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A scoping review to map evidence regarding key domains and questions in the management of non-traumatic wrist disorders.
INTRODUCTION: Non-traumatic wrist disorders (NTWD) are commonly encountered yet sparse resources exist to aid management. This study aimed to produce a literature map regarding diagnosis, management, pathways of care and outcome measures for NTWDs in the United Kingdom. METHODS: An interdisciplinary team of clinicians and academic researchers used Joanna Briggs Institute guidelines and the PRISMA ScR checklist in this scoping review. A mixed stakeholder group of patients and healthcare professionals identified 16 questions of importance to which the literature was mapped. An a-priori search strategy of both published and non-published material from five electronic databases and grey literature resources identified records. Two reviewers independently screened records for inclusion using explicit eligibility criteria with oversight from a third. Data extraction through narrative synthesis, charting and summary was performed independently by two reviewers. RESULTS: Of 185 studies meeting eligibility criteria, diagnoses of wrist pain, De Quervain's syndrome and ulna-sided pain were encountered most frequently, with uncontrolled non-randomised trial or cohort study being the most frequently used methodology. Diagnostic methods used included subjective questioning, self-reported pain, palpation and special tests. Best practice guidelines were found from three sources for two NTWD conditions. Seventeen types of conservative management, and 20 different patient-reported outcome measures were suggested for NTWD. CONCLUSION: Substantial gaps in evidence exist in all parts of the patient journey for NTWD when mapped against an analytic framework (AF). Opportunities exist for future rigorous primary studies to address these gaps and the preliminary concerns about the quality of the literature regarding NTWD.
Impact of COVID-19 on vascular patients worldwide: analysis of the COVIDSurg data.
BACKGROUND: The COVIDSurg collaborative was an international multicenter prospective analysis of perioperative data from 235 hospitals in 24 countries. It found that perioperative COVID-19 infection was associated with a mortality rate of 24%. At the same time, the COVER study demonstrated similarly high perioperative mortality rates in vascular surgical patients undergoing vascular interventions even without COVID-19, likely associated with the high burden of comorbidity associated with vascular patients. This is a vascular subgroup analysis of the COVIDSurg cohort. METHODS: All patients with a suspected or confirmed diagnosis of COVID-19 in the 7 days prior to, or in the 30 days following a vascular procedure were included. The primary outcome was 30-day mortality. Secondary outcomes were pulmonary complications (adult respiratory distress syndrome, pulmonary embolism, pneumonia and respiratory failure). Logistic regression was undertaken for dichotomous outcomes. RESULTS: Overall, 602 patients were included in this subgroup analysis, of which 88.4% were emergencies. The most common operations performed were for vascular-related dialysis access procedures (20.1%, N.=121). The combined 30-day mortality rate was 27.2%. Composite secondary pulmonary outcomes occurred in half of the vascular patients (N.=275, 45.7%). CONCLUSIONS: Mortality following vascular surgery in COVID positive patients was significantly higher than levels reported pre-pandemic, and similar to that seen in other specialties in the COVIDSurg cohort. Initiatives and surgical pathways that ensure vascular patients are protected from exposure to COVID-19 in the peri-operative period are vital to protect against excess mortality.
The impact of inter-infection time on antimicrobial resistance profiles in women with multiple urinary tract infections over time
Background: Urinary tract infection (UTI) treatment in primary care is increasingly complicated by antimicrobial resistance (AMR), and antimicrobial susceptibility profiles are rarely available to prescribers at the point of prescription. Susceptibility profiles from previous urine culture results could inform prescribing, but little is known about associations between previous and current susceptibilities and the impact of time between infections (inter-infection time) on these associations. Methods: We analyzed routinely collected healthcare records of women ≥16 years in Oxfordshire, UK, who had ≥2 culture-positive urine specimens consistent with a UTI between 2013-2019. We used generalized additive logistic models to estimate associations between resistance to each of eight commonly prescribed antibiotics at first UTI and at second UTI and their interaction with inter-infection time, adjusted for age and calendar year. Results: In 10,216 women, significant associations were observed between AMR at first and second UTIs. For all antibiotics, these were largest for short inter-infection times. Pivmecillinam resistance at first UTI (OR:41.70, 95% CI:27.70-62.80), followed by fosfomycin (OR:19.90, CI:13.66-28.92), and ciprofloxacin resistance (OR:19.65, 95% CI: 16.30-23.75), were strongly associated with resistance to the same antibiotic at the second UTI for inter-infection times ≤3 months. Lower magnitude associations were observed for other antibiotics. For UTIs caused by E. coli only, these associations were generally larger. Conclusions: In a cohort of women experiencing UTIs, AMR at the first UTI and inter-infection time were key determinants of AMR in the second UTI. This information could inform empiric antimicrobial treatment to limit treatment failure in women with recurrent UTI.
Reducing routine group and save testing in emergency laparoscopic appendicectomy surgery: a quality improvement project assessing the triple bottom line.
INTRODUCTION: There is compelling evidence supporting the omission of routine group and save (G&S) testing pre-operatively in emergency laparoscopy where appendicitis is suspected. Most studies are retrospective; however, one study prospectively demonstrated safe application in laparoscopic cholecystectomies only. We sought to assess safety, cost, and environmental and social savings-the triple bottom line-of omitting routine G&S testing in laparoscopic appendicectomies, by undertaking a quality improvement project at a busy district general hospital. METHODS: All patients who underwent an emergency laparoscopy +/- appendicectomy, between 1 November 2020 and 31 October 2021, were retrospectively reviewed, and cross-referenced to haematological testing and blood product dispensation data. A cost of £15 was applied to processed G&S samples and £1.89 to rejected samples. A carbon cost of 1,066 g CO2 emissions (CO2 e) was applied to all samples. We then prospectively undertook a 6-month pilot intervention to omit routine G&S testing in these cases. Patients from either cohort who required blood transfusions underwent a deep dive to identify risk factors. RESULTS: Pre-intervention, 281/392 (71.7%) of patients had valid G&S samples prior to their procedure and no patient required blood products during their episode. Post-intervention, 56/189 (29.1%) patients had valid G&S samples. One patient with chronic anaemia required a preoperative blood transfusion. Pre-intervention, G&S testing cost £22.24 and 1.7 kg CO2 e per laparoscopy. Post-intervention, the cost reduced to £9.78 and 0.7 kg CO2 e per laparoscopy. The intervention saved £5,021 and 353 kg CO2 e, and our institution has adopted a selective approach, based on clinical risk, for these cases indefinitely. CONCLUSION: Routine G&S testing in emergency laparoscopy +/- appendicectomy is unnecessary, costing money and time and producing carbon emissions. With effective communication of risk-mitigating factors, practice can shift from high to low rates of preoperative testing. There are further savings accessible by applying this method to other surgical procedures using a risk-based approach.
Overseas general practitioners (GPs) and opioid prescriptions in England.
The substantial recent rise in opioid prescription rates, along with increasing evidence of misuse and associated morbidity and mortality, raises serious concerns about the appropri- ateness of these drugs for pain management. This study investigates prescription behaviour differences across opioid drug categories between UK-trained and overseas-trained GPs. Us- ing panel data covering all English practices from 2018 to 2021, we find a strong association between practices with more overseas GPs and opioid prescription patterns. Regional dif- ferences emerge, with GPs from North America prescribing more opioids and those from Africa and Asia prescribing less, relative to the UK-trained counterparts. Heterogeneous cultural norms, different training environments, and varying epidemiological patterns might explain these different prescribing behaviours. Comprehensive cross-country assessments of GP competencies could identify areas for targeted training, helping to align the practices of foreign-trained GPs with UK standards while supporting the attraction of global talent.
Use of Machine Learning to Compare Disease Risk Scores and Propensity Scores Across Complex Confounding Scenarios: A Simulation Study.
PURPOSE: The surge of treatments for COVID-19 in the second quarter of 2020 had a low prevalence of treatment and high outcome risk. Motivated by that, we conducted a simulation study comparing disease risk scores (DRS) and propensity scores (PS) using a range of scenarios with different treatment prevalences and outcome risks. METHOD: Four methods were used to estimate PS and DRS: logistic regression (reference method), least absolute shrinkage and selection operator (LASSO), multilayer perceptron (MLP), and XgBoost. Monte Carlo simulations generated data across 25 scenarios varying in treatment prevalence, outcome risk, data complexity, and sample size. Average treatment effects were calculated after matching. Relative bias and average absolute standardized mean difference (ASMD) were reported. RESULT: Estimation bias increased as treatment prevalence decreased. DRS showed lower bias than PS when treatment prevalence was below 0.1, especially in nonlinear data. However, DRS did not outperform PS in linear or small sample data. PS had comparable or lower bias than DRS when treatment prevalence was 0.1-0.5. Three machine learning (ML) methods performed similarly, with LASSO and XgBoost outperforming the reference method in some nonlinear scenarios. ASMD results indicated that DRS was less impacted by decreasing treatment prevalence compared to PS. CONCLUSION: Under nonlinear data, DRS reduced bias compared to PS in scenarios with low treatment prevalence, while PS was preferable for data with treatment prevalence greater than 0.1, regardless of the outcome risk. ML methods can outperform the logistic regression method for PS and DRS estimation. Both decreasing sample size and adding nonlinearity and nonadditivity in data increased bias for all methods tested.
Investigating the lymphatic system in intestinal inflammation
We set out to understand the colonic lymphatic vasculature in the context of outflow from the colon, with the ambition of using this knowledge to develop methods to promote exit of inflammatory cells from the tissue as an alternative way to treat patients with inflammatory bowel disease. Our studies converged on the identification of tissue folds as central anatomical units that orchestrate interstitial fluid outflow from the colon. We observed that the luminal surface of the mammalian colon is characterised by undulations of the mucosa and submucosa forming tissue folds. In humans these included haustral folds and intrahaustral folds of lesser prominence between muscular bands of taenia coli. Mice lacked taenia coli and haustra but nonetheless possessed folds, especially in the proximal colon. The functional significance of these colonic tissue undulations, beyond increasing surface area for absorption, had not previously been determined. Here, through murine in vivo and 3D imaging studies, we show that tissue folds orchestrated the collection and outflow of interstitial fluid from the colon. We demonstrate that lymphatics line the base of colonic crypts and specifically branched toward the epithelium within folds. Colonic folds functioned as reservoirs feeding lymphatic and venous outflow, and phagocytic scavenging by fold-associated mononuclear phagocytes augmented this reservoir property. Colonic lymphoid follicles were enriched within these tissue folds, surrounded by lymphatics and postcapillary venules. Human colonic lymphoid follicles were likewise positioned within the elevation of tissue folds. Our findings suggest that colonic folds are distinct anatomical units conserved across species that organise uptake, immunosurveillance, and outflow of interstitial cargo, while restraining the spread of inflammation. Indeed, the loss of tissue folds during ulcerative colitis may facilitate distal-to-proximal spread of pathology.
A new model measuring bacterial phagocytosis and phagolysosomal oxidation in humans using the intradermal injection of methylene blue-labeled Escherichia coli.
Phagocytosis is an important leukocyte function; however, using existing models it cannot be measured in human tissues in vivo. To address this, we characterized a new phagocytosis model using intradermal methylene blue-labeled Escherichia coli injection (MBEC). Methylene blue (MB) is a licensed human medicine and bacterial stain potentially useful for labeling E. coli that is safe for human injection. Ex vivo coculture of leukocytes with MBEC caused MB to transfer into neutrophils and macrophages by phagocytosis. During this, a "red shift" in MB fluorescence was shown to be caused by phagolysosomal oxidation. Hence, MBEC coculture could be used to measure phagocytosis and phagolysosomal oxidation in humans, ex vivo. In healthy volunteers, inflammatory exudate sampling using suction blisters 2 to 24 h after intradermal MBEC injection showed that tissue-acquired neutrophils and monocytes contained more MB than their circulating counterparts, whereas blood and inflamed tissue T, B, and natural killer cells were MBlo. This was validated with spectral flow cytometry by visualizing the MB emission spectrum in tissue-acquired neutrophils. Neutrophil MB emission spectra demonstrated more red shift at 24 h compared with earlier time points, in keeping with progressive phagolysosomal MB oxidation in neutrophils over time in vivo. This new MBEC model can therefore measure bacterial phagocytosis and phagolysosomal oxidation in human skin, in vivo. This has a number of important research applications, e.g. in studying human phagocyte biology, testing novel antimicrobials, and understanding why certain groups such as males, the elderly or those with diabetes, recent surgery, or malnutrition are at increased risk of bacterial infection.
Changing life expectancy in European countries 1990-2021: a subanalysis of causes and risk factors from the Global Burden of Disease Study 2021.
BACKGROUND: Decades of steady improvements in life expectancy in Europe slowed down from around 2011, well before the COVID-19 pandemic, for reasons which remain disputed. We aimed to assess how changes in risk factors and cause-specific death rates in different European countries related to changes in life expectancy in those countries before and during the COVID-19 pandemic. METHODS: We used data and methods from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to compare changes in life expectancy at birth, causes of death, and population exposure to risk factors in 16 European Economic Area countries (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, and Sweden) and the four UK nations (England, Northern Ireland, Scotland, and Wales) for three time periods: 1990-2011, 2011-19, and 2019-21. Changes in life expectancy and causes of death were estimated with an established life expectancy cause-specific decomposition method, and compared with summary exposure values of risk factors for the major causes of death influencing life expectancy. FINDINGS: All countries showed mean annual improvements in life expectancy in both 1990-2011 (overall mean 0·23 years [95% uncertainty interval [UI] 0·23 to 0·24]) and 2011-19 (overall mean 0·15 years [0·13 to 0·16]). The rate of improvement was lower in 2011-19 than in 1990-2011 in all countries except for Norway, where the mean annual increase in life expectancy rose from 0·21 years (95% UI 0·20 to 0·22) in 1990-2011 to 0·23 years (0·21 to 0·26) in 2011-19 (difference of 0·03 years). In other countries, the difference in mean annual improvement between these periods ranged from -0·01 years in Iceland (0·19 years [95% UI 0·16 to 0·21] vs 0·18 years [0·09 to 0·26]), to -0·18 years in England (0·25 years [0·24 to 0·25] vs 0·07 years [0·06 to 0·08]). In 2019-21, there was an overall decrease in mean annual life expectancy across all countries (overall mean -0·18 years [95% UI -0·22 to -0·13]), with all countries having an absolute fall in life expectancy except for Ireland, Iceland, Sweden, Norway, and Denmark, which showed marginal improvement in life expectancy, and Belgium, which showed no change in life expectancy. Across countries, the causes of death responsible for the largest improvements in life expectancy from 1990 to 2011 were cardiovascular diseases and neoplasms. Deaths from cardiovascular diseases were the primary driver of reductions in life expectancy improvements during 2011-19, and deaths from respiratory infections and other COVID-19 pandemic-related outcomes were responsible for the decreases in life expectancy during 2019-21. Deaths from cardiovascular diseases and neoplasms in 2019 were attributable to high systolic blood pressure, dietary risks, tobacco smoke, high LDL cholesterol, high BMI, occupational risks, high alcohol use, and other risks including low physical activity. Exposure to these major risk factors differed by country, with trends of increasing exposure to high BMI and decreasing exposure to tobacco smoke observed in all countries during 1990-2021. INTERPRETATION: The countries that best maintained improvements in life expectancy after 2011 (Norway, Iceland, Belgium, Denmark, and Sweden) did so through better maintenance of reductions in mortality from cardiovascular diseases and neoplasms, underpinned by decreased exposures to major risks, possibly mitigated by government policies. The continued improvements in life expectancy in five countries during 2019-21 indicate that these countries were better prepared to withstand the COVID-19 pandemic. By contrast, countries with the greatest slowdown in life expectancy improvements after 2011 went on to have some of the largest decreases in life expectancy in 2019-21. These findings suggest that government policies that improve population health also build resilience to future shocks. Such policies include reducing population exposure to major upstream risks for cardiovascular diseases and neoplasms, such as harmful diets and low physical activity, tackling the commercial determinants of poor health, and ensuring access to affordable health services. FUNDING: Gates Foundation.