Nebulised unfractionated heparin may attenuate COVID-19 ARDS by reducing pulmonary microvascular thrombosis, blocking SARS-CoV-2 entry into cells, and decreasing lung inflammation. COVID-19 patients with a raised D-dimer have areas of pulmonary hypoperfusion on CT perfusion scans of the lung and have increased mortality risk. This was a phase Ib/IIa open-label multi-centre, randomised controlled trial. The study was designed to evaluate whether nebulised unfractionated heparin decreased D-dimer concentrations, with safety as a co-primary outcome. Forty patients were recruited, with 20 patients into each group. Mean age was 56.6 (SD 11.5) in the heparin group and 51.3 (SD 14.7) in the standard care group, while 60% of participants were male. There was no change in D-dimers from baseline to day 10 (heparin group mean change - 316.5, [SD 1840.3] and control group mean change - 321.7 [SD 3589.4]; p = 0.996). Fourteen patients suffered at least one serious adverse event, 9 patients the Heparin group and 5 in the control group. Eight patients had one or more bleeding events, 5 in the heparin group and 3 in the control group, but were no cases of pulmonary bleeding, of severe haemorrhage or of heparin-induced thrombocytopenia. Patients receiving heparin therapy had lower PaO2/FiO2 ratios, increased oxygenation indices, and decreased ROX index profiles, up to day 10. The time to separation from respiratory support, and the time to ICU or hospital discharge was similar in both groups. There were 3 deaths in the Heparin group and 2 in the control group. Nebulised unfractionated heparin was safe and well tolerated, but did not reduce D-dimer concentrations, and worsened oxygenation indices in patients with COVID-19 ARDS.
Abstract Background Artificial intelligence, through improved data management and automated summarisation, has the potential to enhance intensive care unit (ICU) care. Large language models (LLMs) can interrogate and summarise large volumes of medical notes to create succinct discharge summaries. In this study, we aim to investigate the potential of LLMs to accurately and concisely synthesise ICU discharge summaries. Methods Anonymised clinical notes from ICU admissions were used to train and validate a prompting structure in three separate LLMs (ChatGPT, GPT-4 API and Llama 2) to generate concise clinical summaries. Summaries were adjudicated by staff intensivists on ability to identify and appropriately order a pre-defined list of important clinical events as well as readability, organisation, succinctness, and overall rank. Results In the development phase, text from five ICU episodes was used to develop a series of prompts to best capture clinical summaries. In the testing phase, a summary produced by each LLM from an additional six ICU episodes was utilised for evaluation. Overall ability to identify a pre-defined list of important clinical events in the summary was 41.5 ± 15.2% for GPT-4 API, 19.2 ± 20.9% for ChatGPT and 16.5 ± 14.1% for Llama2 ( p = 0.002). GPT-4 API followed by ChatGPT had the highest score to appropriately order a pre-defined list of important clinical events in the summary as well as readability, organisation, succinctness, and overall rank, whilst Llama2 scored lowest for all. GPT-4 API produced minor hallucinations, which were not present in the other models. Conclusion Differences exist in large language model performance in readability, organisation, succinctness, and sequencing of clinical events compared to others. All encountered issues with narrative coherence and omitted key clinical data and only moderately captured all clinically meaningful data in the correct order. However, these technologies suggest future potential for creating succinct discharge summaries.
A group of 163 men in the Hamilton, Ont. region who had suffered a myocardial infarction were enrolled in a rehabilitation program of physical activity. These men constituted one cohort of a multicentre collaborative study designed to determine the effects of regular exercise of differing intensity on morbidity and mortality over a 4-year period.The noncompliance rate was 43% for the men who could have participated for 1 year, 46% of whom were classified as noncompliers within 1 month of entry into the program. There was no difference in overall compliance between the men exercising at high intensity and those exercising at low intensity; lack of motivation or interest was the most common reason for their leaving the program. Those leaving the program early tended to have a type A behaviour pattern (they were aggressive, ambitious and competitive, with a chronic sense of time urgency), were inactive during their leisure time, had had at least two previous infarctions and smoked. These characteristics suggest that the men leaving the program early may have been those at greatest risk for a further myocardial infarction.
Abstract Background The deep serratus anterior plane block (SAPB) is a promising novel regional anaesthesia technique for blockade of the anterolateral chest wall. Evidence for the efficacy of SAPB versus other analgesic techniques in thoracic surgery remains inadequate. Aims This study compared ultrasound‐guided continuous SAPB with a surgically placed continuous thoracic paravertebral block (SPVB) technique in patients undergoing videoscopic‐assisted thoracic surgery (VATS). Methods In a single‐centre, double‐blinded, randomized, non‐inferiority study, we allocated 40 patients undergoing VATS to either SAPB or SPVB, with both groups receiving otherwise standardized treatment, including multimodal analgesia. The primary outcome was 48‐hr opioid consumption. Secondary outcomes included numerical rating scale (NRS) for postoperative pain, patient‐reported worst pain score (WPS) as well as functional measures (including mobilization distance and cough strength). Results A 48‐hr opioid consumption for the SAPB group was non‐inferior compared with SPVB. SAPB was associated with improved NRS pain scores at rest, with cough and with movement at 24 hr postoperatively ( p = .007, p = .001 and p = .012, respectively). SAPB was also associated with a lower WPS ( p = .008). Day 1 walking distance was improved in the SAPB group ( p = .012), whereas the difference in cough strength did not reach statistical significance ( p = .071). There was no difference in haemodynamics, opioid side effects, length of hospital stay or patient satisfaction between the two groups. Conclusions The SAPB, as part of a multimodal analgesia regimen, is non‐inferior in terms of 48‐hr opioid consumption compared to SPVB and is associated with improved functional measures in thoracic surgical patients. ClinicalTrials.gov Identifier: NCT03768193. Significance The SAPB interfascial plane block is an efficacious alternative method of opioid‐sparing analgesia in high‐risk thoracic surgical patients as part of an enhanced recovery programme.
Abstract Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI − 0.1% [− 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (− 3.2% [− 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).
The timing and method of treatment of deep palm and finger burns varies widely. Our protocol involves performing full-thickness skin grafts (FTSG) in nonhealing palm burns. We reviewed the functional and cosmetic results after FTSG to the palm. From August 1997 to April 1999, 11 patients (12 palms) underwent excision and FTSG within 2 weeks of injury. A panel of medical and nonmedical professionals evaluated follow-up pictures of the grafts at 1, 2 to 4, and beyond 4 months. Parameters used for evaluation were color match with the unburned skin (1 = no difference to 4 = large difference), graft thickness (1 = flat to 4 = markedly raised), overall appearance (1 = poor to 100 = excellent), and time to maturity. Hand function, as assessed by occupational therapy notes, was also recorded. All 12 grafted palms had a 100% take and healed with minimal scarring. Mean color match scores were 2.4 at 1 month, 1.8 at 2 to 4 months, and 1.6 beyond 4 months. On the graft thickness scale, grafts were given scores of 2.6, 2.2, and 1.9 during the same intervals. The overall appearance was 71 at 1 month, 81 at 2 to 4 months, and 85 beyond 4 months. All grafts except 1 were judged to be mature at 2 to 4 months follow-up. Full passive range of motion was attained in all grafted hands within the period of 2 to 4 months after operation. Early excision and FTSG of deep pediatric palm burns can be performed in the outpatient setting. The grafts have an acceptable color match, are minimally raised, and achieve excellent cosmetic result. The grafts mature within a few months after surgery to allow for rapid return to normal range of motion. FTSG should be considered as a first choice for deep palm burns.
We reviewed the antenatal HIV testing history, clinical presentation and outcome of 25 infants diagnosed with HIV between 1 January 2001 and 31 December 2005 in a tertiary referral hospital in London. Of the 25 cases, 21 had received antenatal care in the UK. Twelve mothers had not had an antenatal HIV test, four had tested positive antenatally, while five had had a negative HIV test on antenatal booking, implying seroconversion in pregnancy. When mothers had not been diagnosed antenatally, infants presented with severe infections, which were fatal in six cases. The majority (65%) of the children have long-term neurological sequelae. HIV seroconversion is an important cause of infant HIV in the UK.
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