Interdisciplinary diabetes care teams operating on the interface between primary and specialty care are associated with improved outcomes of care: findings from the Leuven Diabetes Project

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes mellitus is a complex, progressive disease which requires a variety of quality improvement strategies. Limited information is available on the feasibility and effectiveness of interdisciplinary diabetes care teams (IDCT) operating on the interface between primary and specialty care. A first study hypothesis was that the implementation of an IDCT is feasible in a health care setting with limited tradition in shared care. A second hypothesis was that patients who make use of an IDCT would have significantly better outcomes compared to non-users of the IDCT after an 18-month intervention period. A third hypothesis was that patients who used the IDCT in an Advanced quality Improvement Program (AQIP) would have significantly better outcomes compared to users of a Usual Quality Improvement Program (UQIP).</p> <p>Methods</p> <p>This investigation comprised a two-arm cluster randomized trial conducted in a primary care setting in Belgium. Primary care physicians (PCPs, n = 120) and their patients with type 2 diabetes mellitus (n = 2495) were included and subjects were randomly assigned to the intervention arms. The IDCT acted as a cornerstone to both the intervention arms, but the number, type and intensity of IDCT related interventions varied depending upon the intervention arm.</p> <p>Results</p> <p>Final registration included 67 PCPs and 1577 patients in the AQIP and 53 PCPs and 918 patients in the UQIP. 84% of the PCPs made use of the IDCT. The expected participation rate in patients (30%) was not attained, with 12,5% of the patients using the IDCT. When comparing users and non-users of the IDCT (irrespective of the intervention arm) and after 18 months of intervention the use of the IDCT was significantly associated with improvements in HbA1c, LDL-cholesterol, an increase in statins and anti-platelet therapy as well as the number of targets that were reached. When comparing users of the IDCT in the two intervention arms no significant differences were noted, except for anti-platelet therapy.</p> <p>Conclusion</p> <p>IDCT's operating on the interface between primary and specialty care are associated with improved outcomes of care. More research is required on what team and program characteristics contribute to improvements in diabetes care.</p> <p>Trial registration</p> <p>NTR 1369.</p

Planning a cluster randomized trial with unequal cluster sizes: practical issues involving continuous outcomes

BACKGROUND: Cluster randomization design is increasingly used for the evaluation of health-care, screeening or educational interventions. At the planning stage, sample size calculations usually consider an average cluster size without taking into account any potential imbalance in cluster size. However, there may exist high discrepancies in cluster sizes. METHODS: We performed simulations to study the impact of an imbalance in cluster size on power. We determined by simulations to which extent four methods proposed to adapt the sample size calculations to a pre-specified imbalance in cluster size could lead to adequately powered trials. RESULTS: We showed that an imbalance in cluster size can be of high influence on the power in the case of severe imbalance, particularly if the number of clusters is low and/or the intraclass correlation coefficient is high. In the case of a severe imbalance, our simulations confirmed that the minimum variance weights correction of the variation inflaction factor (VIF) used in the sample size calculations has the best properties. CONCLUSION: Publication of cluster sizes is important to assess the real power of the trial which was conducted and to help designing future trials. We derived an adaptation of the VIF from the minimum variance weights correction to be used in case the imbalance can be a priori formulated such as "a proportion (γ) of clusters actually recruit a proportion (τ) of subjects to be included (γ ≤ τ)"

Predictors of glycemic control among patients with Type 2 diabetes: A longitudinal study

BACKGROUND: Diabetes is the sixth leading cause of death and results in significant morbidity. The purpose of this study is to determine what demographic, health status, treatment, access/quality of care, and behavioral factors are associated with poor glycemic control in a Type 2 diabetic, low-income, minority, San Diego population. METHODS: Longitudinal observational data was collected on patients with Type 2 diabetes from Project Dulce, a program in San Diego County designed to care for an underserved diabetic population. The study sample included 573 patients with a racial/ethnic mix of 53% Hispanic, 7% black, 18% Asian, 20% white, and 2% other. We utilized mixed effects models to determine the factors associated with poor glycemic control using hemoglobin A1C (A1C) as the outcome of interest. A multi-step model building process was used resulting in a final parsimonious model with main effects and interaction terms. RESULTS: Patients had a mean age of 55 years, 69% were female, the mean duration of diabetes was 7.1 years, 31% were treated with insulin, and 57% were obese. American Diabetes Association (ADA) recommendations for blood pressure and total cholesterol were met by 71% and 68%, respectively. Results of the mixed effects model showed that patients who were uninsured, had diabetes for a longer period of time, used insulin or multiple oral agents, or had high cholesterol had higher A1C values over time indicating poorer glycemic control. The younger subjects also had poorer control. CONCLUSION: This study provides factors that predict glycemic control in a specific low-income, multiethnic, Type 2 diabetic population. With this information, subgroups with high risk of disease morbidity were identified. Barriers that prevent these patients from meeting their goals must be explored to improve health outcomes

Peripheral chondrosarcoma progression is associated with increased type X collagen and vascularisation

Endochondral bone formation requires a cartilage template, known as the growth plate, and vascular invasion, bringing osteoblasts and osteoclasts. Endochondral chondrocytes undergo sequences of cell division, matrix secretion, cell hypertrophy, apoptosis, and matrix calcification/mineralisation. In this study, two critical steps of endochondral bone formation, the deposition of collagen X-rich matrix and blood vessel attraction/invasion, were investigated by immunohistochemistry. Fourteen multiple osteochondromas and six secondary peripheral chondrosarcomas occurring in patients with multiple osteochondromas were studied and compared to epiphyseal growth plate samples. Mutation analysis showed all studied patients (expect one) to harbour a germ-line mutations in either EXT1 or EXT2. Here, we described that homozygous mutations in EXT1/EXT2, which are causative for osteochondroma formation, are likely to affect terminal chondrocyte differentiation and vascularisation in the osteocartilaginous interface. Contrastingly, terminal chondrocyte differentiation and vascularisation seem to be unaffected in secondary peripheral chondrosarcoma. In addition, osteochondromas with high vascular density displayed a higher proliferation rate. A similar apoptotic rate was observed in osteochondromas and secondary peripheral chondrosarcomas. Recently, it has been shown that cells with functional EXT1 and EXT2 are outnumbering EXT1/EXT2 mutated cells in secondary peripheral chondrosarcomas. This might explain the increased type X collagen production and blood vessel attraction in these malignant tumours

Evaluation of a health promotion program in children: Study protocol and design of the cluster-randomized Baden-Württemberg primary school study [DRKS-ID: DRKS00000494]

<p>Abstract</p> <p>Background</p> <p>Increasing prevalences of overweight and obesity in children are known problems in industrialized countries. Early prevention is important as overweight and obesity persist over time and are related with health problems later in adulthood. "Komm mit in das gesunde Boot - Grundschule" is a school-based program to promote a healthier lifestyle. Main goals of the intervention are to increase physical activity, decrease the consumption of sugar-sweetened beverages, and to decrease time spent sedentary by promoting active choices for healthy lifestyle. The program to date is distributed by 34 project delivery consultants in the state of Baden-Württemberg and is currently implemented in 427 primary schools. The efficacy of this large scale intervention is examined via the Baden-Württemberg Study.</p> <p>Methods/Design</p> <p>The Baden-Württemberg Study is a prospective, stratified, cluster-randomized, and longitudinal study with two groups (intervention group and control group). Measurements were taken at the beginning of the academic years 2010/2011 and 2011/2012. Efficacy of the intervention is being assessed using three main outcomes: changes in waist circumference, skinfold thickness and 6 minutes run. Stratified cluster-randomization (according to class grade level) was performed for primary schools; pupils, teachers/principals, and parents were investigated. An approximately balanced number of classes in intervention group and control group could be reached by stratified randomization and was maintained at follow-up.</p> <p>Discussion</p> <p>At present, "Komm mit in das Gesunde Boot - Grundschule" is the largest school-based health promotion program in Germany. Comparative objective main outcomes are used for the evaluation of efficacy. Simulations showed sufficient power with the existing sample size. Therefore, the results will show whether the promotion of a healthier lifestyle in primary school children is possible using a relatively low effort within a school-based program involving children, teachers and parents. The research team anticipates that not only efficacy will be proven in this study but also expects many other positive effects of the program.</p> <p>Trial registration</p> <p>German Clinical Trials Register (DRKS), DRKS-ID: DRKS00000494</p

Activation of Akt by the Bacterial Inositol Phosphatase, SopB, is Wortmannin Insensitive

Salmonella enterica uses effector proteins translocated by a Type III Secretion System to invade epithelial cells. One of the invasion-associated effectors, SopB, is an inositol phosphatase that mediates sustained activation of the pro-survival kinase Akt in infected cells. Canonical activation of Akt involves membrane translocation and phosphorylation and is dependent on phosphatidyl inositide 3 kinase (PI3K). Here we have investigated these two distinct processes in Salmonella infected HeLa cells. Firstly, we found that SopB-dependent membrane translocation and phosphorylation of Akt are insensitive to the PI3K inhibitor wortmannin. Similarly, depletion of the PI3K regulatory subunits p85α and p85ß by RNAi had no inhibitory effect on SopB-dependent Akt phosphorylation. Nevertheless, SopB-dependent phosphorylation does depend on the Akt kinases, PDK1 and rictor-mTOR. Membrane translocation assays revealed a dependence on SopB for Akt recruitment to Salmonella ruffles and suggest that this is mediated by phosphoinositide (3,4) P2 rather than phosphoinositide (3,4,5) P3. Altogether these data demonstrate that Salmonella activates Akt via a wortmannin insensitive mechanism that is likely a class I PI3K-independent process that incorporates some essential elements of the canonical pathway

A cluster randomized trial to improve adherence to evidence-based guidelines on diabetes and reduce clinical inertia in primary care physicians in Belgium: study protocol [NTR 1369]

Contains fulltext : 70617.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Most quality improvement programs in diabetes care incorporate aspects of clinician education, performance feedback, patient education, care management, and diabetes care teams to support primary care physicians. Few studies have applied all of these dimensions to address clinical inertia. AIM: To evaluate interventions to improve adherence to evidence-based guidelines for diabetes and reduce clinical inertia in primary care physicians. DESIGN: Two-arm cluster randomized controlled trial. PARTICIPANTS: Primary care physicians in Belgium. INTERVENTIONS: Primary care physicians will be randomly allocated to 'Usual' (UQIP) or 'Advanced' (AQIP) Quality Improvement Programs. Physicians in the UQIP will receive interventions addressing the main physician, patient, and office system factors that contribute to clinical inertia. Physicians in the AQIP will receive additional interventions that focus on sustainable behavior changes in patients and providers. OUTCOMES: Primary endpoints are the proportions of patients within targets for three clinical outcomes: 1) glycosylated hemoglobin < 7%; 2) systolic blood pressure differences </=130 mmHg; and 3) low density lipoprotein/cholesterol < 100 mg/dl. Secondary endpoints are individual improvements in 12 validated parameters: glycosylated hemoglobin, low and high density lipoprotein/cholesterol, total cholesterol, systolic blood pressure, diastolic blood pressure, weight, physical exercise, healthy diet, smoking status, and statin and anti-platelet therapy. PRIMARY AND SECONDARY ANALYSIS: Statistical analyses will be performed using an intent-to-treat approach with a multilevel model. Linear and generalized linear mixed models will be used to account for the clustered nature of the data, i.e., patients clustered withinimary care physicians, and repeated assessments clustered within patients. To compare patient characteristics at baseline and between the intervention arms, the generalized estimating equations (GEE) approach will be used, taking the clustered nature of the data within physicians into account. We will also use the GEE approach to test for differences in evolution of the primary and secondary endpoints for all patients, and for patients in the two interventions arms, accounting for within-patient clustering. TRIAL REGISTRATION: number: NTR 1369