Optimizing Care for Adults with Congenital Heart Disease: Results of a Conjoint Analysis Based on a Nationwide Sample of Patients Included in the German National Register.

(1) Background: Congenital heart disease (CHD) requires lifelong specialized care. Failure to follow up and gaps in care are common in this group and lead to increased morbidity/mortality. We evaluated patients' perceived needs and expectations regarding specialized care using state-of-the-art statistical and market research techniques based on a nationwide sample of CHD patients. (2) Methods: A random sample of adults with CHD registered in the German National Register for Congenital Heart Defects were invited to answer an adaptive online questionnaire based on the conjoint analysis (CA) technique. CA determines the relative importance of various aspects of health care provision and allows individuals to trade between characteristics, thus recognizing limited resources. (3) Results: 637 patients participated (mean age 33.8 ± 12.6 years; 55.6% female; disease complexity: simple defect 12.6%, moderate complexity 40.3%, complex CHD 40.2%) in the analysis. Patients assigned the highest relative importance to aspects of patient-physician communication, physician qualifications, waiting time, medical care, and medical equipment. Comfort-related aspects such as driving time or hotel aspects of care received much lower scores. We identified four well-defined clusters of patients with differing expectation patterns: (i) time sensitive patients; (ii) excellence seeking patients; (iii) continuity seekers, and (iv) support seeking patients. (4) Conclusions: Adult CHD patients rank effective patient-physician interaction and communication as the most important factors. As we identified significant heterogeneity between CHD patients, centers should cater for individual preferences and integrate individual needs into treatment plans to prevent failure to follow up and ensure patient compliance.

Determination of dialysis dose: a clinical comparison of methods.

BACKGROUND: Guidelines recommend regular measurements of the delivered hemodialysis dose Kt/V. Nowadays, automatic non-invasive online measurements are available as alternatives to the conventional method with blood sampling, laboratory analysis, and calculation. METHODS: In a prospective clinical trial, three different methods determining dialysis dose were simultaneously applied: Kt/V(Dau) (conventional method with Daugirdas' formula), Kt/V(OCM) [online clearance measurement (OCM) with urea distribution volume V based on anthropometric estimate], and Kt/V(BCM) [OCM measurement with V measured by bioimpedance analysis (Body Composition Monitor)]. RESULTS: 1,076 hemodialysis patients were analyzed. The dialysis dose was measured as Kt/V(Dau) = 1.74 ± 0.45, Kt/V(OCM) = 1.47 ± 0.34, and Kt/V(BCM) = 1.65 ± 0.42. The difference between Kt/V(OCM) and Kt/V(BCM) was due to the difference between anthropometric estimated V(Watson) and measured V(BCM). Compared to Kt/V(Dau), Kt/V(OCM) was 15% lower and Kt/V(BCM) 5% lower. Kt/V(Dau) was incidentally prone to falsely high values due to operative errors, whereas in these cases OCM-based measurements Kt/V(OCM) and Kt/V(BCM) delivered realistic values. CONCLUSIONS: The automated OCM Kt/V(OCM) with anthropometric estimation of urea distribution volume was the easiest method to use, but Kt/V(BCM) with measured urea distribution volume was closer to the conventional method.

Increasing pressure ulcer rates and changes in delivery of care: a retrospective analysis at a University Clinic.

AIM: To evaluate the relation between pressure ulcers and delivery of care. BACKGROUND: No decrease of pressure ulcer rates could be recognised in acute hospital care, despite intensive efforts in prevention. Furthermore, reports show increasing rates. DESIGN: Retrospective analysis of hospital data. METHODS: The study included all inpatients from year 1 (2003/2004) and 4 (2006/2007) of the interdisciplinary decubitus project. Information on ulcers was recorded at admission, discharge and in case of new events. We analysed the effect of age, length of stay, operation and intensive care episode. In logistic regression, we used the existence of ulcers and the appearance of new ulcers as dependent variables. RESULTS: Parallel to a decrease in the number of inpatients, age, length of stay and operation frequency rose between 2003 and 2007. Higher age, longer length of stay, operation, intensive care episode and year 4 raise the odds for ulcers in univariate and with exception of operation in multivariate analyses. With exception of operation and year 4, the same variables raise the odds for new ulcers, too. CONCLUSIONS: The increase of pressure ulcer frequency could be related to changes in delivery of care. The adverse event pressure ulcer will become more important in hospital care. RELEVANCE TO CLINICAL PRACTICE: There is no decrease in pressure ulcer rates, albeit enormous efforts in prevention. Hospital care has been facing changes in case mix. Age, length of stay and intensive care episodes are related to increasing ulcer rates at a University Clinic. Nursing management has to be aware of additional workload for pressure ulcer management in the future.

Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension.

BACKGROUND: Patients with hypertension may require combination therapy to attain the blood pressure targets recommended by US and European treatment guidelines. Combination therapy with a calcium channel blocker and an angiotensin II-receptor blocker would be expected to provide enhanced efficacy. OBJECTIVES: Two studies were conducted to compare the efficacy of various combinations of amlodipine and valsartan administered once daily with their individual components and placebo in patients with mild to moderate essential hypertension (mean sitting diastolic blood pressure [MSDBP] >/=95 and < 110 mm Hg). A secondary objective was to evaluate safety and tolerability. METHODS: The 2 studies were multinational, multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group trials. In study 1, patients were randomized to receive amlodipine 2.5 or 5 mg once daily, valsartan 40 to 320 mg once daily, the combination of amlodipine 2.5 or 5 mg with valsartan 40 to 320 mg once daily, or placebo. In study 2, patients were randomized to receive amlodipine 10 mg once daily, valsartan 160 or 320 mg once daily, the combination of amlodipine 10 mg with valsartan 160 or 320 mg once daily, or placebo. The primary efficacy variable in both studies was change from baseline in MSDBP at the end of the study. Secondary variables included the change in mean sitting systolic blood pressure (MSSBP), response rate (the proportion of patients achieving an MSDBP <90 mm Hg or a >/= 10-mm Hg decrease from baseline), and control rate (the proportion of patients achieving an MSDBP <90 mm Hg). Safety was assessed in terms of adverse events (spontaneously reported or elicited by questioning), vital signs, and laboratory values. RESULTS: A total of 1911 patients were randomized to treatment in study 1 (1022 amlodipine + valsartan; 507 valsartan; 254 amlodipine; 128 placebo); 1250 were randomized to treatment in study 2 (419, 415, 207, and 209, respectively). In all treatment groups in both studies, the majority of patients were white (79.5% study 1, 79.4% study 2) and male (53.5% and 50.3%, respectively). The overall mean age was 54.4 years in study 1 and 56.9 years in study 2. The mean weight of patients in study 1 was higher than that in study 2 (88.8 vs 79.7 kg). The overall baseline mean sitting BP was 152.8/99.3 mm Hg in study 1 and 156.7/99.1 mm Hg in study 2. With the exception of a few combinations that included amlodipine 2.5 mg, the combination regimens in both studies were associated with significantly greater reductions in MSDBP and MSSBP compared with their individual components and placebo (P < 0.05). A positive dose response was observed for all combinations. The highest response rate in study 1 was associated with the highest dose of combination therapy (amlodipine 5 mg + valsartan 320 mg: 91.3%). Amlodipine 5 mg, valsartan 320 mg, and placebo were associated with response rates of 71.9%, 73.4%, and 40.9%, respectively. In study 2, the 2 doses of combination therapy were associated with similar response rates (amlodipine 10 mg + valsartan 160 mg: 88.5%; amlodipine 10 mg + valsartan 320 mg: 87.5%). Amlodipine 10 mg was associated with a response rate of 86.9%; valsartan 160 and 20 mg were associated with response rates of 74.9% and 72.0%, respectively; and placebo was associated with a response rate of 49.3%. Control rates followed a similar pattern. The incidence of peripheral edema with combination therapy was significantly lower compared with amlodipine monotherapy (5.4% vs 8.7%, respectively; P = 0.014), was significantly higher compared with valsartan monotherapy (2.1%; P < 0.001), and did not differ significantly from placebo (3.0%). CONCLUSIONS: In these adult patients with mild to moderate hypertension, the combination of amlodipine + valsartan was associated with significantly greater blood pressure reductions from baseline compared with amlodipine or valsartan monotherapy or placebo. The incidence of peripheral edema was significantly lower with combination therapy than with amlodipine monotherapy.

Problem focused integration of information, quality and process management with empirical research: The example of the Essen Interdisciplinary Pressure Ulcer Project.

Issues of information management, quality management, process management, and empirical research are often seen independently from each other. In the Essen interdisciplinary pressure ulcer project, they were integrated to establish a synergy between quality of care, economics and research. The electronic documentation of events and supplementary information was done with the hospital wide patient administration system. Feedback and automatically requests were used for quality improvement. Codes for reimbursement are generated from the clinical documentation. Research studies had been based on the routine documentation. Prerequisite was the cooperation of all relevant groups, nurses, physicians, informaticians, theoreticians and medical controller. In the future, it will be necessary to extend the approach to other relevant nursing problems and to replace the redundant documentation (paper-based as well as electronic) by an electronic health record.

COMBO-FISH for focussed fluorescence labelling of gene domains: 3D-analysis of the genome architecture of abl and bcr in human blood cells.

Structural analysis and nanosizing of gene domains requires not only high-resolution microscopy but also improved techniques of fluorescence labelling strongly focussed on the gene domains. To investigate the architecture of abl and bcr in blood cell nuclei forming the Philadelphia chromosome in CML, we applied COMBO-FISH using specifically colocalising combinations of triple strand forming oligonucleotide probes for abl on chromosome 9 and bcr on chromosome 22. Each probe set consisting of 31 homopyrimidine oligonucleotides was computer selected from the human genome database. Measurements by 3D microscopy were compared to results obtained after standard FISH using commercially available abl/bcr BAC probes. The relative radial fluorescence distributions in lymphocyte cell nuclei of healthy donors in comparison to cell nuclei of blood cells of CML patients showed a strong correlation in the location of abl and bcr for both labelling techniques. The absolute distances of the homologous bcr domains and the abl domain-nuclear center-abl domain angles in cell nuclei of CML donors differed significantly from those of healthy donors only when COMBO-FISH was applied. These results indicate that COMBO-FISH may be more sensitive than standard FISH in case of slight modifications in the genome architecture.

Pressure ulcers in secondary care: incidence, prevalence, and relevance.

OBJECTIVE: To compare point and period prevalence rates. DESIGN: Descriptive, cohort, cross-sectional survey. PARTICIPANTS: From a cohort of 25,075 cases, information on pressure ulcer status on admission was recorded for 20,283 cases. From 3237 selected cases, the pressure ulcer team made 2234 assessments. MAIN OUTCOME MEASURES: Point prevalence, period prevalence, and incidence rates. MAIN RESULTS: The cohort showed a period prevalence rate of 1.4% and an incidence rate of 0.6%. Patients with a pressure ulcer were older, were more likely to have had surgery, had longer hospital stays, and had a higher cost weight. The cross-sectional survey revealed a point prevalence rate of 5.3%. Patients within the cross-sectional survey had longer lengths of stay, were more likely to have had surgery, and presented a higher cost weight in comparison with the cohort. CONCLUSIONS: In an unselected hospital sample one can expect a period prevalence rate of 2% and a point prevalence rate of 10%. As demonstrated by the present study, differences between the 2 prevalence measurements are mainly due to the confounding of point prevalence rates by length of stay. Length of stay determines the probability of inclusion in a cross-sectional study and should be considered in pressure ulcer trials in the future.

Development of a long-acting insulin analog using albumin fusion technology.

The primary therapeutic goal for the treatment of diabetes is maintenance of a long-term, near-normoglycemic condition and prevention of the onset or progression of the complications associated with the disease. Although several analogs of human insulin have been developed, the currently prescribed long-acting insulin analogs do not provide a stable basal glycemia for more than a few hours. Here, we report the development of Albulin, a long-acting insulin analog obtained by direct gene fusion of a single-chain human insulin to human serum albumin. Albulin showed an elimination t(1/2) of approximately 7 h in normoglycemic mice. In vitro pharmacodynamic profiles for Albulin characterized by receptor binding, inhibition of gluconeogenesis, induction of glucose uptake, and global regulation of gene expression in relevant cell types showed that Albulin produced similar activity profiles compared with that of recombinant human insulin. A single Albulin administration in vivo normalized blood glucose level in diabetic mice in a relatively peakless and sustained (24-h) fashion. A further reduction in glucose levels was achieved by administering a recombinant human insulin a few hours after Albulin injection in mice, indicating the potential for Albulin therapy in combination with available fast-acting insulin derivatives. In summary, Albulin displays characteristics of a potent long-acting insulin analog that can be evaluated for use as a novel insulin therapy for patients with insulin-dependent diabetes.

An integrated functional genomics screening program reveals a role for BMP-9 in glucose homeostasis.

A coordinated functional genomics program was implemented to identify secreted polypeptides with therapeutic applications in the treatment of diabetes. Secreted factors were predicted from a diverse expressed-sequence tags (EST) database, representing >1,000 cDNA libraries, using a combination of bioinformatic algorithms. Subsequently, approximately 8,000 human proteins were screened in high-throughput cell-based assays designed to monitor key physiological transitions known to be centrally involved in the physiology of type 2 diabetes. Bone morphogenetic protein-9 (BMP-9) gave a positive response in two independent assays: reducing phosphoenolpyruvate carboxykinase (PEPCK) expression in hepatocytes and activating Akt kinase in differentiated myotubes. Purified recombinant BMP-9 potently inhibited hepatic glucose production and activated expression of key enzymes of lipid metabolism. In freely fed diabetic mice, a single subcutaneous injection of BMP-9 reduced glycemia to near-normal levels, with maximal reduction observed 30 hours after treatment. BMP-9 represents the first hepatic factor shown to regulate blood glucose concentration. Using a combination of bioinformatic and high-throughput functional analyses, we have identified a factor that may be exploited for the treatment of diabetes.