[Re-use of medical data for research. What do the Dutch think of the requirement for explicit consent?]. / Hergebruik van medische gegevens voor onderzoek. Wat vindt de Nederlander van het toestemmingsvereiste?

OBJECTIVE: How do healthcare consumers perceive the use of medical data for scientific research, within the framework of protection of their personal data? DESIGN: Survey among 731 members of the Healthcare Consumer Panel of the Netherlands Institute for Health Services Research (NIVEL). METHOD: A written and online questionnaire was used, consisting of general questions and 4 cases per respondent. The questions concerned the degree of trust respondents have in the use of previously registered data for different kinds of healthcare research, and their willingness to make data available under various conditions without being asked for explicit consent. RESULTS: Respondents showed a high degree of trust in scientific researchers and physicians concerning the re-use of medical data for research. A majority agreed that it is not necessary to be explicitly asked for consent for this kind of research, providing they are informed: one-third found their autonomy in being able to decide to be more important than scientific progress; three-quarters found explicit permission unnecessary as long as the data is well-protected and only used for scientific research. CONCLUSION: Data protection in research should be proportional to the risks of misuse and the benefits of the use of the data for research. A large majority of healthcare users trust the researchers, and the existing codes of conduct protect data sufficiently. Therefore, we see no need for stricter requirements for the use of health data, which would unnecessarily limit healthcare research. We do consider greater transparency about the research process to be necessary, in order to maintain a proper balance between personal-data protection and the need to emphasise the necessity for learning in the healthcare system.

[Cost-utility analysis; uncertainties restrict applicability]. / Kostenutiliteitsanalyse; onzekerheden beperken toepasbaarheid.

Assumptions and choices are inherent to cost-utility analysis, the economic technique that provides a generic measure for the quantification of the efficiency of various health-care services. Uncertainty prevails on many of them: on the definition of the output of health care as health gain, on its expression in quality-adjusted life years (QALYs), on the choice of measurement instruments that should provide comparable information across all disease categories, on the choice of the procedure to value health states, on the relative importance of the judgments of patients and the general public, on the quantification of various types of costs, and on the question as to whether, and then how, future health gains should be discounted. The conclusion is that the results of a cost-utility analysis should be interpreted with caution. For the time being, cost-utility analysis cannot be used for direct comparisons of efficiency across all types of health-care services.

[Centenary of the Health Council of the Netherlands. VII. Influencing the human brain in the future]. / Honderd jaar Gezondheidsraad. VII. Hersenbeïnvloeding in de toekomst.

On the occasion of its centenary, the Health Council of the Netherlands issued an advisory report on future possibilities for influencing the human brain. The Council foresees that, in the future, it will probably become possible to prevent or extensively delay diseases such as dementia and Parkinson's disease. The burden of many mental disorders will be markedly relieved by early detection and treatment. Developments are to be expected in the fields of function enhancement, pharmacotherapy, psychotherapy and electrostimulation. The promising developments aimed at the prevention of brain disorders have important ethical and societal implications which require uninterrupted attention.

Randomized study of two different target levels of glycemic control within the acceptable range in type 2 diabetes. Effects on well-being at 1 year.

OBJECTIVE: A randomized trial with 1-year follow-up was conducted in 23 general practices to study the relationship between target values for glycemic control and well-being in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 176 patients with type 2 diabetes, aged 40-75 years, were included. General practitioners were encouraged to make decisions according to a standardized step-up regimen until the target level of glycemic control was reached. The random allocation to a strict or a less strict target level of glycemic control (fasting capillary glucose < 6.5 or < 8.5 mmol/l), change in HbA1c and fasting glucose, and initiating insulin or treatment with oral hypoglycemic agents were studied as putative determinants of scores on a type 2 diabetes symptom checklist, a profile of mood states, an affect balance scale, and general well-being. Adjustments were made for baseline scores on the outcome at issue. RESULTS: Positive affect (an odds ratio [OR] [95% CI] of 0.39 [0.19-0.83]) and perceived treatment burden (OR 0.48 [0.23-0.98]) were unfavorably altered in the group randomly allocated to stricter target levels (fasting capillary glucose < 6.5 mmol/l). Patients who had a decrease in HbA1c of 1% or more tended to have comparatively favorable mood (OR displeasure score 0.35 [0.13-0.94]) and general well-being scores at 1 year (ORs of having unfavorable scores ranged from 0.4 to 0.5, NS). CONCLUSIONS: Perceived treatment burden and positive effect are unfavorably affected by random allocation to a strict target level for glycemic control. Improved glycemic control is associated with favorable mood and possibly general well-being in type 2 diabetes.

Low prevalence of antibodies to GAD65 in a 50- to 74-year-old general Dutch population. The Hoorn Study.

OBJECTIVE: To assess the prevalence of antibodies to GAD65 (GAD65-A) in relation to glucose tolerance disturbances and to blood glucose-lowering therapy in a general Dutch population. RESEARCH DESIGN AND METHODS: A population sample of 2,350 Dutch subjects, age 50-74 years, agreed to undergo an oral glucose tolerance test (OGTT). They were classified as having normal glucose tolerance, impaired glucose tolerance, newly detected diabetes, or known diabetes. GAD65-A levels were measured in serum by means of a standardized radioligand assay and subsequently were expressed as indexes. The prevalence rates were defined as the proportions of individuals of each category of glucose tolerance exceeding the value of the index at the 99th percentile of the entire study population. RESULTS: The prevalence rates and the 95% CIs of GAD65-A were 0.7% (0.4-1.2%) in cases of normal glucose tolerance, 2.4% (0.9-5.3%) in impaired glucose tolerance, 0% (0-3.3%) in newly detected diabetes, according to the World Health Organization (WHO) criteria, and 3.5% (0.7-10.0%) in known diabetes. A total of 2 out of 3 subjects with GAD65-A indexes above the 99th percentile and 10 out of 18 subjects with GAD65-A indexes above the 85th percentile received insulin therapy for their diabetes, which showed an association between GAD65-A and insulin therapy CONCLUSIONS: Low prevalence rates of latent autoimmunity to GAD were found in 50- to 74-year-old Dutch subjects with normal and abnormal glucose tolerance, and GAD65-A was associated with insulin use in known diabetic subjects.

Performance of an NIDDM screening questionnaire based on symptoms and risk factors.

OBJECTIVE: To investigate to what extent a short questionnaire on symptoms and risk factors can be used to identify people at increased risk for undiagnosed NIDDM. RESEARCH DESIGN AND METHODS: A general population sample of 2,364 Caucasian subjects, age 50-74 years, not known to have diabetes, completed a questionnaire on diabetes-related symptoms and risk factors. Subsequently, they underwent an oral glucose tolerance test. A backward stepwise multiple logistic regression was carried out with the absence or presence of newly detected diabetes as the dependent variable and the items from the questionnaire as the independent variables. The selected items were included in a new symptom risk questionnaire, which was evaluated in a different population sample of 786 subjects, age 45-74 years, not known to have diabetes and compared with existing questionnaires. RESULTS: The newly developed symptom-risk questionnaire contains questions concerning the following items, which were independently and significantly (P < 0.05) associated with the presence of previously undiagnosed diabetes: pain during walking with need to slow down, shortness of breath when walking with people of the same age, frequent thirst, age, sex, obesity, parent or sibling with diabetes, use of antihypertensive drugs, and reluctance to use a bicycle for transportation. The 1993 American Diabetes Association questionnaire, the 1995 Herman et aL (17) questionnaire, and the newly developed symptom-risk questionnaire had sensitivities of 59, 72, and 72%; specificities of 57, 55, and 56%; positive predictive values of 5.6, 6.4, and 6.5%; and negative predictive values of 97, 98, and 98%, respectively. CONCLUSIONS: The newly developed symptom-risk questionnaire has good performance characteristics, and the advantage of a variable cutoff makes it a useful screening tool for NIDDM in general practice.

Carotid artery stenosis is related to blood glucose level in an elderly Caucasian population: the Hoorn Study.

Cross-sectional associations between carotid artery stenosis (CAS) on the one hand, and parameters of glycaemia and specific insulin levels on the other, were investigated in an age, sex, and glucose tolerance stratified random sample from a 50-74-year-old Caucasian population. Subjects treated with insulin or oral hypoglycaemic agents were classified as having known diabetes mellitus (KDM) (n = 66). Using two oral glucose tolerance tests, and based on the World Health Organisation criteria, all other participants were classified as having a normal (NGT) (n = 287), an impaired (IGT) (n = 169) or a diabetic (NDM) (n = 106) glucose tolerance. CAS was defined haemodynamically using duplex scanning. The crude prevalences of only moderate (16-49%) CAS were 6.6%, 7.1%, 5.7% and 12.1% in NGT, IGT, NDM and KDM subjects, respectively. For any severe (> or = 50%) CAS, crude prevalences were 2.8%, 4.7%, 9.4% and 7.6%. The prevalence of any severe CAS was higher in NDM (p < 0.01) and KDM subjects (p = 0.07) than in NGT subjects. The prevalence of a history of stroke or transient ischaemic attack was 1.7%, 1.8%, 2.8% and 1.5% in NGT, IGT, NDM and KDM, respectively. In univariate logistic regression analysis, HbA1c, serum fructosamine, fasting and 2-h post-load glucose were significantly associated with any severe CAS. In multivariate analyses controlling for other risk factors, only HbA1c and 2-h post-load plasma glucose remained significantly associated (odds ratios: 1.29 per % and 1.09 per mmol/l, respectively) in separate models. No association could be shown between either fasting or 2-h post-load specific insulin and any severe CAS in either univariate or multivariate analyses. In conclusion, HbA1c and 2-h post-load plasma glucose are independently associated with any severe CAS, whereas specific insulin is not.

Peripheral somatic nerve function in relation to glucose tolerance in an elderly Caucasian population: the Hoorn study.

Only sparse and contradictory data are available on peripheral somatic nerve function in relation to the total range of glucose tolerance. A random sample (n = 708) of people, stratified by age, sex, and glucose tolerance, from a Caucasian population aged 50 to 74 years was invited to undergo an examination including measures of large-fibre nerve function (ankle and knee reflexes, vibration sense, vibratory perception threshold (VPT) at the foot) and one measure of small-fibre function (thermal discrimination threshold (TDT) at the foot). A total of 267 subjects with a normal glucose tolerance (NGT), 167 with impaired glucose tolerance (IGT), 90 with newly diagnosed diabetes mellitus (NDM), and 73 with previously known diabetes (KDM) were included. KDM was associated with the highest prevalence of large-fibre nerve dysfunction. Within the range from NGT to NDM, most large-fibre function measures showed a decline with decreasing glucose tolerance. The TDT showed a decrease with an increase in fasting and post-load insulin levels (p < 0.05). We conclude that glucose intolerance is associated with impaired peripheral large-fibre nerve function, an association which seems to apply even in the non-diabetic range. Higher insulin levels were associated with a better small-fibre nerve function.

Symptoms and well-being in relation to glycemic control in type II diabetes.

OBJECTIVE: To describe the cross-sectional relation between glycemic control and physical symptoms, emotional well-being, and general well-being in patients with type II diabetes. RESEARCH DESIGN AND METHODS: The study population consisted of 188 patients with type II diabetes between 40 and 75 years of age. Patients were treated with blood glucose-lowering agents or had either a fasting venous plasma glucose level > or = 7.8 mmol/l or an HbA1c level > 6.1%. Multiple regression analyses were performed. Dependent variables were scores on the Type II Diabetes Symptom Checklist, the Profile of Mood States, the Affect Balance Scale, and questions regarding general well-being. The primary determinant under study was HbA1c. In addition, age, sex, neuroticism (indicating a general tendency to complain), insulin use, and comorbidity were included as determinants in all analyses. Other potential determinants taken into consideration were hypoglycemic complaints, marital status, diabetes duration, cardiovascular history, blood pressure, BMI, waist-to-hip ratio, perceived burden of treatment, and smoking. None of these potential determinants had to be included to correct confounding of the relation between HbA1c and well-being scores. RESULTS: Higher HbA1c levels were significantly associated with higher symptom scores (total score, hyperglycemic score, and neuropathic score), with worse mood (total score, displeasure score, depression, tension, fatigue), and with worse general well-being. The relative risks varied between 1.02 and 1.36 for each percentage difference in HbA1c. The relation between HbA1c and some mood states was modified by neuroticism: in the less neurotic patient (i.e., one who is less inclined to complain), the relation was more evident. CONCLUSIONS: These data suggest that better glycemic control in type II diabetes is associated with fewer physical symptoms, better mood, and better well-being, in a nonhypoglycemic HbA1c range.

A semiquantitative food frequency questionnaire for use in epidemiologic research among the elderly: validation by comparison with dietary history.

A self-administered semiquantitative food frequency questionnaire including 75 food items and providing information on the habitual intake of 31 nutritional parameters, based on the intake of protein, fat, carbohydrate, fiber and 11 vitamins and minerals, was developed for use in epidemiologic research on chronic disease among the elderly, such as diabetes and cardiovascular disease. By means of detailed frequency and quantity questions, specifications of types of food, preparation methods and seasonal variation, the questionnaire was expected to be an improvement on existing instruments. The relative validity of the questionnaire was examined in 74 men and women, aged 50-75, by comparison with a modified dietary history. Systematic differences were absent or negligible for all nutrients, except vitamin C. Bias depending on the level of intake could be ruled out for all but seven nutrients. Pearson correlation coefficients for estimates from the questionnaire and dietary history were on average 0.71 (range: 0.65-0.78) and 0.66 (range: 0.36-0.81) for macronutrients, and vitamins and minerals, respectively. Classifying individual intake estimates into tertiles of the distribution for both methods, on average 62.4 and 54.7% of the intakes were categorized into the same tertile and 3.9 and 5.9% into the opposite tertile for macronutrients, vitamins and minerals, respectively. These results demonstrate an acceptable relative validity for this newly developed questionnaire, as compared to the dietary history method.

Peripheral arterial disease in relation to glycaemic level in an elderly Caucasian population: the Hoorn study.

We investigated the cross-sectional association between peripheral arterial disease and glycaemic level in an age, sex, and glucose tolerance stratified random sample from a 50-74-year-old Caucasian population. Subjects treated with oral hypoglycaemic agents or insulin were classified as having known diabetes mellitus (KDM) (n = 67). Using two oral glucose tolerance tests, and based on World Health Organisation criteria, all other participants were categorized as having a normal (NGT) (n = 288), an impaired (IGT) (n = 170), or a diabetic (NDM) (n = 106) glucose tolerance. Prevalence rates of ankle-brachial pressure index less than 0.90 were 7.0%, 9.5%, 15.1% and 20.9% in NGT, IGT, NDM and KDM subjects, respectively (chi-square test for linear trend: p < 0.01). Prevalence rates of any peripheral arterial disease (ankle-brachial pressure index < 0.90, at least one monophasic or absent Doppler flow curve or vascular surgery) were 18.1%, 22.4%, 29.2% and 41.8% in these categories (chi-square test for linear trend: p < 0.0001). The prevalence of any peripheral arterial disease was higher in KDM and NDM than in NGT (p < 0.03, p < 0.0001, respectively), whereas no statistically significant difference was demonstrated between IGT and NGT. The same applied when using the ankle-brachial pressure index criterion. Logistic regression analyses showed that any arterial disease was significantly associated with HbA1c, fasting and 2-h post-load plasma glucose after correction for cardiovascular risk factors (odds ratios and 95% confidence intervals 1.35; 1.10-1.65 per %, 1.20; 1.06-1.36 and 1.06; 1.01-1.12 per mmol/l, respectively), whereas it was not associated with fasting and 2-h post-load specific insulin. Ankle-brachial pressure indices were not associated with either plasma glucose parameters or insulin in univariate or multivariate analyses. In conclusion, parameters of glucose tolerance are independently associated with any peripheral arterial disease, whereas insulin is not.

Sensory thresholds in older adults: reproducibility and reference values.

To evaluate the test-retest reproducibility of vibratory perception (VPT) and thermal discrimination (TDT) thresholds on the foot in older adults, we examined 20 50-76-year-old subjects with, and 19 without non-insulin-dependent diabetes mellitus. Adjusted reference values for both thresholds were obtained by assessing the relations with age, body height, and sex among 216 subjects with normal glucose tolerance, of the same age, sampled randomly from a geographically defined general population. The VPT appeared to be more reproducible than the TDT (reliability coefficient 0.89 vs. 0.54). The reproducibility of the VPT was inversely related to age and better for men than for women. Diabetes and glycemic level did not affect the reproducibility of either threshold. Both thresholds were related to age and height. Women had a higher VPT than men. The relations between sex and sensory thresholds at the lower limb, reported in previous studies, were probably confounded by height.