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1.
Thromb Res ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33840477

RESUMO

BACKGROUND: It is unclear whether cardiopulmonary exercise intolerance in patients with chronic obstruction of the inferior vena cava (IVC) is reversible following endovascular IVC reconstruction. METHODS: In 17 patients (mean age 45 ± 15 years, 71% men) with post-thrombotic syndrome due to IVC obstruction and preserved left ventricular ejection fraction (mean 58 ± 3%), we performed cardiopulmonary exercise testing before and 3 months after IVC reconstruction (mean 4.1 ± 1.5 implanted stents). The median time from latest episode of deep vein thrombosis to intervention was 150 (interquartile range 102-820) days. RESULTS: At baseline, 12 (71%) patients reported New York Heart Association (NYHA) class II or III symptoms, 76% did not achieve >85% of predicted oxygen uptake at peak exercise (mean 61.8 ± 13.7%). After IVC reconstruction, the following changes were observed at anaerobic threshold: work rate increased by 14.6 W, 95%CI (-0.7; 30.0), oxygen uptake increased by 1.8 ml/kg, 95%CI (0.3; 3.3). Oxygen pulse increased by 1.95 ml per beat, 95%CI (1.12; 2.78), corresponding to a mean relative increase of 22.5%, 95%CI (12.4; 32.7) (p < 0.001). The following changes were observed at peak exercise: work rate increased by 48.1 W, 95%CI (27.8; 68.4), oxygen uptake increased by 6.4 ml/kg, 95%CI (3.8; 9.1). Oxygen pulse increased by 2.68 ml per beat, 95%CI (1.60; 3.76), corresponding to a mean relative increase of 29.4%, 95%CI (17.7; 41.2) (p < 0.001). At follow-up, 5 (29%) patients remained in NYHA class II. CONCLUSIONS: In patients with chronic IVC obstruction, cardiopulmonary exercise intolerance as a result of impaired cardiac filling is at least partially reversible following endovascular IVC reconstruction. STUDY REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02433054.

2.
Acta Ophthalmol ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33829646

RESUMO

PURPOSE: Lemierre syndrome is a life-threatening condition characterized by head/neck bacterial infection, local suppurative thrombophlebitis and septic embolic complications in a range of sites of distant organs. No prior study focused on the course and characteristics of ophthalmic complications of Lemierre syndrome. METHODS: We analysed data of 27 patients with ophthalmic complications from a large cohort of 712 cases with Lemierre syndrome reported globally between 2000 and 2017. We focused on initial manifestations, early (in-hospital) course and long-term ophthalmic deficits at the time of hospital discharge or during postdischarge follow-up. The study protocol was registered in the International Prospective Register of Systematic Reviews PROSPERO (CRD42016052572). RESULTS: Nine (33%) patients were women; the median age was 20 (Q1-Q3: 15-33) years. Fusobacterium spp. was involved in 56% of cases. The most prevalent initial manifestations were decreased vision (35%) and periocular oedema (38%), followed by impaired eye movements/nerve palsy (28%) and proptosis (28%). Venous involvement, notably cerebral vein thrombosis (70%) and ophthalmic vein thrombosis (55%), explained the symptomatology in most cases. Septic embolism (7%), orbital abscesses (2%) and carotid stenosis (14%) were also present. Ophthalmic sequelae were reported in 9 (33%) patients, often consisting of blindness or reduced visual acuity, and nerve paralysis/paresis. CONCLUSION: Ophthalmic complications represent a severe manifestation of Lemierre syndrome, often reflecting an underlying cerebral vein thrombosis. Visual acuity loss and long-term severe complications are frequent. We call for an interdisciplinary approach to the management of patients with Lemierre syndrome and the routine involvement of ophthalmologists.

3.
Vasc Med ; : 1358863X211000420, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33829921

RESUMO

Mondor disease is characterized by an acute painful thrombophlebitis occurring at specific anatomical sites. Data on its incidence, characteristics of clinical presentation, and course are unavailable to date. We studied the course of Mondor disease in patients diagnosed and followed at the University Hospital Zurich (Switzerland) between 2004 and 2020. The primary study outcomes were a diagnosis of active cancer either at the time of clinical diagnosis of Mondor disease or within 1 year, as well as 1-year all-cause death and recurrent Mondor disease. We included 45 patients and classified them into one of the three Mondor disease subgroups: thoracic (n = 26), penile (n = 12), or axillary (n = 7). The median age was 39 (Q1-Q3: 30-45) years and 44% of patients were men. Surgery was the likely cause of Mondor disease in 53.8% of patients with a thoracic form, 41.7% of those with a penile location, and all of those with an axillary location. Known active cancer was present in nine (20%) of 45 patients at baseline. One-year follow-up was available for 43 patients (median 94 months), whereas 6-month data were available for the remaining two patients. During the available follow-up, no patient had a new diagnosis of cancer. In conclusion, one in five patients with Mondor disease had known cancer at the time of diagnosis. During follow-up, the rate of new cancer diagnosis and death was negligible, providing reassurance about the good prognosis of this condition. Based on these preliminary data, extended cancer screening besides what is recommended by current guidelines for the general population might not be necessary in patients with Mondor disease.

4.
Eur J Intern Med ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33810940

RESUMO

INTRODUCTION: Sex and the presence of specific provoking risk factors, along with age, influence the presentation and prognosis of venous thromboembolism (VTE). We investigated the presentation, course and quality of life in women and men with acute VTE classified according to their VTE provoking factors. METHODS: PREFER in VTE is an international, non-interventional registry of patients with a first episode of acute symptomatic VTE. Baseline provoking factors were classified as follows: major transient, minor transient, active cancer, and none identifiable. The primary outcome was recurrent VTE. Quality of life and treatment satisfaction were secondary outcomes. RESULTS: Of 3,455 patients with acute VTE, 1,623 (47%) were women. The mean age at the time of VTE was 61 (SD 18) in women, 60 (SD 15) in men. The distribution of provoking risk factors was similar between sexes, despite a tendency for higher frequency of minor and major transient risk factors in women, and cancer or unprovoked VTE in men. At 12-month follow-up, VTE recurrence was reported in 74 (6.5%) women and 80 (6.4%) men (absolute risk difference -0.1%, 95% CI -1.9%; +2.1%). In patients with unprovoked VTE, the VTE recurrence rate was 38/612 (6.2%) in women and 53/798 (6.6%) in men (absolute risk difference -0.4, 95% CI -3.0; +2.1%). Multivariable Cox regressions confirmed the absence of sex differences. Quality of life and treatment satisfaction scores one year after VTE were lower in women than in men irrespective of the provoking risk factors (p<0.001 for both scores). CONCLUSIONS: Despite differences in the provoking risk factors for VTE, women and men had a similar rate VTE recurrence at one year. After acute VTE, women had lower quality of life and treatment satisfaction scores.

7.
Health Qual Life Outcomes ; 19(1): 40, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536042

RESUMO

BACKGROUND: An increasing number of subjects are recovering from COVID-19, raising the need for tools to adequately assess the course of the disease and its impact on functional status. We aimed to assess the construct validity of the Post-COVID-19 Functional Status (PCFS) Scale among adult subjects with confirmed and presumed COVID-19. METHODS: Adult subjects with confirmed and presumed COVID-19, who were members of an online panel and two Facebook groups for subjects with COVID-19 with persistent symptoms, completed an online survey after the onset of infection-related symptoms. The number and intensity of symptoms were evaluated with the Utrecht Symptom Diary, health-related quality of life (HrQoL) with the 5-level EQ-5D questionnaire, impairment in work and activities with the Work Productivity and Activity Impairment questionnaire and functional status with the PCFS Scale. RESULTS: 1939 subjects were included in the analyses (85% women, 95% non-hospitalized during infection) about 3 months after the onset of infection-related symptoms. Subjects classified as experiencing 'slight', 'moderate' and 'severe' functional limitations presented a gradual increase in the number/intensity of symptoms, reduction of HrQoL and impairment in work and usual activities. No differences were found regarding the number and intensity of symptoms, HrQoL and impairment in work and usual activities between subjects classified as experiencing 'negligible' and 'no' functional limitations. We found weak-to-strong statistical associations between functional status and all domains of HrQoL (r: 0.233-0.661). Notably, the strongest association found was with the 'usual activities' domain of the 5-level EQ-5D questionnaire. CONCLUSION: We demonstrated the construct validity of the PCFS Scale in highly-symptomatic adult subjects with confirmed and presumed COVID-19, 3 months after the onset of symptoms.


Assuntos
/fisiopatologia , Convalescença , Qualidade de Vida , Adulto , Bélgica , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Reprodutibilidade dos Testes , Inquéritos e Questionários
8.
Chest ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33548221

RESUMO

BACKGROUND: Few data are available on the long-term course and predictors of quality of life (QoL) following acute pulmonary embolism (PE). RESEARCH QUESTION: What are the kinetics and determinants of disease-specific and generic health-related QoL 3 and 12 months following an acute PE? STUDY DESIGN AND METHODS: The Follow-up after Acute Pulmonary Embolism (FOCUS) study prospectively followed up consecutive adult patients with objectively diagnosed PE. Patients were considered for study who completed the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire at predefined visits 3 and 12 months following PE. The course of disease-specific QoL as assessed using the PEmb-QoL and the impact of baseline characteristics using multivariable mixed effects linear regression were studied; also assessed was the course of generic QoL as evaluated by using the EuroQoL Group 5-Dimension 5-Level utility index and the EuroQoL Visual Analog Scale. RESULTS: In 620 patients (44% women; median age, 62 years), overall disease-specific QoL improved from 3 to 12 months, with a decrease in the median PEmb-QoL score from 19.4% to 13.0% and a mean individual change of -4.3% (95% CI, -3.2 to -5.5). Female sex, cardiopulmonary disease, and higher BMI were associated with worse QoL at both 3 and 12 months. Over time, the association with BMI became weaker, whereas older age and previous VTE were associated with worsening QoL. Generic QoL also improved: the mean ± SD EuroQoL Group 5-Dimension 5-Level utility index increased from 0.85 ± 0.22 to 0.87 ± 0.20 and the visual analog scale from 72.9 ± 18.8 to 74.4 ± 19.1. INTERPRETATION: In a large cohort of survivors of acute PE, the change of QoL was quantified between months 3 and 12 following diagnosis, and factors independently associated with lower QoL and slower recovery of QoL were identified. This information may facilitate the planning and interpretation of clinical trials assessing QoL and help guide patient management. CLINICAL TRIAL REGISTRATION: German Clinical Trials; No.: DRKS00005939.

9.
Thromb Res ; 198: 135-138, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33338976

RESUMO

BACKGROUND: Thrombosis and pulmonary embolism appear to be major causes of mortality in hospitalized coronavirus disease 2019 (COVID-19) patients. However, few studies have focused on the incidence of venous thromboembolism (VTE) after hospitalization for COVID-19. METHODS: In this multi-center study, we followed 1529 COVID-19 patients for at least 45 days after hospital discharge, who underwent routine telephone follow-up. In case of signs or symptoms of pulmonary embolism (PE) or deep vein thrombosis (DVT), they were invited for an in-hospital visit with a pulmonologist. The primary outcome was symptomatic VTE within 45 days of hospital discharge. RESULTS: Of 1529 COVID-19 patients discharged from hospital, a total of 228 (14.9%) reported potential signs or symptoms of PE or DVT and were seen for an in-hospital visit. Of these, 13 and 12 received Doppler ultrasounds or pulmonary CT angiography, respectively, of whom only one patient was diagnosed with symptomatic PE. Of 51 (3.3%) patients who died after discharge, two deaths were attributed to VTE corresponding to a 45-day cumulative rate of symptomatic VTE of 0.2% (95%CI 0.1%-0.6%; n = 3). There was no evidence of acute respiratory distress syndrome (ARDS) in these patients. Other deaths after hospital discharge included myocardial infarction (n = 13), heart failure (n = 9), and stroke (n = 9). CONCLUSIONS: We did not observe a high rate of symptomatic VTE in COVID-19 patients after hospital discharge. Routine extended thromboprophylaxis after hospitalization for COVID-19 may not have a net clinical benefit. Randomized trials may be warranted.


Assuntos
/epidemiologia , Alta do Paciente , Embolia Pulmonar/epidemiologia , Tromboembolia Venosa/epidemiologia , Trombose Venosa/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , /mortalidade , Feminino , Humanos , Incidência , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Fatores de Risco , Fatores de Tempo , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/mortalidade , Trombose Venosa/diagnóstico , Trombose Venosa/mortalidade
10.
Circ Cardiovasc Interv ; : CIRCINTERVENTIONS120009673, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33272030

RESUMO

BACKGROUND: Angioplasty with stent placement is a therapeutic option for patients with acute thrombotic, postthrombotic, and nonthrombotic obstruction of the iliofemoral veins or inferior vena cava. Previous studies of steel-alloy stents described variable patency rate across indications. METHODS: The prospective Swiss Venous Stent Registry includes patients treated with self-expandable nitinol stents for deep venous obstruction. Routine follow-up visits include serial duplex ultrasound for stent patency assessment. The primary outcome was primary stent patency. The secondary outcome was venous thromboembolisms. We studied the rate of stent occlusion and potentially contributing factors. RESULTS: We included 379 patients: 160 with acute thrombotic, 193 with postthrombotic, and 26 with nonthrombotic deep vein obstruction. The mean age was 46±18 years; 55% were women. The cumulative 3-year primary patency rate was 80.5% (95% CI, 73.0%-88.0%) for acute thrombotic, 59.2% (95% CI, 50.4%-68.0%) for postthrombotic, and 100% for nonthrombotic obstruction (log-rank, P<0.0001). Annualized rates of stent occlusion or venous thromboembolism were 7.8 (acute thrombotic), 15.0 (postthrombotic), and 0 (nonthrombotic) events/100 patient-years. In a multivariable Cox regression model, postthrombotic femoral veins at baseline (hazard ratio, 2.64 [95% CI, 1.53-4.56]) and the number of stents (hazard ratio, 1.22 [95% CI, 1.06-1.40]) were associated with stent occlusion after conditioning for age, sex, and clinically relevant factors. CONCLUSIONS: The rate of stent occlusion (patency loss) and venous thromboembolism varies substantially across indications, also with dedicated venous nitinol stents. Patients with postthrombotic femoral veins and those who received multiple stents were characterized by the highest risk. REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02433054.

11.
Thromb Haemost ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33202448

RESUMO

OBJECTIVE: In patients with cancer-associated venous thromboembolism (VTE), the risk of recurrence is similar after incidental and symptomatic events. It is unknown whether the same applies to incidental VTE not associated with cancer. METHODS AND RESULTS: We compared baseline characteristics, anticoagulation therapy, all-cause mortality, and VTE recurrence rates at 90 days between patients with incidental (n = 131; 52% without cancer) and symptomatic (n = 1,931) VTE included in the SWIss Venous ThromboEmbolism Registry (SWIVTER). After incidental VTE, 114 (87%) patients received anticoagulation therapy for at least 3 months. The mortality rate was 9.2% after incidental and 8.4% after symptomatic VTE for hazard ratio (HR) 1.10 (95% confidence interval [CI] 0.49-2.50). After adjustment for competing risk of death, recurrence rate was 3.1 versus 2.8%, respectively, for sub-HR 1.07 (95% CI 0.39-2.93). These results were consistent among cancer (mortality: 15.9% vs. 12.6%; HR 1.32, 95% CI 0.67-2.59; recurrence: 4.8% vs. 4.7%; HR 1.02, 95% CI 0.30-3.42) and noncancer patients (mortality: 2.9% vs. 2.1%; HR 1.37, 95% CI 0.33-5.73; recurrence: 1.5% vs. 2.3%; HR 0.63, 95% CI 0.09-4.58). Patients with incidental VTE who received anticoagulation therapy for at least 3 months had lower mortality (4% vs. 41%) and recurrence rate (1% vs. 18%) compared with those who did not. CONCLUSION: In SWIVTER, more than half of incidental VTE events occurred in noncancer patients who often received anticoagulation therapy. Among noncancer patients, early mortality and recurrence rates were similar after incidental versus symptomatic VTE. Our findings suggest that anticoagulation therapy for incidental VTE may be beneficial regardless of the presence of cancer.

16.
J Thromb Haemost ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073460

RESUMO

BACKGROUND: Severe prekallikrein deficiency (PK deficiency) is an autosomal-recessive condition thought to be very rare. Recently we reported that the previously unnoticed variant c.451dupT, p.Ser151Phefs*34 in KLKB1, which is listed in databases aggregating genome data, causes PK deficiency and is common in Africans according to gnomAD (allele frequency 1.43%). PATIENTS/METHODS: The most common African (c.451dupT) and European (c.1643G>A, p.Cys548Tyr) PK deficiency causing KLKB1 variants were analyzed in two population-based collectives of 300 Nigerian and 300 German subjects. Genome databases were evaluated for variant frequencies and ethnicity of the subjects. The geographic origin of PK-deficient cases due to 451dupT was assessed. RESULTS: Two of five patients with PK deficiency caused by homozygous 451dupT were African, one African American, one from Oman, and one of unknown origin. The frequency of 451dupT was 1.17% in the Nigerian collective (7/600 alleles); none had Cys548Tyr. Subjects with 451dupT were found among different Nigerian ethnicities. Both variants were absent in the European collective. Database research was compatible with these findings, even though mainly data of African Americans (451dupT: 1.12%-1.78%) was accessible. A relevant number of non-American Africans are included only in the 1000Genomes collective: 451dupT frequency was 1.29% in native Africans and 1.56% in African Caribbeans. CONCLUSIONS: This study underlines the higher prevalence of PK deficiency among people with African descent compared to Europeans. In order to avoid delay of necessary surgical procedures in patients of African origin, diagnostic algorithms for isolated, unexplained, activated partial thromboplastin time prolongation in these subjects should include PK deficiency screening.

17.
Thromb Res ; 196: 494-499, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33091703

RESUMO

Lemierre syndrome is a rare but potentially fatal condition characterized by septic thrombophlebitis of the head and neck district, preferentially affecting adolescents and young adults and manifesting as a complication of a local bacterial infection - typically, a pharyngotonsillitis or an abscess. It is historically associated with the Gram-negative anaerobic rod Fusobacterium necrophorum and with thrombophlebitis of the internal jugular vein. However, its definition has never been firmly established, and its spectrum within the continuum of bacteria-associated thrombophlebitis may be larger than what presumed so far. Recent evidence suggests that its prognosis remains serious even one hundred years after its first description, with considerable rates of in-hospital complications, death, and long-term sequelae. There are no specific guidelines on its management other than usual antibiotic stewardship, with ongoing debate on the potential role of therapeutic-dose anticoagulation. We provide an overview of current evidence on the definition, epidemiology, clinical presentation, prognosis and management of this condition and present the background and rationale of the Bacteria-Associated Thrombosis/Thrombophlebitis and LEmierre syndrome (BATTLE) registry: an ambispective, disease-specific, non-population based, multicentre clinical registry of global reach and multidisciplinary scope, specifically designed to address the limitations of current evidence and to provide patients and physicians with clinically viable information to guide management and improve the outcomes of those affected by these conditions.

18.
Lancet Respir Med ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33058771

RESUMO

BACKGROUND: Pulmonary embolism (PE)-related mortality is decreasing in Europe. However, time trends in the USA and Canada remain uncertain because the most recent analyses of PE-related mortality were published in the early 2000s. METHODS: For this retrospective epidemiological study, we accessed medically certified vital registration data from the WHO Mortality Database (USA and Canada, 2000-17) and the Multiple Cause of Death database produced by the Division of Vital Statistics of the US Centers for Disease Control and Prevention (CDC; US, 2000-18). We investigated contemporary time trends in PE-related mortality in the USA and Canada and the prevalence of conditions contributing to PE-related mortality reported on the death certificates. We also estimated PE-related mortality by age group and sex. A subgroup analysis by race was performed for the USA. FINDINGS: In the USA, the age-standardised annual mortality rate (PE as the underlying cause) decreased from 6·0 deaths per 100 000 population (95% CI 5·9-6·1) in 2000 to 4·4 deaths per 100 000 population (4·3-4·5) in 2006. Thereafter, it continued to decrease to 4·1 deaths per 100 000 population (4·0-4·2) in women in 2017 and plateaued at 4·5 deaths per 100 000 population (4·4-4·7) in men in 2017. Among adults aged 25-64 years, it increased after 2006. The median age at death from PE decreased from 73 years to 68 years (2000-18). The prevalence of cancer, respiratory diseases, and infections as a contributing cause of PE-related death increased in all age categories from 2000 to 2018. The annual age-standardised PE-related mortality was consistently higher by up to 50% in Black individuals than in White individuals; these rates were approximately 50% higher in White individuals than in those of other races. In Canada, the annual age-standardised mortality rate from PE as the underlying cause of death decreased from 4·7 deaths per 100 000 population (4·4-5·0) in 2000 to 2·6 deaths per 100 000 population (2·4-2·8) in 2017; this decline slowed after 2006 across age groups and sexes. INTERPRETATION: After 2006, the initially decreasing PE-related mortality rates in North America progressively reached a plateau in Canada, while a rebound increase was observed among young and middle-aged adults in the USA. These findings parallel recent upward trends in mortality from other cardiovascular diseases and might reflect increasing inequalities in the exposure to risk factors and access to health care. FUNDING: None.

19.
Trials ; 21(1): 770, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907635

RESUMO

OBJECTIVES: The OVID study will demonstrate whether prophylactic-dose enoxaparin improves survival and reduces hospitalizations in symptomatic ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation. TRIAL DESIGN: The OVID study is conducted as a multicentre open-label superiority randomised controlled trial. PARTICIPANTS: Inclusion Criteria 1. Signed patient informed consent after being fully informed about the study's background. 2. Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days and eligible for ambulatory treatment. 3. Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or body temperature >37.5° C. 4. Ability of the patient to travel to the study centre by private transportation, performed either by an accompanying person from the same household or by the patient themselves 5. Ability to comply with standard hygiene requirements at the time of in-hospital visit, including a face mask and hand disinfectant. 6. Ability to walk from car to study centre or reach it by wheelchair transport with the help of an accompanying person from the same household also complying with standard hygiene requirements. 7. Ability to self-administer prefilled enoxaparin injections after instructions received at the study centre or availability of a person living with the patient to administer enoxaparin. Exclusion Criteria 1. Any acute or chronic condition posing an indication for anticoagulant treatment, e.g. atrial fibrillation, prior venous thromboembolism (VTE), acute confirmed symptomatic VTE, acute coronary syndrome. 2. Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history, comorbidity or predisposing strong risk factors for thrombosis: a. Any of the following events occurring in the prior 30 days: fracture of lower limb, hospitalization for heart failure, hip/knee replacement, major trauma, spinal cord injury, stroke, b. previous VTE, c. histologically confirmed malignancy, which was diagnosed or treated (surgery, chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or inoperable. 3. Any clinically relevant bleeding (defined as bleeding requiring hospitalization, transfusion, surgical intervention, invasive procedures, occurring in a critical anatomical site, or causing disability) within 30 days prior to randomization or sign of acute bleeding. 4. Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute intracranial haemorrhage. 5. Haemoglobin <8 g/dL and platelet count <50 x 109 cells/L confirmed by recent laboratory test (<90 days). 6. Subjects with any known coagulopathy or bleeding diathesis, including known significant liver disease associated with coagulopathy. 7. Severe renal insufficiency (baseline creatinine clearance <30 mL/min calculated using the Cockcroft-Gault formula) confirmed by recent laboratory test (<90 days). 8. Contraindications to enoxaparin therapy, including prior heparin-induced thrombocytopenia and known hypersensitivity. 9. Current use of dual antiplatelet therapy. 10. Participation in other interventional studies over the past 30 days. 11. Non-compliance or inability to adhere to treatment or lack of a family environment or support system for home treatment. 12. Cognitive impairment and/or inability to understand information provided in the study information. Patient enrolment will take place at seven Swiss centres, including five university hospitals and two large cantonal hospitals. INTERVENTION AND COMPARATOR: Patients randomized to the intervention group will receive subcutaneous enoxaparin at the recommended dose of 4,000 IU anti-Xa activity (40 mg/0.4 ml) once daily for 14 days. Patients randomized to the comparator group will receive no anticoagulation. MAIN OUTCOMES: Primary outcome: a composite of any hospitalization or all-cause death occurring within 30 days of randomization. SECONDARY OUTCOMES: (i) a composite of cardiovascular events, including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke within 14 days, 30 days, and 90 days of randomization; (ii) each component of the primary efficacy outcome, within 14 days, 30 days, and 90 days of randomization; (iii) net clinical benefit (accounting for the primary efficacy outcome, composite cardiovascular events, and major bleeding), within 14 days, 30 days, and 90 days of enrolment; (iv) primary efficacy outcome, within 14 days, and 90 days of enrolment; (v) disseminated intravascular coagulation (ISTH criteria, in-hospital diagnosis) within 14 days, 30 days, and 90 days of enrolment. RANDOMISATION: Patients will undergo block stratified randomization (by age: 50-70 vs. >70 years; and by study centre) with a randomization ratio of 1:1 with block sizes varying between 4 and 8. Randomization will be performed after the signature of the informed consent for participation and the verification of the eligibility criteria using the electronic data capture software (REDCAP, Vanderbilt University, v9.1.24). BLINDING (MASKING): In this open-label study, no blinding procedures will be used. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size calculation is based on the parameters α = 0.05 (2-sided), power: 1-ß = 0.8, event rate in experimental group, pexp = 0.09 and event rate in control group, pcon = 0.15. The resulting total sample size is 920. To account for potential dropouts, the total sample size was fixed to 1000 with 500 patients in the intervention group and 500 in the control group. TRIAL STATUS: Protocol version 1.0, 14 April 2020. Protocol version 3.0, 18 May 2020 Recruiting start date: June 2020. Last Patient Last Visit: March 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04400799 First Posted: May 26, 2020 Last Update Posted: July 16, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Anticoagulantes/administração & dosagem , Betacoronavirus/patogenicidade , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Enoxaparina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Trombose/prevenção & controle , Anticoagulantes/efeitos adversos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Enoxaparina/efeitos adversos , Estudos de Equivalência como Asunto , Interações Hospedeiro-Patógeno , Humanos , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Trombose/sangue , Trombose/diagnóstico , Trombose/virologia , Fatores de Tempo , Resultado do Tratamento
20.
Heart ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907824

RESUMO

OBJECTIVES: Current international guidelines advocate the application of bleeding risk scores only to identify modifiable risk factors, but not to withhold treatment in patients at high risk of bleeding. VTE-BLEED (ActiVe cancer, male with uncontrolled hyperTension, anaEmia, history of BLeeding, agE and rEnal Dysfunction) is a simple bleeding risk score that predicts major bleeding (MB) in patients with venous thromboembolism, but has never been evaluated in patients with atrial fibrillation (AF). We sought to evaluate VTE-BLEED in patients with AF included in the Randomised Evaluation of Long-term anticoagulant therapY (RE-LY) trial, to assess whether score classes (high vs low bleeding risk) interact with the tested dabigatran doses (150 vs 110 mg twice daily), and to investigate whether dose reductions based on this interaction might help to lower the incidence of the composite outcome MB, stroke/systemic embolism or death. METHODS: The score was calculated in the safety population of RE-LY (n=18 040) and recalibrated for AF (AF-adapted VTE-BLEED or AF-BLEED). HRs were calculated to evaluate the score's predictive accuracy for MB. The risk ratios (RRs) for the composite outcome comparing dabigatran 150 and 110 mg twice daily were calculated for the high-risk group. RESULTS: AF-BLEED classified 3534 patients (19.6%) at high bleeding risk, characterised by a 2.9-fold to 3.4-fold higher risk of bleeding than low bleeding risk patients, across the treatment arms. High bleeding risk patients randomised to 110 mg twice daily had a lower incidence of the composite outcome than those randomised to 150 mg twice daily, for an RR of 0.52 (95% CI 0.35 to 0.78). Compared with the label criteria for dose reduction, AF-BLEED identified an additional 11% of patients who might have benefited from dose reduction. CONCLUSIONS: AF-BLEED identified patients with AF at high risk of bleeding. Our findings raise the hypothesis that dabigatran 110 mg twice daily might be considered in patients classified as high risk according to the AF-BLEED score. This study provides a basis for future studies to explore safe dose reductions of direct oral anticoagulants in selected patient groups based on bleeding scores.

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