[Quality assurance of drug prescription in primary health care. A new database software makes the drug therapy surveillance easier]. / Kvalitetsarbete kring läkemedelsförskrivning i primärvården. Nytt databasprogram underlättar uppföljning av läkemedelsbehandling.

Quality assurance of drug prescription is a pre-requisite for rational drug use. From 22 health-care centres in the south-western area of the Stockholm County Council region, drug-prescription data were obtained from the patients' computerised medical recordings. This could be done with the aid of a specially designed database program. The drug-prescription data from the 22 health-care centres were collected and compiled in a central unit. Thereafter the results were brought back to the health-care centres, in which the quality assurance of drug prescription could be started.

The effects of alcohol consumption on mortality and morbidity: a 26-year follow-up study.

OBJECTIVE: To investigate the long-term effects of the consumption of alcohol on mortality and morbidity. METHOD: A sample of 32,185 (50.5% female) individuals was randomly selected from the 450,000 inhabitants of Stockholm County, Sweden, in 1969. Alcohol consumption data were obtained from postal questionnaires; response rate was 87% (n = 28,001). Data on mortality and morbidity were obtained from the National Cause of Death Register, the Cancer Register and the Inpatient Register 1971-1996. RESULTS: The reference groups were moderate consumers of alcoholic beverages. High-consumption men had increased risks of mortality from cardiovascular diseases (relative risk ratio [RR] = 1.28; 95% confidence interval [CI]: 1.12-1.46), accidents or poisoning (RR = 2.10; CI: 1.67-2.65) and gastrointestinal diseases (RR = 4.65; CI: 2.93-7.36). High-consumption women had an increased risk of mortality only from accidents or poisoning (RR = 2.95; CI: 1.82-4.78) and gastrointestinal diseases (RR = 3.60; CI: 1.40-9.24). For low-consumption women, there was an increased risk of mortality from cardiovascular diseases (RR = 1.25; CI: 1.07-1.47). Low-consumption men also had an increased mortality from cardiovascular diseases (RR = 1.23; CI: 1.05-1.44). The results with respect to morbidity almost mirrored the results for mortality, with one exception; for low-consumption men, the morbidity from cardiovascular diseases was not increased. CONCLUSIONS: The mortality and morbidity associated with different levels of alcohol consumption are associated with the same diseases, which suggests that alcohol may be one of the causative factors for these diseases. The reasons for the differences between genders, regarding responses to the negative effects of alcohol consumption, are still unknown.

A moderate intake of wine is associated with reduced total mortality and reduced mortality from cardiovascular disease.

OBJECTIVE: The aim of this study was to investigate the effects of the consumption of wine, beer and distilled spirits on total mortality and on mortality from cardiovascular disease. METHOD: The consumption of wine, beer and distilled spirits was assessed in 1,828 individuals by a psychiatrist. Subjects were selected according to expected level of need for health services, from a random sample of 24,043 individuals aged 18-65 years. Mortality was recorded after 22 years and the results related to those for the individuals not exposed to the factor examined. The results were adjusted for age, expected level of need for health services, total alcohol consumption, gender, body-mass index, tobacco use and social class. RESULTS: Intake of wine once a week or more (compared with intake of wine less than once a week or not at all) was associated with a relative risk ratio of 0.58 for total mortality (95% CI: 0.40-0.84) and a relative risk ratio of 0.49 for mortality from cardiovascular disease (95% CI: 0.27-0.90). The risk reduction seemed to be confined to those consumers of wine who had an intake of less than 140 grams of alcohol per week and consumed the beverage once a week. Ex-drinkers had an increased relative risk ratio in total mortality compared with lifelong abstainers and individuals who consumed less than 50 grams of alcohol per week (relative risk ratio = 2.64; 95% CI: 1.56-4.49). CONCLUSIONS: A low to moderate intake of wine seems, unlike the consumption of distilled spirits and beer, to be associated with reduced total mortality and reduced mortality from cardiovascular disease.

Validity of two questions on alcohol use in a health survey questionnaire.

The aim of this study was to investigate whether consumers of high and low levels of alcohol could be identified by two questions about alcohol use in a postal questionnaire survey. A sample of 2,300 persons aged 18 64 years from Stockholm county were sent a masked postal questionnaire comprising 30 questions about their health and functioning. Two questions concerned their alcohol consumption. One year later the subjects underwent a psychiatric health examination, which included an assessment of their alcohol use. The two questions about alcohol consumption identified high alcohol consumers with a relatively high sensitivity and specificity, of 64% and 87%, respectively, and thus are useful for identifying high alcohol consumers in health surveys using questionnaires.

Diabetic neuropathy in elderly Type 2 diabetic patients: effects of insulin treatment.

OBJECTIVES: To study the occurrence of diabetic neuropathy and the effect of insulin treatment in elderly Type 2 diabetic patients. MATERIAL AND METHODS: In 38 patients and 20 controls symptoms and neurophysiological examinations including electroneurography, vibration perception and temperature discrimination thresholds were investigated. Patients were randomized to insulin (n = 18) or sulfonylurea (n = 16) treatment and were re-investigated after 1 year. RESULTS: Neuropathy was present in 21/38 patients (56%). It was asymptomatic in 17/38 (45%) and symptomatic in 4/38 (11%). The occurrence of neuropathy was less common in healthy controls, 3/20 (15%) (P < 0.01). Temperature discrimination thresholds was the test that most often revealed pathology. The metabolic control after 1 year was significantly improved in the insulin treated group and unchanged in the sulfonylurea treated group. There were no changes as regards occurrence of neuropathy between or within the two treatment groups after 1 year. CONCLUSION: Diabetic neuropathy is common among elderly Type 2 diabetic patients. It is mostly asymptomatic. Improvement was not seen after 1 year of insulin treatment.

Effects of an assessment of needs for medical and social services on long-term mortality: a randomized controlled study.

BACKGROUND: The aim of this study was to investigate the long-term effects of one general health screening on mortality. METHOD: After stratification and randomization of a population of 450,000 inhabitants, two groups were formed, an intervention group of 3064 people and a control group of 29,122 people. From the National Cause of Death Register, data were collected as regards death and causes of deaths for 1970-1990. RESULTS: Multivariate analysis was used to correct for known confounders. We then found no differences between the groups regarding deaths from all causes, cardiovascular diseases, cancer or accidents and poisoning. CONCLUSIONS: One general health screening seems to have little, if any value in preventing fatal diseases.

Insulin treatment of elderly type 2 diabetic patients: effects on retinopathy.

Insulin treatment is reportedly associated with the transient progression of retinopathy, possibly with the development of macular oedema in middle-aged Type 2 diabetic patients. The purpose of this study was to investigate the effect of insulin treatment on eye-grounds in elderly (> 65-year-old) Type 2 diabetic patients with secondary failure of oral antidiabetic-drug therapy. Eye examinations were performed in 37 patients randomized to insulin (n = 19) or sulphonylurea (n = 16) treatment and re-investigated after one year. Insulin treatment reduced HbA1c from 9.3% to 7.3% (p < 0.001) after one year. In the sulphonylurea-treated group, HbA1c did not change (9.1 vs. 9.3%). At the start, 65% of the patients had retinopathy, and after one year progression was noted in 7/35 patients (20%; 5 insulin- and 2 sulphonylurea-treated). In the insulin-treated group, the 5 patients with progression had higher initial fasting blood-glucose levels than other patients in the group (15.8 vs 13.1 mmol/L, p < 0.05). Initial HbA1c levels did not differ between the groups (9.8 vs. 9.1%, n.s.), nor the reduction of HbA1c levels during treatment (2.2 vs. 1.3% n.s.). Thus, diabetic retinopathy in this study was common among elderly Type 2 diabetic patients. The progression of retinopathy may in fact be associated with insulin treatment or improvement of metabolic control.

Starting insulin therapy in elderly non-insulin-dependent diabetic patients at a health care centre. Methodological and economic aspects.

OBJECTIVE: To try to start insulin therapy in elderly non-insulin-dependent diabetes mellitus (NIDDM) patients with secondary failure in primary health care, and compare costs for starting treatment in a health care centre and in a day-care clinic in a hospital. DESIGN: Time and costs for start of insulin were calculated. SETTING: A health care centre in Stockholm, Sweden. SUBJECTS: Fourteen consecutive patients in the health care centre and a control group of 14 patients in the day-care clinic. RESULTS: Metabolic control in both groups improved significantly. Total time spent with the district nurse to start insulin treatment was 3 hours during about 7 weeks with a total cost of SEK 1100 in the health care centre. In the day-care clinic patients were admitted 5.6 days with a total cost of SEK 6100-10900. CONCLUSIONS: Elderly patients can learn the injection technique and manage insulin therapy, which results in good metabolic control. Insulin treatment can be started in primary health care. With elderly patients it takes time, but it is far more cost-effective in primary health care than at the hospital.

Effect of metabolic control on 24-h ambulatory blood pressure in elderly non-insulin-dependent diabetic patients.

OBJECTIVES: To assess the effect of improved metabolic control with insulin therapy on blood pressure (BP) in elderly non-insulin-dependent diabetes mellitus (NIDDM) patients having secondary failure of oral antidiabetic drug therapy. METHODS: Elderly NIDDM patients on maximal sulfonylurea treatment and showing poor metabolic control, but without symptoms of decompensation, were studied in a randomized prospective trial. One group was treated with insulin and the other was kept on oral treatment. Ambulatory BP measurements over 24 h were performed at the start and after 6 and 12 months. RESULTS: Metabolic control in the insulin-treated, but not in the sulfonylurea-treated group, improved significantly. Body weight increased in the insulin-treated and decreased in the sulfonylurea-treated group. We found no changes in BP in the two treatment groups, whether studied during the 24-h period or during the daytime or night time when divided into longer (22.00 to 06.00 hours) or shorter (01.00 to 07.00 hours) time periods in the night. CONCLUSIONS: No change in BP was noted in elderly diabetic patients when the metabolic control was improved by insulin treatment. Their weight gain may have counteracted the effect of the improved metabolic control on BP. Thus, elderly NIDDM patients seem not to have any benefits from insulin treatment as regards BP control.

24-hour ambulatory blood pressure monitoring in elderly normotensive individuals and its reproducibility after one year.

To study ambulatory blood pressure (ABP) and its reproducibility in healthy normotensive elderly subjects, 34 individuals were randomly selected. Their ages were 65 years (n = 10), 70 years (n = 10), 75 years (n = 8) and 80 years (n = 6). SpaceLabs 90207 system was used and one initial and a follow-up measurement after one year was performed. It was found that 24h ABP easily could be recorded in elderly subjects. A mean of 97% of the measurements were successful and only two of 34 subjects dropped out because of measurement failures. Nocturnal blood pressures were lower in all age groups and in both sexes. The standard deviations of the differences between the baseline and one year measurements were for the daytime period 8/4 mmHg and for the nighttime period 12/8 mmHg. In conclusion, ABP is easily accepted as a clinical method in normotensive elderly subjects. In all subjects there is a reduction of the nocturnal blood pressure and the reproducibility of ABP after one year is good.

Pharmacokinetics and pharmacodynamics of trandolapril after repeated administration of 2 mg to young and elderly patients with mild-to-moderate hypertension.

The new angiotensin-converting enzyme (ACE) inhibitor trandolapril 2 mg was administered daily for 10 consecutive days to young (mean age +/- SEM 44.1 +/- 2.3 years; n = 10) and elderly (mean age +/- SEM 69.3 +/- 0.9 years; n = 14) patients with mild-to-moderate hypertension. All groups had similar baseline blood pressures: mean 164/100 mm Hg. Maximal plasma ACE inhibition on day 10 and residual inhibition 24 h after the last dose was the same, irrespective of age: young, 85.2 and 57.4%; elderly 89.1 and 59.8%, respectively. There was no difference between the results on day 1 for the young and elderly groups. The absorption of trandolapril was rapid (< 1 h in all groups). The peak plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were slightly higher in the older group, but the elimination half-life (t1/2) was the same, with no accumulation after repeat dosing. A steady-state plasma concentration of the active metabolite of trandolapril, trandolaprilat, was reached after 4 days in the two groups, with similar accumulation ratios (young, 1.48; elderly, 1.49). At steady state, the Cmax and AUC 0-24 h for trandolaprilat were similar in the two groups: young, 7.49 +/- 0.98 ng/ml and 82.27 +/- 6.95 ng/ml/h; elderly, 8.35 +/- 0.67 ng/ml/h and 96.75 +/- 5.67 ng/ml/h. Maximal reductions in systolic/diastolic blood pressures (at 6 h postdose) were -14.1%/-16.1% in young patients and -14.6%/-17.5% for the elderly. Significant blood pressure reduction persisted for 48 h after the last dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Subcutaneous adipose tissue blood flow in the abdominal and femoral regions in obese women: effect of fasting.

Subcutaneous adipose tissue blood flow (ATBF) was measured by the local clearance of 133Xe from the abdominal and femoral regions of nine individuals with non-endocrine obesity before and after seven days of fasting. Fifteen non-obese individuals served as controls. In the obese group ATBF was similar in the abdominal and femoral regions, 1.7 +/- 0.2 and 1.8 +/- 0.2 ml/min/100 g adipose tissue, respectively. In contrast, in the non-obese group the abdominal ATBF was higher, 4.1 +/- 0.6 and 2.4 +/- 0.2 ml/min/100 g adipose tissue, respectively (P < 0.01). During fasting, ATBF in the abdominal region increased by 45% (P < 0.01), but it remained unchanged in the femoral region. The mechanisms behind the differences in responses to fasting in the two regions are unsettled but may depend on regional differences in lipolytic activity and responses to vasoactive substances. Furthermore, the vasodilator response to fasting in the abdominal region in combination with the higher lipolytic rate in that region may be a pathophysiological factor behind the increased cardiovascular morbidity associated with abdominal obesity.

In vivo interactions between beta-1 and beta-2 adrenoceptors regulate catecholamine tachyphylaxia in human adipose tissue.

Catecholamine tachyphylaxia was investigated in human s.c. adipose tissue in situ by using microdialysis. The tissue was dialyzed with adrenergic agents (10(-8) mol/l) and the glycerol concentration (lipolysis index) was determined. Perfusion with adrenaline caused a 3-fold rise in the glycerol concentration, which peaked at 30 min and then (within 1 hr) declined to a level 75% higher than base line; the latter elevation was constant for at least 2 hr. Noradrenaline or isoprenaline in the absence and presence of a selective beta-2 receptor antagonist, or the selective beta-1 adrenergic agonist dobutamine, caused a 2- to 2.5-fold transient lipolytic response which also peaked at 30 min but then (within 3 hr) declined to the base-line level. On the other hand, isoprenaline plus a selective beta-1 receptor antagonist or the beta-2 selective adrenergic agonist terbutaline caused a constant lipolytic effect for at least 3 hr. Noradrenaline or adrenaline plus a nonselective beta adrenergic antagonist as well as the alpha-2 selective adrenergic antagonist clonidine caused a sustained antilipolytic action for at least 3 hr. In conclusion, the adrenoceptor subtypes involved in lipolysis regulation in humans have different in vivo sensitivities to homologous desensitization. Beta-2 and alpha-2 adrenoceptors are resistant in this respect whereas activation of beta-1 adrenoceptors leads to rapid desensitization. However, simultaneous beta-1 and beta-2 receptor activation is accompanied by different degrees of tachyphylaxia, indicating regulatory in vivo interactions within this receptor family in human adipose tissue.

Effects of lipolytic and antilipolytic agents on glucose transport in human fat cells.

The effects of lipolytic and antilipolytic agents on glucose transport and glycerol production in isolated human fat cells was investigated. Insulin and various adenylate cyclase inhibitors caused a dose-dependent stimulation of 3-O-methyl glucose transport. The maximum effects were 245 per cent and 100 per cent, respectively. The lipolytic agents isoprenaline, forskolin and dibutyryl cyclic AMP also caused dose-dependent stimulation of 3-O-methyl glucose transport, the maximum effect being about 100 per cent. Enprofylline counteracted the 3-O-methyl glucose transport-stimulating effect of both the lipolytic and antilipolytic agents but altered only the effect of antilipolytic agents on glycerol production. Enprofylline alone had no effect on 3-O-methyl glucose transport activity but stimulated glycerol production. It is on 3-O-methyl glucose transport activity but stimulated glycerol production. It is concluded that stimulation as well as inhibition of lipolysis at different steps in the lipolytic system is associated with acceleration of glucose transport in human fat cell which does not seem dependent upon the lipolysis rate.

Beta-adrenoreceptor subtype expression in human liver.

The pharmacological and gene expressions of beta 1- and beta 2-adrenoceptor subtypes (BAR1 and BAR2) were investigated in human liver by radioligand binding assays, adenylate cyclase experiments, and RNA excess solution hybridization. [125I]Cyanopinodolol, nonlabeled adrenergic agents, and BAR1/BAR2 cRNA were used as probes. The relationship between binding sites for BAR1 and BAR2 was markedly different from that between the basal mRNA expression for the two receptor subtypes. Plasma membranes as well as a microsomel-enriched fraction contained binding sites only for BAR2. The potency of BAR agonists and antagonists in stimulating adenylate cyclase activity of plasma membranes was typical of a BAR2 response. Northern blot analysis of total cellular RNA isolated from liver tissue showed hybridization of the BAR1 probe to a mRNA species of 2.5-2.6 kilobases and of the BAR2 probe to a mRNA species of 2.2-2.3 kilobases. The basal level of BAR1 mRNA was 5-fold higher than of BAR2 mRNA, as assayed by solution hybridization. No difference in BAR subtype mRNA stability was observed, as indicated by a mRNA half-life of approximately 5.5 h for both receptor subtypes. It is concluded that specific factors are involved in the steady state regulation of BAR subtype expression in human liver. This tissue contains solely BAR2 owing to a posttranscriptional block of basal BAR1 expression.

In situ studies of catecholamine-induced lipolysis in human adipose tissue using microdialysis.

The effects of catecholamines on lipolysis in situ were investigated in humans. Subcutaneous adipose tissue was microdialyzed with solvents containing adrenergic agents. Norepinephrine caused a rapid increase in the glycerol level in adipose tissue (lipolysis index) that was further increased by the alpha adrenoreceptor blocker phentolamine. At 10(-11) mol/l of norepinephrine caused a 100% stimulation of lipolysis (P less than .025). In the presence of phentolamine the lipolytic effects of catecholamines at 10(-12) mol/l was isoproterenol greater than epinephrine greater than norepinephrine. All these three lipolytic catecholamines caused a transient increase in the adipose tissue dialysate glycerol level, which peaked after 20 to 30 min of catecholamine exposure and then declined. The apparent tachyphylaxia could not be overcome by a gradual increase of the catecholamine concentration from 10(-12) to 10(-8) mol/l. However, the selective alpha-2 adrenoreceptor agonist clonidine caused a continuous and dose-dependent decrease in the dialysate glycerol level; the minimum effective concentration was 10(-9) mol/l. In conclusion, catecholamines have a lipolytic effect in situ at much lower concentrations than those in the circulation. This effect is transient and is related to beta adrenoreceptors. In additio, catecholamines have alpha adrenoreceptor-mediated effects on lipolysis in situ.

In vivo subcutaneous adipose tissue glucose kinetics after glucose ingestion in obesity and fasting.

The kinetic pattern of subcutaneous adipose tissue extracellular glucose following glucose ingestion was investigated in vivo with a microdialysis technique in normal-weight (n = 21) and obese subjects (n = 18) before and after a 7-day fast (n = 9). A dialysis probe (4 x 0.5 mm) was implanted subcutaneously, and was continuously perfused (5 microliters/min). The tissue dialysate glucose concentration was determined in 15-min samples before and during a period of 180 min after a 75-g oral glucose load. A comparison was made between the tissue dialysate concentrations and the venous blood glucose levels. In all study groups the increase in subcutaneous tissue dialysate glucose following glucose ingestion paralleled that in blood, with a time-lag of up to 15 min. In the normal-weight subjects the maximum relative increase in abdominal adipose tissue dialysate glucose was 25% higher (p less than 0.005) than the corresponding blood glucose level, and the total relative glucose level (area under curve, AUC) in abdominal fat was 20% (p less than 0.01) higher than in blood. In contrast, the kinetics of gluteal subcutaneous tissue dialysate and blood glucose levels were similar. In the obese patients before the fasting period the maximum relative glucose level in abdominal fat was almost twice as high as in blood (p less than 0.005), and the total glucose level (AUC) was 50% higher than the blood glucose AUC (p less than 0.005). After the fast, on the other hand, almost identical relative dynamics of abdominal subcutaneous tissue and blood glucose levels were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic regulation of lipolysis in situ at rest and during exercise.

The adrenergic regulation of lipolysis was investigated in situ at rest and during standardized bicycle exercise in nonobese healthy subjects, using microdialysis of the extracellular space in subcutaneous adipose tissue. The glycerol concentration was about two times greater in adipose tissue than in venous blood. At rest, the glycerol concentration in adipose tissue was rapidly increased by 100% (P less than 0.01) after the addition of phentolamine to the ingoing perfusate, whereas addition of propranolol did not alter the adipose tissue glycerol level. Glycerol in adipose tissue and plasma increased during exercise and decreased in the postexercise period. Propranolol in the perfusate almost completely inhibited the increase in the tissue dialysate glycerol during the exercise-postexercise period. Phentolamine, however, was completely ineffective in this respect. During exercise, the lipolytic activity was significantly more marked in abdominal than in gluteal adipose tissue; this was much more apparent in women than in men. Thus, in vivo lipolysis in subcutaneous adipose tissue is regulated by different adrenergic mechanisms at rest and during exercise. Alpha-adrenergic inhibitory effects modulate lipolysis at rest, whereas beta-adrenergic stimulatory effects modulate lipolysis during exercise. In addition, regional differences in lipolysis are present in vivo during exercise, which seem governed by factors relating to sex.