[Experiences of older multimorbid persons during the COVID-19 pandemic: a qualitative study]. / Erfahrungen älterer, multimorbider Menschen in der COVID-19-Pandemie: eine qualitative Studie.

BACKGROUND/OBJECTIVE: The COVID-19 pandemic and the accompanying preventive measures have shaped social life in unexpected ways. Because older persons with multiple chronic conditions have a high risk of a severe medical outcome, it has been strongly recommended that social contacts be curtailed in order to minimize risks of infection. While this appears to be alarming from a psychosocial point of view, it has been shown that older persons exhibit a high degree of equanimity and a good ability to cope with the crisis. The aim of the study was to describe the attitudes of multimorbid older people to the pandemic, their social contacts and their experiences with medical care. MATERIAL AND METHODS: This cross-sectional qualitative survey was based on 21 semi-structured short interviews of older patients with multiple chronic conditions during inpatient health care, at 4 different points in time: July 2020, September 2020, November 2020 and January 2021. The data were analyzed by qualitative content analysis. RESULTS: The statements of 21 participants (aged 58-88 years) were assessed. Over the course of the COVID-19 pandemic it became apparent that participants experienced the pandemic differently, both from an individual perspective and over time. While high infection rates were accompanied by serious concerns about health, periods of moderate infection risk were dominated by worry about social changes. In older persons there was a great sense of acceptance of the preventive measures. CONCLUSION: Our study exemplarily illustrates the attitudes and concerns of older persons who suffer from multiple chronic conditions over the course of the pandemic. Our data show that older persons reacted with equanimity to the novel medical and social circumstances.

Management of neonatal thrombocytopenia in a context of maternal antiplatelet alloimmunization: Expert opinion of the French-speaking working group.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, seen in 1/800-1000 neonates. FNAIT is the most common cause of early-onset isolated severe neonatal thrombocytopenia in maternity wards. The most feared complication of this disorder is intracranial hemorrhage, leading to death or neurological sequelae. There is no systematic screening of at-risk pregnancies and FNAIT is often discovered when fetal or neonatal bleeding is observed. A working group on fetomaternal platelet alloimmunization was created in 2017, under the auspices on the French Group of Thrombosis and Hemostasis (GFHT). The first objective of this group was to survey clinical practices for treatment of thrombocytopenic neonates in a context of suspected or confirmed FNAIT.

Treatment options for severe pulmonary embolism during pregnancy and the postpartum period: a systematic review.

Essentials The evidence on how to manage life-threatening pregnancy-related pulmonary embolism (PE) is scarce. We systematically reviewed all available cases of (sub)massive PE until December 2016. Thrombolysis in such severe PE was associated with a high maternal survival (94%). The major bleeding risk was much greater in the postpartum (58%) than antepartum period (18%). SUMMARY: Background Massive pulmonary embolism (PE) during pregnancy or the postpartum period is a rare but dramatic event. Our aim was to systematically review the evidence to guide its management. Methods We searched Pubmed, Embase, conference proceedings and the RIETE registry for published cases of severe (submassive/massive) PE treated with thrombolysis, percutaneous or surgical thrombectomy and/or extracorporeal membrane oxygenation (ECMO), occurring during pregnancy or within 6 weeks of delivery. Main outcomes were maternal survival and major bleeding, premature delivery, and fetal survival and bleeding. Results We found 127 cases of severe PE (at least 83% massive; 23% with cardiac arrest) treated with at least one modality. Among 83 women with thrombolysis, survival was 94% (95% CI, 86-98). The risk of major bleeding was 17.5% during pregnancy and 58.3% in the postpartum period, mainly because of severe postpartum hemorrhages. Fetal deaths possibly related to PE or its treatment occurred in 12.0% of cases treated during pregnancy. Among 36 women with surgical thrombectomy, maternal survival and risk of major bleeding were 86.1% (95% CI, 71-95) and 20.0%, with fetal deaths possibly related to surgery in 20.0%. About half of severe postpartum PEs occurred within 24 h of delivery. Conclusions Published cases of thrombolysis for massive PE during pregnancy and the postpartum period suggest a high maternal and fetal survival (94% and 88%). In the postpartum period, given the high risk of major bleeding with thrombolysis, other therapeutic options (catheter [or surgical] thrombectomy, ECMO) may be considered if available.

Pre-pregnancy BMI, delivery BMI, gestational weight gain and the risk of postpartum venous thrombosis.

OBJECTIVE: To characterize the risk of postpartum venous thromboembolism (VTE) associated with body-mass-index (BMI) in both pre-pregnancy and at delivery, and with gestational weight gain (GWG). METHODS: In a population-based, case-control study, we identified all women in Washington State with ICD-9 codes for VTE in the postpartum period between 2003 and 2011. Controls were women without VTE in the postpartum period, matched by delivery year to cases. Pre-pregnancy BMI, delivery BMI, and covariates were abstracted from birth certificates. Adjusted logistic regression models separately estimated postpartum VTE risk associated with categories of BMI in pre-pregnancy and at delivery. RESULTS: Cases (n=289) had a higher mean BMI than controls (n=4208) pre-pregnancy (29.9kg/m(2) and 26.3kg/m(2), respectively) and at delivery (34.8kg/m(2) vs. 31.4kg/m(2), respectively), with similar gestational weight gains. Compared with women with a normal pre-pregnancy BMI (18.5-24.9kg/m(2)), overweight (BMI 25-29.9kg/m(2)) and obese (BMI≥30kg/m(2)) women were at a 1.5-fold and 1.8-4 fold greater risk of postpartum VTE, respectively, with greatest risks in women with class III obesity (BMI≥40kg/m(2): OR 4.0, 95%CI 2.7-6.3). Observed associations of delivery BMI with postpartum VTE were less strong than those of pre-pregnancy BMI. Large weight gains during pregnancy (>22kg) also contributed to greater VTE risks (OR 1.5, 95%CI 1.0-2.2). CONCLUSION: Maternal BMI is an important risk factor for postpartum VTE, grading from weak in overweight women to very strong in women with class III obesity. Care providers may prefer to use pre-pregnancy BMI, along gestational weight gain, when stratifying the risk of postpartum VTE at delivery.

[Treatment preferences of elderly patients with mental disorders]. / Behandlungswünsche von älteren Menschen mit psychischen Erkrankungen.

BACKGROUND: Successful treatment in psychosomatic medicine requires intrinsic motivation of the patient and the belief that the chosen therapeutic option can help. Depression, somatization disorder and generalized anxiety disorder (GAD) are frequent mental disorders in the elderly population. Finding a suitable and successful treatment for elderly people with mental disorders is often difficult. Undertreatment and the utilization of inappropriate healthcare services are frequent. OBJECTIVE: Treatment preferences of elderly patients with mental disorders were ascertained in order to evaluate the motivation for psychotherapy or other therapeutic measures. MATERIAL AND METHODS: The data were derived from the 8-year follow-up of the epidemiological study on chances of prevention, early recognition and optimized therapy of chronic diseases in the elderly population (ESTHER), a population-based cohort study in Saarland, Germany. A total of 3124 patients aged 55-84 years were included in this analysis. The treatment preferences were documented using a questionnaire with 12 different answer categories. The occurrence of depression, somatization disorder and GAD was collated using the patient health questionnaire (PHQ-D). RESULTS: Physiotherapy and inpatient rehabilitation were the most frequently named treatment preferences in all three subgroups of patients with mental disorders. Psychotherapy was the preferred treatment for 18.3 % of depressive patients, for 15.0 % of somatization patients and for 15.7 % of GAD patients. CONCLUSION: Mentally ill elderly patients in Germany preferred physical treatment techniques, such as physiotherapy and inpatient rehabilitation over psychotherapy. Discussion is needed over the reasons for these findings and the clinical implications.

Recombinant human FVIIa for reducing the need for invasive second-line therapies in severe refractory postpartum hemorrhage: a multicenter, randomized, open controlled trial.

BACKGROUND: Case reports on recombinant human factor VIIa (rhuFVIIa) use in women with severe postpartum hemorrhage (PPH) showed encouraging results, but no randomized controlled trial (RCT) is available. PATIENTS AND METHODS: Eighty-four women with severe PPH unresponsive to uterotonics were randomized to receive one early single rhuFVIIa infusion (n = 42) or standard care (no rhuFVIIa; n = 42). The primary efficacy outcome measure was the reduction of the need for specific second-line therapies, such as interventional hemostatic procedures, for blood loss and transfusions. The primary safety outcome measure was the number of deaths and thrombotic events during the 5 days following rhuFVIIa infusion. RESULTS: rhuFVIIa was associated with a reduction in the number of patients who needed second-line therapies compared with controls (standard care). Specifically, 39/42 (93%) patients in the standard care arm received second-line therapies and 22/42 (52%) patients in the rhuFVIIa arm (absolute difference, 41%; range, 18-63%; relative risk RR, 0.56 [0.42-0.76]). The delivery mode (vaginal or Cesarean section) did not affect the primary outcome. No death occurred. Two venous thrombotic events were recorded in the rhuFVIIa arm: one ovarian vein thrombosis and one deep vein thrombosis with a non-severe pulmonary embolism. CONCLUSION: This open RCT in women with severe PPH refractory to uterotonics shows that rhuFVIIa reduces the need for specific second-line therapies in about one in three patients, with the occurrence of non-fatal venous thrombotic events in one in 20 patients.

Racial and ethnic differences in the risk of postpartum venous thromboembolism: a population-based, case-control study.

BACKGROUND: Venous thromboembolism (VTE) is a major contributor of maternal morbidity and mortality. Whether maternal race/ethnicity is associated with the risk of postpartum VTE remains unclear. METHODS AND RESULTS: We conducted a population-based, case-control study in Washington State, from 1987 through 2011. Cases comprised all women with selected International Classification of Diseases, Ninth Edition, Clinical Modification codes for hospitalized VTE within 3 months post-delivery. Controls were randomly selected postpartum women who did not experience a VTE. Characteristics of women and their deliveries were abstracted from birth certificates. Using logistic regression models, we compared the risk of postpartum VTE in black, Asian, and Hispanic women with that in non-Hispanic white women, after adjustment for maternal characteristics (age, body mass index, parity, education), pregnancy complications, and delivery methods. RESULTS: Our study comprised 688 cases and 10 246 controls. Among controls, the mean age and body mass index were 27.5 years and 26.3 kg m(-2) , respectively. Compared with white women, black and Asian women had a greater and lower risk of postpartum VTE (adjusted odds ratio [OR] 1.50, 95% confidence interval [CI] 1.10-2.04 and OR 0.67, 95%CI 0.48-0.94, respectively). A lower risk was present in Hispanic women (adjusted OR 0.80, 95% CI 0.61-1.06) but was not statistically significant. In subgroup analyses, we observed an increased risk for black compared with white women among women who delivered via cesarean section (OR 2.03, 95% CI 1.34-3.07) but not among vaginal deliveries (OR 1.03, 95% CI 0.61-1.74). CONCLUSIONS: Maternal race/ethnicity is associated with the risk of postpartum VTE, independently of other risk factors, and should be considered when assessing the use of thromboprophylaxis after delivery.

NF-κB is activated from endosomal compartments in antiphospholipid antibodies-treated human monocytes.

BACKGROUND: The antiphospholipid antibody syndrome (APS) is an autoimmune disease associated with arterial or venous thrombosis and/or recurrent fetal loss and is caused by pathogenic antiphospholipid antibodies (aPLA). We recently demonstrated that Toll-like receptor 2 (TLR2) and CD14 contribute to monocyte activation of aPLA. OBJECTIVE: To study the mechanisms of cell activation by aPLA, leading to pro-coagulant and pro-inflammatory responses. METHODS AND RESULTS: For this study, we used purified antibodies from the plasmas of 10 different patients with APS and healthy donors. We demonstrate that aPLA, but not control IgG, co-localizes with TLR2 and TLR1 or TLR6 on human monocytes. Blocking antibodies to TLR2, TLR1 or TLR6, but not to TLR4, decreased TNF and tissue factor (TF) responses to aPLA. Pharmacological and siRNA approaches revealed the importance of the clathrin/dynamin-dependent endocytic pathway in cell activation by aPLA. In addition, soluble aPLA induced NF-κB activation, while bead-immobilized aPLA beads, which cannot be internalized, were unable to activate NF-κB. Internalization of aPLA in monocytes and NF-κB activation were dependent on the presence of CD14. CONCLUSION: We show that TLR2 and its co-receptors, TLR1 and TLR6, contribute to the pathogenicity of aPLA, that aPLA are internalized via clathrin- and CD14-dependent endocytosis and that endocytosis is required for NF-κB activation. Our results contribute to a better understanding of the APS and provide a possible therapeutic approach.

[Thrombotic risk in myeloproliferative neoplasms: what the general practitioner needs to know]. / Risque thrombotique en cas de néoplasies myéloprolifératives: ce que devrait savoir le médecin praticien.

Polycythaemia vera, essential thrombocythemia and primary myelofibrosis are stem cell-derived clonal haemopathies classified in the group of myeloproliferative neoplasms. Their clinical course may be complicated by both arterial and venous (sometimes in unusual sites) thrombotic events. Although general risk factors contribute to the prevalence of thrombotic events in this population, some other risk factors are specifically associated with the myeloproliferative neoplasms. The treatment options are aspirin, anticoagulation, cytoreduction and phlebotomies.

[New oral anticoagulants: from theory to practice]. / Hémostase. Nouveaux anticoagulants oraux: de la théorie à la pratique.

Physicians are confronted with many new antithrombotic drugs, either antiplatelet agents or new oral anticoagulants (NOAC). Targets of NOAC are specific (either anti-IIa or antiXa) and clinical studies have shown that NOAC are as efficacious and as safe as "old" anticoagulants (heparin, low molecular weight heparin, vitamin K antagonists); moreover they present some advantages. Indeed, NOAC have a wide therapeutic window and do not require laboratory monitoring. Therefore, it is very tempting to prescribe them on a large scale basis in patients at risk or having thromboembolic diseases. However, things are not so simple in the day-to-day practice and this review aims at answering in a brief and simplified manner to some questions.

Identification and weighting of the most critical "real-life" drug-drug interactions with acenocoumarol in a tertiary care hospital.

PURPOSE: The objective of this study was to identify the most clinically relevant drug-drug interactions (DDIs) at risk of affecting acenocoumarol safety in our tertiary care university hospital, a 2,000 bed institution. METHODS: We identified DDIs occurring with acenocoumarol by combining two different sources of information: a 1-year retrospective analysis of acenocoumarol prescriptions and comedications from our Computerized Physician Order Entry (CPOE) system (n = 2,439 hospitalizations) and a retrospective study of clinical pharmacology consultations involving acenocoumarol over the past 14 years (1994-2007) (n = 407). We classified these DDIs using an original risk-analysis method. A criticality index was calculated for each associated drug by multiplying three scores based on mechanism of interaction, involvement in a supratherapeutic international normalized ratio (INR) (≥ 6) and involvement in a severe bleeding. RESULTS: One hundred and twenty-six DDIs were identified and weighted. Twenty-eight drugs had a criticality index ≥ 20 and were therefore considered at high risk for interacting with acenocoumarol by increasing its effect: 75% of these drugs involved a pharmacokinetic mechanism and 14 % a pharmacodynamic mechanism. An unknown mechanism of interaction was involved in 11 % of drugs. CONCLUSION: Twenty-eight specific drugs were identified as being at high risk for interacting with acenocoumarol in our hospital using an original risk-analysis method. Most analyzed drugs interact with acenocoumarol via a pharmacokinetic mechanism. Actions such as the implementation of alerts in our CPOE system should be specifically developed for these drugs.

[New anticoagulants: better knowledge, better prescriptions]. / Hémostase. Nouveaux anticoagulants: bien les connaître pour bien les prescrire.

New oral anticoagulants are already or will be soon available. They have shown good efficacy and safety in various studies (prevention and treatment of venous thromboembolism, atrial fibrillation). Their arrival will probably modify the prescription of the current anticoagulant agents. However some precaution should be given in their use pending post marketing studies. Although these new drugs are intended to replace mostly vitamin K antagonists, a place will remain for "old" anticoagulants during the next years.

Eculizumab in acute recurrence of thrombotic microangiopathy after renal transplantation.

Renal thrombotic microangiopathy (TMA) is a severe complication of systemic lupus erythematosus (SLE), which is associated with the presence of antiphospholipid (aPL) antibodies. In its most fulminant form, TMA leads to a rapid and irreversible end-stage renal failure. Eculizumab, an anti-C5 monoclonal antibody, is a novel therapy of choice for patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome. Here, we report the case of a 27-year-old woman, known for SLE and end-stage renal disease due to fulminant TMA. Both aPL antibodies and antinucleosome antibodies were positive. The patient underwent a living-related kidney transplantation with immediate production of urine. Although serum creatinine was remaining high, a graft biopsy, performed on day 6, demonstrated a TMA recurrence. Despite a treatment with plasma exchange, the situation got worse and dialysis was started. Eculizumab treatment was subsequently administered and renal function improved rapidly. Three months after transplantation, serum creatinine was at 100 µmol/L, without proteinuria. This case illustrates the benefit of eculizumab therapy in a fulminant recurrence of TMA after kidney transplantation, resistant to classical therapy.

[Update on new antithrombotic treatments]. / Hémostase. Le point sur tes nouveaux antithrombotiques.

Update on new antithrombotic treatments Antithrombotic treatments are frequently prescribed in different clinical situations. Classical anticoagulants have some disadvantages. New anticoagulants have emerged recently. Fondaparinux is now prescribed for both prophylaxis and treatment of venous thromboembolism. Two drugs are particularly interesting: rivaroxaban and dabigatran. Concerning the new antiplatelet agents, many molecules such as prasugrel, ticagrelor, cangrelor, SCH530348 or terutroban have appeared recently. They are directed either to the P2Y12 receptor or to other original targets. Studies have shown an increased bleeding risk for some of them as well as unexpected side effects. In the next future, these new molecules could allow a more individualised prescription of antithrombotic agents.

[Advantages of capillary INR monitoring for oral anticoagulation]. / Avantages du contrôle de l'anticoagulation orale par INR capillaire.

More and more patients are treated with long term oral anticoagulation. The time spent in therapeutic range is often limited since many factors affect INR. Too high or too low INRs increase respectively the hemorrhagic or thromboembolic risks. INR monitoring by a capillary device either in autonomy (self-management) by some selected patients or in relation with the treating physician (self-control), allows increasing the time spent in therapeutic range. Capillary INR monitoring can also be made at the medical office: it is less invasive and provides a quicker answer than a venous INR.

The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study.

BACKGROUND: Diagnosis of the antiphospholipid syndrome (APS) is difficult as a result of limited specificity of existing assays for detecting clinically relevant antiphospholipid antibodies. Anti-beta2-glycoprotein I (beta 2GPI) antibodies play a central role in the disease process of APS. OBJECTIVES: We have investigated the relation between antiphospholipid antibodies with specificity for domain I of beta 2GPI and thrombosis/pregnancy morbidity in an international multicenter study. PATIENTS/METHODS: Four hundred and seventy-seven patients derived from nine different centres met the inclusion criterion of having anti-beta 2GPI antibodies in their plasma/serum. Clinical data and results of tests for lupus anticoagulant, anti-cardiolipin antibodies and anti-beta 2GPI antibodies were established at the different centres of inclusion. After being re-tested for the presence of IgG and/or IgM anti-beta 2GPI antibodies, the samples were tested for the presence of IgG-directed against domain I of beta 2GPI and results were correlated with the thrombotic and obstetric history. RESULTS: Re-testing for the presence of anti-beta 2GPI antibodies resulted in inclusion of 442/477 patients. IgG class anti-domain I antibodies were present in plasma of 243/442 patients (55%). 201/243 (83%) had a history of thrombosis. This resulted in an odds ratio of 3.5 (2.3-5.4, 95% confidence interval) for thrombosis. Anti-domain I IgG antibodies were also significantly correlated with obstetric complications [odds ratio: 2.4 (1.4-4.3, 95% confidence interval)]. CONCLUSION: In this multicenter study, the detection of IgG antibodies that are directed against domain I of beta 2GPI proved to be more strongly associated with thrombosis and obstetric complications than those detected using the standard anti-beta 2GPI antibody assay.