Introduction: Segmental arterial mediolysis (SAM) is nonatherosclerotic and noninflammatory arteriopathy. It commonly affects the abdominal vasculature. There is uncertainty about its presentation, radiological findings, prognosis and management. Hypothesis: The goal of this study is to describe the clinical course and evaluate risk factors for disease progression. Method: Retrospective review of all cases diagnosed with SAM at the Mayo clinic between 2001 and 2014. Medical records were reviewed for demographics, risk factors, laboratory, imaging findings and treatment options at presentation and during follow-up visits. A non-parametric Wilcoxon-rank-sum test and the Chi-Square test were used. Results: Out of 247 reviewed cases, 114 patients were confirmed with SAM and included in the analysis. (69%) were male and a majority (84%) had no other connective tissue disorder. Mean age was (52) years old. Pre-existing hypertension was identified in (48%), hyperlipidemia (31%), migraine (11%) and smoking (32%). The most common symptoms at presentation were abdominal pain (70%), flank pain (21%), back pain (8%) and chest pain (5%). Only (30%) of patients had recurrent symptoms and most (89%) had negative inflammatory markers. On angiography the following arteries were commonly affected: renal (51%), celiac (43%), superior mesenteric (49%), and iliac (18%). At presentation (85%) of patients were found to have mesenteric arterial dissection; (45%) aneurysms; (14%) wind or wall thickening; (21%) occlusion; and (38%) with evidence of end organ ischemia or infarct. 82 patients were followed up with a CT angiogram for an average of 19 months, 17 (20.73%) had evidence of disease progression. (22%) required revascularization. Aspirin (47%) was the most common treatment used followed by anticoagulation (38%), beta blocker (35%) and ACEI/ARB (29%). Risk factors for disease progression are being male (P<0.0173), Hypertension (P<0.0128), hyperlipidemia (P<= 0.0044). The use of antiplatelets and ACEI/ARB was not associated with disease stability. Conclusion: SAM is an arteriopathy that affects the mesenteric arteries in middle age men. Conservative management with control of risk factors and close follow up are preferred approach.
The Effectiveness of Palate Re-Repair for Treating Velopharyngeal Insufficiency: A Systematic Review and Meta-Analysis
Background: Palate re-repair has been proposed as an effective treatment for velopharyngeal insufficiency (VPI) with a low risk of obstructive sleep apnea (OSA). The authors conducted a systematic review and meta-analysis to determine the proportion of patients achieving normal speech resonance following palate re-repair for VPI, the proportion developing OSA, and the criteria for patient selection that are associated with increased effectiveness. Methods: PubMed, Embase, and Scopus were searched from inception through April 2018 for English language articles evaluating palate re-repair for the treatment of VPI in patients with a repaired cleft palate. Inclusion criteria included reporting of hypernasality, nasal air emission, nasometry, additional VPI surgery, and/or OSA outcomes. Meta-analysis was conducted using random effects models. Risk of bias was assessed regarding criteria for patient selection, blinding of outcome assessors, and validity of speech assessment scale. Results: Eighteen studies met inclusion criteria. The incidence of achieving no consistent hypernasality follow palate re-repair was 61% (95% confidence interval [CI]: 44%-75%). The incidence of additional surgery for persistent VPI symptoms was 21% (95% CI: 12%-33%). The incidence of OSA was 28% (95% CI: 13%-49%). Criteria for selecting patients to undergo re-repair varied, with anterior/sagittal position of palatal muscles (33%) and small velopharyngeal gap (22%) being the most common. No specific patient selection criteria led to superior speech outcomes ( P = .6572). Conclusions: Palate re-repair achieves normal speech resonance in many but not all patients with VPI. Further research is needed to identify the specific examination and imaging findings that predict successful correction of VPI with re-repair.
Trends in Disease Presentation, Management, Cost of Care and Outcomes: A Comprehensive Look at Racial Disparities in Multiple Myeloma (MM)
Abstract Background: Disparities in MM survival among different racial groups persist despite improvements in overall survival (OS). We report a comprehensive review of the SEER Medicare database to elucidate the causes of differences in disease presentation, management practices, cost of care and their relationships to outcomes among the MM patients (pts) from different racial groups. Methods: Pts diagnosed with MM between 1991-2010 with continuous Medicare coverage (1 year prior to diagnosis-date of death/end of 2012) were included. MM complications (MM-C); hypercalcemia (C), renal dysfunction (R), anemia (An), bone fractures (B), dialysis (D) occurring prior to/within 30 days of MM diagnosis (at diagnosis; AT-D), or any time later (after diagnosis; AF-D) were summarized. Demographics, survival (PEDSAF files) and disease characteristics, drug/stem cell transplant (SCT) utilization (NCH, OUTSAF, PDESAF files) were obtained. Trends in incidence of MM-C, treatment type over time (proportional odds) and their association with race (logistic regressions) were compared. Associations between race, MM-C AT-D and MM related death using Fine and Gray's competing risk methods were analyzed. Medicare claims adjusted for inflation (2013) within the first 6 months (mth)/total MM care were summed by drug and total charges. Median cost of care by race and year of diagnosis were evaluated by Kruskal-Wallis (univariate) and proportional odds models (multivariate). Results: A total of 35842 pts (52.1% males) with median age of 76 yr (range 18-104) were included. Mutually exclusive racial subgroups were: White (W, 72%), Hispanic (H: 7.3%), African-American (AA, 16.2%), Asian (A, 4.1%), other (0.3%). A significantly increasing trend in the prevalence of all MM-C AT-D was seen over time (all p<0.001). For AF-D, all MM-C initially increased but decreased from 2006-2010 except D that showed continued increase (Fig 1A). For race, MM-C were significantly different, with AA having the most C, R, An and D while W having the most B (Fig 1B). Inferior OS was seen with male gender (p=0.006), increasing age, earlier years of diagnosis, belonging to W or H race, C, R and B (all p<0.001), but not with An (p=0.298) or D (p=0.378). Trends in OS over time showed a significant interaction with race in 1991-1995 (p<0.001), 1996-2000 (p=0.004) and 2001-2005 (p<0.001) but not in 2006-2010 (p=0.182), possibly due to shorter follow up. Medicare claims analysis showed that pts receiving any treatment increased from 12.8% in 1991-1995 to 59.3% in 2006-2010 (p<0.001). Specific therapy utilization, including SCT and all drug classes/agents evaluated increased except for cytotoxic chemotherapy utilization (melphalan/cyclophosphamide), which decreased (Fig 2A). Any therapy utilization was significantly different by race (p<0.001) with highest for H (36.5%) and lowest for AA (31.6%). Specific treatments differed significantly by race (Fig 2B). Cost of care analysis showed significant increase over years for median drug claims (0.23k to 3.63k) and total claims (5.11k to 27.8k) during first 6 mth as well as for any time after MM diagnosis (drug: 1.3k to 9.9k, total: 21.9k to 84k) (p<0.001 for all). Median drug claims in first 6 mth were highest among AA (1.3k) and lowest among A (0.63k) (p<0.001). Same was true for total claims in first 6 mth (p<0.001). For any time after diagnosis, H had the highest drug (p<0.001) and total (p=0.081) claims. There were significant interactions between year of diagnosis, race and cost of care with H seeing the highest increase in drug claims in first 6 mth (p<0.001) and any time (p=0.002). Conclusion: MM-C have generally decreased AF-D due to improved therapeutics although AA continue to have the highest rates of MM-C. Our data shows that utilization and cost of MM care have increased tremendously with resulting improved outcomes, but significant racial disparities persist. These disparities may be in part due to impaired access to new agents from lack of supplemental insurance for certain racial groups. Drug utilization and cost of care disparities may also be due to differences in co-morbidities, MM-C or access leading to differential healthcare utilization and should be explored in order to ameliorate disparities in outcomes. Disclosures Ailawadhi: Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy.
Day +30 and Day +100 CD33 Chimerisms Predict Survival after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelofibrosis
Abstract Background: Donor cell chimerisms are tested at frequent intervals after allogeneic hematopoietic stem cell transplantation (alloHSCT). However, the predictive value of this testing in patients with myelofibrosis (MF) is not well-defined. In this study, our primary objective is to evaluate the correlation of day 30 and day 100 donor cell chimerism and overall survival (OS) in patients (pts) who undergo alloHSCT for MF. Methods: Charts were reviewed for pts who underwent alloHSCT for MF at Mayo Clinic in Arizona, Minnesota and Florida between January 2005 and December 2015. Patients who died within 30 days of alloHSCT were excluded. Chimerism studies were evaluated in the peripheral blood for CD3 and CD33 fractions at day +30 (D30) and day +100 (D100). Cut-off value of 100% and less than 100% was used because of limited variability below 100%. Standard statistical methods were used to compare continuous and categorical variables. The Kaplan-Meier method was used to provide survival curves. Results: Baseline characteristics: Sixty three consecutive patients who underwent alloHSCT for MF since January 2005 until December 2015, and had D30 and/or D100 chimerism studies available were included in the study. Of these, 24 (38%) were female. Median age at diagnosis was 56 years (range, 19 - 73 years) and median age at AHSCT was 58 years (range, 19 - 73 years). Dynamic International Prognostic Scoring System-Plus (DIPSS-Plus) risk category at the time of alloHSCT was high in 31 (49%), intermediate-2 in 30 (48%) and intermediate-1 in 2 (3%) pts. JAK2 V617F mutation status was available in 61 pts and was positive in 35 (57%) pts. Nineteen (30%) pts had been treated with a JAK2 inhibitor prior to alloHSCT. Fifty-two (83%) pts had at least grade-2 fibrosis in bone marrow at the time of HCT. Transplantation: Median time from diagnosis to AHSCT was 12.9 months (range, 2.3 - 248.2 months). Fifty-five (87%) received a reduced intensity conditioning (RIC) regimen while 8 (13%) received myeloablative conditioning regimen. Of these 55 pts, RIC regimens used were busulfan fludarabine based regimen in 15 (27%), fludarabine melphalan based regimen in 18 (33%) and fludarabine melphalan carmustine in 22 (40%) pts. Donor source was matched related in 30 (48 %), matched unrelated in 28 (44%), single-antigen mismatched related in 4 (6%) and mismatched unrelated in 1 (2%). Peripheral blood stem cells were used in all AHSCTs. Outcomes: Median follow-up was 24.4 months (range, 1.5 - 83.6 months). Amongst pts who had <100% donor chimerism at D30 in CD33 fraction, 2 had 90%, 1 had 80% and 2 had zero% donor chimerism. At D100, 1 pt had 95%, 1 had 90%, 1 had 60%, 2 had 5% and 1 had zero% donor chimerism. Eighteen out of 57 (32%) pts who had 100% donor chimerism in CD33 fraction at D30 had died at the time of analysis compared to 4 out of 5 (80%) patients with less than 100% (p=0.03). Eight out of 38 pts (21%) who had 100% donor chimerism in CD33 fraction at D100 died versus 3 out of 6 (50%) with less than 100% (p=0.12). There was no significant survival effect of CD3 chimerism (p values=0.68, 0.59). Of the 23 deaths that had occurred at the time of analysis, cause of death was disease progression or relapse in 8 (35%), graft versus host disease in 6 (26%), transplant related (sepsis / engraftment failure) in 5 (22%) and unrelated causes in 4 (17%). Survival analysis: As depicted in the Kaplan Meier curve (figure 1), median overall survival (OS) for pts with 100% donor chimerism in CD33 fraction at day 30 was not reached while for <100% donor chimerism was 16 months (p=0.04). Survival at 3 years for patients with 100% CD33 donor chimerism at D30 was 65% while it was 40% for pts with less than 100%. Also, survival at 3 years for patients with 100% CD33 donor chimerism at day 100 was 75% compared to 50% for patients with less than 100%. Conclusions: In our study, 100% donor chimerism in CD33 fraction is associated with improved survival after alloHSCT for MF compared to pts with less than 100%. Further understanding regarding the reason for this relationship is critical. Larger studies to replicate these results would be imperative to validate these findings. Disclosures Mesa: Incyte: Research Funding; Ariad: Consultancy; Promedior: Research Funding; Novartis: Consultancy; Celgene: Research Funding; Gilead: Research Funding; CTI Biopharma: Research Funding; Galena: Consultancy.
Racial Disparity in Drug Utilization Among Multiple Myeloma Patients: A SEER Medicare Analysis
Abstract Background: Patient (Pt) outcomes have improved significantly in multiple myeloma (MM) due to widespread use of novel therapeutic agents and stem cell transplant (SCT) butoutcome disparities among racial/ethnic groups exist. Differences in access to and utilization of novel therapeutics are likely contributing factors. We performed an analysis of the SEER-Medicare database to explore such differences. Methods: Pts with a confirmed MM diagnosis between 2007-2009 and continuous Medicare coverage from 1 year prior to diagnosis through end of 2012 were included. Medicare Part D data (oral medications) is not available prior to 2007 so utilization analysis of lenalidomide (LEN), thalidomide (THAL) and bortezomib (BORT) was performed from 2007-2009. Demographic/survival data (PEDSAF files) and drug/SCT utilization (NCH, OUTSAF, PDESAF files) were obtained (HCPCS/NCH codes). Categorical and continuous variables were compared using /Fisher tests and Wilcoxon tests, respectively. Gender, age, and year-adjusted p-values were calculated using logistic regression. A proportional odds model was used to detect time-dependent trends in drug usage within 12 months of MM diagnosis across year of diagnosis by race. Separate multivariate models were fit for each drug adjusting for gender, age, drug use and race. Associations between drug use and overall survival (OS) were examined using a time dependent proportional hazards model. Results: A total of 5358 MM pts were included (any Medicare claims) with 2733 (51%) males. Mutually exclusive race categories were White (W; 67%), African-American (AA; 18%), Hispanic (H; 10%) and Asian (A; 5%). Median follow up was 2.4 yrs. Baseline pt characteristics were significantly different for age with AA being the youngest at diagnosis (p<0.001) and for gender (p<0.001) with W having the largest (53.4%) and AA the smallest (45.2%) proportion of males. Medicare claims capture only pts without any supplemental insurance and so drug utilization in this database was much lower than expected for all subgroups. Year-wise comparison showed that LEN use within the first year of MM diagnosis increased from 2007 to 2009 (16.5% to 27.7%; p<0.001) and there was a significant decrease in median days to first dose (p=0.002). Over the same period, use of THAL decreased (26.6% to 14.6%; p<0.001) while use of BORT (7.8% to 15.4%; p<0.001), SCT (3.3% to 6.2%; p<0.001) and more than 1 novel agent (2.5% to 5.7%; p<0.001) increased significantly. Utilization patterns within first year of MM diagnosis were significantly different among racial subgroups for LEN, THAL, BORT, SCT and >1 novel agent use. (Figure 1) No significant difference was seen for days to first dose of LEN/THAL for any race but for BORT, H got first dose in median 117 days after diagnosis as compared to median 46-51 days for other races (p=0.025). During the first year after diagnosis, W and AA had higher BORT only usage while H and A had a higher LEN/THAL only usage (p<0.001). For drug use by year and race, a significant increase in LEN use was seen from 2007 to 2009 in W (p<0.001), AA (p=0.001) and A (p<0.001) but not H (p=0.26) while THAL use decreased significantly for all races. BORT use increased significantly for all except A (p=0.602) and SCT use increased significantly for all except AA (p=0.068). Inferior OS was significantly associated with older age (p<0.001) and males (p<0.001). LEN/THAL use within the first year of diagnosis did not affect OS while BORT use within the first year of diagnosis increased mortality risk (HR 1.18, p=0.021). SCT use improved OS (HR 0.52, p<0.001). Conclusions: In this comprehensive analysis of MM therapeutics utilization, we noted significant variability among different racial groups. The use of LEN, BORT and SCT has increased while THAL has decreased over time but disparities exist in utilization among different races, with lower use of LEN in AA, lower use of BORT in A and significantly delayed use of BORT in H, which are all notable since racial/ethnic minorities are fast growing in the US population mix and seem to have inequitable utilization and/or access. Inferior survival with early BORT use may represent selection bias of pts with more advanced/aggressive disease. These trends need to be examined in larger sample sizes especially from commercial payers to eliminate drug access and utilization disparities and achieve equitable benefit of therapeutic advances across all racial subgroups. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Ailawadhi: Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy.
Breast Cancer Screening: Women's Attitudes and Beliefs in Light of Updated United States Preventive Services Task Force and American Cancer Society Guidelines
Objective. To determine whether results of the nasopharyngeal FilmArray respiratory panel (NP-FARP) influenced antibiotic decisions. Methods. We reviewed the medical records of nonintensive care unit (ICU) inpatients that had an NP-FARP performed at our institution between June 2013 and June 2014. The inpatient records were reviewed 48 hours after the NP-FARP for the following data: demographic information; NP-FARP, serum procalcitonin, and methicillin-resistant Staphylococcus aureus nasal swab (MRSA NS) results; antibiotics prior and post-48 hours of the NP-FARP result; and the current immunosuppression status. Clinical outcome data were not obtained. Patients were categorized into those who had a positive (+) or a negative (−) NP-FARP. We further subdivided these two categories into groups A, B, and C based on the antibiotic modifications 48 hours after their NP-FARP result. Group A included patients who were never initiated on antimicrobial therapy. Patients whose antibiotics were discontinued or deescalated were placed in group B. Patients with antibiotic escalation or continuation without change constituted group C. We compared and analyzed groups A, B, and C in the (+) and (−) NP-FARP cohorts. Results. A total of 545 patients were included. There were 143 (26%) patients with positive and 402 (74%) patients with negative NP-FARPs. Comparison of groups A, B, and C between those with a (+) and (−) NP-FARP were as follows: (+) A and (−) A, 28/143 (20%) and 84/402 (21%); (+) B and (−) B, 59/143 (41%) and 147/402 (37%); and (+) C and (−) C, 56/143 (39%) and 171/402 (43%), respectively. We found no statistically significant differences between groups (+) A versus (−) A, (+) B versus (−) B, and (+) C versus (−) C with respect to age, gender, MRSA NS result, procalcitonin result, or concurrent immunosuppression. Conclusion. In non-ICU inpatients, NP-FARP alone or in combination with procalcitonin or MRSA NS did not influence antibiotic decisions during the study period.
The Yips: Methods to Identify Golfers with a Dystonic Etiology/Golfer’s Cramp
ABSTRACT Purpose To determine whether quantitative methods could separate golfers with a possible dystonic cause of the “yips” from those that appear to be nondystonic. Methods Twenty-seven golfers completed 10 two-handed and 10 right hand–only putts. Surface EMG assessed forearm muscle co-contraction and motion detectors monitored wrist and putter movements. Based on a videotape review, golfers were grouped into those with yips of dystonic etiology, those with the yips nondystonic, and those with no yips. Results On video review of two-handed putting, five golfers had yips that appeared to be dystonic, nine had yips that did not appear to be dystonic, and 13 had no yips. During two-handed putting co-occurrence of a yipped putt and wrist flexor/extensor and/or pronator/supinator co-contraction was significantly more frequent in those with dystonic yips. The dystonic group had no increase in the number of yipped putts or yips with co-contraction when putting right hand only, whereas the nondystonic group had significantly more yipped putts and more yipped putts with co-contraction with right hand only. Conclusions Quantitative methods were identified that appear to identify golfers with a dystonic etiology for the yips. It is not just the frequency of yips nor just specific motion patterns alone, rather it is also a combination of yips with co-occurring co-contraction when putting with two hands, and then right hand only, that distinguished this possible etiology. Despite being a small study, identifying a dystonic pattern, even in a nonpressure indoor setting, may aid in assessment and possible monitoring of treatment.
Anticholinergic Medications and Cognitive Function in Late Midlife