Malnutrition, nutritional interventions and clinical outcomes of patients with acute small bowel obstruction : results from a national, multicentre, prospective audit

Objective: The aim of this study was to assess the nutritional status of patients presenting with small bowel obstruction (SBO), along with associated nutritional interventions and clinical outcomes. Design: Prospective cohort study. Setting: 131 UK hospitals with acute surgical services. Participants: 2069 adult patients with a diagnosis of SBO were included in this study. The mean age was 67.0 years and 54.7% were female. Primary and secondary outcome measures: Primary outcome was in-hospital mortality. Secondary outcomes recorded included: major complications (composite of in-hospital mortality, reoperation, unplanned intensive care admission and 30-day readmission), complications arising from surgery (anastomotic leak, wound dehiscence), infection (pneumonia, surgical site infection, intra-abdominal infection, urinary tract infection, venous catheter infection), cardiac complications, venous thromboembolism and delirium. Results: Postoperative adhesions were the most common cause of SBO (49.1%). Early surgery (<24 hours postadmission) took place in 30.0% of patients, 22.0% underwent delayed operation and 47.9% were managed non-operatively. Malnutrition as stratified by Nutritional Risk Index was common, with 35.7% at moderate risk and 5.7% at severe risk of malnutrition. Dietitian review occurred in just 36.4% and 55.9% of the moderate and severe risk groups. In the low risk group, 30.3% received nutritional intervention compared with 40.7% in moderate risk group and 62.7% in severe risk group. In comparison to the low risk group, patients who were at severe or moderate risk of malnutrition had 4.2 and 2.4 times higher unadjusted risk of in-hospital mortality, respectively. Propensity-matched analysis found no difference in outcomes based on use or timing of parenteral nutrition. Conclusions: Malnutrition on admission is associated with worse outcomes in patients with SBO, and marked variation in management of malnutrition was observed. Future trials should focus on identifying effective and cost-effective nutritional interventions in SBO

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Outcomes following small bowel obstruction due to malignancy in the national audit of small bowel obstruction

Introduction Patients with cancer who develop small bowel obstruction are at high risk of malnutrition and morbidity following compromise of gastrointestinal tract continuity. This study aimed to characterise current management and outcomes following malignant small bowel obstruction. Methods A prospective, multicentre cohort study of patients with small bowel obstruction who presented to UK hospitals between 16th January and 13th March 2017. Patients who presented with small bowel obstruction due to primary tumours of the intestine (excluding left-sided colonic tumours) or disseminated intra-abdominal malignancy were included. Outcomes included 30-day mortality and in-hospital complications. Cox-proportional hazards models were used to generate adjusted effects estimates, which are presented as hazard ratios (HR) alongside the corresponding 95% confidence interval (95% CI). The threshold for statistical significance was set at the level of P ≤ 0.05 a-priori. Results 205 patients with malignant small bowel obstruction presented to emergency surgery services during the study period. Of these patients, 50 had obstruction due to right sided colon cancer, 143 due to disseminated intraabdominal malignancy, 10 had primary tumours of the small bowel and 2 patients had gastrointestinal stromal tumours. In total 100 out of 205 patients underwent a surgical intervention for obstruction. 30-day in-hospital mortality rate was 11.3% for those with primary tumours and 19.6% for those with disseminated malignancy. Severe risk of malnutrition was an independent predictor for poor mortality in this cohort (adjusted HR 16.18, 95% CI 1.86 to 140.84, p = 0.012). Patients with right-sided colon cancer had high rates of morbidity. Conclusions Mortality rates were high in patients with disseminated malignancy and in those with right sided colon cancer. Further research should identify optimal management strategy to reduce morbidity for these patient groups

National prospective cohort study of the burden of acute small bowel obstruction

Background Small bowel obstruction is a common surgical emergency, and is associated with high levels of morbidity and mortality across the world. The literature provides little information on the conservatively managed group. The aim of this study was to describe the burden of small bowel obstruction in the UK. Methods This prospective cohort study was conducted in 131 acute hospitals in the UK between January and April 2017, delivered by trainee research collaboratives. Adult patients with a diagnosis of mechanical small bowel obstruction were included. The primary outcome was in‐hospital mortality. Secondary outcomes included complications, unplanned intensive care admission and readmission within 30 days of discharge. Practice measures, including use of radiological investigations, water soluble contrast, operative and nutritional interventions, were collected. Results Of 2341 patients identified, 693 (29·6 per cent) underwent immediate surgery (within 24 h of admission), 500 (21·4 per cent) had delayed surgery after initial conservative management, and 1148 (49·0 per cent) were managed non‐operatively. The mortality rate was 6·6 per cent (6·4 per cent for non‐operative management, 6·8 per cent for immediate surgery, 6·8 per cent for delayed surgery; P = 0·911). The major complication rate was 14·4 per cent overall, affecting 19·0 per cent in the immediate surgery, 23·6 per cent in the delayed surgery and 7·7 per cent in the non‐operative management groups (P < 0·001). Cox regression found hernia or malignant aetiology and malnutrition to be associated with higher rates of death. Malignant aetiology, operative intervention, acute kidney injury and malnutrition were associated with increased risk of major complication. Conclusion Small bowel obstruction represents a significant healthcare burden. Patient‐level factors such as timing of surgery, acute kidney injury and nutritional status are factors that might be modified to improve outcomes

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Medication Reviews by a Clinical Pharmacist at an Irish University Teaching Hospital

Purpose: Pharmacist-led medication reviews in hospitals have shown improvement in patient outcomes. The aim of this study is to describe the prevalence and nature of pharmacist interventions (PIs) following a medication review in an Irish teaching hospital. Methods: PIs were recorded over a six-month period in 2015. PIs were assessed by a panel of healthcare professionals (n = 5) to estimate the potential of adverse drug events (ADEs). Descriptive statistics were used for the variables and the chi square test for independence was used to analyse for any association between the variables. Results: Of the 1216 patients (55.8% female; median age 68 years (interquartile range 24 years)) who received a medication review, 313 interventions were identified in 213 patients. 412 medicines were associated with PIs, of which drugs for obstructive airway disease (n = 82), analgesics (n = 56), and antibacterial products for systemic use (n = 50) were the most prevalent. A statistically significant association was found between PI and patient’s age ≥65 years (p = 0.000), as well as female gender (p = 0.037). A total of 60.7% of the PIs had a medium or high likelihood of causing an ADE. Conclusion: Pharmacist-led medication review in a hospital setting prevented ADEs. Patients ≥65 years of age and female patients benefited the most from the interventions

Reverse epitope mapping of the E2 glycoprotein in antibody associated hepatitis C virus.

The humoral immune system responds to chronic hepatitis C virus (HCV) infection by producing neutralising antibodies (nAb). In this study we generated three HCV pseudoparticles in which E1E2 glycoprotein sequence was targeted by the host humoral immune system. We used patient derived virus free Fabs (VF-Fabs) obtained from HCV genotype 1a (n = 3), genotype 1b (n = 7) and genotype 3a (n = 1) for neutralisation of HCVpp produced in this study both individually and in combination. Based on the available anti-HCV monoclonal nAb mapping information we selected amino acid region 384-619 for conformational epitope mapping. Amongst our notable findings, we observed significant reduction in HCVpp infectivity (p<0.05) when challenged with a combination of inter genotype and subtype VF-Fabs. We also identified five binding motifs targeted by patient derived VF-Fab upon peptide mapping, of which two shared the residues with previously reported epitopes. One epitope lies within an immunodominant HVR1 and two were novel. In summary, we used a reverse epitope mapping strategy to identify preferred epitopes by the host humoral immune system. Additionally, we have combined different VF-Fabs to further reduce the HCVpp infectivity. Our data indicates that combining the antigen specificity of antibodies may be a useful strategy to reduce (in-vitro) infectivity

A budget impact analysis of a clinical medication review of patients in an Irish university teaching hospital

To measure the net benefit of a pharmacist-led medication review in acute public hospitals. To identify and measure the resources used when completing a pharmacist-led medication review, an observational study was conducted in an acute urban university teaching hospital. Health Information and Quality Authority guidelines were used to value resources used in a pharmacist-led medication review. Model inputs included demographic data, probability of adverse drug events associated with the pharmacist interventions, estimates of future discharges and cost data. The cost of a pharmacist-led medication review and savings generated from avoidance of adverse drug events were estimated and projected over a 5-year period, using hospital discharge rates taken from the hospital inpatient enquiry system and the census of population. Using the per-patient cost of a medication review, the annual cost of delivering a bi-weekly medication review is projected to vary between €6 m and €6.4 m over a 5-year period from 2017 to 2021. The per-patient net benefit of a bi-weekly medication review is €45.88. Therefore, the projected annual net benefit of a bi-weekly medication review is between €29.5 m and €31.2 m over the 5-year period of 2017 to 2021. Introducing a pharmacist-led medication review for each inpatient saves in the short and longer term. The results are consistent with previous findings. Substantial savings were estimated, regardless of variation in model parameters tested in sensitivity analysis