Comparison of randomization techniques for clinical trials with data from the HOMERUS-trial.

BACKGROUND: Several methods of randomization are available to create comparable intervention groups in a study. In the HOMERUS-trial, we compared the minimization procedure with a stratified and a non-stratified method of randomization in order to test which one is most appropriate for use in clinical hypertension trials. A second objective of this article was to describe the baseline characteristics of the HOMERUS-trial. METHODS: The HOMERUS population consisted of 459 mild-to-moderate hypertensive subjects (54% males) with a mean age of 55 years. These patients were prospectively randomized with the minimization method to either the office pressure (OP) group, where antihypertensive treatment was based on office blood pressure (BP) values, or to the self-pressure (SP) group, where treatment was based on self-measured BP values. Minimization was compared with two other randomization methods, which were performed post-hoc: (i) non-stratified randomization with four permuted blocks, and (ii) stratified randomization with four permuted blocks and 16 strata. In addition, several factors that could influence outcome were investigated for their effect on BP by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS: Minimization and stratified randomization did not lead to significant differences in 24-h ABPM values between the two treatment groups. Non-stratified randomization resulted in a significant difference in 24-h diastolic ABPM between the groups. Factors that caused significant differences in 24-h ABPM values were: region, centre of patient recruitment, age, gender, microalbuminuria, left ventricular hypertrophy and obesity. CONCLUSION: Minimization and stratified randomization are appropriate methods for use in clinical trials. Many outcome factors should be taken into account for their potential influence on BP levels. Recommendation. Due to the large number of potential outcome factors that can influence BP levels, minimization should be the preferred method for use in clinical hypertension trials, as it has the potential to randomize more outcome factors than stratified randomization.

Potentials and pitfalls for nutrition counselling in general practice.

This paper was based on collaborative research efforts from Wageningen University and the University Medical Centre St Radboud in The Netherlands and describes the rationale for web-based nutrition counselling applications in general practice as well as some of the frequently used models and theories (predominantly the Stages of Change Model). General practitioners can play an important role in cardiovascular risk reduction by giving nutrition counselling to patients at elevated cardiovascular risk. Unfortunately, general practitioners perceive barriers that may limit their nutrition counselling practices. Some of these barriers may be overcome using computer and Internet technologies. Computerized reminders for preventive services, and websites with reliable high-quality information may prove to be valuable additions to usual care. Cooperation with dietitians may also lead to improvements in nutrition counselling in general practice. For example, general practitioners could use their unique position to create awareness and motivation among patients. They could subsequently refer motivated patients to dietitians for detailed personal dietary advice.

Role of social support in lifestyle-focused weight management interventions.

Social support is important to achieve beneficial changes in risk factors for disease, such as overweight and obesity. This paper presents the theoretical and practical framework for social support, and the mechanisms by which social support affects body weight. The theoretical and practical framework is supported with a literature review addressing studies involving a social support intervention for weight loss and weight loss maintenance. A major aspect in social support research and practice is the distinction between structural and functional support. Structural support refers to the availability of potential support-givers, while functional support refers to the perception of support. Interventions often affect structural support, for example, through peer groups, yet functional support shows a stronger correlation with health. Although positive correlations between social support and health have been shown, social support may also counteract health behaviour change. Most interventions discussed in this review showed positive health outcomes. Surprisingly, social support was clearly defined on a practical level in hardly any studies, and social support was assessed as an outcome variable in even fewer studies. Future social support intervention research would benefit from clear definitions of social support, a clear description of the intended mechanism of action and the actual intervention, and the inclusion of perceived social support as a study outcome.

[The practice guideline 'Atrial fibrillation' from the Dutch College of General Practitioners; a response from the perspective of general practice]. / De standaard 'atriumfibrilleren' van het Nederlands Huisartsen Genootschap; reactie vanuit de huisartsgeneeskunde.

The practice guideline 'Atrial fibrillation' (AF) from the Dutch College of General Practitioners is a clearly written survey on the diagnosis and treatment of AF in general practice. Rapid cardioversion is no longer an indication for acute referral in AF. As AF, heart failure and COPD often occur simultaneously among elderly people, the exact cause of the symptoms can be unclear. In these complicated cases, with the risk of polypharmacy, a single consultation between general practitioner and cardiologist would be more effective. For control of the rate of ventricular contraction during the treatment of AF, lipophilic beta-blockers are preferable to hydrophilic beta-blockers because the pharmacokinetics in elderly people are substantially different. When there is a high risk of thrombo-embolic complications with AF, treatment with coumarin derivatives is advised. However, little research has been done on this subject among elderly people in a general practice setting. In this age group, the risk of complications due to treatment with coumarin derivatives is sometimes higher than the advantages it offers. This is why the GP should always consider carefully whether or not elderly people with AF should be treated with coumarin derivatives.

[Relationship between te general practice guidelines for the diagnosis of hypertension and the indication for treatment and practice in the Nijmegen region, the Netherlands, 1983-2001]. / Samenhang tussen de huisartsrichtlijnen voor diagnostiek van hypertensie en indicatie tot behandeling en de praktijk in de regio Nijmegen, 1983-2001.

OBJECTIVE: To determine whether patients with hypertension in general practice are diagnosed and treated according to the criteria of the Dutch College of General Practitioners guidelines. DESIGN: Retrospective, descriptive. METHOD: Using data from 9 general practices belonging to the general practice research network of the Academic Medical Centre St Radboud, Nijmegen, the Netherlands, all intake data of newly diagnosed hypertensive patients were collected. Three periods (1983-1991, 1992-1996 and 1997-2001) were studied and compared to the 1991 and 1997 versions of the guidelines. RESULTS: During the study period, 1959 patients with hypertension were registered. In 4% of the men and 3% of the women the hypertension criteria of the time were not met. These figures decreased during the course of the research period. Mean blood pressure at diagnosis was above 160/100 mmHg, even in patients with diabetes. The additional risk factors were recorded increasingly frequently (cholesterol level, smoking behaviour, body-mass index). In 1991, 63% were treated with medication (the other 37% only received lifestyle advice). During the last period, 86% received medication, while the indication to prescribe medication according to the guidelines increased from 40% to 81%. The increase may be ascribed to the new guideline recommendation of one risk factor as an indication to treat patients with mild hypertension instead of two. CONCLUSION: Almost all patients in whom the participating general practitioners diagnosed hypertension fulfilled the criteria. The difference in threshold values for diagnostic measurements and medicinal treatment means that people with mild hypertension are not always registered and consequently risk being forgotten by their general practitioner.

Cardiovascular risk factors and disease in general practice: results of the Nijmegen Cohort Study.

The relationship between risk factors and cardiovascular disease (CVD) was determined using data from the Nijmegen Cohort study, an 18-year prospective study. In 1977, cardiovascular risk factors were measured in 7092 Caucasian males and females from six general practices: age, smoking, serum cholesterol, blood pressure, body mass index and a family history of CVD were related to subsequent CVD mortality and morbidity. Most patients had more than one risk factor in particular among men. A significant relationship between risk factors and CVD was demonstrated. In men, a relative risk (RR) of 1.8 was found for both high blood pressure and smokers. A positive family history yielded a RR of 1.8. The risk increased gradually with the number of risk factors; 38% of the group with all risk factors suffered a CVD within 18 years. In women, comparable RRs were found but the low absolute risk of CVD should indicate against the treatment of cardiovascular risk factors.

Blood pressure and cardiovascular morbidity and mortality in a Dutch population: the Nijmegen cohort study.

BACKGROUND: The objective was to determine the influence of systolic blood pressure and diastolic blood pressure on the development of coronary heart disease over an 18-year period in a Dutch general practice population. METHODS: The Nijmegen Cohort Study is a prospective cohort study with an 18-year follow-up. In 1977 systolic blood pressure, diastolic blood pressure, and other cardiovascular risk factors were measured in 7,092 Caucasians, men and women. The screening took place in six general practices, participating in a university registration network. Cardiovascular disease and all mortality was registrated during the 1977-1995 period. A Cox proportional hazard model was performed separately for men and women with the first onset of a coronary heart disease as the outcome variable. Age, smoking, serum cholesterol, blood pressure, and socioeconomic class were included as independent variables. RESULTS: During the 18-year follow-up period, 205 men and 63 women suffered a nonfatal myocardial infarction. During this time, 205 deaths were identified, of which 54 were cardiovascular. Of all deaths, 139 were noncardiovascular, of which 10% were due to accident or suicide, while in 12 participants the cause of death was uncertain. The analysis indicated that both the systolic and the diastolic blood pressure were independently associated with the likelihood for developing coronary heart disease, as were the other risk factors. For coronary heart disease, the significant risk ratios for the systolic blood pressure were 1.6 for men and 2.1 for women. For the diastolic blood pressure a risk ratio was found of 1.4 for men and 2.0 for women. CONCLUSION: A significant relation between blood pressure and coronary heart disease was demonstrated. As mean blood pressures, cholesterol levels, smoking habits, and socioeconomic class in this cohort did not differ from other figures in The Netherlands, extrapolation of the results to the Dutch population is possible.

Changes in serum total cholesterol levels over 18 years in a cohort of men and women: The Nijmegen Cohort Study.

BACKGROUND: This study aimed to investigate to what extent cholesterol levels change in individuals in different age groups over an 18-year period. Factors that contribute to the changes, with respect to prevention of cardiovascular disease, were taken into account. METHODS: In 1977 serum cholesterol, systolic and diastolic blood pressures, body mass index, and smoking habits were measured in a cohort of 7,092 patients (men and women from 20 to 50 years of age) from six general practices in The Netherlands. In 1995, a sample of 2,600 of these same patients were invited to take part in a similar screening program; 2,335 patients, consisting of 1,171 men and 1,164 women, agreed to participate. Patients were derived from both high-risk and low- to normal-risk category in 1977. The differences in cholesterol between 1977 and 1995 were calculated and cholesterol levels were tracked over the study period by determining Pearson correlation coefficients. A multiple linear regression analysis was performed to investigate the determinants influencing the changes in cholesterol level. RESULTS: The mean cholesterol levels rose during the study period in all age groups. The highest mean increase in men was 1.23 mmol/L, or 20%, in the youngest age group (20-24 years), and in women the maximum mean increase was 1.12 mmol/L, or 17%, in the age group 40-44 years. Correlation coefficients between the 1977 and 1995 readings varied from 0.63 in the youngest age group to 0.41 in the oldest. Body weight change during the study period, more than initial body weight, was found to have influenced the rise in serum cholesterol. At basic screening, 19.2% of the men and 12.4% of the women had cholesterol levels of 6. 5 mmol/L or higher, as against 35.8 and 36.8%, respectively, in 1995. CONCLUSIONS: Over an 18-year period cholesterol level increased in most subjects, at a younger age in men than in women. The highest increase in women took place during the menopausal period. Weight gain, more than baseline weight, had a positive influence on the increase in cholesterol.

Development of blood pressure and the incidence of hypertension in men and women over an 18-year period: results of the Nijmegen Cohort Study.

The objective of this study was to determine the factors that influence diastolic blood pressure (DBP) and the incidence of hypertension. In 1977, DBP and cardiovascular risk factors were measured in 7092 men and women. In 1995, 2335 subjects participated at a second screening. Those patients already under hypertension treatment in 1977 were excluded. The DBP tracking was studied in subjects not under hypertension treatment during the study. Hypertension was defined on two ways in the analysis: under current hypertension treatment or a DBP > 95 mmHg measured at rescreening in 1995. Forty-seven percent of the subjects with a DBP < 75 mmHg in 1977 remained in the same category of DBP in 1995, and 7% had become hypertensive. Of the 75-84 mmHg group in 1977, 40% stayed in the same category in 1995 and 15% became hypertensive. Of the 85-94 mmHg category, 30% stayed in the same category and 30% became hypertensive in 1995. Of the highest category in 1977 (> 95 mmHg), 64% were still in that category in 1995. Baseline DBP in 1977 had the highest predictive value for future DBP. Weight gain over the years increased the risk for future hypertension: in contrast, there was no risk at a low DBP without weight gain. There is no need for regular check-ups for those patients with a low DBP who experience no weight gain. Borderline DBP (85-95 mmHg), together with weight gain, increases the risk of development of hypertension. The risk was especially high for men in the lower socioeconomic class.

Consumption of fructooligosaccharides does not favorably affect blood glucose and serum lipid concentrations in patients with type 2 diabetes.

BACKGROUND: Fructooligosaccharides have been claimed to lower fasting glycemia and serum total cholesterol concentrations, possibly via effects of short-chain fatty acids produced during fermentation. OBJECTIVE: We studied the effects of fructooligosaccharides on blood glucose, serum lipids, and serum acetate in 20 patients with type 2 diabetes. DESIGN: In a randomized, single-blind, crossover design, patients consumed either glucose as a placebo (4 g/d) or fructooligosaccharides (15 g/d) for 20 d each. Average daily intakes of energy, macronutrients, and dietary fiber were similar with both treatments. RESULTS: Compliance, expressed as the proportion of supplements not returned, was near 100% during both treatments. Fructooligosaccharides did not significantly affect fasting concentrations (mmol/L) of serum total cholesterol (95% CI: -0.07, 0.48), HDL cholesterol (-0.04, 0.04), LDL cholesterol (-0.06, 0.34), serum triacylglycerols (-0.21, 0.44), serum free fatty acids (-0.08, 0.04), serum acetate (-0.01, 0.01), or blood glucose (-0.37, 0.40). CONCLUSIONS: We conclude that 20 d of dietary supplementation with fructooligosaccharides had no major effect on blood glucose, serum lipids, or serum acetate in patients with type 2 diabetes. This lack of effect was not due to changes in dietary intake, insufficient statistical power, or noncompliance of the patients.

Long-term effect of nutritional counseling: a study in family medicine.

This paper reports research using data in the Nijmegen Family Practice Monitoring Project. One part of the research is follow-up, after 17 y, of a 1977 trial of dietary advice for patients with hypertension or a family history of premature cardiovascular disease. In the intervention group, 840 patients were given health education every 2 mo by trained practice nurses for 1 y. There were 497 patients with similar coronary risk factors in the control group, who received usual care. One year after the intervention a significant decrease was found (and published) in serum cholesterol concentrations and blood pressure in the intervention group. By the time of the 1995 reexaminations, however, there were no differences in coronary risk factors between the two groups. Blood pressures had come down, more so in the control group, and the percentage of smokers had decreased equally in both groups. There were no significant differences in intake of dietary fat or in type of fat. The lack of difference was still found when the groups were divided into those with serum cholesterol concentrations > and < 6.5 mmol/L. A second part of the research was to investigate in 1995 the relation between patients' stage of change of fat intake and their dietary intake. It was found that those in stage 5 (sustaining desired changes in behavior) had the lowest saturated fat intake. Since 1977 both groups have been treated equally if hypertension was diagnosed. The two groups were not managed differently with regard to dietary advice after 1977.

[Left ventricular hypertrophy; differences in the diagnostic and prognostic value of electrocardiography and echocardiography]. / Linkerventrikelhypertrofie; verschillen in diagnostische en prognostische waarde van elektrocardiografie en echocardiografie.

OBJECTIVE: To compare the electrocardiogram (ECG) and the echocardiogram for demonstration of left ventricular hypertrophy (LVH) and the prognostic values of these methods. DESIGN: Literature study. SETTING: Department of General Practice, Social and Nursing Home Medicine, R.C. University of Nijmegen, the Netherlands. METHOD: Using articles retrieved by means of a search action in Medline (1962-January 1996), a study was made of the differences between determination of LVH by ECG and by echocardiography with regard to the sensitivities and specificities for measuring anatomical LVH, and their predictive values concerning cardiovascular morbidity and mortality. RESULTS: The sensitivity of echocardiography for the prediction of anatomical LVH (88-93%) exceeded that of ECG (21-54%), while both methods had a high specificity (77-97%). ECG-LVH seemed a better predictor of cardiovascular complications than echo-LVH. CONCLUSION: Echocardiography is the better instrument for screening for LVH, but ECG should keep its place in the diagnostics of LVH in view of its high predictive value for morbidity and mortality and its availability to primary health care. In regard to LVH, echocardiography measures only morphological disorders, while ECG also detects functional disorders.

[Patellar chondropathy in family practice]. / Chondropathia patellae in de huisartspraktijk.

Aim of the investigation was to study the frequency and prognosis of patellar chondropathy in general practice. As far as the frequency was concerned a secondary analysis was done of data from the Nijmegen Continuous Morbidity Registration (4 general practices, 12,000 patients). The prognosis was studied in patients in these practices with at least one episode of patellar chondropathy in the years 1985-1988. The GPs were asked about the diagnostic criteria they used. The registration showed an average of 6 new cases of patellar chondropathy per 1000 patient-years; in 7% of the cases the GPs referred a patient for specialist care. To study the prognosis patients were asked to fill in a questionnaire. Response was 84%, 178 questionnaires were analysed. The female-male ratio of the respondents was 2, 60% were younger than 60 years. In 44% of the cases the complaints subsided within 6 months. Interventions such as X-ray and physiotherapy depended on severity, duration and frequency of the knee complaints.

Development of hypertension in obese subjects seen in general practice.

A group of 317 overweight men and 565 overweight women was compared with an age-matched normal control group of 444 men and 627 women in order to establish whether hypertension was more often recorded in the obese group. This was done by analysing the continuous morbidity registration of four general practices with a follow-up of up to 17 years. The risk of hypertension was found to be three to four times higher in overweight persons than in those of normal weight, and in women a linear relationship was found between the degree of overweight and the incidence of hypertension. The fat distribution was studied in 292 overweight persons, and fat deposited predominantly in the abdominal region was found to be related to the prevalence of hypertension, particularly in subjects under 50 years of age. Along with the degree of overweight, therefore, the fat distribution might be a useful aid in the early detection of hypertension. Since it is difficult to achieve long-term success in the treatment of overweight, its prevention merits special attention in general practice.