Adverse Drug Reaction Probability Research Articles

Dilated Cardiomyopathy and Acute Liver Injury Associated with Combined Use of Ephedra, γ-Hydroxybutyrate, and Anabolic Steroids

Anabolic-androgenic steroids are synthetic derivatives of testosterone that some athletes have used to enhance muscle mass and improve their athletic performance. Ephedrine is a potent sympathomimetic agent that can lead to cardiomyopathy similar to that seen with catecholamine excess. Adverse cardiovascular events attributed to anabolic steroid and ephedra use, such as arrhythmias, myocardial infarction, cardiomyopathy, and sudden death, are rarely reported. Bodybuilders have used gamma-hydroxybutyrate, a potent secretagogue of growth hormone, to promote muscle development. Although dilated cardiomyopathy is a known complication of excess growth hormone levels, it has not been associated with use of gamma-hydroxybutyrate. A healthy 40-year-old man was admitted to our hospital for new-onset congestive heart failure and severe acute hepatitis that developed several months after he began using anabolic-androgenic steroids, ephedra, and gamma-hydroxybutyrate supplements. Analysis with an objective causality assessment scale revealed a probable adverse drug reaction between the patient's use of anabolic steroids, ephedra, and gamma-hydroxybutyrate and the development of his cardiomyopathy and acute liver injury.

Syncopes et lipothymies d’origine iatrogène

Syncope or presyncope related to adverse drug reactions are well-known. On the other hand, little is known about the specific role of different drugs. Over one six year period, 1611 patients were referred in our hospital for syncope or presyncope, including 688 in the cardiology department. Among these patients, 420 were 70 years old or more. The search for an adverse drug reaction was systematic, with the help of the French method for causality of adverse drug reaction: knowledge of “extrinsic” criteria (bibliographical data relating to the drug involved); moreover, score on the basis of “intrinsic”, chronological and symptomatic criteria. Seventy five patients (11% of the group with syncope leading to admission in cardiology department) were thus retained: score =I2, “possible adverse drug reaction”, for 28 patients (37%); score =I3, “probable adverse drug reaction”, for 47 patients (63%). Score I4, “definite adverse drug reaction” was not used since it required the readministration of the drug to prove the iatrogenic effect. Average age was 78 years, with a female majority of 69%. Seventy two patients (96%) had previous cardiovascular disease, 37 (50%) previously experienced syncope or presyncope. In addition to the basic assessment, a Holter recording was performed among 56 patients, finding a drug-induced arrhythmia in three cases. In the majority of the patients (59 patients, 79%), the adverse drug reaction consisted of hypotension, clinically obvious in 49 cases. In ten cases, vasovagal syndrome facilitated by the drugs was diagnosed by a tilt-test. The other side effects were eight rhythm disorders and eight severe metabolic disorders. The treatments were always multiple. The involved drug was a cardiovascular therapy in 66% of the cases. The other drug classes were primarily represented by uroselective alpha 1-adrenergic blocking drugs (12%) and psychotropic ones (22%). Among the cardiovascular treatments, ACE inhibitors and diuretics, generally in association, were involved (59%). This study confirms the role for antihypertensive drugs in iatrogenic syncope, its great frequency in elderly patients but also the responsibility of another drug class less often reported, the uroselective alpha 1-adrenergic blocking drugs.

Is decreased libido associated with the use of HMG‐CoA‐reductase inhibitors?

To describe patients with decreased libido during use of a HMG-CoA-reductase-inhibitor, and to discuss causality and pharmacological hypotheses for this association by analysis of the adverse drug reactions (ADR) database of the Netherlands Pharmacovigilance Centre Lareb. Eight patients were identified as having decreased libido during use of statins. In two of these cases testosterone levels were determined and appeared to be decreased. Decreased libido is a probable adverse drug reaction of HMG-CoA-reductase-inhibitors and is reversible. The ADR may be caused by low serum testosterone levels, mainly due to intracellular cholesterol depletion.

Psychiatric side effects of indomethacin in parturients.

To examine the central nervous system side effects of the non-steroidal anti-inflammatory drug (NSAID) indomethacin in a case-series of obstetric patients. The hospital records of patients experiencing any postpartum complication between 1994 and 1999 were reviewed for adverse drug reactions (ADR) attributed to indomethacin. Additional cases of indomethacin-induced adverse effects were identified through reports to the nursing administration and the Saskatchewan ADR reporting program. The Naranjo ADR probability scale was applied to all cases. Thirty-two patients experienced a psychiatric reaction after receiving indomethacin for postpartum pain. The symptoms were often severe and included dizziness, anxiety, fear, agitation, affective lability, depersonalization, paranoia, and hallucinations. There was no past psychiatric history documented in any of the cases. This study identifies a possible ADR to indomethacin occurring in postpartum patients. Whether the vulnerability to these neuropsychiatric reactions is randomly distributed or if parturients are at increased risk is yet to be determined. Proposed mechanisms of these side effects include a postpartum dopamine supersensitivity exacerbated by prostaglandin inhibition as well as a structural similarity between serotonin and indomethacin. The severity of the reactions to indomethacin in parturients and the potential for these disturbing psychiatric side effects to compromise the safety of both mother and infant have led to the use of alternative analgesics including different classes of NSAIDs for this population at our institution.

Adverse drug events in emergency department patients

Study Objective: Adverse drug events (ADEs) have been studied in hospitalized patients. Less is known about this common type of injury in emergency department patients. This study seeks to measure the risks, incidence, severity, and costs of ADEs in an ED population. Methods: ED charts of visits to a university-affiliated tertiary-care ED occurring between March 1 and May 31, 1997, were retrospectively reviewed. The main outcome measures were ADE incidence, severity, and total cost. Visits identified by investigators as containing a suspected ADE were further assessed by using the Naranjo Adverse Drug Reaction (ADR) probability scale. Events judged as probable ADEs (Naranjo ADR probability scale score of >4) were compared with ED control visits best matched by age for disposition, survival, severity, payer, sex, race, age, number of drugs, and total cost. Results: Of 13,602 visits, 13,004 records were available. Three hundred twenty-one had suspected and 217 had probable ADEs (1.7% of evaluable encounters); these were compared with visits by 217 age-matched control patients. Insulin and warfarin were the most commonly responsible drugs. Patients with ADEs were older (mean age 45.1 versus 36.8 years; mean difference 8.3; 95% confidence interval [CI] 3.7 to 12.9), were more often women (odds ratio [OR] 1.48; 95% CI 1.01 to 2.16), took more drugs (mean number of drugs 4.1 versus 1.9; mean difference 2.2; 95% CI 1.7 to 2.8), and were hospitalized more frequently (OR 2.29; 95% CI 1.33 to 3.94) than control patients. Conclusion: ADEs encompassed an important segment of ED encounters and annual health care costs. ED screening may provide useful information about the epidemiology of outpatient ADEs. [Hafner JW Jr, Belknap SM, Squillante MD, Bucheit KA. Adverse drug events in emergency department patients. Ann Emerg Med. March 2002;39:258-267.]

Medication Errors and Adverse Drug Events in Nursing Homes: Problems, Causes, Regulations, and Proposed Solutions

The Institute of Medicine (IOM) report To Err is Human: Building a Safer Health System has focused national attention on quality of care and the prevalence of medical errors in the healthcare system. According to the report, medical errors are responsible for a large number of deaths and additional morbidity in healthcare facilities and increased cost to the healthcare system. 1 Kohn LT Corrigan JM Donaldson MS To Err is Human: Building a Safer Health System. The Institute of Medicine National Academy Press, Washington, DC1999 Google Scholar A large proportion of medical errors are medication-related. 2 Leape LL Brennan TA Laird N et al. The nature of adverse events in hospitalized patients: Results of the Harvard medical practice study II. N Engl J Med. 1991; 324: 377-384 Crossref PubMed Scopus (2855) Google Scholar Medication-related errors and other adverse drug reactions are known collectively as adverse drug events (ADEs), defined as “any injury resulting from the medical use of a drug.” 3 Bates DW Spell N Cullen DJ et al. The costs of adverse drug events in hospitalized patients. JAMA. 1997; 277: 307-311 Crossref PubMed Google Scholar , 4 Gurwitz JH Field TS Avorn J et al. Incidence and preventability of adverse drug events in nursing homes. Am J Med. 2000; 109: 87-94 Abstract Full Text Full Text PDF PubMed Scopus (526) Google Scholar ADEs occur across the entire healthcare delivery system and are most common in older people, particularly those in hospitals and nursing homes. 5 Rothschild JN Bates DW Leape LL Preventable medical injuries in older patients. Arch Intern Med. 2000; 160: 2717-2728 Crossref PubMed Scopus (220) Google Scholar , 6 Gurwitz JH Sanchez-Cross T Eckler MA Matulis J The epidemiology of adverse and unexpected events in the long-term care setting. J Am Geriatr Soc. 1994; 42: 33-38 Crossref PubMed Scopus (74) Google Scholar ADEs are the adverse events most common in hospitalized patients 2 Leape LL Brennan TA Laird N et al. The nature of adverse events in hospitalized patients: Results of the Harvard medical practice study II. N Engl J Med. 1991; 324: 377-384 Crossref PubMed Scopus (2855) Google Scholar and the second most common adverse event in nursing home residents. 6 Gurwitz JH Sanchez-Cross T Eckler MA Matulis J The epidemiology of adverse and unexpected events in the long-term care setting. J Am Geriatr Soc. 1994; 42: 33-38 Crossref PubMed Scopus (74) Google Scholar In a report to Congress published in January 2000, 7 United States General Accounting Office. Adverse drug events. The magnitude of health risk is uncertain because of limited incidence data. Report to congressional requesters. GAO/HEHS-00–21. Washington, DC, January 2000. Google Scholar the United States General Accounting Office (GAO) reviewed available studies and concluded that the magnitude of health risk, as well as the cost, is uncertain because of limited incidence data and the difficulty inherent in recognition and identification of ADEs. However, studies reviewed in the report showed a rate of 0.56 ADEs per 100 patients admitted to hospitals in Colorado and Utah and 0.72 in New York. 8 Brennan TA Leape LL Laird NM et al. Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard medical practice study I. New Engl J Med. 1991; 324: 370-376 Crossref PubMed Scopus (3435) Google Scholar , 9 Thomas EJ Studdert DM Burstin HR et al. Incidence and types of adverse events and negligent care in Utah and Colorado. Med Care. 2000; 38: 261-271 Crossref PubMed Scopus (1241) Google Scholar In nursing homes, two studies reported an incidence of 0.44 to 0.71 per patient month. 10 Gerety MB Cornell JE Plichta DT Eimer M Adverse events related to drugs and drug withdrawal in nursing home residents. J Am Geriatr Soc. 1993; 41: 1326-1332 Crossref PubMed Scopus (84) Google Scholar , 11 Cooper JW Drug-related problems in a geriatric long term care facility. J Am Geriatr Soc. 1986; 37: 323-326 Google Scholar Another study in 332 nursing home residents showed an incidence of 134 ADEs per 100 admissions. 12 Cooper JW Probable adverse drug reactions in rural geriatric nursing home population: A four year study. J Am Geriatr Soc. 1996; 44: 194-197 PubMed Google Scholar A recently published study conducted in 18 Massachusetts nursing homes 4 Gurwitz JH Field TS Avorn J et al. Incidence and preventability of adverse drug events in nursing homes. Am J Med. 2000; 109: 87-94 Abstract Full Text Full Text PDF PubMed Scopus (526) Google Scholar found an incidence of 1.89 ADEs per 100 resident/months and potential ADEs in an additional 0.65 per 100 resident/months.

Incidence of lethal adverse drug reactions in the comprehensive hospital drug monitoring, a 20-year survey, 1974-1993, based on the data of Berne/St. Gallen.

Realising the limitations of spontaneous drug monitoring systems concerning the epidemiological aspects, a comprehensive program was founded. It was based on previous publications from the US, Canada and Northern Ireland, mainly those of the BCDSP (Boston Collaborative Drug Surveillance Programme). Drug monitoring was carried out by a group of physicians which included the medical head of each of the divisions of internal medicine, a statistician and an informatician. Only probable or definite drug event relationships were included. A probable event is defined as one in which the drug interaction was more likely to be the cause than any non-drug-related cause. The same criteria were valid for the lethal reactions. In the present evaluation, we found 26 probable lethal adverse drug reactions out of a total of 48,005 patients consecutively admitted to the divisions of internal medicine of three Swiss teaching hospitals during the years 1974-1993, an incidence of 0.054%. The median age of the cohort was 68 years (range 11-103 years), of which 49% were women. The median hospital stay was 14 days and the median number of drugs was eight per patient. The patients with a lethal outcome were presented under the eight pharmacologic-therapeutic classes of drugs and the classification proposed by NS Irey. This is based on long histopathologic experience and helps to identify preventable risks.

Herbal Supplements: Considerations in Dental Practice

Over-the-counter natural herb products constitute a rapidly growing market in the United States. As with conventional medications, the health care provider needs to be aware of these products' effects, side effects, advantageous synergies, and possible or probable adverse drug reactions. This paper will present 20 of the most frequently used herbs in the United States and discuss appropriate precautions and herb-drug interactions of possible concern in clinical dental practice.

Adverse drug reaction-related hospitalizations of nursing facility patients: a 4-year study.

The purpose of this study was to document adverse drug reaction (ADR)-related hospitalizations from a nursing facility population. This 4-year prospective observational study used monthly repeated measures of 332 residents present for 30 or more days. The review included admission and monthly drug regimen review for each resident. Each probable ADR was sent with monthly reports to attending physicians and charge nurses. There were 64 ADR-associated hospitalizations in 52 of the 332 residents (15.7%). The most common events were for nonsteroidal anti-inflammatory drugs (NSAIDs) (30), psychotropic-related fall with fracture (14), digoxin toxicity (5), and insulin hypoglycemia (4). Five patients had recurrence of the hospitalization for the same problem. A significant factor noted between ADR hospitalized and non-ADR residents was the number of medications per patient (7.9 +/- 2.6 vs 3.3 +/- 1.3) for the same number of problems. Adverse drug reaction-related hospitalizations may affect as many as one of every seven nursing home residents and appear to be related to polypharmacy as well as inattention to patient history of contraindications and previous ADRs.

Drug-induced attack of bronchial asthma in inpatients: a 20-year survey of the Comprehensive Hospital Drug Monitoring Programme on adverse drug reactions, Berne/St. Gallen.

Epidemiological aspects of attacks of bronchial asthma related to drugs are prospectively studied in inpatients of three teaching hospitals in the Comprehensive Hospital Drug Monitoring (CHDM)-programme. Results are based on 34,840 individual patients (among 48,005 consecutive admissions) in the years 1974-1993. Between 1974 and 1993, every patient admitted to any of the three medical clinics in the CHDM programme was monitored for any suspicion of an adverse drug reaction (ADR); every drug exposure period during hospital stay was registered. Nineteen patients (0.05% of the 34,840 individual patients) had at least one attack of bronchial obstruction during hospitalisation, considered as probable or definite ADR. The frequency related to exposure periods in response to penicillins is 0.014%, to non-steroidal anti-inflammatories (NSAIDs) 0.0145, to acetyl salicylic acid (ASA) 0.018%, to paracetamol 0.008% and to beta-adrenoceptor blockers 0.26%. Of the 12 patients reacting to a drug with an allergic or idiosyncrasy/intolerance type of bronchial obstruction, 7 had a history of bronchial asthma (extrinsic or intrinsic), and 3 had the diagnosis chronic obstructive pulmonary disease (COPD). A history of bronchial asthma or COPD is confirmed to be a risk factor for this particular ADR. Of the seven patients with a bronchial obstruction to beta-adrenoceptor blockers, five were diagnosed with COPD, while two had neither COPD nor bronchial asthma. The relative risk for this pharmacological reaction in COPD patients was 96 (95% confidence interval 45-208) compared with non-COPD patients in the group of 3244 exposed to beta-adrenoceptor blockers.

Adverse drug reactions: report of the Australian Veterinary Association Adverse Drug Reaction Subcommittee, 1994.

Seventy-seven reports of suspected adverse drug reactions (ADRs) were received by the Adverse Drug Reaction Subcommittee (ADRSc) of the Australian Veterinary Association from April 1993 to December 1994 inclusive. The number of reports received/number of animals involved per species were: dogs (32/44), cats (18/31), horses (17/48), and cattle (10/21). Of these, 49 (64%) were classified as definite ADRs and 9 (12%) as probable ADRs. In 11 (14%) reports an ADR could not be substantiated or there was insufficient information available to make a decision. Eight reports were not classified because the manufacturer and the ADRSc disagreed as to the appropriate classification. Sixteen reports involved apparent hypersensitivity reactions, which resulted in death on 6 occasions. Six reports were associated with 'off label' use and 1 report with use of an expired product. Of the definite, probable and unclassified reports of suspect ADRs, the most frequent types of drugs involved were antimicrobial drugs (13 reports), anthelmintics (13), insecticides (11), vaccines (10), nonsteroidal anti-inflammatory preparations (5), chondroprotective agents (4),anaesthetic/sedative agents (4) and vitamin preparations (2). Single reports concerning definite, probable or unclassified ADRs to a vasodilator, a corticosteroid, a local anaesthetic and a disinfectant were received.

Probable adverse drug reactions in a rural geriatric nursing home population: a four-year study.

To quantitate probable adverse drug reactions (ADRs) in a geriatric nursing homes population. A repeated measures prospective study. Two nursing home populations in rural Georgia. All 332 residents present for 30 or more days over a 4-year period. Admission and monthly drug regimen review for each resident, Naranjo algorithm assessment of each ADR, with monthly reports to attending physicians and follow-up within the next month. There were 444 probable ADRs in 217 of 332 residents (67.4%) during this period. The 217 residents had a mean 1.9 +/- 1.3 probable adverse drug reactions (range, 1-9). The ADR group differed statistically from the rest of the population only in the number of drugs per patient (7.8 +/- 2.6 vs 3.3 +/- 1.3), which was almost twice the number of active problems present in both the ADR (4.0 +/- 0.9) and non-ADR populations (3.8 +/- 1.4). The organ systems most commonly involved in the 444 ADRs observed were cardiovascular (188), central nervous system (129), gastrointestinal (82), endocrine (41), immune (17), hematologic (7), pulmonary (6), and renal (5). The drugs most commonly implicated in ADRs were, in decreasing order, diuretics, antipsychotics, anxiolytics, potassium supplements, digoxin, NSAIDs, insulin, theophylline, H2-receptor antagonists, antiinfectives, anticonvulsants, and thyroid supplements. There were 39 multiple drug ADRs in 34 patients. In decreasing order the drug classes in multiple ADRs were CNS depressants, antihypertensives, potassium-altering therapy, and NSAIDs. Numerous patients had repetitions of the same ADR, especially with antipsychotics, NSAIDs, and insulin. ADRs are a common occurrence in a geriatric nursing home population, and may be related to inadequate attention to the patients history as well as to unrealistic therapeutic endpoints.

Drug use and adverse drug reactions in 105 elderly patients admitted to a general medical ward.

To examine the influence of admission to hospital on the number of drugs used by the elderly and to study the occurrence of adverse drug reactions (ADRs), their contribution to the need for hospitalization and the relation to hospital stay. Drug use and its sequelae were studied by one observer in 105 patients aged 65 years and older, successively admitted to a general medical ward. Naranjo's algorithm was used to estimate the probability of an ADR. Multiple regression analysis was used to measure interrelationships between variables. There was a slight but significant increase in drug use per patient (4.9 prescriptions on admission, 5.3 at discharge); 120 ADRs occurred, 57 on admission, 63 during stay. Two ADRs were potentially fatal. Drugs most often involved were diuretics, ADRs occurring mainly on admission. During stay in hospital antimicrobials were mainly responsible. There was a strong correlation of both ADRs on admission and ADRs during stay with duration of hospital stay. ADRs did not correlate with the number of drugs in use on admission or with the number of diagnoses. A direct correlation between the occurrence of ADRs and age could not be confirmed, when corrected for possible confounding factors. Fourteen of 105 admissions were definitely or probably drug-induced; diuretics were incriminated 6 times. Drug use per patient corresponded with that in the literature. Thirty-seven per cent of patients experienced a definite or probable ADR. The percentage of drug-induced admissions (14.7%) agrees with the literature, although the drugs involved (mainly diuretics in our study) were markedly different. The occurrence of ADRs, both on admission and during stay is correlated with the duration of hospital stay, but not with drugs in use or with the number of diagnoses.

Adverse Drug Reactions: Report of the Australian Veterinary Association Adverse Drug Reaction Subcommittee, 1993

Fifty-nine reports of suspected adverse drug reactions (ADRs) were received by the Adverse Drug Reaction Subcommittee of the Australian Veterinary Association from April 1992-March 1993 inclusive. The number of reports received/number of animals involved per species was: dogs (30/43); cats (11/14); horses (8/10); cattle (9/30); ferret (1/1). Of these, 37 (63%) were classified as definite ADRs and 12 (20%) as probable ADRs. In 10 (17%) reports an ADR could not be substantiated or there was insufficient information available to make a decision. Twenty-three reports involved apparent hypersensitivity reactions and 5 reports were associated with 'off-label' use. Of the definite and probable reports of suspect ADRs the most frequent types of drugs involved were antimicrobials (9 reports), anthelmintics (9 reports), vaccines (7 reports), insecticides (6 reports), vitamin preparations (6 reports), topical anti-inflammatory/antimicrobial/antifungal skin preparations (3 reports) and nonsteroidal anti-inflammatory preparations (3 reports). Single reports concerning definite or probable ADRs to an anticholinergic, an anaesthetic agent, a corticosteroid, an anabolic steroid and a chondroprotective drug were received.

Triazolam use in a university medical center

The results of a drug-use evaluation (DUE) of triazolam at a university medical center are reported. The DUE was conducted at three institutions in a medical center complex with over 1100 beds. Indicators and thresholds were developed by the DUE subcommittee and approved by each institution's pharmacy and therapeutics committee. The medical charts of patients for whom triazolam was prescribed during January through March 1991 were reviewed. The relationship between the occurrence of adverse drug reactions (ADRs) and triazolam use was evaluated with the Naranjo ADR probability scale. Of 192 patients whose medical charts were reviewed, 123 (64%) were prescribed 0.125-mg doses. Patients who were > 70 years of age were more likely than younger patients to be prescribed this low dose (84% versus 60%). Fifty-four patients (28%) received no doses; a median of two doses (range, 1-46) were received by the remaining 138 patients. Twelve (9%) of those 138 patients experienced ADRs considered to be possibly (n = 10) or probably (n = 2) related to triazolam. Possible triazolam-associated reactions consisted of confusion (four cases), weakness and lethargy (four), and dizziness (two); probable triazolam-associated ADRs were confusion (one case) and next-day somnolence (one). Factors potentially contributing to ADRs included the presence of concomitant diseases or medications, the total number of doses received, and patient age. Of 138 hospitalized patients who had been given one or more doses of triazolam, 12 had had possible or probable triazolam-associated ADRs. The use of low doses and short-term therapy, particularly in elderly patients, may reduce the likelihood of ADRs.

Adverse drug reactions: report of the Australian Veterinary Association Adverse Drug Reaction Subcommittee, 1992.

Fifty-nine reports of suspected adverse drug reactions (ADRs) were received by the Adverse Drug Reaction Subcommittee of the Australian Veterinary Association from February 1991-March 1992 inclusive. The number of reports received/number of animals involved per species was: dogs (23/24); cats (20/30); horses (4/4); cattle (7/10); sheep (3/745); poultry (1/580); pigs (1/8). Of these, 38 (64%) were classified as definite ADRs and 9 (15%) as probable ADRs. In 10 (17%) reports an ADR could not be substantiated or there was insufficient information available to make a decision. Two reports involved veterinarians inadvertently overdosing animals. Eighteen reports involved apparent hypersensitivity reactions and 6 reports involved probable drug interactions. Four reports involved the use of drugs at appropriate doses but in inappropriate clinical situations, and 3 reports were associated with 'off-label' use.

Case report: Multisystem failure following intravenous iopamidol

A case of life-threatening adverse effects following intravenous administration of a non-ionic contrast medium is reported. The patient, a 68-year-old diabetic hypertensive male with dyspnoea and cough had an abnormal chest radiograph, revealing congestive heart failure and an enlarged right hilum. Computed tomography (CT) of the chest was performed using 100 cm3 of intravenous iopamidol. Within half an hour the patient developed abdominal cramping, vomiting, and diarrhoea, followed by hypotension, tachycardia, fever to 40 degrees C, and delirium. His course was complicated by disseminated intravascular coagulation, rhabdomyolysis, renal failure, respiratory arrest, and atrial fibrillation. There was no evidence of infection, neoplastic disease, or myocardial infarction. Over the next month the patient slowly recovered. One other case report implicates a contrast agent with a similar syndrome. The features of this case fulfil the criteria for a probable adverse drug reaction of a type and severity rarely encountered.

Age Effects on Patient Drug Attribution Judgments

Data were obtained on patients' attribution of symptoms using two different post-marketing surveillance methods. In the patient-initiated method, outpatients were randomly assigned to have a printed notice conspicuously attached to the outside of their medication bags; the "outsert" requested the patients to monitor themselves during the next 2 weeks and to report via a toll-free telephone number any new or unusual symptoms. In the staff-initiated method, other patients filling the same target drug prescriptions did not receive any outsert but were identified at the pharmacy for a telephone interview 10 to 14 days later. The target drugs were chosen from two classes for which the major adverse drug reactions (ADRs) are well identified: oral antibiotics and tricyclic antidepressants. During the interview, for each reported symptom the patient was asked whether it might have been caused by the target drug. Results indicated that older patients, irrespective of the surveillance method or the drug class, appear to be capable of discriminating probable ADRs at least as well as or possibly better than younger patients.

Is Age an Independent Risk Factor of Adverse Drug Reactions in Hospitalized Medical Patients?*

To study the incidence and the risk factors of adverse drug reactions. Multicenter survey. Hospitalized care: 22 internal medicine and 19 geriatric wards. All patients (n = 9,148) consecutively admitted during two observation periods of 2 months. Incidence of adverse drug reactions. The mean age was 67.1 +/- 0.17 years (median 72); the mean duration of hospital stay was 18.1 +/- 0.19 days (median 14). Each patient was administered 5.1 +/- 0.03 (median 5) drug prescriptions. The incidence of probable or definite adverse drug reactions was 5.8% (532/9,148). In univariate analysis, the incidence of adverse drug reactions increased from 3.3% at under age 50 to 6.5% at age 70-79 and decreased over age 80 (5.8%). In multivariate logistic regression, taking more than four drugs (OR = 2.94, CI = 2.38-3.62), staying in hospital more than 14 days (OR = 2.82, CI = 2.26-3.52), having more than 4 active medical problems (OR = 1.78, CI = 1.29-2.45), staying in a medical ward instead of geriatric ward (OR = 1.33, CI = 1.09-1.63), and drinking alcohol (OR = 1.28, CI = 1.03-1.58) were positively correlated with adverse drug reactions occurrence (P less than 0.05). Age, gender, and smoking cigarettes were not significant predictors of adverse drug reactions. Age is not an independent risk factor of adverse drug reactions, and good geriatric care can reduce the incidence of adverse drug reactions.

Syncope and Presyncope Associated With Probable Adverse Drug Reactions

The purpose of this study was to determine whether syncope and presyncope were associated with drug therapy in 70 patients referred to a tertiary care ambulatory clinic. Drug use information was obtained, validated, and classified by its potential to cause syncope and presyncope. Utilizing a standardized adverse drug reaction algorithm, nine (13%) of the 70 patients were rated as having probable drug-induced syncope and presyncope events. Overall, 12 medications were implicated. Patients with probable adverse drug reactions were older, and taking more medications, or taking an antihypertensive. Seven of the nine patients with probable adverse drug reactions were previously classified as having syncope of unknown origin after their initial clinic evaluation. Syncope and presyncope are commonly associated with adverse drug reactions, especially in the elderly and those taking multiple medications.