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Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery
No full textBackground: Cardiac surgery triggers a strong inflammatory reaction, which carries significant clinical consequences. Corticosteroids have been suggested as a potential perioperative strategy to reduce inflammation and help prevent postoperative complications. However, the safety and effectiveness of perioperative corticosteroid use in adult cardiac surgery is uncertain. This is an update of the 2011 review with 18 studies added. Objectives: Primary objective: to estimate the effects of prophylactic corticosteroid use in adults undergoing cardiac surgery with cardiopulmonary bypass on the: - co-primary endpoints of mortality, myocardial complications, and pulmonary complications; and - secondary outcomes including atrial fibrillation, infection, organ injury, known complications of steroid therapy, prolonged mechanical ventilation, prolonged postoperative stay, and cost-effectiveness. Secondary objective: to explore the role of characteristics of the study cohort and specific features of the intervention in determining the treatment effects via a series of prespecified subgroup analyses. Search methods: We used standard, extensive Cochrane search methods to identify randomised studies assessing the effect of corticosteroids in adult cardiac surgery. The latest searches were performed on 14 October 2022. Selection criteria: We included randomised controlled trials in adults (over 18 years, either with a diagnosis of coronary artery disease or cardiac valve disease, or who were candidates for cardiac surgery with the use of cardiopulmonary bypass), comparing corticosteroids with no treatments. There were no restrictions with respect to length of the follow-up period. All selected studies qualified for pooling of results for one or more endpoints. Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, and cardiac and pulmonary complications. Secondary outcomes were infectious complications, gastrointestinal bleeding, occurrence of new post-surgery atrial fibrillation, re-thoracotomy for bleeding, neurological complications, renal failure, inotropic support, postoperative bleeding, mechanical ventilation time, length of stays in the intensive care unit (ICU) and hospital, patient quality of life, and cost-effectiveness. We used GRADE to assess the certainty of evidence for each outcome. Main results: This updated review includes 72 randomised trials with 17,282 participants (all 72 trials with 16,962 participants were included in data synthesis). Four trials (6%) were considered at low risk of bias in all the domains. The median age of participants included in the studies was 62.9 years. Study populations consisted mainly (89%) of low-risk, first-time coronary artery bypass grafting (CABG) or valve surgery. The use of perioperative corticosteroids may result in little to no difference in all-cause mortality (risk with corticosteroids: 25 to 36 per 1000 versus 33 per 1000 with placebo or no treatment; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.75 to 1.07; 25 studies, 14,940 participants; low-certainty evidence). Corticosteroids may increase the risk of myocardial complications (68 to 86 per 1000) compared with placebo or no treatment (66 per 1000; RR 1.16, 95% CI 1.04 to 1.31; 25 studies, 14,766 participants; low-certainty evidence), and may reduce the risk of pulmonary complications (risk with corticosteroids: 61 to 77 per 1000 versus 78 per 1000 with placebo/no treatment; RR 0.88, 0.78 to 0.99; 18 studies, 13,549 participants; low-certainty evidence). Analyses of secondary endpoints showed that corticosteroids may reduce the incidence of infectious complications (risk with corticosteroids: 94 to 113 per 1000 versus 123 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.76 to 0.92; 28 studies, 14,771 participants; low-certainty evidence). Corticosteroids may result in little to no difference in incidence of gastrointestinal bleeding (risk with corticosteroids: 9 to 17 per 1000 versus 10 per 1000 with placebo/no treatment; RR 1.21, 95% CI 0.87 to 1.67; 6 studies, 12,533 participants; low-certainty evidence) and renal failure (risk with corticosteroids: 23 to 35 per 1000 versus 34 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.69 to 1.02; 13 studies, 12,799; low-certainty evidence). Corticosteroids may reduce the length of hospital stay, but the evidence is very uncertain (-0.5 days, 0.97 to 0.04 fewer days of length of hospital stay compared with placebo/no treatment; 25 studies, 1841 participants; very low-certainty evidence). The results from the two largest trials included in the review possibly skew the overall findings from the meta-analysis. Authors' conclusions: A systematic review of trials evaluating the organ protective effects of corticosteroids in cardiac surgery demonstrated little or no treatment effect on mortality, gastrointestinal bleeding, and renal failure. There were opposing treatment effects on cardiac and pulmonary complications, with evidence that corticosteroids may increase cardiac complications but reduce pulmonary complications; however, the level of certainty for these estimates was low. There were minor benefits from corticosteroid therapy for infectious complications, but the evidence on hospital length of stay was very uncertain. The inconsistent treatment effects across different outcomes and the limited data on high-risk groups reduced the applicability of the findings. Further research should explore the role of these drugs in specific, vulnerable cohorts. Trial registration: ClinicalTrials.gov NCT03002259.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005566.pub4/ful
The Effects of Preoperative Glycaemic Control (HbA1c) on Bariatric and Metabolic Surgery Outcomes: Data from a Tertiary-Referral Bariatric Centre in the UK.
No full textBackground: Current recommendations advocate the achievement of an optimal glucose control (HbA1c 69 mmol/mol (N = 67) as well as a continuous variable. Results: A total of 269 patients with T2D were included in this study. Patients underwent primary Roux en-Y gastric bypass (RYGB, n = 136), Sleeve Gastrectomy (SG, n = 124), insertion of gastric band (n = 4) or one-anastomosis gastric bypass (OAGB, n = 4). No significant differences in the rates of complications were observed between the two groups of pre-operative HbA1c cut-off values. No HbA1c threshold was observed for glycaemic control that would affect the peri- and post-operative complications following BMS. Conclusions: We observed no associations between pre-operative HbA1C values and the risk of peri- and post-operative complications. In the context of a specialist multidisciplinary weight management programme, optimising pre-operative HbA1C to a recommended target value prior to BMS may not translate into reduced risks of peri- and post-operative complications. Keywords: Bariatric surgery; Complications; Glycated haemoglobin; HbA1c; Intensive care; Length of stay; Mortality; Peri-operative; Post-operative; Type 2 diabetes
Clinical significance and resource burden of double duct sign in non-jaundiced patients
No full textAim The study aims to determine the incidence of malignancy at presentation and subsequent risk of malignancy (at 12 months follow-up) in a cohort of patients with double duct sign (DDS) on cross-sectional imaging but no visible stigmata of jaundice. The study also correlates malignancy with liver enzyme dysfunction and estimates the resource burden incurred during the investigation of these patients. Methods A search for the key term "double duct sign" was undertaken in the radiological database of a tertiary hepatopancreatobiliary (HPB) centre between March 2017 and March 2022. Radiological reports, clinic letters, blood results, and multidisciplinary team meeting (MDT) outcomes were reviewed during this period and at one year. The national tariff payment system was reviewed to identify tariffs for different investigations required for the cohort and to calculate the total cost incurred. Results Ninety-seven patients with DDS were identified. Sixty-four patients (66%) had a normal bilirubin (0-21 µmol/L) at presentation and were included in the analysis. Seven patients (10.9%) were diagnosed with malignant peri-ampullary tumours, and 21 (32.8%) were diagnosed with benign diseases. In 34 patients (53%) with DDS, the underlying cause remained uncharacterised. Most patients had mild abnormalities of liver enzymes, but two patients (4.3%) were diagnosed with malignant peri-ampullary tumours despite having normal serological values. Patients who had a benign diagnosis and/or who had cancer excluded without a definitive diagnosis did not go on to develop a malignancy at 12 months follow-up. However, in those patients where the underlying aetiology could not be characterised, extended surveillance was required with a total of 80 MDT discussions and multiple surveillance scans (103 CT and 65 MRI scans). Twenty-six patients underwent endoscopic ultrasound (EUS) with three patients requiring more than one EUS examination (29 investigations in total). The cost of these investigations was £38,926.89. Conclusion This study confirms that DDS even in patients without clinical jaundice or with normal liver enzymes requires careful investigation to exclude malignancy despite the resource burden this entails. This supports previously reported results in the literature, and despite the increased use of cross-sectional imaging, DDS remains a clinically significant finding. Large cohort risk stratification studies would be useful to determine clinical urgency and allow the appropriate allocation of resources.https://www.cureus.com/articles/232968-clinical-significance-and-resource-burden-of-double-duct-sign-in-non-jaundiced-patients#!
Identification of human-generated vs AI-generated research abstracts by health care professionals
No full texthttps://jamanetwork.com/journals/jamapediatrics/article-abstract/281813
The use of pembrolizumab monotherapy for the management of head and neck squamous cell carcinoma (HNSCC) in the UK
No full textPembrolizumab has received approval in the UK as first-line monotherapy for recurrent and/or metastatic HNSCC (R/M HNSCC) following the results of the KEYNOTE-048 trial, which demonstrated a longer overall survival (OS) in comparison to the EXTREME chemotherapy regimen in patients with a combined positive score (CPS) ≥1. In this article, we provide retrospective real-world data on the role of pembrolizumab monotherapy as first-line systemic therapy for HNSCC across 18 centers in the UK from March 20, 2020 to May 31, 2021. 211 patients were included, and in the efficacy analysis, the objective response rate (ORR) was 24.7%, the median progression-free survival (PFS) was 4.8 months (95% confidence interval [CI]: 3.6-6.1), and the median OS was 10.8 months (95% CI 9.0-12.5). Pembrolizumab monotherapy was well tolerated, with 18 patients having to stop treatment owing to immune-related adverse events (irAEs). 53 patients proceeded to second-line treatment with a median PFS2 of 10.2 months (95% CI: 8.8-11.5). Moreover, patients with documented irAEs had a statistically significant longer median PFS (11.3 vs. 3.3 months; log-rank p value = <.001) and median OS (18.8 vs. 8.9 months; log-rank p value <.001). The efficacy and safety of pembrolizumab first-line monotherapy for HNSCC has been validated using real-world data.https://onlinelibrary.wiley.com/doi/10.1002/ijc.3496
Analysis of guideline recommendations for treatment of asthma exacerbations in children: a Pediatric Emergency Research Networks (PERN) study
No full textRationale: There is significant practice variation in acute paediatric asthma, particularly severe exacerbations. It is unknown whether this is due to differences in clinical guidelines. Objectives: To describe and compare the content and quality of clinical guidelines for the management of acute exacerbations of asthma in children between geographic regions. Methods: Observational study of guidelines for the management of acute paediatric asthma from institutions across a global collaboration of six regional paediatric emergency research networks. Measurements and main results: 158 guidelines were identified. Half provided recommendations for at least two age groups, and most guidelines provided treatment recommendations according to asthma severity.There were consistent recommendations for the use of inhaled short-acting beta-agonists and systemic corticosteroids. Inhaled anticholinergic therapy was recommended in most guidelines for severe and critical asthma, but there were inconsistent recommendations for its use in mild and moderate exacerbations. Other inhaled therapies such as helium-oxygen mixture (Heliox) and nebulised magnesium were inconsistently recommended for severe and critical illness.Parenteral bronchodilator therapy and epinephrine were mostly reserved for severe and critical asthma, with intravenous magnesium most recommended. There were regional differences in the use of other parenteral bronchodilators, particularly aminophylline.Guideline quality assessment identified high ratings for clarity of presentation, scope and purpose, but low ratings for stakeholder involvement, rigour of development, applicability and editorial independence. Conclusions: Current guidelines for the management of acute paediatric asthma exacerbations have substantial deficits in important quality domains and provide limited and inconsistent guidance for severe exacerbations.https://adc.bmj.com/content/109/6/468.lon
Psychological interventions for mood and cognition after stroke and transient ischaemic attack: A protocol for an umbrella review
Get PDF: © 2024 Kontou E et al. This is an open access article distributed under the terms of the Creative Commons Attribution License
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.BACKGROUND: People who have had a stroke or a Transient Ischaemic Attack (TIA) can experience psychological and/or cognitive difficulties. The body of research for psychological and neuropsychological interventions after stroke is growing, however, published systematic reviews vary in scope and methodology, with different types and severity of strokes included, and at times, diverse conclusions drawn about the effectiveness of the interventions evaluated. In this umbrella review, we aim to systematically summarise the existing systematic reviews evaluating psychological interventions for mood and cognition post-stroke/TIA. METHODS: We will conduct this umbrella review according to the JBI Manual for Evidence Synthesis. The following databases will be searched from inception: Cochrane Database of Systematic Reviews, Database of Reviews of Effects (DARE), MEDLINE, Embase, CINAHL, PsycINFO, and Epistemonikos. Systematic reviews with or without meta-analysis published until the search date will be included. Reviews including psychological interventions addressing mood and/or cognition outcomes for any stroke type or severity will be screened for eligibility. A narrative synthesis, including content analysis, will be used. Each stage of the review will be processed by two independent reviewers and a third reviewer will be considered to resolve disagreements. The methodological quality of the included reviews will be assessed using AMSTAR 2. DISCUSSION: Existing systematic reviews provide varied evidence on the effectiveness of psychological interventions post-stroke/TIA. This umbrella review aims to summarise knowledge and evidence on different types of psychological and neuropsychological interventions targeting mood and cognition. Findings will highlight important knowledge gaps and help prioritise future research questions. SYSTEMATIC REVIEW REGISTRATION: This protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) on November 15, 2022; PROSPERO CRD42022375947.https://f1000research.com/articles/13-199/v
Randomized phase 3 trial of the hypoxia modifier nimorazole added to radiation therapy with benefit assessed in hypoxic head and neck cancers determined using a gene signature (NIMRAD)
No full textPurpose: Tumor hypoxia is an adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). We assessed whether patients with hypoxic HNSCC benefited from the addition of nimorazole to definitive intensity modulated radiation therapy (IMRT). Methods and materials: NIMRAD was a phase 3, multicenter, placebo-controlled, double-anonymized trial of patients with HNSCC unsuitable for concurrent platinum chemotherapy or cetuximab with definitive IMRT (NCT01950689). Patients were randomized 1:1 to receive IMRT (65 Gy in 30 fractions over 6 weeks) plus nimorazole (1.2 g/m2 daily, before IMRT) or placebo. The primary endpoint was freedom from locoregional progression (FFLRP) in patients with hypoxic tumors, defined as greater than or equal to the median tumor hypoxia score of the first 50 patients analyzed (≥0.079), using a validated 26-gene signature. The planned sample size was 340 patients, allowing for signature generation in 85% and an assumed hazard ratio (HR) of 0.50 for nimorazole effectiveness in the hypoxic group and requiring 66 locoregional failures to have 80% power in a 2-tail log-rank test at the 5% significance level. Results: Three hundred thirty-eight patients were randomized by 19 centers in the United Kingdom from May 2014 to May 2019, with a median follow-up of 3.1 years (95% CI, 2.9-3.4). Hypoxia scores were available for 286 (85%). The median patient age was 73 years (range, 44-88; IQR, 70-76). There were 36 (25.9%) locoregional failures in the hypoxic group, in which nimorazole + IMRT did not improve FFLRP (adjusted HR, 0.72; 95% CI, 0.36-1.44; P = .35) or overall survival (adjusted HR, 0.96; 95% CI, 0.53-1.72; P = .88) compared with placebo + IMRT. Similarly, nimorazole + IMRT did not improve FFLRP or overall survival in the whole population. In total (N = 338), 73% of patients allocated nimorazole adhered to the drug for ≥50% of IMRT fractions. Nimorazole + IMRT caused more acute nausea compared with placebo + IMRT (Common Terminology Criteria for Adverse Events version 4.0 G1+2: 56.6% vs 42.4%, G3: 10.1% vs 5.3%, respectively; P < .05). Conclusions: Addition of the hypoxia modifier nimorazole to IMRT for locally advanced HNSCC in older and less fit patients did not improve locoregional control or survival.https://www.redjournal.org/article/S0360-3016(23)08184-1/fulltex
Community seroprevalence of SARS-CoV-2 in children and adolescents in England, 2019-2021
Get PDFThis article relates to a research study that included patients or members of the workforce as study participants from GP practices in Nottingham and Nottinghamshire.Objective: To understand community seroprevalence of SARS-CoV-2 in children and adolescents. This is vital to understanding the susceptibility of this cohort to COVID-19 and to inform public health policy for disease control such as immunisation. Design: We conducted a community-based cross-sectional seroprevalence study in participants aged 0-18 years old recruiting from seven regions in England between October 2019 and June 2021 and collecting extensive demographic and symptom data. Serum samples were tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins using Roche assays processed at UK Health Security Agency laboratories. Prevalence estimates were calculated for six time periods and were standardised by age group, ethnicity and National Health Service region. Results: Post-first wave (June-August 2020), the (anti-spike IgG) adjusted seroprevalence was 5.2%, varying from 0.9% (participants 10-14 years old) to 9.5% (participants 5-9 years old). By April-June 2021, this had increased to 19.9%, varying from 13.9% (participants 0-4 years old) to 32.7% (participants 15-18 years old). Minority ethnic groups had higher risk of SARS-CoV-2 seropositivity than white participants (OR 1.4, 95% CI 1.0 to 2.0), after adjusting for sex, age, region, time period, deprivation and urban/rural geography. In children <10 years, there were no symptoms or symptom clusters that reliably predicted seropositivity. Overall, 48% of seropositive participants with complete questionnaire data recalled no symptoms between February 2020 and their study visit. Conclusions: Approximately one-third of participants aged 15-18 years old had evidence of antibodies against SARS-CoV-2 prior to the introduction of widespread vaccination. These data demonstrate that ethnic background is independently associated with risk of SARS-CoV-2 infection in children
Epidemiology and management of pediatric group A streptococcal pneumonia with parapneumonic effusion: an observational study
No full textBackground: During autumn/winter 2022, UK pediatricians reported an unseasonal increase in invasive group A streptococcal infections; a striking proportion presenting with pneumonia with parapneumonic effusion. Methods: Clinicians across the United Kingdom were requested to submit pseudonymized clinical data using a standardized report form for children (<16 years) admitted between September 30, 2022 and February 17, 2023, with microbiologically confirmed group A streptococcal pneumonia with parapneumonic effusion. Results: From 185 cases submitted, the median patient age was 4.4 years, and 163 (88.1%) were previously healthy. Respiratory viral coinfection was detected on admission for 101/153 (66.0%) children using extended respiratory pathogen polymerase chain reaction panel. Molecular testing was the primary method of detecting group A streptococcus on pleural fluid (86/171; 50.3% samples). Primary surgical management was undertaken in 171 (92.4%) children; 153/171 (89.4%) had pleural drain inserted (96 with fibrinolytic agent), 14/171 (8.2%) had video-assisted thoracoscopic surgery. Fever duration after admission was prolonged (median, 12 days; interquartile range, 9-16). Intravenous antibiotic courses varied in length (median, 14 days; interquartile range, 12-21), with many children receiving multiple broad-spectrum antibiotics, although evidence for additional bacterial infection was limited. Conclusions: Most cases occurred with viral coinfection, a previously well-recognized risk with influenza and varicella zoster, highlighting the need to ensure routine vaccination coverage and progress on vaccines for other common viruses (eg, respiratory syncytial virus, human metapneumovirus) and for group A streptococcus. Molecular testing is valuable to detect viral coinfection and confirm invasive group A streptococcal diagnosis, expediting the incorporation of cases into national reporting systems. Range and duration of intravenous antibiotics administered demonstrated the need for research on the optimal duration of antimicrobials and improved stewardship.https://journals.lww.com/pidj/fulltext/9900/epidemiology_and_management_of_pediatric_group_a.906.asp