Antithrombotic secondary prophylaxis with low dose of apixaban or rivaroxaban in the onco-hematologic patients: comparison with non-neoplastic patients.

Management of cancer-associated thrombosis (CAT) is usually performed employing low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs). Low-intensity DOACs are the mainstay for extended duration therapy for VTE in non-oncologic patients. The aim of our study was to evaluate the efficacy and the safety of low doses of apixaban or rivaroxaban as secondary prophylaxis in patients affected by hematological malignancies with follow-up > 12 months. We report an observational, retrospective, single-center study that evaluated consecutive patients referred to our center between January 2016 and January 2023. The DOACs were administered at full dose during the acute phase of VTE and then at low dose for the extended phase. We included 154 patients: 53 patients affected by hematological malignancies compared to 101 non-neoplastic patients. During full-dose treatment, no thrombotic recurrences were observed in the two groups. During low-dose therapy, 2 (1.9%) thrombotic events (tAE) were observed in the control group. During full-dose treatment, the rate of bleeding events (bAE) was 9/154 (5.8%): 6/53 (11%) in hematological patients and 3/101 (2.9%) in non-hematological patients (p = 0.0003). During low-dose therapy, 4/154 (2.6%) bAE were observed: 3/53 (5.5%) in the hematologic group and 1 (1%) in the control group (p = 0.07). We found encouraging data on the safety and efficacy of low doses of DOACs as secondary prophylaxis in the onco-hematologic setting; no thrombotic complications were observed, and the incidence of hemorrhagic events was low.

Low-dose apixaban or rivaroxaban as secondary prophylaxis of upper extremity deep vein thrombosis.

Upper extremity deep vein thrombosis (UEDVT) may occur without inciting factor or may be secondary to malignancy, surgery, trauma, central venous catheter or related to thoracic outlet syndrome (TOS). International guidelines recommend anticoagulant treatment for at least three months, in particular the use of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). No data on extended anticoagulant therapy and reduced dose of DOACs have been reported in patients affected by UEDVT with persistent thrombotic risk (active cancer, major congenital thrombophilia) or without affected vein recanalization. In our retrospective observational study, including 43 patients, we treated secondary UEDVT with DOACs. In the acute phase of thrombosis (median time of 4 months), we used therapeutic dose of DOACs; the 32 patients with permanent thrombotic risk factors or without recanalization of the UEDVT were shifted to low-dose DOACs (apixaban 2.5 mg twice daily or rivaroxaban 10 mg daily). During therapy with full-dose DOACs, 1 patient presented recurrence of thrombosis; no thromboembolic events were observed during treatment with low-dose DOACs. During full-dose treatment, 3 patients presented minor hemorrhagic complications; no hemorrhagic events were observed during DOACs at low dose. We think our preliminary data could support the indication to extend the anticoagulation with dose reduction of DOACs in patients affected by UEDVT and no-transient thrombotic risk. These data should be confirmed in randomized controlled prospective study.

Bleeding phenotype and correlation with factor XI (FXI) activity in congenital FXI deficiency: results of a retrospective study from a single centre.

Bleeding phenotype in factor XI (FXI)-deficient patients is variable, and not related to baseline FXI:Act. Aims of our study were to describe the characteristics and the management of surgery and deliveries in FXI-deficient patients, and to investigate the relationship between the haemorrhagic phenotype and the baseline FXI:Act. Ninety-five patients were diagnosed and followed in our centre for a median follow-up of 0.9 years (0.1-36.2); median FXI:Act of all patients: 38% (0.5-69%). Fifty-six patients (59%) experienced bleeding episodes not surgery-related. Prior to diagnosis, 64 patients underwent 132 surgeries, and after diagnosis, 23 patients underwent 36 surgeries. Globally 26 of 168 surgeries were prophylactically treated, whereas 142 of 168 were not. As regard as surgeries performed without prophylaxis, 30 bleeding events (21%) occurred in 21 patients. At diagnosis, the median FXI:Act of bleeding and non-bleeding patients was 28% and 37%, respectively, without statistically significant difference between the two groups (P = 0.26). As regard as surgeries performed under prophylactic treatment just 1 bleeding event occurred. Prior to diagnosis, 31 spontaneous deliveries (SD) and eight caesarian sections (CS) were performed without prophylaxis: 4 postpartum haemorrhages (10.5%) occurred (patients FXI:Act: 2%, 6%, 27%, 52.3% respectively). After diagnosis, four SD and five CS were performed with prophylaxis: no postpartum haemorrhages occurred. We confirm the wide bleeding phenotype variability in FXI-deficient patients, not related to the baseline FXI:Act levels. We highlight the importance of performing a correct diagnosis and follow-up, because a good management of prophylactic treatment, dramatically reduces the bleeding rate in case of surgery or deliveries.

"Zeus" a new oral anticoagulant therapy dosing algorithm: a cohort study.

The demand for oral anticoagulant therapy (OAT) has constantly increased during the last ten years with an extended use of computer assistance. Many mathematical algorithms have been projected to suggest doses and time to next visit for patients on OAT. We designed a new algorithm: "Zeus". A "before-after" study was planned to compare the efficacy and safety of this algorithm dosing OAT with manual dosage decided by the same expert physicians according to the target of International Normalized Ratio (INR). The study analysed data of 1876 patients managed with each of the two modalities for eight months, with an interval of two years between them. The aim was to verify the increased quality of therapy by time spent in INR target and efficiency and safety of Zeus algorithm. Time in therapeutic range (TTR) was significantly (p < 0.0001) higher during the algorithm dosing period in comparison with the TTR during manual management period (62.3% vs 50.3%). The number of PT/INR tests above 5 was significantly (p < 0.001) reduced by algorithm suggested prescriptions in comparison with manual those (254 vs 537 times). The anticoagulant drug amount prescribed according to the algorithm suggestions was significantly (p < 0.0001) lower than that of the manual method. The number of clinical events observed in patients during the algorithm management time was significantly (p < 0.05) lower than that in those managed with the manual dosage. This study confirms the clinical utility of the computer-assisted OAT and shows the efficacy and safety of the Zeus algorithm.

Prevalence of allo-immunization anti-HLA and anti-integrin alphaIIbbeta3 in Glanzmann Thromboasthenia patients.

SUMMARY: Platelet transfusions, main therapy of Glanzmann Thromboasthenia (GT), can induce an allo-immunization against human leucocyte antigen and integrin alphaIIbbeta3. We have investigated in our GT patients the rate of allo-immunization and of refractoriness to platelet transfusions. From 1975 until December 2005, we have followed 17 GT patients: 14 type 1, 3 variant type; nine females, eight males; median age at diagnosis 9.8 years (range 1-44.5); median age at the time of the study 35.5 years (range 23.6-68.5). In our patients, 121 bleeding episodes occurred (24 severe, 37 moderate, and 60 mild). Ten major and 22 minor surgical procedures have been performed. Two spontaneous deliveries and three caesarian sections with five live births were performed; moreover, one late foetal loss occurred, and one voluntary abortion was performed. Sixteen of 17 patients have been transfused at least once in life with platelets and/or red blood cells (RBC). All transfused patients have been investigated for the presence of anti-HLA and anti-integrin alphaIIbbeta3 allo-antibodies. The positiveness of allo-antibodies has been demonstrated in 4/16 transfused patients (25%): isolated for anti-HLA in two; isolated for anti-integrin alphaIIbbeta3 in one; and combined in one. In spite of the presence of allo-antibodies, platelet transfusions have always been effective and the haemostasis was not compromised.

How long can we give interleukin-2? Clinical and immunological evaluation of AML patients after 10 or more years of IL2 administration.

We have treated 20 patients, affected by acute myelogenous leukemia in advanced phase of the disease, with intravenous high-dose recombinant interleukin-2 (IL2) as induction treatment, achieving a complete remission (CR) in 11/20 of patients (55%). All CR patients were planned to receive a maintenance program with lower subcutaneous doses of IL2 until relapse. Currently, 5/11 patients are alive in continuous complete remission with a minimum follow-up of 9 years from IL2 induction. In the aim to investigate the treatment's side-effects during or after prolonged IL2 therapy, we decided to submit these patients to a clinical and immunological evaluation. Four patients have been evaluated as one, who independently stopped IL2 after 6 years, refused the check-up. No organ-specific treatment sequelae that may decrease the quality of life or may be life-threatening were found, concerning renal, liver and cardiovascular function. Endocrine abnormalities were detected in three patients, the most serious being a severe hypothyroidism, which prompted cessation of IL2 maintenance after 6 years and required thyroid supplementation treatment. Immunological studies were carried out prior to the last IL2 cycle and showed high levels of CD3-positive T cells expressing the IL2 receptor alpha chain (CD25), both in the peripheral blood and in the bone marrow. Our study shows that low-dose IL2 can be given for a prolonged period of time without serious organ-specific late sequelae and with a good quality of life.

[Measles seroprevalence among pediatricians in a teaching hospital]. / Soroprevalência de sarampo entre pediatras de um hospital-escola.

OBJECTIVE: A measles outbreak occurred in S. Paulo state, during 1996 and 1997, resulting in 20,921 cases. Forty seven percent of the cases occurred in people between 20 and 29 years of age, and one of the control strategies of the Department of Health was the vaccination of health care workers. The prevalence of antibodies against measles among the hospital pediatricians was investigated. METHODS: One hundred and fifty samples were taken from volunteer pediatricians to test for measles antibodies using ELISA. A questionnaire about their having had measles and the vaccine was filled out. RESULTS: Of the 150 doctors, 122 (81.4%) were female and 28 (18.6%) male, of between 23 and 46 years of age (mean and median 27 years). The majority (98%-147/150) had protective levels of antibodies against measles (>100 UI/ml); 118 (80.3%-118/147) without and 29 (19.7%-29/147) with a history of measles. Only 3 pediatricians (2%-3/150), had negative serology, 2 without and 1 with a history of measles. Out of the 118 without history of measles, 79 (67%-39/118) in spite of the protective level of antibodies against measles, did not know if they, had been vaccinated. Out of the 79 vaccinated pediatricians, 64 (81%-64/79), had been vaccinated 25 years before, and still maintained protective levels of antibodies. Of the 3 doctors with negative serologies only one declared that he had been vaccinated. CONCLUSIONS: Measles seroprevalence among pediatricians of this hospital is high, especially due to preceding vaccination. On the other hand, the 2% of pediatricians with negative serology, in an epidemic situation could constitute a significant population for the acquisition and dissemination of the disease.

Use of undiluted whole cow's milk is effective for the routine treatment of children with acute diarrhea and severe dehydration.

A comparison is made between two groups of children aged 1-24 months and admitted to a teaching University Hospital due to acute diarrhea and severe dehydration. One group (n = 119) received a diluted cow's milk formula and the other (n = 109) a full-strength formula. Duration of diarrhea was similar: In the group that received full-strength milk weight gain was greater during diarrhea (5.03 vs. 1.80 g/kg/day, P < 0.01) and during the hospital stay (5.39 vs. 2.33 g/kg/day, P < 0.001). Weight for height z-scores and weight for height as percentage of median improved during the hospital stay only in the group that received the full-strength formula. Full-strength cow's milk seems to be an adequate routine regimen even for children with acute diarrhea that must be treated for severe dehydration. In developing countries diarrhea and dehydration are a disease of small children. As rates of exclusive breast feeding are low, mainly in the urban setting, cow's milk is the main and sometimes the only food available. Lactose-free formulae are priced out of reach of the poor people and in Latin America there is no accepted tradition for use of fermented milk products. Our study is an indication that use of undiluted cow's milk may be effective for the routine treatment of acute diarrhea in children that must be treated as inpatients due to severe dehydration.

[Continuous nebulization with terbutaline sulfate under tent inhalation. Evaluation of the efficacy in children 2 to 5 years of age in asthmatic crises]. / Nébulisation continue avec sulfate de terbutaline sous tente d'inhalation. Evaluation de l'efficacité chez l'enfant de 2 á 5 ans en crise d'asthme.

This study investigated the efficacy of a system for continuous nebulization of terbutaline sulphate in the treatment of acute asthmatic crises in children. The equipment consisted of a condensation nebulizer attached to a 40 liter acrylic tent placed around the patient's head. A prospective, randomized and open clinical trial was conducted. Twenty eight children, 2 to 5 year-old, in acute asthmatic crises were selected. Fourteen were nebulized with terbutaline sulphate while in the control group the aerosolization was proceeded only with half diluted physiologic serum. All patients were administered aminophyline intravenously. The parameter used to evaluate the efficacy of the terbutaline sulphate nebulizing system was clinical improvement measured by the Wood-Downes Score. Two additional parameters indicating terbutaline sulphate absorption were used: reduction of potassium seric levels and positive chronotropic effect. The group treated with terbutaline sulphate showed greater clinical improvement than control group at the 12 hour protocol evaluation as well as lower seric potassium level. A positive chronotropic effect was also observed at the final protocol evaluation. The data showed, preliminarily, that (a) the system for continuous nebulization of terbutaline sulphate was effective in treatment of children's acute asthmatic crises, and (b) there was evidence attesting to the absorption of terbutaline sulphate by the children treatment with it.

[Evaluation of the therapeutic efficacy of dexamethasone in meningococcal meningitis] / Avaliação da eficácia terapêutica da dexametasona na meningite meningocócica.

OBJECTIVE: To evaluate the efficacy of dexamethasone as an auxiliary therapeutic tool to the antibiotics in hospitalized children with meningococcal meningitis. METHODS: A retrospective clinical comparative study was undertaken with children from a pediatric ward affected by laboratory proved meningococcal meningitis at a university hospital. Cases of children in state of shock at admission or deceased in the first 24 hours were excluded. During the period from 1987 to 1989 33 children were treated only with antibiotics (group A), while from 1990 to 1993 other 66 children received additionally dexamethasone (12mg/m2/24h) by intravenous route during four days beginning at the admission to the hospital (group B). The two groups were evaluated at baseline through prognostic scores and analysis of their clinical and laboratorial characteristics obtained from data recorded at the admission. The parameters to evaluate dexamethasone efficacy were the comparative number of neurologic and systemic complications detected at the hospital, and the liquoric profile (leukocyte count, glucose and protein content) verified between day 9 and day 11 of hospitalization. RESULTS: The profile of the two groups (A and B) were homogeneously evaluated by the illness severity scores and their clinical and laboratorial characteristics. Nine complications were recognized in group A (27.2%) and 21 (31.8%) among those of group B, difference not significant. Likewise, there were not observed liquoric differences between the two groups related to the chimiocytologic pattern. CONCLUSIONS: No effect of dexamethasone therapy to prevent neurologic and systemic meningococcal meningitis complications was observed during hospitalization. Similarly no favorable effect in relation to the liquoric pattern verified between day 9 and day 11 of hospitalization was recognized.

Prevalence of serotypes and antimicrobial resistance of streptococcus pneumoniae strains isolated from Brazilian children with invasive infections. Pneumococcal Study Group in Brazil for the SIREVA Project. Regional System for Vaccines in Latin America.

A laboratory surveillance study was developed in Brazil in 1993 to determine capsular types and antimicrobial susceptibility of Streptococcus pneumoniae strains. By studying 360 strains isolated from children with invasive infections in three different cities, 8 out of 34 types were identified as being the most prevalent and considered as the reference group for further analyses. This group comprised 77.7% of all strains studied, and includes the types 1, 5, 6A/B, 9V, 14, 19F, 19A, and 23F. The prevalence of this reference group was significantly higher among strains isolated from children with pneumonia than meningitis. Similarly, this group was more prevalent among strains isolated from children 3 to 6 years of age than from children under 2 years of age. Most strains (78.6%) were found to be susceptible to penicillin and only 1.4% showed high resistance to this antibiotic. However, intermediate resistance to penicillin was detected in 20% of the strains. This laboratory surveillance will be maintained and extended to other cities of Brazil to better define and monitor the trends of pneumococcal infections for proper control and prevention.

Social expenditure and demographic evolution: a dynamic approach.

PIP: "This paper provides an analysis of the impact of the population ageing on social expenditure.... A dynamic macrosimulation model...is applied to assess the impact of the ageing of the population on the Italian social security, health care and education systems. The main conclusions are that around 2030 social expenditure will reach a peak despite the 1995 reform of the pension system. A further cut in pension expenditure is therefore needed to [offset] the increase in the share of the retired as a proportion of the active population." (EXCERPT)^ieng

[Idiopathic primary pulmonary hemosiderosis: treatment with cyclophosphamide and prednisone]. / Hemossiderose pulonmar idiopática tratada com ciclofosfamida e prednisona.

The authors present the case of a child diagnosed as having idiopathic pulmonary hemosiderosis at five years of age who had a good clinical outcome at the age of ten years. Initially the patient was treated with prednisone and chloroquine with poor results. When cyclophosphamide was added to prednisone, the patient demonstrated clinical and radiological remission. To date, the patient has been followed for one year without any medication, and has had only one limited episode of hemosiderosis. The authors also suggest that the therapeutic regimen with cyclophosphamide and prednisone may be useful for some selected cases.