Difference in Incontinence Pad Use between Patients after Radical Prostatectomy and Cancer-Free Population with Subgroup Analysis for Open vs. Minimally Invasive Radical Prostatectomy: A Descriptive Analysis of Insurance Claims-Based Data.

PURPOSE: to quantify and compare pre- and post-surgical incontinence pad use between men treated with radical prostatectomy (RP) for prostate cancer (PCa) and cancer-free controls, using population-based Austrian insurance claims data. METHODS: Men who underwent RP for treating PCa between 2013-2015 were identified. Cancer-free men ≥45 years with and without benign prostate hyperplasia (BPH) were used as controls. Longitudinal data on ICD-diagnoses, type of surgery, prescribed incontinence pads, and hospitals' surgery volumes were aggregated between 2011-2018 to capture pre- and up to three years post-RP follow-up. Monthly rates of pad use were calculated and compared between RP types and cancer-free controls. RESULTS: A total of 6248 RP patients, 7158 cancer-free men with BPH, and 50,257 cancer-free men without BPH were analyzed. Comparing to pre-RP (0.03, 95%CI: 0.02-0.05), RP resulted in significantly higher rates of prescribed pads (at 3 months: 12.61, 95%CI: 11.59-13.65; 12 months: 6.71, 95%CI: 6.10-7.34; 36 months: 4.91, 95%CI: 3.76-4.62). These rates were also higher than those for cancer free controls (with BPH:0.06, 95%CI: 0.04-0.09; without BPH:0.12, 95%CI: 0.10-0.14). The rate of prescribed pads after surgery continued to decline over time and remained higher among men who underwent minimally invasive RP compared to those who underwent an open procedure. CONCLUSION: Despite progress in surgical techniques, post-RP incontinence remains a prevalent adverse event. The rate of pad usage steadily improved over the first three years post RP. The rate of patients with incontinence needing pads was higher among those who were treated minimally invasive compared to open approach.

Epidemiology and Treatment of Patients with Haemophilia in Austria-Update from the Austrian Haemophilia Registry.

The Austrian Haemophilia Registry collects epidemiological data on patients with haemophilia, on treatment modalities and potential side effects. The Registry covers more than 85% of the assumed total number of haemophilia patients in Austria. This report summarizes data on 753 patients: 84.3% (635) have haemophilia A and 15.7% (118) have haemophilia B. Patients' median age is 34 years (range: 1-93 years). Of the total cohort, 39.0% (294) patients have severe haemophilia, 11.3% (85) moderate haemophilia, and 49.4% (372) mild haemophilia. Of the patients with severe haemophilia, 38.4% (113) have been infected with hepatitis C virus (HCV) and 12.6% (37) are human immunodeficiency virus (HIV) positive. Overall, 10.6% (67) of patients with haemophilia A and 1.7% (2) of those with haemophilia B have had an inhibitor in their history. Among patients with severe haemophilia, 68.4% (201) receive prophylaxis and 28.6% (84) receive on-demand therapy. There are 65.0% (191) patients with severe haemophilia who are treated with recombinant products. In conclusion, most patients with severe haemophilia receive prophylactic treatment. HCV and HIV infections are still important issues in the Austrian haemophilia population.

FVIII-binding IgG modulates FVIII half-life in patients with severe and moderate hemophilia A without inhibitors.

The substantial variability in pharmacokinetic parameters in hemophilia patients A poses a challenge for optimal treatment with factor VIII (FVIII) products. We investigated the effect of FVIII-specific immunoglobulin G (IgG) on FVIII half-life in a cohort of 42 adult patients with severe and moderate hemophilia A without inhibitors. Fifteen (35.7%) of 42 patients tested positive for FVIII-binding IgG with titers ≥1:20 in the initial antibody screen, 9 of these 15 patients had FVIII-specific antibodies with titers ≥1:40, mostly low-to-moderate-affinity IgG1 and IgG3, and 1 had high-affinity IgG4 and later developed low-titer FVIII inhibitors. His brother with low-to-moderate-affinity IgG1 and IgG3 also later developed low-titer FVIII inhibitors. The presence of FVIII-specific IgG subclass titer ≥1:40 antibodies was significantly associated with shorter FVIII half-life (median, 7.8 hours [interquartile range, 6.6-9.2 hours]) vs 10.4 hours [interquartile range, 8.9-13.8 hours]); the regression coefficient adjusted for log age and log von Willebrand factor (VWF) antigen was -0.32 (P = .004), accounting for 16.9% of the observed variability of FVIII half-life in our cohort. Our data indicate a significant contribution of non-neutralizing FVIII-specific IgG to FVIII half-life reduction in hemophilia A patients. Thus, screening for FVIII-specific IgG could be beneficial in tailoring FVIII prophylactic regimens.

[Treatment of haemophilia in Austria]. / Hämophiliebehandlung in Österreich.

This guideline which is endorsed by the Austrian Society of Haemophilia, the Austrian Society of Paediatrics, and the Austrian Society of Haematology & Medical Oncology is intended to give a clear and practical guidance for diagnosing and treating haemophilia in Austria. In the treatment of haemophilia there are few controlled interventional trials, and recommendations usually have a rather low level of evidence.The main basis for this paper are the new international guidelines by the World Federation of Hemophilia, published in 2013. These were adapted according to the local situation and experience.Covered topics are diagnostics, control visits, pharmacological treatment options, prophylaxis and treatment in children and adults, possible problems arising in haemophilia carriers and special aspects like home therapy, options for venous catheters, management of various traumas, bleedings and interventions, including dental procedures, and last not least inhibitors and their treatment.

Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A.

Neutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into account. In the INSIGHT study, we analyzed the association between F8 mutation and inhibitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL). This analysis included 1112 nonsevere hemophilia A patients from 14 centers in Europe and Australia that had genotyped at least 70% of their patients. Inhibitor risk was calculated as Kaplan-Meier incidence with cumulative number of exposure days as the time variable. During 44 800 exposure days (median, 24 exposure days per patient; interquartile range [IQR], 7-90), 59 of the 1112 patients developed an inhibitor; cumulative incidence of 5.3% (95% confidence interval [CI], 4.0-6.6) after a median of 28 exposure days (IQR, 12-71). The inhibitor risk at 50 exposure days was 6.7% (95% CI, 4.5-8.9) and at 100 exposure days the risk further increased to 13.3% (95% CI, 9.6-17.0). Among a total of 214 different F8 missense mutations 19 were associated with inhibitor development. These results emphasize the importance of F8 genotyping in nonsevere hemophilia A.

The influence of thrombophilia on the long-term survival of patients with a history of venous thromboembolism.

Data on the long-term survival following venous thromboembolism (VTE) are rare, and the influence of thrombophilia has not been evaluated thus far. Our aim was to assess thrombophilia-parameters as predictors for long-term survival of patients with VTE. Overall, 1,905 out-patients (99 with antithrombin-, protein C or protein S deficiency, 517 with factor V Leiden, 381 with elevated factor VIII and 160 with elevated homocysteine levels, of these 202 had a combination and 961 had none of these risk factors) were included in the study between September 1, 1994 and December 31, 2007. Retrospective survival analysis showed that a total of 78 patients (4.1%) had died during the analysis period, among those four of definite or possible pulmonary embolism and four of bleeding. In multivariable analysis including age and sex an association with increased mortality was found for hyperhomocysteinemia (hazard ratio 2.0 [1.1.-3.5]) whereas this was not the case for all other investigated parameters. We conclude that the classical hereditary thrombophilia risk factors did not have an impact on the long-term survival of patients with a history of VTE. Thus our study supports the current concept that thrombophilia should not be a determinant for decision on long term anticoagulation. However, hyperhomocysteinaemia, known as a risk factor for recurrent VTE and arterial disease, might impact survival.

Identification of an ancient haemophilia A splice site mutation.

INTRODUCTION: To date, numerous mutations resulting in haemophilia A are known and recorded at HAMSTeRS. We identified a new splice site mutation in intron 6 of the F8 gene (T to G transition at position -14; c.788-14T>G) in seven not knowingly related patients, who all suffer from mild haemophilia A. RNA analysis of blood cells indicated that this mutation leads to the preferred generation of a transcript lacking the complete exon 7 (without frameshift). METHODS: To determine whether the mutation represented a founder mutation we analyzed intragenic (intronic) and extragenic short tandem repeat (STR) regions and constructed haplotypes in the 7 patients and 128 apparently healthy male control individuals. RESULTS: In the 128 healthy control individuals, 109 different haplotypes were found. Surprisingly, also the 7 patients carried 3 different haplotypes. However, by genealogy reconstruction using BATWING we could identify an ancestral haplotype on which the mutation apparently occurred. This haplotype - DXS9897:12-DXS1073:21-HA472:64-DXS1108:26 - was frequent and was found in three patients, but was also present in four control individuals who did not carry the splice site mutation. CONCLUSION: Our data indicate that the splice site mutation occurred in an individual carrying a relatively common haplotype. While the mutation was passed on through generations, the haplotypes identified in the seven patients derived from this founder haplotype but were changed by later mutations in the STR regions.

Inhibitor development in two patients with mild haemophilia A - spontaneous disappearance and no recurrence of the inhibitor after re-challenge.

Inhibitors against factor VIII (FVIII) complicate the treatment of patients with haemophilia. In mild haemophilia, the development of antibodies against FVIII is rare. However, the occurrence of an inhibitor in mild haemophilia changes the bleeding phenotype from mild to severe, and thus becomes a major clinical problem. We report on two patients with mild haemophilia A (FVIII level 8 and 27%, respectively), who have a missense mutation in exon 16 (G to A transition in codon 1773) and exon 22 (T to C transition in codon 2096), respectively. Both mutations have not been described in the Haemophilia A Mutation, Structure Test and Resource Site. Our patients developed high titer inhibitors following an intensive FVIII replacement therapy due to a muscle bleeding and after a polytrauma. During the presence of the inhibitor, AICC or FVIIa was successfully used as bypassing agent. In both patients the inhibitor disappeared spontaneously. Years after the development of the inhibitor, the patients again received FVIII concentrates. Reappearance of the inhibitor was not observed in either patient. The reported cases indicate that inhibitors in patients with mild haemophilia might be transient and disappear spontaneously. Therefore, the necessity of immune tolerance therapy, which is costly and strenuous for the patients, should be critically examined for each individual patient and a watch and wait strategy might be advisable.