A lifestyle intervention to reduce Type 2 diabetes risk in Dutch primary care: 2.5-year results of a randomized controlled trial.

AIMS: To determine the effectiveness of a 2.5-year lifestyle intervention for Type 2 diabetes prevention in Dutch general practice compared with usual care. METHODS: A randomized controlled trial of 925 individuals at high risk for Type 2 diabetes (FINDRISC-score ≥ 13) in 14 general practices in the Netherlands. Intervention consisted of lifestyle counselling from the nurse practitioner and the general practitioner. Usual care consisted of oral and written information at the start of the study. Study groups were compared over 2.5 years regarding changes in clinical and lifestyle measures. RESULTS: Both groups showed modest changes in body weight, glucose concentrations, physical activity and dietary intake [weight: intervention group, -0.8 (5.1) kg, usual care group, -0.4 (4.7) kg, (P=0.69); fasting plasma glucose: intervention group, -0.17 (0.4) mmol/l, usual care group, -0.10 (0.5) mmol/l, (P=0.10)]. Differences between groups were significant only for total physical activity and fibre intake. In the intervention group, self-efficacy was significantly higher in individuals successful at losing weight compared with unsuccessful individuals. No significant differences in participant weight loss were found between general practitioners and nurse practitioners with different levels of motivation or self-efficacy. CONCLUSIONS: Diabetes risk factors could significantly be reduced by lifestyle counselling in Dutch primary care. However, intervention effects above the effects attributable to usual care were modest. Higher participant self-efficacy seemed to facilitate weight loss. Lack of motivation or self-efficacy of professionals did not negatively influence participant guidance.

An active strategy to identify individuals eligible for type 2 diabetes prevention by lifestyle intervention in Dutch primary care: the APHRODITE study.

BACKGROUND: Several trials have shown the potential of lifestyle intervention programmes for prevention of type 2 diabetes. The effectiveness of implementation of these programmes into daily practice is now being studied in several countries. The 'Active Prevention in High Risk individuals of Diabetes Type 2 in Eindhoven' (APHRODITE) study investigates whether type 2 diabetes prevention by lifestyle intervention is effective in Dutch primary care. In this article we describe the process of recruiting the study participants. OBJECTIVE: To assess the reach of an active strategy to recruit participants for a programme on type 2 diabetes prevention by lifestyle intervention in Dutch primary care. METHODS: A diabetes risk questionnaire was sent to general practice patients aged 40-70 years. Individuals with a risk score above threshold were invited for an admission interview with the GP and an oral glucose tolerance test (OGTT). All individuals with non-diabetic glucose levels were asked to participate in the intervention study. RESULTS: In total, 8752 (54.6%) of the individuals returned the questionnaire in time. Of all high-risk individuals (n = 1533), 73.1% contacted their practice to schedule a consultation with the GP. Response rates varied significantly among practices. CONCLUSIONS: Using invitational letters, a substantial amount of individuals could be motivated to participate in a programme on type 2 diabetes prevention by lifestyle intervention in Dutch primary care. Further research is needed on what kind of strategy would be most effective and efficient to screen for individuals at high risk for type 2 diabetes in primary care.

Development of an antibody-capture IgM-enzyme-linked immunosorbent assay for diagnosis of acute Epstein-Barr virus infections.

An anti-EBV IgM-ELISA was developed using the antibody-capture principle, to be used for the diagnosis of acute infectious mononucleosis (IM). The test was based on anti-human IgM-coated microtiter plates; nuclei of EBV producer cells were used for antigen; conjugate was prepared by labeling sheep anti-EBV IgG with horseradish peroxidase. The specificity of the anti-EBV IgM-ELISA was studied with a panel of sera from acute infections with hepatitis A virus, rubella virus, Toxoplasma gondii and cytomegalovirus, and sera positive for rheumatoid factors, positive for antinuclear antibodies, as well as with sera from normal blood donors and pregnant women. Specificity in these panels was 98.4%. In a clinical study with 449 sera from patients with IM-like symptoms, 109 of 109 confirmed patients were detected by the anti-EBV IgM-ELISA. Specificity of the anti-EBV IgM-ELISA in this clinical study was 99.7%. The anti-EBV IgM-ELISA detected several acute EBV patients who had negative heterophile antibody titers.

Diagnosis of fetal rubella infection by nucleic acid hybridization.

The efficacy of nucleic acid hybridization for the diagnosis of rubella infection in experimental and clinical materials was compared with immunoblot and virus isolation techniques. Our results showed that nucleic acid hybridization is specific and rapid but gives false-negative results when compared with conventional virus isolation in some experimental although not in clinical materials so far examined. For this reason, a failure to demonstrate rubella virus in fetal specimens by this method alone cannot yet be taken as a sole criterion for ruling out fetal rubella infection.

A sol-particle immunoassay for determination of anti-rubella antibodies; development and clinical validation.

A sol-particle immunoassay (SPIA) was developed for determination of anti-rubella antibodies. The test is based on antibody-coated gold sol particles, which may agglutinate in the presence of rubella haemagglutinin antigen. The agglutination which gives a decrease in optical density can be inhibited by specific antibodies present in sera incubated with the immunochemical reagents. The test is performed in microtitration plates and results can be read in a plate-reader. Clinical validation studies were performed comparing the anti-rubella SPIA with the haemagglutination inhibition test and with the latex agglutination test. The sensitivity of the SPIA was calculated to be 99%; the specificity of the test was at least 99.5%. The anti-rubella SPIA is highly suitable for large-scale screening to determine the rubella immune-status.

A one-step enzyme-linked immunosorbent assay to detect anti-CMV antibodies; development and clinical validation.

A simple one-step ELISA to detect anti-CMV antibodies was developed. The test was based on the inhibition principle, and used anti-CMV coated microtitre plates, CMV nuclear antigen and anti-CMV Fab'-HRP conjugate; total assay time was 1.5 h. The use of Fab'-HRP conjugates improved discrimination between positive and negative sera as compared with IgG-HRP conjugates. In an in-house clinical study, the one-step ELISA showed a 98.4% correlation with the latex agglutination test. The test could be demonstrated to be suitable for both serum and citrate- or EDTA-plasma specimens; heparin-plasma gave somewhat higher absorbance values. In an external clinical validation, the one-step ELISA showed a 99.5% correlation with the latex agglutination test, and was found to be highly suitable for screening of blood donor specimens in a blood bank setting.

Development of CMV antibody tests and their clinical evaluation.

An anti-CMV ELISA was developed in which monoclonal antibodies to immobilize the CMV antigens are used. The test was compared with the IHA test and there was 98.6% agreement. Using the CF test as a referee, sensitivity and specificity of the ELISA were calculated to be 98.6 and 99.0%, respectively. The seroconversion rate among Dutch donors was estimated from the age-related prevalence of anti-CMV antibodies to be about 0.4%. Specific anti-CMV IgM was searched for in a large donor population using an antibody-capture IgM ELISA; 1 of 600 donor sera was found positive. This makes it unlikely that screening for IgM anti-CMV will effectively prevent posttransfusion CMV infections. In order to meet the demand for simpler tests, a one-step ELISA was recently developed, based on the inhibition principle. Preliminary studies with this test indicate a high sensitivity and specificity.

Clinical validation of an antibody-capture anti-rubella IgM-ELISA.

An antibody-capture IgM-ELISA using monoclonal antibodies for conjugate was subjected to clinical validation with respect to sensitivity and specificity. In 103 serum specimens, known to contain anti-rubella IgM by a sucrose density gradient method, IgM was found by the ELISA in 99 sera. In a second study, 16 out of 17 acute rubella infections were detected by the IgM-ELISA. In 17 out of 17 vaccinees, a specific IgM response could be demonstrated. Specificity of the antibody-capture ELISA was found to be high; no interference was seen in 60 rheumatoid-factor positive sera, in 100 highly positive IgG sera or 10 sera with anti-CMV IgM. Only one out of 100 sera with heterophile antibodies showed a positive response. In acute rubella infections, IgM was shown to be detectable from 1 to 4 days after onset of illness up to about 12 wk, with peak values at about 1 wk after onset.

Diagnosis of acute toxoplasmosis by an enzyme immunoassay for specific immunoglobulin m antibodies.

A recently developed enzyme-linked immunosorbent assay for detection of immunoglobulin M (IgM) class antibodies to Toxoplasma gondii was evaluated with respect to specificity and sensitivity. By using an antibody capture principle and F(ab')2 conjugates, interference of rheumatoid factors was absent. No cross-reactions with anti-toxoplasma IgG occurred, and no interference with antinuclear antibodies was found. A large-scale study with about 1,500 clinical specimens revealed a 100% specificity. By testing 79 sera from patients with acute-phase acquired toxoplasmosis, sensitivity was found to be 97%. In routine clinical practice, the IgM-enzyme-linked immunosorbent assay proved to be a more sensitive tool for diagnosis than the immunofluorescent-antibody test. The course of IgM-enzyme-linked immunosorbent assay antibodies in acute patients was studied; IgM reached peak levels within 1 month after onset of illness, and could be demonstrated up to an average of 8 months after onset.

Enzyme-linked immunosorbent assay for detection of immunoglobulin M antibodies against Toxoplasma gondii.

A new principle that uses anti-immunoglobulin M-coated polystyrene microtiter plates for the detection of immunoglobulin M antibodies against Toxoplasma gondii by an enzyme-linked immunosorbent assay was developed.

An outbreak of hepatitis A in an institution for the mentally retarded.

From December 1977 until April 1978 a hepatitis A outbreak occurred in an institution for the mentally retarded. The institution housed 311 residents and had a staff of 308. The outbreak was studied by enzyme-linked immunosorbent assays for hepatitis A antigen and antibodies, and by liver function tests in serum. When the investigations started, 13 residents and one staff member were ill and already seropositive; 34 of the 182 residents that were seronegative at that time and 12 of the 223 seronegative staff members subsequently developed disease. Out of the 60 cases 32 were asymptomatic; 19 cases with jaundice were seen. Normal human immunoglobulin was administered to a large part of the seronegative group, but the effect is difficult to interpret as the immunoglobulin was often given after the presumed time of infection and failed to protect. Elevated liver enzyme levels were demonstrated in 38 of 60 patients.

A new principle for the detection of specific IgM antibodies applied in an ELISA for hepatitis A.

A new test principle for the detection of specific IgM-class antibodies was developed and applied in an Enzyme-Linked Immuno Sorbent Assay (ELISA) for the detection of hepatitis A IgM antibodies. A solid phase coated with anti-IgM was incubated successively with serum sample, specific antigen, and enzyme-labeled F (ab')2 fragments from IgG antibodies against the antigen and enzyme substrate. F(ab')2 fragments were used to avoid interference with rheumatoid factor. Specificity and sensitivity are very high. This test principle appears generally applicable in the diagnosis of infectious and parasitic diseases by testing only one serum sample.