Objectives: To gather information on patient‐level factors associated with risk of adverse drug events (ADEs) that may allow focus of prevention efforts on patients at high risk.
Design: Nested ...case‐control study.
Setting: Large multispecialty group practice in New England.
Participants: All Medicare enrollees cared for by a multispecialty group practice during 1 year (N=30,397 person‐years from July 1, 1999, through June 30, 2000). For each patient with an ADE, a control was randomly selected.
Measurements: Data were ed from medical records on age, sex, comorbidities, and medication use at the time of the event.
Results: ADEs were identified in 1,299 older adults. Independent risk factors included being female and aged 80 and older. There were dose‐response associations with the Charlson Comorbidity Index and number of scheduled medications. Patients taking anticoagulants, antidepressants, antibiotics, cardiovascular drugs, diuretics, hormones, and corticosteroids were at increased risk. In the analysis of preventable ADEs, the dose‐response relationship with comorbidity and number of medications remained. Patients taking nonopioid analgesics (predominantly nonsteroidal antiinflammatory drugs and acetaminophen), anticoagulants, diuretics, and anti‐seizure medications were at increased risk.
Conclusion: Prevention efforts to reduce ADEs should be targeted toward older adults with multiple medical conditions or taking multiple medications, nonopioid analgesics, anticoagulants, diuretics, and antiseizure medications.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Glomerular-derived proteins may activate tubular cells to express the macrophage-directed chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2). Macrophages at interstitial sites have a central ...role in directing renal scarring. We have prospectively assessed the relationship between albuminuria, urinary MCP-1/CCL2, interstitial macrophage infiltration, in situ damage, and clinical outcomes in a large group of patients with chronic kidney disease. We studied 215 patients and quantified albumin–creatinine ratio (ACR), urinary MCP-1/CCL2, interstitial macrophage numbers, and in situ damage. ACR correlated with urinary MCP-1/CCL2 (correlation 0.499; P<0.001), interstitial macrophage numbers (correlation 0.481; P<0.001), and index of chronic damage (correlation 0.363; P<0.001). Macrophage numbers closely correlated with in situ damage (correlation 0.755; P<0.001). By multivariate analysis ACR, urinary MCP-1/CCL2, and interstitial macrophage numbers were interdependent. By Kaplan–Meier survival analysis albuminuria, urinary MCP-1/CCL2, interstitial macrophages, and chronic damage predict the outcome. ACR, macrophage numbers, chronic damage, and creatinine independently predicted renal survival. The association of ACR with other variables was strongest in patients with less advanced disease states. There is a close association between albuminuria, urinary MCP-1/CCL2, and interstitial macrophage infiltration with in situ damage and clinical outcomes. These findings support the hypothesis that albuminuria triggers tubular MCP-1/CCL2 expression with subsequent macrophage infiltration. These processes may represent the dominant pathway for the progression of renal injury before the establishment of advanced renal scarring
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rheology and turbidity measurements were performed under similar thermal histories to probe the relationship between thermoreversible gelation and phase separation for a set of three methylcellulose ...(MC) materials with similar degrees of substitution (DS) and contrasting molecular weights after hydration in cold water. Frequency-independent loss tangents were used to identify the gel point (T gel) in MC solutions well over the chain overlap concentration (c ≥ 10c*). Transmittance of 633 nm laser light through the solutions revealed that all MC solutions cloud upon gelling, with a relative transmittance of 86% closely associated with the gel point. The gelation temperature of MC solutions was found to decrease with increasing MC concentration and the results for all molecular weights superposed. Using gel and cloud points, a phase diagram was constructed which reveals that clear MC solutions transition directly into turbid gels. Frequency-independent storage moduli of fully developed MC gels scaled with φ2.3, consistent with theory and experiment of entangled systems. Gelation of MC has strong dependence on heating rate while the melting of the gel has little dependence on cooling rate, suggesting that thermogelation of MC proceeded by a nucleation and growth mechanism rather than spinodal decomposition.
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IJS, KILJ, NUK, PNG, UL, UM
CONTEXT: Adverse drug events, especially those that may be preventable, are among the most serious concerns about medication use in older persons cared for in the ambulatory clinical setting. ...OBJECTIVE: To assess the incidence and preventability of adverse drug events among older persons in the ambulatory clinical setting. DESIGN, SETTING, AND PATIENTS: Cohort study of all Medicare enrollees (30 397 person-years of observation) cared for by a multispecialty group practice during a 12-month study period (July 1, 1999, through June 30, 2000), in which possible drug-related incidents occurring in the ambulatory clinical setting were detected using multiple methods, including reports from health care providers; review of hospital discharge summaries; review of emergency department notes; computer-generated signals; automated free-text review of electronic clinic notes; and review of administrative incident reports concerning medication errors. MAIN OUTCOME MEASURES: Number of adverse drug events, severity of the events (classified as significant, serious, life-threatening, or fatal), and whether the events were preventable. RESULTS: There were 1523 identified adverse drug events, of which 27.6% (421) were considered preventable. The overall rate of adverse drug events was 50.1 per 1000 person-years, with a rate of 13.8 preventable adverse drug events per 1000 person-years. Of the adverse drug events, 578 (38.0%) were categorized as serious, life-threatening, or fatal; 244 (42.2%) of these more severe events were deemed preventable compared with 177 (18.7%) of the 945 significant adverse drug events. Errors associated with preventable adverse drug events occurred most often at the stages of prescribing (n = 246, 58.4%) and monitoring (n = 256, 60.8%), and errors involving patient adherence (n = 89, 21.1%) also were common. Cardiovascular medications (24.5%), followed by diuretics (22.1%), nonopioid analgesics (15.4%), hypoglycemics (10.9%), and anticoagulants (10.2%) were the most common medication categories associated with preventable adverse drug events. Electrolyte/renal (26.6%), gastrointestinal tract (21.1%), hemorrhagic (15.9%), metabolic/endocrine (13.8%), and neuropsychiatric (8.6%) events were the most common types of preventable adverse drug events. CONCLUSIONS: Adverse drug events are common and often preventable among older persons in the ambulatory clinical setting. More serious adverse drug events are more likely to be preventable. Prevention strategies should target the prescribing and monitoring stages of pharmaceutical care. Interventions focused on improving patient adherence with prescribed regimens and monitoring of prescribed medications also may be beneficial.
To assess the incidence of and risk factors for adverse drug events in the long-term care setting.
We performed a cohort study of all long-stay residents of two academic long-term care facilities ...over a period of up to 9 months during 2000 to 2001. We assessed the number of adverse drug events, the severity of events (classified as less serious, serious, life threatening, or fatal), and whether the events were preventable. A case-control study was nested within the prospective study to identify resident-level risk factors for the occurrence of adverse drug events.
There were 815 adverse drug events, of which 42% were judged preventable. The overall rate of adverse drug events was 9.8 per 100 resident-months, with a rate of 4.1 preventable adverse drug events per 100 resident-months. Errors associated with preventable events occurred most often at the stages of ordering and monitoring. Residents taking medications in several drug categories were at increased risk of a preventable adverse event. In multivariate analyses, the adjusted odds ratio was 3.4 (95% confidence interval CI: 2.0 to 5.9) for those taking antipsychotic agents, 2.8 (95% CI: 1.6 to 4.7) for those taking anticoagulants, 2.2 (95% CI: 1.2 to 4.0) for those taking diuretics, and 2.0 (95% CI: 1.1 to 3.7) for those taking antiepileptics.
Our findings reinforce the need for a special focus on the ordering and monitoring stages of pharmaceutical care for preventing adverse drug events in the long-term care setting. Patients taking antipsychotic agents, anticoagulants, diuretics, and antiepileptics are at increased risk.
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GEOZS, IJS, NUK, OILJ, UL, UM
Depsipeptide, FR901228, has demonstrated potent in vitro and in vivo cytotoxic activity against murine and human tumor cell lines. In the laboratory, it has been shown to be a histone deacetylase ...(HDAC) inhibitor. In a phase I trial of depsipeptide conducted at the National Cancer Institute, 3 patients with cutaneous T-cell lymphoma had a partial response, and 1 patient with peripheral T-cell lymphoma, unspecified, had a complete response. Sézary cells isolated from patients after treatment had increased histone acetylation. These results suggest that inhibition of HDAC is a novel and potentially effective therapy for patients with T-cell lymphoma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sex differences in locomotor performance may precede the onset of sexual maturity and/or arise concomitantly with secondary sex characteristics. Here, we present the first study to quantify the ...terrestrial locomotor morphology, energetics and kinematics in a species, either side of sexual maturation. In domestic leghorn chickens (Gallus gallus domesticus) sexual maturation brings about permanent female gravidity and increased male hind limb muscle mass. We found that the sexes of a juvenile cohort of leghorns shared similar maximum sustainable speeds, while in a sexually mature cohort maximum sustainable speeds were greater by 67% (males) and 34% (females). Furthermore, relative to that in juveniles of the same sex, the absolute duration of leg swing was longer in mature males and shorter in mature females. Consequently, the proportion of a stride that each limb was in contact with the ground (duty factor) was higher in sexually mature females compared to males. Modulation of the duty factor with the development of secondary sex characteristics may act to minimize mechanical work in males; and minimise mechanical power and/or peak force in females. A greater incremental response of mass-specific metabolic power to speed in males compared to females was common to both age cohorts and, therefore, likely results from physiological sexual dimorphisms that precede sexual maturation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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