Value assignment of the WHO 2nd International Standard von Willebrand factor,concentrate (09/182)

To cite this article: Hubbard AR, Hamill M, Beeharry M, Bevan SA, Heath AB, on behalf of the SSC sub‐committee on von Willebrand factor of ISTH. Value assignment of the WHO 2nd International Standard von Willebrand factor, concentrate (09/182). J Thromb Haemost 2011; 9 : 1638–40.DOI: 10.1111/j.1538‐7836.2011.04365.x .     

A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study)

Summary. Background: Prevention of arthropathy is a major goal of hemophilia treatment. While studies in adults have demonstrated an impact of prophylaxis on the incidence of joint bleeds and patients’ well‐being in terms of improved quality of life (QoL), it is unclear whether or not prophylaxis influences the outcome and perception of well‐ of children with hemophilia. Objective: This randomized controlled study compared the efficacy of prophylaxis with episodic therapy in preventing hemarthroses and image‐proven joint damage in children with severe hemophilia A (factor VIII <1%) over a 10‐year time period. Methods: Forty‐five children with severe hemophilia A, aged 1–7 years (median 4), with negative clinical‐radiologic joint score at entry and at least one bleed during the previous 6 months, were consecutively randomized to prophylaxis with recombinant factor VIII (25 IU kg^?1 3 × week) or episodic therapy with ≥25 IU kg^?1 every 12–24 h until complete clinical bleeding resolution. Safety, feasibility, direct costs and QoL were also evaluated. Results: Twenty‐one children were assigned to prophylaxis, 19 to episodic treatment. Children on prophylaxis had fewer hemarthroses than children on episodic therapy: 0.20 vs. 0.52 events per patient per month (P < 0.02). Plain‐film radiology showed signs of arthropathy in six patients on prophylaxis (29%) vs. 14 on episodic treatment (74%) (P < 0.05). Prophylaxis was more effective when started early (≤36 months), with patients having fewer joint bleeds (0.12 joint bleeds per patient per month) and no radiologic signs of arthropathy. Conclusion: This randomized trial confirms the efficacy of prophylaxis in preventing bleeds and arthropathy in children with hemophilia, particularly when it is initiated early in life.     

Prophylaxis therapy in haemophilia A: current situation in Spain

Summary. The Spanish Epidemiological Study in Haemophilia carried out in 2006 enrolled 2400 patients [2081–86.7% with haemophilia A (HA) and 319–13.3% with haemophilia B]; 465 of them (19.4%) were on prophylaxis. These rates were higher in patients with severe haemophilia (45.4%) and severe paediatric cases (72.5%). On the basis of information recorded in this study, we analysed the current situation of prophylaxis therapy administered to patients with HA in Spain, as well as their orthopaedic status. Prophylaxis was used in 399 (19.2%) patients with HA; such prophylaxis was primary (PP) in 20.3% and secondary (SP) in 75.9% of cases. Among severe HA patients, 313 (45.9%) were on prophylaxis (22.3% on PP and 74.7% on SP). Taking into account the patients’ age, 34.7% of severe HA adults were on prophylaxis (6% PP and 92.1% SP), whereas 71.5% of severe HA paediatric patients (40.5% PP and 55.4% SP) received this kind of treatment. Established haemophilic arthropathy (EHA) was detected in 142 from 313 severe HA patients (45.3%) on prophylaxis, but only in 2.9% of patients under PP vs. 59% of patients receiving SP. There was no EHA in adult severe HA patient on PP, whereas 70.4% on SP had joint damage (P < 0.00001). Among paediatric severe HA patients, EHA was detected in 3.3% under PP and 37.8% under SP (P < 0.00001). In conclusion, our data suggest that an early initiation of prophylaxis avoids EHA in the long‐term in patients with severe HA. We should emphasize the early onset of prophylaxis regimens.     

Survival of cervical cancer patients in Germany in the early 21st century: A period analysis by age, histology, and stage

Abstract Purpose. Population-based studies on cervical cancer providing survival estimates by age, histology, and stage have been sparse. We aimed to derive most up-to-date and detailed survival estimates for cervical cancer patients in Germany. Methods. We used a pooled German national dataset including data from 11 cancer registries covering a population of 33 million people. Included were 15 685 patients diagnosed with cervical cancer from 1997 to 2006. Period analysis was performed to calculate the five-year relative survival (RS) 2002-2006. Trends in survival between 2002 and 2006 were examined using model-based period analysis. Age-adjustment was done using five age groups (15-44, 45-54, 55-64, 65-74, and 75 + years). Results. Overall, age-adjusted five-year relative survival in 2002-2006 was 64.7%. A strong age gradient was observed, with five-year RS decreasing from 81.7% in age group 15-49 years to 46.3% in age group 70 + years. Prognosis furthermore strongly varied by stage, with age-adjusted five-year RS reaching 84.6% for localized, 48.2% for regional, and 17.9% for distant stage. From 2002 to 2006, a significant improvement (4.7 percent units) in overall age-adjusted five-year RS was seen. The improvement was most pronounced for age groups 55-64 years (from 54.2 to 65.6%) and 65-74 years (from 50.0 to 58.1%). Conclusion. In this first comprehensive population-based study from Germany, prognosis of cervical cancer strongly varied by age and stage. Prognosis continued to improve, in particular in age range 55-74 years, in the five-year period assessed.     

New Cochrane Systematic Reviews – Cochrane Oral Health Group

ENAMEL MATRIX DERIVATIVE (EMDOGAIN®) FOR PERIODONTAL TISSUE REGENERATION IN INTRABONY DEFECTS (Cochrane Review). In: THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS, ISSUE 4, 2005.Esposito M, Grusovin MG, Coulthard P, Worthington H

Background

Periodontitis is a chronic infective disease of the gums caused by bacteria present in dental plaque. This condition induces the breakdown of the tooth-supporting apparatus until teeth are lost. Surgery may be indicated to arrest disease progression and regenerate lost tissues. Several surgical techniques have been developed to regenerate periodontal tissues including guided tissue regeneration (GTR), bone grafting (BG), and the use of enamel matrix derivative (EMD). EMD is an extract of enamel matrix and contains amelogenins of various molecular weights. Amelogenins are involved in the formation of enamel and periodontal attachment formation during tooth development.

Objectives

The objectives were to test whether EMD is effective, and to compare EMD versus GTR and various BG procedures for the treatment of intrabony defects.

Search strategy

We searched the Cochrane OHG Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. Several journals were hand searched. No language restrictions were applied. Authors of randomized controlled clinical trials (RCTs) who were identified, personal contacts, and the manufacturer were contacted to identify unpublished trials. The most recent search was May 2005.

Selection criteria

Selected studies were RCTs on patients affected by periodontitis having intrabony defects of at least 3 mm treated with EMD compared with open flap debridement, GTR, and various BG procedures with at least 1 year of follow-up. The outcome measures considered were tooth loss, changes in probing attachment levels (PAL), pocket depths (PPD), gingival recessions (REC), bone levels from the bottom of the defects on intraoral radiographs, esthetics, and adverse events. The following time points were to be evaluated: 1, 5, and 10 years.

Data collection & analysis

Screening of eligible studies, assessment of the methodological quality of the trials, and data extraction were conducted in duplicate and independently by 2 authors. Results were expressed as random-effects models using mean differences for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI). It was decided not to investigate heterogeneity, but a sensitivity analysis for the risk of bias of the trials was performed.

Main results

Ten trials were included out of 29 potentially eligible trials. No included trial presented data after 5 years of follow-up, therefore all data refer to the 1-year time point. A meta-analysis including 8 trials showed that EMD-treated sites displayed statistically significant PAL improvements (mean difference 1.2 mm, 95% CI 0.7 to 1.7) and PPD reduction (0.8 mm, 95% CI 0.5 to 1.0) when compared to placebo or control treated sites, although a high degree of heterogeneity was found. Significantly more sites had less than 2 mm PAL gain in the control group, with RR 0.48 (95% CI 0.29 to 0.80). Approximately 6 patients needed to be treated (NNT) to have 1 patient gaining 2 mm or more PAL over the control group, based on a prevalence in the control group of 35%. No differences in tooth loss or esthetic appearance as judged by the patients were observed. When evaluating the only 2 trials at a low risk of bias in a sensitivity analysis, the effect size for PAL was 0.6 mm, which was less than 1.2 mm for the overall result. Comparing EMD with GTR (5 trials), GTR showed a statistically significant increase of REC (0.4 mm) and significantly more postoperative complications. No trials were found comparing EMD with BG.

Reviewers' conclusions

One year after its application, EMD significantly improved PAL levels (1.2 mm) and PPD reduction (0.8 mm) when compared to a placebo or control, however, the high degree of heterogeneity observed among trials suggests that results have to be interpreted with great caution. In addition, a sensitivity analysis indicated that the overall treatment effect might be overestimated. The actual clinical advantages of using EMD are unknown. With the exception of significantly more postoperative complications in the GTR group, there was no evidence of clinically important differences between GTR and EMD.

Abstract

INTERVENTIONS FOR REPLACING MISSING TEETH: DENTAL IMPLANTS IN ZYGOMATIC BONE FOR THE REHABILITATION OF THE SEVERELY DEFICIENT EDENTULOUS MAXILLA (Cochrane Review). In: THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS, ISSUE 4, 2005.Esposito M, Worthington HV, Coulthard P

Background

Dental implants are used for replacing missing teeth. Placing dental implants is limited by the presence of adequate bone volume permitting their anchorage. Several bone-augmentation procedures have been developed to solve this problem. Zygomatic implants are long screw-shaped implants developed as a partial or complete alternative to bone augmentation procedures for the severely atrophic maxilla. One to 3 zygomatic implants can be inserted through the posterior alveolar crest and maxillary sinus to engage the body of the zygomatic bone. A couple of conventional dental implants are also needed in the frontal region of the maxilla to stabilize the prosthesis. The potential main advantages of zygomatic implants could be that in some situations bone grafting may not be needed and a fixed denture could be fitted sooner. Another specific indication for using zygomatic implants could be the need for maxillary reconstruction after maxillectomy in cancer patients.

Objectives

The objective was to test the hypothesis of no difference in outcomes between zygomatic implants with and without bone-augmenting procedures in comparison with conventional dental implants in augmented bone for severely resorbed maxillae.

Search strategy

We searched the Cochrane Oral Health Group's Trial Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE. We hand searched several dental journals. No language restrictions were applied. Personal contacts and all known zygomatic implant manufacturers were contacted to identify unpublished trials. The most recent search was May 2005.

Selection criteria

Studies selected were randomized controlled clinical trials (RCTs) that included patients with severely resorbed maxillae who could not be rehabilitated with conventional dental implants and were treated with zygomatic implants with and without bone grafts versus patients treated with conventional dental implants in conjunction with bone-augmentation procedures having a follow-up of at least 1 year. Outcome measures considered were prosthesis and implant failures, side effects, patient satisfaction, and cost-effectiveness.

Data collection & analysis

Screening of eligible studies, assessment of the methodological quality of trials, and data extraction were to be conducted in duplicate and independently by 2 authors. Results were to be expressed as random-effects models using weighted mean differences for continuous outcomes and risk ratio for dichotomous outcomes with 95% confidence intervals. Heterogeneity was to be investigated including both clinical and methodological factors.

Main results

No RCTs or controlled clinical trials (CCTs) were identified.

Reviewers' conclusions

There is the need for RCTs in this area to assess whether zygomatic implants offer some advantages over alternative bone-augmentation techniques for treating atrophic maxillae.     

Treatment of psoriasis with fumaric acid esters: results of a prospective multicentre study

Systemic treatment of psoriasis with fumaric acid esters (FAE) has been found effective by empirical means. In recent years clinical studies have confirmed the antipsoriatic activity of a defined mixture of different FAE. The aim of the present prospective multicentre study was to investigate further the efficacy and safety of FAE therapy in a large number of patients with severe psoriasis vulgaris. From 101 patients included in the study 70 completed the treatment period of 4 months. Discontinuation was due to adverse events in seven, lack of efficacy in two, and other reasons, such as non-attendance for scheduled visits, in 22 patients. Evaluation of overall efficacy showed a decrease in psoriasis area and severity index of 80% after 4 months of FAE therapy. Laboratory investigations revealed a slight overall decrease of lymphocytes during the treatment period which was more than 50% below baseline in 10 patients. During weeks 4 and 8 mean eosinophil counts were above the normal range. At the end of FAE therapy elevated eosinophil counts had returned to normal values. None of the patients showed changes in renal function parameters throughout the study. Adverse events were reported in 69% of the patients mainly consisting of gastrointestinal complaints (56%) and flushing (31%). In five patients gastrointestinal complaints and in two patients flushing led to withdrawal from the study. Taken together the results of this multicentre study showed in a large number of patients that systemic FAE treatment is effective in severe psoriasis vulgaris. Transient eosinophilia seems to be a characteristic feature of FAE therapy, while lymphocytopenia is usually mild. Adverse effects are dose-related and consist mainly of gastrointestinal complaints and flushing.     

Low‐molecular‐weight heparin added to aspirin in the prevention of recurrent early‐onset pre‐eclampsia in women with inheritable thrombophilia: the FRUIT‐RCT: a reply to a rebuttal

See also Bujold E, Gouin K, Cote S.Low‐molecular‐weight heparin added to aspirin in the prevention of recurrent early‐onset pre‐eclampsia in women with inheritable thrombophilia: the FRUIT‐RCT: a rebuttal. This issue, pp 1195; de Vries JIP, van Pampus MG, Hague WM, Bezemer PD, Joosten JH, on behalf of FRUIT Investigators. Low‐molecular‐weight heparin added to aspirin in the prevention of recurrent early‐onset pre‐eclampsia in women with inheritable thrombophilia: the FRUIT‐RCT. J Thromb Haemost 2012; 10 : 64–72.