Sucrose-Formulated Recombinant Factor VIII Dosing Flexibility in Prophylaxis Regimens: Experience from Postmarketing Surveillance Studies

Objectives. Prophylaxis regimens for severe hemophilia A allowing more flexible dosing while maintaining efficacy may improve adherence and decrease the cost of prophylaxis. Here, we compared the clinical effectiveness of once- or twice-weekly versus ≥3-times-weekly prophylaxis with sucrose-formulated recombinant factor VIII (rFVIII-FS) in a “real-world” practice setting. Methods. Data from 3 postmarketing studies were pooled. Patients with severe hemophilia A receiving ≥1 prophylaxis infusion/wk of rFVIII-FS for ≥80% of a prophylaxis observation period (≥5 months) were included. Patients were categorized based on physician-assigned treatment regimens of 1-2 prophylaxis injections/wk (n=63) or ≥3 prophylaxis injections/wk (n=76). Descriptive statistics were determined for annualized bleeding rates (ABRs). Results. Median (quartile 1; quartile 3) ABR for all bleeds was 2.0 (0; 4.0) in the 1-2 prophylaxis injections/wk group and 3.9 (1.5; 9.3) in the ≥3 prophylaxis injections/wk group. Median ABRs for joint, spontaneous, and trauma-related bleeds were numerically lower with 1-2 prophylaxis injections/wk. As an estimate of prophylaxis success, 63% (≥3 prophylaxis injections/wk) to 84% of patients (1-2 prophylaxis injections/wk) had ≤4 annualized joint bleeds. Conclusions. Dosing flexibility and successful prophylaxis with rFVIII-FS were demonstrated. Very good bleeding control was achieved with both once-twice-weekly and ≥3-times-weekly prophylaxis dosing regimens

Guideline adherence and patient satisfaction in the treatment of inflammatory bowel disorders – an evaluation study

Background: Crohn's disease (CD) and ulcerative colitis (UC) are the most frequent inflammatory bowel disorders (IBD). IBD cause a significant burden to society due to extensive health care utilization from the first clinical symptoms until diagnosis and thereafter due to direct and indirect costs. Besides the socio-economic impact of CD and UC, gastrointestinal and extraintestinal symptoms affect quality of life, but there is remarkably little data about the quality of treatment as assessed by patient satisfaction, quality of life and adherence to guidelines. Thus the aim of this study was to identify variables that influence quality of treatment and quality of life as well as patient satisfaction. Methods: The Essener Zirkel Study was a cross sectional study of 86 IBD-patients with a confirmed diagnosis of CD or UC. They were recruited at primary, secondary and tertiary care settings. Quality of treatment, quality of life and patient satisfaction were evaluated. Consulting behaviour and number of examinations, duration of disease and variables regarding adherence to guidelines were evaluated, too. Results: 59 (69%) patients had CD and 27 had UC (31%). 19% spent more than four years until the suspected diagnosis of IBD was confirmed and visited more than five physicians. All patients showed a significantly reduced quality of life compared to the 1998 German normative population. In spite of being under medical treatment, nearly half of the patients suffered from strong quality of life restricting symptoms. Over all, 35% described their treatment as moderate or bad. Patients who consulted psychotherapists and non-medical practitioners suffered significantly less from depression. Conclusion: Besides structural deficiencies due to the health care policy, we revealed the adherence to guidelines to be a problem area. Our findings support the assumption, that providing better health care and especially maintaining constant patient-physician communication improves patient satisfaction.Claudia Pieper, Sebastian Haag, Stefan Gesenhues, Gerald Holtmann, Guido Gerken and Karl-Heinz Jöcke

Discovery: an interactive resource for the rational selection and comparison of putative drug target proteins in malaria

<p>Abstract</p> <p>Background</p> <p>Up to half a billion human clinical cases of malaria are reported each year, resulting in about 2.7 million deaths, most of which occur in sub-Saharan Africa. Due to the over-and misuse of anti-malarials, widespread resistance to all the known drugs is increasing at an alarming rate. Rational methods to select new drug target proteins and lead compounds are urgently needed. The Discovery system provides data mining functionality on extensive annotations of five malaria species together with the human and mosquito hosts, enabling the selection of new targets based on multiple protein and ligand properties.</p> <p>Methods</p> <p>A web-based system was developed where researchers are able to mine information on malaria proteins and predicted ligands, as well as perform comparisons to the human and mosquito host characteristics. Protein features used include: domains, motifs, EC numbers, GO terms, orthologs, protein-protein interactions, protein-ligand interactions and host-pathogen interactions among others. Searching by chemical structure is also available.</p> <p>Results</p> <p>An <it>in silico</it> system for the selection of putative drug targets and lead compounds is presented, together with an example study on the bifunctional DHFR-TS from <it>Plasmodium falciparum</it>.</p> <p>Conclusion</p> <p>The Discovery system allows for the identification of putative drug targets and lead compounds in Plasmodium species based on the filtering of protein and chemical properties.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Evidence of Workplace Interventions—A Systematic Review of Systematic Reviews

Work environment factors are highly correlated with employees&rsquo; health and well-being. Our aim was to sum up current evidence of health promotion interventions in the workplace, focusing on interventions for the prevention of musculoskeletal disorders, psychological and behavioral disorders as well as interventions for older employees and economic evaluations. We conducted a comprehensive literature search including systematic reviews published from April 2012 to October 2017 in electronic databases and search engines, websites of relevant organizations and institutions. It consisted of simple and specific terms and word combinations related to workplace health promotion based on the search strategy of a previous review. After full-text screening, 74 references met the eligibility criteria. Using the same search strategy, there was a higher proportion of relevant high-quality studies as compared with the earlier review. The heterogeneity of health promotion interventions regarding intervention components, settings and study populations still limits the comparability of studies. Future studies should also address the societal and insurer perspective, including costs to the worker such as lost income and lost time at work of family members due to caregiving activities. To this end, more high-quality evidence is needed

Evaluierung der Qualität der Versorgung von Patienten mit chronischen Darmerkrankungen (unter besonderer Berücksichtigung der Patientenzufriedenheit) am Beispiel des "Essener Zirkels"

Ziel der vorliegenden Untersuchung war es, mittels einer Stichprobe von 170 Patienten aus Essen und Umgebung die Versorgung von Patienten mit chronischen Darmerkrankungen zu evaluieren. Außerdem sollten Patientenkarrieren beschrieben werden sowie die Lebensqualität und das Inanspruchnahmeverhalten und deren Beziehung zur Patientenzufriedenheit untersucht werden. Damit sollten im Rahmen des Projekts „Essener Zirkel“ Variablen, die die Qualität der Versorgung beeinflussen, identifiziert werden. Das Reizdarmsyndrom (RDS) ist eine der häufigsten Erkrankungen des Magen-Darm-Traktes. Die Zahl der an chronisch entzündlichen Darmerkrankungen (CED) erkrankten in Deutschland wird auf ca. 300.000 geschätzt. Es handelt sich um eine konsekutive Querschnittsstudie, die unter Koordination des Instituts für Medizinische Informatik, Biometrie und Epidemiologie (IMIBE) am Universitätsklinikum Essen in Zusammenarbeit mit der Abteilung für Gastroenterologie und Hepatologie durchgeführt wurde. Die Gesamtstichprobe umfasste 170 Patienten im Alter von 18 bis 75 Jahren, von den 131 in die Studie eingeschlossen werden konnten. Hiervon litten 86 unter einer CED, davon 59 unter einem Morbus Crohn und 27 unter einer Colitis ulcerosa. Die Lebensqualität von CED- und vor allem RDS-Patienten war im Vergleich zur deutschen Normstichprobe deutlich reduziert. Hinsichtlich der Patientenzufriedenheit wurden vier Hauptprobleme identifiziert: 1. Lange Dauer bis zur richtigen Diagnose, 2. Mangelnde Information durch behandelnde Ärzte, 3. Unpersönlicher Umgang und 4. Mangelnde Abstimmung zwischen Allgemeinmediziner und Facharzt bzw. Facharzt und Klinik. Die Zufriedenheit der Patienten, die alternative Behandlungsangebote nutzten, ist signifikant höher als die der übrigen. Die Dauer bis zur richtigen Diagnose bzw. die Anzahl der bis dahin aufgesuchten Ärzte korreliert ebenfalls signifikant mit der Zufriedenheit der Befragten. Die Ergebnisse dieser Arbeit zeigen strukturelle Mängel in der Versorgung, die sich negativ auf die Patientenzufriedenheit auswirken. Aber auch in der Prozessqualität bestehen Defizite. All dies beeinträchtigt schließlich die Ergebnisqualität. Neben den klinischen Indikatoren sind auch psychosoziale Indikatoren aussagekräftig. Die Studienergebnisse weisen darauf hin, dass eine enge Zusammenarbeit zwischen allen Beteiligten notwendig ist für eine effiziente Diagnose und Therapie

Zytokeratinexpression der Paukenhöhlenschleimhaut bei chronischer seromuköser Otitis media

Problem: Verändert sich das Zytokeratinexpressionsmuster der Promontoriumsschleimhaut infolge chronischer Otitis media? Methode: Proben von an chronischer Otitis media erkrankten Probanden und Proben von gesunden Probanden wurden immunhistochemisch auf die Zytokeratine CK 7, CK 8, CK 18, CK 19 untersucht und lichtmikroskopisch ausgewertet. Ergebnis: Der immunhistochemische Nachweis der Zytokeratinexpression zeigte bei der Krankengruppe keine wesentlichen Abweichungen von der Vergleichsgruppe. CK 7 zeigte sich in beiden Gruppen negativ. Diskussion: Aufgrund des unterschiedlichen Zytokeratinexpressionsmusters von Zylinderepithel aus dem Respirationstrakt und Zylinderepithel vom Promontorium könnte die in der Grundlagenforschung verbreitete Hypothese in Frage gestellt werden, daß sich die Promontoriumsschleimhaut embryonal vom Respirationstrakt ableite