Mortality from COVID-19 shows a strong relationship with age and pre-existing medical conditions, as does mortality from other causes. We aimed to investigate how specific factors are differentially ...associated with COVID-19 mortality as compared to mortality from causes other than COVID-19.
Working on behalf of NHS England, we carried out a cohort study within the OpenSAFELY platform. Primary care data from England were linked to national death registrations. We included all adults (aged ≥18 years) in the database on 1st February 2020 and with >1 year of continuous prior registration; the cut-off date for deaths was 9th November 2020. Associations between individual-level characteristics and COVID-19 and non-COVID deaths, classified according to the presence of a COVID-19 code as the underlying cause of death on the death certificate, were estimated by fitting age- and sex-adjusted logistic models for these two outcomes.
17,456,515 individuals were included. 17,063 died from COVID-19 and 134,316 from other causes. Most factors associated with COVID-19 death were similarly associated with non-COVID death, but the magnitudes of association differed. Older age was more strongly associated with COVID-19 death than non-COVID death (e.g. ORs 40.7 95% CI 37.7-43.8 and 29.6 28.9-30.3 respectively for ≥80 vs 50-59 years), as was male sex, deprivation, obesity, and some comorbidities. Smoking, history of cancer and chronic liver disease had stronger associations with non-COVID than COVID-19 death. All non-white ethnic groups had higher odds than white of COVID-19 death (OR for Black: 2.20 1.96-2.47, South Asian: 2.33 2.16-2.52), but lower odds than white of non-COVID death (Black: 0.88 0.83-0.94, South Asian: 0.78 0.75-0.81).
Similar associations of most individual-level factors with COVID-19 and non-COVID death suggest that COVID-19 largely multiplies existing risks faced by patients, with some notable exceptions. Identifying the unique factors contributing to the excess COVID-19 mortality risk among non-white groups is a priority to inform efforts to reduce deaths from COVID-19.
Wellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, Health Data Research UK.
Purpose: Our purpose was to analyze the anatomy and quantitative contributions of the hip capsular ligaments. Methods: The stabilizing roles of the medial and lateral arms of the iliofemoral ...ligament, pubofemoral ligament, and ischiofemoral ligament were examined in 12 matched pairs of fresh-frozen cadaveric hips (6 male and 6 female hips). The motion at the hip joint was measured in internal and external rotation through ranges of motion from 30° flexion to 10° extension along a neutral swing path. The motion was standardized by use of frame stabilization and motion tracking. Results: There is a clear and consistent ligamentous pattern within the hip corresponding to a distinct function and contribution to internal and external rotation. On releasing the ischiofemoral ligament, the greatest gain in range of motion was that of internal rotation. The largest increase of motion by releasing the pubofemoral ligament was observed in external rotation, especially during extension. The release of the medial and lateral arms of the iliofemoral ligament each gave the greatest increase of motion in external rotation, with the lateral arm release providing more range of motion in flexion and in a neutral position. The lateral arm release also showed a significant motion increase in internal rotation, primarily in extension. Conclusions: The ischiofemoral ligament controls internal rotation in flexion and extension. The lateral arm of the iliofemoral ligament has dual control of external rotation in flexion and both internal and external rotation in extension. The pubofemoral ligament controls external rotation in extension with contributions from the medial and lateral arms of the iliofemoral ligament. Together, these findings can have significant clinical applications. Clinical Relevance: When abnormal muscular and osseous pathology can be eliminated as a cause of instability or restrictive range of motion, the understanding of the independent functions of the hip ligaments will aid in defining accurate assessment and nonsurgical and arthroscopic treatment techniques.
This Enhanced Recovery After Surgery Guideline for postoperative care in cesarean delivery will provide best practice, evidenced-based recommendations for postoperative care with primarily a maternal ...focus.
The pathway process for scheduled and unscheduled cesarean delivery for this Enhanced Recovery After Surgery cesarean delivery guideline will consider time from completion of cesarean delivery until maternal hospital discharge.
The literature search (1966–2017) used Embase and PubMed to search medical subject headings that included “Cesarean Section,” “Cesarean Delivery,” “Cesarean Section Delivery,” and all postoperative Enhanced Recovery After Surgery items. Study selection allowed titles and abstracts to be screened by individual reviewers to identify potentially relevant articles. Metaanalyses, systematic reviews, randomized controlled studies, nonrandomized controlled studies, reviews, and case series were considered for each individual topic. Quality assessment and data analyses evaluated the quality of evidence, and recommendations were evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation system as used and described in previous Enhanced Recovery After Surgery Guidelines.
The Enhanced Recovery After Surgery cesarean delivery guideline/pathway has created a pathway for postoperative care. Specifics include sham feeding, nausea and vomiting prevention, postoperative analgesia, nutritional care, glucose control, thromboembolism prophylaxis, early mobilization, urinary drainage, and discharge counseling. A number of elements of postoperative care of women who undergo cesarean delivery are recommended, based on the evidence.
As the Enhanced Recovery After Surgery cesarean delivery pathway (elements/processes) are studied, implemented, audited, evaluated, and optimized by the maternity care teams, there will be an opportunity for focused and optimized areas of care and recommendations to be further enhanced.
Study question What is the association between clarithromycin use and cardiovascular outcomes?Methods In this population based study the authors compared cardiovascular outcomes in adults aged 18 or ...more receiving oral clarithromycin or amoxicillin during 2005-09 in Hong Kong. Based on age within five years, sex, and calendar year at use, each clarithromycin user was matched to one or two amoxicillin users. The cohort analysis included patients who received clarithromycin (n=108 988) or amoxicillin (n=217 793). The self controlled case series and case crossover analysis included those who received Helicobacter pylori eradication treatment containing clarithromycin. The primary outcome was myocardial infarction. Secondary outcomes were all cause, cardiac, or non-cardiac mortality, arrhythmia, and stroke.Study answer and limitations The propensity score adjusted rate ratio of myocardial infarction 14 days after the start of antibiotic treatment was 3.66 (95% confidence interval 2.82 to 4.76) comparing clarithromycin use (132 events, rate 44.4 per 1000 person years) with amoxicillin use (149 events, 19.2 per 1000 person years), but no long term increased risk was observed. Similarly, rate ratios of secondary outcomes increased significantly only with current use of clarithromycin versus amoxicillin, except for stroke. In the self controlled case analysis, there was an association between current use of H pylori eradication treatment containing clarithromycin and cardiovascular events. The risk returned to baseline after treatment had ended. The case crossover analysis also showed an increased risk of cardiovascular events during current use of H pylori eradication treatment containing clarithromycin. The adjusted absolute risk difference for current use of clarithromycin versus amoxicillin was 1.90 excess myocardial infarction events (95% confidence interval 1.30 to 2.68) per 1000 patients.What this study adds Current use of clarithromycin was associated with an increased risk of myocardial infarction, arrhythmia, and cardiac mortality short term but no association with long term cardiovascular risks among the Hong Kong population.Funding, competing interests, data sharing ID was funded by grants from the Medical Research Council for this project. LS was funded by a grant from the Wellcome Trust. The authors have no competing interests. No additional data are available.
This paper reviews the scientific knowledge on the use of a lanthanum modified bentonite (LMB) to manage eutrophication in surface water. The LMB has been applied in around 200 environments worldwide ...and it has undergone extensive testing at laboratory, mesocosm, and whole lake scales. The available data underline a high efficiency for phosphorus binding. This efficiency can be limited by the presence of humic substances and competing oxyanions. Lanthanum concentrations detected during a LMB application are generally below acute toxicological threshold of different organisms, except in low alkalinity waters. To date there are no indications for long-term negative effects on LMB treated ecosystems, but issues related to La accumulation, increase of suspended solids and drastic resources depletion still need to be explored, in particular for sediment dwelling organisms. Application of LMB in saline waters need a careful risk evaluation due to potential lanthanum release.
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•High phosphorus binding efficiency of the lanthanum modified bentonite.•Efficiency is reduced by the presence of humic substances and competing oxyanions.•Low eco-toxicological and human health risks.•Long term investigation are suggested to verify the impact on the ecosystem.
The Greenland ice sheet has been one of the largest sources of sea-level rise since the early 2000s. However, basal melt has not been included explicitly in assessments of ice-sheet mass loss so far. ...Here, we present the first estimate of the total and regional basal melt produced by the ice sheet and the recent change in basal melt through time. We find that the ice sheet’s present basal melt production is 21.4 +4.4/−4.0 Gt per year, and that melt generated by basal friction is responsible for about half of this volume. We estimate that basal melting has increased by 2.9 ± 5.2 Gt during the first decade of the 2000s. As the Arctic warms, we anticipate that basal melt will continue to increase due to faster ice flow and more surface melting thus compounding current mass loss trends, enhancing solid ice discharge, and modifying fjord circulation.
This Enhanced Recovery After Surgery (ERAS) Guideline for perioperative care in cesarean delivery will provide best practice, evidenced-based, recommendations for preoperative, intraoperative, and ...postoperative phases with, primarily, a maternal focus. The focused pathway process for scheduled and unscheduled cesarean delivery for this ERAS Cesarean Delivery Guideline will consider from the time from decision to operate (starting with the 30–60 minutes before skin incision) to hospital discharge. The literature search (1966–2017) used Embase and PubMed to search medical subject headings that included “Cesarean Section,” “Cesarean Section,” “Cesarean Section Delivery” and all pre- and intraoperative ERAS items. Study selection allowed titles and abstracts to be screened by individual reviewers to identify potentially relevant articles. Metaanalyses, systematic reviews, randomized controlled studies, nonrandomized controlled studies, reviews, and case series were considered for each individual topic. Quality assessment and data analyses that evaluated the quality of evidence and recommendations were evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation system, as used and described in previous ERAS Guidelines. The ERAS Cesarean Delivery Guideline/Pathway has created a maternal focused pathway (for scheduled and unscheduled surgery starting from 30–60 minutes before skin incision to maternal discharge) with ERAS cesarean delivery consensus recommendations preoperative elements (anesthetic medications, fasting, carbohydrate supplementation, prophylactic antibiotics/skin preparation, ), intraoperative elements (anesthetic management, maternal hypothermia prevention, surgical technique, hysterotomy creation and closure, management of peritoneum, subcutaneous space, and skin closure), perioperative fluid management, and postoperative elements (chewing gum, management of nausea and vomiting, analgesia, timing of food intake, glucose management, antithrombotic prophylaxis, timing of ambulation, urinary management, and timing of maternal and neonate discharge). Limited topics for optimized care and for antenatal education and counselling and the immediate neonatal needs at delivery are discussed. Strong recommendations for element use were given for preoperative (antenatal education and counselling, use of antacids and histamine, H2 receptor antagonists, 2-hour fasting and small meal within 6 hours surgery, antimicrobial prophylaxis and skin preparation/chlorhexidine-alcohol), intraoperative (regional anesthesia, prevention of maternal hypothermia forced warm air, warmed intravenous fluids, room temperature), perioperative (fluid management for euvolemia and neonatal immediate care needs that include delayed cord clamping), and postoperative (fluid management to prevent nausea and vomiting, antiemetic use, analgesia with nonsteroidal antiinflammatory drugs/paracetamol, regular diet within 2 hours, tight capillary glucose control, pneumatic compression stocking for venous thromboembolism prophylaxis, immediate removal of urinary catheter). Recommendations against the element use were made for preoperative (maternal sedation, bowel preparation), intraoperative (neonatal oral suctioning or increased inspired oxygen), and postoperative (heparin should not be used routinely venous thromboembolism prophylaxis). Because these ERAS cesarean delivery pathway recommendations (elements/processes) are studied, implemented, audited, evaluated, and optimized by the maternity care teams, this will create an opportunity for the focused and optimized areas of care research with further enhanced care and recommendation.
ObjectivesTo explore whether UK primary care databases arising from two different software systems can be feasibly combined, by comparing rates of Huntington’s disease (HD, which is rare) and 14 ...common cancers in the two databases, as well as characteristics of people with these conditions.DesignDescriptive study.SettingPrimary care electronic health records from Clinical Practice Research Datalink (CPRD) GOLD and CPRD Aurum databases, with linked hospital admission and death registration data.Participants4986 patients with HD and 1 294 819 with an incident cancer between 1990 and 2019.Primary and secondary outcome measuresIncidence and prevalence of HD by calendar period, age group and region, and annual age-standardised incidence of 14 common cancers in each database, and in a subset of ‘overlapping’ practices which contributed to both databases. Characteristics of patients with HD or incident cancer: medical history, recent prescribing, healthcare contacts and database follow-up.ResultsIncidence and prevalence of HD were slightly higher in CPRD GOLD than CPRD Aurum, but with similar trends over time. Cancer incidence in the two databases differed between 1990 and 2000, but converged and was very similar thereafter. Participants in each database were most similar in terms of medical history (median standardised difference, MSD 0.03 (IQR 0.01–0.03)), recent prescribing (MSD 0.06 (0.03–0.10)) and demographics and general health variables (MSD 0.05 (0.01–0.09)). Larger differences were seen for healthcare contacts (MSD 0.27 (0.10–0.41)), and database follow-up (MSD 0.39 (0.19–0.56)).ConclusionsDifferences in cancer incidence trends between 1990 and 2000 may relate to use of a practice-level data quality filter (the ‘up-to-standard’ date) in CPRD GOLD only. As well as the impact of data curation methods, differences in underlying data models can make it more challenging to define exactly equivalent clinical concepts in each database. Researchers should be aware of these potential sources of variability when planning combined database studies and interpreting results.
Purpose
Signal detection is a crucial step in the discovery of post‐marketing adverse drug reactions. There is a growing interest in using routinely collected data to complement established ...spontaneous report analyses. This work aims to systematically review the methods for drug safety signal detection using routinely collected healthcare data and their performance, both in general and for specific types of drugs and outcomes.
Methods
We conducted a systematic review following the PRISMA guidelines, and registered a protocol in PROSPERO. MEDLINE, EMBASE, PubMed, Web of Science, Scopus, and the Cochrane Library were searched until July 13, 2021.
Results
The review included 101 articles, among which there were 39 methodological works, 25 performance assessment papers, and 24 observational studies. Methods included adaptations from those used with spontaneous reports, traditional epidemiological designs, methods specific to signal detection with real‐world data. More recently, implementations of machine learning have been studied in the literature. Twenty‐five studies evaluated method performances, 16 of them using the area under the curve (AUC) for a range of positive and negative controls as their main measure. Despite the likelihood that performance measurement could vary by drug‐event pair, only 10 studies reported performance stratified by drugs and outcomes, in a heterogeneous manner. The replicability of the performance assessment results was limited due to lack of transparency in reporting and the lack of a gold standard reference set.
Conclusions
A variety of methods have been described in the literature for signal detection with routinely collected data. No method showed superior performance in all papers and across all drugs and outcomes, performance assessment and reporting were heterogeneous. However, there is limited evidence that self‐controlled designs, high dimensional propensity scores, and machine learning can achieve higher performances than other methods.
AbstractObjectiveTo determine if trimethoprim use for urinary tract infection (UTI) is associated with an increased risk of acute kidney injury, hyperkalaemia, or sudden death in the general ...population.DesignCohort study.SettingUK electronic primary care records from practices contributing to the Clinical Practice Research Datalink linked to the Hospital Episode Statistics database.ParticipantsAdults aged 65 and over with a prescription for trimethoprim, amoxicillin, cefalexin, ciprofloxacin, or nitrofurantoin prescribed up to three days after a primary care diagnosis of UTI between April 1997 and September 2015.Main outcome measuresThe outcomes were acute kidney injury, hyperkalaemia, and death within 14 days of a UTI treated with antibiotics.ResultsAmong a cohort of 1 191 905 patients aged 65 and over, 178 238 individuals were identified with at least one UTI treated with antibiotics, comprising a total of 422 514 episodes of UTIs treated with antibiotics. The odds of acute kidney injury in the 14 days following antibiotic initiation were higher following trimethoprim (adjusted odds ratio 1.72, 95% confidence interval 1.31 to 2.24) and ciprofloxacin (1.48, 1.03 to 2.13) compared with amoxicillin. The odds of hyperkalaemia in the 14 days following antibiotic initiation were only higher following trimethoprim (2.27, 1.49 to 3.45) compared with amoxicillin. However, the odds of death within the 14 days following antibiotic initiation were not higher with trimethoprim than with amoxicillin: in the whole population the adjusted odds ratio was 0.90 (95% confidence interval 0.76 to 1.07) while among users of renin-angiotensin system blockers the odds of death within 14 days of antibiotic initiation was 1.12 (0.80 to 1.57). The results suggest that, for 1000 UTIs treated with antibiotics among people 65 and over, treatment with trimethoprim instead of amoxicillin would result in one to two additional cases of hyperkalaemia and two admissions with acute kidney injury, regardless of renin-angiotensin system blockade. However, for people taking renin-angiotensin system blockers and spironolactone treatment with trimethoprim instead of amoxicillin there were 18 additional cases of hyperkalaemia and 11 admissions with acute kidney injury.ConclusionTrimethoprim is associated with a greater risk of acute kidney injury and hyperkalaemia compared with other antibiotics used to treat UTIs, but not a greater risk of death. The relative risk increase is similar across population groups, but the higher baseline risk among those taking renin-angiotensin system blockers and potassium-sparing diuretics translates into higher absolute risks of acute kidney injury and hyperkalaemia in these groups.
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