Incidence of graft-versus-host-disease in Germany:evidence from health care claims data

Objective Graft-versus-host disease (GvHD) can occur as an immunological response after an allogeneic hematopoietic cell transplantation (allo-HCT). Due to the rarity of the disease, German epidemiological data are scarce. Moreover, not all cases of GvHD are properly documented in daily practice. Against this background, this study aims at providing new estimates on the incidence of GvHD in Germany. Methods Based on a large German claims database, a retrospective longitudinal analysis was conducted over a 6-year period. Patients were selected that received allo-HCT between 2014 and 2015. Follow up period was 3 years. To adjust the incidence for undocumented cases, steroid prescriptions after an allo-HCT was used as an approximation. Based on both documented and undocumented GvHD patients, incidence rates were calculated for the population of the German statutory health insurance (SHI). Results Among 4,395,540 eligible database enrollees 3,737,317 were continuously insured. Among them we identified 297 patients who received an allo-HCT between 2014 and 2015. Depending on the extrapolation method, this corresponds to a yearly incidence of 2415-2840 for the SHI population. Of the 297 patients, 134 (i.e., 45.1%) developed a documented GvHD within three years after the transplantation which translates into a yearly incidence of 1125-1300 GvHD patients. Based on the medication regimens, we identified 83 additional patients with an suspected GvHD without a documented diagnosis. Extrapolated to the German SHI population, our estimates suggest that the annual incidence of GvHD, including undocumented cases, could be as high as 1822-2105, which is higher than previously reported. Conclusion More patients may be affected by GvHD in Germany than reported. Appropriate adjustments need to be made when utilizing administrative data.</p

Incidence of graft-versus-host-disease in Germany:evidence from health care claims data

Objective Graft-versus-host disease (GvHD) can occur as an immunological response after an allogeneic hematopoietic cell transplantation (allo-HCT). Due to the rarity of the disease, German epidemiological data are scarce. Moreover, not all cases of GvHD are properly documented in daily practice. Against this background, this study aims at providing new estimates on the incidence of GvHD in Germany. Methods Based on a large German claims database, a retrospective longitudinal analysis was conducted over a 6-year period. Patients were selected that received allo-HCT between 2014 and 2015. Follow up period was 3 years. To adjust the incidence for undocumented cases, steroid prescriptions after an allo-HCT was used as an approximation. Based on both documented and undocumented GvHD patients, incidence rates were calculated for the population of the German statutory health insurance (SHI). Results Among 4,395,540 eligible database enrollees 3,737,317 were continuously insured. Among them we identified 297 patients who received an allo-HCT between 2014 and 2015. Depending on the extrapolation method, this corresponds to a yearly incidence of 2415-2840 for the SHI population. Of the 297 patients, 134 (i.e., 45.1%) developed a documented GvHD within three years after the transplantation which translates into a yearly incidence of 1125-1300 GvHD patients. Based on the medication regimens, we identified 83 additional patients with an suspected GvHD without a documented diagnosis. Extrapolated to the German SHI population, our estimates suggest that the annual incidence of GvHD, including undocumented cases, could be as high as 1822-2105, which is higher than previously reported. Conclusion More patients may be affected by GvHD in Germany than reported. Appropriate adjustments need to be made when utilizing administrative data.</p

Deep Brain Stimulation in KMT2B-Related Dystonia: Case Report and Review of the Literature With Special Emphasis on Dysarthria and Speech

Objective: KMT2B-related dystonia is a progressive childhood-onset movement disorder, evolving from lower-limb focal dystonia into generalized dystonia. With increasing age, children frequently show prominent laryngeal or facial dystonia manifesting in dysarthria. Bilateral deep brain stimulation of the globus pallidus internus (GPi-DBS) is reported to be an efficient therapeutic option. Especially improvement of dystonia and regaining of independent mobility is commonly described, but detailed information about the impact of GPi-DBS on dysarthria and speech is scarce. Methods: We report the 16-months outcome after bilateral GPi-DBS in an 8-year-old child with KMT2B-related dystonia caused by a de-novo c.3043C>T (p.Arg1015*) non-sense variant with special emphasis on dysarthria and speech. We compare the outcome of our patient with 59 patients identified through a PubMed literature search. Results: A remarkable improvement of voice, articulation, respiration and prosodic characteristics was seen 16 months after GPi-DBS. The patients' speech intelligibility improved. His speech became much more comprehensible not only for his parents, but also for others. Furthermore, his vocabulary and the possibility to express his feelings and wants expanded considerably. Conclusion: A positive outcome of GPi-DBS on speech and dysarthria is rarely described in the literature. This might be due to disease progression, non-effectiveness of DBS or due to inadvertent spreading of the electrical current to the corticobulbar tract causing stimulation induced dysarthria. This highlights the importance of optimal lead placement, the possibility of horizontal steering of the electrical field by applying directional stimulation with segmented leads as well as the use of the lowest possible effective stimulation intensity

Incidence of graft-versus-host-disease in Germany: evidence from health care claims data

Objective Graft-versus-host disease (GvHD) can occur as an immunological response after an allogeneic hematopoietic cell transplantation (allo-HCT). Due to the rarity of the disease, German epidemiological data are scarce. Moreover, not all cases of GvHD are properly documented in daily practice. Against this background, this study aims at providing new estimates on the incidence of GvHD in Germany. Methods Based on a large German claims database, a retrospective longitudinal analysis was conducted over a 6-year period. Patients were selected that received allo-HCT between 2014 and 2015. Follow up period was 3 years. To adjust the incidence for undocumented cases, steroid prescriptions after an allo-HCT was used as an approximation. Based on both documented and undocumented GvHD patients, incidence rates were calculated for the population of the German statutory health insurance (SHI). Results Among 4,395,540 eligible database enrollees 3,737,317 were continuously insured. Among them we identified 297 patients who received an allo-HCT between 2014 and 2015. Depending on the extrapolation method, this corresponds to a yearly incidence of 2415-2840 for the SHI population. Of the 297 patients, 134 (i.e., 45.1%) developed a documented GvHD within three years after the transplantation which translates into a yearly incidence of 1125-1300 GvHD patients. Based on the medication regimens, we identified 83 additional patients with an suspected GvHD without a documented diagnosis. Extrapolated to the German SHI population, our estimates suggest that the annual incidence of GvHD, including undocumented cases, could be as high as 1822-2105, which is higher than previously reported. Conclusion More patients may be affected by GvHD in Germany than reported. Appropriate adjustments need to be made when utilizing administrative data

Treatment Pathways and Health Outcomes of German Patients with Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation: A Retrospective Health Claims Data Analysis

Background: Although chronic graft-versus-host-disease (cGvHD) is an important long-term complication after allogenic hematopoietic cell transplantation (allo-HCT) and is associated with increased healthcare resource utilization, real-world evidence is scarce. Objectives: The aim of the study was to evaluate survival of patients with cGvHD in Germany and to analyze hospitalization and treatment patterns. Patients and Methods: Based on a German claims database with 4.9 million enrollees, a retrospective longitudinal analysis covering a 6-year period between 2013 and 2018 was conducted. Patients with allo-HCT in 2014 or 2015 (index date) and no record of transplantation or documentation of GvHD 365 days prior to index were included. Patients who subsequently developed a cGVHD were compared with those who did not develop a cGVHD within 3 years after index date. cGVHD cases were identified based on documented International Classification of Diseases, Tenth Revision (ICD-10) diagnosis and treatment algorithms. Since the onset of cGvHD is defined at 100 days after allo-HCT, only those alive beyond day 100 were considered in the survival analysis. Patients who did not survive the first 100 days after allo-HCT were censored to prevent a selection bias due to early mortality within patients without GvHD. Survival rates were plotted using the Kaplan–Meier estimator. The number of hospitalizations and average lengths of stay as well as treatment patterns were descriptively examined. Results: Overall, 165 cGvHD patients were identified and compared with 43 patients without cGVHD. Short-term survival rates were better for patients with cGvHD; the 6-month survival probability was 95.8% for patients with cGVHD and 83.7% for patients without cGVHD. However, long-term survival was better in patients without GvHD; The 30-month survival probability was 65.5% for patients with cGVHD and 76.7% for patients without cGVHD. While overall 90% of cGvHD patients were hospitalized at least once, the share was only half for patients without GvHD (44%). 78.2% of patients with cGVHD received corticosteroids in combination with other predefined immunosuppressants. Conclusion: Findings from this study reveal a high disease burden associated with cGvHD. This underlines the high medical need for new interventional strategies to improve survival and morbidity after allo-HCT

The VEGF/Rho GTPase signalling pathway:a promising target for anti-angiogenic/anti-invasion therapy

\u3cp\u3eIt has become increasingly apparent that current antiangiogenic therapy elicits modest effects in clinical settings. In addition, it remains challenging to treat cancer metastasis through antiangiogenic regimes. Rho GTPases are essential for vascular endothelial growth factor (VEGF)-mediated angiogenesis and are involved in tumour cell invasion. This review discusses novel therapeutic strategies that interfere with Rho GTPase signalling and further explores this network as a target for anticancer therapy through interference with tumour angiogenesis and invasion. Recent findings describe the development of innovative Rho GTPase inhibitors. Positive clinical effects of Rho GTPase targeting in combination with conventional anticancer therapy is of increasing interest.\u3c/p\u3