Treatment trends for haemophilia A and haemophilia B in the United States: results from the 2010 practice patterns survey.

Frequent evaluation of haemophilia treatment is necessary to improve patient care. The 2010 Practice Patterns Survey (PPS) investigated current trends in haemophilia treatment in the United States, as reported by nurses. The aim was to document practice patterns for haemophilia A and haemophilia B Survey questionnaires were sent to nurses at haemophilia treatment centres (HTCs) across the United States. Seventy-one of 126 HTCs (56%) responded to the survey. Factor dosage across treatment modalities ranged from 20 to 50 IU kg(-1) for severe haemophilia A. Dosage for severe haemophilia B was more variable (<40 to >100 IU kg(-1)). On-demand dosing regimens were inconsistent for haemophilia A and more so for haemophilia B. Rates of adherence to prescribed treatment were similar for both haemophilia types (∼80%). The main barrier to adherence was identified as inconvenience. More bleeding episodes occurred in adults (16.6 bleeding episodes per year) with severe haemophilia A than in younger patients (11.3 bleeding episodes per year) before switching patients to prophylaxis. For both haemophilia types, most patients who switched from prophylaxis to on-demand treatment were aged 13-24 years; these patients also had the lowest adherence (60-71%). More paediatric patients with severe haemophilia A and inhibitors (53%) received prophylactic bypassing therapy than their haemophilia B counterparts (38%). Adults with severe haemophilia A faced challenges in relation to co-morbidities and long-term care. This PPS provides insights into previously unexplored aspects of haemophilia care that will serve to increase awareness and promote discussion of current issues affecting haemophilia patient care.

Current prescription of prophylactic factor infusions and perceived adherence for children and adolescents with haemophilia: a survey of haemophilia healthcare professionals in the United States.

The primary goal of prophylaxis in patients with severe haemophilia is to convert the phenotype from severe to moderate and to prevent the development of chronic arthropathy. Prior studies have demonstrated that prophylaxis decreases episodes of joint bleeds and chronic arthropathy. Effectiveness depends on prescription of prophylaxis and adherence to the prescribed regimen. The aim of this study was to determine if prescription of prophylaxis for children with haemophilia and perceptions of adherence to prophylaxis have changed since publication of the Joint Outcome Study (JOS). A questionnaire was sent, in electronic and written formats, to health professionals who provide care to children with haemophilia at US haemophilia treatment centres (HTCs). The response rate was 56 of 128 (44%) of the targeted HTCs. There were a few missing data and denominators are provided. All responses agreed with the results of the JOS and 30/55 (55%) reported the JOS increased their prescription of prophylaxis. Nineteen of 56 (34%) physicians or HTC staff reported that they had not prescribed prophylaxis within the last year due to concerns about adherence, and 19/56 (34%) reported they had stopped prophylaxis due to concerns about adherence within the last year. Predicted adherence decreased with increasing age. Prescription of prophylaxis appears to be increasing since publication of the JOS. Strategies to improve adherence may increase the likelihood of physician prescription of prophylaxis and make prophylaxis easier to implement for individual patients, thereby improving the clinical outcome of children and adults with haemophilia.

Immune tolerance therapy utilizing factor VIII/von Willebrand factor concentrate in haemophilia A patients with high titre factor VIII inhibitors.

Factor VIII (FVIII) inhibitors remain a serious complication of treatment for patients with haemophilia A. Immune tolerance induction (ITI) can eliminate inhibitors in the majority of patients, but there are major concerns related with this therapy. Investigators have raised the possibility that the use of FVIII/von Willebrand factor (FVIII/VWF) concentrates may improve the success rate of ITI and may shorten the duration of therapy necessary to attain tolerance. This retrospective study describes 25 patients at five institutions in the USA, who were treated with FVIII/VWF concentrate as part of their ITI. These were all patients who were considered poor prognosis because of clinical and laboratory characteristics, which made ITI less likely to be successful or because of a poor response to initial ITI with a monoclonal/recombinant FVIII concentrate. Overall success (complete tolerization) was 32% with another 40% attaining partial tolerization, but not complete tolerization. Of those patients attaining only partial tolerization, two patients ultimately discontinued ITI and had return of their high titre inhibitors. Eight percent of patients failed to attain either partial or complete tolerization and discontinued ITI. Another 24% are continuing with ITI but have titres of >10 BU. This study adds further retrospective data to the information regarding the use of FVIII/VWF concentrate in ITI.

Pyrococcus abyssi alkaline phosphatase: the dimer is the active form.

Alkaline phosphatases (APs), E.C. 3.1.3.1, are non-specific phosphomonoesterases optimally active under alkaline conditions. They are classically known to be homodimeric metalloenzymes. This quaternary structure has been considered necessary for activity, although the relationship between quaternary structure and activity is not well understood. Recombinant Pyrococcus abyssi AP was previously isolated and characterized, appearing to have two active quaternary structures on native polyacrylamide gel electrophoresis: a monomer and a homodimer. The purpose of the present work was to determine the actual quaternary structure of P. abyssi AP in solution, by isolating each of the two quaternary forms and establishing the parameters governing the assembly and dissociation of the dimer. pH appeared to be an important parameter: in acidic media, the monomer/dimer ratio shifted towards monomer. Buffer composition also affected the quaternary structure: at the same pH, in potassium phosphate buffer, the two quaternary structures were observed, whereas in tris(hydroxymethyl)aminomethane hydrochloride buffer, only the dimer was observed. Metals bound to the enzyme were found to be involved in the stability of the quaternary structure. Indeed, the P. abyssi AP obtained upon removal of the metals was monomeric. Reactivation of the latter was achieved with variable efficiency. From these experiments, no active monomer could be isolated, leading the conclusion that the active form of P. abyssi AP is the homodimer.

Surveillance of infections acquired in intensive care: usefulness in clinical practice.

Nosocomial infection surveillance is common in the USA and in some European countries but in Italy few hospitals use it. In order to evaluate its usefulness in clinical practice we performed a one year prospective epidemiological study that included 178 patients, admitted to an intensive care unit (ICU) for more than 48 h. Median ICU stay was 16 days. Trauma and neurological diseases accounted for 65% of admissions. The selected population had high severity scores and required a large number of invasive procedures for diagnosis and therapy. The most common infections were: pneumonia 46/1000 ventilator-days; urinary tract infections 17/1000 catheter-days; central venous catheter infections 14.5/1000 catheter-days with 1.7/1000 CVC-related sepsis; bacteraemic sepsis 12/1000 ICU-days. The most frequent pathogens were Staphylococcus aureus,Pseudomonas aeruginosa, other Gram-negative aerobes and Candida spp. Antimicrobial resistance was substantial, with 68% methicillin-resistance in S. aureus and 76% of P. aeruginosa displaying antibiotic resistance. Severe sepsis or septic shock occurred in 30 patients (8/1000 ICU-days), and three patients died from septic shock of unknown origin (10% case fatality rate). There were no case fatalities for pneumonia and bacteraemic sepsis. Overall, ICU-acquired infections were not associated with an increased risk of death.

Characterization of a highly thermostable alkaline phosphatase from the euryarchaeon Pyrococcus abyssi.

This work reports the first isolation and characterization of an alkaline phosphatase (AP) from a hyperthermophilic archaeon. An AP gene from Pyrococcus abyssi, a euryarchaeon isolated from a deep-sea hydrothermal vent, was cloned and the enzyme expressed in Escherichia coli. Analysis of the sequence showed conservation of the active site and structural elements of the E. coli AP. The recombinant AP was purified and characterized. Monomeric and homodimeric active forms were detected, with a monomer molecular mass of 54 kDa. Apparent optimum pH and temperature were estimated at 11.0 and 70 degrees C, respectively. Thus far, P. abyssi AP has been demonstrated to be the most thermostable AP, with half-lives at 100 and 105 degrees C of 18 and 5 h, respectively. Enzyme activity was found to be dependent on divalent cations: metal ion chelators inhibited activity, whereas the addition of exogenous Mg(II), Zn(II), and Co(II) increased activity. The enzyme was inhibited by inorganic phosphate, but not by molybdate and vanadate. Strong inhibitory effects were observed in the presence of thiol-reducing agents, although cysteine residues of the P. abyssi AP were not found to be incorporated within intra- or interchain disulfide bonds. In addition, P. abyssi AP was demonstrated to dephosphorylate linear DNA fragments with dephosphorylation efficiencies of 93.8 and 84.1% with regard to cohesive and blunt ends, respectively.

Implantable venous access devices in children with hemophilia: a report of low infection rates.

OBJECTIVE: The objective of this study was to define the efficacy and complications of implantable venous access devices (IVADs) in children with hemophilia. STUDY DESIGN: Records were reviewed on all patients with congenital blood coagulation disorders monitored at two children's hospitals in whom one or more central venous catheters had been placed. RESULTS: Since 1989 external and implantable central venous catheters have been inserted to enhance venous access for regular factor concentrate infusion in 45 patients with hemophilia ranging in age from 8 months to 19.5 years (median 7.4 years); 37 patients had factor VIII deficiency and 8 factor IX deficiency. Hemorrhagic complications of catheter placement were infrequent and minor. In the 41 patients having one or more IVADs in place for a median of 31 months, only six episodes of bacteremia occurred in 5 patients during 44,070 days of follow-up. The overall rate of bacteremia complicating IVADs in these patients was 0.14 episodes per 1000 catheter days. Other catheter-related complications were uncommon. Catheters are still in place in 33 patients for a median of 32 months. CONCLUSION: The low risk of infection and other complications associated with the use of IVADs makes the use of these devices attractive in the treatment of patients with hemophilia who require frequent venous access for factor concentrate infusions.

Bedside burr hole for intracranial pressure monitoring performed by intensive care physicians. A 5-year experience.

OBJECTIVE: To assess the results of a 5-year experience with bedside burr hole for intracranial pressure (ICP) monitoring performed by intensive care physicians. DESIGN: Prospective, observational study in 120 patients. SETTING: A general-neurologic Intensive Care Unit in a University Hospital. PATIENTS: Patients admitted for acute neural lesion requiring ICP monitoring. METHOD: A 2.71 mm burr hole was made with positioning of a subarachnoid screw, through which a miniaturized fiberoptic, tip transducer device (Camino) was advanced and inserted 2 mm in the frontal cortex. MAIN RESULTS: Over a 5-year period 120 patients, mainly with severe head trauma, underwent ICP monitoring. None of the planned patients was excluded because of technical difficulties. No life-threatening complications were reported, and the overall morbidity rate related to the ICP monitor was 3.3%. Complications were infectious in nature, with 2.5% wound infections and 0.8% meningitis. Although seven patients bled when opening the dura, no intracranial hematomas were recorded due to the ICP monitor. The fiberoptic device was left in place for 5 +/- 1.6 (SD) days (range 1-12 days). Five patients (4.1%) required catheter substitution due to breakage of the system components (fiberoptics). CONCLUSIONS: Bedside insertion of a ICP monitor performed by intensive care physicians is a safe procedure, with a complication rate comparable to other series published by neurosurgeons. The overall morbidity rate is comparable to, or even lower than, that caused by central vein catheterization.

Use of ethyl chloride topical anesthetic to reduce procedural pain in pediatric oncology patients.

Pediatric cancer patients often become anxious, agitated, combative, and uncooperative due to the pain or fear of pain during invasive procedures. Generally, it is not the actual administration of medicines that produces this reaction, but the fear of the needle stick itself. Increased education and implementation of coping mechanisms is often not enough to allay this fear. The tangible solution of using ethyl chloride, an anesthetic spray, before port sticks, lumbar punctures, and bone marrow aspirations, was instituted by the hematology-oncology clinic to determine if the pain, emotional trauma, and fear of cancer treatments could be reduced in oncology patients. Survey results on 60 patients and 60 parents/caretakers showed that when given the choice to use the spray or to refuse its use, 68% of the parents thought that the patient had more of a sense of control and, thus, involvement in their treatment. Seventy-eight percent of the patients reported experiencing less pain associated with procedures. Staff noted an increase in cooperation, less combativeness, and more compliance with treatment. Perceiving the child's discomfort diminished, 87% of the parents/caretakers report feeling less anxious and, therefore, more capable of being supportive to each other and their child. These results verified the staff's perceptions of the advantages of using this noninvasive anesthetic. Ethyl chloride is an easy, effective, concrete approach to reducing procedural pain in pediatric oncology patients.