The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate

This study was designed to investigate a long-term therapeutic strategy for the management of recurring atopic dermatitis (AD) in adults using fluticasone propionate (FP) ointment (Cutivate^TM) whereby FP could help to prevent a relapse of AD once symptoms were under control. Adult patients with chronic, moderate to severe AD entered this multicentre study. All patients were initially treated with FP 0.005% (g/g) ointment in two different regimens. Patients whose AD had been completely healed by these treatments then entered a long-term treatment phase applying FP or placebo ointment once daily, two times per week for 16 weeks to 'known' healed lesions. By the end of the initial treatment period, mean SCORAD values had significantly ( P  < 0.0005) improved from baseline. Patients who entered the maintenance phase and were treated with intermittent FP for up to 16 weeks, demonstrated its superior efficacy ( P  = 0.018) over placebo, maintaining the improvements achieved after the initial treatment phase, reducing risk of relapse and delaying time to relapse ( P  = 0.013). No significant changes were detected in either treatment group in serum cortisol levels or in skin thickness measurements. Intermittent FP applied two times per week maintained a significant level of control, and delayed relapse of AD by comparison with placebo.     

Endometrial cancer: accuracy of the finding of a well differentiated tumor at dilatation and curettage compared to the findings at subsequent hysterectomy

Abstract. Obermair A, Geramou M, Gücer F, Denison U, Graf AH, Kapshammer E, Medl M, Rosen A, Wierrani F, Neunteufel W, Frech I, Speiser P, Kainz C, Breitenecker G, Austrian Gynecologic Oncology Group. Endometrial cancer: accuracy of the finding of a well differentiated tumor at dilatation and curretage compared to the findings at subsequent hysterectomy.
The objective of this study was to examine the accuracy of the finding of a histologically well differentiated endometrial carcinoma at dilatation and curettage (D & C) prior to hysterectomy. A retrospective multicentric chart review of 137 endometrial cancer patients was conducted, including all patients in whom a well differentiated endometrial carcinoma had been diagnosed by D & C. Histopathologic grading as determined by D & C was compared with the grading established at the final histologic examination after hysterectomy. Seventy-eight percent of all cases in which a well differentiated tumor was diagnosed with D & C were confirmed as well differentiated endometrial carcinomas, whereas 20.4% had to be upgraded as moderately differentiated tumors after evaluation of the hysterectomy specimen. In one case in which a uterine adenocarcinoma was diagnosed by D & C, a well differentiated adenocarcinoma was found to be combined with a carcinosarcoma in the hysterectomy specimen. In order to avoid false findings of a well differentiated tumor, the histologic grade should be confirmed by intraoperative frozen section examination. This is especially important in cases in which surgical staging was not planned initially.     

The prothrombin time/international normalized ratio (PT/INR) Line: derivation of local INR with commercial thromboplastins and coagulometers – two independent studies

Summary. Background: The WHO scheme for prothrombin time (PT) standardization has been limited in application, because of its difficulties in implementation, particularly the need for mandatory manual PT testing and for local provision of thromboplastin international reference preparations (IRP). Methods: The value of a new simpler procedure to derive international normalized ratio (INR), the PT/INR Line, based on only five European Concerted Action on Anticoagulation (ECAA) calibrant plasmas certified by experienced centres has been assessed in two independent exercises using a range of commercial thromboplastins and coagulometers. INRs were compared with manual certified values with thromboplastin IRP from expert centres and in the second study also with INRs from local ISI calibrations. Results: In the first study with the PT/INR Line, 8.7% deviation from certified INRs was reduced to 1.1% with human reagents, and from 7.0% to 2.6% with rabbit reagents. In the second study, deviation was reduced from 11.2% to 0.4% with human reagents by both local ISI calibration and the PT/INR Line. With rabbit reagents, 10.4% deviation was reduced to 1.1% with both procedures; 4.9% deviation was reduced to 0.5% with bovine/combined reagents with local ISI calibrations and to 2.9% with the PT/INR Line. Mean INR dispersion was reduced with all thromboplastins and automated systems using the PT/INR Line. Conclusions: The procedure using the PT/INR Line provides reliable INR derivation without the need for WHO ISI calibration across the range of locally used commercial thromboplastins and automated PT systems included in two independent international studies.     

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.     

Mortality and cancer incidence in persons with Down's syndrome, their parents and siblings

A cohort study of 1425 persons with Down's syndrome (DS), and of their parents (447 mothers, 435 fathers) and siblings (1176), was set up to investigate death rates from various causes and cancer incidence patterns. In individuals with DS the all-cause death rate was six times that of the national population (SMR = 622: 95% CI 559–693), the excess being attributable to many different causes. These included: leukaemia (SMR = 1304: 95% CI 651–2334); diabetes mellitus (SMR = 982: 95% CI 267–2515); Alzheimer's disease (SMR = 22028: 95% CI 7137–51326); epilepsy (SMR = 1727: 95% CI 744–3403); and congenital anomalies (SMR = 4987: 95% CI 4175–5955). The overall survival showed marked improvements for successive birth cohorts, particularly at young ages. For mothers and fathers of persons with DS, all-cause death rates were 20% lower than national rates and there were no significant excesses from any specific cause. For siblings, all-cause death rates were similar to national rates; the only condition with a significantly raised mortality ratio was colo-rectal cancer (SMR = 793: 95% CI 216–2031), but this may well be a chance finding.