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Prophylactic Treatment (prophylactic + treatment)
Selected AbstractsA Double-Blind Comparison of OnabotulinumtoxinA (BOTOX®) and Topiramate (TOPAMAX®) for the Prophylactic Treatment of Chronic Migraine: A Pilot StudyHEADACHE, Issue 10 2009Ninan T. Mathew MD Background., There is a need for effective prophylactic therapy for chronic migraine (CM) that has minimal side effects. Objective., To compare the efficacy and safety of onabotulinumtoxinA (BOTOX®, Allergan, Inc., Irvine, CA) and topiramate (TOPAMAX®, Ortho-McNeil, Titusville, NJ) prophylactic treatment in patients with CM. Methods., In this single-center, double-blind trial, patients with CM received either onabotulinumtoxinA, maximum 200 units (U) at baseline and month 3 (100 U fixed-site and 100 U follow-the-pain), plus an oral placebo, or topiramate, 4-week titration to 100 mg/day with option for additional 4-week titration to 200 mg/day, plus placebo saline injections. OnabotulinumtoxinA or placebo saline injection was administered at baseline and month 3 only, while topiramate oral treatment or oral placebo was continued through the end of the study. The primary endpoint was treatment responder rate assessed using Physician Global Assessment 9-point scale (+4 = clearance of signs and symptoms and ,4 = very marked worsening [about 100% worse]). Secondary endpoints included the change from baseline in the number of headache (HA)/migraine days per month (HA diary), and HA disability measured using Headache Impact Test (HIT-6), HA diary, Migraine Disability Assessment (MIDAS) questionnaire, and Migraine Impact Questionnaire (MIQ). The overall study duration was approximately 10.5 months, which included a 4-week screening period and a 2-week optional final safety visit. Follow-up visits for assessments occurred at months 1, 3, 6, and 9. Adverse events (AEs) were documented. Results., Of 60 patients randomized to treatment (mean age, 36.8 ± 10.3 years; 90% female), 36 completed the study at the end of the 9 months of active treatment (onabotulinumtoxinA, 19/30 [63.3%]; topiramate, 17/30 [56.7%]). In the topiramate group, 7/29 (24.1%) discontinued study because of treatment-related AEs vs 2/26 (7.7%) in the onabotulinumtoxinA group. Between 68% and 83% of patients for both onabotulinumtoxinA and topiramate groups reported at least a slight (25%) improvement in migraine; response to treatment was assessed using Physician Global Assessment at months 1, 3, 6, and 9. Most patients in both groups reported moderate to marked improvements at all time points. No significant between-group differences were observed, except for marked improvement at month 9 (onabotulinumtoxinA, 27.3% vs topiramate, 60.9%, P = .0234, chi-square). In both groups, HA/migraine days decreased and MIDAS and HIT-6 scores improved. Patient-reported quality of life measures assessed using MIQ after treatment with onabotulinumtoxinA paralleled those seen after treatment with topiramate in most respects. At month 9, 40.9% and 42.9% of patients in the onabotulinumtoxinA and topiramate groups, respectively, reported ,50% reduction in HA/migraine days. Forty-one treatment-related AEs were reported in 18 onabotulinumtoxinA-treated patients vs 87 in 25 topiramate-treated patients, and 2.7% of patients in the onabotulinumtoxinA group and 24.1% of patients in the topiramate group reported AEs that required permanent discontinuation of study treatment. Conclusions., OnabotulinumtoxinA and topiramate demonstrated similar efficacy in the prophylactic treatment of CM. Patients receiving onabotulinumtoxinA had fewer AEs and discontinuations. [source] Botulinum Toxin Type A (Botox) for Prophylactic Treatment of Chronic Daily Headache: A ResponseHEADACHE, Issue 3 2006Ninan T. Mathew MD No abstract is available for this article. [source] The Clinical Noncompliance of Oral Sotalol/Magnesium for Prophylactic Treatment of Atrial Fibrillation After Coronary Artery Bypass GraftingJOURNAL OF CARDIAC SURGERY, Issue 4 2007Giovanni Mariscalco M.D. The present aim was to study the clinical compliance of a suggested prophylactic treatment, oral sotalol, and magnesium. Methods: Coronary-bypass patients without clinical contraindications to receive oral sotalol (80 mg twice daily) and magnesium supplementation were enrolled (n = 49) with an intention-to-treat strategy and being compared with a matched control group (n = 844). A protocol listed exclusion criteria of clinical compliance that was postoperatively evaluated prior to and during treatment. Results: Twenty-seven of the 49 enrolled patients (55%) were compliant to sustain the treatment according to the protocol. The remaining patients were postoperatively excluded, mainly because of hemodynamic reasons, of whom 14 were noncompliant to initiate any treatment. The AF occurrence in the compliant group was 7% versus 36% in noncompliant patients (p = 0.035), and 24% in the control group (p = 0.076). However, with an intention-to-treat policy the overall AF incidence became 18%. The subgroups of enrolled patients demonstrated skewing phenomena. The noncompliant group had higher requirement for inotropic support (p = 0.029) and longer aortic cross-clamp time (p = 0.048) compared to compliant patients. Further, the body weight of noncompliant patients was markedly lower than in the compliant counterpart (p = 0.015). Conclusions: The tested treatment protocol showed limited compliance among routine cardiac-surgery patients, and further, introduced a biased selection of patients that skewed the results and may have partly explained the treatment effect. [source] Migraine-Related Vertigo: Diagnostic Criteria and Prophylactic TreatmentTHE LARYNGOSCOPE, Issue 10 2006Arturo Maione MD Abstract Objective/Hypothesis: The objective of this prospective, observational study was to evaluate the efficacy of migraine pharmacologic prophylaxis on a group of vertiginous patients considered affected by migraine-related vertigo on the basis of precise criteria of inclusion. Methods: Fifty-three patients affected by migraine-related vertigo were selected from a cohort of 652 vertiginous patients referred to our Dizziness Unit from March 2001 to June 2005. Inclusion criteria were at least five vertigo attacks occurred in any period of time or dizziness and/or positional vertigo for at least 6 months; migraine, past or present, and/or a family history of migraine and/or motion intolerance; and exclusion of other causes. Patients were submitted to migraine pharmacologic prophylaxis selected on the basis of the characteristics of the patients and of the drug side effects. The efficacy of the treatment was evaluated after 6 months by questionnaire divided into five outcome categories (resolution, substantial control, moderate control, minimal control, no improvement or worsening) and, for the patients with recurrent vertiginous attacks, also reporting the percentage reduction of the attack frequency. Results: Thirty-six patients completed the study and were submitted to analysis of the results: 10 reported complete resolution of symptoms, 15 substantial control, 7 moderate control, one minimum control and 3 no improvement. Thirty-three of them had recurrent vertigo: 19 reported complete disappearance of the attacks, 8 reduction of the frequency >50%, 5 reduction <50%, and one no reduction. Conclusions: Migraine prophylactic treatment shows encouraging results in patients with migraine-related vertigo selected with our criteria of inclusion: 69.3% reported satisfactory control of symptoms (sum of complete resolutions and substantial controls) and 81.8% had at least a 50% reduction of the vertiginous episodes frequency. [source] Enhancement of haemostatic efficacy of plasma-derived FVIII by formulation with PEGylated liposomesHAEMOPHILIA, Issue 5 2009I. DAYAN Summary., We have shown previously that PEGylated liposomes (PEGLip) bind recombinant FVIII (rFVIII) with high affinity and specificity. This binding resulted in a significant extension of the biological activity of rFVIII as demonstrated in animal models and in clinical trials. In the present study we found that PEGLip bind plasma-derived factor VIII (pdFVIII). PEGLip binding did not affect potency or stability in vitro and did not alter levels of FVIII activity in vivo immediately after injection. However, formulation of pdFVIII with PEGLip led to several important improvements. Twenty-four and 30 hours after injection, FVIII activity levels were significantly higher in haemophilic mice injected with PEGLip-pdFVIII than in mice injected with standard pdFVIII. Half life, area under the curve and mean residence time were increased while clearance was decreased. In vivo efficacy was evaluated in a tail vein transection assay performed in haemophilic mice. Prophylactic treatment with PEGLip-pdFVIII was much more effective in prolonging survival in this assay than similar treatment with standard pdFVIII. These results suggest that formulation of pdFVIII with PEGLip has the potential to improve patient care by prolonging the biological efficacy of pdFVIII and reducing the frequency of FVIII infusions. [source] European data of a clinical trial with a sucrose formulated recombinant factor VIII in previously treated haemophilia A patientsHAEMOPHILIA, Issue 2002C. Rothschild Summary., To increase the safety of antihaemophilic treatment, the production process of full-length recombinant factor VIII (FVIII) KOGENATE® Bayer (Kogenate®FS)has been modified. Human albumin is no longer added as stabilizer during purification and in final formulation. Instead, the new KOGENATE® Bayer production process uses sucrose as a stabilizer in the formulation and adds solvent/detergent virus inactivation step. An European clinical trial was carried out in Germany and France in previously treated patients with severe haemophilia A who had more than 100 exposure days to exogenous FVIII. Pharmacokinetic data was analysed according to one-stage and chromogenic assays. Efficacy and safety during home therapy and in surgical procedures were evaluated; inhibitor formation was carefully monitored. Safety and efficacy were evaluated in 33 European patients for 24 months. Patients received more than 13 million IU KOGENATE® Bayer. Over 75% of patients accrued more than 100 exposure days with the new product. Of 875 bleeding episodes, 90.7% were treated with 1 or 2 infusions and 75.8% of responses to treatment were rated as ,excellent' or ,good'. Prophylactic treatment was the most common mode of therapy (60.7% of infusions). The product was well-tolerated and FVIII recovery studies were consistent throughout the study period. Only 0.26% of adverse events were reported to be drug related. No evidence of de novo inhibitor formation was observed. Overall, KOGENATE® Bayer was efficacious, safe and well-tolerated for the treatment of haemophilia A in multitransfused patients. [source] Prophylactic treatment of severe factor X deficiency with prothrombin complex concentrateHAEMOPHILIA, Issue 2 2001P. A. Kouides Factor X (FX) deficiency is an autosomal recessive trait that occurs in fewer than 1 in 500 000 people. Not surprisingly, reports of prophylactic treatment for FX deficiency are exceedingly rare. We now report our experience of the use of prophylactic therapy in a FX-deficient patient. This 18-year-old African-American male presented at the age of 4½ years with an FX level < 1%. Treatment was on demand with prothrombin complex concentrates (PCCs) given at two times the dose per kilogram of body weight for factor IX. He experienced frequent epistaxis, soft tissue bleeding and joint bleeding. The development of a target joint (right ankle) prompted the initiation of prophylactic treatment in the beginning of 1998 to the present with 30 units kg,1 Profilnine twice per week via a home infusion programme. If breakthrough bleeding occurred, he was instructed to infuse another dose. He was instructed that Profilnine should not be infused in more than two doses in 24 h or on more than three consecutive days. A trough level drawn 48 h post-infusion showed an FX level of 30%. In the initial 12 months with prophylactic treatment, there was no breakthrough bleeding. Subsequently, with an additional 11 months of follow-up, he has reported one bleed. He rates his quality of life improved since starting prophylactic treatment. There have been no thrombotic events. Prophylaxis with PCC for FX deficiency with adequate education and follow-up can be performed capably in the home setting with a resultant decrease in the frequency of bleeding and attendant complications. [source] Neurological dysfunction in dogs following attenuation of congenital extrahepatic portosystemic shuntsJOURNAL OF SMALL ANIMAL PRACTICE, Issue 12 2000P. L. C. Tisdall Eleven of 89 dogs (12 per cent) developed neurological signs within six days of surgical attenuation of a congenital extrahepatic portosystemic shunt. Neurological signs were not associated with hepatic encephalopathy or hypoglycaemia. Signs varied in severity from non-progressive ataxia (three dogs) to generalised motor seizures (four dogs), progressing to status epilepticus (three dogs). In a further four cases, ataxia and disorientation were treated vigorously with anticonvulsant medication, presumably preventing the development of seizures. Two dogs that developed status epilepticus died or were eventually euthanased. All other animals survived, although some had persistent neurological deficits. Postligation neurological complications were not prevented by gradual shunt attenuation. Prophylactic treatment with phenobarbitone (5 to 10 mg/kg preoperatively, followed by 3 to 5 mg/kg every 12 hours for three weeks) did not significantly reduce the incidence of neurological sequelae (2/31 [6 per cent] dogs with phenobarbitone vs 9/58 [16 per cent] without phenobarbitone; P = 0.2). However, no animal receiving phenobarbitone experienced generalised motor seizures or status epilepticus. In conclusion, these observations suggest that postligation neurological syndrome comprises a spectrum of neurological signs of variable severity. Perioperative treatment with phenobarbitone may not reduce the risk of neurological sequelae, but may reduce their severity. [source] Prophylactic Bisphosphonate Treatment Prevents Bone Fractures After Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2007M. Bodingbauer A randomized controlled prospective open-label single center trial was performed. At the time of transplantation patients were randomly assigned to one of two treatment arms: The study group of 47 patients received zoledronic acid (ZOL, 8 infusions at 4 mg during the first 12 months after LT), calcium (1000 mg/d) and vitamin D (800 IE/d). The control group consisted of 49 patients who received calcium and vitamin D at same doses (CON). The incidence of bone fractures or death was predefined as the primary endpoint. Secondary endpoints included bone mineral density (BMD), serum biochemical markers of bone metabolism, parameters of trabecular bone histomorphometry and mineralization density distribution (BMDD). Patients were followed up for 24 months. Analysis was performed on an intention-to-treat basis. The primary endpoint fracture or death was reached in 26% of patients in the ZOL group and 46% in the CON group (p = 0.047, log rank test). Densitometry results were different between the groups at the femoral neck at 6 months after LT (mean+/-SD BMD ZOL: 0.80 ± 0.19 g/cm2 vs. CON: 0.73 ± 0.14 g/cm2, p = 0.036). Mixed linear models of biochemical bone markers showed less increase of osteocalcin in the ZOL group and histomorphometry and BMDD indicated a reduction in bone turnover. Prophylactic treatment with the bisphosphonate zoledronic acid reduces bone turnover and fractures after liver transplantation. [source] Tephrosia purpurea Ameliorates N-Diethylnitrosamine and Potassium Bromate-Mediated Renal Oxidative Stress and Toxicity in Wistar RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2001Naghma Khan 1999). The present study was designed to investigate a chemopreventive efficacy of T. purpurea against N-diethylnitrosamine-initiated and potassium bromate-mediated oxidative stress and toxicity in rat kidney. A single intraperitoneal dose of N-diethylnitrosamine (200 mg/kg body weight) one hr prior to the dose of KBrO3 (125 mg/kg body weight) increases microsomal lipid peroxidation and the activity of xanthine oxidase and decreases the activities of renal antioxidant enzymes viz., catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase, phase II metabolizing enzymes such as glutathione-S-transferase and quinone reductase and causes depletion in the level of renal glutathione content. A sharp increase in blood urea nitrogen and serum creatinine has also been observed. Prophylactic treatment of rats with T. purpurea at doses of 5 mg/kg body weight and 10 mg/kg body weight prevented N-diethylnitrosamine-initiated and KBrO3 promoted renal oxidative stress and toxicity. The susceptibility of renal microsomal membrane for iron ascorbate-induced lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.01). The depleted levels of glutathione, the inhibited activities of antioxidant enzymes, phase II metabolizing enzymes and the enhanced levels of serum creatinine and blood urea nitrogen were recovered to a significant level (P<0.01). All the antioxidant enzymes were recovered dose-dependently. Our data indicate that T. purpurea besides a skin antioxidant can be a potent chemopreventive agent against renal oxidative stress and carcinogenesis induced by N-diethylnitrosamine and KBrO3. [source] C1 inhibitor deficiency: consensus documentCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005M. M. Gompels Summary We present a consensus document on the diagnosis and management of C1 inhibitor deficiency, a syndrome characterized clinically by recurrent episodes of angio-oedema. In hereditary angio-oedema, a rare autosomal dominant condition, C1 inhibitor function is reduced due to impaired transcription or production of non-functional protein. The diagnosis is confirmed by the presence of a low serum C4 and absent or greatly reduced C1 inhibitor level or function. The condition can cause fatal laryngeal oedema and features indistinguishable from gastrointestinal tract obstruction. Attacks can be precipitated by trauma, infection and other stimulants. Treatment is graded according to response and the clinical site of swelling. Acute treatment for severe attack is by infusion of C1 inhibitor concentrate and for minor attack attenuated androgens and/or tranexamic acid. Prophylactic treatment is by attenuated androgens and/or tranexamic acid. There are a number of new products in trial, including genetically engineered C1 esterase inhibitor, kallikrein inhibitor and bradykinin B2 receptor antagonist. Individual sections provide special advice with respect to diagnosis, management (prophylaxis and emergency care), special situations (childhood, pregnancy, contraception, travel and dental care) and service specification. [source] GASTRIC FUNDIC VARICES: HEMODYNAMICS AND NON-SURGICAL TREATMENTDIGESTIVE ENDOSCOPY, Issue 3 2005Seishu Hayashi The hemodynamics and non-surgical treatment of gastric fundic varices (FV) are reviewed. FV are more frequently supplied by the short and posterior gastric veins than esophageal varices (EV), and are formed mostly by large spontaneous shunts in which the gastric or splenic vein is continuous with the left renal vein via the inferior phrenic veins and the suprarenal vein (so-called gastric-renal shunt). Concomitant collaterals such as EV, para-esophageal vein, and para-umbilical vein were also observed in nearly 60% of FV. Endoscopic injection sclerotherapy (EIS) with Histoacryl is thought to be the most approved treatment for hemorrhage from FV, but repeated treatment for residual FV and care for ensuing hepatic failure are required. Balloon-occluded retrograde transvenous obliteration (B-RTO) is a notable interventional radiological procedure specially developed for the elective or prophylactic treatment of FV. If the procedure is technically successful, long-term eradication of treated FV is found in most patients without recurrence. B-RTO includes another significance, obliteration of the unified portal-systemic shunt. Follow-up abdominal CT scan revealed a high incidence of long-term obliteration of the gastric-renal shunt after B-RTO. Benefits such as elevation of serum albumin, improvement in 15-min retention rate of indocyanine green, decrease in blood ammonia levels, and improvement of encephalopathy are sometimes observed. [source] Febrile Seizures: Treatment and PrognosisEPILEPSIA, Issue 1 2000Finn Ursin Knudsen Summary: Recent epidemiologic data indicate that the vast majority of children with febrile seizures have a normal long-term outcome. A precise knowledge of the short- and long-term outcome with or without treatment, and short- and long-term side effects is an important prerequisite for assessing the various treatment strategies. We focus on the impact of short-term or prophylactic treatment on the short- and long-term outcome of various types of febrile seizures. There is universal agreement that daily prophylaxis with antiepileptic agents should never be used routinely in simple febrile seizures, but only in highly selected cases, if at all. Intermittent diazepam (DZP) prophylaxis at times of fever may or may not reduce the recurrence rate, but it does not appear to improve the long-term outcome as compared with short-term seizure control. The treatment may be used to reduce the recurrence rate for a small arbitrarily defined group with multiple simple febrile seizures, complex febrile seizures, especially focal, prolonged or both, febrile status, and when parental anxiety is severe. However, there is no evidence that treatment of simple febrile seizures can prevent the rare cases of later epilepsy, and many children with complex febrile seizures have a benign long-term outcome, even without treatment. Many prefer a "wait and see" policy. An attractive alternative is to treat new febrile seizures with rectal DZP in solution at seizure onset, given by the parents at home to prevent febrile status. Newer, less well documented short-term strategies include nasal, oral, or rectal administration of other benzodiazepines. Short-term seizure control of febrile status and careful parental counseling are the two most important targets of treatment. [source] An evidence-based approach to equine parasite control: It ain't the 60s anymoreEQUINE VETERINARY EDUCATION, Issue 6 2010R. M. Kaplan Summary Most veterinarians continue to recommend anthelmintic treatment programmes for horses that derive from knowledge and concepts more than 40 years old. However, much has changed since these recommendations were first introduced and current approaches routinely fail to provide optimal or even adequate levels of parasite control. There are many reasons for this. Recent studies demonstrate that anthelmintic resistance in equine parasites is highly prevalent and multiple-drug resistance is common in some countries, but few veterinarians take this into account when making treatment decisions or when recommending rotation of anthelmintics. Furthermore, the current approach of treating all horses at frequent intervals was designed specifically to control the highly pathogenic large strongyle, Strongylus vulgaris. But this parasite is now quite uncommon in managed horses in most of the world. Presently, the cyathostomins (small strongyles) are the principal parasitic pathogens of mature horses. The biology and pathogenesis of cyathostomins and S. vulgaris are very different and therefore require an entirely different approach. Furthermore, it is known that parasites are highly over-dispersed in hosts, such that a small percentage of hosts harbour most of the parasites. The common practices of recommending the same treatment programme for all horses despite great differences in parasite burdens, recommending prophylactic treatment of all horses without indication of parasitic disease or knowing what species of parasites are infecting the horses, recommending use of drugs without knowledge of their efficacy and failing to perform diagnostic (faecal egg count) surveillance for estimating parasite burdens and determining treatment efficacy, are all incompatible with current standards of veterinary practice. Consequently, it is necessary that attitudes and approaches to parasite control in horses undergo a complete overhaul. This is best achieved by following an evidence-based approach that takes into account all of these issues and is based on science, not tradition. [source] Benzydamine for prophylaxis of radiation-induced oral mucositis in head and neck cancers: a double-blind placebo-controlled randomized clinical trialEUROPEAN JOURNAL OF CANCER CARE, Issue 2 2009A. KAZEMIAN md, assistant professor We evaluated the efficacy of benzydamine oral rinse for prevention of radiation-induced mucositis. Patients with head and neck cancers, who were referred in 2004,2005, received an oral rinse of either benzydamine or placebo. One hundred patients were randomized in this trial. At the end of the study, 19 patients were excluded from the analysis because they did not use the medication for the assigned period. In the benzydamine group, the frequency of mucositis grade ,3 was 43.6% in contrast to 78.6% in other group (P = 0.001). Grade ,3 mucositis was 2.6 times more frequent in the placebo group. Intensity of mucositis increased up to fourth week of treatment in both groups to grade 2. In the treated group the grade of mucositis was approximately constant to the end of therapy; but in the control group it raised to grade 3 (P < 0.001). The highest grade of mucositis during the treatment time was significantly different between two groups (P = 0.049). The median interval to observation of grade ,2 mucositis was 24 days in the placebo group and 28 days in the benzydamine group (P = 0.12). Benzydamine oral rinse seems to be effective, safe, and well tolerated for prophylactic treatment of radiation-induced oral mucositis in head and neck tumours. [source] The role of prophylaxis in bleeding disordersHAEMOPHILIA, Issue 2010E. 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] The benefits of prophylactic treatment with APCC in patients with haemophilia and high-titre inhibitors: a retrospective case seriesHAEMOPHILIA, Issue 3 2009L. A. VALENTINO Summary., Prophylactic infusion of factor concentrates is a safe, effective intervention for preventing arthropathy in patients with haemophilia; on-demand treatment is insufficient to prevent the orthopaedic complications and subsequent haemophilic arthropathy that stem from recurrent joint haemorrhages. The usefulness of prophylaxis in haemophilia patients without inhibitors suggests that patients with haemophilia and inhibitors could derive similar benefits. In patients with haemophilia and high-titre (>5 BU mL,1) inhibitors, bleeding episodes are treated with bypassing agents such as activated prothrombin complex concentrates (APCCs) and recombinant activated factor VII (rFVIIa, NovoSeven®; Novo Nordisk A/S, Bagsvaerd, Denmark). It is possible to administer bypassing therapy regularly to prevent haemorrhages, with the goal of limiting arthropathy and serious life- and limb-threatening bleeding. The data evaluating the efficacy and safety of this approach in patients with inhibitors are limited, consisting of results from one prospective trial and retrospective case reports. This report describes our experience with the prophylactic use of the APCC Factor Eight Inhibitor Bypassing Activity, Anti-Inhibitor Coagulant Complex, Vapor Heated (FEIBAÔ; Baxter AG, Vienna, Austria). Data from patients at one treatment centre were retrospectively evaluated. Case records of six patients with haemophilia A or B and high-titre inhibitors were identified. When APCC was administered regularly, most patients exhibited a reduction in the numbers of haemorrhages, an improvement in orthopaedic status, and an improvement in quality of life. Prophylaxis with APCC can reduce haemorrhages and halt further joint deterioration in patients with haemophilia and inhibitors. [source] Clinical safety surveillance study of the safety and efficacy of long-term home treatment with ReFacto® utilizing a computer-aided diary: a Nordic multicentre studyHAEMOPHILIA, Issue 1 2009P. PETRINI Summary., A Nordic multicentre, open-label, non-interventional postmarketing surveillance study was carried out during a period of 24 months evaluating safety and efficacy of ReFacto as prophylactic or on-demand replacement therapy in patients with haemophilia A treated by self-medication. Fifty-seven patients were enrolled and studied for safety; efficacy was evaluated in 39 patients who received ReFacto for 24 months and recorded sufficient diary data on a hand-held computer. The compliance of using the device was good in small children, variable in adults and poor in teenagers. The fact that the overall compliance was low constituted a limitation of the number of patients with reliable diary data. Overall safety was rated as excellent or good by the clinicians for all patients at all visits and overall efficacy at 24 months evaluated to be excellent (74%) or good (26%). It was noticed that ,50% of patients/parents reported no absences from school or work owing to bleeding episodes during the study period. Among patients on regular prophylaxis, 6 of the 30 patients (20%) receiving ReFacto experienced no bleeding episodes. A median of four bleeding episodes occurred during the 24-month study period, and 93% of the episodes were resolved with ,2 ReFacto infusions. In the 7 on-demand patients, there was a median of 18 bleeding episodes, 87% of which resolved with ,2 ReFacto infusions. Interestingly, 42% of the ReFacto infusions taken by the patients classified to the on-demand group were registered as prophylactic treatment. In conclusion, ReFacto demonstrated good safety and efficacy in prophylaxis as well as treatment of bleeding episodes. [source] Successful angiographic embolization of recurrent elbow and knee joint bleeds in seven patients with severe haemophiliaHAEMOPHILIA, Issue 1 2009R. KLAMROTH Summary., In haemophilic joints with high-grade arthropathy, bleeds occur that do not respond to replacement therapy of the deficient coagulation factor. The reason may be pathologically reactive angiogenesis in chronic synovitis. Seven patients with severe haemophilia A or haemophilia B experienced recurrent massive bleeds of one elbow joint or knee joint in the absence of trauma. After initial application of factor VIII or IX (fVIII/fIX; 50 IU kg,1 bodyweight), there was only slow and never complete relief of symptoms. Despite intensive secondary prophylaxis maintaining the plasma level of factor concentrate at minimum 50%, new massive bleeds at the same location occurred. Vascular bleeding was suspected. Angiography of the arteries was performed via the femoral artery. Vessels identified as potential bleeding sources were embolized with embolization fluid (ONYX) in eight joints (six elbow and two knee joints). Under low-dose prophylactic treatment (15 IU fVIII or fIX per kg bodyweight for three times per week), no recurrent severe bleed unresponsive to coagulation factor replacement occurred after a mean observation time of 16 months after embolization. The consumption of factor concentrate decreased to one-third of the amount consumed before embolization. In conclusion, angiographic embolization with a non-adhesive liquid embolic agent might be considered as a promising therapeutic and coagulation factor saving option in joint bleeds not responding to replacement of coagulation factor to normal levels. [source] Reformulated BeneFix®: efficacy and safety in previously treated patients with moderately severe to severe haemophilia BHAEMOPHILIA, Issue 3 2007T. LAMBERT Summary. BeneFix®, the only recombinant factor IX (FIX), has been reformulated. The reformulation involves a change in diluent and allows for more concentrated infusions of recombinant FIX. A double-blind, randomized, pharmacokinetic (PK) crossover study demonstrated that reformulated BeneFix was bioequivalent to original BeneFix and follow-up PK evaluation after 6 months of treatment demonstrated the PK stability of reformulated BeneFix after multiple exposures. Favourable efficacy and safety profiles, consistent with those already well-established for original BeneFix, were observed: 81.1% of haemorrhages resolved with only a single infusion; 85.3% of initial treatment response ratings were Excellent or Good; more than half of the subjects using reformulated BeneFix for routine prophylaxis (11 of 17, 64.7%) had no spontaneous haemorrhages during their 6,12 month course of prophylactic treatment, with an overall spontaneous bleeding rate of 0.72 year,1; and for the single surgical procedure (knee washing), treatment was rated Useful. In addition, there was no FIX inhibitor development, allergic-type manifestations, or thrombogenic complications with more than 1100 infusions (nearly 5.2 million IUs) administered in this trial. All efficacy and safety outcomes from this study were achieved with more concentrated recombinant protein infusions than that possible with original BeneFix, and utilization of the 2000 IU per vial dosage strength, newly introduced with the reformulated product, was high (>62%). The reformulation of BeneFix allows smaller delivery volumes and an increased choice of dosage strengths without altering the PK properties (including incremental recovery and half-life) or the established efficacy and safety profile of recombinant FIX. [source] Variability in clinical phenotype of severe haemophilia: the role of the first joint bleedHAEMOPHILIA, Issue 5 2005K. van Dijk Summary., To quantify variation in clinical phenotype of severe haemophilia we performed a single centre cohort study among 171 severe haemophilia patients. Age at first joint bleed, treatment requirement (i.e. annual clotting factor use), annual bleeding frequency and arthropathy were documented. Because treatment strategies intensified during follow-up, patients were stratified in two age groups: patients born 1968,1985 (n = 91), or 1985,2002 (n = 80). A total of 2166 patient-years of follow-up were available (median 12.0 years per patient). Age at first joint bleed ranged from 0.2 to 5.8 years. Patients who had their first joint bleed later needed less treatment and developed less arthropathy. In patients born 1968,1985 during both on-demand and prophylactic treatment, the 75th percentile of annual joint bleed frequency was consistently four times as high as the 25th percentile. In both age groups variation in annual clotting factor use between 25th and 75th percentiles was 1.4,1.5 times for prophylaxis and 3.8 times for on-demand treatment. To conclude, the onset of joint bleeding is inversely related with treatment requirement and arthropathy and may serve as an indicator of clinical phenotype. Thus, providing a starting point for aetiological research and individualization of treatment. [source] A 6-year follow-up of dosing, coagulation factor levels and bleedings in relation to joint status in the prophylactic treatment of haemophiliaHAEMOPHILIA, Issue 6 2004J. Ahnström Summary., The primary aim of this study was to investigate the possible relationship between coagulation factor level and bleeding frequency during prophylactic treatment of haemophilia after stratification of the patients according to joint scores. The secondary aim was to obtain a systematic overview of the doses of coagulation factors prescribed for prophylaxis at the Malmö haemophilia treatment centre during a 6-year period. A retrospective survey of medical records for the years 1997,2002 and pharmacokinetic study results from the 1990s was complemented by collection of blood samples for coagulation factor assay when needed. Information on the dosing and plasma levels of factor VIII or factor IX, joint scores and incidence of bleedings (joint bleeds and ,other bleeds') was compiled. The patients were stratified by age (0,6, 7,12, 13,18, 19,36 and >36 years) and joint score (0, 1,6 and >6). Individual pharmacokinetic parameters of plasma coagulation factor activities (FVIII:C and FIX:C) were estimated. Trough levels during the treatment were calculated, as well as the number of hours per week of treatment during which plasma FVIII:C/FIX:C fell below a 1, 2 or 3% target level. Fifty-one patients with haemophilia A (two moderate, 49 severe) and 13 with haemophilia B (all severe) were included, yielding data for 364 patient-years of treatment. There was a wide range of dosing schedules, the most common ones being three times a week or every other day for FVIII and twice a week or every third day for FIX. The overall relationship between FVIII:C/FIX:C levels and incidence of joint bleeding was very weak, even after stratification of the patients according to joint score. There was no relationship between coagulation factor level and incidence of other bleeds. In this cohort of patients on high-dose prophylactic treatment, dosing was based more on clinical outcome in terms of bleeding frequency than on the aim to maintain a 1% target level of FVIII:C/FIX:C. Some patients did not bleed in spite of a trough level of <1% and others did in spite of trough levels >3%. The practical implication of our findings is that dosing in prophylactic treatment of haemophilia should be individualized. Thus, proposed standard regimens should be implemented only after careful clinical consideration, with a high readiness for re-assessment and individual dose tailoring. [source] Clinical and radiographic scores in haemophilic arthropathies: how well do these correlate to subjective pain status and daily activities?HAEMOPHILIA, Issue 6 2002T. Wallny Summary. Haemophilic patients who reached adulthood before the establishment of prophylactic treatment frequently show multiple and substantial arthropathies. The aim of this study was to determine to what extent haemophiliac's subjective impairment due to arthropathies correlates with objective clinical and radiographic parameters. By means of a questionnaire and a visual analogue scale, we consulted 79 haemophiliacs concerning their joint-pain status, how these were treated and to what extent their daily activities had been affected. Using a scoring system suggested by the Advisory Committee of the World Federation of Haemophilia, clinical evaluation was performed. Radiographs of 60 patients were assessed by means of the Petterson scale. The results were statistically compared. We found a significant correlation between pain intensity and clinical pathology as well as between pain intensity and radiographic joint damage for both knees and for the right ankle. The number of painful joints correlated well with the number of clinically/radiographically affected joints. The more pronounced the objective damage to joints, the more frequently patients claimed to have constant pain, depressive episodes and a dependency on pain-relieving medication. The more pronounced the objectively assessed damage to the knee and ankle joint, the higher the likelihood that the patient suffers from severe joint pain and reduction of activity. Treatment of painful symptoms from arthropathies is often insufficient. Scores and questionnaires may help to define the haemophiliacs pain status more clearly, thereby offering a possibility of assessment and long-term observation. [source] Experience of prophylaxis treatment in children with severe haemophiliaHAEMOPHILIA, Issue 2 2002T. 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] Discontinuation of prophylactic therapy in severe haemophilia: incidence and effects on outcomeHAEMOPHILIA, Issue 6 2001K. Fischer A cohort study was performed to assess adherence to early prophylactic therapy and its effects on outcome in 49 patients with severe haemophilia born 1970,1980. Median age at start of prophylaxis was 5.5 years. The majority (69%) of patients interrupted prophylactic treatment one or more times of their own accord (median total interruption 2.2 years). Patients who discontinued prophylaxis at any point tended to have more arthropathy as measured by the Pettersson scale (median 8 points versus 4 points). One-third of these patients interrupted prophylaxis for longer periods and had permanently stopped taking prophylaxis at a mean age of 20.1 years (mean ± SD duration 4.1 ± 4 years) and consequently experienced 5.4 ± 3.4) joint bleeds per year. This subgroup could be identified by a predictive score based on age at start of prophylaxis, weekly dose of prophylaxis, and joint bleed frequency on prophylaxis. In conclusion, while on prophylaxis, more than two-thirds of patients with severe haemophilia try to discontinue treatment, resulting in slightly more arthropathy. One-third of these patients permanently discontinue prophylaxis in adulthood, while maintaining a low number of joint bleeds. [source] Bacterial endocarditis in a child with haemophilia B: risks of central venous cathetersHAEMOPHILIA, Issue 5 2001D. K. Hothi The use of central venous catheters may be complicated by thrombosis and infection. We report a case of a needle-phobic 5-year-old boy with factor IX deficiency, in whom a portacath was inserted owing to poor compliance with prophylactic treatment. Within a week, he developed a Staphylococcus aureus line infection that was treated with a 2-week course of intravenous antibiotics. One month later he presented with nonspecific symptoms and blood cultures again grew S. aureus. An echocardiogram revealed a large vegetation adherent to the tricuspid valve, confirming the diagnosis of bacterial endocarditis. His clinical course was further complicated by the development of pulmonary emboli. Medical treatment with intravenous antibiotics led to a successful resolution of the endocarditis and pulmonary emboli with a favourable long-term outcome. [source] Prophylactic treatment of severe factor X deficiency with prothrombin complex concentrateHAEMOPHILIA, Issue 2 2001P. A. Kouides Factor X (FX) deficiency is an autosomal recessive trait that occurs in fewer than 1 in 500 000 people. Not surprisingly, reports of prophylactic treatment for FX deficiency are exceedingly rare. We now report our experience of the use of prophylactic therapy in a FX-deficient patient. This 18-year-old African-American male presented at the age of 4½ years with an FX level < 1%. Treatment was on demand with prothrombin complex concentrates (PCCs) given at two times the dose per kilogram of body weight for factor IX. He experienced frequent epistaxis, soft tissue bleeding and joint bleeding. The development of a target joint (right ankle) prompted the initiation of prophylactic treatment in the beginning of 1998 to the present with 30 units kg,1 Profilnine twice per week via a home infusion programme. If breakthrough bleeding occurred, he was instructed to infuse another dose. He was instructed that Profilnine should not be infused in more than two doses in 24 h or on more than three consecutive days. A trough level drawn 48 h post-infusion showed an FX level of 30%. In the initial 12 months with prophylactic treatment, there was no breakthrough bleeding. Subsequently, with an additional 11 months of follow-up, he has reported one bleed. He rates his quality of life improved since starting prophylactic treatment. There have been no thrombotic events. Prophylaxis with PCC for FX deficiency with adequate education and follow-up can be performed capably in the home setting with a resultant decrease in the frequency of bleeding and attendant complications. [source] Elective treatment of the neck in squamous cell carcinoma of the larynx: Clinical experienceHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2003Giuseppe Spriano MD Abstract Background. In head and neck cancer, the best prophylactic treatment for the N0 neck is a subject of debate. Some authors propose lateral selective lymph node dissection (levels II,IV) on the basis of the probability of finding occult metastases in those lymph nodes. A more extensive procedure including Vth level is considered unnecessary because of the low incidence of metastases in the posterior triangle. Methods. We retrospectively evaluated 346 N0 patients affected by laryngeal carcinoma and consecutively treated at the Department of Otorhinolaryngology of the Ospedale di Circolo, Varese, Italy. The patients underwent elective selective neck dissection (levels II,V) for a total of 602 dissected heminecks. Result. Seventy heminecks (11.6%) were pN+, and in 10 of 70 cases (14.3%) level V was involved; in 5 of 10 metastases were isolated. Conclusion. Our retrospective study confirms the probabilistic criteria of the incidence of occult metastasis by level in laryngeal cancer. On the basis of our data Vth level nodes, although very rarely, 10 of 604 (1.6%), are involved with laryngeal cancer. Our approach to routinely dissect Vth level nodes is discussed. © 2003 Wiley Periodicals, Inc. Head Neck 25: 97,102, 2003 [source] A Double-Blind Comparison of OnabotulinumtoxinA (BOTOX®) and Topiramate (TOPAMAX®) for the Prophylactic Treatment of Chronic Migraine: A Pilot StudyHEADACHE, Issue 10 2009Ninan T. Mathew MD Background., There is a need for effective prophylactic therapy for chronic migraine (CM) that has minimal side effects. Objective., To compare the efficacy and safety of onabotulinumtoxinA (BOTOX®, Allergan, Inc., Irvine, CA) and topiramate (TOPAMAX®, Ortho-McNeil, Titusville, NJ) prophylactic treatment in patients with CM. Methods., In this single-center, double-blind trial, patients with CM received either onabotulinumtoxinA, maximum 200 units (U) at baseline and month 3 (100 U fixed-site and 100 U follow-the-pain), plus an oral placebo, or topiramate, 4-week titration to 100 mg/day with option for additional 4-week titration to 200 mg/day, plus placebo saline injections. OnabotulinumtoxinA or placebo saline injection was administered at baseline and month 3 only, while topiramate oral treatment or oral placebo was continued through the end of the study. The primary endpoint was treatment responder rate assessed using Physician Global Assessment 9-point scale (+4 = clearance of signs and symptoms and ,4 = very marked worsening [about 100% worse]). Secondary endpoints included the change from baseline in the number of headache (HA)/migraine days per month (HA diary), and HA disability measured using Headache Impact Test (HIT-6), HA diary, Migraine Disability Assessment (MIDAS) questionnaire, and Migraine Impact Questionnaire (MIQ). The overall study duration was approximately 10.5 months, which included a 4-week screening period and a 2-week optional final safety visit. Follow-up visits for assessments occurred at months 1, 3, 6, and 9. Adverse events (AEs) were documented. Results., Of 60 patients randomized to treatment (mean age, 36.8 ± 10.3 years; 90% female), 36 completed the study at the end of the 9 months of active treatment (onabotulinumtoxinA, 19/30 [63.3%]; topiramate, 17/30 [56.7%]). In the topiramate group, 7/29 (24.1%) discontinued study because of treatment-related AEs vs 2/26 (7.7%) in the onabotulinumtoxinA group. Between 68% and 83% of patients for both onabotulinumtoxinA and topiramate groups reported at least a slight (25%) improvement in migraine; response to treatment was assessed using Physician Global Assessment at months 1, 3, 6, and 9. Most patients in both groups reported moderate to marked improvements at all time points. No significant between-group differences were observed, except for marked improvement at month 9 (onabotulinumtoxinA, 27.3% vs topiramate, 60.9%, P = .0234, chi-square). In both groups, HA/migraine days decreased and MIDAS and HIT-6 scores improved. Patient-reported quality of life measures assessed using MIQ after treatment with onabotulinumtoxinA paralleled those seen after treatment with topiramate in most respects. At month 9, 40.9% and 42.9% of patients in the onabotulinumtoxinA and topiramate groups, respectively, reported ,50% reduction in HA/migraine days. Forty-one treatment-related AEs were reported in 18 onabotulinumtoxinA-treated patients vs 87 in 25 topiramate-treated patients, and 2.7% of patients in the onabotulinumtoxinA group and 24.1% of patients in the topiramate group reported AEs that required permanent discontinuation of study treatment. Conclusions., OnabotulinumtoxinA and topiramate demonstrated similar efficacy in the prophylactic treatment of CM. Patients receiving onabotulinumtoxinA had fewer AEs and discontinuations. [source] How Children and Parents Evaluate the Headache Centre's InterventionHEADACHE, Issue 2 2009Anna Ferrari MD Background., While adult headache patients' satisfaction with treatments has been widely investigated, less attention has been paid to children and adolescent headache patients' opinions and their parents' views. Objective., The aim of our follow-up survey was to analyze the outcomes of the Headache Centre's intervention and the evolution of headache according to patients until the age of 16 and their parents. Methods., We studied all outpatients suffering from episodic primary headache according to International Classification of Headache Disorders 2nd edition criteria, seen for the first time in 2005-2006 at the Headache Centre of the University Hospital of Modena (Italy), and at least one of their parents. The duration of the follow-up ranged from 1 to 3 years. For the purpose of the study, a specific questionnaire was created and administered by a telephone interview. Results., We enrolled 84 patients (38 females, 45%; 46 males, 55%; mean age ± SD: 12.9 ± 2.9 years) with primary headache: migraine without aura 66%, episodic tension-type headache 23%, migraine with aura 11%. At the follow-up, 70% of the patients reported that headache had improved; frequency had decreased significantly more than severity (P = .000, Fisher's exact test), both in those who had followed a prophylactic treatment and in those who had not. A high percentage of the children and parents could precisely indicate trigger factors for headache: especially excessive worrying and studying. The patients reporting an improvement attributed it to pharmacological prophylactic treatment, but also to other factors: first of all, better school results and more happiness than before. Seventy-seven percent of the parents thought that the Headache Centre's intervention had helped them to better understand and manage their children's headache. Conclusions., Children's and adolescents' headache has in most cases a favorable prognosis; the Headache Centre's intervention is considered effective by most parents. We must increase and focus therapeutic efforts addressed to the few patients with worsening headaches in spite of treatment, since these children's/adolescents' headache also is at risk to progress in the adult age. [source] | ||||||||||||||||||||||||||||||||||