[Online Rehab-Need Test (OREST): Effectiveness of an Invitation to Proactive Screening (self-test) for the Need for Medical Rehabilitation Among Individuals Covered by the German Statutory Pension Insurance Agencies in Baden-Württemberg and the Rhine Region]. / Online-Rehabedarfstest (OREST): Wirksamkeit einer Einladung zu einem proaktiven Screening (Selbsttest) auf Bedarf an medizinischen Rehabilitationsmaßnahmen bei Versicherten der Deutschen Rentenversicherung Baden-Württemberg und Rheinland.

PURPOSE: Up to now, there has been a lack of proactive approaches on the part of the rehabilitation providers, while simultaneously a suspected unmet rehabilitation need exists in some groups of insured persons. Therefore, the effectiveness of the invitation to a web-based self-test for rehabilitation needs as a new access route to medical rehabilitation was evaluated. The main question was whether the intervention leads to more approved rehabilitation applications in the follow-up period of 22 months and whether this effect is also apparent after controlling other influencing variables. METHODS: A randomized, controlled study with N=8000 insured persons of two regional statutory pension insurance agencies was conducted to check the effectiveness of the intervention. Insured persons of the intervention group (IG; n=4000) were informed by mail about the web-based self-test and received individual access data for it (user ID and PIN). The control group (CG; n=4000) received no information about the self-test. The primary outcome was the rate of approved rehabilitation applications, the secondary outcome was the application rate regardless of approval. RESULTS: Groups do not differ significantly in terms of primary or secondary outcomes. Even after controlling for other influencing factors, the intervention does not contribute to the prediction of outcomes, but some control variables, such as previous rehabilitation experience, prove to be important predictors for the application. CONCLUSION: The mere offer of a self-test for rehabilitation need by the pension insurance institution has no effect on the application process. Hence a letter from the pension insurance institution as the sole means of access does not appear suitable for increasing the rate of meaningful rehabilitation applications.

[Supporting Patients with Diabetes mellitus type 2 and Obesity in Transfer of Medically Indicated Lifestyle Changes into Everyday Life by a Planning Competence Training in a Randomized Controlled Trial]. / Unterstützung der Lebensstiländerung und Verbesserung der subjektiven Erwerbstätigkeitsprognose bei Patienten mit Diabetes mellitus Typ 2 und Adipositas durch ein Planungskompetenztraining in einem randomisierten Kontrollgruppendesign.

BACKGROUND: Patients with Diabetes mellitus type 2 and/or obesity have difficulties to transfer medically indicated lifestyle changes into everyday life. Hence, this study investigates whether a planning competence training (Planungskompetenztraining, PKT) can support participants of a medical rehabilitation program to foster lifestyle change. METHOD: 467 patients participated in study. Those patients regularly took part in a 3-week program of a rehabilitation clinic between 12/2012 and 08/2014. Using a randomized control group design, training and aftercare effects were controlled (one experimental group [EG] and 3 control groups [KG]. RESULTS: In general, there were no significant differences between the 4 study groups based on an intention-to-treat-analysis. Significant differences were calculated in per-protocol-analysis. Additionally, differences were primarily revealed in a 2 group comparison between participants who participated at training (EG-A and KG-B) vs. those who did not (KG-C und KG-D). CONCLUSION: The implementation of the current training version cannot be recommended for medical rehabilitation. However, in consideration of relevant results a modification of the program could make sense.

[Rehabilitation of Patients with Diabetes]. / Rehabilitation von Patienten mit Diabetes mellitus.

Diabetes prevalence in Germany has increased from 1% in 1960 to around 9,8%. This increase is mainly due to an increase in type 2 diabetes and metabolic syndrome. People with diabetes are classified as multimorbid patients in most cases. The prognosis is determined by secondary diseases and comorbidities.Evidence-based therapy modules are used in the rehabilitation of people with diabetes. Important clinical therapy goals are the avoidance of hypoglycemia and complications, as well as and exerting a favorable influence on comorbidities. For many rehabilitants with type 2 diabetes, one main focus is the transmission of sustainable impulses to change the lifestyle in the foreground.With the emergence of bariatric surgeries, a new successful therapy option is now available for overweight people with type 2 diabetes. The introduction of continuous glucose measurement (CGM) allows for a reduction in the incidence of hypoglycemia and thus an improvement in participation at work and on the road. The new guideline "Diabetes and Road Traffic" specifies the preconditions for fitness to drive in people with diabetes.

Telephone-delivered lifestyle support with action planning and motivational interviewing techniques to improve rehabilitation outcomes.

OBJECTIVE: In this randomized controlled trial, we evaluated the effectiveness of a telephone-delivered intervention based on the Health Action Process Approach (HAPA) after discharge from inpatient rehabilitation to address behavior change, emotional status, and glycemic control in patients with Type 2 diabetes. DESIGN: In a German rehabilitation center, 249 patients with Type 2 diabetes were separated into randomized groups, either a 12-month telephone follow-up support group or the usual care group. The counselor identified personal target areas and intervention modules and developed with the patient an individualized action plan for the telephone support. To enhance motivational processes, they used motivational interviewing techniques. Counselors called patients monthly to support the implementation of the personal plans into the patients' daily routines and to screen for emotional problems. Assessments measured exercise, diet, medication adherence, psychological variables, body mass index, HbA1c, and cardiovascular risk. RESULTS: Twelve months after inpatient rehabilitation, the telephone group's rate of physical activity rose by 26% compared with the usual care group's 10%. Patients in the intervention group exhibited greater improvements in terms of their illness burden, psychological well-being, and depression. HbA1c fell in the telephone group but increased in the usual care group (-0.68% vs. 0.12%). The intervention group's cardiovascular risk fell, whereas the usual care group's rose (-0.57 vs. 0.23). CONCLUSION: A theory-based telephone-delivered follow-up intervention utilizing motivational interviewing techniques and focusing on personalized action planning demonstrated improvements in patients' level of activity and health status 12-months postrehabilitation discharge and may be a beneficial supplement to rehabilitation programs. (PsycINFO Database Record

Prophylaxis and quality of life in patients with hemophilia A during routine treatment with ADVATE [antihemophilic factor (recombinant), plasma/albumin-free method] in Germany: a subgroup analysis of the ADVATE PASS post-approval, non-interventional study.

Antihemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM) was evaluated during routine practice in Germany, among consenting subjects of any age with hemophilia A (HA) and no prior exposure to rAHF-PFM. The treating physician chose the dosing and inhibitor testing frequency. Data were captured for 12 months/subject from diaries and clinic records. Of 152 subjects, 69 % had severe HA, and 89 % had >150 exposure 6 days (ED) at baseline. The majority of subjects (63 %) were treated by continuous prophylaxis (CP). Assignment to CP was more likely for subjects ≥2 years of age and for those with FVIII ≤ 2 %. Median FVIII consumption was 3,548 IU/kg/year for CP and 999 IU/kg/year for continuous on-demand (OD) therapy. Median annual bleed rate was 0.82 for CP and 4.06 for OD. Of 1,218 bleeds, 97 % were home-treated and 68 % of evaluable bleeds involved joints. Based on evaluable subjects' worst ratings, 83/91 (91 %) on CP had a rating of excellent/good for all prophylactic assessments, 55/59 (93 %) on CP and 41/42 (98 %) on OD had a rating of excellent/good for all bleeding assessments. The de novo high-titer FVIII inhibitor rate in subjects with >50 ED at baseline was 1/144 (0.69 %; 95 % CI, 0.02 % to 3.81 %). No high-titer inhibitor occurred in patients with severe HA and >50 ED at baseline. Reduced HRQOL physical scores were predicted by older age (p < 0.0001), HIV positivity (p = 0.02), and presence of ≥1 target joint (p = 0.003). ADVATE rAHF-PFM is safe and efficacious for routine CP or OD management of patients with HA.

Need for Prophylactic Treatment in Adult Haemophilia A Patients.

BACKGROUND AND METHODS: A single centre study including 52 German patients aged ≥16 years with severe haemophilia A was performed to compare the amount of clotting factor and outcome between on-demand therapy (26 patients) and continuous prophylaxis (26 patients) over 1 year. RESULTS: Prophylaxis reduced the number of bleeds significantly. Compared to on-demand treatment (20.5 ± 3.0 bleeds/year/patient), under prophylaxis 7.8 ± 1.3 bleeds/year/patient were observed. Joint bleeds were reduced from 12.2 ± 1.5 to 4.7 ± 1.0/year/ patient. In the on-demand group 38% of the patients suffered from more than 2 bleeds/month, whereas in the prophylaxis group no patient was found with more than 2 bleeds/month. Mean annual factor VIII (FVIII) consumption increased from 767 ± 110 IU/kg body weight under on-demand treatment to 2,841 ± 341 IU/kg body weight under continuous prophylaxis, displaying a nearly fourfold increase in FVIII consumption. Furthermore, prophylaxis implies a more than four-fold increase in treatment days which escalated from a mean weekly injection rate of 0.56 ± 0.08 FVIII injections/week when bleeds were treated on demand to 2.52 ± 0.30 FVIII injections/week during prophylaxis. CONCLUSION: Even though the results reflect a benefit also for prophylactically treated patients regarding their bleeding frequency, one has to take into account a substantial increase of the costs for coagulation concentrates when all patients with severe haemophilia A switch to continuous prophylaxis.

A systematic overview of the first pasteurised VWF/FVIII medicinal product, Haemate P/ Humate -P: history and clinical performance.

Patients with von Willebrand disease (VWD) and haemophilia A (HA) lack, to varying degrees, the von Willebrand factor (VWF) and coagulation factor VIII (FVIII) that are critical for normal haemostasis. These conditions in turn make patients prone to uncontrolled bleeding. Historically, patients with severe forms of VWD or HA were crippled before adulthood and their life expectancy was significantly reduced. Over the past decades, specific coagulation factor replacement therapies including Haemate P, have been developed to help patients achieve and maintain normal haemostasis. Haemate P is a human, plasma-derived VWF/FVIII medicinal product, which was first licensed in Germany in 1981 for the treatment of HA-associated bleeding. It has since then come to be accepted as the gold standard for both the treatment and prophylaxis of bleeding in VWD, especially in cases where desmopressin [1-deamino-8-D-arginine vasopressin (DDAVP)] has been ineffective. Haemate P was the first effectively virus-inactivated (pasteurisation: 60 degrees C for 10 h in aqueous solution) FVIII product, whereby the risk of potentially threatening infective complications of plasma-derived products was reduced. Haemate P was also shown to have a VWF multimer profile remarkably close to that of normal plasma. This bibliographic review presents previously unpublished clinical data of Haemate P, based upon internal clinical study reports of the proprietor, CSL Behring, in addition to data already presented in other publications. The data demonstrate a predictable and well-characterised pharmacokinetic profile, and a proven record of short- and long-term safety, while effectively correcting the haemostatic defects in VWD and HA. Recently available data have also shown Haemate P to be of haemostatic value in exceptional clinical circumstances including surgical interventions. By virtue of its plasma-derived combination of VWF and FVIII, in addition to its high VWF:FVIII content ratio (2.4:1), Haemate P is also associated with successful immune tolerance induction in those patients developing inhibitor antibodies. Although the theoretical risk of thromboembolic complications does exist while receiving Haemate P, as it does with any FVIII replacement therapy, the incidence of such complications has remained notably low. Given the robust data that have accumulated for the use of Haemate P, dosing recommendations are also described in this review; the recommendations are tailored to patient-specific contexts including baseline VWF and FVIII levels in plasma and the type of surgical intervention being undertaken. A wide variety of studies have also provided data on paediatric and geriatric populations, all of which have suggested that Haemate P can be safely and effectively used in a wide variety of clinical circumstances.

Spectrum of molecular defects and mutation detection rate in patients with mild and moderate hemophilia A.

The amount of residual F8 (FVIII:C) determines the clinical severity of hemophilia A. Recently, we showed that the mutation detection rate in severely affected male patients (FVIII:C<1% of normal) is virtually 100% when testing for the common intron 22-/intron 1- inversions and big deletions, followed by genomic sequencing of the F8 gene. Here we report on the spectrum of mutations and their distribution throughout the F8 gene sequence in 135 patients with moderate (n=23) or mild (n=112) hemophilia A. In contrast to the severe form of the disorder, analysis on the genomic level failed to detect the molecular defect in approximately 4% of the moderately and in approximately 12% of the mildly affected patients. A total of 36 of the mutations identified in this study are novel. The vast majority of the detected changes were missense. The newly detected amino acid substitutions were scored for potential distant or local conformational changes and influence on molecular stability for every single F8 domain with available structures, using homology modeling. Two molecular changes in the promoter region of the factor VIII gene (c.-112G>A and -219C>T), affecting the core segment (minimal promoter) were detected in two patients with mild hemophilia A. To our knowledge this is the first report on promoter mutations in the F8 gene.

Spectrum of molecular defects and mutation detection rate in patients with severe hemophilia A.

Hemophilia A is the most frequently occurring X-linked bleeding disorder, affecting one to two out of 10,000 males worldwide. Various types of mutations in the F8 gene are causative for this condition. It is well known that the most common mutation in severely affected patients is the intron 22 inversion, which accounts for about 45% of cases with F8 residual activity of less than 1%. Therefore, the aim of the present study was to determine the spectrum and distribution of mutations in the F8 gene in a large group of patients with severe hemophilia A who previously tested negative for the common intron 22 inversion. Here we report on a mutation analysis of 86 patients collected under the above-mentioned criterion. The pathogenic molecular defect was identified in all patients, and thus our detection rate was virtually 100%. Thirty-four of the identified mutations are described for the first time. The newly detected amino acid substitutions were scored for potential gross or local conformational changes and influence on molecular stability for every single F8 domain with available structures, using homology modeling.

Prevalence of small rearrangements in the factor VIII gene F8C among patients with severe hemophilia A.

Hemophilia A is a common X-linked bleeding disorder caused by various types of mutations in the factor VIII gene F8C. The most common intron 22-inversion is responsible for about 40% of the severe hemophilia A cases while large deletions, point mutations and small (less than 100 bp) deletions or insertions are responsible for the disease in the rest of patients. We report on nine novel (6 deletions, two indels and one partial duplication) and five recurrent small rearrangements identified in 15 German patients with severe hemophilia A, negative for the intron 22-inversion. c.2208-2214delTTATTAC/c.2207-2215insCTCTT and c.4665-4678del/c.4664-4678insAAGGAA identified in the present study are the first small indels described in the factor VIII gene. Our analyses suggest that the prevalence of this type of mutations (predominantly located in exon 14) among patients with severe phenotype and negative for the common intron 22-inversion, is about 30%. The correlation between these molecular defects and formation of factor VIII inhibitors as well as the parental origin of the de novo mutations are evaluated. Finally we show that denaturing HPLC (DHPLC) and classic heteroduplex analysis (HA) are able to detect these sequence alterations on 100% and could be preferred as a screening approach when analysing for mutations in factor VIII in severely affected patients.

Seven novel and four recurrent point mutations in the factor VIII (F8C) gene.

Haemophilia A is a X-linked bleeding disorder, caused by deficiency in the activity of coagulation factor VIII due to mutations in the corresponding gene. The most common defect in patients is an inversion of the factor VIII gene that accounts for nearly 45% of individuals with severe hemophilia A. Point mutations and small deletions/insertions are responsible for the majority of cases with moderate to mild clinical course and for half of the severe hemophilia A occurrences. The majority of these mutations are "private", because of the high mutation rate for this particular gene. We report on eleven pathological changes in the factor VIII sequence detected in male patients with haemophilia A or in female obligate carriers. Seven of these mutations are novel [E204N, E265X, M320T, F436C, S535C, N2129M and R2307P] and four have been previously identified [V162M, R527W, R1966X, and R2159C]. Genotype-phenotype correlations and computer prediction analysis on the effect of missense mutations on the secondary structure of the factor VIII protein are performed and the relationships evaluated.