Exposure to medicines among patients admitted for hip fracture and the case-fatality rate at 1 year: a longitudinal study.

PURPOSE: To describe the demographic and clinical characteristics and the pre-fracture exposure to medicines of patients admitted for a hip fracture, and to explore their association with fatal outcome 1 year after the fracture. METHODS: All patients ≥ 65 years old admitted for a hip fracture in a tertiary hospital in Barcelona between January 1 and December 31 2007 were included. Data on the patients' clinical characteristics before and during hospital admission and on pre-fracture exposures to medicines were collected from the clinical records. One-year mortality was checked by approaching the patients and their families and was cross-checked with the national mortality statistics database. A Cox proportional hazards analysis was carried out. RESULTS: Four hundred and fifty-six patients [mean age (SD) 82.9 (7.2) years, 73.5 % female], were admitted with hip fracture during the study period. Almost 80 % of the patients (363, 79.6 %) had three or more associated conditions, and 41.7 % received pre-fracture treatment with five or more drugs. The case-fatality rate during hospital admission was 4.6 % (21 patients). One hundred and seven patients died within 1 year (23.5 %). Advanced age, male gender, two or more associated chronic conditions, cancer, severe cognitive impairment, and treatment with opiates before fracture were significantly associated with the risk of dying. An inverse association was recorded between mortality and pre-hospital exposure to medicines for osteoporosis. CONCLUSIONS: One-quarter of patients admitted for hip fracture died within 1 year after the fracture. Exposure to opiates before hip fracture was associated with an increased 1-year death rate, whereas treatment with drugs for osteoporosis was associated with a decrease in death rate. These results should be confirmed in studies with detailed prospective collection of information on exposure to medicines.

Use of granulocyte colony-stimulating factor (G-CSF) and outcome in patients with non-chemotherapy agranulocytosis.

PURPOSE: The use of granulocyte colony-stimulating factor (G-CSF) in the treatment of non-chemotherapy drug- induced agranulocytosis is controversial. We aimed at assessing the effect of G-CSF on the duration of agranulocytosis. METHODS: To assess the effect of G-CSF on the duration of agranulocytosis, a Cox proportional hazard model with an estimated propensity score covariate adjusting for several prognostic factors was used. RESULTS: One hundred and forty-five episodes of agranulocytosis were prospectively collected from January 1994 to December 2000 in Barcelona (Spain). No differences were found in the case-fatality rate between treated (9 of 101, 8.9%) and not treated (5 of 44, 11.4%) patients. The median time to reach a neutrophil count > or =1.0 x 10(9)/L was 5 days (95%CI 5-6) in patients treated with G-CSF compared to 7 days (95%CI 6-8) in those not treated, with a hazard ratio of 1.58 (95% CI 1.1-2.3). CONCLUSIONS: G-CSF shortens time to recovery in patients with agranulocytosis. However, as an effect on case-fatality has not been recorded, and data on cost-effectiveness are lacking, it would be wise to restrict its use to high-risk patients.

Principios de epidemiología del medicamento

Publicación estructurada en 12 capítulos: \"Estudios de utilización de medicamentos y de farmacovigilancia\", \"Utilización de medicamentos, fármacos esenciales y políticas de salud en países desarrollados y subdesarrollados\", \"Promoción del uso racional de los medicamentos y preparación de guías farmacológicas\", \"Métodos aplicados en estudios descriptivos de utilización de medicamentos\", \"Mecanismos de producción y diagnóstico clínico de los efectos indeseables producidos por medicamentos\", ...

Risk of acute liver injury associated with the use of drugs: a multicentre population survey.

BACKGROUND: Acute liver injury of uncertain aetiology is often drug related and quantitative information about the associated risk is scarce. AIM: To estimate the risk of acute liver injury associated with the use of drugs. METHODS: In a population survey study, 126 cases of acute liver injury were prospectively assembled from January 1993 to December 1999, in patients over 15 years of age, in 12 hospitals in Barcelona (Spain). We estimated the relative risk for each drug as the ratio between the incidence of acute liver injury among the exposed population to the drug and the incidence of acute liver injury among those not exposed to it. Drug consumption data were used to estimate the exposed population. RESULTS: Isoniazid, pyrazinamide, rifampicin, amoxicillin with clavulanic acid, erythromicin, chlorpromazine, nimesulide, and ticlopidine presented the highest risk (point relative risk > 25). Amoxicillin, metoclopramide, captopril and enalapril, furosemide, hydrochlorothiazide, fluoxetine, paroxetine, diazepam, alprazolam, lorazepam, metamizole, low-dose acetylsalicylic acid and salbutamol showed the lowest risk (point relative risk < 5). CONCLUSIONS: This study provides a risk estimation of serious liver disease for various drugs that will be useful in its diagnosis and management, and when comparing with the drug therapeutic benefit in each indication. Some observed associations would be worth specific studies.

Analgesics for pain after traumatic or orthopaedic surgery: what is the evidence--a systematic review.

OBJECTIVE: To assess analgesic drugs in the treatment of postoperative pain after traumatic and orthopaedic surgery (TOS). DESIGN: A systematic review of randomised clinical trials (RCTs). DATA SOURCES: Electronic PubMed, EMBASE, The Cochrane Library, and hand searches. STUDY SELECTION: RCTs of analgesics administered by oral, intramuscular, intravenous, subcutaneous or rectal route, were compared to other analgesics or placebo, in patients under TOS. Study design, characteristics of the study population, analgesic drugs tested, pain intensity and pain relief scores, and adverse effects were assessed. RESULTS: Ninety-two RCTs (9,596 patients) met our inclusion criteria. Forty-two (46%) were placebo-controlled, and 50 (54%) were direct comparisons between non-opioid, opioid, and/or combinations of both. Patients' mean age (SD) was 49 years (18). In most trials, gastrointestinal ulcer, liver and renal diseases were exclusion criteria. Only 30 trials (33%) were double-blind and reported standardised outcomes of pain intensity and pain relief; 19 of these were single-dose, and follow up of analgesic effects lasted no more than 12 h in 23 (77%). Globally, only nine trials (10%) were double blind, described dropouts or withdrawals, performed analysis by intention to treat, and reported the effects magnitude. CONCLUSION: Evidence from RCTs on the treatment of postoperative pain after TOS is inadequate for clinical decision making. Assessment of analgesics in pain after TOS should be based on agreed clinically relevant outcomes, in representative patients, and for longer observation periods. In addition, it should include direct comparisons between candidate drugs or their combinations and between various drug administration schedules.

Utilisation of antihyperglycaemic drugs in ten European countries: different developments and different levels.

AIMS/HYPOTHESIS: The aim of this study was to compare developments in the utilisation of antihyperglycaemic drugs (AHGDs) in ten European countries. SUBJECTS AND METHODS: Data on the yearly utilisation of insulin and oral AHGDs were collected from public registers in Denmark, Finland, Norway, Sweden, Belgium, England, Germany, Italy, Portugal and Spain, and were expressed as defined daily doses per 1,000 inhabitants per day. RESULTS: Total AGHD utilisation increased everywhere, but at different rates and levels. Insulin utilisation doubled in England and Germany, but hardly changed in Belgium, Portugal or Italy. Sulfonylurea utilisation doubled in Spain, England and Denmark but was reduced in Germany and Sweden. Metformin utilisation increased greatly everywhere. There were two- to three-fold differences in AHGD utilisation even between neighbouring countries. In Finland, there were more users of both insulin (+120%) and oral AHGDs (+80%) than in Denmark, and the daily oral AHGD doses were higher. In Denmark and Sweden, AHGD utilisation was equal in subjects aged <45 years, but in those >or=45 years of age, both insulin and oral AHGD utilisation were twice as high in Sweden. CONCLUSIONS/INTERPRETATION: The ubiquitous increase in AHGD utilisation, particularly metformin, seems logical, considering the increasing prevalence of type 2 diabetes and the results of the UK Prospective Diabetes Study. However, the large differences even between neighbouring countries are more difficult to explain, and suggest different habits and attitudes in terms of screening and management of type 2 diabetes.

Upper gastrointestinal bleeding associated with antiplatelet drugs.

BACKGROUND: The risk of major upper gastrointestinal bleeding associated with various antiplatelet drugs and the protection conferred by gastroprotective agents are not well defined. AIM: To estimate the risk of upper gastrointestinal bleeding associated with the use of antiplatelet drugs and its prevention by gastroprotective agents. METHODS: In a case-control study, we compared all cases of upper gastrointestinal bleeding from a gastric or duodenal lesion in patients over 18 years of age (2813 cases), with 7193 matched controls. Odds ratios of upper gastrointestinal bleeding for individual antiplatelet drugs with adjustment for potential confounders were estimated. RESULTS: The individual risks of upper gastrointestinal bleeding were cardiovascular acetylsalicylic acid 4.0 (3.2-4.9), clopidogrel 2.3 (0.9-6.0), dipyridamole 0.9 (0.4-2.0), indobufen 3.8 (1.2-12.2), ticlopidine 3.1 (1.8-5.1) and triflusal 1.6 (0.9-2.7). Concomitant proton pump inhibitors decreased all risk estimates. For acetylsalicylic acid plus a proton pump inhibitor, the odds ratio was 1.1 (0.5-2.6). As a group, antiplatelet drugs accounted for 14.5% of all cases of upper gastrointestinal bleeding, i.e. 58 per million per year (334 per million per year among those older than 70 years). CONCLUSIONS: The risk of upper gastrointestinal bleeding is substantially decreased by the concomitant use of proton pump inhibitors. The risk of acetylsalicylic acid plus a proton pump inhibitor seems lower than that of ticlopidine or clopidogrel.

Medical speciality and pattern of medicines prescription.

OBJECTIVE: To describe the prescribing patterns and their quality in relation to the prescriber's medical specialty in a defined population. METHODS: The study was done on a random sample of all primary care medical prescriptions made through the social security system during 1 year in Andorra, a small European country. Number and type of prescribed medicines, prescribers' medical speciality and patients' age and gender were recorded. Medical specialties considered were General Practice, Paediatrics, Cardiology, Pneumology, Gynaecology, Ophthalmology and Other. A set of various quality indicators [World Health Organisation (WHO)/International Network for Rational Use of Drugs (INRUD) indicators and others] was used. RESULTS: The number of medicines prescribed per encounter varied depending on the prescriber's medical specialty and patient's age. Cardiologists and pneumologists tended to prescribe more medicines than other medical specialties. Patients older than 65 years received more prescriptions than younger adults, mostly at the expense of cardiovascular drugs. The contribution of the various groups and subgroups of medicines and the scores of various prescribing indicators showed wide variability across the medical specialties. CONCLUSION: Prescribing patterns and indicators of prescription quality show wide variability depending on the prescriber's medical specialty. This has important implications for priority setting in information, continuous education and research.

Oral antispastic drugs in nonprogressive neurologic diseases: a systematic review.

OBJECTIVE: To assess the efficacy of oral drugs in the treatment of spasticity in patients with nonprogressive neurologic disease (NPND). METHODS: Systematic review of double-blind randomized controlled trials of antispastic oral drugs in the treatment of spasticity in NPND. DATA SOURCES: Electronic MEDLINE, PubMed, Cochrane Library, and hand searches. RESULTS: Twelve studies (469 patients) were included (6 on stroke, 3 on spinal cord diseases, and 3 on cerebral palsy). Tizanidine was assessed in four trials (276 patients, 142 exposed), dantrolene in four (103, 93), baclofen in three (70, 55), diazepam in two (127, 76), and gabapentin in one (28, all exposed). Most trials were of small size, of short duration, and their methodologic quality was inadequate. Ten trials were controlled with placebo and only two were direct comparisons between drugs. Efficacy outcome variables were heterogeneous. Only four reports described the magnitude of the antispastic effect. The incidence of adverse drug effects (drowsiness, sedation, and muscle weakness) was high. CONCLUSION: Evidence on the efficacy of oral antispastic drugs in NPND is weak and does not include evaluation of patients' quality of life. If any, efficacy is marginal. Adverse drug reactions were common. Better methodologic instruments are needed for the evaluation of antispastic treatment.

Impact of analgesic drug-use guidelines for the management of postoperative pain: a drug utilization study.

OBJECTIVE: Postoperative pain is inadequately treated in many surgical settings. The present study evaluates the impact of analgesic drug-use guidelines in the management of postoperative pain. PATIENTS AND METHODS: A prospective drug utilization study was carried out in 3 stages in a traumatology, orthopedic and rehabilitation tertiary hospital. The first stage, aimed at describing the patterns of use of analgesic strategies in the management of postoperative pain, identified habits, practices and misconceptions regarding this therapeutic area. After this, an ad hoc representative institutional working group agreed on analgesic drug-use guidelines for the management of postoperative pain. These were then published, presented and discussed with surgeons and nurses. After the guidelines had been implemented, their impact was evaluated in terms of the analgesics used, their dosage and their administration schedule. RESULTS: 101 patients were studied before the implementation of the guidelines and 108 patients after. Patients receiving opiate analgesics during the immediate postoperative period increased from 70-94% (p < 0.05). First-choice analgesics used according to the guidelines increased from 40-89% of choices after the implementation of the guidelines (p < 0.05). Administration of analgesics at regular predetermined intervals increased from 45-58% of medical orders, but this increase was not statistically significant (p = 0.07). Prescription of analgesics at adequate doses increased from 67-87% (p < 0.05). CONCLUSION: Education on the treatment of postoperative pain is made up of several messages including the drug of choice and dose regimen. Prescribers seemed more receptive to a change in drug rather than issues related to the correct dose regimen. More research is needed to assess how educational activities can improve the management of postoperative pain.

Bioavailability of two metamizole (dipyrone) solutions as single doses of 2 g versus metamizole capsules.

OBJECTIVE: The aim of this study was to investigate the extent and the rate of absorption of metamizole, appearing in blood as methylaminoantipyrine (MAA), from a new oral solution and a parenteral solution administered by the oral route relative to capsules. METHODS: An open, randomized, 3 single-dose (2 g metamizole), crossover study with intervals of 7 days between periods was performed in 19 male and female healthy volunteers (age 22 - 45 years, body weight 49 - 88 kg, body height 156 - 189 cm). Metamizole metabolites were measured with an HPLC technique. The test formulations were considered bioequivalent with the reference formulation if the 90% confidence limits of the AUC0-->infinity and Cmax ratios and the tmax differences were within the range of 80 - 125%. RESULTS: The 90% confidence limits of the comparisons between capsules (reference) and oral solution, capsules (reference) and ampoules, and ampoules (reference) and oral solution were 98.5 - 117.8, 99.5 - 132.6 and 81.3 - 105.8 for AUC0-->infinity 98.7 - 119, 101.7 to 129.2, and 82.1 - 104.8 for Cmax, and 84.4 to 115.6, 100 - 105.6 and 70.3 - 100 for tmax, respectively. CONCLUSION: The oral solution was bioequivalent to capsules with regard both to the extent and the rate of MAA absorption. Metamizole as oral solution was bioequivalent to reference ampoules in the extent of MAA absorption, but absorption rate was faster. Ampoules showed a higher MAA bioavailability than capsules.

Appropriate initiation of the strand exchange reaction promoted by RecA protein requires ATP hydrolysis.

The DNA-dependent ATPase activity of the Escherichia coli RecA protein has been recognized for more than two decades. Yet, the role of ATP hydrolysis in the RecA-promoted strand exchange reaction remains unclear. Here, we demonstrate that ATP hydrolysis is required as part of a proofreading process during homology recognition. It enables the RecA-ssDNA complex, after determining that the strand-exchanged duplex is mismatched, to dissociate from the synaptic complex, which allows it to re-initiate the search for a "true" homologous region. Furthermore, the results suggest that when non-homologous sequences are present at the proximal end, ATP hydrolysis is required to allow ssDNA-RecA to reinitiate the strand exchange from an internal homologous region.

Beta-adrenergic blocking agents in heart failure: benefits of vasodilating and non-vasodilating agents according to patients' characteristics: a meta-analysis of clinical trials.

BACKGROUND: In patients with heart failure, beta-adrenergic blocking agents reduce overall and cardiovascular mortality. This meta-analysis aimed at clarifying their effect on sudden death, the magnitude of their benefit according to the cause of heart failure, and whether there is any difference between vasodilating and nonvasodilating agents. METHODS: Randomized, clinical trials were included if they evaluated a beta-adrenergic blocking agent without intrinsic sympathomimetic activity, included a control group receiving placebo or standard treatment, evaluated mortality on an intention-to-treat basis, and lasted at least 8 weeks. RESULTS: Twenty-one trials with 5,849 patients (3,130 receiving beta-blockers) were included. Median length of treatment was 6 months. Most patients had mild or moderate heart failure and were treated with angiotensin-converting enzyme inhibitors, diuretics, and digitalis. The beta-blockers significantly reduced overall mortality, cardiovascular mortality, and mortality due to pump failure and sudden death by 34% to 39%. The decrease in overall mortality in patients with ischemic heart disease (IHD) (30%) was no different from that among patients with non-IHD (26%) (P = .08). The reduction in overall mortality was greater with vasodilating than with nonvasodilating agents (45% vs 27%; P = .007), particularly in patients without IHD (62%), compared with those with IHD (22%; P =.03). CONCLUSIONS: In patients with heart failure, beta-blockers reduce total and cardiovascular mortality at the expense of a decrease in mortality due to pump failure and sudden death. The magnitude of the benefit is similar in patients with IHD and in those with non-IHD. Vasodilating beta-blockers have a greater effect on overall mortality than nonvasodilating agents, particularly in patients with non-IHD.

Agranulocytosis induced by pyrithyldione, a sedative hypnotic drug.

OBJECTIVE: Pyrithyldione, a sedative-hypnotic drug with a poor clinical pharmacological development, was associated with anecdotal cases of agranulocytosis in the 1940s in the USA, in the 1960s and 1970s in the ex-Democratic Republic of Germany and in the 1980s in Japan. We describe the estimation of the risk of agranulocytosis associated with its use in Spain, which led to its withdrawal from the market. METHODS: In collaboration with the haematology units of all the hospitals in a defined area (3.3-3.9 x 10(6) inhabitants), all cases of agranulocytosis meeting strict diagnostic criteria were identified. Each case - defined as an episode of agranulocytosis - was reviewed by a haematologist without knowledge of previous drug exposures. Cases and age-, gender- and hospital-matched controls were interviewed with a structured questionnaire about previous drug exposures. In addition, in order to estimate the risk of pyrithyldione-associated agranulocytosis through a case-population approach, its consumption among the cases was compared with its consumption among the general population. RESULTS: After a follow-up of 66.5 x 10(6) person-years, 330 cases of agranulocytosis (230 community cases) were assembled. Reliable information on previous exposures was obtained for 204 cases. They were compared with 1314 controls. Eleven patients (14 cases, 6.9%) and zero controls had been exposed to pyrithyldione. The adjusted OR was 200.11 (CI 95% 22. 62-infinity). All patients were female; none had a fatal outcome; three exhibited positive rechallenge; and all had concomitantly taken other drugs. Although pyrithyldione was a prescription-only medicine, only 8% had been dispensed with medical prescriptions. Assuming the worst case, i.e. that all the exposed cases could be attributed to pyrithyldione, the incidence was 35.6 cases per 100, 000 patient-years (95% CI, 18.9-60.9), which gives a risk ratio estimate of 109.6 (57.5-191.5) if compared with the incidence of agranulocytosis among the non-exposed population [3.26 cases (CI 95% 2.83-3.71) per 10(6) inhabitants and per year]. DISCUSSION: Pyrithyldione was viewed by pharmacists as a mild hypnotic, and apparently this had conferred to this drug an unjustified image of safety. The National Commission of Pharmacovigilance recommended to the Ministry of Health its withdrawal from the market when eight cases of agranulocytosis had been identified. However, it took more than 2 years to withdraw it, and six additional cases occurred in the study area. This illustrates the need for quick regulatory action when pharmacoepidemiological data suggest an unfavourable benefit/risk ratio.

Agranulocytosis associated with calcium dobesilate clinical course and risk estimation with the case-control and the case-population approaches.

OBJECTIVE: Calcium dobesilate is used in the treatment of diabetic retinopathy, chronic venous insufficiency, haemorrhoids and other ill-defined vascular conditions. It has been associated with agranulocytosis in anecdotal reports. We describe the clinical course of a series of patients who developed agranulocytosis while taking this drug, and we estimate the risk by means of both a case-control and a case-population strategy. METHODS: All cases of agranulocytosis meeting strict predefined diagnostic criteria in an area of 3.3 to 3.9 x 106 inhabitants in the period 1980-1998 were identified. Cases and age-, gender- and hospital-matched controls were interviewed with a structured questionnaire including a detailed drug history. Each case was reviewed and confirmed by a haematologist, who was blind with respect to drug exposures. Consumption data were used to estimate the risk of agranulocytosis associated with calcium dobesilate using a case-population approach in which the incidence of agranulocytosis among users of calcium dobesilate was compared with that among the non-exposed population. RESULTS: After a follow up of 68.55 x 10(6) person-years, 345 cases of agranulocytosis (242 community cases) were assembled. Reliable information was obtained from 216 cases. Two patients exhibited positive rechallenge. Twelve cases (5.6%) and 5 of 1380 controls (0.4%) had taken calcium dobesilate in the week before. With the case-control approach, the odds ratio was 23.66 [95% confidence interval (CI), 7.54-74.24], the attributable risk was 5.3% (95% CI, 3.0-9.4), and the number of cases attributable to dobesilate in the study area during the study period was 12.8. The case-population estimates were an incidence of 121.03 cases per 10(6) patient-years, a relative risk of 39.55 (95% CI, 17.96-77.49), an attributable risk of 6.73% (CI 3.4-12.9), and 16.30 cases attributable to dobesilate in the study area during the study period. DISCUSSION: This study adds to evidence indicating that the case-population method is adequate for the study of rare type B adverse drug reactions. An additional advantage of this approach is that the incidence of the disease of interest among those exposed to the drug can be estimated. The risk of agranulocytosis associated with calcium dobesilate should be considered in relation to poor evidence of its clinical efficacy.

Management of postoperative pain in abdominal surgery in Spain. A multicentre drug utilization study.

AIMS: Postoperative pain is common in hospital-admitted patients. Its management is determined by different therapeutic traditions and by the attitudes of health professionals in each hospital. The aim of this study was to describe the patterns of prescription and administration of analgesic drugs used for postoperative pain after abdominal surgery in Spanish hospitals, to know the prevalence and the severity of postoperative pain, and to determine the extent of variability in the management of postoperative pain among the participating centres. METHODS: The study was a multicentre descriptive cross-sectional drug utilization study in 12 Spanish hospitals. The subjects were an unselected sample of consecutive patients undergoing abdominal surgery, admitted between October 1994 and January 1995. For each patient, information about the surgical procedure and the use of analgesics was prospectively collected. The severity of postoperative pain was assessed during the first day after surgery by means of a six-category (none, mild, moderate, severe, very severe, and unbearable) rating scale and a visual analogue scale (VAS). RESULTS: Nine hundred and ninety-three patients (547 men) were included. The most common surgical procedures were inguinal hernia repair (315, 32%), cholecystectomy (268, 27%), appendectomy (140, 14%), bowel resection (137, 14%), and gastric surgery (58, 6%). Fifty-nine percent of patients (587) received nonopioid analgesics only, 9% (89) received opioid analgesics only, and 27% (263) received both opioid and nonopioid analgesics. The most frequently administered drugs were metamizole (667 patients) and pethidine (213 patients). Although in the majority of medical orders the administration of analgesics was scheduled at regular time intervals, the majority of actual doses were given 'as-needed'. The average administered daily doses of all analgesics were lower than those prescribed. Thirty-eight percent (371/967) of patients rated their maximum pain on the first day as severe to unbearable. Wide interhospital variability was recorded in the surgical procedures which had been performed, in the analgesics used, and also in the pain scores referred by patients. The percentage of patients in each centre who suffered severe to unbearable pain varied from 22 to 67%. CONCLUSIONS: In Spain many patients still suffer severe pain after abdominal surgery, and this seems to be due to an inadequate use of analgesics. Wide interhospital variability in the management of postoperative pain and in its prevalence was also recorded.

Topical heparin for the treatment of acute superficial phlebitis secondary to indwelling intravenous catheter. A double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To assess the clinical efficacy of a topical gel containing 1000 IU x g(-1) of heparin, applied three times daily for a maximal period of 7 days to patients with acute superficial phlebitis secondary to indwelling intravenous catheter. METHODS: A Double-blind, randomized, placebo-controlled study was conducted in one of the internal medicine wards of a tertiary General Hospital in Barcelona, Spain. Inpatients of both genders over 18 years of age that developed superficial phlebitis and gave informed consent were included in the study. The sample size estimation was 132 patients. Sixty-six patients were allocated to each group. There were five protocol deviations and 24 withdrawals in the intervention group, and one protocol deviation and 25 withdrawals in the control group. Consequently, 37 patients in the intervention group and 40 in the control group completed the trial. The main outcome measure was the disappearance of the symptoms and signs of superficial phlebitis. Clinical course, investigator's global impression and adverse events were also recorded. RESULTS: According to the intention-to-treat analysis, after treatment for 7 days superficial phlebitis healed in 27 of the 61 patients (44.3%) who received topical heparin, and in 17 of the 65 patients (26.1%) receiving placebo, giving a relative risk [95% confidence interval (CI)] of 1.69 (1.03-2.78). This indicates that six patients (95% CI, 3-72) have to be treated in order to induce one additional healing. The clinical course and the overall clinical impression were similar in both groups. One patient treated with topical heparin developed mild urticaria. CONCLUSION: Topical heparin is safe and effective for the treatment of superficial phlebitis secondary to indwelling intravenous catheter.