[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.

[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.

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 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.

[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 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.

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.

Impending paradoxical embolism. When and how to treat?

Impending paradoxical embolism (IPDE) is the presence of an entrapped thrombus through the patent foramen ovale (PFO). Usually IPDE are diagnosed by echocardiography or thoracic CT-scan performed during the evaluation of patient presenting with a suspicion of pulmonary embolism (PE). We report the case of a 73-year-old patient presenting with a very large IPDE successfully treated with cardiac surgery and we focus our discussion on the treatment modalities of this rare entity (anticoagulation alone, fibrinolytic regimens, cardiac surgery, percutaneous thrombectomy) and on PFO management after IPDE.

[Diagnosis and management of mild bleeding disorders]. / Hémostase. Diagnostic et prise en charge des syndromes hémorragiques dits mineurs.

Although mild bleeding disorders are still poorly defined, they are clinically important since they may be associated with serious hemorrhagic complications during trauma or surgical procedures. These disorders are mainly related to dysfunction of primary or secondary hemostasis. Standardized questionnaires may be of some help in identifying patients who deserve further biological evaluation. Several pharmacological agents are available; however, before prophylactic administration of such drugs, a trade-off between their thrombotic risks and excessive bleeding should be made.

[Inherited thrombophilia and arterial diseases]. / Thrombophilies héréditaires: rôle dans la pathologie artérielle.

Thrombophilia may be defined as an acquired or congenital abnormality of hemostasis predisposing to thrombosis. Some of the inherited abnormalities such as factor V Leiden mutation, factor II G20210A mutation as well as deficiencies in antithrombin, protein C and protein S, are already known to be risk factors for venous thromboembolism. This review focuses on the link between these abnormalities and arterial thrombosis. Routine screening for these disorders is not indicated in most cases of arterial complications, but could be useful in some sub-groups of patients, such as young patients, smokers, patients on oral contraception, or those with premature occlusion after revascularization procedures. Anticoagulation rather than antiplatelet therapy may be preferable for these patients.

[Von Willebrand disease: a common and unrecognized bleeding disorder]. / La maladie de von Willebrand: une diathèse hémorragique fréquente et méconnue.

The von Willebrand factor plays an important role in primary and secondary hemostasis. Von Willebrand disease is due to a quantitative or qualitative abnormality of von Willebrand factor. It is the most frequent constitutional abnormality of hemostasis. The main manifestation of von Willebrand disease is a mucocutaneous hemorrhagic syndrome; however, von Willebrand disease is characterized by an important clinical and biological heterogeneity. Its transmission is autosomal, usually dominant. A screening can be made by a general practitioner on the basis of a good clinical history. It is then important to confirm the diagnosis in a specialized laboratory because an adequate treatment can be prescribed to avoid hemorrhagic complications, in particular at the time of surgical procedures.

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.

Thrombocytopenia during pregnancy. Importance, diagnosis and management.

Thrombocytopenia is observed in 6 to 15% of pregnant women at the end of pregnancy, and is usually moderate. Gestational thrombocytopenia (defined as a mild thrombocytopenia, occurring during the 3 rd trimester with spontaneous resolution postpartum and no neonatal thrombocytopenia) is the most common cause of thrombocytopenia during pregnancy but a low platelet can also be associated with several diseases, either pregnancy specific or not, such as preeclampsia, HELLP syndrome, or idiopathic thrombocytopenic purpura (ITP). The differential diagnosis between ITP and gestational thrombocytopenia is clinically important with regard to the fetus, due to the risk of neonatal thrombocytopenia. However, this differential diagnosis is very difficult during pregnancy. Thrombocytopenia which need to be investigated are the following: thrombocytopenia known before pregnancy, thrombocytopenia occurring during the 1(st) and 2(nd) trimester, platelet count <75 G/l in the 3(rd) trimester or thrombocytopenia in case of pregnancy with complications. Investigations have to be discussed in function of history and clinical examination, gestational age and severity of thrombocytopenia. No treatment is required in case of gestational thrombocytopenia. There are few data to distinguish management of ITP between pregnant and non-pregnant women but management is different because of the potential adverse effects of the treatment for the woman and/or the fetus, the requirement for a good hemostasis at delivery and the risk of neonatal hemorrhage. One important problem is that it is not possible to predict the risk of neonatal thrombocytopenia in babies born from women with ITP.

[Anticoagulation in patients with chronic renal failure]. / Anticoagulation chez l'insuffisant rénal.

Anticoagulation may be difficult to implement in patients suffering from chronic renal failure on account of platelet disorders and impaired clearance of some anticoagulant drugs. Although no adjustment of heparin and coumarin dosage is necessary, more frequent testing of coagulation pathways may be required when these drugs are used in patients with renal failure. Long-term use of LMWH should be implemented cautiously with regular testing of anti-factor Xa activity and a half-dose may be advocated in patients with a creatinine clearance < 30 ml/mn. Danaparoid and thrombin inhibitors should be used mainly in patients suffering from renal failure and heparin-induced thrombocytopenia with regular monitoring of coagulation tests.

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.

D-dimer levels during delivery and the postpartum.

BACKGROUND: D-dimer (DD) measurement has proved to be very useful to exclude venous thromboembolism (VTE) in outpatients. However, during pregnancy, the progressive increase as well as the interindividual variations of DD means that in this instance they are of poor value to rule out VTE. Only a few studies have reported measurements of DD levels in the postpartum. OBJECTIVES: To measure DD sequentially in the puerperium in order to determine when DD levels return to values obtained in non-pregnant women and can again be used in the exclusion of VTE. PATIENTS AND METHODS: After uncomplicated pregnancies, 150 women delivering at term either vaginally (n = 100) or by cesarean section (n = 50) were included. DD levels were measured immediately following delivery and next at days 1, 3, 10, 30 and 45. RESULTS: There was a marked elevation of DD at delivery, especially when instrumental. All DD measurements were above 500 ng mL(-1) at delivery, at day 1 and at day 3 postpartum. A sharp decrease in DD was observed between day 1 and day 3, followed by a slight increase at day 10. At day 30 and day 45, respectively, 79% and 93% of women in the vaginal delivery group and 70% and 83% in the cesarean group had levels below 500 ng mL(-1). Bleeding, breastfeeding and heparin prophylaxis did not modify DD levels significantly. CONCLUSION: Using the Vidas DD new assay, our study provides reference intervals for DD in the postpartum period. Using a cut-off at 500 ng mL(-1), DD measurement for ruling out VTE was found to be useful again 4 weeks after delivery.