MEDICAL ERRORS & ADVERSE DRUG REACTIONS
Note: The information on this website is not a substitute for
diagnosis and treatment by a qualified, licensed professional.
Epidemiology of medical error.
Weingart, SN. et al.
BMJ 2000;320:774-777 ( 18 March ).This article presents a review of current available information on the incidence and nature of medical errors in U.S. hospitals. Medical errors have been estimated to kill 48,000-98,000 Americans each year, and to injure an additional 1 million. These data, however, are likely to significantly underestimate the real extent of the problem, since they only refer to hospital patients, and are not inclusive of errors occurring in nursing homes and other health care settings. In addition, the methods used by investigators to identify adverse medical events can significantly affect the estimates of their prevalence. In a landmark study conducted by the University of Harvard, for example, where the researchers used a stringent definition of error, it was calculated that 3.7% of hospitalized patients experienced an adverse event, which was caused by errors -and was therefore preventable- in two-thirds of cases. In another study, where errors were detected through a computerized model, the incidence of adverse drug reactions in hospitalized patients was estimated to be 1.7%. On the other hand, when Bates and colleagues determined the incidence of adverse drug reactions by reviewing patients' medical charts and by conducting interviews with physicians, they found that 6.5% of hospitalized patients developed an adverse drug reaction, and another 5.5% developed a potential adverse drug reaction; these events were found to be caused by errors in 28% of cases. Furthermore, when trained observers who visited a general surgery unit where asked to evaluate the rate of adverse events, they reported that almost 50% of patients experienced an adverse event, which was serious in 18% of cases. Little research has been conducted on the extent of medical error outside hospital settings. One study revealed that drug-related complications occur in 18% of outpatients. Another study calculated that every year treatment-related complications result in 116 million additional physicians visits, 76 million prescriptions, 17 million emergency department visits, 8 million hospital admissions, 3 million long-term care facility admissions, and 200,000 additional deaths, for a cost of $76.6 billion. These data indicate that the extent of injury caused by preventable errors occurring in health care settings is enormous, and the real dimension of the problem is largely unknown.
Reporting and preventing medical mishaps: lessons from non-medical near miss reporting systems.
Barach, P. and Small S.
BMJ 2000;320:759-763 ( 18 March ).This article reports on some of the data that emerged from the results of two studies conducted by the Institute of Medicine showing that, every year, approximately 100,000 patients die needlessly in the hospital as a result of errors in medical management, and many more are injured. These data, already alarming, become even more preoccupying when considering that, as the article highlights, 50%-96% of adverse events are not reported. These data indicate that preventable deaths from errors in medical management have reached endemic proportions, and that the extent of the injury is largely underestimated.
To Err Is Human: Building a Safer Health System.
Kohn L., Corrigan J., and Donaldson M., Editors; Committee on Quality of Health Care in America, Institute of Medicine.
http://www.iom.eduThe Institute of Medicine (IOM) committee released a report on November 29, 1999 on medical errors in U.S. hospitals. A medical error was defined as "the failure to complete a planned action as intended or the use of a wrong plan to achieve an aim". The report presented the results from two large studies revealing that medical errors occurring in the hospital kill an estimated 44,000 (based on one study) or 98,000 (based on the second study) Americans each year. These estimates do not include errors that may arise in settings other than the hospital such as outpatient clinics, retail pharmacies, nursing homes, home care, and day-surgery clinics. Even considering only the most conservative figure (44,000 deaths per year), medical errors would be the eight leading cause of death, killing more people than breast cancer, AIDS or traffic accidents. The yearly cost resulting from such errors has been estimated at approximately $9 billion. Many of these errors are avoidable, and the IOM called for a 50% reduction in errors over the next 5 years. According to the report, systems designed to ensure public safety are over a decade behind in the health care industry compared to other high-risk industries.
Reducing errors in medicine.
Leape LL.
BMJ 1999;319:136-137 ( 17 July ).This article reports on previous studies demonstrating that injuries from medical care occur in 3.7% to 6.7% of hospital admissions, and are fatal in 13.6% of cases. Over half of these injuries are preventable. From these data it is deduced that, in the U.S., more than 120,000 individuals die each year while in the hospital from errors that are avoidable. The cost of a preventable medication error has been estimated at approximately $4,700 per event.
Medication-prescribing errors in a teaching hospital. A 9-year experience.
Lesar TS, Lomaestro BM, Pohl H.
Arch Intern Med, 157(14):1569-76 1997 Jul 28.In this study 11,186 medication-prescribing errors with a potential for adverse patient outcome were detected and averted by a staff pharmacist of a teaching hospital over a 9-year period. The number of detected errors increased from 522 in the year 1987 to 2115 in 1995, with a significant increased rate of errors per order written, per admission and per patient/day.
Factors related to errors in medication prescribing.
Lesar TS, Briceland L, Stein DS.
JAMA, 277(4):312-7 1997 Jan 22-29.In this study, conducted on a 631-bed tertiary care teaching hospital, 2103 errors with a potential for adverse patient consequences were detected and averted over a 1-year period. Overall, the rate of errors was 3.99 per 1000 written orders.
Medication prescribing errors in a teaching hospital.
Lesar TS, Briceland LL, Delcoure K, Parmalee JC, Masta-Gornic V, Pohl H.
JAMA, 263(17):2329-34 1990 May 2.In this study, conducted in a tertiary care teaching hospital, researchers detected and averted a rate of 3.13 medication-prescribing errors per 1000 physicians' written orders. In 58% of cases, the errors had a potential for adverse patient consequences.
A look into the nature and causes of human errors in the intensive care unit.
Donchin Y, Gopher D, Olin M, Badihi Y, Biesky M, Sprung CL, Pizov R, Cotev S.
Crit Care Med, 23(2):294-300 1995 Feb.In this study, an estimated 1.7 errors per patient per day were detected in the intensive care unit (ICU) of a teaching hospital. For the whole ICU, an average of two severe or potentially detrimental errors occurred each day.
Relationship between medication errors and adverse drug events.
Bates DW, Boyle DL, Vander Vliet MB, Schneider J, Leape L.
J Gen Intern Med 1995 Apr;10(4):199-205.This study evaluated the frequency of medication errors in a sample population of 379 consecutive patients admitted to an urban tertiary care hospital. On average, 0.3 medication errors per patient occurred each day, with half of these errors consisting of missing doses. About 1% of the medication errors resulted in adverse drug events.
A computer alert system to prevent injury from adverse drug events: development and evaluation in a community teaching hospital.
Raschke RA, et al.
JAMA 1998 Oct 21;280(15):1317-20.In this study, a computer alert system was used in a 650-bed university hospital to identify prescription errors with the potential of causing adverse drug events. Errors with such potential were detected at a rate of 64 per 1000 admissions and were unrecognized by physicians prior to notification in 44% of cases.
Improving prescribing patterns for the elderly through an online drug utilization review intervention: a system linking the physician, pharmacist, and computer.
Monane M, Matthias DM, Nagle BA, Kelly MA.
JAMA 1998 Oct 14;280(14):1249-52.In this study, a computer alert system was used to evaluate the appropriateness of medications prescribing in a cohort of 23,269 elderly patients. Overall, the system fired 43,007 alerts for suboptimal medication. In 56% of cases, a pharmacist was able to notify the alert to a physician. Of the notified alerts, 24% resulted in change to a more appropriate drug.
Inappropriate medication is a major cause of adverse drug reactions in elderly patients.
Lindley CM, et al.
Age Ageing 1992 Jul;21(4):294-300.This study evaluated the rate of prescribing of drugs with absolute contraindications or unnecessary, in a sample population of 416 elderly patients consecutively admitted to a teaching hospital. On admission, 11.5% of patients were receiving drugs with absolute contraindications, and 27% were receiving drugs that were unnecessary. Adverse drug reactions (ADRs) occurred in 27% of patients on medication, and half of these reactions were due to drugs with absolute contraindications or unnecessary. ADRs were the cause of hospital admission in 6.3% of patients, and were due to inappropriate prescribing (and were therefore avoidable) in half of the cases.
Inappropriate medication prescribing for the elderly by office-based physicians.
Aparasu RR, Fliginger SE.
Ann Pharmacother 1997 Jul-Aug;31(7-8):823-9.The results of this study show that in 1992, 7.6% of individuals aged 65 and greater received at least 1 of 20 medications that should never be prescribed to the elderly, by their office-based doctor. The authors emphasize how the high rates of inappropriate prescribing by office-based doctor raises concerns on the quality of care they deliver.
Inappropriate drug prescriptions for elderly residents of board and care facilities.
Spore DL, Mor V, Larrat P, Hawes C, Hiris J.
Am J Public Health 1997 Mar;87(3):404-9.The results of this study indicate that a minimum of 20% to 25% of elderly individuals living in board and care facilities receive at least one inappropriate medication (a drug that should be entirely avoided in this age group).
Prescription of contraindicated and interacting drugs in elderly patients admitted to hospital.
Gosney M, et al.
Lancet 1984 Sep 8;2(8402):564-7.The results of this study, conducted on 573 elderly patients admitted to a teaching hospital, show that overall, 3.2% of the prescriptions they received before, during, or after hospital stay, were for drugs that were either contraindicated or that interacted adversely with other drugs. Overall, almost 24% of patients received a contraindicated or interacting drug. Approximately 84% of the inappropriate prescriptions were either preventable or probably preventable.
Do too many cooks spoil the broth? Multiple physician involvement in medical management of elderly patients and potentially inappropriate drug combinations.
Tamblyn RM; McLeod PJ; Abrahamowicz M; Laprise R.
CMAJ, 154(8):1177-84 1996 Apr 15.This study shows that the prevalence of a potentially inappropriate drug combination (PIDC) in a population of elderly Medicare patients ranged from 4% to 20.3%. The greater the number of physician involved in patient care, the higher the risk of PIDC.
A database analysis of potentially inappropriate drug use in an elderly medicaid population.
Piecoro LT, Browning SR, Prince TS, Ranz TT, Scutchfield FD.
Pharmacotherapy 2000 Feb;20(2):221-8.The results of this study, conducted on 64,832 elderly individuals, show that 27% of them had been prescribed at least one inappropriate medication. The rate of irrational prescribing was higher in nursing home residents (33%) than in outpatients (24%).
ADVERSE DRUG REACTIONS AND ADVERSE EVENTS
Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies.
Lazarou J, Pomeranz BH, Corey PN.
JAMA 1998 Apr 15;279(15):1200-5.This study analyzed 39 prospective U.S. studies to determine the incidence of serious and fatal adverse drug reactions (ADRs). Serious ADRs were defined as those requiring hospitalization or resulting in permanent damage. Only ADRs requiring hospital admission or occurring in the hospital were included in the analysis. Overall, the incidence of serious ADRs was 6.7 per 100 patients and that of fatal ADRs was 0.32 per 100 patients. Extrapolation of these data to the entire U.S. population revealed that in 1994 alone, over 2.2 million patients experienced a serious ADR and 106,000 died from this complication. These figures place ADRs between the fourth and sixth leading cause of death in the U.S. These are conservative estimates, since they don't take in consideration possible ADRs, errors in drug administration, patient non-compliance, overdose, drug abuse, therapeutic failures and injuries and deaths occurring in nursing home patients.
Drug-related emergency department visits and hospital admissions.
Prince BS, Goetz CM, Rihn TL, Olsky M.
Am J Hosp Pharm 1992 Jul;49(7):1696-700.This study evaluated the prevalence of different drug-related illnesses in patients visiting the emergency department or admitted to the hospital at one institution during a 4-month period. Drug-related illnesses were found to account for 3% of emergency visits and resulted in hospital admission in approximately 1/4 of cases. Of interest, adverse drug reactions were not the most common type of drug-related illnesses. Overdose or abuse accounted for 35% of drug-related complications, followed by noncompliance (28%), adverse drug reactions (28%), toxicity (8%), and drug interaction (1%).
The role of medication noncompliance and adverse drug reactions in hospitalizations of the elderly.
Col N; Fanale JE; Kronholm P.
Arch Intern Med, 150(4):841-5 1990 Apr.The results of this study, conducted on 315 elderly patients consecutively admitted to the hospital, show that in 28.2% of them, the cause of hospitalization was related to the medication they were taking, and was due to noncompliance with treatment in 11.4% of cases, and to adverse drug reactions in another 16.8%.
Drug-related hospital admissions.
Nelson KM, et al.
Pharmacotherapy 1996 Jul-Aug;16(4):701-7.The results of this study indicate that 73 (16%) of 452 consecutive admissions to a hospital were for drug-related problems. Approximately 55% were due to drug failure, 33% to adverse drug reactions and 12% to drug overdose. About half of the drug-related admissions were preventable.
Recent considerations in nonsteroidal anti-inflammatory drug gastropathy.
Singh G.
Am J Med, 105(1B):31S-38S 1998 Jul 27.This study shows that each year, approximately 107,000 individuals are hospitalized for gastrointestinal (GI) complications derived from nonsteroidal anti-inflammatory drug (NSAID) use and that, among arthritis patients alone, at least 16,500 die as a consequence of NSAID use. These are conservative estimates, since they don't take into account gastrointestinal complications occurring in patients taking over-the-counter NSAIDs. If we consider that every year, in the U.S., there are over 70 million prescriptions written for NSAIDs, and over 30 billion tablets are sold over-the-counter, the number of injuries and death caused by only one type of adverse event related to NSAID use -gastrointestinal complications- reaches staggering figures.
Incidence and types of preventable adverse events in elderly patients: population based review of medical records.
Thomas, EJ. and Brennan TA.
BMJ 2000;320:741-744 ( 18 March ).The results of this study show that hospitalized elderly patients have almost twice the risk of developing preventable adverse reactions, compared to younger patients. The study, conducted on 13 Utah' and 15 Colorado' hospitals, found that the incidence of adverse events leading to prolongation of hospital stay, disability or death in patients younger than 64 years of age is 2.8%, while that of patients aged 65 years or more is 5.3%. The incidence of preventable adverse events is 1.6% in younger patients and 3.0% in older ones, indicating that almost half of the adverse events that occur in hospitalized patients are preventable. Elderly patients, compared to younger ones, experience significantly higher rates of preventable adverse drug reactions, adverse events due to medical procedures, and falls. These data are likely to significantly underestimate the real incidence of adverse events in hospitalized patients, since adverse events were evaluated through medical chart documentation (where the occurrence of an adverse event is often not documented), the evaluation was performed by nurses and general practitioners (and not by specialists), their judgment of an adverse event was not always consistent, the study evaluated only adverse events that prolonged hospital stay or resulted in disability or death, and was conducted on hospitals that were not randomly selected. With this said, death due to preventable adverse events in hospitalized patients, still ranks at least as the 8th cause of mortality in the U.S.
Medication-related visits to the emergency department: a prospective study.
Tafreshi MJ, Melby MJ, Kaback KR, Nord TC.
Ann Pharmacother 1999 Dec;33(12):1252-7.The results of this study show that 28% of visits to the emergency room are related to medications. In the study, one physician and pharmacists evaluated prospectively the percentage of visits to the emergency room that were due to medications in a sample of 253 consecutive patients. In 71 patients (28.1%) the cause of the visit was due to medications, either in the form of adverse drug reaction, or of overprescribing. Over two-thirds of the reactions were judged to be preventable. Cardiovascular medications were the most frequent class of drugs implicated. The cost for each preventable drug-related visit was estimated at $1444. The article emphasizes that the high rate of drug-related visits found in the study is accounted for by the study design (prospective, observational study) and by the presence of drug experts in determining the presence of treatment- complications.
Drug Complications in Outpatients.
Gandhi TK, Burstin HR, Cook EF, Puopolo AL, Haas JS, Brennan TA, Bates DW.
J Gen Intern Med. 2000 Mar;15(3):149-154.The results of this study show that almost 1 out of 5 patients who take prescription drugs experience a treatment-related complication. The study was conducted on 2,248 randomly chosen patients from 11 ambulatory clinics in Massachusetts. Patient interviews and medical chart reviews were conducted to determine the frequency of drug-related adverse reactions. Eighteen percent of patients reported complications from treatment, but only one-sixth of these adverse reactions were reported in the medical chart. Approximately 50% of patients who experienced an adverse reaction sought medical attention as a consequence of it, and 5% of them were hospitalized. These figures show that drug-related complications occur significantly more often than reported in patients' medical charts, leading to extensive utilization of the health care resources and patients' dissatisfaction with quality of care. This study is particularly important because presents rates of adverse drug reactions in outpatient settings, where most of the medications are given, and because reveals how the vast majority of adverse reactions are unreported.
Adverse drug events in elderly patients receiving home health services following hospital discharge.
Gray SL, Mahoney JE, Blough DK.
Ann Pharmacother 1999 Nov;33(11):1147-53.The results of this study show that 20% of elderly individuals who are discharged after hospitalization on medications, experience drug-related adverse effects. The study was conducted on 256 individuals aged 65 or more, who were hospitalized for medical illness and who received, upon discharge, home health nursing services. Twenty-percent of them reported at least one adverse effect from treatment, which involved the gastrointestinal system in approximately one third of cases and the central nervous system in another third. Women and individuals with low cognition were particularly at risk of experiencing treatment-related adverse events.
Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard Medical Practice Study I.
Brennan TA, et al.
N Engl J Med 1991 Feb 7;324(6):370-6.This study evaluated the extent of injuries caused by medical management in a random population of over 30,000 patients hospitalized in the state of New York. Treatment-related injuries occurred in 3.7% of patients and were due to negligence in over a quarter of them. They led to disability lasting less than 6 months in 70% of patients, to permanent disability in 2.6% of cases, and to death in 13.6% of cases. Extrapolation of these data for the whole state of New York showed that in 1984, medical management in the state of New York alone injured approximately 100,000 patients, with 27,000 of these injuries being due to negligence. Elderly patients were particularly at risk of adverse reactions due to negligent care. When these data were later further analyzed (Leape et al. Qual Rev Bull 1993 May;19(5):144-9.), it was shown that two-thirds of the injuries was due to errors, and was therefore potentially preventable.
Computerized surveillance of adverse drug reactions in hospital: implementation.
Levy M, et al.
Eur J Clin Pharmacol 1999 Jan;54(11):887-92.The results of this study, conducted on a sample population of 199 consecutive patients admitted to the medical ward of a hospital, indicate that adverse drug reactions (ADRs) were present in 32% of patients and were the cause of hospitalization in 9% of cases. Twenty-seven percent of ADRs were defined as serious.
Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group.
Bates DW, et al.
JAMA 1995 Jul 5;274(1):29-34.The results of this study, conducted on 4031 hospitalized patients from 11 different units of two tertiary care hospitals, show that the incidence of adverse drug events (ADEs) and potential ADEs in this cohort was 6.5% and 5.5%, respectively. One percent of all ADE were fatal, 12% life-threatening, 30% serious, and 57% significant. Forty-two percent of the serious and life-threatening ADEs were preventable.
Incidence of adverse drug reactions in adult medical inpatients.
Bowman L, Carlstedt BC, and Black CD.
Can J Hosp Pharm 1994 Oct;47(5):209-16.This study estimated that 23.1% of patients admitted to the internal medicine ward of a hospital experience an adverse drug reaction (ADR). Length of hospital stay doubled
in patients with ADR, compared to those without this complication. The severity of ADRs in this study was less than previously reported, with 10% of all ADRs judged to be severe, 53% moderate, and 36% mild.
Adverse drug reaction-related hospitalizations of nursing facility patients: a 4-year study.
Cooper JW.
South Med J 1999 May;92(5):485-90.The results of this study indicate that one every 6-7 nursing home residents is hospitalized for adverse drug reactions (ADRs). The drugs more commonly involved in ADR-related hospitalizations are NSAIDs, psychotropic drugs (for inducing falls), digoxin and insulin. In the sample population evaluated in this study, 10% of patients experienced recurrent hospitalization for the same problem. The risk of being hospitalized increased with the number of medications that nursing home patients received.
Iatrogenic complications in high-risk, elderly patients.
Lefevre F, Feinglass J, Potts S, Soglin L, Yarnold P, Martin GJ, Webster JR.
Arch Intern Med 1992 Oct;152(10):2074-80.This study evaluated the medical records of 120 elderly patients admitted to a large university hospital for congestive heart failure, acute myocardial infarction, or pneumonia, and found that in 58.3% of them, a minimum of one iatrogenic complication occurred. The complication was judged to be potentially preventable in 35.8% of patients.
Adverse drug events in high risk older outpatients.
Hanlon JT, et al.
J Am Geriatr Soc 1997 Aug;45(8):945-8.This study evaluated the frequency of adverse drug events (ADEs) in a cohort of 167 elderly ambulatory patients taking more than 5 scheduled medications. Fifty-eight patients (35%) reported 80 ADEs that were textbook confirmed, of which 95% were predictable. Eleven percent of patients with ADEs were hospitalized, 10% required an emergency room visit and 63% a physician consultation.
Adverse drug events in hospitalized elderly.
Gray SL, Sager M, Lestico MR, Jalaluddin M.
J Gerontol A Biol Sci Med Sci 1998 Jan;53(1):M59-63.The results of this study, conducted on a cohort of 157 patients aged 70 and over consecutively admitted to the hospital, show that 14.6% of them experienced adverse drug reactions (ADRs), that were potentially preventable in half the cases. Upon discharge, 50% of patients with ADRs experienced a decline in one or more activities of daily living, compared to 24% of patients without ADRs.
Adverse drug reactions in an elderly outpatient population.
Schneider JK, Mion LC, Frengley JD.
Am J Hosp Pharm 1992 Jan;49(1):90-6.This study, conducted on a cohort of 463 elderly outpatients, documented 107 adverse drug reactions (ADRs) that occurred in 97 (21%) individuals and caused the hospitalization of 12 of them. Attendance to a geriatric clinic, use of potentially dangerous drug combinations, and use of drugs requiring laboratory monitoring were all associated with an increased risk of experiencing ADRs.
Hospital characteristics associated with adverse events and substandard care.
Brennan TA, et al.
JAMA 1991 Jun 26;265(24):3265-9.This study evaluated 31,000 medical charts from 51 randomly selected NY hospitals, and found that the incidence of patient injuries due to medical treatment varied from 0.2% to 7.9% (mean 3.2%). Rates of adverse events were significantly higher in primary teaching hospitals (4.1%) compared to rural hospitals (1%). The percentage of adverse events due to negligence varied from 1 to 60% (mean 25%) and was significantly lower in teaching hospitals (10.7%) and significantly higher in hospital with a predominance of minority patients.
Physician characteristics and prescribing for elderly people in New Brunswick: relation to patient outcomes.
Davidson W; Molloy DW; BŽedard M.
CMAJ, 152(8):1227-34 1995 Apr 15.This study examined whether mortality and morbidity rates in a community of elderly patients in New Brunswick could be associated with any physician' personal, professional, or practice characteristic. The results of the study revealed that general practitioners with higher patients' mortality rates were more likely to be males, prescribed more drugs, had larger practices, saw more patients and billed more per year compared to doctors with lower mortality rates. In addition, the study found higher rates of hip fractures in patients of doctors who prescribed more frequently antihypertensives, bronchodilators, cholesterol-lowering agents, gastrointestinal drugs and non-steroidal antiinflammatory drugs, who had larger practices, and who billed more per year.
An alternative strategy for studying adverse events in medical care.
Andrews LB, Stocking C, Krizek T, Gottlieb L, Krizek C, Vargish T, Siegler M.
Lancet 1997 Feb 1;349(9048):309-13.This study shows that the frequency of adverse drug reactions (ADRs) reported in medical records may not be a real representation of the actual rate at which these events occur. When trained observers recorded all ADRs discussed at clinical meetings, the actual incidence of serious ADRs among a study group of 1047 patients was 17.7%. With each day of hospital stay, the risk of experiencing an adverse event increased by 6%.
The incident reporting system does not detect adverse drug events: a problem for quality improvement.
Cullen DJ, Bates DW, Small SD, Cooper JB, Nemeskal AR, Leape LL.
Jt Comm J Qual Improv 1995 Oct;21(10):541-8.The results of this study show that adverse drug events (ADEs) occurring in hospitalized patients are rarely reported to the hospital's quality assurance program. In particular, of the 55 ADEs that were detected during the study period, only 3 (6%) had been reported to the incident reporting system, even though 26 of them were serious or life threatening. Fifteen of the ADEs detected were considered preventable. These findings indicate that studies based on data gathered from voluntary reporting of adverse events may be underestimating the incidence of these complications by as much as 94%.
Reporting of adverse drug reactions by hospital doctors and the response to intervention.
McGettigan P, Golden J, Conroy RM, Arthur N, Feely J.
Br J Clin Pharmacol 1997 Jul;44(1):98-100.The results of this study indicate that in Ireland only 45% of doctors from 118 hospitals had ever reported adverse drug reactions (ADRs). When reporting cards were made readily available by placing them inside the patient admission chart and doctors were regularly reminded to report ADRs, the frequency of reports increased by 5 times over a 3-month period. However, the rate of reports declined rapidly after discontinuation of verbal reminders.
Underreporting of suspected adverse drug reactions to newly marketed ("black triangle") drugs in general practice: observational study.
Martin,M, et al.
BMJ 1998;317:119-120 ( 11 July ).The results of this study show that physicians report only 9% of suspected adverse reactions to newly marketed drugs to the Committee on safety of Medicines. Although the highest rate of reporting was for serious adverse drug reactions, still only 32% of serious unlabelled reactions (those that are not listed in the accompanying drug information sheet) and 11% of serious labeled reactions were submitted to the Committee. These data indicate that the large majority of serious adverse drug reactions go unreported.
Adverse drug reactions in a hospital general medical unit meriting notification to the Committee on Safety of Medicines.
Smith CC, et al.
Br J Clin Pharmacol 1996 Oct;42(4):423-9.The results of this study show that suspected adverse drug reactions (ADRs) occur in 6.8% of patients admitted to the hospital and are responsible for the hospitalization in 3/4 of cases. Only 6.3% of adverse drug reactions that, according to current guidelines, should have been notified to the Committee on Safety of Medicines had been actually submitted. The majority of unreported ADRs were for those that caused hospital admissions and involved mostly well-known complications to commonly used drugs.
Differences in perceived and presented adverse drug reactions in general practice.
Ottervanger JP, Valkenburg HA, Grobbee DE, Stricker BH.
J Clin Epidemiol 1998 Sep;51(9):795-9.This study indicates that patients experience significantly more adverse drug reactions (ADRs) than what their physicians are aware of. ADRs to sumatriptan were evaluated through a questionnaire sent to physicians and their patients. To avoid bias, no specific reactions were listed in the questionnaire. The most frequent ADRs reported by patients' physicians were: dizziness (1.7%), nausea or vomiting (1.5%) drowsiness or sedation (1.4%) and chest pain (1.3%). Patients on the other hand reported dizziness (8.1%), chest pain (7.9%), paraesthesia (11.7%), and feeling of heaviness (8%). The authors conclude that post-marketing studies that utilize data from physicians could significantly underestimate the real incidence of adverse drug reactions.
Postmarketing surveillance and adverse drug reactions: current perspectives and future needs.
Brewer T, Colditz GA.
JAMA 1999 Mar 3;281(9):824-9.This article illustrates how spontaneous reporting of adverse drug reactions (ADRs) is not a reliable indicator of the true occurrence of these events. Spontaneous reporting leaves potentially important ADRs undetected, since it cannot adequately assess the incidence of events occurring separated in time from treatment initiation, or consisting of symptoms occurring also in individuals not exposed to the drug.
Age and sex distribution of suspected adverse drug reactions to newly marketed drugs in general practice in England: analysis of 48 cohort studies.
Martin RM, Biswas PN, Freemantle SN, Pearce GL, Mann RD.
Br J Clin Pharmacol 1998 Nov;46(5):505-11.The results of this study, conducted on a cohort of over 510,000 patients, show that women have a 60% increased risk of developing an adverse drug reactions compared to men. Interestingly, the majority of clinical trials are conducted on men.
Adverse drug events in hospitalized patients. A comparison of doctors, nurses and patients as sources of reports.
van den Bemt PM, et al.
Eur J Clin Pharmacol 1999 Apr;55(2):155-8.The results of this study, conducted on a sample population of 620 hospitalized patients, indicate that adverse drug events (ADEs) occur in 29% of patients. Serious ADEs comprised 26% of all ADEs reported by doctors, and were detected three-times as frequently by doctors than by their patients. Adverse reactions to new drugs, on the other hand, were reported more frequently by patients than by their doctors.
Retrospective analysis of the frequency and recognition of adverse drug reactions by means of automatically recorded laboratory signals.
Tegeder I, et al.
Br J Clin Pharmacol 1999 May;47(5):557-564.This study evaluated retrospectively the incidence of adverse drug reactions in hospitalized patients through an automatic system (ALS) that fired signals every time laboratory results revealed abnormalities potentially indicative of an adverse drug reaction (ADR). Eighteen of 98 signals that were alerted were considered as probable ADRs after reviewing laboratory results and patients' charts. In two-thirds of the cases, the attending physician was not aware that an adverse drug reaction had occurred, even though 80% of the reactions were considered predictable.
The nosocomial component of medical care.
A prospective study on the amount, spectrum and costs of medical disturbances in a department of infectious diseases.
Jorup-Ronstrom C, Britton S.
Scand J Infect Dis Suppl 1982;36:150-6.The results of this study, conducted on a cohort of 1271 patients admitted to the infectious disease department of a hospital, show that 11% of the admissions were due to complications to previous medical treatment while 27% of patients developed adverse reactions during hospitalization. Overall, the cost for medical care-related adverse events accounted for 17% of the total department costs.
Visits to office-based physicians in the United States for medication-related morbidity.
Aparasu RR.
J Am Pharm Assoc (Wash) 1999 May-Jun;39(3):332-7.This study indicates that in 1995, approximately 2 million outpatients visits occurred because of medication side effects, and the majority of these visits resulted in a scheduled follow-up visit. The drugs most frequently involved were hormones and synthetic substitutes (13%), followed by antibiotics (11.5%) and cardiovascular drugs (9%). These data indicate that adverse drug reactions leading to consultation of an office-based physician result in significant utilization of health care resources.
Adverse reactions to antibiotic drugs: the present scope of the problem in outpatient care and possibilities for improvement.
Hemminki E.
Int J Health Serv 1981;11(2):283-301.This article shows that in 1974, in the U.S., physicians wrote an average of 1 antibiotic prescription for each inhabitant. Antibiotic-related adverse drug reactions (ADRs) and serious ADRs, occurred in 7.6% and 1.4% of the population, respectively. If antibiotics had been prescribed only when necessary, two-thirds of ADRs would have been prevented; if the drug of choice had been prescribed, 37% of ADRs would have been prevented. If the antibiotic of choice had been prescribed only when necessary, four fifth of all ADRs would have been avoided.
Errors in the treatment of tuberculosis in Baltimore.
Rao SN, Mookerjee AL, Obasanjo OO, Chaisson RE.
Chest 2000 Mar;117(3):734-7.The results of this study show that private physicians often treat tuberculosis (TB) incorrectly, favoring the development of acquired drug resistance and multidrug resistant TB. The study was conducted on 110 patients diagnosed with TB in the city of Baltimore between 1994 and 1995. Almost 40% of patients treated by private physicians were prescribed the wrong treatment regimen, compared to 5% of those treated at the Baltimore City Health Department's Tuberculosis Clinic. Inappropriate management consisting of low-doses antibiotics and short treatment courses is an important cause of treatment failure and acquired antibiotic resistance. The authors estimated the costs of salvage of inadequate treatment at $180,000 per patient.
Complications of care in a medical intensive care unit.
Rubins HB, Moskowitz MA.
J Gen Intern Med 1990 Mar-Apr;5(2):104-9.The results of this study indicate that 14% of patients admitted to a medical intensive care unit of a teaching hospital develop a complication from treatment. Patients with complications tend to be older and more severely ill, and have longer hospital stay and higher mortality rates, compared to those with uncomplicated course (67% vs. 27%). The authors conclude that since mortality rates in these patients exceeded significantly the expected mortality rate of 46%, it is conceivable that complications of care in the MICU independently contribute to in-hospital mortality.
Acute renal failure: clinical outcome and causes of death.
Barretti P; Soares VA.
Ren Fail, 19(2):253-7 1997 Mar.This study shows that the incidence of acute renal failure (ARF) in hospitalized patients is 4.9/1000 patients. Over 46% of patients who develop ARF die. Nephrotoxic drugs are the main cause of ARF in 21% of cases.
Incidence and characteristics of preventable iatrogenic cardiac arrests.
Bedell SE, et al.
JAMA 1991 Jun 5;265(21):2815-20.The results of this study, conducted on all patients hospitalized during a one-year period at Boston's Beth Israel Hospital, show that 28 (14%) of the 203 cardiac arrests suffered by patients had a iatrogenic cause (e.g. medications, medical procedures, or failure to detect warning signs). Sixty-one percent of patients with iatrogenic cardiac arrest died. Approximately 10% of all arrests were due to preventable physicians' errors (lack of attention to patients' history, to findings of physical examination, and to laboratory results).
Iatrogenic congestive heart failure in older adults: clinical course and prognosis.
Rich MW, et al.
J Am Geriatr Soc 1996 Jun;44(6):638-43.This study shows that in 7% of patients aged 70 years or older hospitalized with heart failure the cause is iatrogenic, e.g. the heart failure is induced by medications, by excessive administration of fluids or by a complication of a medical procedure. In this study, in-hospital and one-year mortality rates in patients with iatrogenic heart failure were 32% and 68%, respectively, compared to 9% and 39% in noniatrogenic patients. Iatrogenic vs. noniatrogenic heart failure was associated with a 2.5-fold higher risk of death.
Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognized public health problem.
Page J, Henry D.
Arch Intern Med 2000 Mar 27;160(6):777-84.The results of this study indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) are an important cause of hospitalization for congestive heart failure (CHF) in individuals with or without a history of heart disease. The study was conducted on 365 patients hospitalized for heart failure and 658 controls. Individuals who used NSAIDs in the previous week had a 2-fold increased risk of hospitalization for CHF, compared to non-users. In patients with a history of heart disease, use of NSAIDs was associated with a 10-fold increased risk of hospitalization for CHF. The risk increased with increasing doses of NSAIDs taken in the previous week, and was greater with NSAIDs of long versus short half-life. The authors concluded that NSAIDs could account for approximately 20% of hospitalizations for congestive heart failure. Heart failure affects approximately 4.6 million Americans and this condition represent the most common hospital discharge diagnosis among patients older than 65 years. If this association is casual, as the dose-response relation suggests, cardiovascular morbidity due to NSAIDs would surpass gastro-intestinal NSAID-related morbidity, which alone is responsible for a minimum of 105,000 hospitalizations and 16,500 deaths occurring each year in the U.S. The economic and health consequences of these findings are staggering.
Hospitalizations with adverse events caused by digitalis therapy among elderly Medicare beneficiaries.
Warren JL, McBean AM, Hass SL, Babish JD.
Arch Intern Med 1994 Jul 11;154(13):1482-7.This study indicates that in 1987, more than 3 million Medicare recipients were taking digitalis. During a seven-year study period, among this cohort, 202,011 patients were hospitalized because of adverse reactions to digitalis. This means that, every year, for every 1,000 individuals taking digitalis, 8.53 are hospitalized for adverse drug reactions to the drug.
Contribution of adverse drug reaction to admission rates in an acute psychiatric ward.
Hermesh H, et al.
Acta Psychiatr Scand 1985 Jul;72(1):104-10.The results of this study show that 7.5% of all admission to an acute psychiatric ward, are due to adverse drug reactions. The elderly are particularly at risk of experiencing drug-related complications.
Adverse drug reactions (ADRs) in patients with HIV infection. A prospective study.
Gonzalez-Martin G, et al.
Int J Clin Pharmacol Ther 1999 Jan;37(1):34-40.In this study, the frequency of adverse drug reactions (ADRs) evaluated in a cohort of 50 ambulatory patients with HIV infection was 32%. In 18.5% of patients ADRs were severe and in 70.4% moderate. Trimethroprim-sulfamethoxazole and zidovudine were the most frequent cause of ADRs. Withdrawal of the responsible drug was required in 50% of cases.
Survey of drug-related deaths in Victoria.
Coleridge J; Cameron PA; Drummer OH; McNeil JJ.
Med J Aust, 157(7):459-62 1992 Oct 5.This study evaluated the cause of death in a sample of 231 drug-related deaths reported in Victoria. The primary cause of death was attributed to heroin and morphine in 35% of cases and to prescription drugs in 47% of cases. Tricyclic antidepressants and benzodiazepines were responsible for 14% and 6.5% of deaths, respectively. The mode of death was unclear in most cases and could have been other than suicide.
The manner of death among fatalities where dextropropoxyphene caused or contributed to death.
Jonasson B; Jonasson U; Saldeen T.
Forensic Sci Int, 96(2-3):181-7 1998 Sep 28.In this study, blood sample analyses from 23,691 deceased individuals were evaluated for presence of dextropropoxyphene (DXP), one of the most frequently prescribed pain-medication in Sweden. DXP was found in 1782 samples (7.5%) and was the cause of death in 54% of these cases.
Deaths related to iodinated contrast media reported spontaneously to the U.S. Food and Drug Administration, 1978-1994
Effect of the availability of low-osmolality contrast media.
Spring DB; Bettmann MA; Barkan HE.
Radiology, 204(2):333-7 1997 Aug.This study evaluated the number of iodinated contrast medium-related deaths reported to the U.S. Food and Drug Administration Spontaneous Reporting System from 1967 to 1994. Over a thousand deaths were reported during that period, 855 of which occurred after 1978. There was a 42% increase in deaths each year from 1987 to 1994 mostly associated with use of nonionic contrast media.
Reports of 355 transfusion-associated deaths: 1976 through 1985.
Sazama K.
Transfusion, 30(7):583-90 1990 Sep.This study describes 256 blood transfusion-related deaths reported to the Food and Drug Administration from 1976 to 1985. Fifty-one percent of these deaths were due to transfusion of incompatible blood products.
Autologous donation error rates in Canada.
Goldman M, Remy-Prince S, Trepanier A, Decary F.
Transfusion 1997 May;37(5):523-7.This study shows that although use of autologous blood transfusions should eliminate certain risks associated with transfusions, the possibility of errors, mainly clerical, is still high, with a detected rate of 1 error for every 149 units transfused.
Wristband identification error reporting in 712 hospitals.
A College of American Pathologists' Q-Probes study of quality issues in transfusion practice.
Renner SW, Howanitz PJ, Bachner P.
Arch Pathol Lab Med 1993 Jun;117(6):573-7.Wristband identification of patients is essential to prevent incompatible blood transfusions. This study detected wristband identification errors in 2.2% of patients from 712 hospitals. Absent wristband was the error most frequently encountered, followed by multiple wristbands with different information, incomplete, erroneous and illegible data, and patient wearing another patient' wristband.
ADVERSE DRUG REACTIONS AND ERRORS IN CHILDREN
Drug utilization and reported adverse reactions in hospitalized children.
Mitchell AA, Goldman P, Shapiro S, Slone D.
Am J Epidemiol 1979 Aug;110(2):196-204.This study estimated the frequency of adverse clinical events in a cohort of 1669 hospitalized children at 45.7%. Approximately 17% of the adverse events were drug-related.
A prospective study of adverse drug reactions as a cause of admission to a paediatric hospital.
Martinez-Mir I, et al.
Br J Clin Pharmacol 1996 Sep;42(3):319-24.The results of this study indicate that 4.3% of 512 consecutive hospital admissions of children 1 to 24 months old were probably drug-related. Respiratory drugs, antibiotics, drugs active on the central nervous system and dermatological drugs were the agents most frequently involved.
A prospective study of adverse drug reactions in hospitalized children.
Martinez-Mir I, Garcia-Lopez M, Palop V, Ferrer JM, Rubio E, Morales-Olivas FJ.
Br J Clin Pharmacol 1999 Jun;47(6):681-8.The results of this study, conducted on a cohort of 512 consecutive pediatric patients 1 to 24 months old admitted to the medical ward of a hospital, show that the incidence of adverse drug reactions (ADRs) in this study group was 16.6%. Girls had a 66% higher risk of ADRs. Antibiotics and vaccines were the most frequent cause of ADRs (41.5%).
Adverse drug reactions (ADRs) in hospitalized pediatric patients. A prospective study.
Gonzalez-Martin G, Caroca CM, Paris E.
Int J Clin Pharmacol Ther 1998 Oct;36(10):530-3.The results of this study show that 13.7% of children admitted to the hospital develop an adverse drug reaction (ADR). Ninety-three percent of the ADRs were dose-dependent. Twenty-eight percent were severe and 51% were moderate. Causality assessment determined that 54% of ADRs were probable and 32% possible.
Medication errors in paediatric practice: insights from a continuous quality improvement approach.
Wilson DG; et al.
Eur J Pediatr, 157(9):769-74 1998 Sep.In this prospective study, a multidisciplinary committee evaluated over a 2-year period the incidence of medication errors in pediatric patients. The committee detected 411 errors that occurred in 682 children. Sixty-eight percent of errors were averted prior to drug administration, 24 errors with potential for serious patient adverse reactions were not detected in advance and caused overt clinical consequences in 4 cases.
Errors by paediatric residents in calculating drug doses.
Rowe C; Koren T; Koren G.
Arch Dis Child, 79(1):56-8 1998 Jul.This article shows that a significant number of physicians specializing in childcare prescribe the wrong dose of medication to infants and children. This finding is important, since inappropriate dosage in this age group may be associated with significant morbidity and mortality. Approximately 10% of residents who participated in this study committed a 10-fold dosage error, which may be life threatening.
Prevalence of feeding tube placement errors & associated risk factors in children.
Ellett ML; Maahs J; Forsee S.
MCN Am J Matern Child Nurs, 23(5):234-9 1998 Sep-Oct.The results of this study, conducted on a cohort of 201 hospitalized children who had an enteral tube inserted, show that in approximately 14% of them the feeding tube was misplaced (e.g. the tip of the tube was in the esophagus and in the intestine when it was meant to be in the stomach, or in the esophagus and stomach when it was meant to be in the intestine).
The nature of adverse events in hospitalized patients.
Results of the Harvard Medical Practice Study II.
Leape LL, et al.
N Engl J Med 1991 Feb 7;324(6):377-84.This study analyzed the medical records of 30,195 randomly selected in-hospital patients and found that the incidence of patient injuries due to medical treatment was 3.7%. Forty-eight percent of events were due to surgical procedures, 19% to drug-related complications, 14% to wound infections, and 13% due to technical complications.
Proportion of hospital deaths associated with adverse events.
Garcia-Martin M, et al.
J Clin Epidemiol 1997 Dec;50(12):1319-26.This study shows that 56% of hospital deaths secondary to adverse events are due to surgical complications and 22% are due to hospital-related infections.
The incidence and nature of surgical adverse events in Colorado and Utah in 1992.
Gawande AA, Thomas EJ, Zinner MJ, Brennan TA.
Surgery 1999 Jul;126(1):66-75.This study evaluated the medical records of 15,000 patients hospitalized in Utah and Colorado, and found that the incidence of surgical adverse events in this cohort was 3.0%. Fifty-four percent of surgical adverse events were preventable and this type of complication accounted for 12.2% of all hospital deaths occurring in Utah and Colorado.
Are in-hospital deaths and long stay markers for errors in surgery?
Trošeng T; Janzon L.
Qual Assur Health Care, 2(2):149-59 1990.In this study, surgical errors were found in the care of 23% of patients who died in the hospital during a 1-year study period, in 10% of those who had a long hospital stay, and in 3% of those referred to other departments.
