Thiazolidinediones for type 2 diabetes. New agents reduce insulin resistance but need long term clinical trials.
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Chemical and Drug Induced Liver Injury↗
Biomedical subjects
A Melander
Publications and source records attributed to A Melander.
Increased mortality in Type II diabetic patients using sulphonylurea and metformin in combination: a population-based observational study.
AIMS/HYPOTHESIS: This study analysed cause-specific mortality in Type II (non-insulin-dependent) diabetic patients using either sulphonylurea alone or in combination with metformin. METHODS: Patients were followed from the first day they were taking either the combination or sulphonylurea alone. Odds ratios by Cox regression analyses were adjusted for age, sex, duration of diabetes, study area, year of inclusion and fasting blood glucose at inclusion. RESULTS: We included 169 patients taking sulphonylurea and metformin in combination and 741 patients taking only sulphonylurea. Mean (range) follow-up time was 6.1 (0.1-13.0) years. The adjusted odds ratio for overall mortality was 1.63 (95% confidence interval 1.27-2.09) in patients taking sulphonylurea and metformin combination vs those using sulphonylurea alone. For mortality from ischaemic heart disease and stroke the adjusted odds ratios were 1.73 (95% confidence interval 1.17-2.55) and 2.33 (95% confidence interval 1.17-4.63), respectively. CONCLUSION/INTERPRETATION: There was a higher cardiovascular mortality in Type II diabetic patients taking sulphonylurea and metformin in combination than in those taking only sulphonylurea. Hence, it cannot be excluded that this kind of combination therapy possibly increases cardiovascular mortality. It is feasible that the increased mortality was secondary to a more aggressive type of diabetes in the patients using sulphonylurea and metformin in combination. Combination therapy is known to promote additional blood glucose reduction but there is as yet no evidence that a sulphonylurea and metformin combination is more beneficial on micro- or macrovascular disease than sulphonylurea or metformin alone.
Blood Glucose↗
Effects and pharmacokinetics of oral glibenclamide and glipizide in Caucasian and Chinese patients with type-2 diabetes.
The effects and kinetics of oral glibenclamide (Gb) and glipizide (Gz) were studied in Caucasian and Chinese patients (ten in each group) with type-2 diabetes. In randomised order, 2.5 mg Gb, 2.5 mg Gz or placebo was given orally before the administration of 75 g oral glucose. Concentrations of insulin and proinsulin were determined using radioimmunoassay (RIA) without cross-reactivities, and sulphonylurea concentrations were determined using high-performance liquid chromatography (HPLC). There were no significant interethnic differences in Gb or Gz effects whether on glucose, insulin or proinsulin/insulin ratio at any time point. Following Gz, however, Chinese patients had greater increments of serum proinsulin at 10-30 min compared with Caucasians. Apart from the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of Gz being higher among the Chinese, no significant interethnic differences in pharmacokinetics were found. It appears that the same dosage principles could be used for Caucasian and Chinese patients with type-2 diabetes when Gb or Gz are prescribed.
Adult↗
Pharmacodynamics and pharmacokinetics of intravenous glibenclamide in Caucasian and Chinese patients with type-2 diabetes.
OBJECTIVE: We analysed the kinetics and effects of glibenclamide (Gb) on glucose, insulin and proinsulin secretion in two ethnic groups (10 in each) of type-2 diabetic patients, one of Caucasian, the other of Chinese origin. BACKGROUND: Diabetes mellitus type 2 is a global disease affecting all ethnic groups. There are ethnic differences in both the prevalence and metabolic characteristics of the disease. Important interethnic pharmacodynamic and pharmacokinetic differences have been reported for several drugs. With few exceptions, detailed studies on sulphonylurea are lacking. MATERIAL AND METHODS: The patients were studied on two occasions when either no Gb (control) or 1.25 mg Gb was administered i.v., immediately before the administration of a 75-g oral glucose tolerance test. Concentrations of insulin and proinsulin were determined by means of radioimmunoassay without cross-reactivities. Gb concentration was determined using high-performance liquid chromatography. Pharmacodynamic results were calculated using net areas under the curves, with basal values set as zero. A P value less than 0.05 was considered significant. RESULTS: When glucose was administered orally without Gb, Chinese patients had higher plasma glucose increases at 10 min (7.6 mmol/l x min vs 2.6 mmol/l x min) and higher increases of plasma insulin levels than Caucasians at both 10 min (198 pmol/l x min vs 54 pmol/l x min) and 30 min (2286 pmol/l x min vs 1198 pmol/l x min). When Gb was administered, the plasma glucose increases were reduced, and the increases of serum insulin and proinsulin levels were greater in both ethnic groups. Compared with the basal values (-1 min), proinsulin/insulin ratios (RPI) were lowest at 10-30 min, followed by an increase. Chinese patients had higher increases of serum insulin levels at 10 min (1109 pmol/l x min vs 550 pmol/l x min) and a lower RPI at 30 min (6. 0% vs 7.6%) and 240 min (15.0% vs 21.0%) relative to Caucasians. Serum Gb data were best fitted to a biexponential i.v. model. There were no interethnic differences in any of the pharmacokinetic parameters. CONCLUSION: In summary, following oral glucose administration without Gb, Chinese type-2 diabetic patients had higher plasma insulin levels but also higher plasma glucose levels during the first 10 min, which might reflect reduced insulin sensitivity or more rapid glucose absorption. Gb augmented glucose-induced release of both insulin and proinsulin in both ethnic groups; the effect on insulin secretion was more pronounced. In conclusion, minor pharmacodynamic but no pharmacokinetic differences were found between the two groups. It seems appropriate to employ the same dosage principles when using Gb in Caucasians and Chinese.
Adult↗
Sulphonylurea dose-response relationships: relation to clinical practice.
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Area Under Curve↗
Associations between smoking and beta-cell function in a non-hypertensive and non-diabetic population. Skaraborg Hypertension and Diabetes Project.
AIMS: An increased risk for Type 2 diabetes in male and female smokers has been associated with insulin resistance. However, this might also be the result of an adverse effect on the beta-cell. The aim of the present study was to examine the association between smoking and beta-cell function. METHODS: A community-based, cross-sectional observation study. In 1994, a randomized age-stratified sample of men and women aged > or = 40 years in the city of Skara, Sweden, were invited to a survey of cardiovascular risk factors. In all, 1,109 subjects participated (80%). After the exclusion of subjects with known hypertension or diabetes mellitus, 874 subjects remained to explore. Samples were drawn after an overnight fast. Lifestyle (smoking, physical activity, alcohol consumption) was assessed using a questionnaire. Insulin resistance and insulin secretion were estimated using the homeostasis model assessment (HOMA). RESULTS: Cigarette smoking men (n = 101) had a lower HOMA beta-cell value (58.1), than never-smokers (n = 158, beta-cell value 90.1, P < 0.001). The difference remained with adjustments for age, body mass index, daily alcohol intake and physical exercise habits: 25.9 (95% confidence interval (CI) 9.7-38.8, P = 0.003). Correspondingly, in men the HOMA beta-cell value was lower in current smokers than in ex-smokers (difference 24.3, 95% CI 11.1-35.2, P < 0.001). In women, no significant difference appeared in beta-cell function vs. different smoking status. There was no association between smoking status and insulin resistance. CONCLUSIONS: At least in men, smoking may interfere with beta-cell function. The prevention of Type 2 diabetes should include strategies to stop smoking.
Adult↗
Mortality in elderly men with low psychosocial coping resources using anxiolytic-hypnotic drugs.
OBJECTIVE: Insufficient coping with stress may lead to increased susceptibility for disease and death. Use of anxiolytic-hypnotic drugs has been suggested as a coping strategy, and some opinions have proposed their use as preventive medication. The aim of this study was to estimate if use of anxiolytic-hypnotic drugs counters the increased mortality observed in individuals lacking other coping strategies such as emotional support and social participation. METHODS: A population based cohort study with 10-year (1982/83-1993) survival analysis was performed in 491 men born in 1914, living in the Swedish city of Malmö. RESULTS: Compared with men with a high level of psychosocial coping resources who did not use anxiolytic-hypnotic drugs, men with a low level of psychosocial coping resources had a higher risk of death irrespective whether they used anxiolytic-hypnotic drugs, RR = 1.7 (95% CI 1.1-2.6) or not RR = 1.8 (95%: 1.3-2.5). CONCLUSION: Anxiolytic-hypnotic drugs do not seem to counter increased mortality in elderly men with low psychosocial coping resources.
Adaptation, Psychological↗
[Combination treatment with insulin and metformin in type 2 diabetes. Improves glycemic control and prevents weight gain].
Type II diabetes patients on insulin often show inadequate glycaemic control and weight gain. The rationale for adding metformin in these cases is that it can reduce insulin resistance. The present article reviews the growing body of clinical documentation supporting combination therapy, i.e. placebo-controlled studies in insulin-treated patients and controlled studies with reference therapies in patients not yet treated with insulin. These studies show improvement of glycaemic control and less weight gain. Insulin dosages can be reduced in both type II and type I diabetes. A combination of insulin and metformin is recommended especially for obese type II diabetes patients on high insulin doses.
Blood Glucose↗
Utilization of cardiovascular drugs (blood pressure lowering drugs, lipid lowering drugs and nitrates) and mortality from ischaemic heart disease and stroke. An ecological analysis based on Sweden's municipalities.
OBJECTIVE: To perform an ecological study in an effort to generate questions concerning the preventive impact of various cardiovascular drugs on mortality from stroke and ischaemic heart disease (IHD) in the community, and to explore the association between sales of nitrates and mortality from stroke and IHD. METHODS: Out-patient drug utilization (sales) of blood pressure lowering drugs, lipid lowering drugs and nitrates were categorized in four groups of equal size by quartiles and compared with mortality from IHD and stroke, using the group of municipalities with the lowest utilization as reference, from 1989 to 1993 in 283 of Sweden's 288 municipalities, by Poisson regression. Adjustments were made for population size, age and gender proportions, the utilization rate of cardiovascular drugs other than the tested drug group and location of the municipality. RESULTS: Compared with the group of municipalities with the lowest sales and adjusting only for population size, mortality from IHD and stroke increased with the extent of utilization of blood pressure lowering drugs and nitrates. In contrast, mortality decreased with increased utilization of lipid lowering drugs. After further adjustments by percentage of men, age structure, geographical location (mid-points) of the municipalities, and, as a proxy for cardiovascular disease, the sales of cardiovascular drugs other than the tested drug group, the increased risk associated with blood pressure lowering drugs disappeared, and there was a dose-response association between sales of diuretics and old antihypertensives and decreasing mortality, sales of nitrates continued to be associated with an increased risk, and the low mortality risk associated with sales of lipid lowering drugs persisted. CONCLUSION: Lipid lowering drugs may have a preventive impact in the general population, but the preventive impact of blood pressure lowering drugs, with the exception of diuretics and old antihypertensives, may be low in many municipalities. The safety of nitrates needs more investigation at the individual level.
Antihypertensive Agents↗
Utilisation of codeine and propoxyphene: geographic and demographic variations in prescribing, prescriber and recipient categories.
OBJECTIVES: To assess (1) whether the utilisation of codeine or propoxyphene differs among the three major Swedish cities (Stockholm, Göteborg and Malmö) and between urban and semirural areas; (2) if so, whether it co-varies with the utilisation of other potentially dependence-promoting drugs, benzodiazepines; (3) what influence age, gender and socioeconomic factors have on the prescribing of the two narcotic analgesics; and (4) whether different codeine-prescriber categories have different prescribing habits. METHODS: In Sweden, all pharmacies are owned by one corporation, Apoteket AB. This corporation collects, stores and compiles statistics on all drug sales in Sweden, and data are available both on national, regional, county and municipal levels. The employed unit is defined daily dose (DDD) per 1,000 inhabitants per day. Using the pharmacy computer system while dispensing a drug, prescription patterns can be elucidated. This system describes the number of drug items dispensed, drug amounts and age and gender of patients. Furthermore, data from another, ecological study were used to relate codeine and propoxyphene utilisation to that of benzodiazepines and to various socioeconomic data available from records of the city of Malmö. RESULTS: The utilisation of analgesics in Sweden has increased during a 10-year period. The withdrawal of over-the-counter combinations containing aspirin and low-dose codeine in 1990 resulted only in a transient decrease of codeine use. The utilisation of codeine in Malmö and Göteborg was considerably higher than that in Stockholm and in the rest of Sweden, including the surroundings of Malmö. In Malmö and Göteborg, codeine was most often prescribed by private physicians to middle-aged persons, particularly women. Districts in Malmö with a high utilisation of codeine were associated with unfavourable socioeconomic conditions and a high utilisation of benzodiazepines. The utilisation pattern of propoxyphene showed less or no such deviations. CONCLUSION: The results suggest an inappropriate use of codeine in two major cities in Sweden.
Adolescent↗
Factors influencing the detection rate of drug-related problems in community pharmacy.
This study analyzes relationships between the number of drug-related problems detected in community pharmacy practice and the educational level and other characteristics of pharmacy personnel and their work sites. Random samples of pharmacists, prescriptionists and pharmacy technicians were drawn nationwide in Sweden. One hundred and forty-four (63%) of those meeting the inclusion criteria agreed to take part. The participants documented medication-related problems, interventions and patient variables on a data collection form. The drug-related problems were weighted by the number of patients served by each professional. The regression analysis showed the educational level of the professional to have a statistically significant effect on the detection rate, with pharmacists finding on average 2.5 more drug-related problems per 100 patients than prescriptionists and about 3.6 more than technicians. Previous participation in a study or activity on drug-related problems and the size of the pharmacy also had statistically significant effects on the problem detection rate. The use of open-ended questions to create a dialogue with the patient seemed to be a successful means to discover problems. The results of this study indicate the importance of education and training of pharmacy personnel in detection of drug-related problems. This findings speaks in favor of increasing the pharmacist to other personnel ratio, provided the higher costs will be offset by societal benefits.
Drug-Related Side Effects and Adverse Reactions↗
Differences in treatment and metabolic abnormalities between normo- and hypertensive patients with type 2 diabetes: the Skaraborg Hypertension and Diabetes Project.
AIM: To examine treatment and glucose control in type 2 diabetes patients with and without hypertension, and to explore differences in markers for insulin resistance and beta cell function. METHODS: A community-based, cross-sectional observational study was carried out at the hypertension and diabetes outpatient clinic in primary health care, Skara, Sweden. The subjects were all the 400 patients with type 2 diabetes (202 men, 198 women) who underwent annual follow-up from May 1992 through September 1993; 204 of these also had hypertension. RESULTS: The patients with both type 2 diabetes and hypertension had a higher b.m.i. (mean; 28.9 kg m(-2) (s.d.; 4.4) vs. 27.4 kg m(-2)(4.6)), higher triglycerides (2.0 mmol l(-1)(1.1) vs. 1.7 mmol l(-1)(1.1)), higher LDL/HDL cholesterol ratio (4.3(1.4) vs. 4.1(1.2)) and higher fasting insulin (8.5 mU l(-1)(1.1) vs. 6.6 mU l(-1)(1.1)). Conversely, glucose levels were lower; HbA1c (6.4%(1.4) vs. 6.8%(1.6)) and fasting blood glucose (8.1 mmol l(-1)(2.3) vs. 8.9 mmol l(-1)(2.7)) than in patients with type 2 diabetes alone. By the homeostasis model assessment (HOMA), patients with type 2 diabetes alone had more impaired beta cell function. They also had a higher frequency of insulin treatment (20% vs. 12%) and were less often treated non-pharmacologically (33% vs. 50%). CONCLUSIONS: Patients with type 2 diabetes and hypertension constitute a high risk category with a more atherogenic risk factor profile related to the insulin resistance syndrome. Patients with type 2 diabetes without hypertension seem to constitute a subgroup of type 2 diabetes with predominately impaired beta cell function.
Aged↗
Effects of antihyperglycaemic therapies on proinsulin and relation between proinsulin and cardiovascular risk factors in type 2 diabetes.
AIM: To assess the effect of oral antihyperglycaemic therapy on fasting proinsulin and the relation between proinsulin levels and cardiovascular risk factors in type 2 diabetes. METHODS: One hundred and sixty-five patients with type 2 diabetes, fasting blood glucose concentration (FBG) > or = 6.7 mmol/l, were recruited from five diabetes outpatient clinics in primary health care. Diet and antihyperglycaemic medication, aiming at FBG < 6.7 mmol/l, was maintained for 6 months after completed dose titration in a randomized, double-blind, double-dummy trial with metformin (M), glibenclamide (G) and primary combination of both drugs (MG). The study compared M, G and MG in low dose (MGL) and also different high-dose regimens, i.e. G added to M (M/G), M added to G (G/M) and primary combination (MGH). Outcome measures were fasting proinsulin, glycaemia, body mass index, blood pressure, lipids, insulin and C-peptide. RESULTS: Lower proinsulin levels were found when therapy was initiated with metformin (M vs. G, p = 0.013 and M/G vs. G/M, p = 0.033). M and G were equally effective on glucose levels. In the group as a whole FBG decreased from (mean +/- s.d.) 10.2 +/- 2.7 to 7.0 +/- 1.2 mmol/l with no change in proinsulin. Proinsulin was associated with cardiovascular risk factors, linking high proinsulin to an atherogenic risk marker profile. Mean proinsulin change from baseline was inconsistently associated with markers of insulin resistance. Meal-stimulated glucose (net AUC) decreased after treatment only in those with low baseline proinsulin levels. CONCLUSION: It may be advantageous to initiate oral antihyperglycaemic therapy with metformin rather than with sulphonylurea. High proinsulin levels are associated with an atherogenic-risk marker profile and an impaired therapeutic postprandial glucose response after treatment in patients with type 2 diabetes. Proinsulin change after therapy is inconsistently associated with markers of insulin resistance and unrelated to fasting blood glucose reduction.
Biomarkers↗
[Feared risk factors in connection with calcium antagonists are not to be dismissed].
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Apoptosis↗
Use of calcium channel blockers and risk of suicide: ecological findings confirmed in population based cohort study.
OBJECTIVE: To investigate possible associations between use of cardiovascular drugs and suicide. DESIGN: Cross sectional ecological study based on rates of use of eight cardiovascular drug groups by outpatients. A population based cohort study including users of drugs to control hypertension. SUBJECTS: The ecological study included 152 of Sweden's 284 municipalities. The cohort study included all inhabitants of one Swedish municipality who during 1988 or 1989 had purchased cardiovascular agents from pharmacies within the municipality. Six hundred and seventeen subjects (18.2%) were classified as users of calcium channel blockers and 2780 (81.8%) as non-users. MAIN OUTCOME MEASURES: Partial correlations (least squares method) between rates of use of cardiovascular drugs and age standardised mortality from suicide in Swedish municipalities. Hazard ratios for risk of suicide with adjustments for difference in age and sex in users of calcium channel blockers compared with users of other hypertensive drugs. RESULTS: Among the Swedish municipalities the use of each cardiovascular drug group except angiotensin converting enzyme inhibitors correlated significantly and positively with suicide rates. After adjustment for the use of other cardiovascular drug groups, as a substitute for the prevalence of cardiovascular morbidity, only the correlation with calcium channel blockers remained significant (r = 0.29, P < 0.001). In the cohort study, five users and four non-users of calcium channel blockers committed suicide during the follow up until the end of 1994. The absolute risk associated with use of calcium channel blockers was 1.1 suicides per 1000 person years. The relative risk, adjusted for differences in age and sex, among users versus non-users was 5.4 (95% confidence interval 1.4 to 20.5). CONCLUSIONS: Use of calcium channel blockers may increase the risk of suicide.
Calcium Channel Blockers↗
Socioeconomic factors, morbidity and drug utilization--an ecological study.
The aim of the present study was to elucidate the relations between demographic and socioeconomic factors, morbidity and the utilization of major drug groups in an urban Swedish population. The study was performed as an ecological analysis during November 1991 in the 17 different districts of Malmö, the third largest Swedish city (235,000 inhabitants). The material comprised 86,228 ACT-coded drug items which corresponded to 76% of all prescriptions dispensed during the study month. Of these, 43,032, dispensed to patients aged 15-64 years, were analysed in the present work. Age standardized drug utilization was expressed as the number of dispensed Defined Daily Doses per 1000 inhabitants per day. Morbidity was measured in terms of reimbursed days on sick leave. The sociodemographic parameters used were socioeconomic status (SES), employment rate, median income per family, households on social allowance, and ethnicity. For four of the five major pharmacological groups (ATC-groups A, C, J, N and R, i.e. alimentation, circulation, infectious diseases, nervous system and respiration), most pronouncedly group N and least so group R, utilization correlated positively with not only the extent of morbidity but also with an unfavourable socioeconomic situation, high proportion of immigrants, and households on social allowance or with low income and/or with a low employment rate. The utilization of antibiotics (group J), however, instead correlated negatively with these parameters. For all five drug groups, these trends were similar among men and women, albeit with varying strength. In conclusion, socioeconomic factors may have a profound influence on the utilization of several major drug groups. At least in the case of antibiotics, the consequence of this influence is irrational drug use.
Journal Article↗
Pharmacokinetics of glibenclamide and its metabolites in diabetic patients with impaired renal function.
BACKGROUND: Glibenclamide (Gb) may provoke long-lasting hypoglycaemic reactions, and one of the known risk factors is impaired renal function. We have demonstrated Gb to have a terminal elimination half-life of 15 h, and the main metabolites have a hypoglycaemic effect. With few exceptions, detailed studies on second generation sulphonylureas in diabetics with impaired renal function are lacking. Therefore, we analysed the pharmacokinetics of Gb and its active metabolites, 4-trans-hydroxyglibenclamide (M1) and 3-cis-hydroxy-glibenclamide (M2) in this patient group. METHODS: Two groups of 11 diabetic patients with impaired renal function (IRF, iohexol clearance range 7-42 ml.min(-1) . 1.73 m(-2)) or normal renal function (NRF, iohexol clearance range 75-140 ml.min(-1) . 1.73 m(-2)) were compared. A single oral 7-mg dose of Gb was administered after overnight fasting. Serum samples and urine collections were obtained over 48 h and 24 h, respectively. Concentrations of Gb, M1 and M2 were determined by a sensitive and selective high-performance liquid chromatography assay. RESULTS: Peak serum values of M1 (24-85 ng.ml(-1) vs 16-57 ng.ml(-1)), M2 (7-22 ng.ml(-1) vs <5-18 ng.ml(-1)) and M1 + M2 (32-100 ng.ml(-1) vs 23-76 ng.ml(-1)) were higher in the IRF group. AUC and Cmax of Gb were lower and the clearance to bioavailability ratio (CL/f) was higher in the IRF group. AUC and Cmax of M1 were higher and CL/f lower in the IRF group. Much lower amounts of M and M2 were excreted in the urine in the IRF group (7.2% vs 26.4% in 24 h). The fraction of the Gb dose excreted as metabolites (fe(met) 0-24 h), ranged between 0.005 and 0.36 and correlated significantly with renal function measured by iohexol clearance. No other pharmacokinetic differences were found. CONCLUSION: The differences in AUC, Cmax and CL/f of Gb may be explained by a higher free fraction in the IRF group which would increase Gb metabolic clearance. The inverse findings regarding M1 may be explained by the fact that the metabolites are primarily eliminated by the kidneys. After a single dose of Gb, neither Gb, M1 nor M2 seemed to accumulate in diabetic subjects with IRF. As only small amounts of M1 and M2 were excreted in the urine, this indicates one or several complementary non-renal elimination routes, e.g. shunting of metabolised Gb to the biliary excretion route and/or enterohepatic recycling of both metabolites and unmetabolised Gb.
Adult↗
Intra-urban variation of antibiotic utilization in children: influence of socio-economic factors.
OBJECTIVE: The aim of this study was to investigate the intra-urban variation of antibiotic utilization in children in Malmö and to evaluate the influence of socio-economic factors on this variation. METHODS: In an ecological analysis, the variations in antibiotic utilization in children, expressed as defined daily dose (DDD) or as the number of prescriptions per 1000 inhabitants per day, were compared with variations in socio-economic and demographic factors in the 17 administrative districts of the Swedish city of Malmö (235000 inhabitants). RESULTS: There were large between-area differences in antibiotic utilization, especially in children aged 0-6 years. Socio-economic factors reflecting a privileged situation correlated positively with antibiotic utilization. Thus, in districts with a high median family income and a high employment rate, the utilization of antibiotics was higher than in other districts. Conversely, in districts with a high proportion of blue-collar workers, people with foreign backgrounds and recipients of social benefit, antibiotic utilization was comparatively low. In contrast, the utilization of penicillin V relative to other antibiotics showed an opposite pattern, including positive correlations with the proportion of social benefit, immigrants and blue-collar workers and a negative correlation with employment rate. Conversely, the utilization of macrolides in relation to other antibiotics in children aged 0-6 years was highest in districts inhabited by those who were socio-economically privileged. INTERPRETATION: The findings suggest that utilization of antibiotics in children may vary considerably within a city, that it may increase with the degree of parental affluence, and that such affluence may reduce the utilization of penicillin V relative to other antibiotics.
Adolescent↗