PubMed Health⌕ Search

Biomedical subjects

W Schramm

Publications and source records attributed to W Schramm.

At least 19 recordsLinked to original sources
PubMed2006

Antithrombin deficiency and its relationship to severe burns.

Antithrombin (AT) is an important endogenous anticoagulant and exhibits marked anti-inflammatory properties. To evaluate the incidence of AT deficiency in severe burn and its correlation to the variables of the abbreviated burn severity index (ABSI), length of hospital stay (LOS) and mortality we collected data on the substitution of human plasma-derived AT concentrate in 201 consecutive patients suffering from severe burn. One hundred and eight patients (54%) developed AT deficiency during their hospitalisation and, according to our institutional practice, received substitution therapy by continuous infusion to maintain physiological plasma activity (70-120%). The mean administered dose served as a measure of AT deficiency. The percentage of patients in an AT deficient state was highest within the first 5 days after injury. It was 26% on day 1 and between 38% and 41% on days 2-5 and thereafter decreased constantly over time. A multiple regression analysis between the dependent variable mean administered dose of AT concentrate and the independent variables age, total body surface area burned (TBSA), gender, inhalation injury (INHAL), full thickness burn (FTB), LOS and mortality was performed. Age, gender and FTB showed no significant influence on the development of AT deficiency. Increasing TBSA and INHAL clearly increase the risk of developing AT deficiency (p-values 0.0001 and 0.037). The analysis also identified AT deficiency as an independent predictor of LOS and mortality (p-values 0.036 and 0.003). Development of AT deficiency is a frequent event after burn with significant correlation to TBSA and INHAL, increased mortality rates and longer hospital stays.

Anticoagulants↗
PubMed2006

[Health economic aspects of the use of blood and blood products].

An adequate supply of blood components for patients depends on the population's willingness to donate blood as well as on a well-organized blood donation system. In order to ensure the blood supply, a high expenditure is necessary. The article at hand describes two areas of the use of blood and blood products. First, it considers the application of factor concentrates in haemophiliacs (approximately 3000-4000 patients are regularly in need of treatment). For the German statutory health insurance, the estimated yearly expenses for factor concentrates is approx. 450 million Euros, the average costs per patient and year and per treatment center range between 40,903 and 117,597 Euros. The costs for an immune tolerance therapy (ITT) for patients with inhibitors are estimated to be between 70,300 and 3,800,000 Euros for children, depending on the length of the therapy and the degree of severity. In the second part of the article, the authors outline the status quo of the economic evaluation of cellular blood products and present the results of a German cross-sectional survey on the use of erythrocytes in orthopaedic surgery. Within the scope of this hemotherapy study, the transfusion rates vary considerably within the participating treatment centers [elective hip joint replacement (THR): 17 and 94%]. The average blood loss also differs significantly. Comparing the treatment centers, the calculated blood loss during THR shows considerable differences (median blood loss in treatment center with lowest/treatment center with highest blood loss: 883 ml/2,975 ml). The acceptance of low intraoperative hemoglobin values in the clinics is high and diverse. These differences in transfusion procedures between the treatment centers clearly show the need to take effective action in the area of quality assurance in order to make the most of the existent savings potential. Transparency of treatment processes is a necessary condition for an economic assessment and for optimal resource allocation.

Blood Banks↗
PubMed2005

[Economic value of tiotropium in the treatment of chronic obstructive pulmonary disease].

The economic value of tiotropium in patients with moderate to severe COPD was analysed in a cost-effectiveness study for the Swiss public health insurance system. The results show a drop in COPD exacerbations in comparison to Ipratropium, Salmeterol and standard care (without use of anticholinergics and beta-adrenergics). The numbers-needed-to-treat of tiotropium in comparison to the other medications in order to avoid severe exacerbations amounted to 8 patients (ipratropium versus tiotropium), 13 patients (standard care versus tiotropium) and 33 patients (salmeterol versus tiotropium) during 12 months. As a result fewer episodes of hospitalisations and shorter hospital stays can be expected. The direct yearly total cost for COPD therapy is CHF 4788 for tiotropium and CHF 5820 for ipratropium. Furthermore, they amount to CHF 4881 and CHF 4920 for salmeterol and standard care. The higher acquisition cost for tiotropium is compensated by fewer exacerbations. No other medication was similarly cost-effective with regard to total cost and number of exacerbations.

Albuterol↗
PubMed2005

Lactate: early predictor of morbidity and mortality in patients with severe burns.

A severe burn results in a devastating and unique derangement called burn shock. Historically, resuscitation has been guided by a combination of basic laboratory values, invasive monitoring and clinical findings, but the optimal guide to the endpoint of resuscitation remains controversial. One-hundred sixty-six patients, who were admitted to our Burn Unit, were enrolled in this prospective study. Resuscitation of these patients was undertaken according to the current standard of care. Parkland formula was used as a first approximation of acquired fluid administration rates and fluid administration was adapted in order to meet clinical needs. The aim of this study was to evaluate if plasma lactate is a useful parameter to estimate the severity of a burn shock. One of the main objectives was to evaluate, if the lactate clearance adds additional information. The results of this study indicate that the initial lactate level (Day 0) is a useful parameter to separate survivors from non-survivors. Moreover, a significant marker of shock and resuscitation was observed in evaluating the lactate clearance on Day 1. A better chance of survival occurs when resuscitation results in a lactate clearance to normal values within 24h (survival was 68% if the lactate reached normal values, compared to 32% if the lactate level remained supra-normal). In summary, we believe that measuring lactate and lactate clearance may help to detect critically injured patients either for adequacy of treatment, or selection of other therapeutic options.

Biomarkers↗
PubMed2005

Analysis of mRNA in hemophilia A patients with undetectable mutations reveals normal splicing in the factor VIII gene.

BACKGROUND: haemophilia A (HA) is characterized by partial or total deficiency of factor VIII (FVIII) protein activity. It is caused by a broad spectrum of mutations in the FVIII gene. Despite tremendous improvements in mutation screening methods, in about 2% of HA patients no DNA change could be found, even after sequencing the whole coding part of the FVIII gene including the flanking splice sites, as well as the promotor and the 3' UTR regions. OBJECTIVES, PATIENTS AND METHODS: In the present study we performed a detailed RNA analysis of three groups of patients. The first included control patients with known splicing defects, the second included two patients with already identified nucleotide changes close to splicing sites, that could potentially alter the normal splicing process, and a third group of 11 unrelated patients whose genomic DNA have already been screened for mutations by DHPLC and direct sequencing with no mutation being identified. RESULTS: Both candidate splice site mutations were shown to result in either skipping or alternative splicing of at least one exon, therefore these DNA changes must be considered as causal for the patients' HA phenotype. In contrast, no abnormalities on the RNA level were observed in any of 11 unrelated patients without mutations in the FVIII gene. CONCLUSIONS: These findings exclude mutations that could be located deep in the introns and affecting either normal splicing or lead to mechanisms causing some unknown rearrangements of the FVIII gene. In fact, our results point to the presence of still unknown factor(s) causing HA, which might be either allelic or in the close proximity of the FVIII gene or non-allelic associated with other genetic loci that are involved in the processing of the FVIII protein.

DNA Mutational Analysis↗
PubMed2004

[Disease modelling in diabetes mellitus].

Disease modelling increasingly plays an important role in planning and implementing medical decision making in diabetes care. For a general practitioner it is difficult to find access to application, benefit, arithmetic background and quality criteria of modelling. This review provides a comprehensive overview about the current methods in disease modelling in order to access quality criteria for disease modelling and modelling studies in diabetes care. The following criteria are essential for good quality in disease modelling: adequate choice of data sources, assessment of medical and economic data according to criteria of evidence-based medicine, reasonable time horizons, realistic use of discounting and inflation rates, representative target populations and a realistic perspective of the cost-benefit analysis. Furthermore, validation of disease models and the adequate use of those instruments are of importance.

Computer Simulation↗
PubMed2004

Treatment patterns and cost-of-illness of severe haemophilia in patients with inhibitors in Germany.

To evaluate current treatment patterns and resource utilization as well as related cost in the management of severe haemophilia patients with inhibitors in Germany, a cost-of-illness study was conducted. Generally, data were generated by structured literature search. Missing data were collected by expert interviews. All data were validated by a panel of German experts in haemophilia care. In Germany, immune tolerance therapy (ITT) is first-line therapy in inhibitor management for children in the initial year after inhibitor development, particularly for high responders (HR). In adult HR patients ITT is applied but to a remarkably lower extent than in children. To treat bleeding episodes, factor VIII (FVIII) is first-line therapy in low responders (LR). For paediatric HR patients, bleeds are mainly treated with recombinant FVIIa (rFVIIa). In adult HR patients, activated prothrombin complex concentrate (aPCC) and rFVIIa are more equally distributed as treatment options. Treatment costs were calculated for paediatric patients (15 kg) and adult patients (75 kg) from third party payers' perspective. Cost for ITT ranges from Euro 70,290 (2 months; LR) to Euro 3 812,400 (24 months; with aPCC; HR) in a paediatric patient. For an adult patient ITT cost ranges from Euro 287,500 (6 months; LR) to Euro 17,253,000 (36 months; HR). For on average 12.5 acute bleeds, average annual treatment costs amount to Euro 77,000 for a child and Euro 354,000 for an adult. Assessing the results it has been taken into consideration that ITT can last longer and annual number of bleeds can be extremely higher than on average 12.5 episodes. This indicates more health care resource consumption in some patients.

Adult↗
PubMed2004

[Clotting factor concentrates].

Topics of this survey are the indications and use of plasma-derived and recombinant coagulation factor concentrates. These substitution therapies need to be handled carefully by weighing up their effectiveness against the long and short term side effects in the individual patient.

Blood Coagulation Disorders↗
PubMed2003

Health-related quality of life assessment in adult haemophilia patients: a systematic review and evaluation of instruments.

The objective of this study was to review and evaluate the performance of health-related quality of life (HRQL) and other health status measures used in studies of adult haemophilia and provide recommendations for future research. A systematic literature review was performed to identify HRQL and health status measures used in haemophilia. Literature was identified using medical databases, Internet and manual searches. The search was restricted to articles published in English since 1986. Ninety-six abstracts were located; 19 relevant articles were selected for detailed review. Three main types of HRQL measures were identified: generic psychometric-based HRQL (SF-36 and SF-12), utility-based HRQL [EQ-5D and Health Utilities Index (HUI)], and musculoskeletal-specific HRQL (Arthritis Impact Measurement Scale 2, AIMS 2) instruments. No patient-rated haemophilia-specific HRQL instrument was found. The SF-36, the EQ-5D, and the HUI were able to discriminate haemophilia patient subgroups with respect to disease severity and HIV comorbidity status. Sixteen additional scales were identified that were used to measure the different aspects of physical, psychological, and social functioning of patients. There were no clinical studies of haemophilia carried out that employed HRQL instruments, thus responsiveness of these instruments could not be evaluated. The variety of instruments used in haemophilia studies highlights the need for a tool that can capture the full impact of haemophilia and its treatment on patients' HRQL. Developing such a tool poses the unique challenge of accounting for common comorbidities, such as HIV and chronic hepatitis that may have a greater HRQL impact than the underlying disease.

Health Status↗
PubMed2003

Physical training increases isometric muscular strength and proprioceptive performance in haemophilic subjects.

Sufficient muscular strength and proprioception lessen the risk of joint damage, however, both are impaired in haemophilic subjects. The aim of the study was to investigate proprioceptive performance and isometric muscular strength before and after a specialized training in haemophilic subjects (H) compared with two groups of control subjects (C). Nine subjects with severe haemophilia A, and eight 'active' C (AC) without haemophilia took part in a physical training programme over a 6-month period. Eleven 'passive' C (PC) were requested to avoid any additional training during this period. Proprioceptive performance and isometric strength were determined before and after the training programme. The maximal isometric muscular strength in the legs, bilaterally measured by knee extensor (and leg press) was increased (P < 0.05) by 34% (29%) after training in the H and by 20% (28%) in the AC groups while remaining unchanged in the PC group. The performance in one-leg-stand tests after training was increased (P < 0.05) in the H and AC groups. An improvement of angle reproduction of 20 degrees and 40 degrees (P < 0.05) in the H compared with the PC groups was seen in the tests. Quantitative sensory testing by the tuning fork showed an increase (P < 0.05) in performance of both H and AC groups. The results of the present study confirm that specific sports therapy focused on proprioceptive function and accompanied by gentle strength training with low resistance and 20-25 repetitions is able to increase proprioceptive performance and muscular strength with a minimal stress to the joints. It is strongly recommended that specialized sports therapy be included as an integral component of the complete treatment regimen of haemophilic subjects.

Adolescent↗
PubMed2003

Economics of prophylactic treatment.

Clinical studies have shown significant improvement in outcomes with the use of prophylactic treatment, as well as apparent gains in health-related quality of life. Given the high cost and still limited availability of factor concentrates, physicians, insurers and governments require cost-effectiveness data to evaluate competing treatments (eg prophylactic vs. on-demand treatment) and to set priorities within the context of each country's financial resources. To date, the few published studies of the cost-effectiveness of haemophilia prophylaxis have generally focused on the reduction in frequency of bleedings as an intermediate outcome, and not on long-term health outcomes, such as the development of arthropathy and its social and economic costs. Since all prophylactic measures are investments for the future, long-term economic consequences need to be carefully studied and evaluated.

Cost of Illness↗
PubMed2003

Consensus perspectives on prophylactic therapy for haemophilia: summary statement.

Participants in an international conference on prophylactic therapy for severe haemophilia developed a consensus summary of the findings and conclusions of the conference. In the consensus, participants agreed upon revised definitions for primary and secondary prophylaxis and also made recommendations concerning the need for an international system of pharmacovigilance. Considerations on starting prophylaxis, monitoring outcomes, and individualizing treatment regimens were discussed. Several research questions were identified as needing further investigation, including when to start and when to stop prophylaxis, optimal dosing and dose interval, and methods for assessment of long-term treatment effects. Such studies should include carefully defined cohorts, validated orthopaedic and quality-of-life assessment instruments, and cost-benefit analyses.

Consensus Statements as Topic↗
PubMed2003

[2% Haemophilia A patients without mutation in the FVIII gene].

In Germany, approximately 6,000 patients are suffering from haemophilia A. Screening methods cover 97% of the mutations. For the other patients the coding sequences of the FVIII gene have to be sequenced in total. Out of 1,350 patients, no mutation was observed in 80 patients. In 5 patients, we observed an inversion in intron 1. Known mutations were detected in 16 patients, and in 19 cases novel mutations were characterized (14 in coding regions and 5 in flanking introns). The mutations are mainly base pair substitutions, small deletions or insertions (max. 4 bp) and predicted to cause amino acid exchanges or frameshifts leading to premature stop codons. Moreover, 5 polymorphisms were identified in exons 14 and 26 as well as in introns 7 and 19. Further studies are necessary to identify their causative effects. Surprisingly, in 23 patients out of this subgroup of 80, no mutation was identified in the FVIII gene. Therefore, mutations in non-coding areas or even in other genes have to be considered responsible for the haemophilia A like phenotype. One of them codes for the von Willebrand factor (vWF). We confirmed in two of our cases mutations in the vWF gene.

Base Sequence↗
PubMed2003

[Significance of mutation analysis in patients with haemophilia A].

Haemophilia A represents the most frequent hereditary bleeding disorder in humans. The disease is caused by mutations within the factor VIII gene leading to decreased or absent factor VIII activities with a bleeding tendency depending on the degree of factor VIII deficiency. Nowadays, the causative mutations can be routinely detected and have substantially improved diagnostic and understanding of the pathophysiology of haemophilia A. Identification of the gene defects in haemophilic families have enabled fast and save carrier diagnosis. The correlation of the genetic defects with the clinical course revealed that the type of mutation represents the most important genetic predisposing factor for inhibitor formation, the most severe complication of treatment with factor VIII concentrates. Mitigated clinical courses of haemophilia A were shown to be due to special types of mutations or the presence of concomitant thrombophilic mutations. Molecular models of the factor VIII protein allowed to investigate the effects of specific mutations thus giving new insights in the structure/function relationship of the factor VIII molecule. These findings might promote the development of novel recombinant factor VIII concentrates with higher efficacy, longer half life and reduced immunogenicity.

Exons↗
PubMed2003

[Characterization of factor VIII antibody epitopes from haemophilia A patients using cellulose bound FVIII peptide libraries].

Approximately 30% of patients suffering from severe haemophilia A develop antibodies against factor VIII (FVIII) neutralizing the effect of the pro-coagulant activity of intravenously injected FVIII as a complication of replacement therapy. Generally, various epitopes on the FVIII molecule are bound by these antibodies. The detailed structure of such epitopes is unknown. In this study epitopes on the FVIII molecule are identified using solid phase bound peptide arrays carrying the whole amino acid sequence of FVIII as small oligopeptides. The binding of FVIII antibodies by specific peptide sequences on the array indicates potential epitopes. FVIII antibodies of inhibitor patients and healthy blood donors are currently investigated by this method. Identified epitopes may lead to new concepts in therapy aiming at avoidance of inhibitor formation or improvement of inhibitor eradication. As participant of the 'haemophilia A' consortium dealing with genotype/phenotype correlation in haemophilia A we investigate, if the site or type of the mutation correlates with the epitopes, and if there is any relation between epitopes and clinical course. Furthermore, the influence of epitopes on therapeutical effects and the outcome of immune tolerance induction is under scrutiny.

Autoantibodies↗
PubMed2003

[The national GTH haemophilia registry as database within the scope of the German human genome project].

The Committee of Haemophilia of the GTH has established a central registry for all German centers treating patients with haemophilia. The intention was to establish a suitable system for collecting and analyzing epidemiological data relevant to bleeding disorders. The registry provides the database within the scope of the German Human-Genome-Project. The set goal is the complete molecular characterization of the genetic mutations on chromosome X of haemophilia A patients in Germany and subsequent correlation with the phenotype. An electronic network is applied for communication. A Java-application was developed for online electronic data acquirement by the participating centers. Offline data entry and sending encrypted data carriers is possible, too. A high level of security is assured by personalized access. Data are anonymized and scrambled by secure encoding. The concept was confirmed by the official data security offices. A considerable improvement for the epidemiological sciences and a better basis on therapy for patients with bleeding disorders is expected. Furthermore the registry is available for other scientific projects.

Chromosomes, Human, X↗