PREvention of VENous Thromboembolism in Hemorrhagic Stroke Patients - PREVENTIHS Study: A Randomized Controlled Trial and a Systematic Review and Meta-Analysis.

BACKGROUND: In this randomized trial, currently utilized standard treatments were compared with enoxaparin for the prevention of venous thromboembolism (VTE) in patients with intracerebral hemorrhage (ICH). METHODS: Enoxaparin (0.4 mg daily for 10 days) was started after 72 h from the onset of ICH. The primary outcome was symptomatic or asymptomatic deep venous thrombosis as assessed by ultrasound at the end of study treatment. The safety of enoxaparin was also assessed. We included the results of this study in a meta-analysis of all relevant studies comparing anticoagulants with standard treatments or placebo. RESULTS: PREVENTIHS was prematurely stopped after the randomization of 73 patients, due to the low recruitment rate. The prevalence of any VTE at 10 days was 15.8% in the enoxaparin group and 20.0% in the control group (RR 0.79 [95% CI 0.29-2.12]); 2.6% of enoxaparin and 8.6% of standard therapy patients had severe bleedings (RR 0.31 [95% CI 0.03-2.82]). When these results were meta-analyzed with the results of the selected studies (4,609 patients; 194 from randomized trials), anticoagulants were associated with a nonsignificant reduction in any VTE (OR 0.81; 95% CI 0.43-1.51), in pulmonary embolism (OR 0.53; 95% CI, 0.17-1.60), and in mortality (OR 0.85; 95% CI 0.64-1.12) without increase in hematoma enlargement (OR 0.97; 95% CI, 0.31-3.04). CONCLUSIONS: In patients with acute ICH, the use of anticoagulants to prevent VTE was safe but the overall level of evidence was low due to the low number of patients included in randomized clinical trials.

The management of patients with venous thromboembolism in Italy: insights from the PREFER in VTE registry.

Venous thromboembolism (VTE) is the third most common cardiovascular disease. Real-life data on the clinical presentation, risk factors, diagnosis, and treatment of VTE in Italy and Europe are required to optimize the management of this disease. The PREFER in VTE registry, a prospective non-interventional real-life study, was designed to assess clinical characteristics and management of patients with VTE, use of health care resources, and on-treatment patient quality of life. Eligible consecutive patients with objectively diagnosed VTE were enrolled in the registry and followed up for 12 months. Between January and December 2013, 816 Italian and 1027 patients from 6 European countries other than Italy (European patients) were enrolled in the registry, and followed up until December 2014. Italian patients were the oldest (mean age 65.7 years) among the European patients. The Italian patients with a history of cancer were 24.6 % of whom 63.2 % had an active cancer (18.2 and 57.0 %, respectively, in Europe). Parenteral heparin was given, as initial treatment, in 73.8 % of Italian patients (66.4 % in Europe); VKA in combination with other treatments in 45.8 % (34.7 % in Europe); and VKA as the only anticoagulant treatment in 24.4 % (17.2 % in Europe). Of the Italian patients, 43.2 and 90.6 % of patients were hospitalized for deep vein thrombosis and pulmonary embolism, respectively; 65.4 % were admitted to the hospital through the emergency department. Following a real world approach, PREFER in VTE shows that the Italian patients, among and compared to the European patients, are the oldest, have a history of cancer more commonly, receive an initial treatment with heparin more commonly, and are more commonly hospitalized, particularly if affected by PE.

Holter monitoring to detect silent atrial fibrillation in high-risk subjects: the Perugia General Practitioner Study.

Atrial fibrillation (AF) is diagnosed for the first time in about 5 % of patients admitted for acute ischemic stroke. Advanced aged and arterial hypertension are risk factors for AF. We evaluated the prevalence of silent AF in subjects with advanced age and systemic arterial hypertension. Subjects of both gender, aged 65 years or more with systemic arterial hypertension were randomly identified from the patient lists of the participating general practitioners in the Perugia area, in Italy. Study subjects underwent baseline 12-lead ECG and, if this did not show AF, 48-h Holter monitoring was performed. AF was known and confirmed by 12-lead ECG in 4 out of the 308 evaluated subjects (1.3 %). Baseline 12-lead ECG showed no cases of silent AF. Holter monitoring was performed in 300 subjects, mean age 70 ± 4. Twenty-six recordings were not evaluable for the presence of artifacts; therefore, 274 subjects were included in the analysis. Holter monitoring showed AF in 27 out of 274 subjects (10 %; 95 % confidence interval 6.4-13.5 %); AF was longer than 30 s in four of the subjects. In 56 additional subjects, Holter monitoring revealed excessive supraventricular ectopic activity (20 %; 95 % confidence interval 15.3-24.7 %). Holter monitoring was able to detect silent AF in about 10 % of subjects aged 65 or above with systemic arterial hypertension. The risk of stroke associated with screened silent AF should be carefully evaluated.

Fatal Nocardia farcinica Bacteremia Diagnosed by Matrix-Assisted Laser Desorption-Ionization Time of Flight Mass Spectrometry in a Patient with Myelodysplastic Syndrome Treated with Corticosteroids.

Nocardia farcinica is a Gram-positive weakly acid-fast filamentous saprophytic bacterium, an uncommon cause of human infections, acquired usually through the respiratory tract, often life-threatening, and associated with different clinical presentations. Predisposing conditions for N. farcinica infections include hematologic malignancies, treatment with corticosteroids, and any other condition of immunosuppression. Clinical and microbiological diagnoses of N. farcinica infections are troublesome, and the isolation and identification of the etiologic agent are difficult and time-consuming processes. We describe a case of fatal disseminated infection in a patient with myelodysplastic syndrome, treated with corticosteroids, in which N. farcinica has been isolated from blood culture and identified by Matrix-Assisted Laser Desorption-Ionization Time of Flight Mass Spectrometry. The patient died after 18 days of hospitalization in spite of triple antimicrobial therapy. Nocardia farcinica infection should be suspected in patients with history of malignancy, under corticosteroid therapy, suffering from subacute pulmonary infection,and who do not respond to conventional antimicrobial therapy. Matrix-Assisted Laser Desorption-Ionization Time of Flight Mass Spectrometry can be a valuable tool for rapid diagnosis of nocardiosis.

Influenza vaccination and vitamin K antagonist treatment: a placebo-controlled, randomized, double-blind crossover study.

BACKGROUND: Among millions of persons vaccinated against influenza virus each year, many are older patients treated with several drugs, including vitamin K antagonists (VKAs), among which warfarin is the most commonly used. Due to high interpatient and intrapatient variability, the therapeutic dose of VKA has to be individualized by monitoring of international normalized ratio (INR) values. The objectives of this study were to evaluate variation in the INR and warfarin weekly dose variation after influenza vaccination administration and to follow up patients for related hemorrhagic and thrombotic events to evaluate the safety of the influenza vaccine and to assess the immunogenicity of the influenza vaccination in patients receiving VKAs. METHODS: One hundred four patients on a stable VKA regimen and with an indication for influenza vaccination were randomized to receive influenza vaccination and subsequent placebo administration, or vice versa. All patients were tested for coagulation variables, clinical events, and antibody response against vaccine components. RESULTS: Similar mean prothrombin times, expressed as the INR and VKA weekly dose, were found in patients after receiving vaccine or placebo. The absence of any vaccination effect on VKA treatment was confirmed using a linear mixed-effects model. The percentages of time that patients were in therapeutic range were 70.7% after receiving vaccine and 72.4% after receiving placebo (P = .57). There were no fatal or major bleeding events and 11 minor mucocutaneous hemorrhagic events. After vaccination, the percentage of seroprotected patients ranged from 92.0% to 100.0% depending on the vaccine antigen examined. CONCLUSIONS: Influenza vaccination had no significant effect on INR values or warfarin sodium weekly doses. Close monitoring of INR values is not required after influenza vaccination in patients on stable long-term VKA regimens. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00222638.

Low-molecular-weight heparin and cancer survival: review of the literature and pooled analysis of 1,726 patients treated for at least three months.

BACKGROUND: Heparin has been the main subject of intensive investigation and clinical use because of its therapeutic anticoagulant properties. It also exhibits many other biological activities, and it was claimed that it shows a beneficial effect on cancer spreading. Searching for papers investigating the effect of low-molecular-weight heparin (LMWH) on cancer mortality we found clinical trials and meta-analyses which showed a reduction in the mortality rate in cancer patients. However, the biological rationale of this effect for a short treatment with LMWH remains unclear. We wanted to check if similar results were achieved in cancer patients treated with LMWH for a longer period of time. AIM: To evaluate the effect on cancer mortality of a 3-month treatment with LMWH by performing a meta-analysis of published studies comparing LMWH and oral anticoagulants (OA) in the prevention of recurrent venous thromboembolism (VTE). MATERIALS AND METHODS: Computerized searches of Medline and Embase were performed; clinical trials were also located through colleagues and hand scanning of meeting proceedings. Eligibility of the studies and extraction of data were performed by two authors using a standard form. The meta-analysis was performed assuming a fixed-effect model. RESULTS: Eight studies were identified that fulfilled our predefined criteria for a total of 1,726 patients. After a mean of 8.6 months of follow-up, 327 patients had died of cancer, 160 in the LMWH group and 167 in the OA control group (OR 0.95, 95% CI 0.73-1.23; z = 0.42; p = 0.67). Considering cancer mortality in 948 cancer patients the figures were 160/472 in the LMWH group and 167/476 in the OA control group (OR 0.96, 95% CI 0.73-1.25; z = 0.33; p = 0.74). CONCLUSIONS: In 1,726 patients randomized to receive a long-term course of at least 3 months of LMWH or OA for the treatment of VTE, no effect on cancer mortality was found.