Selection effects may account for better outcomes of the German Disease Management Program for type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>The nationwide German disease management program (DMP) for type 2 diabetes was introduced in 2003. Meanwhile, results from evaluation studies were published, but possible baseline differences between DMP and usual-care patients have not been examined. The objective of our study was therefore to find out if patient characteristics as socio-demographic variables, cardiovascular risk profile or motivation for life style changes influence the chance of being enrolled in the German DMP for type 2 diabetes and may therefore account for outcome differences between DMP and usual-care patients.</p> <p>Methods</p> <p>Case control study comparing DMP patients with usual-care patients at baseline and follow up; mean follow-up period of 36 ± 14 months. We used chart review data from 51 GP surgeries. Participants were 586 DMP and 250 usual-care patients with type 2 diabetes randomly selected by chart registry. Data were analysed by multivariate logistic and linear regression analyses. Significance levels were p ≤ 0.05.</p> <p>Results</p> <p>There was a better chance for enrolment if patients a) had a lower risk status for diabetes complications, i.e. non-smoking (odds ratio of 1.97, 95% confidence interval of 1.11 to 3.48) and lower systolic blood pressure (1.79 for 120 mmHg vs. 160 mmHg, 1.15 to 2.81); b) had higher activity rates, i.e. were practicing blood glucose self-monitoring (1.67, 1.03 to 2.76) and had been prescribed a diabetes patient education before enrolment (2.32, 1.29 to 4.19) c) were treated with oral medication (2.17, 1.35 to 3.49) and d) had a higher GP-rated motivation for diabetes education (4.55 for high motivation vs. low motivation, 2.21 to 9.36).</p> <p>Conclusions</p> <p>At baseline, future DMP patients had a lower risk for diabetes complications, were treated more intensively and were more active and motivated in managing their disease than usual-care patients. This finding a) points to the problem that the German DMP may not reach the higher risk patients and b) selection bias may impair the assessment of differences in outcome quality between enrolled and usual-care patients. Suggestions for dealing with this bias in evaluation studies are being made.</p

The disease management program for type 2 diabetes in Germany enhances process quality of diabetes care - a follow-up survey of patient's experiences

<p>Abstract</p> <p>Background</p> <p>In summer 2003 a disease management program (DMP) for type 2 diabetes was introduced on a nationwide basis in Germany. Patient participation and continuity of care within the DMP are important factors to achieve long-term improvements in clinical endpoints. Therefore it is of interest, if patients experience any positive or negative effects of the DMP on their treatment that would support or hamper further participation. The main objective of the study was to find out if the German Disease Management Program (DMP) for type 2 diabetes improves process and outcome quality of medical care for patients in the light of their subjective experiences over a period of one year.</p> <p>Methods</p> <p>Cohort study with a baseline interview and a follow-up after 10.4 ± 0.64 months. Data on process and outcome measures were collected by telephone interviews with 444 patients enrolled and 494 patients not enrolled in the German DMP for type 2 diabetes. Data were analyzed by multivariate logistic regression analyses.</p> <p>Results</p> <p>DMP enrolment was significantly associated with a higher process quality of care. At baseline enrolled patients more often reported that they had attended a diabetes education course (OR = 3.4), have ≥ 4 contacts/year with the attending physician (OR = 3.3), have at least one annual foot examination (OR = 3.1) and one referral to an ophthalmologist (OR = 3.4) and possess a diabetes passport (OR = 2.4). Except for the annual referral to an ophthalmologist these parameters were also statistically significant at follow-up. In contrast, no differences between enrolled and not enrolled patients were found concerning outcome quality indicators, e.g. self-rated health, Glycated hemoglobin (GHb) and blood pressure. However, 16-36% of the DMP participants reported improvements of body weight and/or GHb and/or blood pressure values due to enrolment - unchanged within one year of follow-up.</p> <p>Conclusions</p> <p>In the light of patient's experiences the DMP enhances the process quality of medical care for type 2 diabetes in Germany. The lack of significant differences in outcome quality between enrolled and not enrolled patients might be due to the short program duration. Our data suggest that the DMP for type 2 diabetes should not be withdrawn unless an evidently more promising approach is found.</p

Multimorbidity Patterns in the Elderly: A New Approach of Disease Clustering Identifies Complex Interrelations between Chronic Conditions

Objective: Multimorbidity is a common problem in the elderly that is significantly associated with higher mortality, increased disability and functional decline. Information about interactions of chronic diseases can help to facilitate diagnosis, amend prevention and enhance the patients ’ quality of life. The aim of this study was to increase the knowledge of specific processes of multimorbidity in an unselected elderly population by identifying patterns of statistically significantly associated comorbidity. Methods: Multimorbidity patterns were identified by exploratory tetrachoric factor analysis based on claims data of 63,104 males and 86,176 females in the age group 65+. Analyses were based on 46 diagnosis groups incorporating all ICD-10 diagnoses of chronic diseases with a prevalence $ 1%. Both genders were analyzed separately. Persons were assigned to multimorbidity patterns if they had at least three diagnosis groups with a factor loading of 0.25 on the corresponding pattern. Results: Three multimorbidity patterns were found: 1) cardiovascular/metabolic disorders [prevalence female: 30%; male: 39%], 2) anxiety/depression/somatoform disorders and pain [34%; 22%], and 3) neuropsychiatric disorders [6%; 0.8%]. The sampling adequacy was meritorious (Kaiser-Meyer-Olkin measure: 0.85 and 0.84, respectively) and the factors explained a large part of the variance (cumulative percent: 78 % and 75%, respectively). The patterns were largely age-dependent an

IGLV3-21*01 is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling

The prognosis of chronic lymphocytic leukemia (CLL) depends on different markers, including cytogenetic aberrations, oncogenic mutations, and mutational status of the immunoglobulin (Ig) heavy-chain variable (IGHV) gene. The number of IGHV mutations distinguishes mutated (M) CLL with a markedly superior prognosis from unmutated (UM) CLL cases. In addition, B cell antigen receptor (BCR) stereotypes as defined by IGHV usage and complementarity-determining regions (CDRs) classify ∼30% of CLL cases into prognostically important subsets. Subset 2 expresses a BCR with the combination of IGHV3-21-derived heavy chains (HCs) with IGLV3-21-derived light chains (LCs), and is associated with an unfavorable prognosis. Importantly, the subset 2 LC carries a single-point mutation, termed R110, at the junction between the variable and constant LC regions. By analyzing 4 independent clinical cohorts through BCR sequencing and by immunophenotyping with antibodies specifically recognizing wild-type IGLV3-21 and R110-mutated IGLV3-21 (IGLV3-21R110), we show that IGLV3-21R110-expressing CLL represents a distinct subset with poor prognosis independent of IGHV mutations. Compared with other alleles, only IGLV3-21*01 facilitates effective homotypic BCR-BCR interaction that results in autonomous, oncogenic BCR signaling after acquiring R110 as a single-point mutation. Presumably, this mutation acts as a standalone driver that transforms IGLV3-21*01-expressing B cells to develop CLL. Thus, we propose to expand the conventional definition of CLL subset 2 to subset 2L by including all IGLV3-21R110-expressing CLL cases regardless of IGHV mutational status. Moreover, the generation of monoclonal antibodies recognizing IGLV3-21 or mutated IGLV3-21R110 facilitates the recognition of B cells carrying this mutation in CLL patients or healthy donors

Which chronic diseases and disease combinations are specific to multimorbidity in the elderly? Results of a claims data based cross-sectional study in Germany

<p>Abstract</p> <p>Background</p> <p>Growing interest in multimorbidity is observable in industrialized countries. For Germany, the increasing attention still goes still hand in hand with a small number of studies on multimorbidity. The authors report the first results of a cross-sectional study on a large sample of policy holders (n = 123,224) of a statutory health insurance company operating nationwide. This is the first comprehensive study addressing multimorbidity on the basis of German claims data. The main research question was to find out which chronic diseases and disease combinations are specific to multimorbidity in the elderly.</p> <p>Methods</p> <p>The study is based on the claims data of all insured policy holders aged 65 and older (n = 123,224). Adjustment for age and gender was performed for the German population in 2004. A person was defined as multimorbid if she/he had at least 3 diagnoses out of a list of 46 chronic conditions in three or more quarters within the one-year observation period. Prevalences and risk-ratios were calculated for the multimorbid and non-multimorbid samples in order to identify diagnoses more specific to multimorbidity and to detect excess prevalences of multimorbidity patterns.</p> <p>Results</p> <p>62% of the sample was multimorbid. Women in general and patients receiving statutory nursing care due to disability are overrepresented in the multimorbid sample. Out of the possible 15,180 combinations of three chronic conditions, 15,024 (99%) were found in the database. Regardless of this wide variety of combinations, the most prevalent individual chronic conditions do also dominate the combinations: Triads of the six most prevalent individual chronic conditions (hypertension, lipid metabolism disorders, chronic low back pain, diabetes mellitus, osteoarthritis and chronic ischemic heart disease) span the disease spectrum of 42% of the multimorbid sample. Gender differences were minor. Observed-to-expected ratios were highest when purine/pyrimidine metabolism disorders/gout and osteoarthritis were part of the multimorbidity patterns.</p> <p>Conclusions</p> <p>The above list of dominating chronic conditions and their combinations could present a pragmatic start for the development of needed guidelines related to multimorbidity.</p

Specialist involvement and referral patterns in ambulatory medical care for patients with dementia in Germany: results of a claims data based case-control study

<p>Abstract</p> <p>Background</p> <p>To analyze the referral processes from general practitioners to specialists and among specialists for dementia patients in the time periods before, during and after the diagnosis in Germany.</p> <p>Methods</p> <p>In this case-control study claims data from 1,848 insurants with incident dementia aged 65 years and more and 7,392 matched controls were compared over a two-year period covering the pre-incidence, incidence and post-incidence time periods.</p> <p>Results</p> <p>We found an increase in referrals of 30% in the incidence quarter, mainly from general practice to neuropsychiatry and from there to radiology. Referrals to clinical chemistry and other disciplines for dementia-specific reasons were negligible in amount. 34% of incident cases had at least one contact with a neuropsychiatrist during the year of incidence, and the majority of them visited this specialist repeatedly during that year. Only a minority (13.5%) of patients was referred to radiology for imaging. Referrals to other specialists declined whereas self-referrals did not increase.</p> <p>Conclusions</p> <p>The referral rates to relevant specialists (neuropsychiatry, radiology and clinical chemistry) are far less frequent than proposed in German guidelines. More research is needed to explain the gape between guidelines and daily care and to find ways for a better implementation of guidelines in ambulatory care. Guidelines should not only deal with diagnostic procedures and therapeutic options but also consider questions of applicability in daily clinical practice and propose effective organizational models of care provision.</p

Direkte kardiale Effekte von Injektionsanästhetika am Modell des isolierten septischen Rattenherzens

Die kardiale Dysfunktion im Rahmen der Sepsis, die septische Kardiomyopathie, stellt einen ernstzunehmenden Faktor in Bezug auf den Krankheitsverlauf dar. Der teilweise inapparente Verlauf und eine zudem erschwerte Diagnostik stellen tagtäglich eine besondere Herausforderung für die Intensivmediziner dar. Da eine spezifische Therapie der septischen Kardiomyopathie derzeit nicht vorhanden ist, kommen allgemeine Maßnahmen der Inten-sivmedizin und Sepsistherapie zur Anwendung. Mögliche Interaktionen bzw. direkte Effekte der angewendeten Medikamente auf die bereits eingeschränkte kardiale Funktion liegen bis-lang nicht ausreichend vor. Die vorliegende Studie untersuchte vergleichend die direkten kardialen Effekte von fünf verschiedenen Injektionsanästhetika bei äquimolaren Konzentra-tionen auf das septische Herz im Langendorff-Modell. Die erhobenen Ergebnisse zeigen am isolierten septischen Rattenherzen, dass S(+)-Ketamin, Propofol, Etomidat, Midazolam und Methohexital dosisabhängig in unterschiedlicher Schwere und Form auf die Herzparameter wirken. Der schon von Paracelcus (1493-1541) getätigte Ausspruch „Dosis sola venenum facit“ findet sich auch in dieser Studie wieder. Im Konzentrationsbereich von 1*10-8 M bis 1*10-6 M sieht man bei keinem der fünf getesteten Medikamente eine signifikante Wirkung. In höheren Bereichen von 1*10-5 M bis 1*10-4 M weisen besonders S(+)-Ketamin und Propofol teilweise gegenläufige Wirkungen auf. Propofol zeigt die stärkste kardiodepressive Wirkung aller Medikamente auf, wohingegen S(+)-Ketamin eine eher neutrale bzw. positive kardiale Wirkung ausübt. Etomidat zeigt in dieser Studie die geringsten kardialen Wirkungen. Vor diesem Hintergrund stellt sich die Frage, inwiefern S(+)-Ketamin eine denkbare Alternative zu Etomidat darstellt, da derzeitig die Gabe von Etomidat aufgrund der potentiellen immunkompromittierenden Eigenschaften in der Sepsis kontrovers diskutiert wird. Wenngleich eine klinische Übertragbarkeit nur sehr eingeschränkt möglich ist, scheint S(+)-Ketamin bei der Betrachtung der erhobenen positiven kardialen und beschriebenen immunmodulatorischen Effekte auf das isolierte septische Herz bzw. auf die Sepsis und ins-besondere vor dem Hintergrund der fehlenden Nebennierenwirkung eine adäquate Alternative zu Etomidat darzustellen

The impact of crystalloidal and colloidal infusion preparations on coronary vascular integrity, interstitial oedema and cardiac performance in isolated hearts

Introduction: Recent data suggested an interaction between plasma constituents and the endothelial glycocalyx to be relevant for vascular barrier function. This might be negatively influenced by infusion solutions, depending on ionic composition, pH and binding properties. The present study evaluated such an influence of current artificial preparations. Methods: Isolated guinea pig hearts were prepared in a modified Langendorff mode and perfused with Krebs-Henseleit buffer augmented with 1g% human albumin. After equilibration the perfusion was switched to replacement of one half buffer by either isotonic saline (NaCl), ringer's acetate (Ri-Ac), 6% and 10% hydroxyethyl starch (6% and 10% HES, resp.), or 4% gelatine (Gel), the artificial colloids having been prepared in balanced solution. We analysed glycocalyx shedding, functional integrity of the vascular barrier and heart performance. Results: While glycocalyx shedding was not observed, diluting albumin concentration towards 0.5g% by artificial solutions was associated with a marked functional breakdown of vascular barrier competence. This effect was biggest with isotonic saline and significantly attenuated with artificial colloids, the difference in the pressure dependent transvascular fluid filtration (basal vs. during infusion in groups NaCl, Ri-Ac, 6% HES, 10% HES and Gel, n = 6 each) being 0.31 +/- 0.03 vs. 1.00 +/- 0.04; 0.27 +/- 0.03 vs. 0.81 +/- 0.03; 0.29 +/- 0.03 vs. 0.68 +/- 0.02; 0.32 +/- 0.03 vs. 0.59 +/- 0.08 and 0.31 +/- 0.04 vs. 0.61 +/- 0.03 g/5min, respectively. Heart performance was directly related to pH value (7.38 +/- 0.06, 7.33 +/- 0.03, 7.14 +/- 0.04, 7.08 +/- 0.04, 7.25 +/- 0.03), the change in the rate pressure product being 21,702 +/- 1969 vs. 21,291 +/- 2,552; 22,098 +/- 2,115 vs. 14,114 +/- 3,386; 20,897 +/- 2,083 vs. 10,671 +/- 1,948; 21,822 +/- 2,470 vs. 10,047 +/- 2,320 and 20,955 +/- 2,296 vs. 15,951 +/- 2,755 mmHg x bpm, respectively. Conclusions: It appears important to maintain the pH value within a physiological range to maintain optimal myocardial contractility. Using colloids prepared in calcium-containing, balanced solutions for volume replacement therapy may attenuate the breakdown of vascular barrier competence in the critically ill