Intensive support to improve clinical decision making in cardiovascular care: a randomised controlled trial in general practice

Objective: To evaluate the effects of feedback reports combined with outreach visits from trained non-physicians on the clinical decision making of general practitioners (GPs) in cardiovascular care.

Design: Pragmatic cluster controlled trial with randomisation of practices to support (intervention group) or no special attention (control group); analysis after 2 years.

Setting: 124 general practices in The Netherlands.

Participants: 185 GPs.

Main outcome measures: Compliance rates for 12 evidence-based indicators for the management of patients with hypertension, hypercholesterolaemia, angina pectoris, or heart failure. The evaluation relied on the prospective recording of patient encounters by the participating GPs.

Results: The GPs reported 30 101 clinical decisions at baseline and 22 454 decisions after the intervention. A significant improvement was seen for five of the 12 indicators: assessment of risk factors in patients with hypercholesterolaemia (odds ratio 2.04; 95% CI 1.44 to 2.88) or angina pectoris (3.07; 1.08 to 8.79), provision of information and advice to patients with hypercholesterolaemia (1.58, 1.17 to 2.13) or hypertension (1.55, 1.35 to 1.77), and checking for clinical signs of deterioration in patients with heart failure (4.11, 2.17 to 7.77). Single handed practices, non-training practices, and practices with older GPs gained particular benefit from the intervention.

Conclusions: Intensive support from trained non-physicians can alter certain aspects of the clinical decision making of GPs in cardiovascular care. The effect is small and the strategy needs further development.

     

CARD15 in inflammatory bowel disease and Crohn''s disease phenotypes: An association study and pooled analysis

BACKGROUND: Three major polymorphisms of the Caspase-Activation Recruitment Domain containing protein 15 gene have been described to be associated with Crohn's disease. Genotype-phenotype studies reported in literature provide conflicting data on disease localisation and behaviour. We investigated the relation of Caspase-Activation Recruitment Domain containing protein 15 with inflammatory bowel disease and Crohn's disease phenotypic characteristics in a large Dutch cohort and performed a pooled analysis on inflammatory bowel disease patients and Crohn's disease phenotypic characteristics reported in association studies. METHODS: We genotyped 781 cases and 315 controls for the R702W, G908R and 1007fsinsC variants and for six microsatellite markers in and close to Caspase-Activation Recruitment Domain containing protein 15. In the pooled analysis data of 7201 inflammatory bowel disease patients and 3720 controls from 20 studies were included. RESULTS: Association was found for Crohn's disease with R702W and 1007fsinsC, including several disease characteristics, and not for ulcerative colitis. In the pooled analysis all three common Caspase-Activation Recruitment Domain containing protein 15 variants showed strong association with Crohn's disease (p<0.00001; odds ratio varying from 3.0 for single heterozygotes to 14.7 for compound heterozygotes) and not with ulcerative colitis. Phenotype analysis showed association with small bowel involvement, stricturing and penetrating disease. CONCLUSION: Caspase-Activation Recruitment Domain containing protein 15 is associated with Crohn's disease and not with ulcerative colitis. All three common Crohn's disease-associated variants are associated with small bowel involvement, the G908R and 1007fsinsC alleles also being associated with a complicated disease course.     

Genetic analysis as a valuable key to diagnosis and treatment of periodic Fever.

We describe 2 Dutch patients with recurrent fever attacks undiagnosed for more than 40 years. The diagnosis of periodic fever was made when molecular analysis revealed novel mutations in the tumor necrosis factor (TNF) receptor gene (TNFRSF1A), establishing the diagnosis of TNF receptor-associated periodic syndrome. This syndrome is an autosomal dominant disorder characterized by recurring episodes of fever, arthralgia, and skin lesions that is caused by mutations in the 55-kd TNFRSF1A gene. This finding has facilitated treatment for TNF receptor-associated periodic syndrome because blocking of TNF signaling seems to alleviate the symptoms. Use of a short course of recombinant p75TNFR:Fc fusion protein (etanercept) induced prolonged remission in one patient.     

Prevalence of hepatitis C in the general population in the Netherlands

BACKGROUND: Chronic hepatitis C virus (HCV) is transmitted by blood-blood contact and this leads to high HCV prevalence in risk populations such as haemophilia patients and intravenous drug users. The prevalence in the general Dutch population is unknown, although it appears to be very low in screened blood donors (0.0169%). AIM: The objective of this study is to estimate the prevalence of HCV in a general population sample living in an urbanized region in the Netherlands. METHODS: We randomly selected 2200 EDTA blood samples that had been submitted for analysis of biochemical parameters to a regional servicing laboratory for general practitioners (SHO, Arnhem/Nijmegen, the Netherlands). HCV antibody testing was performed using a three-step approach. For initial screening, an enzyme immunoassay (Bioelisa HCV 4.0, Biokit, Spain) was used. Positive samples were subjected to a second, microparticle enzyme-linked immunoassay (AxSYM HCV version 3.0, Abbott laboratories, IL , USA). Genotypes were determined by Line Probe Assay. RESULTS: A total of four persons (two females, two males) (0.2%) tested positive for HCV antibodies. The average OD/cut-off ratio of the screening assay was 2.9 (range 1.0 to 7.3) and serological findings were confirmed using a specific second immunoassay. HCV RNA (genotype 1b) was found in the sera of two persons. CONCLUSION: The HCV prevalence in our sample of the Dutch population was 0.2% which accords with earlier estimates from prevalence studies in the Netherlands.     

Ribavirin rather than PEG-interferon pharmacodynamics predict nonresponse to antiviral therapy in naive chronic hepatitis C patients

Twenty to fifty per cent of patients with chronic hepatitis C (CHC) experience nonresponse to current antiviral therapy, which may relate in part to ribavirin or PEG-interferon pharmacodynamics. We evaluated potential relevance of various factors for nonresponse. Two hundred forty-two naive CHC patients who received in a previous trial at least 24 weeks of antiviral therapy, including PEG-interferon alfa-2b and ribavirin, were analysed. Of them, 53% were infected with hepatitis C virus (HCV) genotype 1-4, 71% exhibited high viral load and 32% had severe fibrosis/cirrhosis. After 24 weeks of treatment, 39 patients (16%) were nonresponders. In multivariate analysis, lower serum ribavirin concentrations, HCV genotype 1-4 and higher baseline γ-GT predicted nonresponse. Week-24 ribavirin concentrations (2.2 vs 2.8 mg/L, P < 0.001), average ribavirin doses (14.5 vs 15.2 mg/kg per day, P = 0.03) and week-24 haemoglobin decreases (1.7 vs 2.0 mm, P = 0.02) were lower in nonresponders. Nonresponse rates increased progressively at decreasing ribavirin concentrations: 4%, 11%, 13% and 36% in case of serum ribavirin concentrations ≥4, 3-4, 2-3 and ≤2 mg/L, respectively (P = 0.001). Ribavirin concentrations correlated with both week-24 haemoglobin decreases (r = 0.42, P < 0.001) and ribavirin doses (r = 0.17, P = 0.01). Subgroup analysis in HCV genotype 1-4 patients revealed essentially the same results. Nonresponse was exceptional in HCV genotype 2-3 patients and associated with ribavirin concentrations <2 mg/L. Presumed interferon-related factors (average PEG-interferon doses and decreases in leucocytes, granulocytes, platelets and body weight) did not differ between nonresponders and responders. In conclusion, ribavirin- rather than PEG-interferon-related factors are independent and potentially modifiable predictors of nonresponse in treatment-naive CHC patients.