Frank Nobels

Chromogranin A : its clinical value as marker of neuroendocrine tumours

Chromogranin A (CgA) belongs to a family of secretory proteins that are present in dense‐core vesicles of neuroendocrine cells. Owing to its widespread distribution in neuroendocrine tissues, it can be used as an excellent immunohistochemical marker of neoplasms of neuroendocrine origin. It can also serve as serum marker of neuroendocrine activity because it is co‐released with the peptide hormone content of the secretory granules. The serum concentration of CgA is elevated in patients with various neuroendocrine tumours. Elevated levels are strongly correlated with tumour volume. Although its sensitivity and specificity cannot compete with that of the specific hormonal secretion products of most of these tumours, it can nevertheless have useful clinical applications. Neuroendocrine tumours for which no peptide marker is available usually retain the capacity to secrete CgA. CgA can thus be used as serum marker for these so‐called ‘non‐functioning’ endocrine tumours. Moreover, in patients with carcinoids and phaeochromocytomas, CgA is a more stable and thus more easily manageable marker than plasma levels of respectively serotonin and catecholamines and their urinary metabolites. Its role as an important general neuroendocrine marker may be extended in the future by the development of immunoscintigraphy of membrane‐bound CgA, allowing in vivo visualization of neuroendocrine neoplasms.

Body of evidence supporting the clinical use of 3D multisegment foot models: A systematic review

BACKGROUND A critical component in the characterization of foot mechanics during clinical gait analysis is the quantitative measurement of foot kinematics. Currently, the use of 3D multisegment foot models (3DMFMs) is popular in gait laboratories as it would seem to be an adequate tool for the in vivo analysis of dynamic foot kinematics. This systematic review identifies and evaluates current evidence for the use of 3DMFMs in clinical gait analysis. METHODS A targeted search strategy traced full papers that fulfilled the inclusion and exclusion criteria. The papers were classified and evaluated for quality using a custom made quality appraisal form. FINDINGS Forty-one manuscripts were included yielding a total number of fifteen 3DMFMs. Generally, study procedures and sample selection were adequately described; however, the methodological quality varied widely. Evidence regarding the repeatability of the identified models also varied widely. Models facing the highest level of scientific credibility were characterized by adequate repeatability indices obtained from between-trial, between-day and between and within assessor studies. Generally, the highest reliability indices were found for the sagittal plane kinematics. Within-subject variability was found to be the lowest, contrarily, between-subject and between-day variabilities were found to be highest. INTERPRETATION Reported repeatability indices such as the coefficient of multiple correlation, standard deviation and standard error of measurement provide evidence for the continued use of 3DMFMs. While a number of published models exist, there is no adequate evidence available to support their clinical use. More reliability and validity studies are needed to confirm adequate measurement properties of 3DMFMs.

Tight perioperative glucose control is associated with a reduction in renal impairment and renal failure in non-diabetic cardiac surgical patients

IntroductionAcute renal failure after cardiac surgery increases in-hospital mortality. We evaluated the effect of intra- and postoperative tight control of blood glucose levels on renal function after cardiac surgery based on the Risk, Injury, Failure, Loss, and End-stage kidney failure (RIFLE) criteria, and on the need for acute postoperative dialysis.MethodsWe retrospectively analyzed two groups of consecutive patients undergoing cardiac surgery with cardiopulmonary bypass between August 2004 and June 2006. In the first group, no tight glycemic control was implemented (Control, n = 305). Insulin therapy was initiated at blood glucose levels > 150 mg/dL. In the group with tight glycemic control (Insulin, n = 745), intra- and postoperative blood glucose levels were targeted between 80 to 110 mg/dL, using the Aalst Glycemia Insulin Protocol. Postoperative renal impairment or failure was evaluated with the RIFLE score, based on serum creatinine, glomerular filtration rate and/or urinary output. We used the Cleveland Clinic Severity Score to compare the predicted vs observed incidence of acute postoperative dialysis between groups.ResultsMean blood glucose levels in the Insulin group were lower compared to the Control group from rewarming on cardiopulmonary bypass onwards until ICU discharge (p < 0.0001). Median ICU stay was 2 days in both groups. In non-diabetics, strict perioperative blood glucose control was associated with a reduced incidence of renal impairment (p = 0.01) and failure (p = 0.02) scoring according to RIFLE criteria, as well as a reduced incidence of acute postoperative dialysis (from 3.9% in Control to 0.7% in Insulin; p < 0.01). The 30-day mortality was lower in the Insulin than in the Control group (1.2% vs 3.6%; p = 0.02), representing a 70% decrease in non-diabetics (p < 0.05) and 56.1% in diabetics (not significant). The observed overall incidence of acute postoperative dialysis was adequately predicted by the Cleveland Clinic Severity Score in the Control group (p = 0.6), but was lower than predicted in the Insulin group (1.2% vs 3%, p = 0.03).ConclusionsIn non-diabetic patients, tight perioperative blood glucose control is associated with a significant reduction in postoperative renal impairment and failure after cardiac surgery according to the RIFLE criteria. In non-diabetics, tight blood glucose control was associated with a decreased need for postoperative dialysis, as well as 30-day mortality, despite of a relatively short ICU stay.

Supporting diabetes self-management in primary care: Pilot-study of a group-based programme focusing on diet and exercise

AIMS To develop and implement a group self-management education programme for people with type 2 diabetes at the community level in primary care. This pilot-study intended to evaluate the feasibility, acceptability and long-term effects (12-18 months) of this programme on emotional distress, HbA1c, BMI and actual behaviour. METHODS An empowerment-based, theory-driven education programme was evaluated in a before-after design. The programme focused on behaviour assessment, goal-setting, problem solving and tailored information. A diabetes specialist nurse conjointly with a dietician or psychologist led five 2-hour sessions and a follow-up meeting after 3 months. RESULTS Forty-four people participated in 5 groups. BMI decreased with 0.45 kg/m(2) (95%CI 0.01-0.89) at 12-month and with 0.53 kg/m(2) (95%CI 0.02-1.04) at 18-month follow-up. HbA1c declined from 7.4% (+/-1.3) to 6.8% (+/-0.8) (p=0.040) and the PAID-score diminished from 28 (+/-20) to 18 (+/-13) (p=0.006) at 12-month post-intervention. These changes were only partly sustained at 18-month follow-up. Actual behaviour changed modestly. CONCLUSION Introducing the group education programme in primary healthcare is worthwhile (feasibility and effectiveness). A detailed description of the intervention is offered. Further research should explore the actual education process in greater depth.

Dynamic Tight Glycemic Control During and After Cardiac Surgery Is Effective, Feasible, and Safe

BACKGROUND: Tight blood glucose control reduces mortality and morbidity in critically ill patients, but intraoperative glucose control during cardiac surgery is often difficult, and risks hypoglycemia. In this study, we evaluated the safety and efficacy of a nurse-driven insulin protocol (the Aalst Glycemia Insulin Protocol) for achieving a target glucose level of 80–110 mg/dL during cardiac surgery and in the intensive care unit (ICU). METHODS: We included 483 nondiabetics and 168 diabetics scheduled for cardiac surgery with cardiopulmonary bypass. To anticipate rapid perioperative changes in insulin requirement and/or sensitivity during surgery, we developed a dynamic algorithm presented in tabular form, with rows representing blood glucose ranges and columns representing insulin dosages based on the patients’ insulin sensitivity. The algorithm adjusts insulin dosage based on blood glucose level and the projected insulin sensitivity (e.g., reduced sensitivity during cardiopulmonary bypass and normalizing sensitivity after surgery). RESULTS: A total of 18,893 blood glucose measurements were made during and after surgery. During surgery, the mean glucose level in nondiabetic patients was within targeted levels except during (112 ± 17 mg/dL) and after rewarming (113 ± 19 mg/dL) on cardiopulmonary bypass. In diabetics, blood glucose was decreased from 121 ± 40 mg/dL at anesthesia induction to 112 ± 26 mg/dL at the end of surgery (P < 0.05), with 52.9% of patients achieving the target. In the ICU, the mean glucose level was within targeted range at all time points, except for diabetics upon ICU arrival (113 ± 24 mg/dL). Of all blood glucose measurements (operating room and ICU), 68.0% were within the target, with 0.12% of measurements in nondiabetics and 0.18% in diabetics below 60 mg/dL. Hypoglycemia < 50 mg/dL was avoided in all but four (0.6%) patients (40 mg/dL was the lowest observed value). CONCLUSIONS: The Aalst Glycemia Insulin Protocol is effective for maintaining tight perioperative blood glucose control during cardiac surgery with minimal risk of hypoglycemia.

In vivo imaging of pituitary tumours using a radiolabelled dopamine D2 receptor radioligand

OBJECTIVE Knowledge of the dopamine D2 receptor status of pituitary tumours may play a predictive role in differential diagnosis and therapeutic decisions. This study was performed to evaluate the value of pituitary dopamine D2 receptor scintigraphy with (S)‐2‐hydroxy‐3‐123I‐iodo‐6‐methoxy‐N‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]benzamide (123I‐IBZM) in the diagnostic evaluation of patients with pituitary tumours.

Implementation of a program for type 2 diabetes based on the Chronic Care Model in a hospital-centered health care system: "the Belgian experience"

BackgroundMost research publications on Chronic Care Model (CCM) implementation originate from organizations or countries with a well-structured primary health care system. Information about efforts made in countries with a less well-organized primary health care system is scarce. In 2003, the Belgian National Institute for Health and Disability Insurance commissioned a pilot study to explore how care for type 2 diabetes patients could be organized in a more efficient way in the Belgian healthcare setting, a setting where the organisational framework for chronic care is mainly hospital-centered.MethodsProcess evaluation of an action research project (2003–2007) guided by the CCM in a well-defined geographical area with 76,826 inhabitants and an estimated number of 2,300 type 2 diabetes patients. In consultation with the region a program for type 2 diabetes patients was developed. The degree of implementation of the CCM in the region was assessed using the Assessment of Chronic Illness Care survey (ACIC). A multimethod approach was used to evaluate the implementation process. The resulting data were triangulated in order to identify the main facilitators and barriers encountered during the implementation process.ResultsThe overall ACIC score improved from 1.45 (limited support) at the start of the study to 5.5 (basic support) at the end of the study. The establishment of a local steering group and the appointment of a program manager were crucial steps in strengthening primary care. The willingness of a group of well-trained and motivated care providers to invest in quality improvement was an important facilitator. Important barriers were the complexity of the intervention, the lack of quality data, inadequate information technology support, the lack of commitment procedures and the uncertainty about sustainable funding.ConclusionGuided by the CCM, this study highlights the opportunities and the bottlenecks for adapting chronic care delivery in a primary care system with limited structure. The study succeeded in achieving a considerable improvement of the overall support for diabetes patients but further improvement requires a shift towards system thinking among policy makers. Currently primary care providers lack the opportunities to take up full responsibility for chronic care.Trial registration numberClinicalTrials.gov Identifier: NCT00824499

Combined Conn's and Cushing's syndrome : an unusual presentation of adrenal adenoma

In most aldosterone-producing adenomas (APA) dedifferentiation occurs with formation of transitional cells, bearing characteristics of both glomerulosa and fasciculata cells. These cells are able to produce cortisol, and their aldosterone production follows the circadian rhythm of ACTH. Usually, no clinical signs of cortisol excess develop, since the cortisol production remains under ACTH feedback control. Only a few cases have been described with autonomous cortisol secretion, not suppressible by low dose dexamethasone. We present a patient with an APA, synthesizing enough cortisol to cause the typical clinical expression of Cushings syndrome. Possible etiopathological mechanisms are discussed.

Effectiveness of the introduction of a Chronic Care Model-based program for type 2 diabetes in Belgium

BackgroundDuring a four-year action research project (2003-2007), a program targeting all type 2 diabetes patients was implemented in a well-defined geographical region in Belgium. The implementation of the program resulted in an increase of the overall Assessment of Chronic Illness Care (ACIC) score from 1.45 in 2003 to 5.5 in 2007. The aim of the follow-up study in 2008 was to assess the effect of the implementation of Chronic Care Model (CCM) elements on the quality of diabetes care in a country where the efforts to adapt primary care to a more chronic care oriented system are still at a starting point.MethodsA quasi-experimental study design involving a control region with comparable geographical and socio-economic characteristics and health care facilities was used to evaluate the effect of the intervention in the region. In collaboration with the InterMutualistic Agency (IMA) and the laboratories from both regions a research database was set up. Study cohorts in both regions were defined by using administrative data from the Sickness Funds and selected from the research database. A set of nine quality indicators was defined based on current scientific evidence. Data were analysed by an institution experienced in longitudinal data analysis.ResultsIn total 4,174 type 2 diabetes patients were selected from the research database; 2,425 patients (52.9% women) with a mean age of 67.5 from the intervention region and 1,749 patients (55.7% women) with a mean age of 67.4 from the control region. At the end of the intervention period, improvements were observed in five of the nine defined quality indicators in the intervention region, three of which (HbA1c assessment, statin therapy, cholesterol target) improved significantly more than in the control region. Mean HbA1c improved significantly in the intervention region (7.55 to 7.06%), but this evolution did not differ significantly (p = 0.4207) from the one in the control region (7.44 to 6.90%). The improvement in lipid control was significantly higher (p = 0.0021) in the intervention region (total cholesterol 199.07 to 173 mg/dl) than in the control region (199.44 to 180.60 mg/dl). The systematic assessment of long-term diabetes complications remained insufficient. In 2006 only 26% of the patients had their urine tested for micro-albuminuria and only 36% had consulted an ophthalmologist.ConclusionAlthough the overall ACIC score increased from 1.45 to 5.5, the improvement in the quality of diabetes care was moderate. Further improvements are needed in the CCM components delivery system design and clinical information systems. The regional networks, as they are financed now by the National Institute for Health and Disability Insurance (NIHDI), are an opportunity to explore how this can be achieved in consultation with the GPs. But it is clear that, simultaneously, action is needed on the health system level to realize the installation of an accurate quality monitoring system and the necessary preconditions for chronic care delivery in primary care (patient registration, staff support, IT support).Trial RegistrationTrial registration number: ClinicalTrials.gov Identifier: NCT00824499

Benchmarking Is Associated With Improved Quality of Care in Type 2 Diabetes The OPTIMISE randomized, controlled trial

OBJECTIVE To assess prospectively the effect of benchmarking on quality of primary care for patients with type 2 diabetes by using three major modifiable cardiovascular risk factors as critical quality indicators. RESEARCH DESIGN AND METHODS Primary care physicians treating patients with type 2 diabetes in six European countries were randomized to give standard care (control group) or standard care with feedback benchmarked against other centers in each country (benchmarking group). In both groups, laboratory tests were performed every 4 months. The primary end point was the percentage of patients achieving preset targets of the critical quality indicators HbA1c, LDL cholesterol, and systolic blood pressure (SBP) after 12 months of follow-up. RESULTS Of 4,027 patients enrolled, 3,996 patients were evaluable and 3,487 completed 12 months of follow-up. Primary end point of HbA1c target was achieved in the benchmarking group by 58.9 vs. 62.1% in the control group (P = 0.398) after 12 months; 40.0 vs. 30.1% patients met the SBP target (P < 0.001); 54.3 vs. 49.7% met the LDL cholesterol target (P = 0.006). Percentages of patients meeting all three targets increased during the study in both groups, with a statistically significant increase observed in the benchmarking group. The percentage of patients achieving all three targets at month 12 was significantly larger in the benchmarking group than in the control group (12.5 vs. 8.1%; P < 0.001). CONCLUSIONS In this prospective, randomized, controlled study, benchmarking was shown to be an effective tool for increasing achievement of critical quality indicators and potentially reducing patient cardiovascular residual risk profile.