Lancet
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Randomized Controlled Trial Multicenter Study
Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.
Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis, inflammation, hepatocellular injury, and progressive liver fibrosis. Resmetirom (MGL-3196) is a liver-directed, orally active, selective thyroid hormone receptor-β agonist designed to improve NASH by increasing hepatic fat metabolism and reducing lipotoxicity. We aimed to assess the safety and efficacy of resmetirom in patients with NASH. ⋯ Madrigal Pharmaceuticals.
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Randomized Controlled Trial
Results of a 6-week treatment with 10 mg prednisolone in patients with hand osteoarthritis (HOPE): a double-blind, randomised, placebo-controlled trial.
Hand osteoarthritis is a prevalent joint condition that has a high burden of disease and an unmet medical need for effective therapeutic options. Since local inflammation is recognised as contributing to osteoarthritic complaints, the Hand Osteoarthritis Prednisolone Efficacy (HOPE) study aimed to investigate the efficacy and safety of short-term prednisolone in patients with painful hand osteoarthritis and synovial inflammation. ⋯ Dutch Arthritis Society.
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Randomized Controlled Trial Multicenter Study
Anaesthetic depth and complications after major surgery: an international, randomised controlled trial.
What’s all the fuss?
Significant observational evidence suggested an association between mortality and deep anaesthesia, in particular a 2017 meta-analysis. However it has been suspected that anaesthetic depth may merely be a surrogate marker for intraoperative hypotension, a well-established risk factor for post-operative mortality and morbidity.
With this large RCT, the Balanced Anaesthesia Study Group has shown that deep general anaesthesia is not associated with an increase 1-year mortality.
What did they do?
The researchers conducted an ambitious, large (6,644 patients), multi-center, randomised controlled trial. Patients aged ≥60 years undergoing major surgery (expected ≥2h surgery and ≥2d hospital stay) were randomised to receive volatile general anaesthesia targeting BIS 50 or BIS 35.
To minimise intra-operative blood pressure as a confounder, anaesthetists were required to specify a target MAP before BIS-group allocation.
They found...
Not only was there no mortality difference between the BIS 50 and BIS 35 groups, there were also no major or moderate morbidity differences, or difference in recovery or length of stay. BIS targets were adequately achieved, though not perfect, and MAP was clinically similar for both groups.
Context is everything
This is about as high-quality as a large, modern study looking at longer-term outcomes can get. It is widely applicable to most populations and common general anaesthetic scenarios, except for a few important caveats:
- Very few ASA 4 (5%) patients were enrolled.
- Only volatile-maintenance anaesthesia was studied not propofol/TIVA.
- We can draw no conclusion regarding the consequences of extreme-depth (ie. BIS << 35).
- The actual depth difference between the BIS-35 and BIS-50 groups was not as much as perhaps ideal: mean BIS 39 vs 47 respectively...
Final thought
...there was (only) one case of awareness in the light-depth BIS 50 group, despite 39% of patients receiving volatile < 0.7 MAC.
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Randomized Controlled Trial Multicenter Study
Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial.
Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum-etoposide) in treatment-naive patients with ES-SCLC. ⋯ AstraZeneca.
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Randomized Controlled Trial Multicenter Study
Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study.
Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response. ⋯ Merck Sharp & Dohme.