definition, that the implicit responsibility for LLL has shifted onto the individual, or that the meaning of the term has shifted from a humanistic one linked to the personal development and a better society to a neoliberal one that involves growth, competition, globalisation and human capital theory. This study is based on interviews with nine trade union representatives on their understandings of lifelong learning. The results showed that while LLL was positively viewed by most, there was virtually no communication vis-à-vis members on the topic, most trade unions have no policy regarding LLL, and responses from representatives were sometimes self-conflicting

Experimental acute pancreatitis in PAP/HIP knock‐out mice

[Background and aims]: PAP/HIP was first reported as an additional pancreatic secretory protein expressed during the acute phase of pancreatitis. It was shown in vitro to be anti-apoptotic and anti-inflammatory. This study aims to look at whether PAP/HIP plays the same role in vivo. [Methods]: A model of caerulein-induced pancreatitis was used to compare the outcome of pancreatitis in PAP/HIP-/- and wild-type mice. [Results]: PAP/HIP-/- mice showed the normal phenotype at birth and normal postnatal development. Caerulein-induced pancreatic necrosis was, however, less severe in PAP/HIP -/- mice than in wild-type mice, as judged by lower amylasemia and lipasemia levels and smaller areas of necrosis. On the contrary, pancreas from PAP/HIP-/- mice was more sensitive to apoptosis, in agreement with the anti-apoptotic effect of PAP/HIP in vitro. Surprisingly, pancreatic inflammation was more extensive in PAP/HIP-/- mice, as judged from histological parameters, increased myeloperoxidase activity and increased pro-inflammatory cytokine expression. This result, in apparent contradiction with the limited necrosis observed in these mice, is, however, in agreement with the anti-inflammatory function previously reported in vitro for PAP/HIP. This is supported by the observation that activation of the STAT3/SOCS3 pathway was strongly decreased in the pancreas of PAP/HIP-/- mice and by the reversion of the apoptotic and inflammatory phenotypes upon administration of recombinant PAP/HIP to PAP/HIP-/- mice. [Conclusion]: The anti-apoptotic and anti-inflammatory functions described in vitro for PAP/HIP have physiological relevance in the pancreas in vivo during caerulein-induced pancreatitis.This work was supported in part by grant FIS PI050599 from the Instituto de Salud Carlos III and from INSERM. MG is the recipient of a post-vert (INSERM) fellowship and EF-P is the recipient of a Ramón y Cajal research contract.Peer Reviewe

COAST (Cisplatin Ototoxicity Attenuated by Aspirin Trial): A phase II double blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing loss

BackgroundCisplatin has the highest ototoxic potential of platinum containing drugs leaving 50% of patients with a permanent and irreversible hearing-loss, and associated reduction in quality of life. There are no preventative treatment strategies to minimise this common side-effect. Both cisplatin and gentamicin are thought to damage hearing through a common mechanism involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin induced ototoxicity. We tested the hypothesis that aspirin could reduce ototoxicity from cisplatin based chemotherapy.Method94 patients were recruited into a phase II, double blind, placebo controlled, 2-arm trial, and randomised 1:1 from multiple tumour-sites (head and neck, thoracic, bladder, germ cell) in the U.K. Patients underwent pure tone audiometry (PTA) before, and following their final cisplatin dose at 7 and 90 days. Patients received aspirin 975mg tid and omeprazole 20 mg od, or placebos; from the day before, to 2 days after their cisplatin dose, for each cisplatin cycle. The primary endpoint was total hearing difference, comparing pre- and post-cisplatin PTA at 6 and 8kHz in both ears.ResultsAlthough aspirin was well-tolerated, it did not protect protect hearing in patients receiving cisplatin [mean difference 9.38 60% CI (-1.45, 20.22) one sided p-value of 0.233 in favour of placebo 71% (56/79) patients demonstrated hearing loss following cisplatin administration (median loss of 35db IQR 0-90 range -85 to 180, mean 42.4 SD 56.3). The extent of hearing-loss was not associated with cisplatin dose, age or hearing loss at presentation. Patients undergoing treatment for head and neck malignancy experienced the biggest hearing loss.ConclusionAspirin was well-tolerated but did not protect hearing suggesting that cisplatin and gentamicin may have distinct ototoxic mechanisms or that cisplatin is more ototoxic, requiring larger protective doses. Cisplatin induced ototoxicity results in significant morbidity and further research is required to prevent it.<br/

COAST (Cisplatin Ototoxicity Attenuated by Aspirin Trial): A phase II double blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing loss

BackgroundCisplatin has the highest ototoxic potential of platinum containing drugs leaving 50% of patients with a permanent and irreversible hearing-loss, and associated reduction in quality of life. There are no preventative treatment strategies to minimise this common side-effect. Both cisplatin and gentamicin are thought to damage hearing through a common mechanism involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin induced ototoxicity. We tested the hypothesis that aspirin could reduce ototoxicity from cisplatin based chemotherapy.Method94 patients were recruited into a phase II, double blind, placebo controlled, 2-arm trial, and randomised 1:1 from multiple tumour-sites (head and neck, thoracic, bladder, germ cell) in the U.K. Patients underwent pure tone audiometry (PTA) before, and following their final cisplatin dose at 7 and 90 days. Patients received aspirin 975mg tid and omeprazole 20 mg od, or placebos; from the day before, to 2 days after their cisplatin dose, for each cisplatin cycle. The primary endpoint was total hearing difference, comparing pre- and post-cisplatin PTA at 6 and 8kHz in both ears.ResultsAlthough aspirin was well-tolerated, it did not protect protect hearing in patients receiving cisplatin [mean difference 9.38 60% CI (-1.45, 20.22) one sided p-value of 0.233 in favour of placebo 71% (56/79) patients demonstrated hearing loss following cisplatin administration (median loss of 35db IQR 0-90 range -85 to 180, mean 42.4 SD 56.3). The extent of hearing-loss was not associated with cisplatin dose, age or hearing loss at presentation. Patients undergoing treatment for head and neck malignancy experienced the biggest hearing loss.ConclusionAspirin was well-tolerated but did not protect hearing suggesting that cisplatin and gentamicin may have distinct ototoxic mechanisms or that cisplatin is more ototoxic, requiring larger protective doses. Cisplatin induced ototoxicity results in significant morbidity and further research is required to prevent it.<br/