Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation.

CONTEXT: Patients who have atrial fibrillation (AF) have an increased risk of stroke, but their absolute rate of stroke depends on age and comorbid conditions. OBJECTIVE: To assess the predictive value of classification schemes that estimate stroke risk in patients with AF. DESIGN, SETTING, AND PATIENTS: Two existing classification schemes were combined into a new stroke-risk scheme, the CHADS( 2) index, and all 3 classification schemes were validated. The CHADS( 2) was formed by assigning 1 point each for the presence of congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus and by assigning 2 points for history of stroke or transient ischemic attack. Data from peer review organizations representing 7 states were used to assemble a National Registry of AF (NRAF) consisting of 1733 Medicare beneficiaries aged 65 to 95 years who had nonrheumatic AF and were not prescribed warfarin at hospital discharge. MAIN OUTCOME MEASURE: Hospitalization for ischemic stroke, determined by Medicare claims data. RESULTS: During 2121 patient-years of follow-up, 94 patients were readmitted to the hospital for ischemic stroke (stroke rate, 4.4 per 100 patient-years). As indicated by a c statistic greater than 0.5, the 2 existing classification schemes predicted stroke better than chance: c of 0.68 (95% confidence interval [CI], 0.65-0.71) for the scheme developed by the Atrial Fibrillation Investigators (AFI) and c of 0.74 (95% CI, 0.71-0.76) for the Stroke Prevention in Atrial Fibrillation (SPAF) III scheme. However, with a c statistic of 0.82 (95% CI, 0.80-0.84), the CHADS( 2) index was the most accurate predictor of stroke. The stroke rate per 100 patient-years without antithrombotic therapy increased by a factor of 1.5 (95% CI, 1.3-1.7) for each 1-point increase in the CHADS( 2) score: 1.9 (95% CI, 1.2-3.0) for a score of 0; 2.8 (95% CI, 2.0-3.8) for 1; 4.0 (95% CI, 3.1-5.1) for 2; 5.9 (95% CI, 4.6-7.3) for 3; 8.5 (95% CI, 6.3-11.1) for 4; 12.5 (95% CI, 8.2-17.5) for 5; and 18.2 (95% CI, 10.5-27.4) for 6. CONCLUSION: The 2 existing classification schemes and especially a new stroke risk index, CHADS( 2), can quantify risk of stroke for patients who have AF and may aid in selection of antithrombotic therapy.

Adverse outcomes and predictors of underuse of antithrombotic therapy in medicare beneficiaries with chronic atrial fibrillation.

BACKGROUND AND PURPOSE: Antithrombotic therapy can prevent strokes and transient ischemic attacks (TIAs) in carefully selected patients who have chronic nonvalvular atrial fibrillation (NVAF). Our objectives were 3-fold: to document the use of warfarin and aspirin therapy in Missouri Medicare beneficiaries with chronic NVAF; to identify factors associated with warfarin and aspirin underuse; and to determine the association between prescription of warfarin and aspirin at hospital discharge and adverse outcomes in this elderly, frail population. METHODS: We linked chart reviews from all Missouri hospitals to Medicare claims data from 1993 to 1996. From chart reviews, we documented Medicare beneficiaries' demographic factors, comorbid conditions, and antithrombotic therapy prescribed at the time of hospital discharge. From Medicare claims, we determined the date of outcomes-death from any cause or hospitalization for an ischemic event (a stroke, a TIA, or a myocardial infarction). RESULTS: Only 328 (55%) of the 597 Medicare beneficiaries were prescribed antithrombotic therapy at hospital discharge: 34% received warfarin and 21% received aspirin. Advanced age, female gender, and rural residency predicted underuse of antithrombotic therapy. After controlling for these factors, as well as stroke risk factors and contraindications to anticoagulation, the prescription of warfarin was associated with a 24% relative risk reduction (RRR) in adverse outcomes (P=0.003). Prescription of aspirin was associated with a nonsignificant 5% RRR in these events (P=0.56). CONCLUSIONS: The underuse of antithrombotic therapy in Medicare beneficiaries who have NVAF is associated with measurable adverse outcomes. The benefit of warfarin therapy may extend to frail, elderly patients, a group that was excluded from randomized controlled trials. The role of antiplatelet therapy in this population deserves further study because many of these patients have relative contraindications to warfarin.

Underutilization of antithrombotic therapy in elderly rural patients with atrial fibrillation.

BACKGROUND: Antithrombotic agents are underutilized in elderly patients with atrial fibrillation. In a peer-review audit of antithrombotic use in Missouri, rural patients were given antithrombotic therapy less often than rural patients for unclear reasons. METHODS AND RESULTS: The charts of 597 hospitalized Medicare patients discharged between October 1, 1993, and December 31, 1994, from urban and rural hospitals in Missouri were reviewed. In addition to antithrombotic therapy prescribed at the time of discharge, patient and physician information, relative contraindications to antithrombotic therapy, and risk factors for stroke were identified. Rural and urban patients were similar in terms of age, sex, and risk factors for stroke. At least one stroke risk factor was noted in 87% of rural patients and in 84% of urban patients. Urban patients were more likely to have a relative contraindication to antithrombotic therapy compared with rural patients (66% vs 54%, P =.04) but received antithrombotic therapy more often (58% vs 47%, P =.02). Cardiologists prescribed antithrombotic therapy significantly more often than noncardiologists (69% vs 52%, P =.003). CONCLUSIONS: Elderly rural patients with atrial fibrillation receive antithrombotic therapy less frequently than urban patients despite having a similar high-risk profile and fewer relative contraindications. Primary care physicians prescribe antithrombotic therapy less often than cardiologists, which is one of the reasons for this underutilization.

Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol.

We have developed a relative binding affinity-serum modified access (RBA-SMA) assay to determine the effect of serum on the access of xenoestrogens to estrogen receptors within intact cultured MCF-7 human breast cancer cells. We used this assay to predict low dose activity of two xenoestrogens in mice. In serum-free medium, bisphenol A, a component of polycarbonates and of resins used to line metal food cans, showed a lower relative binding affinity (RBA; 0.006%) than octylphenol (0.072%) and nonylphenol (0.026%), which are used as surfactants in many commercial products (all RBAs are relative to estradiol, which is equal to 100%). In 100% serum from adult men, bisphenol A showed a higher RBA (0.01%) than in serum-free medium and thus enhanced access to estrogen receptors relative to estradiol. In contrast, octylphenol showed a 22-fold decrease in RBA (0.0029%) and nonylphenol showed a 5-fold decrease in RBA (0.0039%) when measured in adult serum. This indicates that, relative to estradiol, serum had less of an inhibitory effect on the cell uptake and binding in MCF-7 cells of bisphenol A, while serum had a greater inhibitory effect on octylphenol and nonylphenol relative to estradiol. Extrapolation of these relative activities in adult serum predicted that the estrogenic bioactivity of bisphenol A would be over 500-fold greater than that of octylphenol in fetal mouse serum. Bisphenol A and octylphenol were fed to pregnant mice at 2 and 20 micrograms/kg/day. Exposure of male mouse fetuses to either dose of bisphenol A, but to neither dose of octylphenol, significantly increased their adult prostate weight relative to control males, which is consistent with the higher predicted bioactivity of bisphenol A than octylphenol in the RBA-SMA assay. In addition, our findings show for the first time that fetal exposure to environmentally relevant parts-per-billion (ppb) doses of bisphenol A, in the range currently being consumed by people, can alter the adult reproductive system in mice.

Opportunities for improving the care of patients with community-acquired pneumonia.

In Missouri, community-acquired pneumonia is the second leading cause of hospital admission in the Medicare population. Analysis of 1993 discharges revealed that more than 18,000 Medicare patients were admitted to acute care hospitals with a principal diagnosis of pneumonia. Statewide, the case fatality rate for these admissions was 9.6%, with an average length of stay of 8.2 days. Under the auspices of Medicare's Health Care Quality Improvement Program, the Missouri Patient Care Review Foundation (MPCRF) collaborated with five hospitals in the state on a project to enhance the outcomes and quality of care for patients admitted with community-acquired pneumonia. Narrowing the focus to bacterial community-acquired pneumonia, the five hospitals agreed to collect data, for a specified period, on each Medicare patient admitted with this diagnosis. The hospitals were encouraged to implement recommended critical pathways and guidelines for the initial management and treatment of community-acquired pneumonia. MPCRF assumed responsibility for data management activities for the project as well as production of feedback reports that were shared routinely with the hospitals. Although evaluation of the project continues, preliminary analysis of claims data for admissions occurring after process changes were implemented indicates that there has been improvement in the two outcome measures, patient mortality and length of stay. These results suggest that monitoring of key process indicators, coupled with ongoing analysis and feedback, has potential for facilitating positive change in the quality of care for patients with community acquired pneumonia.

Nest defense and survival of offspring in highly aggressive wild Canadian female house mice.

Nest defense behavior was examined in wild female house mice (Mus domesticus) that were derived from a stock initially trapped in Alberta, Canada. The first objective was to determine whether behavior toward pups prior to mating was related to the intensity of postpartum aggression in a variety of social situations. Therefore, prior to the experiments we screened virgin females for their behavior toward a newborn pup [60% of the females exhibited infanticide and 40% were noninfanticidal: 7% were parental (retrieved and hovered over the pup) and 33% ignored the pup]. Infanticidal and noninfanticidal females were then mated with males and used in four experiments. In Experiment 1 the females were housed individually prior to deliver, while in Experiment 2 the females were allowed to remain with their mates; in both situations all females successfully reared litters of similar sizes. Male and female intruders (that had all exhibited infanticide when previously tested with a pup) were placed separately into a test cage containing a lactating female during the first four days after delivery. Regardless of the presence of the stud male, previously infanticidal females were more aggressive (exhibited more attacks per min) toward both male and female intruders than were previously noninfanticidal females; infanticidal females also exhibited more of both forms of attack (offensive and defensive) and also attacked with greater intensity than did noninfanticidal females. The number of attacks toward intruders of both sexes increased for both infanticidal and noninfanticidal females between Day 1-4 postpartum, but very high rates of attack were observed on all days by the lactating females, including the day of delivery. In Experiments 3 and 4 only the most aggressive (previously infanticidal) females were tested. In Experiment 3, two unrelated, unfamiliar females were mated separately and then were housed together just prior to delivery, which was planned to occur 3-4 days apart. In 5 of the 15 cages, all pups disappeared on the day of delivery of the second female to deliver her litter. In the remaining 10 cages, it appeared that none of the pups produced by the 20 females were killed. Thus, in this experiment, 66% of pups survived to Day 4 postpartum. In Experiment 4, two previously infanticidal female siblings, which had been housed together since birth, were placed together with a stud male. In all 9 cages only one female became pregnant and delivered pups, but only 3 litters survived to Day 4 (no litters were observed being attacked during intruder tests).(ABSTRACT TRUNCATED AT 400 WORDS)

Estrogenic pesticides: binding relative to estradiol in MCF-7 cells and effects of exposure during fetal life on subsequent territorial behaviour in male mice.

Numerous chemicals released into the environment by man are able to disrupt the functioning of the endocrine system by binding to estrogen receptors in estrogen-responsive cells. The ability of o,p'-dichlorodiphenyl trichloroethane (DDT) and methoxychlor to compete with estradiol for binding to estrogen receptors in MCF-7 cells (relative binding affinity; RBA) was examined in both serum-free medium and 100% serum; this is referred to as a relative binding affinity-serum modified access (RBA-SMA) assay. RBA's ranged from 0.04% for o,p'-DDT (which showed enhanced access to cells in serum relative to serum-free medium) to 0.004% for methoxychlor (which did not show enhanced access in serum). Based on these findings, these pesticides, along with diethylstilbestrol (DES) as a positive control, were fed to pregnant mice from days 11-17 of pregnancy. When the male offspring were examined in adulthood for their rate of urine marking in a novel territory (territorial behaviour), the rate of urine marking increased dramatically with low doses of DES (relative to controls) and then decreased significantly at the highest dose administered prenatally. Relative binding in MCF-7 cells accurately predicted the doses of o,p'-DDT and methoxychlor that produced the same results, providing support for the hypothesis that effects on behaviour were mediated by binding to estrogen receptors in the developing brain.