University Of Michigan Health System Research Articles

Oncotype Dx Results in Multiple Primary Breast Cancers

PURPOSETo determine whether multiple primary breast cancers have similar genetic profiles, specifically Oncotype Dx Recurrence Scores, and whether obtaining Oncotype Dx on each primary breast cancer affects chemotherapy recommendations.METHODSA database of patients with hormone receptor-positive, lymph node-negative, breast cancer was created for those tumors that were sent for Oncotype Dx testing from the University of Michigan Health System from 1/24/2005 to 2/25/2013.Retrospective chart review abstracted details of tumor location, histopathology, distance between tumors, Oncotype Dx results, and chemotherapy recommendations.RESULTSSix hundred and sixty-six patients for whom Oncotype Dx testing was sent were identified, with 22 patients having multiple breast tumor specimens sent. Of the 22 patients who had multiple samples sent for analysis, chemotherapy recommendations were changed in 6 of 22 patients (27%) based on significant differences in Oncotype Dx Recurrence Scores. Qualitatively, there seems to be a greater difference in genetic profile in tumors appearing simultaneously on different breasts when compared to multiple tumors on the same breast. There was no association between distance between tumors and difference in Oncotype Dx scores for tumors on the same breast.CONCLUSIONSOncotype Dx testing on multiple primary breast cancers altered management in regards to chemotherapy recommendations and should be considered for multiple primary breast cancers.

Communication-And-Resolution Programs: The Challenges And Lessons Learned From Six Early Adopters

In communication-and-resolution programs (CRPs), health systems and liability insurers encourage the disclosure of unanticipated care outcomes to affected patients and proactively seek resolutions, including offering an apology, an explanation, and, where appropriate, reimbursement or compensation. Anecdotal reports from the University of Michigan Health System and other early adopters of CRPs suggest that these programs can substantially reduce liability costs and improve patient safety. But little is known about how these early programs achieved success. We studied six CRPs to identify the major challenges in and lessons learned from implementing these initiatives. The CRP participants we interviewed identified several factors that contributed to their programs' success, including the presence of a strong institutional champion, investing in building and marketing the program to skeptical clinicians, and making it clear that the results of such transformative change will take time. Many of the early CRP adopters we interviewed expressed support for broader experimentation with these programs even in settings that differ from their own, such as systems that do not own and control their liability insurer, and in states without strong tort reforms.

GME Innovations Grant Program at the University of Michigan Health System—Fostering Changes in Education and Clinical Care

Changes in graduate medical education (GME) have resulted in curricula, goals and objectives, and assessment methods becoming more formal, yet there is little financial support for the educational research required to develop better teaching approaches and assessment tools. We sought to encourage the development of new educational tools and assessment methods to improve the overall conduct of GME at the University of Michigan. The University of Michigan Health System has recently established a new educational grant that is designed to foster innovative educational research in GME. We describe the experience with a new and robust internal educational grant, including the source of funding, mechanisms for reviewing and assessing the proposals, the types of proposals that have currently been funded, and the effect and results of these studies on GME at the University of Michigan Health System. Projects funded by the grant have changed the curriculum in the involved programs, and many have resulted in sustained changes, including new methodologies in the simulation center, the development of an "academy" of faculty physicians with significant teaching expertise, and the creation of web-based teaching and assessment tools for "just in time" learning, and have been disseminated at national meetings and in peer-reviewed journals. The GME Innovations Grant Program at the University of Michigan Health System has been successful to date, funding 11 proposals during the course of 6years. Some of these proposals have resulted in permanent changes and additions to residency training programs.

Managing Hypothermia in Cardiac Arrest and Rewarming

Many institutions are currently utilizing therapeutic hypothermia to target cardiac arrest as well as different types of brain injuries. Confounding issues including accidental hypothermia as well as the need to carefully rewarm patients with some types of physiological monitoring strategies are an area of active investigation and discussion. This particular session brought together experts in the field from cardiology, surgery, and trauma to discuss current strategies for managing hypothermia and temperature maintenance in various patients with different types of disorders. Dr. Eric Zoog, medical director of the Emergency Department, Mississippi Baptist Medical Center, provided an interesting summation of how he and his colleagues developed a successful hypothermia program in a community hospital. Several important points were made in terms of the processes, including convincing various services to help with this important program. Dr. Robert Silbergleit, Department of Emergency Medicine, University of Michigan Health System, discussed his experience in various clinical trials, including the use of hypothermia in cardiac arrest as well as patients undergoing aneurysm surgery. His experience emphasized the importance of introducing careful strategies to monitor brain function during cooling and rewarming phases. Dr. Josh Levine, Department of Neurology, University of Pennsylvania, discussed the use of hypothermia in various brain injury conditions. Most importantly, he and his colleagues have been investigating the importance of developing surrogate biomarkers that could aid in the assessment of the status of the brain. Most importantly, these biomarkers could be used to individualize treatments based on active processes. This session had a very interesting question-and-answer exchange, again emphasizing the interest in using therapeutic hypothermia and temperature management strategies during various emergency situations.

Airway Management in Patients with Subglottic Stenosis

We describe a pilot study investigating the airway techniques used in the anesthetic management of subglottic stenosis. We searched the electronic clinical information database of the University of Michigan Health System for cases of subglottic stenosis in patients undergoing surgery. Demographics, airway techniques, incidence of hypoxemia, and technique failure were extracted from 159 records. A lower incidence of hypoxemia was found between the 4 most commonly used techniques and the less common techniques. We detected no difference in outcome between individual techniques. This study suggests a larger prospective multicenter study is required to further investigate these outcomes in patients with subglottic stenosis.

The Sensitivity and Specificity of Frozen-Section Histopathology in the Management of Benign Oral and Maxillofacial Lesions

The management of odontogenic cysts and tumors typically requires a biopsy, which may present significant challenges and prompt an additional visit to the operating room before definitive treatment. The aim of this study was to determine the validity of frozen-section diagnosis in the management of benign oral and maxillofacial lesions, allowing intraoperative diagnosis followed by definitive treatment under the same general anesthetic. A retrospective chart review of patients treated at the University of Michigan Health System was performed. Patients of all ages who had a diagnosis of a benign maxillofacial lesion by frozen-section and permanent histopathology reports were included for analysis. Patients were identified using the Current Procedural Terminology code for enucleation and curettage and International Classification of Diseases, Ninth Revision codes for benign cysts or tumors of skull, face, or lower jaw. Of 450 patients reviewed, 214 had intraoperative frozen-section examination available for comparison with permanent histopathology. There were 121 men (56.5%) and 93 women (43.5%), with amean age of 41years. Compared with final permanent histopathology, the overall sensitivity of frozen sections was 92.1%. Frozen-section histopathology had a sensitivity greater than 90% and a specificity greater than 95% for the diagnosis of dentigerous cyst and keratocyst odontogenic tumor. In this study of 214 patients with benign maxillofacial lesions, frozen-section histopathology was found to be a valid diagnostic modality with high sensitivity, specificity, and positive and negative predictive values. These results and analysis support the use of frozen-section histopathology for the treatment of benign maxillofacial lesions and underscore its value in the management of these lesions.

Invited Commentary

HomeRadioGraphicsVol. 33, No. 7 PreviousNext Pediatric ImagingInvited CommentaryJonathan R. DillmanJonathan R. DillmanAuthor AffiliationsDepartment of Radiology, University of Michigan Health System, C.S. Mott Children’s Hospital Ann Arbor, MichiganJonathan R. DillmanPublished Online:Nov 1 2013https://doi.org/10.1148/rg.337135154MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In

Gastrointestinal bleeding and subsequent risk of thromboembolic events during support with a left ventricular assist device

Modern left ventricular assist devices (LVAD) require anti-coagulation (AC) with warfarin and anti-platelet therapy to prevent thromboembolic complications in patients. Gastrointestinal bleeding (GI) is a significant adverse event in these patients and treatment typically requires reduction or elimination of AC or anti-platelet therapy. It is not known whether alterations in AC to treat GI bleeding influence subsequent risk of thromboembolic (TE) events during LVAD support. Between July 2003 and September 2011, 389 patients (308 male) underwent implantation of a continuous-flow LVAD at the University of Michigan Health System and the Mayo Clinic. Median age at implant was 60 years (range 18 to 79 years). Outcomes were analyzed for the association of GI bleeding events and subsequent TE events, defined as stroke, transient ischemic attack, hemolysis or suspected or confirmed pump thrombosis. Median survival was 10 months (maximum 7.2 years, total 439 patient-years). TE events occurring within the first 30 days were not counted. Overall survival and freedom from an outcome event were assessed using the Kaplan-Meier method. Associations between GI bleeding and subsequent TE events and survival impact were analyzed as time-dependent covariates. One hundred ninety-nine GI bleeding episodes occurred in 116 of 389 patients (30%) for an event rate of 0.45 GI bleed/patient-year of support. One hundred thirty-eight TE events occurred in 97 of 389 patients (25%) for an event rate of 0.31 TE event/patient-year of support. Median time from LVAD implant to first GI bleed was 5 months (range 1 to 116 months) and to first TE event was 6 months (range 1 to 29 months). For patients who had a TE event after GI bleed, the median interval was 5 months (range 0.5 to 25 months). TE events were 7.4-fold more likely in patients who had a prior GI bleed (range 4.9- to 11.1-fold) (p < 0.001); however, neither the presence of GI bleeding (0.7 to 1.2) nor a TE event (0.8 to 2.0) portended a lower overall survival. Patients who had GI bleeding were at significantly higher risk for a subsequent TE event. Although the exact cause of this relationship is unknown, it suggests that a reduction in anti-coagulation and anti-platelet management to treat GI bleeds may contribute to this risk.

Temporal Morphomics as a Model for Determining Preoperative Risk of Blood Transfusion in Nonsyndromic Craniosynostosis Patients

Estimates of blood loss during craniosynostosis surgeries have ranged from 42 to 126 percent of infant's total blood volume. Currently, no risk model has been developed to determine the likelihood of needing a blood transfusion. The authors propose an objective model, based on patients' three-dimensional anatomical characteristics, to stratify the likelihood of needing perioperative packed red blood cells. High-throughput image analysis from already ordered preoperative computed tomographic scans was used to reconstruct the three-dimensional anatomy of the temporalis muscle and overlying temporal fat pad. Using these morphomic measurements, the authors created a risk assessment model of the amount of packed red blood cells infused based on morphomic variations in temporal soft tissue. The authors evaluated 139 infants with nonsyndromic craniosynostosis from the University of Michigan Health System. Results show the need for blood transfusion ranged from 94.1 percent among patients in the smallest quartile for temporal fat pad volume compared with 65.7 percent among the group with the largest quartile for temporal fat pad volume (p = 0.0057). Using multivariable linear regression, temporal fat pad volume (p = 0.012) and fat pad thickness (p = 0.036) were independent predictors for amount of packed red blood cells required. The authors demonstrate that patients with diminished temporal fat pad volume are significantly more likely to need increased packed red blood cell transfusions. In addition, by use of multivariable linear regression, their data suggest that temporal fat pad volume and thickness were independent predictors for the amount of required transfusion of packed red blood cells.

Geography Lessons: Scrutinizing State-by-State Differences in Inpatient Gastroparesis Care

Gastroparesis is defined as a slowing of gastric emptying, a condition that has been associated with nausea, vomiting, and related symptoms. Few papers have addressed its prevalence and incidence and have characterized factors related to health care utilization for this condition. A recent population-based analysis reported prevalence per 100,000 for definite gastroparesis (defined by typical symptoms with documented delayed gastric emptying) of 9.6 for men versus 37.8 for women [1]. Age-adjusted incidences per 100,000 person-years calculated from the same population were 2.4 for men and 9.8 for women. Nevertheless, these data may not be generalizable due to its unique locale, Olmsted County, Minnesota, a highly educated, relatively homogeneous population medically well served by the Mayo Clinic. Furthermore, the impact of geography, demographics, and socioeconomic factors on hospitalization rates for gastroparesis and on other parameters of health resource usage has not heretofore been reported in the medical literature. The article by Bielefeldt in this issue represents an important addition to the literature, providing voluminous new information relating to regional profiles of inpatient care for gastroparesis (Table 1). The study utilized the State Inpatient Databases, which accumulate demographic and clinical information from 90 % of hospitalizations in 46 states. For this investigation, the International Diagnosis Code (ICD-9) for gastroparesis (536.3) was queried from 2007 through 2010 for 35 states. The most striking findings were the greater-than-fourfold differences in admission rates for this condition. It is possible that states with high admission percentages are the main contributors to the previously reported increase in hospitalizations for gastroparesis [2]. Twofold geographic differences in length of stay and nursing home transfers were also observed. Among demographic factors, higher hospitalization rates were related to female sex, greater state population, lower incomes, admission to large centers, and Medicare coverage. Clinically, heart failure was associated with increased admissions, whereas diabetes was inversely related to hospitalizations. Admission data correlated roughly with rates of endoscopy and in older individuals, gastrostomy placement, both of which also showed wide state-to-state variability. Conversely, enteral or parenteral nutrition initiation did not strictly relate to hospitalization rates. Finally, higher numbers of overall admissions but lower percentages of admissions with gastroparesis as a primary diagnosis were associated with inpatient mortality as were age [65 years, female sex, poverty, and endoscopies. The author concluded that disease-dependent and socioeconomic factors contribute to regional differences in inpatient health care for gastroparesis. Although the analyses by Bielefeldt were broad-ranging, other administrative factors related to differences in coding may have contributed to apparent regional variations in inpatient care of gastroparesis. The author did attempt to address this issue by comparing ICD-9 coding for gastroparesis versus dyspepsia. Yet, annual admissions for dyspepsia were only 2–3 % of those for gastroparesis in this study. Although hospitalization data for functional dyspepsia are lacking for the United States, its prevalence in the community exceeds 5 % and its inpatient costs are greater than threefold higher than for non-dyspeptics [3]. Thus, it is likely the coding of this disorder within this database did not consistently capture all functional W. L. Hasler (&) Division of Gastroenterology, University of Michigan Health System, 3912 Taubman Center, 5362, Ann Arbor, MI 48109, USA e-mail: whasler@med.umich.edu; whasler@umich.edu

The relationship between phenotype, ribotype, and clinical disease in human Clostridium difficile isolates

Since 2000, Clostridium difficile isolates of ribotype 027 have been linked to outbreaks in North America and Europe and also an increased rate of colectomy and death among infected individuals. It has been proposed that enhanced sporulation and toxin production were associated with this apparent increase in virulence of 027 isolates. Since only a limited number of isolates have been examined, the relationship of these phenotypes to a specific ribotype, and as well as to clinical disease severity, remains controversial. 106 recent clinical isolates from the University of Michigan Health System were characterized for the ability to sporulate, produce viable spores, grow in rich media, and produce toxins in vitro. Significant variation was observed between isolates for each of these phenotypes. Isolates of ribotype 027 produced higher levels of toxin and exhibited slower growth compared to other ribotypes. Importantly, increased spore production did appear to be relevant to severe C. difficile infection, as determined by available clinical meta-data. These data provide the first significant difference between isolates from severe vs. less severe disease based on an in vitro C. difficile phenotype and suggest that clinical outcome is better predicted by bacterial attributes other than ribotype.

Discussion

Los Angeles, Calif.; and Ann Arbor, Mich. From the Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Southern California, and the Department of Surgery, Section of Plastic Surgery, University of Michigan. Received for publication November 24, 2012; revised November 27, 2012. Disclosure:The authors have no financial interest to declare in relation to the content of this Discussion or of the associated article. Kevin C. Chung, M.D., M.S.; Section of Plastic Surgery, University of Michigan Health System, 2130 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, Mich. 48109-0340, [email protected]

Emergence of Carbapenemase-Producing Klebsiella pneumoniae of Sequence Type 258 in Michigan, USA

The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) in our hospital increased beginning in 2009. We aimed to study the clinical and molecular epidemiology of these emerging isolates. We performed a retrospective review of all adult patients with clinical cultures confirmed as CPE by positive modified Hodge test from 5/2009- 5/2010 at the University of Michigan Health System (UMHS). Clinical information was obtained from electronic medical records. Available CPE isolates were analyzed by polymerase chain reaction (PCR) and sequencing of the 16S rRNA encoding gene and blaKPC locus. Multilocus sequence typing (MLST) was used to characterize Klebsiella pneumoniae isolates. Twenty six unique CPE isolates were obtained from 25 adult patients. The majority were Klebsiella pneumoniae (n=17). Other isolates included K. oxytoca (n=3), Citrobacter freundii (n=2), Enterobacter cloacae (n=2), Enterobacter aerogenes (n=1) and Escherichia coli (n=1). Molecular characterization of 19 available CPE isolates showed that 13 (68%) carried the KPC-3 allele and 6 (32%) carried the KPC-2 allele. Among 14 available K. pneumoniae strains, 12 (86%) carried the KPC-3 allele and belonged to a common lineage, sequence type (ST) 258. The other 2 (14%) K. pneumoniae isolates carried the KPC-2 allele and belonged to two unique STs. Among these ST 258 strains, 67% were isolated from patients with prior exposures to health care settings outside of our institution. In contrast, all CPE isolates carrying the KPC-2 allele and all non ST 258 CPE isolates had acquisition attributable to our hospital.Molecular epidemiology of carbapenemase producing K. pneumoniae suggests that KPC-3 producing K. pneumoniae isolates of a common lineage, sequence type (ST 258), are emerging in our hospital. While ST 258 is a dominant sequence type throughout the United States, this study is the first to report its presence in Michigan.

Laboratory Test Utilization Program

In 2008, the University of Michigan Health System (UMHS) created a Laboratory Test Utilization Program that included the establishment of a Laboratory Formulary Committee under the imprimatur of the Faculty Group Practice, the Office of Clinical Affairs, the Department of Pathology, and UMHS hospital administration. A critical component of the program is UM-CareLink, an order entry system for inpatients and inpatient-like venues. UM-CareLink allows very basic decision support comment prompts. Through the application of peer-reviewed medical evidence, input by medical content experts, excellent cooperation by medical staff, and close oversight by Pathology of the Sendout Laboratory, this program has led to a robust process of test utilization oversight, excellent communication with clinical services, and significant UMHS activity-adjusted reductions in laboratory expense.

Investigational drug service advanced pharmacy practice experience (APPE)

Although the Accreditation Council for Pharmacy Education (ACPE) and the American College of Clinical Pharmacy (ACCP) provide standards and guidelines for required APPEs (community pharmacy, hospital or health system pharmacy, inpatient/acute care general medicine, and ambulatory care) and there are some published descriptions of other elective APPEs, there is little information regarding the provision of an elective APPE focusing on Investigational drug service (IDS) and/or clinical research. The purpose of this paper is to describe the IDS APPE that was developed by the University of Michigan Health System (UMHS) IDS pharmacists in conjunction with the University of Michigan College of Pharmacy (UM COP). The IDS APPE is a four-week full-time program consisting of interaction with various IDS team members, topic discussions, opportunities for writing, and participation in IDS operations. Each week of the IDS APPE features a specific central theme, which includes both discussion topics and hands-on activities. While IDS practices may vary in size and scope, they all fulfill core regulatory requirements related to management of drugs used in clinical trials. Therefore, the IDS APPE description can be adapted and applied to other IDS practices in an effort to provide structure and foundation to the education of pharmacy students on an IDS APPE rotation. Further, it can be adapted into a general clinical research rotation with emphasis on the role of the pharmacist in the management of clinical trials and conduction of research for institutions that do not have a dedicated pharmacy service for clinical research (i.e., IDS).

Atrial Fibrillation Through the Years

Information about a real patient is presented in stages (boldface type) to an expert clinician (Dr Valentin Fuster), who responds to the information, sharing his reasoning with the reader (regular type). A discussion by the authors follows. A 61-year-old man presents with 2 weeks of exertional dyspnea. Pertinent medical history includes hypertension, nephrolithiasis, and internal hemorrhoids. He takes no medications and has no known drug allergies. His father died after a myocardial infarction at 57 years of age. He formerly smoked 1 pack of cigarettes daily for 15 years but ceased tobacco use 10 years before presentation. He ingests 2 glasses of alcohol weekly and denies illicit drug use. His caffeine intake is limited. He is an architect and is married, with healthy children. On physical examination, his temperature is 98.0°F, blood pressure is 130/85 mm Hg bilaterally, pulse is irregular at 130 beats per minute, and respiratory rate is 18 breaths per minute with an oxygen saturation of 97% while breathing room air. He is a slender white man in no distress. His jugular venous pressure is elevated at 14 cm H 2 O. There is no thyromegaly, and the carotid upstrokes are brisk, without bruits. Cardiovascular examination reveals a rapid and irregular heart rhythm with variation in the intensity of the first heart sound. The point of maximal impulse is not displaced. The remainder of the chest and abdominal examination is within normal limits. The extremities are warm and show mild pitting edema. Laboratory testing is significant for normal renal function and electrolytes, but a hemogram reveals a mild thrombocytopenia of 90 000 platelets/μL. ECG demonstrates atrial fibrillation (AF) with an average ventricular rate of 123 bpm ( Figure 1 ). Figure 1. The 12-lead ECG showing atrial fibrillation with a rapid ventricular rate. Dr Valentin Fuster : This is a …

Center for Telehealth and Cybermedicine Research, University of New Mexico Health Sciences Center: A Model of a Telehealth Program Within an Academic Medical Center

An overview of the Center for Telehealth and Cybermedicine Research at the University of New Mexico Health Sciences Center was presented along with several other national and international programs as part of the of a symposium-workshop on telehealth, "Sustaining and Realizing the Promise of Telemedicine," held at the University of Michigan Health System in Ann Arbor, MI, May 18-19, 2012 and hosted by the University of Michigan Telemedicine Resource Center and its Director, Rashid Bashshur. This article describes our Center, its business plan, and a view to the future.

Novel Temporalis Muscle and Fat Pad Morphomic Analyses Aids Preoperative Risk Evaluation and Outcome Assessment in Nonsyndromic Craniosynostosis

Analytical morphomics is the term we created to describe an innovative, highly automated, anatomically indexed processing of 3D medical imaging data captured during the course of a patients' preoperative CT scan. Our specific aim is to determine the efficacy of craniofacial morphomic indices (CMI) such as temporalis muscle and temporal fat pad morphometric values to predict blood transfusion requirement and hospital stay in a cohort of children with nonsyndromic craniosynostosis (NSC). High-throughput, semi-automated image analysis was used to reconstruct the 3-dimensional anatomy of the temporalis muscle and temporal fat pad and to quantify CMIs. The prognostic effect of CMI on clinical outcomes were evaluated among all NSC patients and compared across various craniosynostosis subtypes using Wilcoxon nonparametric tests and Kendall's τ to determine significance. Using preoperative CT images, we evaluated 117 children with NSC from the University of Michigan Health System. Results demonstrate that increased temporal fat pad volume and local temporalis muscle volume are associated with better clinical outcomes in craniosynostosis patients. More specifically, temporal fat pad volume was shown to be a significant predictor of perioperative blood transfusion requirements (P = 0.0033) and increased temporal muscle volume correlated with decreased hospital stay (P = 0.016) when controlling for other covariates including age, sex, weight, and preoperative hematocrit. In addition, the same significant predictors were found when examining individual subtypes of craniosynostosis. Our findings demonstrate that maxillofacial CT scans provide a useful quantitative index reflecting general patient health, risk stratification, and probabilities of intervention in addition to their previously established ability to determine the specific pathology of the patient. We demonstrate that temporal morphomics predict the incidence of blood transfusion, hospital stay, and serve as a proxy for fitness in patients undergoing craniosynostosis surgery.

Prolonged QT Interval Diagnosis Suppression by a Widely Used Computerized ECG Analysis System

Clinicians commonly rely on automated diagnostic interpretations for initial, point-of-care identification of ECG abnormalities. Our study goal was to investigate how one widely used computerized ECG analysis system performs in labeling prolongation of heart rate-corrected QT interval (QTc), an arrhythmia risk marker. ECGs acquired in 2009-2010 from patients ≥18 years old within the University of Michigan Health System, analyzed by the Marquette 12SL ECG Analysis Program (GE Healthcare), and exhibiting sinus rhythms with heart rate <100 beats per minute and QRS duration <120 ms constituted our database. Of 97 046 study ECGs (48.2% from males), a prolonged 12SL-calculated QTc value (ie, ≥470 ms in females >60 years old, and ≥460 ms in other sex/age groups) was displayed in 16 235 (16.7%). Nonetheless, for only 7709 (47.5%) of these ECGs with prolonged QTc did the automated interpretation include an accompanying "Prolonged QT" diagnostic statement. Such prolonged QT under-reporting was manifest across all patient environments and reflected algorithmic suppression of the diagnosis, attributable to ECG waveform-based criteria, in 8526 (52.5%) ECGs with prolonged QTc. Of the latter ECGs with prolonged QT diagnosis suppression, the computer declared 3588 (42.1%) "Normal" despite QTc prolongation. In evaluating an adult patient whose 12SL-interpreted ECG lacks a prolonged QT diagnostic statement (assuming sinus rhythm <100 beats per minute and QRS duration <120 ms), physicians should examine the actual QTc value displayed on the report before concluding that this parameter is normal. Assessment of the clinical impact of prolonged QT diagnosis suppression by ECG waveform-based criteria is warranted.

Cerebral Amyloid Deposition and Serotoninergic Innervation in Parkinson Disease

BACKGROUND Prior studies suggest that serotoninergic neurotransmission reduces β-amyloid (Aβ) production. OBJECTIVE To determine whether serotoninergic system degeneration in Parkinson disease promotes Aβ deposition, using in vivo positron emission tomographic probes of serotonin system integrity and Aβ deposition. DESIGN, SETTING, AND PATIENTS Cross-sectional study of 13 subjects with Parkinson disease from the movement disorders clinics at the University of Michigan Health System and Veterans Affairs Ann Arbor Healthcare System, with positron emission tomography using the serotonin transporter ligand carbon 11 ([11C])-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfaryl)-benzonitrile (DASB) and the Aβ ligand [11C]Pittsburgh compound B. RESULTS Inverse correlations were found between DASB and Pittsburgh compound B distribution volume ratios in the neocortex (ρ=-0.577; P=.04) and striatum (ρ=-0.780; P=.002). CONCLUSION Serotoninergic system degeneration in Parkinson disease may promote the development of cerebral amyloidopathy.