Population-based drug-related anaphylaxis in children and adolescents captured by South Carolina Emergency Room Hospital Discharge Database (SCERHDD) (2000-2002)

PURPOSE: Anaphylaxis is a life-threatening condition; drug-related anaphylaxis represents approximately 10% of all cases. We assessed the utility of a statewide emergency department (ED) database for identifying drug-related anaphylaxis in children by developing and validating an algorithm composed of ICD-9-CM codes. METHODS: There were 1 314,760 visits to South Carolina (SC) emergency departments (EDs) for patients <19 years in 2000-2002. We used ICD-9-CM disease or external cause of injury codes (E-codes) that suggested drug-related anaphylaxis or a severe drug-related allergic reaction. We found 50 cases classifiable as probable or possible drug-related anaphylaxis and 13 as drug-related allergic reactions. We used clinical evaluation by two pediatricians as the 'alloyed gold standard'1 for estimating sensitivity, specificity, and positive predictive value (PPV) of our algorithm. RESULTS: ED-treated drug-related anaphylaxis in the SC pediatric population was 1.56/100,000 person-years based on the algorithm and 0.50/100,000 person-years based on clinical evaluation. Assuming the disease codes we used identified all potential anaphylaxis cases in the database, the sensitivity was 1.00 (95%CI: 0.79, 1.00), specificity was 0.28 (95%CI: 0.16, 0.43), and the PPV was 0.32 (0.20, 0.47) for the algorithm. Sensitivity analyses improved the measurement properties of the algorithm. CONCLUSIONS: E-codes were invaluable for developing an anaphylaxis algorithm although the frequently used code of E947.9 was often incorrectly applied. We believe that our algorithm may have over-ascertained drug-related anaphylaxis patients seen in an ED, but the clinical evaluation may have under-represented this diagnosis due to limited information on the offending agent in the abstracted ED records. Post-marketing drug surveillance using ED records may be viable if clinicians were to document drug-related anaphylaxis in the charts so that billing codes could be assigned properly.     

Illicit drug use in young adults and subsequent decline in general health: the Coronary Artery Risk Development in Young Adults (CARDIA) Study

BACKGROUND: The long-term health consequences of drug use among healthy young adults in the general population are not well described. We assessed whether drug use predicted decline in general self-rated health (GSRH) in a community-based cohort, healthy at baseline. METHODS: A prospective cohort of 3124 young adults (20-32 years old) from four US cities, the Coronary Artery Risk Development in Young Adults Study, was followed from 1987/1988 to 2000/2001. All reported "Good" or better GSRH at baseline, with reassessment in 2000/2001. Drug use in 1987/1988 was as follows: 812 participants were Never Users; 1554 Past Users Only; 503 Current Marijuana Users Only; 255 Current Hard Drug Users (e.g. cocaine, amphetamines, opiates). Analyses measured the association of drug use (1987/1988) with decline to "Fair" or "Poor" GSRH in 2000/2001, adjusting for biological and psychosocial covariates. RESULTS: Reporting health decline were: 7.2% of Never Users; 6.5%, Past Use Only; 7.0%, Current Marijuana Only; 12.6%, Current Hard Drugs (p<0.01). After multivariable adjustment, Current Hard Drug Use in 1987/1988 remained associated with health decline (Odds Ratio (OR), referent Never Use: 1.83, 95% confidence interval (CI) 1.07-3.12). The health decline associated with Current Hard Drugs appeared to be partly mediated by tobacco smoking in 2000/2001, which independently predicted health decline (OR 1.66, 95% CI 1.08-2.50) and weakened the apparent effect of Current Hard Drugs (OR 1.21, 95% CI 0.62-2.36). CONCLUSIONS: Hard drug use in healthy young adults, even when hard drug use stops, is associated with a subsequent decrease in general self-rated health that may be partially explained by persistent tobacco use.     

Glafenine-associated anaphylaxis as a cause of hospital admission in the Netherlands

Summary In 1981 generalized anaphylaxis was registered on 166 occasions in Dutch general and academic hospitals. Clinical details of 120 of those patients revealed that in 107 anaphylaxis was either probable (n=90) or possible (n=17), whereas in 13 cases some other reaction than anaphylaxis had occurred. The series of confirmed cases contained 46 men and 61 women, with mean ages of 47 y and 48 y, respectively.There was a complete recovery in 102 patients and two patients died. Hypotension was present in 79 cases (74%), dyspnoea in 34 cases (32%) and a skin reaction, mainly urticaria, erythema or angioedema, was mentioned in 62 cases (58%). Most cases of anaphylaxis were drug-induced (76%), the main causes being the analgesic glafenine and contrast media. Glafenine was mentioned as the cause in 36% of all admissions for drug-induced anaphylaxis. Only 3.7% of cases had been reported to the voluntary reporting scheme of the Netherlands Centre for Monitoring of Adverse Reactions to Drugs.On the basis of reimbursement data, the risk of developing severe anaphylaxis to glafenine was estimated at 11.7–19.3-fold relative to indomethacin, and 13.4–20.2-fold relative to oral penicillins.     

Characteristics of admissions to residential drug treatment agencies in New South Wales, 1988-92: II. Alcohol problems

The Clients at Residential Agencies (CARA) database of the New South Wales Drug and Alcohol Directorate was analysed for trends in admissions of clients with alcohol problems over the years 1988-92. There were no changes in the mean age and sex ratio of admissions, with the treatment population in all years predominantly males in their mid-thirties. There was a decrease in the proportion of clients who were employed full-time (25.1-16.4%), and an increase in admissions with criminal histories (45.7-59.3%). More than half of admissions in all years had alcohol problems of greater then 10 years' standing. The percentage of people who had never been in treatment before decreased from 44.4% in 1988 to 18.7% in 1992.     

Which drugs cause preventable admissions to hospital? A systematic review

AIMS: Previous systematic reviews have found that drug-related morbidity accounts for 4.3% of preventable hospital admissions. None, however, has identified the drugs most commonly responsible for preventable hospital admissions. The aims of this study were to estimate the percentage of preventable drug-related hospital admissions, the most common drug causes of preventable hospital admissions and the most common underlying causes of preventable drug-related admissions. METHODS: Bibliographic databases and reference lists from eligible articles and study authors were the sources for data. Seventeen prospective observational studies reporting the proportion of preventable drug-related hospital admissions, causative drugs and/or the underlying causes of hospital admissions were selected. Included studies used multiple reviewers and/or explicit criteria to assess causality and preventability of hospital admissions. Two investigators abstracted data from all included studies using a purpose-made data extraction form. RESULTS: From 13 papers the median percentage of preventable drug-related admissions to hospital was 3.7% (range 1.4-15.4). From nine papers the majority (51%) of preventable drug-related admissions involved either antiplatelets (16%), diuretics (16%), nonsteroidal anti-inflammatory drugs (11%) or anticoagulants (8%). From five studies the median proportion of preventable drug-related admissions associated with prescribing problems was 30.6% (range 11.1-41.8), with adherence problems 33.3% (range 20.9-41.7) and with monitoring problems 22.2% (range 0-31.3). CONCLUSIONS: Four groups of drugs account for more than 50% of the drug groups associated with preventable drug-related hospital admissions. Concentrating interventions on these drug groups could reduce appreciably the number of preventable drug-related admissions to hospital from primary care.     

Preventing and managing drug-induced anaphylaxis.

Drug-induced anaphylaxis and anaphylactoid reactions have increased in frequency with more widespread use of pharmaceutical agents. Anaphylaxis is a systemic, severe immediate hypersensitivity reaction caused by immunoglobulin (Ig) E-mediated immunological release of mediators of mast cells and basophils. An anaphylactoid reaction is an event similar to anaphylaxis but is not mediated by IgE. The incidence of anaphylactic or anaphylactoid reactions differs amongst classes of medications. Antibacterials are the most usual offenders, and penicillins are the most studied. Other compounds commonly causing reactions include non-steroidal anti-inflammatory drugs, anaesthetics, muscle relaxants, latex and radiocontrast media. Prevention, if possible, is the purpose of detailed patient history taking and physical examination. Simple strategies can be employed to decrease the risk of anaphylaxis. These include consideration of the route of drug administration, identification of patients with known causes of anaphylaxis, and the knowledge that certain medications cross react and are contraindicated in those with known history of anaphylaxis. Tests are available, and include IgE-specific skin tests and radioallergosorbent tests. Penicillins are the only compounds whose antigenic determinants are well documented, it is therefore difficult to determine the negative predictive value of other compounds tested. Oral challenge remains an alternative, though entails risk. Desensitisation procedures, as well as gradual dose escalation protocols, are available and can be implemented based on patient history and diagnostic testing. The management of anaphylaxis is based on control of the airway, breathing and circulation. Treatment consists of epinephrine (adrenaline) and supportive measures. Rapid diagnosis and intervention are important in these life-threatening reactions. After stabilisation, all individuals with a documented history of anaphylaxis require a Medic-Alert bracelet or necklace, and an identification card for their wallet or purse.     

Impact of hospitalization on blood pressure control in Italy: results from the Italian Group of Pharmacoepidemiology in the Elderly (GIFA)

STUDY OBJECTIVES: To evaluate whether hospitalization affects blood pressure control in hypertensive patients, and to identify factors associated with attainment of adequate blood pressure control and with aggressive pharmacologic treatment. DESIGN: Retrospective study. SETTING: Eighty-one hospitals throughout Italy. PATIENTS: A total of 3,304 patients (59% women, 41% men) with a diagnosis of hypertension and uncontrolled blood pressure values at hospital admission. MEASUREMENTS AND MAIN RESULTS: Patients' blood pressures were surveyed during study periods from 1988-1997. Controlled blood pressure was defined according to the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (systolic < 140 mm Hg, diastolic < 90 mm Hg). Aggressive pharmacologic treatment was defined as an increase in the number of antihypertensive drugs that the patient was receiving at hospital discharge compared with the number of drugs on admission. Adequate blood pressure control was achieved in only 767 (23.2%) patients, but the proportion increased in each subsequent survey Age (odds ratio [OR] for 10-year increase 0.82, 95% confidence interval [CI] 0.76-0.88) and male sex (OR 0.79, 95% CI 0.65-0.94) were associated with reduced likelihood of achieving adequate blood pressure control. In contrast, coronary heart disease (OR 1.38, 95% CI 1.14-1.66), year of survey (1995 vs 1988: OR 1.47, 95% CI 1.19-1.82; 1997 vs 1988: OR 1.27, 95% CI 1.02-1.42), length of hospital stay (medium vs lower tertile OR 1.20, 95% CI 0.96-1.49; higher vs lower tertile OR 1.42, 95% CI 1.13-1.77), and increase in number of antihypertensive drugs prescribed (OR 1.21, 95% CI 1.02-1.42 for one drug increase) were associated with improved blood pressure control. In 1753 (53.1%) patients, the number of antihypertensive drugs increased during their hospital stay. Younger age, fewer drugs on admission, lower comorbidity index, diagnosis of chronic heart failure, lengthy hospital stay, and increasing baseline values of systolic and diastolic blood pressure were associated with aggressive pharmacologic treatment. CONCLUSION: Adequate blood pressure control was achieved in only 25% of patients with hypertension despite a trend toward improvement in recent years. Advanced age was one of the main factors associated with less aggressive pharmacologic treatment and with inadequate blood pressure control.     

575例抗精神疾病药品不良反应报告分析

目的探讨抗精神疾病药品的不良反应。方法采用药品不良反应/事件报告表,对精神病医院住院患者的药品不良反应资料进行分析。结果在575例不良反应中,涉及25种抗精神疾病药品,其中10种药品发生了3种以上不良反应,2种药品发生了5种不良反应。68%的不良反应发生在用药后15天内。不良反应发生率11.83%。结论抗精神疾病药品不良反应以白细胞减少、心电异常、肝功能异常、锥体外系反应、过敏反应等多见。建议在初期用药应慎重。     

A decade of intensive care unit trauma admissions in Auckland

AIMS: To describe the demographics, nature and severity of injury of trauma admissions to a New Zealand urban Intensive Care Unit (ICU) over a ten year period; to determine differences in injury characteristics between patients received from inside and outside the local trauma catchment area; and to calculate incidence rates in the local population served, to identify high risk groups of patients. METHODS: We carried out a cross-sectional analysis of a prospective ICU patient registry. Data on all trauma admissions from 1988 to 1997 to the ICU of a large New Zealand urban hospital were studied with respect to age, gender, ethnicity, injury type and severity, and referral status. National Census data for the ICU catchment area were used to calculate incidence rates for local admissions. RESULTS: A total of 2305 trauma patients were admitted over the period of the study, accounting for 25% of all ICU admissions. The median age was 28 years and 75% were males. Blunt trauma, mostly due to motor vehicle crashes, accounted for 95% of admissions and penetrating trauma was very rare. The median Injury Severity Score (ISS) was 26 and most life threatening injuries occurred in the head region. Referred admissions were more severely injured and had a higher prevalence of severe head injury than local admissions. The ICU trauma admission rate for local patients was 34.6 per 100,000 person-years. Males had a higher rate than females in all age groups. New Zealand Europeans made up the majority of admissions, but Maori and Pacific Island males had the highest incidence rates. CONCLUSIONS: This study identified trauma as a major component of the ICU population. ICU trauma admissions were characterised by young males with head injuries resulting from motor vehicle crashes. Referred admissions were more severely injured than local admissions and would thus distort the estimated incidence of trauma in the local geographic region served. Calculation of incidence rates highlighted a significantly higher risk of ICU trauma admission amongst Maori and Pacific Islands people than New Zealand Europeans.     

Documentation and evaluation of adverse drug reactions (ADR)--contribution from a poison information center

The Department of Clinical Pharmacology in Jena is a pharmacovigilance center in a study on intensified spontaneous adverse drug reaction reporting. Physicians specialized in clinical pharmacology screen admissions to the Department of Internal Medicine for possible adverse drug reactions. Because of the collaboration between the Pharmacology Department and the nearby Poison Information Center (PIC) in Erfurt the question occurred whether the latter might contribute to adverse drug reaction monitoring. We compared the ADR registered by the intensified spontaneous reporting system in 1999 with those of the PIC during the same period. Each symptom observed was regarded as 1 case. Every suspected drug was also treated separately. The symptoms were classified using adverse reaction terminology. The drugs were classified according to the WHO Anatomical Therapeutic Chemical (ATC) classification index. The causality assessment was based upon bibliographic data and the method of Bégaud et al. [1985]. Only possible, probable or very probable ADR were compared. The PIC registered mainly psychiatric and nervous system disorders sedation and extrapyramidal disorders were the most frequent reactions - unlike the pharmacovigilance study which registered primarily gastrointestinal and heart rate disorders. The PIC registered mainly drugs used in the therapy of disorders of the central nervous system, i.e. mostly psycholeptics and drugs acting on the alimentary tract, mostly anticholinergics. Drugs for the therapy of sensory organs disorders were frequent owing to the systemic and local adverse drug effects of anticholinergic mydriatics. The PIC and pharmacovigilance centers can benefit from co-operation. The PIC provides easy access to qualified drug information and is thus a useful tool in ADR evaluation. Although the number of adverse reactions assessed was small, their evaluation revealed problems in drug usage which would not otherwise be reported. The evaluation has enlarged the pool of ADR data which is the basis for signal detection.     

Risk factors associated with adverse drug reactions following hospital admission : a prospective analysis of 907 patients in two german university hospitals

BACKGROUND: Since the 1970s, studies have examined potential risk factors associated with adverse drug reactions (ADRs) in a variety of settings. However, no pharmacoepidemiological study exists that incorporates clinical and laboratory parameters in a multiple regression model in order to consider predictors for ADRs. OBJECTIVES: To characterize risk factors associated with ADRs in patients admitted to university hospital departments of internal medicine. DESIGN AND SETTING: Intensive pharmacovigilance was carried out in departments of internal medicine of two university hospitals. All admissions were followed prospectively for the occurrence of ADRs by members of a pharmacoepidemiological team consisting of physicians, pharmacologists and pharmacists. To identify patients at high risk for experiencing ADRs, patient histories and several clinical and laboratory data, determined at the time of admission, were taken into consideration. In addition to the drug prescribed, 40 parameters defined vital status at admission. These included temperature, heart rate, blood pressure (systolic-diastolic), body mass index, nicotine and alcohol use, and first laboratory test results after admission on nutrition status, inflammation, liver, kidney, pancreas or thyroid status, electrolytes, blood count and coagulation. RESULTS: 907 patients were observed during the study period. The mean age of the study population was 60 +/- 16 years. The median number of different drugs administered per patient during hospitalization was 9.6 +/- 7.7. In 345 patients, 592 ADRs were evaluated: 33.4% possible, 61.5% probable and 4.7% highly probable. Two ADR-related deaths were observed during the study period. Analysing ADR predictors, 17 of 40 parameters reached significance in univariate analysis, but only five in a multivariate binary regression model: raised temperature (odds ratio [OR] 1.609; 95% CI 1.133, 2.285), low erythrocyte levels (OR 0.386; 95% CI 0.194, 0.768), low thrombocyte levels (OR 0.788, 95% CI 0.627, 0.989), high number of drugs (OR 1.117; 95% CI 1.076, 1.159) and female sex (OR 1.562; 95% CI 0.785, 2.013) were independent predictors for ADRs. CONCLUSION: For the patients investigated, of the large number of clinical data available only five independent factors predict ADR occurrence. Taking these results into account, physicians will be able to focus early on patients at risk for ADRs. To minimize ADR occurrence, ADR predictors should be integrated into the clinical pathway.     

Characteristics of admissions to residential drug treatment agencies in New South Wales, 1988-92: I. Illicit drug problems

The Clients at Residential Agencies (CARA) database of the New South Wales Drug and Alcohol Directorate was analysed for trends in admissions of clients with illicit drug problems over the years 1988-92. The mean age of admissions rose from 26.8 years to 27.9 years over the study period. There was a small increase in the proportion of male admissions to agencies (66.5% in 1988 to 69.9% in 1992). The proportion of admissions reporting opiates as their primary drug problem declined from 81% to 65%, while the proportion of admissions for stimulant problems doubled in that period (8% to 16%), as did those for cannabis (3.6% to 8.7%). There was a significant increase in the proportions of admissions who had drug problems of 10 or more years' standing (34.9-41.3%). The proportion of admissions that had never been in treatment decreased from 51% to 15% over the study period. Admissions with prior methadone experience rose from 37% to 69% between 1988 and 1992.     

Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999

OBJECTIVES: To present an update on drug-induced pancreatitis reported to the Danish Committee on Adverse Drug Reactions. DESIGN: Retrospective study of spontaneous case reports to the Danish reporting system on adverse drug reactions. METHODS: All cases of suspected drug-induced pancreatitis reported to the Danish Committee on Adverse Drug Reactions from 1968 to 1999 were analysed. Three cases were excluded leaving 47 cases for analysis. RESULTS: Drug-induced pancreatitis made up 0. 1% of all the reports to the committee from 1968 to 1999. The proportion seemed to increase and was 0.3% during the last 8 years. The 47 cases corresponded to 0.1% of the number of patients discharged due to pancreatic disease (without cancers) per year in Denmark. Serious courses were frequent as indicated by death and hospitalisation being reported in 4 (9%) and 32 (68%) cases, respectively. Death occurred after valproate (two cases), clomipramine (one case) and azathioprine (one case). Definite relationship was stated for mesalazine (three cases), azathioprine (two cases) and simvastatin (one case) on the basis of re-challenge. A possible or probable causality was considered for a further 30 drugs including 5-acetylsalicylic acid agents, angiotensin-converting enzyme inhibitors, estrogen preparations, didanosine, valproate, codeine, antiviral agents used in acquired immunodeficiency syndrome therapy, various lipid-reducing agents, interferon, paracetamol, griseofulvin, ticlopine, allopurinol, lithium and the MMR (measles" mumps/rubella) vaccination. CONCLUSION: Drug-induced pancreatitis is rarely reported. The incidence may be increasing and the course is often serious. This is the first report on definite simvastatin-induced pancreatitis. Further studies on the pancreotoxic potential of drugs are warranted.     

Crack cocaine use in a cohort of methadone maintenance patients

We examined crack use in a cohart of methadone patients originally enrolled in 1984–1986. Crack use questions were added to the study in 1987. Of the 494 methadone patients originally enrolled, 228 subjects remained in methadone and were re-interviewed in 1987–1988, and 234 remained in methadone and were re-interviewed in 1988–1989. Approximately one-quarter of the subjects were using crack at each of the 1987–1988 and 1988–1989 data collection points, and only 3% of the subjects were using crack at daily or greater frequencies at each of the 1987–1988 and 1988–1989 interviews. Concurrent crack use was associated with (a) the number of noninjected drugs being used; (b) the number of IV drug-using sexual partners; (c) drug injection; and (d) the use of nonheroin opiates. Persistent crack use, defined as use in both 1987–1988 and 1988–1989, was associated with previous noninjected drug use and previous suicide attempts. While the potential problem of crack use among methadone patients should not be minimized, it appears that, compared to illicit drug injectors not in treatment, being in methadone maintenance may offer a protective effect against crack use.     

The quality of information on monitoring for haematological adverse drug reactions

AIMS: To examine the adequacy of instructions to monitor for haematological adverse drug reactions in the Summary of Product Characteristics. METHODS: We searched the United Kingdom eMedicines Compendium to identify instructions to monitor for haematological adverse drug reactions, and selected 84 Summaries of Product Characteristics for nonhaematological drugs, which were then scored independently by five clinicians, using a scale we devised, the Systematic Instructions for Monitoring (SIM) score. A subset of comparable summaries from Australian and United States summaries was also examined. RESULTS: The SIM scores for the five clinicians agreed well: Kendall's coefficient of concordance = 0.937, P < 0.0001. The median SIM score for the 84 UK summaries was 13 [95% confidence interval (CI) for median 12, 15] out of a possible 31. Over 40% fell below a hypothetical minimally acceptable score of 12/31. SIM scores were on average 2.0 (95% CI 0.4, 3.8) higher for Australian summaries; US summaries had intermediate scores that did not significantly differ from those in Australia or the UK. CONCLUSIONS: Instructions on monitoring for adverse drug reactions are often inadequate. Pharmaceutical companies and regulatory agencies should produce clear guidance on monitoring, and the data to support it.