Molecular epidemiology of CTX-M-producing escherichia coli isolates at a tertiary medical center in western pennsylvania

A combination of phenotypic and genotypic methods was used to investigate 70 unique Escherichia coli clinical isolates identified as producing extended-spectrum beta-lactamases (ESBLs) at a medical center in Pittsburgh, PA, between 2007 and 2008. Fifty-seven isolates (81%) produced CTX-M-type ESBLs, among which CTX-M-15 was predominant (n = 46). Isolates producing CTX-M-2, -9, -14, and -65 were also identified. One CTX-M-producing isolate coproduced CMY-2 cephalosporinase. Ten isolates (14%) produced SHV-type ESBLs, either SHV-5 or SHV-7. Two isolates produced only CMY-2 or -32. Pulsed-field gel electrophoresis revealed the presence of two major clusters of CTX-M-15-producing E. coli isolates, one in phylotype B2 (n = 15) and the other in phylotype A (n = 19). Of four phylotype B2 isolates that were able to transfer the bla(CTX-M-15)-carrying plasmids, three showed fingerprints related (>60%) to those of plasmids from phylotype A isolates. In phylotype B2, all CTX-M-15-producing isolates, as well as three isolates producing CTX-M-14, two producing SHV-5, and one producing SHV-7, belonged to the international epidemic clone defined by serotype O25:H4 and sequence type 131. The plasmids from eight of nine CTX-M-15-producing E. coli isolates of phylotype A that were examined were highly related to each other and were also found in two isolates belonging to phylotype D, suggesting horizontal transfer of this bla(CTX-M-15)-carrying plasmid between phylotypes. Our findings underscore the need to further investigate the epidemiology and virulence of CTX-M-producing E. coli in the United States

Twenty-year observational study of paediatric tonsillitis and tonsillectomy

Introduction: Tonsillectomy is now only indicated in the UK when specific criteria are met, as outlined by the Scottish Intercollegiate Guidelines Network (SIGN) and The National Institute for Health and Care Excellence (NICE). As a result, fewer numbers of tonsillectomy are being performed. Tonsillectomy is the primary treatment for recurrent tonsillitis; therefore, we hypothesise that acute admissions to hospital with tonsillitis and infective complications will have risen since criteria were introduced. Our aim was to assess the rates of acute hospital admissions with tonsillitis in children and the factors associated with this. Methods: Data were provided by Information Service Division for all under 16s in Scotland between 1996/1997 and 2016/2017. Socioeconomic background was determined from the Scottish Index of Multiple Deprivation (SIMD) score. Poisson regression analysis was used to model predictors of surgery and correlation analysis to study the relationship between tonsillitis and other factors. Results: 60 456 tonsillectomies were performed. The number of tonsillectomies dropped significantly following the introduction of SIGN guidelines, and the rates of tonsillitis increased; however, admissions with tonsillitis were already on an upward trajectory. Children from the most deprived areas were 72.0% (95% CI 60% to 85%, p<0.001) more likely to receive tonsillectomy and were also more likely to be admitted with tonsillitis than the least deprived areas. Conclusion: Tonsillectomy and tonsillitis rates are highest in the most deprived; postulated reasons include antibiotic stewardship and difficulty accessing primary care. Current guidelines on tonsillectomy may be disproportionately harmful in children from deprived households

Performance of Cardiovascular Disease Risk Scores in People Diagnosed With Type 2 Diabetes:External Validation Using Data From the National Scottish Diabetes Register

Objective: To evaluate the performance of five cardiovascular disease (CVD) risk scores developed in diabetes populations and compare their performance to QRISK2. Research Design and Methods: A cohort of people diagnosed with type 2 diabetes between 2004 and 2016 was identified from the Scottish national diabetes register. CVD events were identified using linked hospital and death records. Five-year risk of CVD was estimated using each of QRISK2, ADVANCE (Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation), Cardiovascular Health Study (CHS), New Zealand Diabetes Cohort Study (NZ DCS), Fremantle Diabetes Study, and Swedish National Diabetes Register (NDR) risk scores. Discrimination and calibration were assessed using the Harrell C statistic and calibration plots, respectively. Results: The external validation cohort consisted of 181,399 people with type 2 diabetes and no history of CVD. There were 14,081 incident CVD events within 5 years of follow-up. The 5-year observed risk of CVD was 9.7% (95% CI 9.6, 9.9). C statistics varied between 0.66 and 0.67 for all risk scores. QRISK2 overestimated risk, classifying 87% to be at high risk for developing CVD within 5 years; ADVANCE underestimated risk, and the Swedish NDR risk score calibrated well to observed risk. Conclusions: None of the risk scores performed well among people with newly diagnosed type 2 diabetes. Using these risk scores to predict 5-year CVD risk in this population may not be appropriate

Cohort profile : the Scottish Diabetes Research Network national diabetes cohort - a population-based cohort of people with diabetes in Scotland

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Peer reviewedPublisher PD

Key stages in mammary gland development: The mammary end bud as a motile organ

In the rodent, epithelial end buds define the tips of elongating mammary ducts. These highly motile structures undergo repeated dichotomous branching as they aggressively advance through fatty stroma and, turning to avoid other ducts, they finally cease growth leaving behind the open, tree-like framework on which secretory alveoli develop during pregnancy. This review identifies the motility of end buds as a unique developmental marker that represents the successful integration of systemic and local mammotrophic influences, and covers relevant advances in ductal growth regulation, extracellular matrix (ECM) remodeling, and cell adhesion in the inner end bud. An unexpected growth-promoting synergy between insulin-like growth factor-1 and progesterone, in which ducts elongate without forming new end buds, is described as well as evidence strongly supporting self-inhibition of ductal elongation by end-bud-secreted transforming growth factor-β acting on stromal targets. The influence of the matrix metalloproteinase ECM-remodeling enzymes, notably matrix metalloproteinase-2, on end bud growth is discussed in the broader context of enzymes that regulate the polysaccharide-rich glycosaminoglycan elements of the ECM. Finally, a critical, motility-enabling role for the cellular architecture of the end bud is identified and the contribution of cadherins, the netrin/neogenin system, and ErbB2 to the structure and motility of end buds is discussed

Quality standards for the management of alcohol-related liver disease: consensus recommendations from the British Association for the Study of the Liver and British Society of Gastroenterology ARLD special interest group

Objective Alcohol-related liver disease (ALD) is the most common cause of liver-related ill health and liver-related deaths in the UK, and deaths from ALD have doubled in the last decade. The management of ALD requires treatment of both liver disease and alcohol use; this necessitates effective and constructive multidisciplinary working. To support this, we have developed quality standard recommendations for the management of ALD, based on evidence and consensus expert opinion, with the aim of improving patient care.Design A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology ALD Special Interest Group developed the quality standards, with input from the British Liver Trust and patient representatives.Results The standards cover three broad themes: the recognition and diagnosis of people with ALD in primary care and the liver outpatient clinic; the management of acutely decompensated ALD including acute alcohol-related hepatitis and the posthospital care of people with advanced liver disease due to ALD. Draft quality standards were initially developed by smaller working groups and then an anonymous modified Delphi voting process was conducted by the entire group to assess the level of agreement with each statement. Statements were included when agreement was 85% or greater. Twenty-four quality standards were produced from this process which support best practice. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice and an audit tool provided.Conclusion It is hoped that services will review their practice against these recommendations and key performance indicators and institute service development where needed to improve the care of patients with ALD

Emergence of methicillin resistance predates the clinical use of antibiotics

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics(1). Here we show that particular lineages of methicillin-resistant Staphylococcus aureus-a notorious human pathogen-appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two beta-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development

Metformin and the gastrointestinal tract

Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, recent evidence also implicates the gut as an important site of action. Metformin has a number of actions within the gut. It increases intestinal glucose uptake and lactate production, increases GLP-1 concentrations and the bile acid pool within the intestine, and alters the microbiome. A novel delayed-release preparation of metformin has recently been shown to improve glycaemic control to a similar extent to immediate-release metformin, but with less systemic exposure. We believe that metformin response and tolerance is intrinsically linked with the gut. This review examines the passage of metformin through the gut, and how this can affect the efficacy of metformin treatment in the individual, and contribute to the side effects associated with metformin intolerance

SurgiCal Obesity Treatment Study (SCOTS) : a prospective, observational cohort study on health and socioeconomic burden in treatment-seeking individuals with severe obesity in Scotland, UK

Objectives: There is a lack of evidence to inform the delivery and follow-up of bariatric surgery for people with severe obesity. The SurgiCal Obesity Treatment Study (SCOTS) is a national longitudinal cohort of people undergoing bariatric surgery. Here, we describe characteristics of the recruited SCOTS cohort, and the relationship between health and socioeconomic status with body mass index (BMI) and age. Participants/Methods: 445 participants scheduled for bariatric surgery at any of 14 centres in Scotland, UK, were recruited between 2013 and 2016 for this longitudinal cohort study (1 withdrawal); 249 completed health-related preoperative patient-reported outcome measures. Regression models were used to estimate the effect of a 10-unit increase in age or BMI, adjusting for sex, smoking and socioeconomic status. Results: Mean age was 46 years and median BMI was 47 kg/m2. For each 10 kg/m2 higher BMI, there was a change of −5.2 (95% CI −6.9 to –3.5; p<0.0001) in Rand 12-item Short Form Survey Physical Component Summary (SF-12 PCS), −0.1 (95% CI −0.2 to –0.1; p<0.0001) in EuroQoL 5-level EQ-5D version index score and 14.2 (95% CI 10.7 to 17.7; p<0.0001) in Impact of Weight on Quality of Life-Lite Physical Function Score. We observed a 3.1 times higher use of specialist aids and equipment at home (OR: 3.1, 95% CI 1.9 to 5.0; p<0.0001). Broadly, similar results were seen for each 10-year higher age, including a change of −2.1 (95% CI −3.7 to –0.5; p<0.01) in SF-12 PCS. Conclusions: A higher BMI combined with older age is associated with poor physical functioning and quality of life in people seeking bariatric surgery treatment. Policy-makers must consider the health and care needs of these individuals and invest to provide increased access to effective weight management. Trial registration number: ISRCTN47072588