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The RNA binding subset of adenosine antibodies.

Hapten specific antibodies were elicited against adenosine-BSA conjugate (Ado-BSA) in rats. By radiohapten assay, two major populations of hapten specific antibodies were identified. They were directed against either adenosine trialcohol (Aox-red) or morpholino-adenosine (Morph-Ade). The association constant (Ka) for the 3H-Aox-red binding population was determined to be 1.02 X 10(7) M-1. Majority of the Aox-red specific antibodies were cross-reactive with Morph-Ade, but they did not cross-react at all with adenosine(A) or deoxyadenosine (dA). 3H-A binding subsets were actually Morph-Ade specific and constitute less than 10% of the hapten specific antibodies. The Ka value for the 3H-A binding was determined to be 4.5 X 10(6) M-1. A very minor and highly cross-reactive subset of Morph-Ade specific antibodies participate in RNA binding. Though a larger proportion of Morph-Ade specific antibodies interact with 3H-A, only a fraction of them bind to RNA. The extreme cross-reactivity and hence, the highly adaptive nature of the binding sites of the antibodies interacting with RNA, might be a stringent requirement for recognising adenine residues of nucleic acids in solution.

Adenosine↗

Comparison of transepidermal water loss, capacitance and pH values in the skin between intrinsic and extrinsic atopic dermatitis patients.

Atopic dermatitis (AD), with the prevalence rate of around 10 to 15%, is characterized by an intensely pruritic skin lesions with typical distribution and morphology. Recently, AD is divided into extrinsic type (ADe) and intrinsic type (ADi) according to the laboratory findings and associated diseases. ADe is well-known for high IgE level, positive response to food- or aero-allergens, whereas ADi has clinically similar skin lesions and distribution patterns of AD with normal serum IgE levels, negative in vitro test for environmental or food allergens and without associated atopic diseases. To instrumentally evaluate the differences of skin involvement and functions between ADi and ADe, we checked the transepidermal water loss (TEWL), capacitance and pH in both types of childhood AD and age-matched control. The proportion of ADi was around 20% in all AD patients (10/51). Our experiment suggested possible differences between ADi and ADe. Antecubital fossa is a famous involvement site of childhood type of AD, where both types of AD patients showed higher TEWL and decreased capacitance. ADe patients showed increased TEWL in all sites and lower hydration in 4 sites, whereas ADi patients showed no significant differences of TEWL and hydration in forehead, cheek, and back of leg.

Adolescent↗

Comparison of P388D1 mouse macrophage cell line and human monocytes for assay of dengue-2 infection-enhancing antibodies.

Tissue culture-adapted dengue 2 virus (DEN 2), strain 16681, exhibits antibody-dependent enhancement of infection (ADE) in P388D1 cells, a mouse macrophage-like cell line. ADE is dependent upon maintaining DEN 2 multiplicity of infection at between 0.1 and 0.001, and can be simply measured in multi-well plastic plates. The assay uses either trypsinized or non-trypsinized P388D1 cells at 5 x 10(5) cells per ml, an appropriate dilution of DEN 2 virus, and a source of antibody, and is most conveniently performed without further washing of stationary cultures, which are incubated in 5% CO2. Trypsinization of P388D1 cells prior to the addition of virus-serum mixtures reduced infection in control cultures thus increasing ADE. When cells were washed after incubation of virus-serum mixtures for 1 hour, a paradoxical increase of infection in cultures exposed to virus plus normal serum was noted, which reduced the sensitivity of the ADE assay. Using human cord blood sera, ADE titers measured in human monocytes and P388D1 cells were closely similar. This convenient and economical assay will facilitate large scale biological and epidemiological studies of dengue virus enhancing antibodies.

Animals↗

An examination of adverse drug event monitoring practices in U.S. hospitals.

Unfortunately, the reasons for respondents' negative attitudes and perceptions toward ADE monitoring are not entirely clear because they generally are not related to time or staff constraints. There was some indication that poor medical record documentation was a contributing factor; however, this problem can be addressed through education of physicians and nurses as to the importance of capturing and reporting ADE data. Other research has demonstrated that substantial effort and diligence are required on the part of all members of the health care team to capture ADEs consistently. Fortunately or unfortunately--depending on the perspective--the motivation and at least the initial energy to establish and maintain an effective ADE monitoring program have to come from the pharmacy department. The greatest fear is that many pharmacists simply will be apathetic to the issue and not devote the time and energy necessary to capture and process ADE information effectively.

Adverse Drug Reaction Reporting Systems↗

Novel uncompetitive N-methyl-D-aspartate (NMDA)-receptor antagonist MRZ 2/579 suppresses ethanol intake in long-term ethanol-experienced rats and generalizes to ethanol cue in drug discrimination procedure.

Previous findings suggested that drugs modulating glutamatergic neurotransmission could be useful in the treatment of alcohol dependence. This study examined the effects of chronic and acute treatment with MRZ 2/579 (1-amino-1,3,3,5,5-pentamethyl-cyclohexane hydrochloride), a novel uncompetitive N-methyl-D-aspartate receptor antagonist, on voluntary ethanol intake in long-term ethanol-experienced rats. Rats were implanted with mini-osmotic pumps delivering either 9.6 mg/day MRZ 2/579 or vehicle, and the effects of treatment on the alcohol deprivation effect (ADE) were studied in a four-bottle home cage-drinking paradigm. The same rats were tested for a second ADE 3 weeks later in the absence of the drug. In a second experiment long-term ethanol-experienced rats trained in an operant free-choice ethanol self-administration paradigm with concurrent water received acute MRZ 2/579 treatment (0-4 mg/kg i.p.) before a 23-h session either during basal drinking or during the ADE. In an additional experiment, MRZ 2/579 (0.5-4 mg/kg i.p.) was tested for generalization to the ethanol cue in a drug discrimination procedure. Chronic MRZ 2/579 treatment selectively abolished the increased ethanol intake during the ADE. This effect depended on the presence of the drug. Acute MRZ 2/579 treatment (2 and 4 mg/kg) had a short-lasting reductive effect on lever pressing for ethanol, but not for water, both during the ADE and basal drinking. MRZ 2/579 dose dependently generalized to the ethanol cue in the drug discrimination experiment. It is concluded that MRZ 2/579 might exert its reducing effect on ethanol intake by substituting for some of the stimulus properties of ethanol.

Alcohol Drinking↗

The skin of atopic dermatitis patients contains a novel enzyme, glucosylceramide sphingomyelin deacylase, which cleaves the N-acyl linkage of sphingomyelin and glucosylceramide.

We have demonstrated previously that there is an abnormal expression of sphingomyelin (SM) deacylase in the epidermis of patients with atopic dermatitis (ADe). In the present study, we have prepared N-[palmitic acid-1-(14)C]SM and N-[palmitic acid-1-(14)C]glucosylceramide (GCer) to use as substrates and have quantified SM deacylase activity by detecting the release of [(14)C]palmitic acid in extracts of the stratum corneum or the epidermis of ADe patients. In studies using [palmitic acid-1-(14)C]SM as a substrate, a pH dependency of catalytic activity with a peak at pH 5.0 was found. Preparative SDS/PAGE using an extract of ADe epidermis revealed that the molecular mass of SM deacylase is 40000 Da, which is consistent with its apparent molecular mass of 42000 Da estimated by gel-filtration analysis of stratum corneum extracts. Analytical isoelectric focusing (IEF) chromatography demonstrated that the pI values of SM deacylase, beta-glucocerebrosidase (GlcCDase), sphingomyelinase (SMase) and acid ceramidase were 4.2, 7.4, 7.0 and 5.7, respectively. In enzymic analysis using pI-4.2 SM deacylase partially purified by IEF, which had no detectable contamination with acid ceramidase, GlcCDase or SMase, radio-TLC analysis revealed that radiolabelled sphingosylphosphocholine or [1-(14)C]palmitic acid was enzymically liberated from [choline-methyl-(14)C]SM or N-[palmitoyl-1-(14)C]GCer, respectively, used as substrates. Further the pI-4.2 protein purified from extracts of the stratum corneum of ADe patients was able to hydrolyse N-[palmitoyl-1-(14)C]SM and GCer, but not N-[palmitoyl-1-(14)C]ceramide. These results indicate that a hitherto undiscovered epidermal enzyme, termed here glucosylceramide sphingomyelin deacylase, is expressed in the skin of ADe patients, which plays an important role in ceramide deficiency (including acylceramides) in the stratum corneum.

Carboxylic Ester Hydrolases↗

Effects of concurrent access to multiple ethanol concentrations and repeated deprivations on alcohol intake of alcohol-preferring rats.

BACKGROUND: The alcohol deprivation effect (ADE) is a temporary increase in the voluntary intake of ethanol solutions following a period of alcohol deprivation. Multiple deprivations can prolong the expression of an ADE. This study examined the effects of initial deprivation length, concurrent exposure to multiple ethanol concentrations, and number of deprivation exposures on the magnitude and duration of the ADE in alcohol-preferring (P) rats. METHODS: Adult female P rats received 24-hr free-choice access to 10, 20, and 30% ethanol and water for 6 weeks. Rats were then randomly assigned to three groups; one group served as a nondeprived control, whereas the other two groups were initially deprived of ethanol for 2 or 8 weeks. The ethanol solutions were restored to both deprived groups for 2 weeks before the groups were deprived of ethanol for another 2 weeks. This cycle was repeated three times for a total of four deprivations. RESULTS: After the initial ethanol deprivation period, both deprived groups displayed a similar 2-fold increased ethanol intake (g/Kg/day) during the initial 24-hr period when ethanol was restored. Both deprived groups showed greater than 2-fold increases in intake of the 20 and 30% ethanol solutions after re-exposure. Ethanol consumption returned to baseline levels within 2 weeks, before the subsequent deprivation period. Multiple deprivations increased the magnitude of the ADE over that observed in the first deprivation during the initial 24-hr period of re-exposure and prolonged the duration of the ADE. In addition, repeated deprivations increased ethanol intake in the first 2-hr period of re-exposure and produced blood ethanol levels in excess of 150 mg/100 ml. CONCLUSIONS: Alterations in the reinforcing and/or aversive effects of alcohol occurred after a single prolonged deprivation and were enhanced with repeated deprivations.

Animals↗

Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720.

The Cancer and Leukemia Group B conducted a phase 3 trial of the P-glycoprotein modulator PSC-833 in untreated acute myeloid leukemia patients aged 60 years and older. Patients were randomized to 1 of 2 regimens, with doses determined in a prior phase 1 study, consisting of cytarabine 100 mg/m(2)/d by 7-day infusion, with daunorubicin 60 mg/m(2) and etoposide 100 mg/m(2) daily for 3 days (ADE), or daunorubicin 40 mg/m(2) and etoposide 60 mg/m(2) for 3 days with PSC-833, 2.8 mg/kg over 2 hours, and then 10 mg/kg/d by 3-day infusion (ADEP). The ADEP arm was closed after randomization of 120 patients (61 to ADE and 59 to ADEP) because of excessive early mortality. Rates of complete remission, nonresponse, and death were 46%, 34%, and 20% for ADE, versus 39%, 17%, and 44% for ADEP (P =.008). Nevertheless, disease-free survival (median 7 vs 8 months; P =.38) and overall survival (approximately 33% alive at 1 year) did not differ and were similar to historical results. Although the number of patients was limited, ADE patients whose pretreatment cells exhibited PSC-833-modulated dye efflux in vitro (n = 22) had worse outcomes than those without efflux (n = 11) (complete remission, nonresponse, and death rates of 41%, 41%, and 18%, compared with 91%, 9%, and 0%; P =.03), but with ADEP outcomes were nearly identical. Moreover, for patients with PSC-833-modulated efflux, median disease-free survival was 5 months with ADE and 14 months with ADEP (P =.07). Further modulation trials in older patients must await the design of less-toxic regimens.

Aged↗

[Medicinal iatrogenics in hospitals. A survey on a given day].

OBJECTIVE: Medicinal iatrogenics are responsible for hospital admissions but also occur in hospitals. In view of the lack of knowledge, prevalence and nature of the adverse drug-related events (ADE) in the Bichat-Claude Bernard hospital group in Paris, and because of the potential severity of the latter, the Local drug committee has decided to develop a policy to manage these risks. METHOD: The first stage consisted in a transversal study on a given day in the departments in which patients are hospitalised for more than 24 hours, in order to assess the prevalence, severity and preventability of ADE and to search for factors of risk. RESULTS: 107 ADE were observed in 89 patients on the day of the survey (9.9% global prevalence of ADE [CI 95%: 8.8% - 11.0%]). Among the latter, 57 patients had exhibited at least one adverse event during their hospitalisation, i.e., a prevalence of 6.3% ([CI 95%: 4.7% - 7.9%] ). Two thirds of these patients were hospitalised in medical departments. These nosocomial ADE (nosocomial adverse drug events) were serious or severe in 73% of cases and 25% could have been avoided. The only clearly identified risk factor was the number of drugs prescribed. CONCLUSION: This review has drawn the attention of the medical and paramedical community to the need to define vigilance markers, and has provided some elements of response that should be further completed by a prospective cohort study.

Adult↗

Critical gaps in the world's largest electronic medical record: Ad Hoc nursing narratives and invisible adverse drug events.

The Veterans Health Administration (VHA), of the U.S. Department of Veteran Affairs, operates one of the largest healthcare networks in the world. Its electronic medical record (EMR) is fully integrated into clinical practice, having evolved over several decades of design, testing, trial, and error. It is unarguably the world's largest EMR, and as such it makes an important case study for a host of timely informatics issues. The VHA consistently has been at the vanguard of patient safety, especially in its provider-oriented EMR. We describe here a study of a large set of adverse drug events (ADEs) that eluded a rigorous ADE survey based on prospective EMR chart review. These numerous ADEs were undetected (and hence invisible) in the EMR, missed by an otherwise sophisticated ADE detection scheme. We speculate how these invisible nursing ADE narratives persist and what they portend for safety re-engineering.

Adverse Drug Reaction Reporting Systems↗

Antibody-dependent enhancement of dengue virus infection mediated by bispecific antibodies against cell surface molecules other than Fc gamma receptors.

It is known that antibodies to dengue viruses at subneutralizing concentrations enhance dengue virus infection of Fc gamma R+ cells. This phenomenon called antibody-dependent enhancement (ADE) occurs when virus-antibody complexes bind to the Fc gamma R via the Fc portion of the Ig. It has been hypothesized that ADE may be responsible for the pathogenesis of the severe manifestations of dengue virus infection including dengue hemorrhagic fever/dengue shock syndrome. To further analyze the mechanisms of ADE, we prepared bispecific antibodies by chemically cross-linking antidengue virus antibodies to antibodies specific for Fc gamma RI or Fc gamma RII and the non-Fc R molecules beta2 microglobulin, CD15 or CD33 and examined whether these bispecific antibodies could enhance infection. Bispecific antibodies targeting dengue virus to Fc gamma RI or Fc gamma RII enhanced dengue virus infection, consistent with previous reports using conventional antibodies. Furthermore, bispecific antibodies targeting dengue virus to beta2 microglobulin, CD15 or CD33 also enhanced dengue virus infection. Bispecific antibody mediated ADE was inhibited by pretreating the cells with the appropriate blocking mAb. These results indicate that cell surface molecules other than Fc gamma R can mediate ADE and suggest that the Fc gamma R does not provide a unique signal necessary for enhanced infection. We hypothesize that directing dengue virus to the cell surface by a bispecific antibody facilitates the interaction between dengue virus and its receptor, thereby increasing its infectivity.

Antibodies, Viral↗

Complement-mediated, antibody-dependent enhancement of HIV-1 infection in vitro is characterized by increased protein and RNA syntheses and infectious virus release.

Antibody-dependent enhancement (ADE) of human immunodeficiency virus type 1 (HIV-1) infection in vitro has been described recently and was shown to occur by two mechanisms: either participation of the alternative pathway of complement or to involve an Fc receptor-mediated, complement-independent mechanism. Complement-mediated ADE results in an accelerated cytopathic effect in target cells that can abrogate the protective properties of neutralizing antibodies. This study characterizes the surface antigens of MT-2 cells using flow cytometric analysis and shows that these cells express high levels of both CD4 and complement receptor type 2 (CR2) while several CD4+ cell lines that do not demonstrate complement-mediated ADE lack high levels of complement receptors. Further, utilizing MT-2 cell cultures, it is demonstrated that complement-mediated ADE of HIV-1 infection is conferred by the sera from more than 80% of HIV-1 antibody-positive individuals (N = 85). Complement-mediated ADE of HIV-1 infection causes an acceleration of several parameters indicative of HIV-1 infection in vitro including increased HIV-1 antigen synthesis as detected by indirect immunofluorescence, RNA accumulation as measured by a solution hybridization protocol, reverse transcriptase release, and progeny virus production.

Cell Line↗

Ketamine and the arrhythmogenic dose of epinephrine in cats anesthetized with halothane and isoflurane.

Epinephrine-induced arrhythmias were studied in 4 cats (group A), using a 4 X 4 Latin square design. Each cat was anesthetized 4 times, 1 week apart, with halothane (1.5% end expired), isoflurane (2.0% end expired), and halothane or isoflurane preceded by ketamine administered IM (8.8 mg/kg). Lead II of the ECG and femoral artery pressure were recorded. Epinephrine was infused in progressively doubled rates (initial rate = 0.125 micrograms/kg/min) for a maximum of 2.5 minutes or until at least 4 ventricular premature depolarizations occurred within 15 s of each other. The arrhythmogenic dose of epinephrine (ADE; micrograms/kg) was calculated as the product of infusion rate and time to arrhythmia. The ADE (means +/- SD) during anesthesia with halothane alone and with ketamine-halothane anesthesia were 1.33 +/- 0.65 and 1.37 +/- 0.59 micrograms/kg, respectively; during anesthesia with isoflurane alone and ketamine-isoflurane anesthesia, the ADE were 9.34 +/- 1.29 and 16.16 +/- 3.63 micrograms/kg, respectively. The ADE was significantly greater (P less than 0.05) during isoflurane anesthesia and ketamine-isoflurane anesthesia than during halothane anesthesia. The percentages of change in systolic blood pressure (means +/- SD) at the ADE during halothane, ketamine-halothane, isoflurane, and ketamine-isoflurane were 31 +/- 34, 41 +/- 17, 127 +/- 27, and 148 +/- 57, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Halothane-catecholamine arrhythmias in swine (Sus scrofa).

The arrhythmogenic dose of epinephrine (ADE) was determined in 6 pigs during steady-state anesthesia (1.5% halothane in O2) and steady-state anesthesia plus xylazine (1.1 mg X kg-1 X hr-1; IV infusion) and after either prazosin (alpha 1) or metoprolol (beta 1) adrenergic blockade during halothane-xylazine (H-X) anesthesia. A constant infusion (1, 2, 3, 5, and 10 micrograms X kg-1 X min-1) of freshly mixed epinephrine (100 micrograms X ml-1 in saline solution) was used to determine ADE. The ADE was defined as the total dose of epinephrine which produced 4 or more continuous or intermittent, premature, ventricular contractions within a 15-s period. The mean epinephrine total dose values during 1.5% halothane anesthesia, H-X anesthesia alone, or H-X anesthesia after either prazosin (0.1 mg X kg-1) or metoprolol (0.5 mg X kg-1) adrenergic blockade were 3.60 +/- 0.844, 2.68 +/- 0.402, 11.85 +/- 3.804, and 5.17 +/- 0.587 micrograms X kg-1, respectively. Xylazine administration did not significantly decrease ADE, although mean arterial pressure significantly increased. Prazosin administration significantly increased ADE and was associated with an increased heart rate and a decreased mean arterial pressure. We conclude that alpha 1-blockade with prazosin is more protective to epinephrine-induced arrhythmias in H-X-anesthetized pigs than is beta 1-blockade with metoprolol.

Anesthesia↗

Alterations in the arrhythmogenic dose of epinephrine after xylazine or medetomidine administration in halothane-anesthetized dogs.

Eight dogs (12.5 to 21.5 kg) were assigned at random to each of 3 groups that were not given glycopyrrolate (HS, HX, HM) and to each of 3 groups that were given glycopyrrolate (HGS, HGX, HGM). Dogs were anesthetized with halothane (1.31% end-tidal concentration), and ventilation was controlled (PCO2 35 to 40 mm of Hg end-tidal concentration). Glycopyrrolate was administered IV and IM at a dosage of 11 micrograms/kg of body weight, each. Saline solution, xylazine (1.1 mg/kg, IM), or medetomidine (15 micrograms/kg, IM) was administered 10 minutes after baseline arrhythmogenic dose of epinephrine (ADE) determination. Redetermination of the ADE at the same infusion rate was started 10 minutes after drug administration. Arrhythmogenic dose was determined by constant infusion of epinephrine at rates of 1.0 and 2.5 micrograms/kg/min. The ADE was defined as the total dose of epinephrine inducing at least 4 ectopic ventricular depolarizations within 15 seconds during a 3-minute infusion or within 1 minute after the end of the infusion. Total dose was calculated as the product of infusion rate and time to arrhythmia. Statistical analysis of the differences between baseline ADE and posttreatment ADE for groups HS, HX, and HM was performed by use of one-way ANOVA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

Alterations in the arrhythmogenic dose of epinephrine after xylazine or medetomidine administration in isoflurane-anesthetized dogs.

Eight dogs (body weight, 12.5 to 21.5 kg) were assigned at random to each of 3 treatment groups (IS, IX, IM) that were not given glycopyrrolate and to each of 3 groups that were given glycopyrrolate (IGS, IGX, IGM). Dogs were anesthetized with isoflurane (1.95% end-tidal concentration), and ventilation was controlled (PCO2, 35 to 40 mm of Hg end-tidal concentration). Glycopyrrolate was administered IV and IM at a dosage of 11 micrograms/kg of body weight, each. Saline solution, xylazine (1.1 mg/kg, IM), or medetomidine (15 micrograms/kg, IM) was administered 10 minutes after baseline ADE determination. Redetermination of the ADE at the same infusion rate was started 10 minutes after drug administration. Arrhythmogenic dose was determined by constant infusion of epinephrine at rates of 1.0, 2.5, and 5.0 micrograms/kg/min. The ADE was defined as the total dose of epinephrine that induced at least 4 ectopic ventricular depolarizations within 15 seconds during a 3-minute infusion, or within 1 minute after the end of the infusion. Total dose was calculated as the product of infusion rate and time to arrhythmia. Statistical analysis of the differences between baseline and treatment ADE values was performed by use of one-way ANOVA. Mean +/- SEM baseline ADE values for groups IS, IX, and IM were 1.55 +/- 0.23, 1.61 +/- 0.28, and 1.95 +/- 0.65 micrograms/kg, respectively. Differences for groups IS, IX, and IM were -0.12 +/- 0.05, -0.31 +/- 0.40, and -0.17 +/- 0.26, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

Physicians' decisions to override computerized drug alerts in primary care.

BACKGROUND: Although computerized physician order entry reduces medication errors among inpatients, little is known about the use of this system in primary care. METHODS: We calculated the override rate among 3481 consecutive alerts generated at 5 adult primary care practices that use a common computerized physician order entry system for prescription writing. For detailed review, we selected a random sample of 67 alerts in which physicians did not prescribe an alerted medication and 122 alerts that resulted in a written prescription. We identified factors associated with the physicians' decisions to override a medication alert, and determined whether an adverse drug event (ADE) occurred. RESULTS: Physicians overrode 91.2% of drug allergy and 89.4% of high-severity drug interaction alerts. In the multivariable analysis using the medical chart review sample (n = 189), physicians were less likely to prescribe an alerted medication if the prescriber was a house officer (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08-0.84) and if the patient had many drug allergies (OR, 0.70; 95% CI, 0.53-0.93). They were more likely to override alerts for renewals compared with new prescriptions (OR, 17.74; 95% CI, 5.60-56.18). We found no ADEs in cases where physicians observed the alert and 3 ADEs among patients with alert overrides, a nonsignificant difference (P =.55). Physician reviewers judged that 36.5% of the alerts were inappropriate. CONCLUSIONS: Few physicians changed their prescription in response to a drug allergy or interaction alert, and there were few ADEs, suggesting that the threshold for alerting was set too low. Computerized physician order entry systems should suppress alerts for renewals of medication combinations that patients currently tolerate.

Adult↗

Quality of adverse drug experience reports submitted by pharmacists and physicians to the FDA.

The US Food and Drug Administration (FDA)'s Spontaneous Adverse Experience Reporting System is a computerized database with over one million adverse drug experience (ADE) reports. In 1992, the FDA received over 100,000 ADE reports and pharmacists were major contributors to these reports. In 1993, the FDA launched MEDWatch, a new initiative to enhance direct reporting of adverse events by health professionals. thus far, majority of reports to MEDWatch are from pharmacists. Drug regulatory agencies of some countries do not accept reports submitted by pharmacists. We performed a study to assess the quality of information in ADE reports submitted directly to the FDA by pharmacists and physicians and compared that with manufacturer-channelled 15-day reports. We evaluated 589 ADE reports with serious outcomes associated with nine new molecular entities. Data were analysed using Epi Info. Our results showed no substantial difference in a subjective assessment of the quality of information in the reports submitted by pharmacists or physicians, irrespective of whether these reports were submitted directly or via manufacturers. This study suggests that reports from hospital pharmacists are valuable and of comparable quality. We believe that all health professionals contribute to the success of FDA's MEDWatch programme and thereby play an important part in protecting public health by promptly reporting serious adverse events.

Journal Article↗