Three hundred and thirty-three consecutive patients in a medical ward were evaluated in a high-intensity monitoring scheme for drug events as a cause of hospitalization. Taking into consideration only 'definite' and 'probable' drug events, we found 36 cases (10.8%) of all admissions to be drug-related hospitalizations (DRH). Of these, 8.1% were adverse drug reactions and 2.7% were therapeutic failures due to ineffective dosage. In 8 cases (2.4%) the drug event could definitely have been avoided, and a further 13 cases (3.9%) were considered to have been potentially avoidable if appropriate measures had been taken by the health service. In 19 cases (53%) the referring physician was unaware of the drug-related problem. Those patients admitted because of a drug event were taking significantly more drugs than other individuals. The avoidable drug events pointed to the primary health care physicians as the appropriate targets for preventive measures in terms of intensified drug education. The study demonstrated that a reliable estimate of the DRH rate requires active data collection by a qualified health service worker in close collaboration with the patient's family doctor in cases of suspected DRH.

1. In total 1999 consecutive admissions to six medical wards were subjected to a prospective high‐intensity drug event monitoring scheme to assess the extent and pattern of admissions caused by adverse drug reactions (ADRs) or dose related therapeutic failures (TF), in a population‐based design. The wards were sub‐specialised in general medicine, geriatrics, endocrinology, cardiology, respiratory medicine and gastroenterology. 2. Considering definite, probable and possible drug events, the prevalence of drug related hospital admissions was 11.4% of which 8.4% were caused by ADRs and 3.0% by TFs. There were large inter‐department differences. 3. The six classes of drugs most frequently involved in admissions caused by ADRs were anti‐rheumatics and analgesics (27%), cardiovascular drugs (23%), psychotropic drugs (14%), anti‐diabetics (12%), antibiotics (7%), and corticosteroids (5%). Noncompliance accounted for 66% of the TFs with diuretics and anti‐asthmatics most frequently involved. 4. The pattern of drugs involved in ADRs was compared with the regional drug sales statistics. Drugs with a particularly high rate of ADR related admissions per unit dispensed were nitrofurantoin and insulin (617 and 182 admissions per 1,000,000 defined daily doses), while low rates were seen for diuretics and benzodiazepines (10 and 7 admissions per 1,000,000 defined daily doses). Confidence intervals were wide. 5. Patients who had their therapy prescribed by a hospital doctor had a slightly higher prevalence of drug events than those who were treated by a general practitioner (12.6% vs 11.8%). The reverse applied for drug events assessed as avoidable (3.3% vs 4.6%). Although these differences were not statistically significant, it may suggest general practitioners as the appropriate target for interventive measures.(ABSTRACT TRUNCATED AT 250 WORDS)

1 The effect of clomipramine and desipramine on diabetic neuropathy symptoms was examined in a double-blind, randomised, placebo controlled, cross-over study for 2 + 2 + 2 weeks. Drug doses were adjusted according to the sparteine phenotype, i.e. extensive metabolisers were treated with 75 mg clomipramine day-1 and 200 mg desipramine day-1 whereas poor metabolisers were treated with 50 mg day-of both drugs. Nineteen patients completed the study. 2 Plasma concentration of clomipramine plus desmethylclomipramine was 70-510 nm in extensive metabolisers, vs 590 and 750 nm in two poor metabolisers. Desipramine levels were 130-910 nM, vs 860 and 880 nM. 3 Both clomipramine and desipramine significantly reduced the symptoms of neuropathy as measured by observer-and self rating in comparison with placebo. Clomipramine tended to be more efficacious than desipramine. Patients with a weak or absent response on clomipramine had lower plasma concentrations (clomipramine plus desmethylclomipramine < 200 nM) than patients with a better response. For desipramine a relationship between plasma concentration and effect was not established. 4 Side effect ratings did not differ for clomipramine and desipramine and on both drugs three patients withdrew due to side effects. 5 Compared with earlier results obtained with imipramine dosed on the basis of plasma level monitoring, clomipramine and desipramine on fixed doses appeared less efficacious whereas the side effect profiles were the same. At least for clomipramine, appropriate dose adjustment on the basis of plasma level monitoring may increase the efficacy.

Three hundred and sixty-six consecutive patients admitted to a department of cardiology were evaluated for drug events as a cause of admission. The drug events considered were adverse drug reactions (ADR) and dose-related therapeutic failures (DTF). 'Definite' or 'probable' drug events accounted for 15 admissions (4.1%, 95% confidence limits 2.3-6.7%), of which eleven were ADR and four were DTF. With the inclusion of six 'possible' drug events, the rate of drug-related hospitalizations (DRH) was 5.7%. DRHs were characterized by a preponderance of acute admissions and elderly patients. Hypokalaemia (less than 3.5 mM) was observed in 27 (16%) patients receiving diuretics, and could be related to four cases of arrhythmias (two 'probable' and two 'possible' ADR). The average serum potassium level was similar in diuretic treated patients with or without drugs to counteract hypokalaemia, irrespective of the drugs chosen. Among the 15 'definite'/'probable' DRHs, five were considered to be due to an error in prescription, and a further five cases were judged to have been avoidable had appropriate measures been taken by prescribing physicians. A DRH educational intervention programme should primarily deal with non-compliance or with prescription of diuretics or digoxin, since these problems constitute the majority of cases of DRH. No specific group of doctors could be targeted as responsible for DRH, avoidable or not.

OBJECTIVETo determine the effect of treatment with insulin aspart compared with NPH insulin, together with metformin/placebo and rosiglitazone/placebo. The hypothesis was that combined correction of major pathogenetic defects in type 2 diabetes would result in optimal glycemic control.RESEARCH DESIGN AND METHODSThis study was a 2-year investigator-driven randomized partly placebo-controlled multicenter trial in 371 patients with type 2 diabetes on at least oral antiglycemic treatment. Patients were assigned to one of eight treatment groups in a factorial design with insulin aspart at mealtimes versus NPH insulin once daily at bedtime, metformin twice daily versus placebo, and rosiglitazone twice daily versus placebo. The main outcome measurement was change in A1C.RESULTSA1C decreased more in patients treated with insulin aspart compared with NPH (−0.41 ± 0.10%, P < 0.001). Metformin decreased A1C compared with placebo (−0.60 ± 0.10%, P < 0.001), as did rosiglitazone (−0.55 ± 0.10%, P < 0.001). Triple therapy (rosiglitazone, metformin, and any insulin) resulted in a greater reduction in A1C than rosiglitazone plus insulin (−0.50 ± 0.14%, P < 0.001) and metformin plus insulin (−0.45 ± 0.14%, P < 0.001). Aspart was associated with a higher increase in body weight (1.6 ± 0.6 kg, P < 0.01) and higher incidence of mild daytime hypoglycemia (4.9 ± 7.5 vs. 1.7 ± 5.4 number/person/year, P < 0.001) compared with NPH.CONCLUSIONSInsulin treatment of postprandial hyperglycemia results in lower A1C than treatment of fasting hyperglycemia, at the expense of higher body weight and hypoglycemic episodes. However, insulin therapy has to be combined with treatment of both peripheral and liver insulin resistance to normalize blood glucose, and in this case, the insulin regimen is less important.