Citations

We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV 1 ], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV 1 , worse dyspnoea and higher ADO index compared to other clusters ( p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.

137 Background: LUTS are one of the most common reasons patients visit urologists. These symptoms have not been typically associated with the development of prostate cancer (CaP). However, we hypothesized that visiting a physician for LUTS may modify the diagnostic intensity for CaP compared to population controls. Methods: We examined data from a longitudinal, population-based cohort of 2,447 men between 40 and 79 years old who were followed prospectively from 1990 to 2010. Participants completed the American Urological Association Symptom Index (AUASI) every two years. Self-reported moderate/severe LUTS were defined as an AUASI score >7 (n=1627). Data including the treatment for LUTS (n=874), prostate biopsy (PBx), family history of CaP and diagnosis of CaP were obtained through self-report and review of medical records. Associations between self-reported LUTS, treatment for LUTS, and risk of PBx or CaP were estimated using multivariate Cox proportional hazard models. Results: An interaction was noted between age and LUTS and PBx and CaP diagnosis. In younger men, the diagnosis and treatment of LUTS was associated with increased risk of PBx (HR 2.39: 95% CI 1.83, 3.13) and CaP (HR 3.47: 95% CI 2.38, 5.07). Conversely in older men, treatment for LUTS was associated with a decreased risk of PBx and CaP (Table). Self reported LUTS was not significantly associated with CaP diagnosis in younger men and was protective in older men (Table). Conclusions: There is a differential effect of LUTS on prostate cancer testing and diagnosis when stratified by age. The reason for this difference is unclear, but appears to be due largely to diagnostic intensity rather than a true biologic association between LUTS and CaP. [Table: see text]

Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) –targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody–drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. Methods In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review. Results T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. Conclusion T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast cancer.

Abstract Welander distal myopathy is a rare autosomal dominant disorder characterized by muscle weakness in the hands and feet. Exome sequencing of affected families discovered a segregating p.Glu384Lys pathogenic variant in TIA-1 as the main genetic cause of Welander distal myopathy. TIA-1 encodes an RNA-binding protein which serves as a key component of stress granules. This protein also regulates splicing and translation of mRNA. Our patient developed progressive weakness in his hands and feet during his late 40s that was misdiagnosed as a neuropathy that caused muscle atrophy. Follow-up genetic testing revealed a p.Glu384Lys pathogenic variant in TIA-1, and he was then diagnosed with Welander distal myopathy. Our case report underlines the importance of electrodiagnostic and genetic testing of patients.

Abstract Background Anti–tumor necrosis factor alpha ( TNF ‐α) agents are used to treat a variety of autoimmune and inflammatory conditions, including psoriasis. Paradoxically, numerous reports have documented new‐onset or exacerbation of psoriasis or psoriasiform skin lesions ( PSO ) in patients treated with these agents for conditions other than PSO—particularly in adults with inflammatory bowel disease ( IBD ). Not much is known regarding similar cases in children. Methods A retrospective chart review was performed on children younger than 19 years of age with IBD seen at the Mayo Clinic between 2003 and 2015 who developed new‐onset or recurrent PSO while undergoing anti‐ TNF ‐α therapy. Results Fourteen children developed PSO while undergoing anti‐ TNF ‐α therapy for IBD . All three anti‐ TNF ‐α agents (infliximab, adalimumab, certolizumab) used to treat IBD in this series led to induction or recurrence of PSO lesions. The median time to development of PSO was 11 months (range 0–48 mos), the median age was 15 years (range 12.5–17.5 yrs), and 57% of patients were male. IBD activity was quiescent in 93% of cases at PSO onset. Seven patients (50%) discontinued their initial anti‐ TNF ‐α therapy because of their skin disease. Ultimately, four patients (29%) had to discontinue all anti‐ TNF ‐α therapy to induce PSO resolution. Conclusion TNF ‐α antagonist–induced PSO in children with IBD is a rarely reported adverse reaction. PSO onset has a variable latency, but usually occurs during IBD remission, with a slight male bias. Nearly half of patients required a change in their initial anti‐ TNF ‐α agent despite conventional skin‐directed therapies, and one‐third of patients discontinued all anti‐ TNF ‐α therapy because of PSO .

Summary Objectives To evaluate obesity and overweight in children with congenital adrenal hyperplasia ( CAH ) and associations with glucocorticoids, fludrocortisone and disease control. Adjusting body mass index‐for‐height‐age ( BMI HA ) percentile is proposed to correct misclassification of obese/overweight status in CAH children with advanced bone age and tall‐for‐age stature. Design Longitudinal. Patients One hundred and ninety‐four children with CAH seen from 1970 to 2013: 124 salt wasting ( SW ); 70 simple virilizing ( SV ); 102 females. Measurements Body mass index (BMI) end‐points were overweight (85–94 percentile) and obese (≥95 percentile). Results Approximately 50% of the children had at least one BMI measurement ≥95 percentile and about 70% had at least one ≥85 percentile. Using BMI HA percentiles, obesity incidence decreased slightly in SW children (47–43%) and markedly in SV children (50–33%); however, overweight status was not reduced. Only 6% of SW and 1% of SV children were persistently obese (≥3 clinic visits) when BMI HA was applied, whereas overweight status persisted in 35% of SW and 33% of SV children. Most obesity or overweight when using BMI HA occurred before age 10 and there was no association with hydrocortisone (HC) or fludrocortisone dosing. Adiposity rebound for SW children occurred by 3·3 years and in SV females by age 3·8 years, over a year earlier than the adiposity rebound for healthy children. Conclusion Children with CAH are at higher risk for early onset obesity and overweight with or without using BMI HA but rates of persistent obesity were lower than previously reported. Careful HC dosing during early childhood is needed to prevent increased weight gain and an early adiposity rebound.

Abstract Background: Human papillomavirus (HPV) vaccination rates in the United States remain low and lag behind other recommended adolescent vaccines. Studies evaluating the association of geographic and area-level characteristics with HPV vaccination rates provide a valuable resource for public health planning. Method: We used the Rochester Epidemiology Project data linkage system to ascertain HPV vaccination rates between 2010 and 2015 in a 7-county region of southern Minnesota. Geocoded individual patient data were spatially linked to socioeconomic data from the American Community Survey at the census block group level. Bayesian hierarchical logistic regression was used to model incident vaccination rates, adjusting for individual- and area-level sociodemographic characteristics, and geolocation. Geolocation was modeled as an approximated Gaussian field using a Stochastic Partial Differential Equations approach. All models were estimated using Integrated Nested Laplace Approximations. Results: In adjusted models, increasing age and female sex were associated with increased HPV vaccination. Lower socioeconomic status was associated with decreased rates of initiation [adjusted odds ratio (AOR); 95% confidence interval = 0.90 (0.86–0.95)], completion of the second dose [AOR = 0.88 (0.83–0.93)], and completion of the third dose [AOR = 0.85 (0.80–0.92)]. Geographic spatial analysis demonstrated increased odds of vaccination for the eastern region and in the greater Rochester metropolitan area, showing significant spatial variation not explained by individual level characteristics and ACS block group-level data. Conclusions: HPV vaccination rates varied geographically and by individual and geographically indexed sociodemographic characteristics. Impact: Identifying geographic regions with low HPV vaccination rates can help target clinical and community efforts to improve vaccination rates. Cancer Epidemiol Biomarkers Prev; 26(4); 533–40. ©2017 AACR. See all the articles in this CEBP Focus section, “Geospatial Approaches to Cancer Control and Population Sciences.”

Background: The association of central arterial stiffness and pressure pulsatility with mild cognitive impairment (MCI) and dementia is not well characterized in the population-based setting. Objective: The aim of this study was to quantify the cross-sectional association of arterial stiffness and pressure pulsatility with MCI and dementia among 4,461 older white and black adults from the population-based Atherosclerosis Risk in Communities Study-Neurocognitive Study. Methods: We used race-stratified multinomial logistic regression to evaluate associations of percentile cut points of carotid-femoral pulse wave velocity, central systolic blood pressure, central pulse pressure, and pulse pressure amplification with MCI and dementia versus no cognitive impairment. Results: Among whites, those with carotid-femoral pulse wave velocity or central systolic blood pressure ≥75th percentile had a higher prevalence of MCI compared to participants <75th percentile (conditional odds ratio (OR); 95% confidence interval (CI): 1.27 (1.02, 1.56) and 1.28 (1.04, 1.57), respectively) and those with central pulse pressure ≥75th percentile had a higher prevalence of MCI (OR 1.27 (95% CI: 1.03, 1.58)) and dementia (OR 1.76 (95% CI: 1.06, 2.92) compared to participants <75th percentile. Also among whites, those with pulse pressure amplification ≤25th percentile had a higher prevalence of dementia compared to participants >25th percentile (OR 1.65; (95% CI: 1.01, 2.70). Weaker associations were seen among black participants. Conclusion: Higher arterial stiffness and pulsatility were associated with MCI and dementia in white participants. Longitudinal characterization of the observed associations is warranted to assess whether arterial stiffness and pressure pulsatility predict MCI and dementia among older adults.