Farmer, Sara A.

AbstractIntroductionConventional Z‐scores are generated by subtracting the mean and dividing by the standard deviation. More recent methods linearly correct for age, sex, and education, so that these “adjusted” Z‐scores better represent whether an individual's cognitive performance is abnormal. Extreme negative Z‐scores for individuals relative to this normative distribution are considered indicative of cognitive deficiency.MethodsIn this article, we consider nonlinear shape constrained additive models accounting for age, sex, and education (correcting for nonlinearity). Additional shape constrained additive models account for varying standard deviation of the cognitive scores with age (correcting for heterogeneity of variance).ResultsCorrected Z‐scores based on nonlinear shape constrained additive models provide improved adjustment for age, sex, and education, as indicated by higher adjusted‐R2.DiscussionNonlinearly corrected Z‐scores with respect to age, sex, and education with age‐varying residual standard deviation allow for improved detection of non‐normative extreme cognitive scores.

Abstract Abstract 1241 Background: Hospitalization (with or without surgery) is a major risk factor for incident venous thromboembolism (VTE); however, the contribution of interim hospitalization to risk of recurrent VTE is unknown. Objective: To estimate risk of recurrent VTE related to interim hospitalization by conducting a population-based longitudinal review of provider-linked detailed medical records. Methods: We performed a nested case-cohort study. The cohort consisted of all Olmsted County residents with incident VTE 1988–2000 and ≥1 day follow-up. Cases were cohort members with recurrent VTE. Subjects were followed for all interim hospitalizations and warfarin use from incident VTE until earliest of emigration, death, recurrent VTE, or 12/31/2005. Data were analyzed using Cox proportional hazards and time dependent covariates to test for the effects of interim hospitalization and prophylaxis on VTE recurrence, adjusting for gender and age at incident VTE. Analyses were limited to subjects who survived free of death and recurrent VTE for ≥ 6 months. Results: Of 1262 incident VTE events (cohort), there were 309 VTE recurrences (cases). We randomly sampled 272 subjects from the cohort and 163 cases. Of the random samples, 210 incident events and 83 cases survived ≥ 6 months free of death and recurrent VTE and form our analysis population. The rate of secondary (interim) prophylaxis was approximately 50% for both incident events and cases, and was not predictive of recurrence (p=0.73). Male gender and interim hospitalization were associated with increased VTE recurrence even after adjusting for age at incident VTE and use of secondary warfarin prophylaxis. The hazard of recurrent VTE was nearly 10-fold higher for subjects with interim hospitalization versus those with none (HR: 9.6; 95% CI: 6.6, 13.8); men had a 1.5-fold increased recurrence rate compared with women (HR: 1.5; 95% CI: 1.1, 2.1). Conclusions: Our results, for the first time, show the importance of interim hospitalization as a predictor of VTE recurrence. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Recent trends in the incidence of venous thromboembolism (VTE), including idiopathic vs. non-idiopathic VTE, have not been well described. Objective: To estimate the incidence of deep vein thrombosis (DVT) and pulmonary embolism with or without DVT (PE), and describe trends in incidence. Methods: Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN residents with an incident DVT and PE over the 35-year period, 1966–2000 (n=3342). For all cases, the complete medical records in the community were reviewed for demographic and baseline characteristics previously identified as risk factors for VTE. Generalized linear models assuming a Poisson error structure, and using a log link function, and a log (population) offset will be used to assess the relationship of crude incidence rates to gender, year of diagnosis and age at diagnosis. Results: The overall average age- and sex-adjusted annual VTE incidence was 122 per 100,000 person-years (DVT, 56 per 100,000; PE, 66 per 100,000), with higher age-adjusted rates among men than women (134 versus 115 per 100,000, respectively). VTE incidence rates increased exponentially with age for both genders, ranging from 4 to 1110 per 100,000 for age groups 0–19 to 90–110 years. Compared to the 5-year period, 1981–85 (when non-invasive diagnostic testing became routinely available), the overall VTE incidence through 2000 remains unchanged. However, the DVT incidence and the PE incidence significantly increased and decreased, respectively, adjusting for age and gender (p<0.001 for both). The overall age- and sex-adjusted annual incidence of idiopathic VTE was 11.7 per 100,000 person-years (DVT, 6.6 per 100,000; PE, 5.1 per 100,000), with age-adjusted rates also higher among men than women (15.1 vs. 9.1 per 100,000). Interestingly, again compared to 1981–85, idiopathic VTE incidence decreased for 1991–95 (p=0.001) and 1996–2000 (p=0.32), adjusting for age and gender. Idiopathic DVT incidence decreased for 1991–95 (p=0.09), and idiopathic PE incidence decreased for both 1991–95 (p=0.004) and 1996–2000 (p=0.03). The overall age- and sex-adjusted annual incidence of non-idiopathic VTE was 109.4 per 100,000 (DVT, 48.4 per 100,000; PE, 60.7 per 100,000), again, with age-adjusted rates higher in men than women (115.1 vs. 106.8 per 100,000). Non-idiopathic DVT incidence increased steadily since 1981–85 (p=0.006, p<0.001, and p<0.001 for increasing DVT incidence for 1986–1990–1991–1995–1996–2000, respectively, adjusting for age and gender). Non-idiopathic PE incidence, however, remained unchanged for 1986–2000. Conclusions: VTE remains a major national health problem, especially among the elderly. Despite improved VTE prophylaxis efficacy and utilization, the overall incidence of VTE remains unchanged. However, the decreasing incidence of idiopathic DVT, and particularly idiopathic PE (with its associated poor survival) raises the possibility that the total number of VTE(PE)-related deaths may also be decreasing, albeit slightly. This hypothesis requires formal testing. The increasing or steady incidence of non-idiopathic DVT and PE, respectively, suggests the need for more widespread, effective VTE prophylaxis.

Background: The standard allergen series used in patch testing contains metals that most commonly cause allergic contact dermatitis, but testing with additional metal allergens is warranted for select patients. Objective: To report our experience with patch testing of metals. Methods: We retrospectively analyzed outcomes of 1,112 patients suspected of having metal allergies. Patients were seen from January 1, 2000, through December 31, 2009. Patch testing was performed with 42 metal preparations (6 in the standard series, 36 in the metal series). Results: Patch testing most commonly was performed for patients with oral disease (almost half the patients), hand dermatitis, generalized dermatitis, and dermatitis affecting the lips, legs, arms, trunk, or face. At least one positive reaction was reported for 633 patients (57%). Metals with the highest allergic patch-test reaction rates were nickel, gold, manganese, palladium, cobalt, Ticonium, mercury, beryllium, chromium, and silver. Metals causing no allergic patch-test reactions were titanium, Vitallium, and aluminum powder. Metals with extremely low rates of allergic patch-test reactions included zinc, ferric chloride, and tin. Reaction rates varied depending on metal salt, concentration, and timing of readings. Conclusion: Many metals not in the standard series were associated with allergic patch-test reactions. The many questions raised by these findings, concerning patch testing with individual metals, will be the subject of future studies.

Background: Hairdressing chemicals may be associated with allergic contact dermatitis. Objective: To review our experience of patch-testing with hairdressing chemicals. Methods: We reviewed results from patients who underwent patch testing with our standard allergen series (including 15 hairdressing chemicals) and a supplementary “hairdresser series” (18 additional hairdressing chemicals) at Mayo Clinic (Rochester, MN; Scottsdale, AZ; and Jacksonville, FL) from January 1, 2000, through December 31, 2008. Results: Two hundred ten patients (mean age, 53.8 years [SD, 16.9 yr]; female, 94.8%) were patch-tested. The most common sites of dermatitis were the scalp, face, and hands. Patients had widely varying occupations. The most common occupations were cosmetologist (10.5%), housewife (9.5%), and beautician (5.2%); 14.3% were retired. The hairdresser series detected 13 additional patients with allergies (6.4%; 204 patients tested with both series) who would not have been detected with the standard allergen series alone. The highest allergic patch-test rates in the supplemental hairdresser series were with ammonium persulfate (14.4%), 4-aminoazobenzene (13.4%), and pyrogallol (9.1%). Conclusions: Patch-testing with hairdressing-specific chemicals (standard series plus supplemental hairdresser series) was appropriate for numerous clinical situations and was not limited to patients in hair care occupations. The supplemental hairdresser series helped identify more patients than would have been identified with the standard series alone.

Background: Few US studies have reported results of patch testing with plastics and glues. Objective: To report our institution's results of testing patients suspected of allergy to plastics and glues with a comprehensive plastics and glues series and to compare these results with previously published data. Methods: Retrospective review of results of patch-testing with plastics and glues allergens at our institution between 2000 and 2007. In total, 444 patients were patch-tested with up to 56 plastics and glues allergens in the specialized series and up to five plastics and glues allergens in a baseline series. Positive-reaction rates were compared to other patch testing reports. Results: Of patients, 97 (22%) had irritant reactions, and 201 (45%) had at least one allergic reaction. Bis(2-dimethylaminoethyl) ether 1%, benzoyl peroxide 1%, epoxy resin, bisphenol F 0.25%, 2-hydroxyethyl methacrylate 2%, and 2-hydroxyethyl acrylate 0.1% had the highest allergy reaction rates. Testing with specialized series identified 193 patients with plastics and glues allergy, of whom 162 were not identified by testing with baseline series alone. Conclusion: For patients suspected of allergy to plastics and glues, patch-testing with specialized series of plastics and glues allergens is an important adjunct to patch-testing with baseline series.

Background: Allergic contact dermatitis from rubber chemicals is increasingly recognized. Objective: To review the results of patch testing with rubber allergens from January 1, 2000, through December 31, 2007. Methods: Patients who underwent patch testing with a specialized series of rubber allergens were identified. Results: In total, 773 patients (64.2% female; mean age, 48.6 years) were patch-tested with a rubber series (27 allergens), and 739 (95.6%) were concomitantly patch-tested with a standard allergen series. Commonly affected sites of dermatitis were the hand (49.7%), foot (15.9%), leg (12.0%), and arm (10.9%). The most common occupations were health care worker (16.3%) and homemaker (6.5%); 11.3% were retired. The rate of allergic reaction to at least one rubber allergen was 245 of 773 (31.7%). The allergens that most commonly yielded positive reactions were 4,4-dithiodimorpholine 1% (28/286 [9.8%]), thiuram mix (56/739 [7.6%]), and diphenylguanidine 1% (57/759 [7.5%]). Conclusion: Rubber is a frequent cause of allergic contact dermatitis. Patch testing with a rubber series improved the ability to diagnose allergic contact dermatitis caused by rubber.

Background: Delayed hypersensitivity reactions to natural rubber latex (NRL) have been recognized. These reactions may contribute to allergic contact dermatitis. We therefore have undertaken patch testing of patients with NRL if they are suspected to have allergic contact dermatitis to rubber. Objective: To review results of patch testing with NRL (January 1, 2000, through December 31, 2007). Methods: Patients suspected of having allergic contact dermatitis from rubber who underwent patch testing with NRL were identified retrospectively. For safety reasons, patients with immediate hypersensitivity to NRL were excluded from patch testing. Results: Of 148 patients patch-tested with NRL, 3 (2.0%) had an allergic patch-test reaction. Conclusions: NRL is as common a cause of allergic contact dermatitis as many of the other allergens included in a specialized rubber allergen series. Patients suspected to be allergic to rubber should be patch-tested with NRL (provided they do not have type 1 hypersensitivity to NRL).

Objective To evaluate survival in patients after radical cystectomy ( RC ) who presented with non‐muscle‐invasive urothelial carcinoma and progressed to muscle invasion during surveillance. Our secondary objective was to evaluate the association between clinical factors before RC and survival. Patients and Methods In all, 981 consecutive M ayo C linic RC patients without a history of radiation or systemic chemotherapy were reviewed. Of these, 190 had RC after they progressed from non‐muscle invasive disease to muscle invasion (progressed to ≥ pT2 ). These patients were compared to 310 patients who had RC before muscle invasion (≤ pT1 ), and 481 patients who had muscle invasion at initial presentation (presented with ≥ pT2 ). Survival estimates were generated using the K aplan– M eier method and compared using the log‐rank test, while adjusted analyses were performed using C ox proportional hazard regression models. Results Patients who progressed to muscle invasion on surveillance had a higher risk of death than patients who initially presented with muscle invasion (overall survival hazard ratio [ HR ] 1.3; 95% confidence interval [ CI ] 1.0, 1.5). The estimated 5‐year cancer‐specific survival was 85.4% for patients presenting with ≤ pT1 , 52.9% for patients who progressed to ≥ pT2 , and 62.4% for patients who presented with ≥ pT2 ( P < 0.001). The corresponding 5‐year overall survival rates were 70.0%, 42.1%, and 49.5% ( P < 0.001). Of the patients who initially presented with non‐muscle‐invasive disease, progression to muscle invasion was associated with increased risk of cancer‐specific death (adjusted HR 2.38; 95% CI 1.6, 3.5). Lack of information about patients who presented without muscle invasion and never received RC is the major limitation of this study. Conclusions Despite close surveillance, many patients who progress to muscle invasion will die from bladder cancer. Patients who progress to muscle invasion on surveillance seem to have particularly aggressive disease and may benefit from multimodal treatments.