Janis F. Yao

Observational safety study of febrile convulsion following first dose MMRV vaccination in a managed care setting

BACKGROUND A combined measles, mumps, rubella, varicella live vaccine (MMRV, Merck and Co., Inc., US) was recently licensed in the US. Pre-licensure clinical trial data showed a significant increase in fever in days 5-12 following MMRV vaccination as compared to the vaccines given separately (MMR+V). This post-licensure retrospective cohort study was undertaken to assess the incidence of febrile convulsion following MMRV. METHODS Children ages 12-60 months who received a first dose of MMRV in February 2006-June 2007 in a managed care organization were included in the study. Subjects were optimally matched on age, sex, and calendar date of vaccination to children who received MMR+V concomitantly in November 2003-January 2006, before MMRV licensure. Potential cases of febrile convulsion were identified through administrative data and adjudicated by expert panel, according to pre-specified criteria. RESULTS During the 30 days post-vaccination, there were 128 and 94 potential convulsion cases among the 31,298 children in the MMRV and MMR+V cohorts, respectively. After review of available medical charts and adjudication, there were 84 cases of confirmed febrile convulsion, 44 (1.41/1000) and 40 (1.28/1000) in the MMRV and MMR+V cohorts, respectively (RR=1.10, 95% CI=0.72, 1.69). In days 5-12 following vaccination, a pre-specified period of interest, the respective numbers were 22 (0.70/1000) and 10 (0.32/1000) (RR=2.20, 95% CI=1.04, 4.65). CONCLUSION These data suggest that the risk of febrile convulsion is increased in days 5-12 following vaccination with MMRV as compared to MMR+V given separately during the same visit, when post-vaccination fever and rash are also increased in clinical trials. While there was no evidence of an increase in the overall month following vaccination, the elevated risk during this time period should be communicated and needs to be balanced with the potential benefit of a combined vaccine.

Esophageal food impaction: epidemiology and therapy. A retrospective, observational study.

Background: Esophageal food impaction is common, but incidence data are lacking and management is controversial. This is a survey of its epidemiology, endoscopic findings, and treatment. Methods: A retrospective study was conducted of 194 adults with 223 episodes of esophageal food impaction in a health maintenance organization. Of these, 192 (99%) patients were followed a median of 31 months (range 1-72) post-disimpaction. Results: The estimated annual incidence rate of episodes was 13.0 per 100,000, and the male:female ratio was 1.7:1. The rate increased with age, especially after the seventh decade. The bolus was meat in 189 (85%) episodes. Flexible esophagoscopy was performed initially in 222 (99.6%) episodes and permitted disimpaction in 218 (98%). The push technique was used alone or in combination with extraction in 186 (84%). Immediate dilation was performed in 172 (79%). There were no major complications. A final diagnosis was made in 171 (88%), including 151 (78%) with a Schatzki’s ring or peptic stricture, and the diagnosis had changed during follow-up in 14 (7%). A diagnosis of Schatzki’s ring was associated with gender (p = 0.03) and decreased with increasing age (p = 0.003), especially among women. Conclusions: Esophageal food impaction is common and can nearly always be treated safely with flexible esophagoscopy, usually with the push technique. (Gastrointest Endosc 2001;53:193-8.)

Epidemiology, Clinical Features, High-Risk Factors, and Outcome of Acute Large Bowel Ischemia

BACKGROUND & AIMS Only a limited amount of important information is available on acute lower bowel ischemia (ALBI). We investigated the epidemiology, clinical aspects, high-risk factors, and outcome of ALBI. METHODS We retrospectively analyzed data collected from 401 patients with 424 hospitalizations with ALBI in a prepaid health system for 7 years. RESULTS The estimated annual incidence of ALBI was 15.6/100,000 patient-years (22.6 female, 8.0 male), with a marked age-related increase. ALBI preceded 400 admissions (94%) and followed surgery or medical admission of 24 patients (6%); 307 (72%) had rectal bleeding and abdominal pain. In 417 episodes, left-sided or transverse (368, 88%) exceeded right-sided or bilateral ALBI (49, 12%). Thirty-one patients (8%) had resection; 15 died (4%). Factors that were independently associated with resection and/or death included right-sided or bilateral distribution (adjusted odds ratio [AOR], 14.64; 95% confidence interval [CI], 4.82-44.50; P < .001), onset after admission (AOR, 7.48; 95% CI, 2.19-25.54; P < .005), hypotension (AOR, 4.45; 95% CI, 1.18-16.76; P < .05), tachycardia (AOR, 4.40; 95% CI, 1.46-13.26; P < .01), warfarin use (AOR, 4.33; 95% CI, 1.21-15.47; P < .05), antibiotic therapy (AOR, 3.94; 95% CI, 1.23-12.64; P < .05), male sex (AOR, 2.65; 95% CI, 1.00-7.05; P = .05), nonsteroidal anti-inflammatory drug use (AOR, 0.15; 95% CI, 0.04-0.53; P < .005), and rectal bleeding (AOR, 0.24; 95% CI, 0.09-0.65; P < .005). During a mean of 2.6 +/- 1.9 years, no patient developed chronic colitis, and 1 (<1%) had stricture dilation. Estimated ALBI recurrence was 3%, 5%, 6%, and 10% at years 1, 2/3, 4, and 5/6, respectively. CONCLUSIONS ALBI is common and agerelated and predominates in female patients. Demographic and clinical variables predict severe ALBI. Chronic sequelae are rare. Recurrence is substantial.

Racial/Ethnic differences in ischemic stroke rates and the efficacy of warfarin among patients with atrial fibrillation.

Background and Purpose— Warfarin reduces stroke risk in studies of predominantly white patients with atrial fibrillation (AF). Whether nonwhites also have lower rates of stroke while treated with warfarin is unclear. Methods— A multiethnic stroke-free cohort hospitalized with nonrheumatic AF was identified in a large health maintenance organization. Stroke risk factors (advanced age, diabetes, hypertension, and heart failure), warfarin use, and anticoagulation intensity were assessed. Crude ischemic stroke rates were calculated by Poisson regression for each group while using and not using warfarin. Cox proportional hazard models were constructed to assess the independent effect of race/ethnicity on ischemic stroke. Results— Between 1995 and 2000, we identified 18 867 AF hospitalizations (78.5% white, 8% black, 9.5% Hispanic, and 3.9% Asian). Over the course of 63 204 person-years follow-up (median, 3.3 years), 1226 ischemic strokes were identified. The percent-time on warfarin did not differ by race/ethnicity. The median percent-time on warfarin that international normalized ratio was 2 to 3 was 54.5% overall, but it was lower in blacks at 47.8%, whereas the other groups had a rate of ≈54%. The rate ratios (95% CI) of ischemic stroke with warfarin compared to without warfarin for whites, blacks, Hispanics, and Asians were 0.79 (0.68 to 0.90), 0.92 (0.65 to 1.30), 0.71 (0.48 to 1.05), and 0.65 (0.34 to 1.23), respectively. Conclusions— In this cohort, we did not observe a statistically significant lower rate of stroke with warfarin therapy among nonwhites (in particular blacks) with previous AF hospitalizations. The relatively small numbers of nonwhites renders our estimates less than precise and should be interpreted with caution.

Fuzzy decision making for medical diagnosis based on fuzzy number and compositional rule of inference

Abstract Klir and Yuan [2] mentioned the medical decision making problem in chapter 17. In this paper we use interval estimation to get fuzzy number r ij and from point estimation we get r ij . Set R =(r ij ) and R ∗ =( r ij ) . Let fuzzy relation of the set P of the patients and the set S of the symptoms be Q =(a ij ) and fuzzy relation of the set S of the symptoms and the set~ D of the diseases be R . From the compositional rule of inference, we have T = Q ∘ R . Therefore, we can have a fuzzy decision making for medical diagnosis. This paper changes R to R ∗ and use T ∗ = Q ∘ R ∗ to do a fuzzy decision making for medical diagnosis.

Diseases and Drugs That Increase Risk of Acute Large Bowel Ischemia

BACKGROUND & AIMS Information is limited on risk factors for acute large bowel ischemia (ALBI). We investigated diseases and drugs associated with ALBI. METHODS We compared patients hospitalized with ALBI and controls through multivariate analysis of prior outpatient/emergency department/inpatient diagnoses and pharmacy dispensing records. RESULTS There were 379 cases and 1516 controls (median age, 69 y; range, 25-97 y; 74.4% female). Disorders that were diagnosed in more cases than controls, based on univariate analysis (P < .05), included hypertension, diabetes, chronic obstructive pulmonary disease, atrial fibrillation, congestive heart failure, depression, asthma, coronary artery disease, dementia, rheumatoid arthritis, irritable bowel syndrome, dialysis dependency, diarrhea, and constipation. Drugs dispensed to more cases than controls were antihypertensives, opioids, statins, female hormones, potentially constipating drugs, histamine H(2)-antagonists, immunomodulators, digoxin, clopidogrel/ticlopidine, taxanes/vinca alkaloids, and antibiotics. In all cases, ALBI was associated independently with hypertension (adjusted odds ratio [AOR], 3.21, 95% confidence interval [CI]; 2.28-4.53; P < .0001), chronic obstructive pulmonary disease (AOR, 3.13; 95% CI, 2.06-4.75; P < .0001), diarrhea (AOR, 2.36; 95% CI, 1.13-4.89; P = .0218), atrial fibrillation (AOR, 2.21; 95% CI, 1.34-3.64; P = .0019), congestive heart failure (AOR, 1.94; 95% CI, 1.11-3.39; P = .0205), diabetes (AOR, 1.82; 95% CI, 1.31-2.53; P = .0004), antibiotics (AOR, 3.30; 95% CI, 2.19-4.96; P < .0001), opioids (AOR, 1.96; 95% CI, 1.43-2.67; P < .0001), and potentially constipating drugs (AOR, 1.75; 95% CI, 1.25-2.44; P = .0012). Analysis of only women revealed similar associations except for diarrhea plus rheumatoid arthritis (AOR, 3.27; 95% CI, 1.07-9.96; P = .0370), irritable bowel syndrome (AOR, 2.72; 95% CI, 1.04-7.14; P = .0424), and female hormones (AOR, 1.88; 95% CI, 1.30-2.73; P = .0009). CONCLUSIONS Heterogeneous diseases and drugs increase the risk of ALBI, consistent with multifactorial pathogenesis.

Effect of Race/Ethnicity on the Efficacy of Warfarin : Potential Implications for Prevention of Stroke in Patients with Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice. It affects approximately 6% of persons over 65 years of age and is independently associated with a 4-to 5-fold higher risk of ischaemic stroke and a 2-fold higher risk of death. Randomized controlled trials have shown that treatment with adjusted-dose oral vitamin K antagonists (primarily warfarin with a target international normalized ratio [INR] of 2.0–3.0) reduces the relative risk of ischaemic stroke by two-thirds (an approximately 3% reduction in annual absolute risk), but is associated with a 0.2% excess annual absolute risk of intracranial haemorrhage (ICH). However, in ‘real world’ studies, the risk reductions in ischaemic stroke with warfarin have been significantly lower (25–50% relative risk reduction) than in selected trial samples. Moreover, more than 90% of patients enrolled in the sentinel trials were White/European. This raises the question of whether the beneficial results of warfarin can be extrapolated to persons of colour. Important differences in stroke risk profile and responsiveness to warfarin exist across racial/ethnic groups, such that one cannot assume a priori that there is a net benefit of warfarin therapy for AF patients of all racial/ethnic groups.Among patients with ischaemic stroke, AF is more likely to be implicated as the cause of stroke in the White population than in other racial/ethnic groups. Furthermore, AF may be a stronger predictor of ischaemic stroke among the White population than in Black or Hispanic/Latino populations. Approximately one-third of strokes in AF patients are noncardioembolic. Warfarin has been shown to be ineffective in preventing recurrent noncardioembolic strokes. Many persons of colour with AF have other risk factors that predispose them to noncardioembolic stroke, which may partially explain why warfarin has been reported to be less efficacious in preventing strokes in non-White patients with AF, even after adjustment for co-morbidities and anticoagulation monitoring. Notably, the background incidence of ICH is higher in Black, Hispanic and Asian patients than in White patients. Any greater than expected increases in bleeding secondary to anticoagulation may potentially offset any benefit gained from cardioembolic stroke reduction, although this has not been fully resolved.Finally, there are racial/ethnic differences in the prevalence of certain polymorphisms in genes that influence warfarin pharmacokinetics and pharmaco-dynamics (e.g. cytochrome P450 2C9 and vitamin K epoxide reductase). The Asian population generally appear to require the lowest daily dose of warfarin to maintain a given INR target, with the White population requiring an intermediate daily dose and the Black population requiring the highest daily dose. These differences must be taken into account when administering warfarin in order to minimize the risk of under-or over-anticoagulation.In summary, warfarin is highly effective in preventing ischaemic strokes in White patients with AF at a modestly higher risk of ICH. Whether the same net clinical benefit extends to persons of colour is unproven. Given the rapidly changing demographic nationally and internationally, additional research is needed to resolve this important question.

Agreement between medical record and parent report for evaluation of childhood febrile seizures.

BACKGROUND The monitoring of vaccine safety is critical to maintaining the public acceptance of vaccines required to ensure their continued success. Methods used to assess adverse events following immunization (AEFI) must accurately reflect their occurrence. Assessment of AEFI is often done via medical record review (MR) or via patient report (PR). However, these sources of data have not previously been compared for the analysis of AEFI. The objective of this study was to evaluate the concordance between MR and PR for young children identified as having had a febrile seizure (FS), an important AEFI, in an integrated health care system. The variables chosen for analysis were those recommended by the Brighton Collaboration Seizure Working Group for the evaluation of generalized seizure as an AEFI [1]. METHODS Parent report from phone interviews and mailed questionnaires was compared to abstracted medical records of 110 children with FS between ages 3 and 60 months. Concordance between PR and MR for characteristics and predisposing factors of FS was assessed by percent total agreement and kappa statistic. RESULTS Percent total agreement between PR and MR was between 43.6 and 100% for variables studied, with 62.5% of items having >70% agreement. However, kappa was poor to fair for all measures (-0.04 to 0.33). While some variables, such as history of seizures in a sibling or parent and several seizure characteristics, were reported more often by PR, other items, such as maximum fever and several concurrent conditions, were reported more often by MR. CONCLUSION These findings demonstrate the limitations of using MR or PR alone to assess febrile seizures in children. This analysis supports the practice of collecting data from both MR and PR to most accurately portray the spectrum of predisposing factors and seizure characteristics when evaluating FS in children whenever feasible.

Implantable Defibrillators for Secondary Prevention of Sudden Cardiac Death in Cardiac Surgery Patients With Perioperative Ventricular Arrhythmias

Background Randomized studies of implantable cardioverter defibrillators (ICD) have excluded sudden cardiac death survivors who had revascularization before or after an arrhythmic event. To evaluate the role of ICD and the effects of clinical variables including degree of revascularization, we studied cardiac surgery patients who had an ICD implanted for sustained perioperative ventricular arrhythmias. Methods and Results The electronic database for Southern California Kaiser Foundation hospitals was searched for patients who had cardiac surgery between 1999 and 2005 and an ICD implanted within 3 months of surgery. One hundred sixty‐four patients were identified; 93/164 had an ICD for sustained pre‐ or postoperative ventricular tachycardia or fibrillation requiring resuscitation. Records were reviewed for the following: presenting arrhythmia, ejection fraction, and degree of revascularization. The primary end point was total mortality (TM) and/or appropriate ICD therapy (ICD‐T), and secondary end points are TM and ICD‐T. During the mean follow up of 49 months, the primary endpoint of TM+ICD‐T and individual end points of TM and ICD‐T were observed in 52 (56%), 35 (38%), and 28 (30%) patients, respectively, with 55% of TM, and 23% of ICD‐T occurring within 2 years of implant. In multivariate risk analysis, none of the following was associated with any of the end points: incomplete revascularization, presenting ventricular arrhythmia, and timing of arrhythmias. Conclusion Our data supports the recent guidelines for ICD in this cohort of patients, as the presence of irreversible substrate and triggers of ventricular arrhythmias, cannot be reliably excluded even with complete revascularization. Further studies are needed to understand this complex group of patients.

Influence of Vascular Access Type on Sex and Ethnicity-Related Mortality in Hemodialysis-Dependent Patients

OBJECTIVES To determine whether sex- and ethnicity-based mortality differences in patients dependent on hemodialysis (hemodialysis patients) are because of prevalence of vascular access type. METHODS Southern California Permanente Medical Group Renal Database, which contained 5821 chronic hemodialysis patients between 2000 and 2008, was studied. RESULTS Mean age of the patients was 62 years, and 59% were male. Of the population, 33% were white; 32%, Hispanic; 23%, African American; 9%, Asian/Pacific Islander; and 3%, other race or ethnicity. Predominant access type over the course of the study was arteriovenous fistula (AVF) in 73%, arteriovenous graft (AVG) in 12%, and tunneled catheter in 14%. There was a higher percentage of AVF in whites (71%) than in African Americans (63%). Risk of death was independently increased by age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.04-1.05), male sex (HR, 1.33; 95% CI, 1.22-1.45), diabetes (HR, 1.22; 95% CI, 1.12-1.33), use of an AVG (HR, 1.51; 95% CI, 1.34-1.71) or a tunneled catheter (HR, 6.45; 95% CI, 5.78-7.20). Compared with whites, African-American race decreased the risk of death (HR, 0.63; 95% CI, 0.56-0.70), as did Asian/Pacific Islander (HR, 0.58; 95% CI, 0.49-0.69), Hispanic (HR, 0.58; 95% CI, 0.51-0.65), and other race (HR, 0.67; 95% CI, 0.52-0.86). CONCLUSION Age, sex, race or ethnicity, access type, and diabetes are independent risk factors for mortality in hemodialysis patients. After controlling for potential confounders, when compared with whites, minorities all demonstrate significantly decreased risk of mortality. African Americans had reduced mortality risk despite a lower prevalence of arteriovenous fistula compared with whites. Male sex increased mortality. Differences in mortality between sexes and ethnicities in this population cannot be accounted for by differences in type of dialysis access.