Global evaluation and outcomes of cholecystectomy: protocol for a multicentre, international, prospective cohort study (GlobalSurg 4)

Introduction Cholecystectomy is one of the most common operations performed worldwide. Although laparoscopic surgery has been the ‘gold-standard’ approach for this operation, there is a paucity of global evidence around the variations of safe provision of cholecystectomy, including low-income and middle-income countries. This international collaborative study will allow contemporaneous data collection on the quality of cholecystectomies using measures covering infrastructure, care processes and outcomes, with the primary aim define the global variation in compliance with preoperative, intraoperative and postoperative audit standards. Methods and analysis Global Evaluation of Cholecystectomy Knowledge and Outcomes is a prospective, international, multicentre, observational cohort study delivered by the GlobalSurg Collaborative. Consecutive patients undergoing cholecystectomy between 31 July 2023 and 19 November 2023 will be recruited, with follow-up at 30 days and 1-year postoperatively. The study will be undertaken at any hospital providing emergency or elective surgical services for biliary disease. The primary endpoint of this study is compliance with preoperative, intraoperative and postoperative audit standards. Secondary outcomes include rates of 30-day complications, achievement of critical view of safety and rates of gallbladder cancer. Ethics and dissemination This project will not affect clinical practice and has been classified as clinical audit following research ethics review at University Hospital Birmingham NHS Trust. The protocol will be disseminated through the international GlobalSurg and CovidSurg network. Trial registration number NCT06223061

Supplemental material for The association between ICU admission and emergency hospital readmission following emergency general surgery

Supplemental Material for The association between ICU admission and emergency hospital readmission following emergency general surgery by Michael A Gillies, Sadia Ghaffar, Ewen Harrison, Catriona Haddow, Lorraine Smyth, Timothy S Walsh, Rupert M Pearse and Nazir I Lone in Journal of the Intensive Care Society</p

Alcoholic chlorhexidine skin preparation or triclosan-coated sutures to reduce surgical site infection: a systematic review and meta-analysis of high-quality randomised controlled trials

Background: WHO and the UK's National Institute for Health and Care Excellence recommend alcoholic chlorhexidine skin preparation and triclosan-coated sutures to prevent surgical site infections (SSIs). Existing meta-analyses that include studies at high risk of bias, combined with the recent publication of large, randomised trials, justify an updated meta-analysis of high-quality randomised controlled trials (RCTs). We aimed to test the rates of SSI according to skin preparation solutions (ie, alcoholic chlorhexidine vs aqueous povidone-iodine) and types of sutures (ie, coated vs uncoated). Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Pubmed, and Cochrane Library databases, with no language restrictions, to identify high-quality RCTs testing either alcoholic chlorhexidine skin preparation (vs aqueous povidone-iodine) or triclosan-coated sutures (vs uncoated sutures), or both, published from database inception to Sept 1, 2021. Patients who received clean-contaminated, contaminated, or dirty surgery were included. We predefined the characteristics of a high-quality trial through an expert consensus process to develop an enhanced Cochrane risk of bias-2 tool specifically for RCTs with a primary outcome of SSI. Data were extracted from published reports. Meta-analysis was performed using a random-effects model and heterogeneity was assessed using the I2 statistic. This systematic review and meta-analysis was prospectively registered in PROSPERO, CRD42021267220. Findings: Of 942 studies identified, 933 were excluded. Four high-quality RCTs (n=7467 patients) were included that tested alcoholic chlorhexidine. No significant difference in SSI rates was noted between alcoholic chlorhexidine and aqueous povidone-iodine (17·9% [667 of 3723 patients] vs 19·8% [740 of 3744 patients]; odds ratio 0·84 [95% CI 0·65–1·06]; p=0·21, I2=53·1%). Five high-quality RCTs were included that tested triclosan-coated sutures (n=8619 patients), with no significant difference noted between triclosan-coated and uncoated sutures (16·8% [733 of 4360 patients] vs 18·4% [784 of 4259 patients]; OR 0·90 [95% CI 0·74–1·09]; p=0·29, I2=36·4%). Interpretation: Contrary to previous meta-analyses, this study did not show a benefit from either alcoholic chlorhexidine skin preparation or triclosan-coated sutures, both of which are more expensive than other readily available alternatives. Global and national guidance should be reconsidered to remove recommendations for their routine use

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Cognitive and psychiatric symptom trajectories 2–3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK

Background: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning. Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2–3 years, and whether symptoms at 2–3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2–3 years were associated with occupation change. People with lived experience were involved in the study. Findings: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2–3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16–1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2–3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2–3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0–48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0–17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2–3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6–31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04–2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21–1·98] for every point increase in CCI-20). Interpretation: Psychiatric and cognitive symptoms appear to increase over the first 2–3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19. Funding: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research.</p

Long term health outcomes in people with diabetes 12 months after hospitalisation with COVID-19 in the UK: a prospective cohort study

Background: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes. Methods: The PHOSP-COVID study is a multicentre, long-term follow-up study of adults discharged from hospital between 1 February 2020 and 31 March 2021 in the UK following COVID-19, involving detailed assessment at 5 and 12 months after discharge. The association between diabetes status and outcomes were explored using multivariable linear and logistic regressions. Findings: People with diabetes who survived hospital admission with COVID-19 display worse physical outcomes compared to those without diabetes at 5- and 12-month follow-up. People with diabetes displayed higher fatigue (only at 5 months), frailty, lower physical performance, and health-related quality of life and poorer cognitive function. Differences in outcomes between diabetes status groups were largely consistent from 5 to 12-months. In regression models, differences at 5 and 12 months were attenuated after adjustment for BMI and presence of other long-term conditions. Interpretation: People with diabetes reported worse physical outcomes up to 12 months after hospital discharge with COVID-19 compared to those without diabetes. These data support the need to reduce inequalities in long-term physical and mental health effects of SARS-CoV-2 infection in people with diabetes. Funding: UK Research and Innovation and National Institute for Health Research. The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and is registered on the ISRCTN Registry (ISRCTN10980107)