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PubMed2006

Automated surveillance for adverse drug events at a community hospital and an academic medical center.

OBJECTIVES: To compare the rates and nature of ADEs at an academic medical center and a community hospital using a single computerized ADE surveillance system. DESIGN: Prospective cohort study of patients admitted to two tertiary care hospitals. Outcome Measure Adverse drug events identified by automated surveillance and voluntary reporting. METHODS: We implemented an automated surveillance system across an academic medical center and a community hospital. Potential events identified by the computer were reviewed in detail by medication safety pharmacists and scored for causality and severity. Findings were compared between the two hospitals, and with voluntary reports from nurses and pharmacists. RESULTS: Over the 8 month study period, 25,177 patients were admitted to the university hospital and 8,029 to the community hospital. There were 1,116 ADEs in 900 patients at the university hospital for an overall rate of 4.4 ADEs per 100 admissions. At the community hospital, 399 patients experienced 501 ADEs for a rate of 6.2 events per 100 admissions. Rates of antibiotic-associated colitis, drug-induced hypoglycemia, and anticoagulation-related ADEs were significantly higher at the community hospital compared with the university hospital. Computerized surveillance detected ADEs at a rate 3.6 times that of voluntary reporting at the university hospital and 12.3 times that at the community hospital. CONCLUSIONS: Operation of a common automated ADE surveillance system across hospitals permits meaningful comparison of ADE rates in different inpatient settings. Automated surveillance detects ADEs at rates far higher than voluntary reporting, and the difference may be greater in the community hospital setting. Community hospitals may experience higher rates of certain types of ADEs compared with academic medical centers.

Academic Medical Centers↗

PubMed2007

Emergency department visits caused by adverse drug events: results of a French survey.

BACKGROUND: Adverse drug events (ADEs) are a substantial cause of hospital admissions. However, little is known about the incidence, preventability and severity of ADEs resulting in emergency department visits. To address this issue, we conducted a prospective survey in emergency departments of French public hospitals. METHODS: This study was performed over two periods of 1 week each, one in June 1999 and one in December 1999, in emergency departments of five university hospitals and five general hospitals throughout France. All patients aged>or=15 years presenting with medical complaints were included in the study. Trauma patients, those with gynaecological conditions and those with alcohol intoxication or intentional drug poisoning were excluded from the study. Each patient was assessed by two local emergency physicians to determine whether the visit was the result of an ADE. All medical records were subsequently validated by an independent group of medical lecturers in iatrogenic disorders. RESULTS: Out of a total of 1937 patients consulting, 1562 were taking at least one drug during the previous week and were included for analysis; 328 (21%; 95% CI 19, 23) of these patients consulted an emergency physician because of an ADE. Patients with ADEs were older than those without (mean age 63.5 vs 54.8 years; p<0.0001). Furthermore, ADE patients were more likely to have a higher severity presentation than the non-ADE group (p=0.019). The number of drug exposures was significantly higher in patients with an ADE than in those without (mean number of medications 5.17 vs 3.82; p<0.0001). On multivariate analysis, only age and the number of medications taken were significantly associated with adverse events. In total, 410 drugs were incriminated in the occurrence of 328 ADEs. The most frequently incriminated drug classes were: (i) psychotropic agents (n=84; 20.5%); (ii) diuretics (n=48; 11.7%), anticoagulants (n=38; 9.3%) and other cardiovascular drugs (n=63; 15.4%); and (iii) analgesics, including NSAIDs (n=57; 13.9%). Preventability could be assessed in 280 of the 328 cases. In 106 cases (37.9%), the ADE was judged to be preventable. CONCLUSION: ADEs leading to emergency department visits are frequent, and many are preventable, confirming that there is a need to develop prevention strategies.

Adult↗

PubMed2003

Cost of opioid-related adverse drug events in surgical patients.

Opioids have demonstrated efficacy and often are drugs of choice in the management of postoperative pain. However, their use is often limited by adverse drug events (ADEs). The objective of this study was to determine the ADE rate in adult surgical patients who received opioids and the impact of opioid ADEs on length of stay (LOS), costs, and mortality. A hospital-based computerized system detected potential ADEs. Adult patients were selected if they received at least one dose of opioid medication during a surgical hospitalization between 1 January 1990 and 31 December 1999. Control patients were matched based on matching length of stay ([LOS] at least as long as time to ADE), age (within 10 years), sex, admission year, major disease category (MDC), and without an ADE. Linear regression models were used to determine the predictors of increased LOS, total hospital costs, and log-transformed total hospital costs. 60,722 patients received opioid medication during their surgical hospitalization and 2.7% experienced an opioid-related ADE. The most common clinical manifestations were nausea and vomiting (67%), and rash, hives, or itching (33.5%). No statistically significant difference was seen in mortality between ADE/non-ADE patients. ADE patients had statistically significant increases in LOS (0.53 days) and in log-transformed cost (16%). The estimated log cost difference of 16%, if applied to the median cost patient in the non-ADE group, averaged US$ 840. Opioid-related ADEs are common in hospitalized patients and increase LOS and total hospital costs.

Economics, Pharmaceutical↗

PubMedDate not supplied

[Prevalence and factors associated with preventable adverse drug events leading to hospital admission].

OBJECTIVE: To determine the prevalence of adverse drug events (ADEs) leading to hospital admission, and to assess those that were potentially preventable, identifying the drug classes involved, types of medication errors and the factors associated with the preventable ADEs. METHOD: An observational study, over a six-month period on ADEs that lead or contributed to hospital admissions, carried out in 6 medical units of a university hospital. RESULTS: A total of 259 ADEs were detected of which 159 (61.4%) were assessed to be potentially preventable. The overall prevalence of admissions directly due to ADEs was of 6.7% (177) and to preventable ADEs of 4.7% (125). In addition, 82 ADEs that contributed to hospital admission were detected. Risk factors for preventable ADEs were patient age of 65-74 (OR = 1.40) or = 75 years (OR = 2.70), self-medication (OR = 15.55), prescription in primary care (OR = 2,88) and the use of narrow therapeutic index drugs (OR = 2.40). The drug classes most frequently involved in preventable ADEs were NSAID and aspirin (32.5%), diuretics (15.3%), antihypertensives (9.1%) and digoxin (7.7%). Inadequate therapy monitoring (20.7%), prescription of an inappropriate drug (15.7%) or of an excessive dosage (12.0%), lack of preventive treatment (15.7%), non-adherence (10.6%) and inappropriate self-medication (10.1%) were the most commonly identified types of error. CONCLUSIONS: A high proportion (4.7%) of hospital admissions are caused by potentially preventable ADEs. Results obtained justified the need to adopt measures directed at improving surveillance and prescription quality, and educating patients in safe drug use, focusing especially on older patients and narrow therapeutic index drugs.

Aged↗

PubMedDate not supplied

Adverse drug events as a cause of hospital admission in the elderly.

BACKGROUND: Previous studies of adverse drug events (ADE) as a cause of hospital admission in the elderly have often been limited in their ability to assess fully the impact and potential for prevention because they either did not include all categories of ADE and/or did not assess severity and preventability. AIMS: To assess the frequency, severity and preventability of ADE causing emergency medical admissions in the elderly. METHODS: Cross-sectional survey of 219 patients aged 75 years and over who were consecutive unplanned admissions to acute medical units of the Royal Hobart Hospital in an 8-week period during August and September 1998. RESULTS: Seventy-three of 240 (30.4%) admissions may have been a result of ADE. Patients admitted because of ADE were taking more drugs than those admitted for other reasons. Most ADE were adverse drug reactions to a single (46%) or multiple drugs (25%). Non-compliance, omission or cessation of indicated treatment accounted collectively for 26% of admissions. Of all ADE admissions 53.4% were considered definitely preventable. The commonest causative drugs were cardiovascular drugs (48.4%), and the commonest manifestations were falls and postural hypotension (24.1%), heart failure (16.9%) and delirium (14.5%). ADE categories in which a high proportion of admissions was both severe and definitely preventable were non-compliance and omission of indicated treatment. CONCLUSIONS: Adverse drug events are a common preventable cause of unplanned medical admissions in the elderly. Non-compliance and omission of indicated treatment are causes of ADE-related admissions that are both preventable and frequently associated with severe ADE.

Aged↗

PubMed1997

Adverse drug events in high risk older outpatients.

OBJECTIVE: To describe the prevalence, types, and consequences of adverse drug events (ADEs) in older outpatients with polypharmacy. DESIGN: A cohort study. SETTING: General Medicine Clinic at the Durham Veterans Affairs Medical Center. PATIENTS: A total of 167 high risk (taking > or = 5 scheduled medications) ambulatory older veterans who participated in a year long health service intervention trial. MEASUREMENTS: Potential ADEs were identified by asking patients during closeout interviews whether, in the past year, they had experienced any side effects, unwanted reactions, or other problems from any medication. All reported medications and corresponding adverse experiences were assessed for plausibility by a research clinical pharmacist using two standard pharmacological textbooks and categorized by predictability, therapeutic class, and organ system. RESULTS: Eighty self-reported ADEs involving 72 medications taken by 58 (35%) of 167 patients were textbook confirmed. Seventy-six of 80 (95%) ADEs were classified as Type A (predictable) reactions. Cardiovascular (33.3%) and central nervous system (27.8%) medication classes were most commonly implicated. Gastrointestinal (30%) and central nervous system (28.8%) ADE symptoms were common. Sixty-three percent of patients with ADEs required physician contacts, 10% emergency room visits, and 11% hospitalization. Twenty percent of medications implicated with ADEs required dosage adjustments, and 48% of ADE-related medications were discontinued. No significant differences (P > .05) were observed when ADE reporters (n = 58) and nonreporters (n = 109) were compared. CONCLUSION: Predictable ADEs are common in high risk older outpatients, resulting in considerable medication modification and substantial healthcare utilization.

Aged↗

PubMed1994

Preventing adverse drug events in hospitalized patients.

OBJECTIVE: To use computerized adverse drug event (ADE) surveillance to help identify methods to reduce the number of ADEs in hospitalized patients. DESIGN: Prospective study of 79,719 hospitalized patients during a 44-month period. SETTING: LDS Hospital, a 520-bed tertiary care center affiliated with the University of Utah School of Medicine, Salt Lake City. INTERVENTION: Sequential study periods of at least one year each were compared. In the first period, data were collected but not reported to physicians, pharmacists, or nurses. In the subsequent study periods, three interventions (computerized alerts of drug allergies, standardized antibiotic administration rates, and timely physician notification of all ADEs) were made to reduce the number of type B (allergic or idiosyncratic reactions) and severe ADEs. RESULTS: In the first study period, we identified 56 type B ADEs during 120,213 patient days. During two subsequent study periods that included alerts to physicians of known drug allergies and standardized antibiotic administration rates, 8 type B events were identified during 113,237 patient days and 18 during 107,868 patient days, respectively (p < 0.002). Early notification of physicians of all confirmed ADEs regardless of severity was associated with a significant reduction of ADEs classified as severe from 41 during 113,859 patient days in the first study period to 12 during 103,071 patient days and 15 during 108,320 patient days in two subsequent study periods, respectively (p < 0.001). CONCLUSIONS: Prospective surveillance of computer-based medical records for known drug allergies and appropriate drug administration rates can reduce the number of type B ADEs. Early ADE detection and notification of physicians permit drug and dosage changes that reduce the progression of mild and moderate ADEs to more severe conditions.

Adverse Drug Reaction Reporting Systems↗

PubMed1999

Relationship between adenosine-induced vascular effects and ATP-sensitive K+ channels.

AIM: To study the relationship between adenosine (Ade) receptors and adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels in rat aorta. METHODS: Isolated rat aorta rings were suspended for isometric force recording. The vascular effects of Ade were assessed in the presence or absence of functional endothelium. The interactions of Ade and pinacidil (Pin) or glibenclamide (Gli) were investigated. RESULTS: In isolated aorta preconstricted with KCl 20 mmol.L-1, Ade 3-300 mumol.L-1 induced relaxation in a concentration-dependent manner; and in 48/99 preparations from 32 rats, Ade induced initial transient constriction followed by sustained relaxation. When the functions of KATP channels were blocked with Gli 1 or 100 mumol.L-1, effects of Ade were characterized by vasoconstriction rather than vasorelaxation. The combination of Pin 1 mumol.L-1 with Ade 100 mumol.L-1 showed no synergic vasodilatory effects and did not affect Ade-induced vasoconstriction. After the removal of endothelium, Ade still induced vasoconstriction and vasorelaxation, and the constrictive effects showed no difference from those in the presence of endothelium, but the potency of vasodilatory effects became weaker with slower decrease in tension. CONCLUSION: The activation of KATP channels is involved in Ade receptor-induced vasodilation.

Adenosine↗

PubMed2000

Alcohol deprivation effect is prolonged in the alcohol preferring (P) rat after repeated deprivations.

BACKGROUND: The alcohol deprivation effect (ADE) is a temporary increase in the ratio of ethanol/total fluid intake and the voluntary intake of ethanol solutions over baseline drinking conditions when ethanol access is reinstated after a period of alcohol deprivation. The ADE has been posited to be an animal model for alcohol craving. The current study examined the effects of initial deprivation length and number of deprivation exposures on the ADE in alcohol-preferring (P) rats. METHODS: Adult female P rats received 24-hr free-choice access to 10% (v/v) ethanol and water for 6 weeks. Rats were then randomly assigned to five groups deprived of ethanol for 0 (control), 2, 4, 6, or 8 weeks (W). All deprived groups were then given 24-hr access to ethanol for 2 weeks before being deprived of ethanol for another 2 weeks. RESULTS: After the initial ethanol deprivation period, the deprived groups displayed a similar 2-fold ADE (e.g., 4-W group; 4.6 +/- 0.5 for baseline vs. 10.5 +/- 0.3 g/kg/day for the 1st reinstatement day) during the initial 24-hr period. Ethanol consumption began to return to control levels 48 (7.1 +/- 0.4 g/kg/day) and 72 (6.4 +/- 0.4 g/kg/day) hrs later. In addition, each deprived group showed increases in the ratio of ethanol/total fluid intake upon reinstatement, and there was a tendency for sustained higher ethanol intake ratios during the first 3 postexposure days for the 4-, 6-, and 8-W groups, but only during the first 2 reinstatement days for the 2-W group. The second deprivation did not increase the magnitude of the ADE over that observed in the first deprivation during the initial 24-hr period of re-exposure, but it did prolong the duration of the ADE into the 2nd and 3rd reinstatement day for the 2-, 4-, and 6-W groups and into the 5th reinstatement day for the 8-W group. CONCLUSIONS: Equivalent robust ADEs can be seen in P rats with deprivation periods of 2-8 W, which suggests that the ADE has a rapid onset and is not affected by the durations of deprivation that were tested. The duration of the ADE was prolonged in P rats exposed to a second deprivation period, suggesting that factors associated with the ADE phenomenon could be strengthened by repeated deprivations.

Alcohol Drinking↗

PubMed2000

The expression of an alcohol deprivation effect in the high-alcohol-drinking replicate rat lines is dependent on repeated deprivations.

BACKGROUND: The alcohol deprivation effect (ADE) is a temporary increase in the ratio of alcohol/total fluid intake and voluntary intake of ethanol (EtOH) solutions over baseline drinking conditions when EtOH access is reinstated after a period of alcohol deprivation. The ADE has been posited to be an animal model for alcohol craving. In the current study, we examined the effects of initial deprivation length and number of deprivation exposures on the ADE in the replicate lines of the high-alcohol-drinking (HAD) rats. METHODS: Adult male HAD-1 and HAD-2 rats received 24 hr free-choice access to 10% (v/v) EtOH and water for 6 weeks. Rats were then assigned to groups deprived of EtOH for 0 (control), or 2 to 8 weeks. All deprived groups were then given 24 hr access to EtOH for 2 weeks before being deprived of EtOH for another 2 weeks. This cycle of 2 weeks of access and 2 weeks of deprivation was carried out for a total of four deprivations. RESULTS: After the initial EtOH deprivation period, EtOH consumption in HAD-1 and HAD-2 rats returned to baseline levels but failed to exhibit either an early onset ADE (initial 2 hr) or prolonged ADE (24 hr). An ADE was observed in two of the four deprived groups for the HAD-1 rats (2 week and 6 week groups) and in all deprived groups for the HAD-2 rats after a second deprivation, and in all deprived groups of both lines after a third deprivation. In the HAD-2 line, but not in the HAD-1 line, the duration of the ADE was prolonged into the second reinstatement day after the fourth deprivation. CONCLUSIONS: The expression of an ADE was observed only after repeated deprivation periods in the HAD lines. The duration of the ADE was prolonged in the HAD-2 line, but not in the HAD-1 line, with repeated deprivations, which suggests a dissociation between selection for alcohol preference and the effects of repeated deprivations on the duration of the ADE.

Alcohol Drinking↗

PubMed2005

Assessing the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project--six sites, United States, January 1-June 15, 2004.

Adverse drug events (ADEs) occur when therapeutic drugs have injurious effects; current systems for conducting national ADE surveillance are limited, and current national estimates of ADE incidence are problematic. In 2003, CDC, in collaboration with the Consumer Product Safety Commission (CPSC) and the Food and Drug Administration (FDA), created the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance (NEISS-CADES) project by adding active surveillance of ADEs to the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP). Because ADEs can be more difficult to identify than other injuries, an independent chart review in a sample of six NEISS-CADES hospitals was conducted to evaluate the sensitivity and predictive value positive (PVP) of ADE identification. This report describes the results of that evaluation, which indicated that although PVP for ADEs was high, the sensitivity was low, particularly for certain types of ADEs. As a result of these findings, additional training on identifying and reporting ADEs was initiated for all NEISS-CADES hospital coders. As more persons in the United States use drug therapies, active, postmarketing surveillance of ADEs can help identify safety problems and guide prevention efforts.

Adverse Drug Reaction Reporting Systems↗

PubMed2026

Nonclinical investigation of the potential of MHAA4549A, an anti-influenza A therapeutic antibody, to mediate antibody-dependent enhancement.

Antibody-dependent enhancement (ADE) of infection and disease is a theoretical safety risk for antiviral antibodies against seasonal viruses with antigenic drift, such as influenza. ADE of infection may occur if virus-specific antibodies at subtherapeutic, nonneutralizing concentrations facilitate virus uptake, thus potentially enhancing virus replication. In contrast, ADE of disease reflects exacerbation of viral disease severity through viral replication-dependent or -independent mechanisms. Because of the theoretical concern of ADE, nonclinical safety assessment of therapeutic anti-influenza antibodies includes a thorough evaluation of ADE potential. The current set of studies was conducted to investigate the potential of MHAA4549A-a broadly specific, neutralizing, therapeutic anti-influenza A antibody-to elicit ADE of infection and disease of influenza H3N2 A/Aichi/2/68 (X31) across a broad dose range. Assessment of ADE was based on totality of results from both in vitro and mouse influenza studies with integration across study endpoints. In vitro studies demonstrated that MHAA4549A can mediate increased X31 entry into human and murine monocytic cells, but increased uptake did not result in enhanced viral replication or release under physiologic conditions. In a mouse model of X31 infection, intravenous administration of MHAA4549A resulted in delayed body weight recovery, but no exacerbation in orthogonal endpoints including mortality, lung viral titers or genomes, lung weights, or severity of influenza pneumonia. Overall, the totality of nonclinical data did not demonstrate any clear indication of ADE of infection at nonneutralizing concentrations, suggesting a low risk for MHAA4549A to cause enhanced influenza A-mediated disease at subtherapeutic doses.

Animals↗

PubMed2006

Medication reconciliation for reducing drug-discrepancy adverse events.

BACKGROUND: Medication reconciliation is a technique for identifying discrepancies in drug regimens prescribed in different care settings or at different time points to inform prescribing decisions and prevent medication errors. OBJECTIVE: This study examined the effect of pharmacist-conducted medication reconciliation on the occurrence of discrepancy-related adverse drug events (ADEs) associated with drugs ordered at the time of a resident's return from the hospital to the nursing home. METHODS: This was a preintervention/postintervention study conducted in a consecutive sample of residents of a 514-bed, urban, not-for-profit nursing home who were hospitalized in its primary referral hospital, an 1171-bed academic tertiary care hospital, and returned to the nursing home between December 2002 and January 2005. In the intervention phase, a pharmacist conducted a reconciliation of drugs ordered on return to the nursing home with those received before hospitalization, and communicated prescribing discrepancies to the physician. The primary outcome was the occurrence of discrepancy-related ADEs, as ascertained by a review of the medical records performed by 2 independent physician raters. RESULTS: During the study period, 168 nursing home residents had 259 hospital stays. The reconciliation intervention identified 696 total prescribing discrepancies, of which physicians responded to 598 (85.9%). Among the 112 cases selected for ADE ascertainment, 11 discrepancy-related ADEs were identified, 1 in the postintervention group and 10 in the preintervention group, for an incidence of 2.3% and 14.5%, respectively (relative risk, 0.16; 95% CI, 0.02-1.2; P = NS). After adjustment for baseline ADE risk, the odds of having a discrepancy-related ADE were significantly lower in the postintervention group compared with the preintervention group (odds ratio, 0.11; 95% CI, 0.01-1.0; P = 0.05). The most commonly identified discrepancy-related ADE was pain from the omission of an analgesic (3/11 [27.3%]), and antibiotics and analgesics were the most common causes of discrepancy-related ADEs (each, 3/11 [27.3%]). CONCLUSIONS: Pharmacist medication reconciliation and communication with the physician reduced discrepancy-related ADEs in these patients transferred between the hospital and nursing home. Studies are needed to identify the most efficient ways of carrying out this task and to adapt the reconciliation process to all care settings.

Aged, 80 and over↗

PubMed2002

Adverse drug events in emergency department patients.

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

Adolescent↗

PubMed2002

Suppression of lipopolysaccharide-induced antiviral transcription factor (STAT-1 and NF-kappa B) complexes by antibody-dependent enhancement of macrophage infection by Ross River virus.

Subneutralizing concentrations of antibody may enhance virus infection by bringing the virus-antibody complex into contact with the cell surface Fc receptors; this interaction facilitates entry of virus into the cell and is referred to as antibody-dependent enhancement (ADE) of infection. Northern analysis of macrophage RNA demonstrated that ADE infection by the indigenous Australian alphavirus Ross River (RRV-ADE) ablated or diminished message for tumor necrosis factor alpha (TNF-alpha), nitric-oxide synthase 2 (NOS2), and IFN regulatory factor 1 (IRF-1), as well as for IFN-inducible protein 10 (IP-10) and IFN-beta; the transcription of a control gene was unaffected. Additionally, electrophoretic mobility-shift assay (EMSA) studies showed that transcription factor IFN-alpha-activated factor (AAF), IFN-stimulated gene factor 3 (ISGF3), and nuclear factor-kappaB (NF-kappaB) complex formation in macrophage nuclear extracts were specifically suppressed post-RRV-ADE infection, emphasizing the capacity for ADE infections to compromise antiviral responses at the transcriptional level. The suppression of antiviral transcription factor complexes was shown to depend on replicating virus and was not simply a result of general antibody-Fc-receptor interaction. Although only a minority of cells ( approximately 15%) were shown to be positive for RRV by immunostaining techniques post ADE, molecular (RT-PCR) analysis showed that unstained cells carried RRV-RNA, indicating a higher level of viral infectivity than previously suspected. Electron microscopy studies confirmed this observation. Furthermore, levels of cellular IL-10 protein were dramatically elevated in RRV-ADE cultures. This evidence demonstrates that RRV can potently disrupt the activation of specific antiviral pathways via ADE infection pathways, and may suggest a significant mechanism in the infection and pathogenesis of other ADE viruses.

Alphavirus Infections↗

PubMed1990

Conformational preferences of modified nucleic acid bases N6-methyl-N6-(N-threonylcarbonyl) adenine and 2-methylthio-N6-(N-threonylcarbonyl) adenine by the quantum chemical PCILO calculations.

Conformational preferences of the hypermodified nucleic acid bases N6-methyl-N6-(N-threonylcarbonyl) Adenine, m6tc6 Ade, and 2-methylthio-N6-(N-threonylcarbonyl) Adenine, mS2 tc6 Ade, have been studied theoretically using the quantum chemical PCILO (Perturbative Configuration Interaction using Localized Orbitals) method. The multidimensional conformational space has been searched using selected grid points formed by combining the various torsion angles which take the favoured values obtained from energy variation with respect to each torsion angle individually. In m6 tc6 Ade and mS 2tc6 Ade alike the threonylcarbonyl substituent preferably orients away (distal) from the imidazole moiety of the adenine ring. And as in the simpler N6-(N-threonylcarbonyl) Adenine, tc6 Ade, the atoms in the ureido group as well as the amino acid carbon atoms C(12) and C(13) remain coplanar with the purine base. As in tc6 Ade, this conformation is stabilized by the intramolecular hydrogen bond between N(11)H of the amino acid and N(1) of the adenine base. The N6-methyl protons, in m6 tc6 Ade, take trans-staggered orientation with respect to the C(6)-N(6) bond. The preferred orientation of the 2-methylthio group is cis to the C(2)-N(3) bond in mS 2tc6 Ade. This is in marked contrast to the modified nucleic acid base 2-methylthio-N6-(delta 2-isopentenyl) Adenine, mS 2i6 Ade, where the 2-methylthio group orients trans to the C(2)-N(3) bond, causing a change in the preferred orientation of the isopentenyl component on methylthiolation. The present results thus indicate that unlike in the isopentenyl adenine the role of further chemical substitutions in threonylcarbonyl adenine may be indirect and less pronounced.

Adenine↗

PubMed2000

Identifying drug safety issues: from research to practice.

PURPOSE: Adverse drug events (ADEs), or injuries due to drugs, are common and often preventable. However, identifying ADEs, potential ADEs, and medication errors can be a major challenge. In this review, we describe methodologies that have been used to identify these events and give strategies for identification in non-study settings. RESULTS: Methods such as voluntary reporting, chart review, and computerized monitoring for events have been most commonly used in studies of ADEs in inpatients. However, voluntary reporting, the method most hospitals currently use, has a very low yield of events. Chart review is much more sensitive but the costs are prohibitive. Computerized monitoring for ADEs (using rules or triggers) is a high yield and relatively inexpensive strategy that should be adopted by organizations. A limitation of this strategy, however, is that it identifies few medication errors and potential ADEs, which are also important. These can be captured through pharmacy logs, chart review, and direct observation. Once events have been identified, they can be classified by type of event, severity, and preventability. In non-study settings, the most practical method for identifying ADEs is computerized monitoring, and for identifying prescribing errors it is pharmacy logs of interventions. Once problems are found, a structure (either individual or committee) must be in place to classify them, identify opportunities for improvement, and carry out the necessary changes. CONCLUSIONS: Health care organizations have the technology to significantly improve their detection of ADEs, medication errors, and potential ADEs. Identification and subsequent classification of events is crucial for quality efforts to improve patient safety.

Adverse Drug Reaction Reporting Systems↗

PubMed2006

Characteristics of extrinsic vs. intrinsic atopic dermatitis in infancy: correlations with laboratory variables.

BACKGROUND: Atopic dermatitis (AD) has been divided into the extrinsic type (ADe) and the intrinsic type (ADi) according to the serum IgE levels and the presence or absence of allergen-specific IgE. Although previous studies have demonstrated differences in the various immunological parameters, the characteristics of AD in infancy have rarely been reported. OBJECTIVES: Our study was performed to analyse the correlations between the laboratory parameters of infantile ADe and ADi. METHODS: We recruited 237 infants with AD and checked the SCORAD index, the number of peripheral blood eosinophils, the serum eosinophil cationic protein (ECP) levels, the total serum IgE levels and the specific serum IgE levels in all the patients. We also checked the serum interleukin (IL)-4 and IL-5 levels in 20 patients with ADe and in 20 with ADi. RESULTS: This study showed many peculiar characteristics of infantile AD. In infancy, ADi was more prevalent than ADe. The eosinophil count, the ECP level and the SCORAD in ADi were lower than in ADe. Furthermore, a group of patients without characteristics of ADi or ADe could be identified. We tentatively classify this group as indeterminate type (ADind) and propose it as a separate entity. The clinical severity was well correlated with the eosinophil count and the serum ECP levels in ADe and ADi. Therefore these two parameters could be used as clinical severity markers in infancy. Infants are more allergic to food, and the variety of specific allergenic responses was connected with clinical severity. A higher eosinophil count, a higher ECP level and a higher detection rate of IL-5 in the peripheral blood of infants with ADe means that eosinophils have a more prominent role in ADe than in ADi. CONCLUSIONS: Infantile AD has many distinctive features in its laboratory variables as compared with AD in other age groups. Clinicians should recognize these facts when they deal with infants with AD, and further studies are warranted on the natural course of infantile AD.

Allergens↗