A Single-Center Comparison of Extended and Restricted THROMBOPROPHYLAXIS with LMWH after Metabolic Surgery

IntroductionMorbid obesity is an important risk factor for developing a venous thromboembolic events (VTE) after surgery. Fast-track protocols in metabolic surgery can lower the risk of VTE in the postoperative period by reducing the immobilization period. Administration of thromboprophylaxis can be a burden for patients. This study aims to compare extended to restricted thromboprophylaxis with low molecular weight heparin (LMWH) for patients undergoing metabolic surgery.MethodsIn this single center retrospective cohort study, data was collected from patients undergoing a primary Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between 2014 and 2018. Patients operated in 2014-2017 received thromboprophylaxis for two weeks. In 2018, patients only received thromboprophylaxis during hospital admission. Patients already using anticoagulants were analyzed as a separate subgroup. The primary outcome measure was the rate of clinically significant VTEs within three months. Secondary outcome measures were postoperative hemorrhage and reoperations for hemorrhage.Results3666 Patients underwent a primary RYGB or SG following the fast-track protocol. In total, two patients in the 2014-2017 cohort were diagnosed with VTE versus zero patients in the 2018 cohort. In the historic group, 34/2599 (1.3%) hemorrhages occurred and in the recent cohort 8/720 (1.1%). Postoperative hemorrhage rates did not differ between the two cohorts (multivariable analysis, p=0.475). In the subgroup of patients using anticoagulants, 21/347(6.1%) patients developed a postoperative hemorrhage. Anticoagulant use was a significant predictor of postoperative hemorrhage (

Peroperative administration of tranexamic acid in sleeve gastrectomy to reduce hemorrhage:a double-blind randomized controlled trial

Introduction: In metabolic surgery, hemorrhage is the most common major complication. This study investigated whether peroperative administration of tranexamic acid (TXA) reduced the risk of hemorrhage in patients undergoing laparoscopic sleeve gastrectomy (SG). Methods: In this double-blind randomized controlled trial, patients undergoing primary SG in a high-volume bariatric hospital were randomized (1:1) to receive 1500-mg TXA or placebo peroperatively. Primary outcome measure was peroperative staple line reinforcement using hemostatic clips. Secondary outcome measures were peroperative fibrin sealant use and blood loss, postoperative hemoglobin, heart rate, pain, major and minor complications, length of hospital stay (LOS), side effects of TXA (i.e., venous thrombotic event (VTE)) and mortality. Results:In total, 101 patients were analyzed and received TXA (n = 49) or placebo (n = 52). There was no statistically significant difference in hemostatic clip devices used in both groups (69% versus 83%, p = 0.161). TXA administration showed significant positive changes in hemoglobin levels (millimoles per Liter; 0.55 versus 0.80, p = 0.013), in heart rate (beats per minute; -4.6 versus 2.5; p = 0.013), in minor complications (Clavien–Dindo ≤ 2, 2.0% versus 17.3%, p = 0.016), and in mean LOS (hours; 30.8 versus 36.7, p = 0.013). One patient in the placebo-group underwent radiological intervention for postoperative hemorrhage. No VTE or mortality was reported. Conclusion: This study did not demonstrate a statistically significant difference in use of hemostatic clip devices and major complications after peroperative administration of TXA. However, TXA seems to have positive effects on clinical parameters, minor complications, and LOS in patients undergoing SG, without increasing the risk of VTE. Larger studies are needed to investigate the effect of TXA on postoperative major complications. Graphical abstract: [Figure not available: see fulltext.]</p

Warfarin Genotyping Reduces Hospitalization Rates Results From the MM-WES (Medco-Mayo Warfarin Effectiveness Study)

ObjectivesThis study was designed to determine whether genotype testing for patients initiating warfarin treatment will reduce the incidence of hospitalizations, including those due to bleeding or thromboembolism.BackgroundGenotypic variations in CYP2C9and VKORC1have been shown to predict warfarin dosing, but no large-scale studies have prospectively evaluated the clinical effectiveness of genotyping in naturalistic settings across the U.S.MethodsThis national, prospective, comparative effectiveness study compared the 6-month incidence of hospitalization in patients receiving warfarin genotyping (n = 896) versus a matched historical control group (n = 2,688). To evaluate for temporal changes in the outcomes of warfarin treatment, a secondary analysis compared outcomes for 2 external control groups drawn from the same 2 time periods.ResultsCompared with the historical control group, the genotyped cohort had 31% fewer hospitalizations overall (adjusted hazard ratio [HR]: 0.69, 95% confidence interval [CI]: 0.58 to 0.82, p < 0.001) and 28% fewer hospitalizations for bleeding or thromboembolism (HR: 0.72, 95% CI: 0.53 to 0.97, p = 0.029) during the 6-month follow-up period. Findings from a per-protocol analysis were even stronger: 33% lower risk of all-cause hospitalization (HR: 0.67, 95% CI: 0.55 to 0.81, p < 0.001) and 43% lower risk of hospitalization for bleeding or thromboembolism (HR: 0.57, 95% CI: 0.39 to 0.83, p = 0.003) in patients who were genotyped. During the same period, there was no difference in outcomes between the 2 external control groups.ConclusionsWarfarin genotyping reduced the risk of hospitalization in outpatients initiating warfarin. (The Clinical and Economic Impact of Pharmacogenomic Testing of Warfarin Therapy in Typical Community Practice Settings [MHSMayoWarf1]; NCT00830570

Bootstrap-assisted tests of symmetry for dependent data

The paper considers the problem of testing for symmetry (about an unknown centre) of the marginal distribution of a strictly stationary and weakly dependent stochastic process. The possibility of using the autoregressive sieve bootstrap and stationary bootstrap procedures to obtain critical values and P-values for symmetry tests is explored. Bootstrap-assisted tests for symmetry are straightforward to implement and require no prior estimation of asymptotic variances. The small-sample properties of a wide variety of tests are investigated using Monte Carlo experiments. A bootstrap-assisted version of the triples test is found to have the best overall performance

Measuring quality of life in rheumatic conditions

Musculoskeletal disorders often have associated pain, functional impairment and work disability, and, not surprisingly, are the most common reasons for utilizing healthcare resources. Rheumatoid arthritis (RA) and fibromyalgia (FM) are causes of musculoskeletal pain and disability. Research indicates that there is a widespread impact of RA and FM on physical, psychological and social factors in affected individuals, and thus, outcome measures that encompass multiple aspects of quality of life are needed. Generic measures of quality of life identify associations between physical conditions and mental health and highlight the need to address psychological functioning to ultimately improve the individuals’ quality of life

Overcoming bortezomib resistance in human B cells by anti-CD20/rituximab-mediated complement-dependent cytotoxicity and epoxyketone-based irreversible proteasome inhibitors

UNLABELLED: BACKGROUND: In clinical and experimental settings, antibody-based anti-CD20/rituximab and small molecule proteasome inhibitor (PI) bortezomib (BTZ) treatment proved effective modalities for B cell depletion in lymphoproliferative disorders as well as autoimmune diseases. However, the chronic nature of these diseases requires either prolonged or re-treatment, often with acquired resistance as a consequence. METHODS: Here we studied the molecular basis of acquired resistance to BTZ in JY human B lymphoblastic cells following prolonged exposure to this drug and examined possibilities to overcome resistance by next generation PIs and anti-CD20/rituximab-mediated complement-dependent cytotoxicity (CDC). RESULTS: Characterization of BTZ-resistant JY/BTZ cells compared to parental JY/WT cells revealed the following features: (a) 10-12 fold resistance to BTZ associated with the acquisition of a mutation in the PSMB5 gene (encoding the constitutive $β$5 proteasome subunit) introducing an amino acid substitution (Met45Ile) in the BTZ-binding pocket, (b) a significant 2-4 fold increase in the mRNA and protein levels of the constitutive $β$5 proteasome subunit along with unaltered immunoproteasome expression, (c) full sensitivity to the irreversible epoxyketone-based PIs carfilzomib and (to a lesser extent) the immunoproteasome inhibitor ONX 0914. Finally, in association with impaired ubiquitination and attenuated breakdown of CD20, JY/BTZ cells harbored a net 3-fold increase in CD20 cell surface expression, which was functionally implicated in conferring a significantly increased anti-CD20/rituximab-mediated CDC. CONCLUSIONS: These results demonstrate that acquired resistance to BTZ in B cells can be overcome by next generation PIs and by anti-CD20/rituximab-induced CDC, thereby paving the way for salvage therapy in BTZ-resistant disease

Studying strategies and types of players:Experiments, logics and cognitive models

How do people reason about their opponent in turn-taking games? Often, people do not make the decisions that game theory would prescribe. We present a logic that can play a key role in understanding how people make their decisions, by delineating all plausible reasoning strategies in a systematic manner. This in turn makes it possible to construct a corresponding set of computational models in a cognitive architecture. These models can be run and fitted to the participants’ data in terms of decisions, response times, and answers to questions. We validate these claims on the basis of an earlier game-theoretic experiment about the turn-taking game “Marble Drop with Surprising Opponent”, in which the opponent often starts with a seemingly irrational move. We explore two ways of segregating the participants into reasonable “player types”. The first way is based on latent class analysis, which divides the players into three classes according to their first decisions in the game: Random players, Learners, and Expected players, who make decisions consistent with forward induction. The second way is based on participants’ answers to a question about their opponent, classified according to levels of theory of mind: zero-order, first-order and second-order. It turns out that increasing levels of decisions and theory of mind both correspond to increasing success as measured by monetary awards and increasing decision times. Next, we use the logical language to express different kinds of strategies that people apply when reasoning about their opponent and making decisions in turn-taking games, as well as the ‘reasoning types’ reflected in their behavior. Then, we translate the logical formulas into computational cognitive models in the PRIMs architecture. Finally, we run two of the resulting models, corresponding to the strategy of only being interested in one’s own payoff and to the myopic strategy, in which one can only look ahead to a limited number of nodes. It turns out that the participant data fit to the own-payoff strategy, not the myopic one. The article closes the circle from experiments via logic and cognitive modelling back to predictions about new experiments

Country and health expenditure are major predictors of withholding anticoagulation in atrial fibrillation patients at high risk of stroke.

BACKGROUND: Guidelines for patients with atrial fibrillation (AF) at high thromboembolic risk recommend oral anticoagulants (OACs) for preventing stroke and systemic embolism (SE). The reasons for guideline non-adherence are still unclear. AIM: The aim is to identify clinical, demographic and non-patient characteristics associated with withholding OAC in patients with AF at high stroke risk. METHODS: Patients in the Global Anticoagulant Registry in the FIELD-AF, newly diagnosed with AF between March 2010 and August 2016, and with CHA2DS2-VASc Score≥2 (excluding sex), were grouped by OAC treatment at enrolment. Factors associated with OAC non-use were analysed by multivariable logistic regression. RESULTS: Of 40 416 eligible patients, 12 126 (30.0%) did not receive OACs at baseline. Globally, OAC prescription increased over time, from 60.4% in 2010-2011 to 74.7% in 2015-2016. Country of enrolment was the major predictor for OAC withholding (χ2-df=2576). Clinical predictors of OAC non-use included type of AF (χ2-df=404), history of bleeding (χ2-df=263) and vascular disease (χ2-df=99). OACs were used most frequently around the age of 75 years and decreasingly with younger as well as older age beyond 75 years (χ2-df=148). Non-cardiologists (χ2-df=201) and emergency room physicians (χ2-df=14) were less likely to prescribe OACs. OAC prescription correlated positively with country health expenditure. CONCLUSIONS: Approximately one out of three AF patients did not receive OAC, while eligible according to the guidelines. Country of enrolment was the major determinant of anticoagulation strategy, while higher country health expenditure was associated with lower likelihood of withholding anticoagulation

A clinician’s guide to management of intra-abdominal hypertension and abdominal compartment syndrome in critically ill patients

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901

Gender differences in health care use among the elderly population in areas of Norway and Finland. A cross-sectional analysis based on the HUNT study and the FINRISK Senior Survey

BACKGROUND: The aim of the study was to examine gender differences in the self-reported use of health care services by the elderly in rural and metropolitan areas of two Nordic countries with slightly different health care systems: Finland and Norway. METHODS: Population based, cross-sectional surveys conducted in Nord-Tröndelag Norway (1995–97) and in rural and metropolitan areas of Finland (1997) were employed. In the Norwegian data, a total of 7,919 individuals, aged 65–74 years old were included, and the Finnish data included 1,500 individuals. The outcome variables comprised whether participants had visited a general practitioner or a specialist, or had received hospital care or physiotherapy during the past 12 months. Gender differences in the use of health care services were analysed by multiple logistic regression, controlling for health status and socio-demographic characteristics. RESULTS: In Norway, elderly women visited a specialist or were hospitalised less often than men. In Finland, elderly women used all health care services except hospital care more often than men. In Norway, less frequent use of specialist care by women was not associated with self-reported health or chronic diseases. CONCLUSION: The findings revealed differences in self-reported use of secondary care among different genders in areas of Norway and Finland