Employment outcomes of people with Long Covid symptoms: community-based cohort study.

BACKGROUND: Evidence on the long-term employment consequences of SARS-CoV-2 infection is lacking. We used data from a large, community-based sample in the UK to estimate associations between Long Covid and employment outcomes. METHODS: This was an observational, longitudinal study using a pre-post design. We included survey participants from 3 February 2021 to 30 September 2022 when they were aged 16-64 years and not in education. Using conditional logit modelling, we explored the time-varying relationship between Long Covid status ≥12 weeks after a first test-confirmed SARS-CoV-2 infection (reference: pre-infection) and labour market inactivity (neither working nor looking for work) or workplace absence lasting ≥4 weeks. RESULTS: Of 206 299 participants (mean age 45 years, 54% female, 92% white), 15% were ever labour market inactive and 10% were ever long-term absent during follow-up. Compared with pre-infection, inactivity was higher in participants reporting Long Covid 30 to <40 weeks [adjusted odds ratio (aOR): 1.45; 95% CI: 1.17-1.81] or 40 to <52 weeks (aOR: 1.34; 95% CI: 1.05-1.72) post-infection. Combining with official statistics on Long Covid prevalence, and assuming a correct statistical model, our estimates translate to 27 000 (95% CI: 6000-47 000) working-age adults in the UK being inactive because of Long Covid in July 2022. CONCLUSIONS: Long Covid is likely to have contributed to reduced participation in the UK labour market, though it is unlikely to be the sole driver. Further research is required to quantify the contribution of other factors, such as indirect health effects of the pandemic.

Acquired haemophilia A: A 15-year population-based review of incidence rate, patient demographics and treatment outcomes.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare bleeding disorder characterized by autoantibodies against coagulation factor VIII (FVIII). Estimates of AHA incidence are largely based on registry data, which may be prone to referral bias. Population-based studies can enhance our understanding of the epidemiology, presentation and outcomes of AHA. METHODS: We conducted a retrospective, population-based cohort study of all AHA diagnosed and treated in Manitoba, Canada over a 15-year period. Using records from the sole provincial reference laboratory, we identified all patients with FVIII inhibitors who did not have congenital haemophilia.  Using a piloted case report form, patient data was ascertained from hospital and bleeding disorder clinic records. RESULTS: From 2006 to 2021, we identified 34 patients with AHA, corresponding to a population-based incidence rate of AHA of 1.78 cases per million per year. The median age at presentation was 76 years and most cases were idiopathic (79%). Almost all patients (97%) presented with bleeding, of which 58% were considered major bleeds and required haemostatic agents in 67%. Longstanding unexplained bleeding symptoms were commonly reported, suggesting delayed diagnosis. Immunosuppressive therapy (IST) was administered in 88% of patients. Remission was achieved in 79% of patients; median time to remission was 2.1 months. There were two deaths due to bleeding. No deaths due to IST were reported. CONCLUSION: The population-based incidence of AHA in Manitoba is 1.78 cases/million/year. Bleeding is common and can be life-threatening. AHA outcomes are encouraging with the use of haemostatic agents and IST. Serious treatment-associated morbidity and mortality is uncommon.

White blood cell count trajectory and mortality in septic shock: a historical cohort study.

PURPOSE: Septic shock is associated with a mortality of 20-40%. The white blood cell count (WBC) at hospital admission correlates with prognosis in septic shock. Here, we explore whether the trajectory of WBC after admission provides further information about outcomes. We aimed to identify groups of patients with different WBC trajectories and the association of WBC trajectory with mortality. METHODS: We included adult patients with septic shock in two academic intensive care units (ICU) in Winnipeg, MB, Canada between 2006 and 2012. We used group-based trajectory analysis to group patients according to their WBC patterns over the first seven days in the ICU. Our primary analysis was the association of WBC trajectory group on 30-day mortality using multivariable Cox proportional hazards regression. RESULTS: We included 917 patients with septic shock. The final model identified seven distinct WBC trajectories. The rising WBC trajectory was independently associated with increased mortality (hazard ratio, 3.41; 95% confidence interval, 1.86 to 6.26; P < 0.001) compared with the stable WBC trajectory. CONCLUSION: In patients with septic shock, distinct and clinically relevant groups can be identified by analyzing WBC trajectories. A rising WBC trajectory was associated with higher mortality.

RéSUMé: OBJECTIF: Le choc septique est associé à une mortalité de 20 à 40 %. La numération leucocytaire à l'admission à l'hôpital est corrélée au pronostic en cas de choc septique. Dans ce manuscrit, nous tentons de déterminer si l'évolution de la numération leucocytaire après l'admission fournit plus d'informations sur les devenirs. Nous avons cherché à identifier des groupes de patients présentant différentes trajectoires d'évolution de numération leucocytaire et l'association entre l'évolution de la numération et la mortalité. MéTHODE: Nous avons inclus des patients adultes atteints d'un choc septique dans deux unités de soins intensifs (USI) universitaires à Winnipeg, Manitoba, Canada entre 2006 et 2012. Nous avons utilisé une analyse de l'évolution basée sur le groupe pour regrouper les patients en fonction du type d'évolution de la numération leucocytaire au cours des sept premiers jours à l'USI. Notre analyse principale consistait à déterminer l'association entre le groupe d'évolution de numération leucocytaire et la mortalité à 30 jours en utilisant une régression multivariable à risque proportionnel de Cox. RéSULTATS: Nous avons inclus 917 patients atteints de choc septique. Le modèle final a identifié sept types de trajectoire d'évolution de numération leucocytaire distincts. Une évolution ascendante de la numération leucocytaire était indépendamment associée à une augmentation de la mortalité (rapport de risque, 3,41; intervalle de confiance à 95 %, 1,86 à 6,26; P < 0,001) par rapport à une évolution de numération leucocytaire stable. CONCLUSION: Chez les patients atteints de choc septique, des groupes distincts et cliniquement pertinents peuvent être identifiés en analysant les trajectoires d'évolution de la numération leucocytaire. Une évolution ascendante de la numération leucocytaire était associée à une mortalité plus élevée.

Prophylactic tranexamic acid use in non-cardiac surgeries at high risk for transfusion.

BACKGROUND: Tranexamic acid (TXA) reduces transfusion in a wide range of surgical populations, although its real-world use in non-cardiac surgeries has not been well described. The objective of this study was to describe prophylactic TXA use in non-cardiac surgeries at high risk for transfusion. METHODS: This is a retrospective cohort study of all adult patients undergoing major non-cardiac surgery at ≥5% risk of perioperative transfusion at five Canadian hospitals between January 2014 and December 2016. Canadian Classification of Health Interventions procedure codes within the Discharge Abstract Database were linked to transfusion and laboratory databases. TXA use was ascertained electronically from The Ottawa Hospital Data Warehouse and via manual chart review for Winnipeg hospitals. For each surgery, we evaluated the percentage of patients who received TXA as well as the specifics of TXA dosing and administration. RESULTS: TXA use was evaluable in 14 300 patients. Overall, 17% of surgeries received TXA, ranging from 0% to 68% among individual surgeries. TXA use was more common in orthopaedic (n = 2043/4942; 41%) and spine surgeries (n = 239/1322; 18%) compared to other surgical domains (n = 109/8036; 1%). TXA was commonly administered as a bolus (n = 2097/2391; 88%). The median TXA dose was 1000 mg (IQR 1000-1000 mg). CONCLUSION: TXA is predominantly used in orthopaedic and spine surgeries, with little uptake in other non-cardiac surgeries at high risk for red blood cell transfusion. Further studies are needed to evaluate the effectiveness and safety of TXA and to understand the barriers to TXA administration in a broad range of non-cardiac surgeries.

Epidemiology of intravenous immune globulin in septic shock: a retrospective cohort analysis of the Premier Healthcare Database.

PURPOSE: Intravenous immune globulin (IVIG) may improve survival in people with septic shock. Current utilization patterns of IVIG are unknown. We sought to characterize adult patients with septic shock requiring vasopressors who received IVIG, describes IVIG regimens, and evaluate determinants of IVIG use in patients with septic shock. METHODS: We conducted a retrospective database study of adult patients with septic shock admitted to US hospitals in the Premier Healthcare Database (from July 2010 to June 2013). We described the proportion of patients with septic shock receiving IVIG, examined IVIG regimens across sites and employed random-effects multivariable regression techniques to identify predictors of IVIG use. RESULTS: Intravenous immune globulin was administered to 0.3% (n = 685) of patients with septic shock; with a median [interquartile range (IQR)] dose of 1 [0.5-1.8] g·kg-1 for a median [IQR] of 1 [1-2] day. Receipt of IVIG was less likely for Black patients (odds ratio [OR], 0.54; 95% confidence interval [CI] 0.41 to 0.72) and patients without private insurance (Medicare OR, 0.73; 95% CI 0.59 to 0.90; Medicaid OR, 0.41; 95% CI 0.30 to 0.57) and more likely for patients with immunocompromise (OR, 6.83; 95% CI 5.47 to 8.53), necrotizing fasciitis (OR, 9.78; 95% CI 6.97 to 13.72), and toxic shock (OR, 56.9; 95% CI 38.7 to 83.7). CONCLUSIONS: Intravenous immune globulin is used infrequently across the US in patients with septic shock. Regimens of IVIG in septic shock may be less intensive than those associated with a survival benefit in meta-analyses. Observed infrequent use supports apparent clinical equipoise, perhaps secondary to limitations of the primary literature. A clinical trial evaluating the role of IVIG in septic shock is needed.

RéSUMé: OBJECTIF: L'immunoglobuline intraveineuse (IGIV) peut améliorer la survie chez les personnes atteintes de choc septique. Les pratiques actuelles d'utilisation de l'IGIV sont inconnues. Nous avons cherché à caractériser les patients adultes en état de choc septique et nécessitant des vasopresseurs qui ont reçu de l'IGIV, à décrire les dosages administrés d'IGIV, et à évaluer les causes déterminantes d'une utilisation d'IGIV chez ces patients. MéTHODE: Nous avons réalisé une étude rétrospective de base de données portant sur des patients adultes atteints de choc septique admis dans des hôpitaux américains et inclus dans la base de données Premier Healthcare (de juillet 2010 à juin 2013). Nous avons décrit la proportion de patients en choc septique recevant de l'IGIV, examiné les posologies utilisées d'IGIV à travers les sites et employé des techniques de régression multivariable à effets aléatoires pour identifier les prédicteurs de l'utilisation d'IGIV. RéSULTATS: L'IGIV a été administrée à 0,3 % (n = 685) des patients présentant un choc septique, avec une dose médiane [écart interquartile (ÉIQ)] de 1 [0,5­1,8] g·kg-1 pour une médiane [ÉIQ] de 1 [1­2] jour. L'administration d'IGIV était moins probable chez les patients noirs (rapport de cotes [RC], 0,54; intervalle de confiance [IC] à 95 %, 0,41 à 0,72) et les patients sans assurance privée (RC Medicare, 0,73; IC 95 %, 0,59 à 0,90; RC Medicaid, 0,41; IC 95 %, 0,30 à 0,57) et plus probable chez les patients immunodéprimés (RC, 6,83; IC 95 %, 5,47 à 8,53), atteints de fasciite nécrosante (RC, 9,78; IC 95 %, 6,97 à 13,72), et en choc toxique (RC, 56,9; IC 95 %, 38,7 à 83,7). CONCLUSION: L'IGIV est rarement utilisée aux États-Unis chez les patients en choc septique. Les dosages d'IGIV utilisés en cas de choc septique pourraient être moins intensifs que ceux associés à un effet bénéfique en matière de survie dans les méta-analyses. L'utilisation peu fréquente observée appuie une équivalence clinique apparente, peut-être secondaire aux limites de la littérature princeps. Une étude clinique évaluant le rôle de l'IGIV dans le choc septique est nécessaire.

Intravenous immune globulin in septic shock: a Canadian national survey of critical care medicine and infectious disease specialist physicians.

PURPOSE: This national survey evaluated the perceived efficacy and safety of intravenous immune globulin (IVIG) in septic shock, self-reported utilization patterns, barriers to use, the population of interest for further trials and willingness to participate in future research of IVIG in septic shock. METHODS: We conducted a cross-sectional survey of critical care and infectious diseases physicians across Canada. We summarized categorical item responses as counts and proportions. We developed a multivariable logistic regression model to identify physician-level predictors of IVIG use in septic shock. RESULTS: Our survey was disseminated to 674 eligible respondents with a final response rate of 60%. Most (91%) respondents reported having prescribed IVIG to patients with septic shock at least once, 86% for septic shock due to necrotizing fasciitis, 52% for other bacterial toxin-mediated causes of septic shock, and 5% for undifferentiated septic shock. The majority of respondents expressed uncertainty regarding the impact of IVIG on mortality (97%) and safety (95%) in septic shock. Respondents were willing to participate in further IVIG research with 98% stating they would consider enrolling their patients into a trial of IVIG in septic shock. Familiarity with published evidence was the single greatest predictor of IVIG use in septic shock (odds ratio, 10.2; 95% confidence interval, 3.4 to 30.5; P < 0.001). CONCLUSIONS: Most Canadian critical care and infectious diseases specialist physicians reported previous experience using IVIG in septic shock. Respondents identified inadequacy of existing research as the greatest barrier to routine use of IVIG in septic shock. Most respondents support the need for further studies on IVIG in septic shock, and would consider enrolling their own patients into a trial of IVIG in septic shock.

RéSUMé: OBJECTIF : Cette enquête nationale a évalué l'efficacité et l'innocuité perçues des immunoglobulines intraveineuses (IgIV) dans le contexte du choc septique, les habitudes d'utilisation autodéclarées, les obstacles à l'utilisation de cette modalité, les populations à explorer pour des études futures et la volonté de participer aux recherches futures sur les IgIV et le choc septique. MéTHODE : Nous avons mené une enquête transversale auprès de médecins intensivistes et spécialistes des maladies infectieuses au Canada. Nous avons résumé les réponses de chaque point catégorique en tant que dénombrement et proportions. Nous avons mis au point un modèle de régression logistique multivariée afin d'identifier les prédicteurs, au niveau des médecins, d'une utilisation des IgIV en cas de choc septique. RéSULTATS : Notre sondage a été acheminé à 674 médecins admissibles et nous avons obtenu un taux de réponse final de 60 %. La plupart (91%) des répondants ont indiqué avoir prescrit des IgIV aux patients en choc septique au moins une fois, 86 % pour un choc septique dû à une fasciite nécrosante, 52 % pour des chocs septiques d'autres étiologies médiées par des toxines bactériennes, et 5 % dans des cas de choc septique non différencié. La majorité des répondants ont exprimé de l'incertitude quant à l'incidence des IgIV sur la mortalité (97 %) et l'innocuité (95 %) lors de choc septique. Les répondants étaient disposés à participer à d'autres recherches sur les IgIV, 98 % déclarant qu'ils envisageraient d'inscrire leurs patients à une étude sur les IgIV et le choc septique. La familiarité avec les données probantes publiées était le plus grand prédicteur d'utilisation d'IgIV dans un contexte de choc septique (rapport de cotes, 10,2; intervalle de confiance à 95 %, 3,4 à 30,5; P < 0,001). CONCLUSION : La plupart des médecins intensivistes et spécialistes des maladies infectieuses canadiens ont rapporté avoir une expérience antérieure d'utilisation d'IgIV en cas de choc septique. Les répondants ont identifié l'insuffisance de la recherche existante comme le plus grand obstacle à l'utilisation systématique d'IgIV dans les cas de choc septique. La plupart des répondants appuient la nécessité d'études plus approfondies sur les IgIV et le choc septique et envisageraient d'inscrire leurs propres patients à une étude sur les IgIV dans un contexte de choc septique.

Variation in prophylactic tranexamic acid administration among anesthesiologists and surgeons in orthopedic surgery: a retrospective cohort study.

PURPOSE: Tranexamic acid (TXA) reduces red blood cell transfusion in various orthopedic surgeries, yet the degree of practice variation in its use among anesthesiologists and surgeons has not been described. To target future knowledge transfer and implementation strategies, and to better understand determinants of variability in prophylactic TXA use, our primary objective was to evaluate the influence of surgical team members on the variability of prophylactic TXA administration. METHODS: This was a retrospective cohort study of all adult patients undergoing primary total hip arthroplasty (THA), hip fracture surgery, and spine fusion ± vertebrectomy at two Canadian hospitals between January 2014 and December 2016. We used Canadian Classification of Health Interventions procedure codes within the Discharge Abstract Database which we linked to the Ottawa Data Warehouse. We described the percentage of patients that received TXA by individual surgery, the specifics of TXA dosing, and estimated the effect of anesthesiologists and surgeons on prophylactic TXA using multivariable mixed-effects logistic regression analyses. RESULTS: In the 3,900 patients studied, TXA was most commonly used in primary THA (85%; n = 1,344/1,582), with lower use in hip fracture (23%; n = 342/1,506) and spine fusion surgery (23%; n = 186/812). The median [interquartile range] total TXA dose was 1,000 [1,000-1,000] mg, given as a bolus in 92% of cases. Anesthesiologists and surgeons added significant variability to the odds of receiving TXA in hip fracture surgery and spine fusion, but not primary THA. Most of the variability in TXA use was attributed to patient and other factors. CONCLUSION: We confirmed the routine use of TXA in primary THA, while observing lower utilization with more variability in hip fracture and spine fusion surgery. Further study is warranted to understand variations in use and the barriers to TXA implementation in a broader population of orthopedic surgical patients at high risk for transfusion.

RéSUMé: OBJECTIF: L'acide tranexamique (ATX) réduit la transfusion d'érythrocytes dans diverses chirurgies orthopédiques. Cependant, les variations de pratique quant à son utilisation parmi les anesthésiologistes et les chirurgiens n'ont pas été décrites. Afin de cibler les stratégies futures de transfert des connaissances et de mise en œuvre, et pour mieux comprendre les déterminants de la variabilité dans l'utilisation prophylactique d'ATX, notre objectif principal était d'évaluer l'influence des membres de l'équipe chirurgicale sur la variabilité de l'administration prophylactique d'ATX. MéTHODE: Il s'agissait d'une étude de cohorte rétrospective de tous les patients adultes subissant une arthroplastie totale primaire de la hanche (ATH), une chirurgie de fracture de la hanche et une fusion intervertébrale ± vertébrectomie dans deux hôpitaux canadiens entre janvier 2014 et décembre 2016. Nous avons utilisé les codes de procédure de la Classification canadienne des interventions en santé dans la Base de données sur les congés des patients, que nous avons liée à la banque de données d'Ottawa. Nous avons décrit le pourcentage de patients qui ont reçu de l'ATX par chirurgie individuelle, les détails du dosage de l'ATX, et avons estimé l'effet des anesthésiologistes et des chirurgiens sur l'ATX prophylactique en réalisant des analyses de régression logistique multivariées à effets mixtes. RéSULTATS: Parmi les 3900 patients étudiés, l'ATX était le plus fréquemment utilisé lors d'une ATH primaire (85 %; n = 1344/1582), avec une utilisation plus faible lors de chirurgie de fracture de la hanche (23 %; n = 342/1506) et de chirurgie de fusion intervertébrale (23 %; n = 186/812). La dose totale médiane [écart interquartile] d'ATX était de 1000 mg [1000 à 1000], administrés dans 92 % des cas sous forme de bolus. Les anesthésiologistes et les chirurgiens ont ajouté une variabilité significative aux probabilités de recevoir de l'ATX lors d'une chirurgie de fracture de la hanche et de fusion, mais pas lors d'ATH primaire. La majeure partie de la variabilité dans l'utilisation d'ATX était attribuable aux facteurs liés au patient et à d'autres facteurs. CONCLUSION: Nous avons confirmé l'utilisation de routine de l'ATX dans l'ATH primaire, tout en observant une utilisation moins répandue et plus variable lors de chirurgie de fracture de la hanche et de fusion intervertébrale. Une étude plus approfondie est nécessaire pour comprendre les variations d'utilisation et les obstacles à la mise en œuvre de l'ATX dans une population plus étendue de patients de chirurgie orthopédique à haut risque de transfusion.

Clinical characterization and hematopoietic stem cell transplant outcomes for congenital sideroblastic anemia caused by a novel pathogenic variant in SLC25A38.

BACKGROUND: Congenital sideroblastic anemia (CSA) constitutes an uncommon category of inherited anemia often associated with pathologic iron accumulation. Pathogenic variants in several genes have been identified as causative for CSA. Autosomal recessive pathogenic variants in the mitochondrial glycine transporter SLC25A38 have been implicated in a subset of patients with CSA. PROCEDURE: We describe seven individuals of Canadian Cree descent with a known or inferred homozygous novel founder missense variant in SLC25A38 (c.560G>A, p.Arg187Gln). RESULTS: All individuals presented as young children (median age 6 months) with severe microcytic, hypochromic anemia associated with pretransfusion iron overload, requiring red cell transfusion support and iron chelation. Six individuals received pyridoxine supplementation; two demonstrating transient partial responses. Three individuals underwent allogeneic hematopoietic stem cell transplantation (HSCT). One individual with significant iron loading died in the posttransplant period due to complications of sepsis. The other two individuals remain transfusion-free following HSCT. CONCLUSIONS: Despite a common genetic etiology, phenotypic variability was noted in this cohort. A transient response to pyridoxine was noted in two individuals but should not be considered a long-term therapeutic strategy. HSCT was curative when performed before significant iron loading occurred. Early identification of CSA and timely HSCT can result in excellent long-term outcomes.

Evolution and Impact of Thrombocytopenia in Septic Shock: A Retrospective Cohort Study.

OBJECTIVES: To characterize the prevalence, incidence, and temporal evolution of thrombocytopenia (platelets < 100 × 10/L) in septic shock and to investigate the independent association of thrombocytopenia on clinical outcomes. DESIGN: Retrospective, propensity-matched, cohort study. SETTING: Two academic ICUs in Winnipeg, Canada. PATIENTS: Nine-hundred eighty adult patients diagnosed with septic shock between 2007 and 2012. INTERVENTIONS: Propensity-matched cohort analysis and Cox proportional hazard model evaluating thrombocytopenia over time. MEASUREMENTS AND MAIN RESULTS: Of 980 adults, 165 patients (16.8%) had thrombocytopenia at ICU admission (prevalent), whereas 271 (27.7%) developed thrombocytopenia during ICU admission (incident). Among patients with incident thrombocytopenia, the median time from ICU admission to thrombocytopenia was 2 days (interquartile range, 1-3 d). Among survivors, the median time from incident thrombocytopenia to platelet recovery was 6 days (interquartile range, 4-8 d). The median time from liberation of vasopressors to recovery of platelets concentration (≥ 100 × 10/L) was 2 days (interquartile range, 0-4 d). In a propensity-matched analysis, thrombocytopenia was associated with increased durations of ICU length of stay (9 vs 6 d; p < 0.01), mechanical ventilation (7 vs 4 d; p < 0.01), and vasopressor use (4 vs 3 d; p < 0.01), as well as increased major bleeding events (41% vs 18%; p < 0.01). In an adjusted Cox proportional hazards model, thrombocytopenia was significantly associated with both increased ICU mortality (hazard ratio, 1.99; 95% CI, 1.51-2.63) and hospital mortality (hazard ratio, 1.93; 95% CI, 1.48-2.51). CONCLUSIONS: Both the prevalence and incidence of thrombocytopenia are high in septic shock. Incident thrombocytopenia occurs early in septic shock, and platelet recovery lags behind clinical recovery. In septic shock, thrombocytopenia is associated with increased length of stay, longer duration of organ support, major bleeding events, and mortality.

Bleeding by the numbers: The utility and the limitations of bleeding scores, bleeding prediction tools, and bleeding case definitions.

A patient's history of bleeding, whether spontaneous or in response to challenges, provides important information about both the likelihood of that patient having a biochemically-defined hemostatic defect, and that patient's risk of future bleeding. Other variables including age, comorbidities and medications influence these probabilities. Scoring systems have been devised in an effort to make the estimates quantitative in specific populations. An example of a bleeding score is the MCMDM1-VWD questionnaire, which was developed to predict the likelihood of a patient having von Willebrand disease. It sums standardized details of the bleeding history, weighted by severity. The HAS-BLED score typifies bleeding prediction tools, developed to predict bleeding during anticoagulant therapy. Although prior bleeding is one item in this score, other comorbidities like hypertension or a history of stroke count for more. A third and related concept is that of bleeding case definitions, which are critical to standardize the reporting of outcomes in trials of antithrombotic agents, and which have entrenched the recognition of different severities of bleeding. We advocate that future efforts should blend some of these features. Information about comorbidities and medication use could refine the interpretation of bleeding events in a bleeding score. So could the introduction of a denominator reflecting the number and duration of challenges to which the patient has been exposed when bleeding might have been expected. More detailed information about the type, frequency and severity of prior bleeding could improve the prognostic power of bleeding prediction tools. More detailed history-based scores might ultimately supersede biochemical testing in many cases.

The efficacy and safety of heparin in patients with sepsis: a systematic review and metaanalysis.

OBJECTIVE: To evaluate the efficacy and safety of heparin in patients with sepsis, septic shock, or disseminated intravascular coagulation associated with infection. DESIGN: Systematic review and metaanalysis. DATA SOURCES: Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, Global Health, Scopus, Web of Science, the International Clinical Trials Registry Platform (inception to April 2014), conference proceedings, and reference lists of relevant articles. STUDY SELECTION AND DATA EXTRACTION: Two reviewers independently identified and extracted trial-level data from randomized trials investigating unfractionated or low molecular heparin administered to patients with sepsis, severe sepsis, septic shock, or disseminated intravascular coagulation associated with infection. Internal validity was assessed in duplicate using the Risk of Bias tool. The strength of evidence was assessed in duplicate using Grading of Recommendations Assessment, Development, and Evaluation methodology. Our primary outcome was mortality. Safety outcomes included hemorrhage, transfusion, and thrombocytopenia. MEASUREMENTS AND MAIN RESULTS: We included nine trials enrolling 2,637 patients. Eight trials were of unclear risk of bias and one was classified as having low risk of bias. In trials comparing heparin to placebo or usual care, the risk ratio for death associated with heparin was 0.88 (95% CI, 0.77-1.00; I2 = 0%; 2,477 patients; six trials; moderate strength of evidence). In trials comparing heparin to other anticoagulants, the risk ratio for death was 1.30 (95% CI, 0.78-2.18; I2 = 0%; 160 patients; three trials; low strength of evidence). In trials comparing heparin to placebo or usual care, major hemorrhage was not statistically significantly increased (risk ratio, 0.79; 95% CI, 0.53-1.17; I2 = 0%; 2,392 patients; three trials). In one small trial of heparin compared with other anticoagulants, the risk of major hemorrhage was significantly increased (2.14; 95% CI, 1.07-4.30; 48 patients). Important secondary and safety outcomes, including minor bleeding, were sparsely reported. CONCLUSIONS: Heparin in patients with sepsis, septic shock, and disseminated intravascular coagulation associated with infection may be associated with decreased mortality; however, the overall impact remains uncertain. Safety outcomes have been underreported and require further study. Increased major bleeding with heparin administration cannot be excluded. Large rigorous randomized trials are needed to evaluate more carefully the efficacy and safety of heparin in patients with sepsis, severe sepsis, and septic shock.

Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis.

Hereditary xerocytosis (HX, MIM 194380) is an autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. Copy number analyses, linkage studies, and exome sequencing were used to identify novel mutations affecting PIEZO1, encoded by the FAM38A gene, in 2 multigenerational HX kindreds. Segregation analyses confirmed transmission of the PIEZO1 mutations and cosegregation with the disease phenotype in all affected persons in both kindreds. All patients were heterozygous for FAM38A mutations, except for 3 patients predicted to be homozygous by clinical and physiologic studies who were also homozygous at the DNA level. The FAM38A mutations were both in residues highly conserved across species and within members of the Piezo family of proteins. PIEZO proteins are the recently identified pore-forming subunits of channels that mediate mechanotransduction in mammalian cells. FAM38A transcripts were identified in human erythroid cell mRNA, and discovery proteomics identified PIEZO1 peptides in human erythrocyte membranes. These findings, the first report of mutation in a mammalian mechanosensory transduction channel-associated with genetic disease, suggest that PIEZO proteins play an important role in maintaining erythrocyte volume homeostasis.

The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis.

INTRODUCTION: Sepsis and septic shock are leading causes of intensive care unit (ICU) mortality. They are characterized by excessive inflammation, upregulation of procoagulant proteins and depletion of natural anticoagulants. Plasma exchange has the potential to improve survival in sepsis by removing inflammatory cytokines and restoring deficient plasma proteins. The objective of this study is to evaluate the efficacy and safety of plasma exchange in patients with sepsis. METHODS: We searched MEDLINE, EMBASE, CENTRAL, Scopus, reference lists of relevant articles, and grey literature for relevant citations. We included randomized controlled trials comparing plasma exchange or plasma filtration with usual care in critically ill patients with sepsis or septic shock. Two reviewers independently identified trials, extracted trial-level data and performed risk of bias assessments using the Cochrane Risk of Bias tool. The primary outcome was all-cause mortality reported at longest follow-up. Meta-analysis was performed using a random-effects model. RESULTS: Of 1,957 records identified, we included four unique trials enrolling a total of 194 patients (one enrolling adults only, two enrolling children only, one enrolling adults and children). The mean age of adult patients ranged from 38 to 53 years (n = 128) and the mean age of children ranged from 0.9 to 18 years (n = 66). All trials were at unclear to high risk of bias. The use of plasma exchange was not associated with a significant reduction in all-cause mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.45 to 1.52, I(2) 60%). In adults, plasma exchange was associated with reduced mortality (RR 0.63, 95% CI 0.42 to 0.96; I(2) 0%), but was not in children (RR 0.96, 95% CI 0.28 to 3.38; I(2) 60%). None of the trials reported ICU or hospital lengths of stay. Only one trial reported adverse events associated with plasma exchange including six episodes of hypotension and one allergic reaction to fresh frozen plasma. CONCLUSIONS: Insufficient evidence exists to recommend plasma exchange as an adjunctive therapy for patients with sepsis or septic shock. Rigorous randomized controlled trials evaluating clinically relevant patient-centered outcomes are required to evaluate the impact of plasma exchange in this condition.

Preoperative therapeutic apheresis for severe medically refractory amiodarone-induced thyrotoxicosis: a case report.

INTRODUCTION: Amiodarone is associated with thyroid dysfunction and life-threatening thyrotoxicosis. In medically refractory cases, or where medical therapy is contraindicated, thyroidectomy may be required. To decrease perioperative thyroid storm and to reduce overall surgical risk, apheresis may be considered preoperatively to restore euthyroidism. CASE DESCRIPTION: We report a 46-year-old female with a history of cardiac arrhythmia and tachycardia-induced cardiomyopathy for which she received amiodarone. Months after discontinuation of amiodarone, the patient presented with wide complex tachycardia and symptoms of thyrotoxicosis. Laboratory testing confirmed severe thyrotoxicosis which was subsequently refractory to medical therapy. Total thyroidectomy was required. Following a total of 10 apheresis treatments, thyroid hormone levels were reduced to near normal levels and the patient's symptoms improved. Thyroidectomy was performed without intraoperative or postoperative complication. DISCUSSION: In the setting of life-threatening, medically refractory amiodarone-induced thyrotoxicosis, therapeutic apheresis can effectively reduce thyroid hormone levels and restore a state of clinical and biochemical euthyroidism.

Impacts of Long COVID on workers: A longitudinal study of employment exit, work hours and mental health in the UK.

BACKGROUND: The COVID-19 pandemic has had enormous implications for the world of work. However, there has been relatively little focus on the employment and workforce challenges of the virus in relation to workforce health, beyond the immediate management of the spread of the disease. There is an important gap in understanding the ongoing workforce issues created by the significant incidence of Long COVID in the population. AIM: This paper examines the effects of Long COVID on employment and workers' mental health to contribute to understanding of work-limiting health conditions and to offer policy implications for COVID-19 and similar health conditions on employment and the workforce. METHODS: A large national panel study for the UK is used to estimate the likelihood of exiting employment as well as on changes in working hours and general mental health and happiness of those who remain in work. The sample includes individuals 16 years and older who were in employment in January/February 2020 and followed during the pandemic 2020-2021. Long COVID is self-reported in the data. Informed by conceptual consideration of employment protection in the UK, two groups of individuals with Long COVID are defined based on the duration of symptoms. Group 1 has Long COVID 5-28 weeks after an infection with COVID-19, which is up to the maximum length of Statutory Sick Pay in the UK. Group 2 has symptoms for 29+ weeks, which is beyond the statutory entitlement to sickness pay. Panel regression models are fitted both with fixed-effects and random-effects. Individual and job characteristics are used as controls Those with no COVID-19 symptoms are the reference group. RESULTS: In between-person comparison, Group 2 is at higher risk of exiting employment compared to those with no COVID-19 symptoms. Between-person estimates of mental health and well-being show negative effects of Long COVID for both groups but these are greatest in Group 2. Within-person estimates suggest that factors associated with earnings mediate the negative Long COVID effects on mental health in Group 1 and that Group 2 adapts to working with Long COVID. Group 1 is at risk of working zero hours (i.e. being on sick leave) but neither Group 1 nor Group 2 have a higher probability of working fewer hours compared to those with no COVID-19 symptoms. The negative impact of Long COVID on working hours stems primarily from working zero hours (sickness leave) rather than working fewer hours, suggesting a lack of accommodation by employers of Long COVID at work. POLICY IMPLICATIONS: The extension of Statutory Sickness Pay and greater flexibility to manage partial (returns to) work would help preserve employment and mental health. Those with Long COVID for 12 months are likely to meet the definition of disability and so have a right to receive reasonable workplace adjustments.

Activated protein C and septic shock: a propensity-matched cohort study*.

BACKGROUND: Septic shock is a highly inflammatory and procoagulant state associated with significant mortality. In a single randomized controlled trial, recombinant human activated protein C (drotrecogin alfa) reduced mortality in patients with severe sepsis at high risk of death. Further clinical trials, including a recently completed trial in patients with septic shock, failed to reproduce these results. OBJECTIVE: To evaluate the effectiveness of recombinant human activated protein C on mortality in a cohort of patients with septic shock and to explore possible reasons for inconsistent results in previous studies. DESIGN: Retrospective, 2:1 propensity-matched, multicenter cohort study. SETTING: Twenty-nine academic and community intensive care units in three countries. PATIENTS: Seven thousand three hundred ninety-two adult patients diagnosed with septic shock, of which 349 received recombinant human activated protein C within 48 hrs of intensive care unit admission between 1997 and 2007. MEASUREMENTS AND MAIN RESULTS: Our primary outcomes were mortality over 30 days and mortality stratified by Acute Physiology and Chronic Health Evaluation II quartile. Using a propensity-matched Cox proportional hazard model, we observed a 6.1% absolute reduction in 30-day mortality associated with the use of recombinant human activated protein C (108/311 [34.7%] vs. 254/622 [40.8%], hazard ratio 0.72, 95% confidence interval 0.52-1.00, p = .05) and noted consistent reductions in mortality among Acute Physiology and Chronic Health Evaluation II quartiles. A time to event analysis showed that the time to appropriate antimicrobials after documented hypotension decreased for each year of study (p = .003), a finding that was congruent with a decrease in annual mortality over the study period (odds ratio 0.96 per year [95% confidence interval 0.93-0.99], p = .003). CONCLUSIONS: In this retrospective, propensity-matched, multicenter cohort study of patients with septic shock, early use of recombinant human activated protein C was associated with reduced mortality. Improvements in general quality of care such as speed of antimicrobial delivery leading to decreasing mortality of patients with septic shock may have contributed to the null results of the recently completed trial of recombinant human activated protein C in patients with septic shock.

Transfusion in orthopaedic surgery : a retrospective multicentre cohort study.

AIMS: Orthopaedic surgeries are complex, frequently performed procedures associated with significant haemorrhage and perioperative blood transfusion. Given refinements in surgical techniques and changes to transfusion practices, we aim to describe contemporary transfusion practices in orthopaedic surgery in order to inform perioperative planning and blood banking requirements. METHODS: We performed a retrospective cohort study of adult patients who underwent orthopaedic surgery at four Canadian hospitals between 2014 and 2016. We studied all patients admitted to hospital for nonarthroscopic joint surgeries, amputations, and fracture surgeries. For each surgery and surgical subgroup, we characterized the proportion of patients who received red blood cell (RBC) transfusion, the mean/median number of RBC units transfused, and exposure to platelets and plasma. RESULTS: Of the 14,584 included patients, the most commonly performed surgeries were knee arthroplasty (24.8%), hip arthroplasty (24.6%), and hip fracture surgery (17.4%). A total of 10.3% of patients received RBC transfusion; the proportion of patients receiving RBC transfusions varied widely based on the surgical subgroup (0.0% to 33.1%). Primary knee arthroplasty and hip arthroplasty, the two most common surgeries, were associated with in-hospital transfusion frequencies of 2.8% and 4.5%, respectively. RBC transfusion occurred in 25.0% of hip fracture surgeries, accounting for the greatest total number of RBC units transfused in our cohort (38.0% of all transfused RBC units). Platelet and plasma transfusions were uncommon. CONCLUSION: Orthopaedic surgeries were associated with variable rates of transfusion. The rate of RBC transfusion is highly dependent on the surgery type. Identifying surgeries with the highest transfusion rates, and further evaluation of factors that contribute to transfusion in identified at-risk populations, can serve to inform perioperative planning and blood bank requirements, and facilitate pre-emptive transfusion mitigation strategies. Cite this article: Bone Jt Open 2021;2(10):850-857.