Hospital admissions for hypertensive crisis in the emergency departments: a large multicenter Italian study.

Epidemiological data on the impact of hypertensive crises (emergencies and urgencies) on referral to the Emergency Departments (EDs) are lacking, in spite of the evidence that they may be life-threatening conditions. We performed a multicenter study to identify all patients aged 18 years and over who were admitted to 10 Italian EDs during 2009 for hypertensive crises (systolic blood pressure ≥220 mmHg and/or diastolic blood pressure ≥120 mmHg). We classified patients as affected by either hypertensive emergencies or hypertensive urgencies depending on the presence or the absence of progressive target organ damage, respectively. Logistic regression analysis was then performed to assess variables independently associated with hypertensive emergencies with respect to hypertensive urgencies. Of 333,407 patients admitted to the EDs over the one-year period, 1,546 had hypertensive crises (4.6/1,000, 95% CI 4.4-4.9), and 23% of them had unknown hypertension. Hypertensive emergencies (n = 391, 25.3% of hypertensive crises) were acute pulmonary edema (30.9%), stroke (22.0%,), myocardial infarction (17.9%), acute aortic dissection (7.9%), acute renal failure (5.9%) and hypertensive encephalopathy (4.9%). Men had higher frequency than women of unknown hypertension (27.9% vs 18.5%, p<0.001). Even among known hypertensive patients, a larger proportion of men than women reported not taking anti-hypertensive drug (12.6% among men and 9.4% among women (p<0.001). Compared to women of similar age, men had higher likelihood of having hypertensive emergencies than urgencies (OR = 1.34, 95% CI 1.06-1.70), independently of presenting symptoms, creatinine, smoking habit and known hypertension. This study shows that hypertensive crises involved almost 5 out of 1,000 patients-year admitted to EDs. Sex differences in frequencies of unknown hypertension, compliance to treatment and risk of hypertensive emergencies might have implications for public health programs.

Intracranial haemorrhage in the Italian population of haemophilia patients with and without inhibitors.

Intracranial haemorrhage (ICH) is the most serious bleeding symptom in haemophiliacs, resulting in high rates of mortality and disabling sequelae. The Association of Italian Haemophilia Centres carried out a retrospective survey (1987-2008) of ICH occurring in haemophiliacs with the goals to establish: (i) incidence, location of bleeding, death rate and disabling sequels; (ii) risk factors for ICH; and (iii) treatment used during the acute phase of ICH and for recurrence prevention. A total of 112 ICH episodes had occurred in 88 patients (78 haemophilia A, 10 haemophilia B), 24 of whom experienced recurrences. The cumulative hazard of ICH for the whole cohort over the entire follow-up period was 26.7 per 1000 patients, and the annualized rate of ICH was 2.50 events per 1000 patients (95% CI 1.90-3.31). The risk of ICH was higher in the youngest children (24.4 per 1000, 95% CI 12.7-47.0 in the first year of age and 14.9, 95% CI 7.1-31.4 in the second year of age) and then progressively rose again after the age of 40. Univariate, bivariate (age-adjusted) and multivariate analysis investigating the effects of patient characteristics on ICH occurrence showed that haemophilia severity and inhibitor status were strongly associated with ICH [severe vs. mild, HR 3.96 (2.39-6.57); inhibitor vs. non-inhibitor 2.52 (1.46-4.35)]. HCV infection was also associated with the risk of ICH [HR 1.83 (1.25-2.69)]. Therapeutic suggestions based upon our experience to control ICH recurrence are provided.

Patient preference for needleless factor VIII reconstitution device: the Italian experience.

BACKGROUND: Needlestick injuries, mostly due to unsafe needle devices, are a frequent adverse event among health care workers and patients on chronic treatment, such as hemophiliacs. To improve the safety of these procedures, a needleless reconstitution system, Bio-Set((R)) has been implemented for the sucrose-formulated recombinant factor VIII (rFVIII-FS) Kogenate((R)) Bayer (Bayer Healthcare, Berlin, Germany). The aim of this study was to collect patients' satisfaction and safety data regarding the administration of rFVIII-FS with this new device. METHODS: This was a multicenter, prospective, postmarketing surveillance study collecting data from seven Italian Haemophilia Centers within the framework of an international project involving patients from nine European countries. The patients were asked to fill out two preference questionnaires (one assessing the old method and one assessing the new method) directly after the training and two further preference questionnaries (assessing the new method) after a period of about 3 and 12 months. RESULTS: A total of 44 male hemophilia A patients were included in the analysis. At the end of the 12-month observation period, physicians assessed the patients' satisfaction with Kogenate((R)) Bayer with Bio-Set((R)) in 40.9% (n = 18) as "very satisfied" and in 45.5% (n = 20) as "satisfied", whereas "not satisfied" ratings were given for 9.1% (n = 4) of patients (data missing from two patients, 4.5%). The compliance of the patients compared with the last method before switch to the Bio-Set((R)) device was rated as "better", "equal", and "worse" in 72.7% (n = 32), 20.5% (n = 9), and 2.3% (n = 1) of patients, respectively. Three patients (6.8%) experienced adverse events, but only one event was related to rFVIII infusion (inhibitor development in a patient who had little prior exposure to rFVIII) itself and not to the new device per se. CONCLUSIONS: The great majority of Italian patients who switched from an older method of rFVIII reconstitution to rFVIII-FS with the new reconstitution method preferred the new method. The ease of use, perceived safety from needlesticks, and the speed of reconstitution were identified as main advantages by the majority of patients.

High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study.

Therapeutic plasma exchange (PE) is the accepted therapy for thrombotic thrombocytopenic purpura (TTP). Because not all patients achieve remission, other treatment modalities have been used in addition to PE, but no randomized clinical trial evaluated their efficacy. The aim of this multicentric study was to compare the effectiveness of standard- versus high-dose methylprednisolone as an adjunctive treatment to PE in the acute phase of TTP. Sixty patients with idiopathic TTP were randomized to receive methylprednisolone 1 mg/kg/die intravenous or 10 mg/kg/die for 3 days, thereafter, 2.5 mg/kg/die in addition to PE. Both dosages of steroids were well tolerated. At the end of induction therapy (day 23), the percentage of patients failing to achieve complete remission was significantly higher in the standard dose (16 of 30) than in the high-dose group (seven of 30). Also, the number of cases without a good response at day 9 and the number of deaths were higher in the standard-dose arm, but the differences did not reach the statistical significance. Results of present study indicate that the association of PE with high-dose instead of standard-dose steroids reduces the percentage of TTP patients that fail to achieve complete remission.

Safety and efficacy of sucrose-formulated full-length recombinant factor VIII: experience in the standard clinical setting.

The safety of full-length sucrose-formulated recombinant factor VIII (rFVIII-FS; Kogenate FS) for up to 24 months of use was evaluated in a postmarketing observational study in Europe. Long-term safety and efficacy data were available for 212 patients with severe haemophilia A, including 13 previously untreated patients (PUPs) and 12 patients with 1-19 exposure days (EDs). Patients accumulated a mean (+/- SD) of 187 (121) EDs to rFVIII-FS and received a total of 39,627 infusions, mainly for prophylaxis and for the treatment of 4,283 spontaneous or trauma-related bleeds during an average observation time of 710 (136) days. Of these bleeding episodes, 85.4% were successfully treated with one or two infusions of rFVIII-FS. Haemostasis was also evaluated during 46 minor to major surgical procedures, and the response to infusion was "excellent" or "good" in all cases. FVIII inhibitor formation was observed in six patients (two de novo; four persistent or recurrent). The de novo cases represent 8.0% (2 of 25) of patients who reported 0-19 previous EDs at study entry. Four of the five patients who reported possible drug-related adverse effects developed inhibitors. The results of this observational study demonstrate the efficacy and safety of rFVIII-FS during normal clinical use in the treatment of patients with severe haemophilia A. Furthermore, these findings are consistent with those of previous phase III clinical studies with rFVIII-FS, particularly with regard to its efficacy and low incidence of inhibitor formation.

MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness.

May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are autosomal dominant macrothrombocytopenias distinguished by different combinations of clinical and laboratory signs, such as sensorineural hearing loss, cataract, nephritis, and polymorphonuclear Döhle-like bodies. Mutations in the MYH9 gene encoding for the nonmuscle myosin heavy chain IIA (NMMHC-IIA) have been identified in all these syndromes. To understand the role of the MYH9 mutations, we report the molecular defects in 12 new cases, which together with our previous works represent a cohort of 19 families. Since no genotype-phenotype correlation was established, we performed an accurate clinical and biochemical re-evaluation of patients. In addition to macrothrombocytopenia, an abnormal distribution of NMMHC-IIA within leukocytes was observed in all individuals, including those without Döhle-like bodies. Selective, high-tone hearing deficiency and cataract was diagnosed in 83% and 23%, respectively, of patients initially referred as having May-Hegglin anomaly or Sebastian syndrome. Kidney abnormalities, such as hematuria and proteinuria, affected not only patients referred as Fechtner syndrome and Epstein syndrome but also those referred as May-Hegglin anomaly and Sebastian syndrome. These findings allowed us to conclude that May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but rather a single disorder with a continuous clinical spectrum varying from mild macrothrombocytopenia with leukocyte inclusions to a severe form complicated by hearing loss, cataracts, and renal failure. For this new nosologic entity, we propose the term "MHY9-related disease," which better interprets the recent knowledge in this field and identifies all patients at risk of developing renal, hearing, or visual defects.