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Primary Prophylaxis (primary + prophylaxis)

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Medical Sciences	100%

Selected Abstracts

Cost-utility analysis of Canadian tailored prophylaxis, primary prophylaxis and on-demand therapy in young children with severe haemophilia A

HAEMOPHILIA, Issue 4 2008
N. RISEBROUGH
Summary. Primary prophylaxis is the emerging standard treatment for boys with severe haemophilia. Tailored (escalating-dose) prophylaxis (EscDose), beginning at a low frequency and escalating with repeated bleeding may prevent arthropathy at a lower cost than standard prophylaxis (SP). From a societal perspective, we compared the incremental cost per joint-haemorrhage that is avoided and quality-adjusted-life-year (QALY) gained of SP and EscDose to on-demand (Demand) therapy in severe haemophilia A boys treated to age 6 using a decision analytic model. Costs included factor VIII (FVIII), professional visits and tests, central venous placement/complications, hospitalization, home programmes and parents' lost work-days. Resource utilization was estimated by surveying 17 Canadian clinics. The natural history of bleeding and other probabilities were determined from a longitudinal chart review (n = 24) and published literature. EscDose costs an additional $3192 per joint-haemorrhage that was avoided compared with Demand whereas SP costs an additional $9046 per joint-haemorrhage that was avoided compared with EscDose. Clinic costs and lost wages were reduced by 60,80% for EscDose and SP compared with Demand. EscDose attained more QALYs than SP and Demand on account of less bleeding than Demand and lower need for ports than SP. The incremental cost per QALY for EscDose vs. Demand was $542 938. EscDose was less expensive with similar QALYs compared to SP. Sensitivity analysis was performed on all probability- and cost-estimates, and showed the model was sensitive to the cost of FVIII and the SP and target joint utilities. In conclusion, prophylaxis will substantially improve clinical outcomes and quality of life compared to Demand treatment, but with substantial cost. [source]

Primary prophylaxis for cryptococcal meningitis

HIV MEDICINE, Issue 3 2004
Laurence John
No abstract is available for this article. [source]

Power Doppler sonography in the diagnosis of hemophilic synovitis , a promising tool

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2008
S. S. ACHARYA
Summary.,Background:,Recurrent hemarthroses in hemophilia results in synovitis and joint arthropathy. Primary prophylaxis when universally instituted at current doses can prevent joint deterioration but is expensive. Alternatively, the selective implementation of prophylaxis would require a more sensitive tool for detecting synovitis than possible with clinical surveillance or plain radiographs. Magnetic resonance imaging (MRI) is such a tool and is utilized for the evaluation of hemophilic joint disease (HJD). However, it is expensive, and requires sedation in younger children precluding its utility for monitoring of synovitis. Ultrasonography (USG) with power Doppler (USG-PDS) has been utilized to detect and quantitate synovial vascularity in other arthritides and could provide an equally effective but less costly tool for HJD, particularly in children who would not require sedation. Objectives:,To determine whether USG-PDS is comparable to MRI in the evaluation of hemophilic synovitis. Patients:,A prospective cohort of 31 subjects including 33 joints (knees, elbows, ankles) underwent dynamic contrast enhanced (DCE)-MRI and USG-PDS. Results:,USG-PDS measurements of synovial thickness(r = 0.70, P < 0.0001) and synovial vascularity (r = 0.73, P < 0.0001) correlated strongly with those obtained with DCE-MRI. A cutoff of PDS intensity of 1.3 decibels (dB) per mm2 was found to yield a sensitivity of 100% and a specificity of 94.1% in 17 joints with/without a history of hemarthroses. Pettersson radiographic scores correlated significantly with synovial thickness in adults but not children. Conclusions:,Our data suggest that USG-PDS may be an inexpensive and easily implemented imaging tool for detecting hemophilic synovitis and could be useful in tailoring effective prophylaxis. [source]

The role of prophylaxis in bleeding disorders

HAEMOPHILIA, Issue 2010
E. BERNTORP
Summary., The rationale for long-term prophylaxis in more severe forms of von Willebrand's disease (VWD) is obvious, as mucosal bleeding and haemophilia-like joint bleeds resulting in chronic morbidity may occur. However, the experience with prophylactic treatment in this group is scanty. An international VWD Prophylaxis Network (VWD PN) was established in 2006. The VWD PN will investigate prophylaxis with retrospective and prospective studies. Eighteen centres in Europe and North America are recruiting patients and an additional 40 centres are preparing for or evaluating participation. In the absence of randomized prospective studies for most rare bleeding disorders, guidelines for prophylaxis are a subject of controversy. In situations where there is a strong family history of bleeding, long-term prophylaxis is administered in selected cases. Short intervals of prophylaxis can also be given before some surgeries or during pregnancy. The benefits of prophylaxis must be balanced by the risk of side effects. Therefore, it is essential to delineate its management in a specialized comprehensive care environment. In haemophilia, decades of clinical experience and numerous retrospective and, recently, prospective studies clearly demonstrate that prophylactic treatment is superior to on-demand treatment, regardless of whether the outcome is the number of joint- or life-threatening bleeds, arthropathy evaluated by X-ray or MRI, or quality of life measured by generic or haemophilia-specific instruments. Optimal prophylactic treatment should be started early in life (primary prophylaxis) but various options exist for the dose and dose interval. These depend on the objective of treatment in the individual patient, which, in turn, is dependent on resources in the health care system. [source]

Forum on: the role of recombinant factor VIII in children with severe haemophilia A

HAEMOPHILIA, Issue 2 2009
M. FRANCHINI
Summary., The development of recombinant FVIII (rFVIII) products, fuelled by the need for improved safety of treatment arising from the dramatic widespread blood-borne virus transmission in the 1970,1980s revolutionized the care of children with haemophilia A over the last two decades. The larger availability of perceived safer replacement therapy associated with the introduction of rFVIII products reassured the haemophilia community and there was a strong push in some Western countries to treat haemophilic children only with rFVIII. Moreover, this significantly contributed in the 1990s to the diffusion outside Northern Europe of prophylactic regimens implemented at an early age to prevent bleeding and the resultant joint damage (i.e. primary prophylaxis), together with the possibility of home treatment. These changes led to a substantial improvement of the quality of life of haemophilic children and of their families. The general agreement that primary prophylaxis represents the first-choice treatment for haemophilic children has been recently supported by two randomized controlled trials carried out with rFVIII products, providing evidence on the efficacy of early prophylaxis over on-demand treatment in preserving joint health in haemophilic children. However, the intensity and optimal modalities of implementation of prophylaxis in children, in particular with respect to the issue of the venous access, are still debated. A number of studies also supports the role of secondary prophylaxis in children, frequently used in countries in which primary prophylaxis was introduced more recently. With viral safety now less than an issue and with the more widespread use of prophylaxis able to prevent arthropathy, the most challenging complication of replacement therapy for children with haemophilia remains the risk of inhibitor development. Despite conflicting data, there is no evidence that the type of FVIII concentrate significantly influences the complex multifactorial process leading to anti-FVIII alloantibodies, whereas other treatment-related factors are likely to increase (early intensive treatments due to surgery or severe bleeds) or reduce (prophylaxis) the risk. Although the optimal regimen is still uncertain, eradication of anti-FVIII antibodies by immune tolerance induction (ITI), usually with the same product administered at inhibitor detection, should be the first-choice treatment for all patients with recent onset inhibitors. This issue applies particularly to children, as most patients undergo ITI at an early age, when inhibitors usually appear. The availability of a stable and long-lasting venous access represents a leading problem also in this setting. These and other topics concerning rFVIII treatment of haemophilic children were discussed in a meeting held in Rome on 27 February 2008 and are summarized in this report. [source]

Cost-utility analysis of Canadian tailored prophylaxis, primary prophylaxis and on-demand therapy in young children with severe haemophilia A

A global view on prophylaxis: possibilities and consequences

HAEMOPHILIA, Issue 2003
A. D. Shapiro
Summary., Prophylactic infusion therapy, both primary and secondary, has proven of great benefit to patients with haemophilia, specifically those with severe disease or bleeding episodes and patterns that have lead to development of arthropathy. At this time, optimal outcome in patients with severe haemophilia has been proven achievable with primary prophylaxis initiated at an early age in a regimen of three times weekly or every other day for patients with factor VIII deficiency, and twice weekly for those with factor IX deficiency. Despite the demonstrated benefit of primary prophylaxis, this treatment regimen has not been uniformly adopted into clinical practice even in developed countries. In developing countries, where issues of allocation of precious health care resources are of paramount importance, access to adequate treatment for persons with haemophilia on a programme of on-demand therapy is not commonly available; the cost of primary prophylaxis, even with intermediate purity plasma-derived factor concentrates or plasma fractions such as cryoprecipitate, renders this treatment the exception rather than the rule. [source]

Experience of prophylaxis treatment in children with severe haemophilia

HAEMOPHILIA, Issue 2 2002
T. T. YEE
The practice of prophylactic treatment of boys with severe haemophilia has been evaluated in our centre. Prophylaxis was started at the median age of 3.7 years (range 0.4,12.7 years) in 38/41 children (93%) under 17 years of age. Median follow-up was 4.1 years (range 0.4,12.7 years). The criteria of primary prophylaxis according to the definition by the European Paediatric Network of Haemophilia Management was fulfilled by 9/38 (24%). Although a majority [76%, 29/38] of the children started prophylaxis after a median number of joint bleeds of 3.5, 70% of the children in this group had clinical joint scores of 0. Intravenous catheter insertion was required at a median age of 15.5 months (range 5,36 months) in 21% of the children, resulting in a catheter infection rate of 1.74 per 1000 catheter days. None developed an inhibitor on prophylaxis and three patients who had low-titre inhibitors (< 5 Bethesda units) prior to prophylaxis had undetectable inhibitors after prophylaxis. The home-treatment training programme required considerable time and cost. As a result, 87% of the children used peripheral venous access and hospital visits declined as prophylaxis became established. Parents' incentives for prophylaxis were that the children undertook many physical activities and sports previously not recommended, there was less parental anxiety and an overall improvement in the quality of life for the whole family. [source]

Changes in treatment strategies for severe haemophilia over the last 3 decades: effects on clotting factor consumption and arthropathy

HAEMOPHILIA, Issue 5 2001
K. Fischer
A cohort study was performed among 214 patients with severe haemophilia, born 1944,1994, to describe changes in treatment over the last 3 decades and its effects on clotting factor consumption and haemophilic arthropathy. Data on treatment strategy, clotting factor consumption, and outcome were collected for 3567 patient years (from 1972 to 1998), and 493 Pettersson scores were analysed. Median follow up was 17 years (range 6,27 years), and median age in 1998 was 27.6 years. Since 1965, replacement therapy, prophylaxis, and home treatment have been used and treatment intensified. Over the last 3 decades, annual clotting factor consumption increased by 260%, for both prophylactic and on-demand treatment. Annual clotting factor consumption kg,1 increased during childhood and appeared to stabilize in early adulthood for patients born 1965,79, who were treated with early replacement therapy or early prophylaxis. In contrast, clotting factor consumption increased continuously for patients born before 1965, who had had no access to replacement therapy during the early years of their life. The annual number of joint bleeds decreased over the years. Arthropathy as measured by the Pettersson score generally became apparent around the age of 15 years and was lowest in patients treated with primary prophylaxis. In conclusion, clotting factor consumption has increased and haemophilic arthropathy has decreased due to the intensification of treatment for severe haemophilia over the last 3 decades. Annual clotting factor consumption stabilizes in adulthood for patients who receive early intensive treatment. [source]

Therapy for primary prophylaxis of varices: And, the winner is ,?

HEPATOLOGY, Issue 2 2003
Ala I. Sharara M.D.
No abstract is available for this article. [source]

The hemodynamic response to medical treatment of portal hypertension as a predictor of clinical effectiveness in the primary prophylaxis of variceal bleeding in cirrhosis

HEPATOLOGY, Issue 5 2000
Carlo Merkel
In the prevention of variceal rebleeding, it is already established that hemodynamic response to drug treatment (decrease in hepatic venous pressure gradient [HVPG] to 12 mm Hg or by >20%) is predictive of clinical effectiveness. In primary prophylaxis very few clinical data are available. We assessed the role of the hemodynamic response to beta-blockers or beta-blockers plus nitrates in predicting clinical efficacy of prophylaxis. A total of 49 cirrhotic patients with varices at risk of bleeding, without prior variceal bleeding, were investigated by hepatic vein catheterization before and after 1 to 3 months of chronic treatment with nadolol or nadolol plus isosorbide mononitrate, and were followed during treatment for up to 5 years. A total of 30 patients (61%) were good hemodynamic responders, and among them in 12 (24%) HVPG was ,12 mm Hg during treatment. During treatment 9 patients had variceal bleeding: 7 were poor responders and 2 were good responders. The probability of bleeding at 3 years of follow-up was significantly higher in poor responders (41%) than in good responders (7%; P = .0008). No patient reaching an HVPG of 12 mm Hg or less during treatment had variceal bleeding during follow-up. Cox's regression analysis showed that poor hemodynamic response was the main factor predicting bleeding (, = 1.91; SE(,) = 0.80; P = .01). During follow-up 11 patients died of hepatic causes. Survival was related to Child-Pugh class and to initial value of HVPG, according to Cox's analysis. In conclusion, the assessment of hemodynamic response to drugs in terms of HVPG is the best predictor of efficacy of prophylaxis of variceal bleeding in patients treated with beta-blockers or beta-blockers plus nitrates. [source]

Early identification of haemodynamic response to pharmacotherapy is essential for primary prophylaxis of variceal bleeding in patients with ,high-risk' varices

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009
P. SHARMA
Summary Background, A beta-blocker is recommended for primary prophylaxis of variceal bleeding; however, only one-third have hepatic venous pressure gradient (HVPG) response. The role of addition of isosorbide-5-mononitrate (ISMN) to beta-blocker and benefits of HVPG-guided ,a la carte' approach remain unclear. Aim, To determine the benefits of HVPG-guided pharmacotherapy in primary prophylaxis of variceal bleeding using beta-blocker and ISMN. Patients and methods, Consecutive patients of cirrhosis, with high-risk varices, with no previous variceal bleeding were included. After baseline HVPG, patients received incremental propranolol to achieve HR of 55/min. After one-month, HVPG was repeated to determine response (<12 mmHg or ,20% reduction). ISMN was added in nonresponders and HVPG repeated. Patients were followed up for 24 months. Results, Of 56 patients (age 47 ± 13, males 79%) from 89 eligible patients, 21 (38%) responded to beta-blocker alone. Six additional patients responded to combination. Thus, overall 48% (27/56) patients responded. Variceal bleeding occurred in seven of 56 (13%) patients [one of 27 (4%) responder, five of 23 (22%) nonresponders and one of six (17%) with unknown response; P = N.S.]. The actuarial probability of variceal bleeding at median 24 months was 4% in responders and 22% in nonresponders (P < 0.05). Ten (18%) patients developed adverse effects to propranolol and six of 35 (17%) to nitrates requiring dose reduction. Risk factors of variceal bleed were grade IV varices and haemodynamic nonresponse. Conclusions, For primary prophylaxis, a beta-blocker is effective in 38% and addition of ISMN raises the response rate to about half of patients. The HVPG-guided ,a la carte' approach may be considered for these patients. [source]

Review article: primary prophylaxis for portal hypertensive bleeding in cirrhosis

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2000
Vlachogiannakos
Variceal bleeding is a consequence of portal hypertension, which in turn is the major complication of hepatic cirrhosis. Given the high rate of mortality of the first bleeding episode, primary prophylaxis to prevent bleeding from varices and portal hypertensive gastropathy is the current optimal therapeutic approach. The difficulty in identification of patients with varices who will bleed, before they do so, can justify a strategy of treating all patients with varices prophylactically. We evaluated the various therapies that have been assessed in randomized controlled trials for prevention of first bleeding, using meta-analysis where applicable. The current first choice treatment is non-selective ,-blockers; it is cheap, easy to administer, and is effective in preventing the first variceal haemorrhage and bleeding from gastric mucosa. Combination drug therapy of ,-blockers and nitrates looks promising, but needs further evaluation in randomized controlled trials. The conflicting results of the randomized studies of endoscopic banding ligation and the small number of patients and clinical events, as well as the cost, do not warrant any change in current practice. However, endoscopic banding ligation may be a reasonable alternative for patients who cannot tolerate, or have contraindications to ,-blockers or no haemodynamic response to the drug therapy, but this must be proved in randomized trials. [source]

Does ICD Indication Affect Quality of Life and Levels of Distress?

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 2 2009
SUSANNE S. PEDERSEN Ph.D.
The implantable cardioverter defibrillator (ICD) is the treatment of choice for life-threatening arrhythmias, with ICD indications having recently been extended to include primary prophylaxis. Despite the medical benefits of the ICD, there is an ongoing debate as to the impact of the ICD on patients' lives, particularly whether primary prophylaxis implantation may impact adversely on patient-centered outcomes such as quality of life (QoL) and distress. We examined the evidence for a role of ICD indication on these patient-centered outcomes. A literature search was conducted on PubMed and Web of Science from 2002 to present, focusing on indication for ICD therapy and patient-centered outcomes (i.e., anxiety, depression, disease-specific, or general QoL). We identified five studies (seven articles) concerning the impact of indication on patient-centered outcomes. Sample sizes varied from 91,426 patients across studies, five of seven articles used a prospective design, and follow-up ranged from 2,12 months. No study reported an effect for indication on patient-centered outcomes. There is no evidence to suggest that patients receiving an ICD for primary prophylaxis have subsequent poorer QoL and greater distress than patients receiving an ICD for secondary prophylaxis. This knowledge may help cardiologists in the clinical management of patients, in particular when discussing ICD implantation with patients. [source]

Dose-intensified treatment of Burkitt lymphoma and B-cell lymphoma unclassifiable, (with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma) in young adults (<50 years): A comparison of two adapted BFM protocols,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010
Sudhir Tauro
The chemotherapy dose-intensity in two adapted German BFM paediatric protocols (BFM 90 and NHL 86) was compared in contemporaneously treated adults <50 years with Burkitt lymphoma and B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (collectively referred to as BL). In BFM 90, primary prophylaxis with Granulocyte-colony-stimulating factor was used, postinduction treatment was started at granulocytes ,0.5 × 109/L (,1.0 × 109/L in NHL 86) with a higher mean methotrexate dose (2.9 g/m2/cycle, n = 23; 1.6 g/m2/cycle in NHL 86, n = 22, P < 0.001). Intervals between consecutive treatment-cycles were shorter in BFM 90 (P < 0.001) with no additional toxicity. However, the two-year failure-free survival with BFM 90 (82%) was similar to that achieved with NHL 86 (72%, P = 0.33). We conclude that BFM 90 enables safe intensification of therapy in young adults with BL compared to NHL 86, but registry-based studies are required to further evaluate the antineoplastic effects and cost-effectiveness of the two therapeutic approaches. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source]

Perioperative venous thrombosis in children: is it time for primary prophylaxis?

PEDIATRIC ANESTHESIA, Issue 2 2007
JUDITH MORGAN
No abstract is available for this article. [source]

A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L-asparaginase,

CANCER, Issue 2 2003
Results of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study
Abstract BACKGROUND Thrombotic events (TEs) are serious secondary complications in children with acute lymphoblastic leukemia (ALL) who receive L-asparaginase (ASP) therapy; however, the prevalence of TEs has not been established. The primary objective of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study was to determine the prevalence of TEs. The secondary objective was to detect any association of TEs with the presence of congenital or acquired prothrombotic disorders. METHODS Children with ALL were screened for TEs at the end of ASP treatment using bilateral venograms, ultrasound, magnetic resonance imaging, and echocardiography. Symptomatic TEs were confirmed by appropriate radiographic tests. All tests were read by a blinded central adjudication committee. RESULTS Twenty-two of 60 children had TEs, a prevalence of 36.7% (95% confidence interval, 24.4,48.8%). TEs were located in the sinovenous system of the brain in 1 patient, the right atrium in 3 patients, and the upper central venous system in 19 patients. TEs detected by venography resulted in 1) 25,100% occlusion, with 1 in 3 patients showing occlusion of > 75% of the greatest vessel dimension, and 2) the presence of collaterals in 60% of patients, with 40% categorized as major. No children with TEs were positive for factor V Leiden or prothrombin gene 20201A, and four of eight children with antiphospholipid antibodies had a TE. CONCLUSIONS The prevalence of TEs is exceedingly high in this population, and it is likely that the extent of occlusion is likely clinically significant. No trend was seen toward an association between TEs and the presence of congenital prothrombotic disorders. A trend was seen toward an association between TEs and antiphospholipid antibodies. Carefully designed clinical trials of primary prophylaxis for the prevention of TEs are required in this patient population. Cancer 2003;97:508,16. © 2003 American Cancer Society. DOI 10.1002/cncr.11042 [source]