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Impact of antibiotic use on patient-level risk of death in 36 million hospital admissions in England.
No full textOBJECTIVES
Initiatives to curb hospital antibiotic use might be associated with harm from under-treatment. We examined the extent to which variation in hospital antibiotic prescribing is associated with mortality risk in acute/general medicine inpatients.
METHODS
This ecological analysis examined Hospital Episode Statistics from 36,124,372 acute/general medicine admissions (≥16y) to 135 acute hospitals in England, 01/April/2010-31/March/2017. Random-effects meta-regression was used to investigate whether heterogeneity in adjusted 30-day mortality was associated with hospital-level antibiotic use, measured in defined-daily-doses (DDD)/1,000 bed-days. Models also considered DDDs/1,000 admissions and DDDs for narrow-spectrum/broad-spectrum antibiotics, parenteral/oral, and local interpretations of World Health Organization Access, Watch, and Reserve antibiotics.
RESULTS
Hospital-level antibiotic DDDs/1,000 bed-days varied 15-fold with comparable variation in broad-spectrum, parenteral, and Reserve antibiotic use. After extensive adjusting for hospital case-mix, the probability of 30-day mortality changed -0.010% (95% CI: -0.064,+0.044) for each increase of 500 hospital-level antibiotic DDDs/1,000 bed-days. Analyses of other metrics of antibiotic use showed no consistent association with mortality risk.
CONCLUSIONS
We found no evidence that wide variation in hospital antibiotic use is associated with adjusted mortality risk in acute/general medicine inpatients. Using low-prescribing hospitals as benchmarks could help drive safe and substantial reductions in antibiotic consumption of up-to one-third in this population
UK 2022 Consensus on Normal Tissue Dose-Volume Constraints for Oligometastatic, Primary Lung and Hepatocellular Carcinoma Stereotactic Ablative Radiotherapy.
No full textThe use of stereotactic ablative radiotherapy (SABR) in the UK has expanded over the past decade, in part as the result of several UK clinical trials and a recent NHS England Commissioning through Evaluation programme. A UK SABR Consortium consensus for normal tissue constraints for SABR was published in 2017, based on the existing literature at the time. The published literature regarding SABR has increased in volume over the past 5 years and multiple UK centres are currently working to develop new SABR services. A review and update of the previous consensus is therefore appropriate and timely. It is hoped that this document will provide a useful resource to facilitate safe and consistent SABR practice
Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement.
No full textGrowth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients
Therapies for Long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study).
No full textINTRODUCTION
Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.
METHODS AND ANALYSIS
A cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.
ETHICS AND DISSEMINATION
Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.
TRIAL REGISTRATION NUMBER
1567490
Hyperdynamic Left Ventricular Ejection Fraction in ICU Patients With Sepsis.
No full textOBJECTIVES
To evaluate the cause and prognosis of hyperdynamic left ventricular ejection fraction in critically ill patients with sepsis.
DESIGN
Retrospective, single-center cohort study.
SETTING
University Hospital ICU, Birmingham, United Kingdom.
PATIENTS
ICU patients who received a transthoracic echocardiogram within 7 days of sepsis between April 2016 and December 2019.
INTERVENTION
None.
MEASUREMENTS AND MAIN RESULTS
The 90-day mortality rates of normal (55-70%), depressed ( 70%) were compared. Multivariate logistic regression analysis was performed to determine the association of left ventricular ejection fraction phenotypes with mortality and the association of clinical variables with left ventricular ejection fraction phenotypes. One thousand fourteen patients met inclusion criteria and were 62 years old (interquartile range, 47-72), with mostly respiratory infections (n = 557; 54.9%). Ninety-day mortality was 32.1% (n = 325). Patients with hyperdynamic left ventricular ejection fraction had a higher mortality than depressed and normal left ventricular ejection fraction cohorts (58.9% [n = 103] vs 34.0% [n = 55] vs 24.7% [n = 167]; p < 0.0001, respectively). After multivariate logistic regression, hyperdynamic left ventricular ejection fraction was independently associated with mortality (odds ratio, 3.90 [2.09-7.40]), whereas depressed left ventricular ejection fraction did not (odds ratio, 0.62 [0.28-1.37]). Systemic vascular resistance was inversely associated with hyperdynamic left ventricular ejection fraction (odds ratio, 0.79 [0.58-0.95]), and age, frailty, and ischemic heart disease were associated with depressed left ventricular ejection fraction.
CONCLUSIONS
Hyperdynamic left ventricular ejection fraction was associated with mortality in septic ICU patients and may reflect unmitigated vasoplegia from sepsis. Depressed left ventricular ejection fraction was not associated with mortality but was associated with cardiovascular disease
The potential of fecal microbiota and amino acids to detect and monitor patients with adenoma.
No full textThe risk of recurrent dysplastic colonic lesions is increased following polypectomy. Yield of endoscopic surveillance after adenoma removal is low, while interval colorectal cancers occur. To longitudinally assess the dynamics of fecal microbiota and amino acids in the presence of adenomatous lesions and after their endoscopic removal. In this longitudinal case-control study, patients collected fecal samples prior to bowel preparation before scheduled colonoscopy and 3 months after this intervention. Based on colonoscopy outcomes, patients with advanced adenomas and nonadvanced adenomas (0.5-1.0 cm) who underwent polypectomy during endoscopy ( = 19) were strictly matched on age, body-mass index, and smoking habits to controls without endoscopic abnormalities ( = 19). Microbial taxa were measured by 16S RNA sequencing, and amino acids (AA) were measured by high-performance liquid chromatography (HPLC). Adenoma patients were discriminated from controls based on AA and microbial composition. Levels of proline ( = .001), ornithine ( = .02) and serine ( = .02) were increased in adenoma patients compared to controls but decreased to resemble those of controls after adenoma removal. These AAs were combined as a potential adenoma-specific panel (AUC 0.79(0.64-0.94)). For bacterial taxa, differences between patients with adenomas and controls were found ( spp.↓, spp.↓, spp.↑, spp.↑ spp.↑), but no alterations in relative abundance were observed after polypectomy. Furthermore, spp. and spp. were significantly correlated with adenoma-specific amino acids. We selected an amino acid panel specifically increased in the presence of adenomas and a microbial signature present in adenoma patients, irrespective of polypectomy. Upon validation, these panels may improve the effectiveness of the surveillance program by detection of high-risk individuals and determination of surveillance endoscopy timing, leading to less unnecessary endoscopies and less interval cancer
Outcomes of patients undergoing elective liver and pancreas cancer surgery during the SARS-CoV-2 pandemic: an international, multicentre, prospective cohort study.
No full textBACKGROUND
The effect of SARS-CoV-2 infection upon HPB cancer surgery perioperative outcomes is unclear. Establishing risk is key to individualising treatment pathways. We aimed to identify the mortality rate and complications risk for HPB cancer elective surgery during the pandemic.
METHODS
International, prospective, multicentre study of consecutive adult patients undergoing elective HPB cancer operations during the initial SARS-CoV-2 pandemic. Primary outcome was 30-day perioperative mortality. Secondary outcomes included major and surgery-specific 30-day complications. Multilevel cox proportional hazards and logistic regression models estimated association of SARS-CoV-2 and postoperative outcomes.
RESULTS
Among 2038 patients (259 hospitals, 49 countries; liver n = 1080; pancreas n = 958) some 6.2%, n = 127, contracted perioperative SARS-CoV-2. Perioperative mortality (9.4%, 12/127 vs 2.6%, 49/1911) and major complications (29.1%, 37/127 vs 13.2%, 253/1911) were higher with SARS-CoV-2 infection, persisting when age, sex and comorbidity were accounted for (HR survival 4.15, 95% CI 1.64 to 10.49; OR major complications 3.41, 95% CI 1.72 to 6.75). SARS-CoV-2 was associated with late postoperative bleeding (11.0% vs 4.2%) and grade B/C postoperative pancreatic fistula (17.9% vs 8.6%).
CONCLUSION
SARS-CoV-2 infection was associated with significantly higher perioperative morbidity and mortality. Patients without SARS-CoV-2 had acceptable morbidity and mortality rates, highlighting the need to protect patients to enable safe ongoing surgery
Meta-analysis of interrupted versus continuous suturing for Roux-en-Y hepaticojejunostomy and duct-to-duct choledochocholedochostomy.
No full textAIMS
To compare outcomes of interrupted (IS) and continuous (CS) suturing techniques for Roux-en-Y hepaticojejunostomy and duct-to-duct choledochocholedochostomy.
METHODS
The study protocol was prospectively registered in PROSPERO (registration number: CRD42021286294). A systematic search of MEDLINE, CENTRAL, and Web of Science and bibliographic reference lists were conducted (last search: 14th March 2022). All comparative studies reporting outcomes of IS and CS in hepaticojejunostomy and choledochocholedochostomy were included and their risk of bias was assessed using ROBINS-I tool. Overall biliary complications, bile leak, biliary stricture, cholangitis, liver abscess, and anastomosis time were the evaluated outcome parameters.
RESULTS
Ten comparative studies (2 prospective and 8 retrospective) were included which reported 1617 patients of whom 1186 patients underwent Roux-en-Y hepaticojejunostomy (IS: 789, CS: 397) and the remaining 431 patients underwent duct-to-duct choledochocholedochostomy (IS: 168, CS: 263). Although use of IS for hepaticojejunostomy was associated with significantly longer anastomosis time (MD: 14.15 min, p=0.0002) compared to CS, there was no significant difference in overall biliary complications (OR: 1.34, p=0.11), bile leak (OR: 1.64, p=0.14), biliary stricture (OR: 0.84, p=0.65), cholangitis (OR: 1.54, p=0.35), or liver abscess (OR: 0.58, p=0.40) between two groups. Similarly, use of IS for choledochocholedochostomy was associated with no significant difference in risk of overall biliary complications (OR: 0.92, p=0.90), bile leak (OR: 1.70, p=0.28), or biliary stricture (OR: 1.07, p=0.92) compared to CS.
CONCLUSIONS
Interrupted and continuous suturing techniques for Roux-en-Y hepaticojejunostomy or duct-to-duct choledochocholedochostomy seem to have comparable clinical outcomes. The available evidence may be subject to confounding by indication with respect to diameter of bile duct. Future high-quality research is encouraged to report the outcomes with respect to duct diameter and suture material
Efficacy And Safety Of Intravenous Iron In Children With Iron Deficiency Anaemia Poorly Compliant To Oral Iron Therapy.
No full textBACKGROUND
Iron deficiency is the most common nutritional deficiency worldwide. Common causes of IDA in children are excessive consumption of cow's milk and prolonged breast feeding with delayed and poor weaning. Oral iron is the first line of treatment in children with IDA but occasionally there is inadequate response due to poor compliance. The objective of this study is to assess the effectiveness and safety of intravenous iron in children with IDA, poorly compliant to oral iron therapy.
Methods
This study consisted of 90 children from 12-60 months with IDA who were not responding adequately to oral iron therapy. Total iron requirement was calculated and given intravenously (IV) in two divided doses over two consecutive days. Participants were followed up at 2 and 4 weeks to assess the rise in haemoglobin level. Any adverse event was also noted. SPSS version 25 was used for statistical analysis.
RESULTS
Of the 90 enrolled children the mean age was 23.1±10.7 months, 47 (52.2%) were males and 43(47.8%) were females. The mean ferritin level before IV iron therapy was 3.75±2.53 ng/ml and mean haemoglobin was 5.9±1.3 g/dL. After IV iron therapy the haemoglobin level was raised to 8.38±1.09 g/dl and 9.74±0.88 g/dl at 2 and 4 weeks respectively which was statistically significant (p<0.05). The adverse events were fever in 3 (3.3%) and urticaria in 2 (2.2%) patients.
CONCLUSIONS
Intravenous iron therapy is effective and safe to raise the haemoglobin levels in children with IDA who are poorly compliant to oral iron therapy
Primary closure versus Graham patch omentopexy in perforated peptic ulcer: A systematic review and meta-analysis.
No full textBACKGROUND
There are different methods to repair a perforated peptic ulcer, the two most frequently used are the Graham patch omentopexy and the primary closure. Currently there is no high-level evidence to provide guidance of the optimal method of repair. The aim of this study is to compare the outcomes of the two methods so as to provide improved guidance for surgeons undertaking this repair.
METHODS
A systematic review and meta-analysis was conducted including any study that compared Graham patch omentopexy with primary closure in adults. Embase, Medline, Cochrane and Google's search engine were searched. The primary outcome was breakdown of the repair resulting in bile leak and the secondary outcomes were mortality, operation time, wound infection and time to start oral intake. The meta-analysis was conducted using Review Manager Software version 5:4. Outcome data were reported as odd ratios and weighted mean differences with their 95% confidence intervals.
RESULTS
Of the 229 studies identified, 6 were suitable for analysis, 4 were retrospective, one was a prospective cohort study and one was a randomized controlled trial. Meta-analysis showed no difference in occurrence of bile leak or mortality between primary closure and Graham patch omentopexy (OR 0.64; 95% (0.26-1.54) & 0.66; 95% (0.25-1.76) respectively). There was no difference in the rates of wound infection OR 0.65; 95% (0.4-1.05). The duration of the operation was shorter in the primary closure group by 5.6 min; 95% (-21 + 10.4).
CONCLUSION
There was no difference in the clinical outcomes between the two modes of repair