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1.  Patient demographic and health factors associated with frequent use of emergency medical services in a mid-sized city 
To optimize healthcare utilization, health outcomes, and costs, research is needed to improve an understanding of frequent users of emergency health services. Frequent use of emergency services is associated with high costs of healthcare and may be indicative of challenges accessing, or poor outcomes of, healthcare. We identified patient demographics and health factors related to frequent use of the emergency medical services (EMS) system of a mid-sized city. Study findings will aid in the development of targeted interventions to improve population health.
We reviewed 9-1-1 call dispatch data and Baltimore City Fire Department EMS records in 2008–10. Frequent use was defined as six or more EMS incidents in the 23 month period. Analyses used census data to compare demographics of EMS users to their population distribution; and examined differences in demographics and health problems of frequent EMS users compared to non-frequent users.
Frequent EMS users (n=1,969) had a range of 6–199 EMS incidents (mean 11.2) during the observation period; and though they accounted for only 1.5% of EMS users, they were involved in 12.0% of incidents. Frequent users, as compared to non-frequent users and to the population, were more likely to be male, African American, or 45 years or older. Of frequent users, the modal age group was 45–54 years, accounting for 29.7% of frequent users, which represented twice this age group’s population distribution. Furthermore, this age group had the greatest overrepresentation of males (63.0% of frequent users), and was the peak age group for substance abuse related incidents (28.0% of frequent users’ incidents in this age group). Frequent users compared to non-frequent users had lower levels of trauma related incidents (5.1% versus 16.7%) and higher levels of medical incidents (94.8% versus 82.9%). As proportions of EMS incidents among frequent versus non-frequent users, respiratory, mental health, and seizure related incidents were highest in the youngest age groups; and substance abuse related incidents were highest in those middle aged (35–44 years and 45–54 years). Of health problems, behavioral health (mental health or substance use) problems most contributed to frequent EMS use (23.4% of frequent users’ incidents). Across all incidents, 65.8% of frequent users had an indication of behavioral health problems, representing a 6.6-fold higher odds than non-frequent users (22.5%). Frequent compared to non-frequent users also had higher levels of select chronic conditions (diabetes: 39.9% vs. 14.6%, respectively; asthma: 40.9% vs. 13.4%; and HIV: 9.1% vs. 2.4%), with unadjusted odds almost 4 to 7 times higher.
The study findings revealed the major role of chronic somatic and behavioral health problems in frequent EMS use; and that rates of frequent use were highest among those middle aged, African American, and male. The results suggest the need for coordination of EMS with community-based, integrated medical and behavioral health services to improve access and utilization of preventive services, with implications for health outcomes and costs. The study demonstrates the value of EMS patient data in identifying at-risk populations and informing novel, targeted approaches to public health intervention.
PMCID: PMC4063348  PMID: 24238312
emergency medical services utilization; prehospital care; frequent use; mental/psychosocial problems; substance abuse; chronic illness/conditions
2.  MRS in Early and Presymptomatic Carriers of a Novel Octapeptide Repeat Insertion in the Prion Protein Gene 
To evaluate the proton MR spectroscopy (1H MRS) changes in carriers of a novel octapeptide repeat insertion in the Prion Protein Gene (PRNP) and family history of frontotemporal dementia with ataxia. Four at-risk mutation carriers and 13 controls were compared using single voxel, short TE, 1H MRS from the posterior cingulate gyrus. The mutation carriers had an increased choline/creatine, p=0.003 and increased myoinositol/creatine ratio, p=0.003. 1H MRS identified differences in markers of glial activity and choline metabolism in pre- and early symptomatic carriers of a novel PRNP gene octapeptide insertion. These findings expand the possible diagnostic utility of 1H MRS in familial prion disorders.
PMCID: PMC3480551  PMID: 22612156
MRS; MRI; familial prion disorders; frontotemporal dementia
3.  EMS runs for suspected opioid overdose: Implications for surveillance and prevention 
Opioid (including prescription opiate) abuse and overdose rates in the US have surged in the past decade. The dearth and limitations of opioid abuse and overdose surveillance systems impede the development of interventions to address this epidemic. We explored evidence to support the validity of emergency medical services (EMS) data on naloxone administration as a possible proxy for estimating incidence of opioid overdose.
We reviewed data from Baltimore City Fire Department EMS patient records matched with dispatch records over a thirteen month time period (2008-2009), and census 2008 data. We calculated incidence rates and patient demographic and temporal patterns of naloxone administration, and examined patient evaluation data associated with naloxone administration. Results were compared to the demographic distributions of the EMS patient and city population and to prior study findings.
Of 116,910 EMS incidents during the study period for patients 15 years and older, EMS providers administered naloxone 1,297 times (1.1% of incidents), an average of 100 administrations per month. Overall incidence was 1.87 administrations per 1,000 population per year. Findings indicated naloxone administration peaked in summer months (31% of administrations), weekends (32%), and late afternoon (4-5:00pm [8%]); and there was a trend toward peaking in the first week of the month. The incidence of suspected opioid overdose was highest among males, whites, and those in the 45-54 year age group. Findings on temporal patterns were comparable to findings from prior studies. Demographic patterns of suspected opioid overdose were similar to medical examiner reports of demographic patterns of fatal drug or alcohol related overdoses in Baltimore in 2008-9 (88% of which involved opioids). The findings on patient evaluation data suggest some inconsistencies with previously recommended clinical indications of opioid overdose.
While our findings suggest limitations of EMS naloxone administration data as a proxy indicator of opioid overdose, the results provide partial support of the data for estimating opioid overdose incidence and suggest ways to improve such data. The study findings have implications for an EMS role in conducting real-time surveillance and treatment and prevention of opioid abuse and overdose.
PMCID: PMC3682796  PMID: 23734988
emergency medical services; heroin/opiate/opioid abuse; Narcan/naloxone; overdose; epidemiology
4.  Characterization of a Family With c9FTD/ALS Associated With the GGGGCC Repeat Expansion in C9ORF72 
Archives of neurology  2012;69(9):1164-1169.
The hexanucleotide repeat in the chromosome 9 open reading frame 72 (C9ORF72) gene was recently discovered as the pathogenic mechanism underlying many families with frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) linked to chromosome 9 (c9FTD/ALS). We report the clinical, neuropsychological, and neuroimaging findings of a family with the C9ORF72 mutation and clinical diagnoses bridging the FTD, parkinsonism and ALS spectrum.
To characterize the antemortem characteristics of a family with c9FTD/ALS associated with the GGGGCC repeat expansion in C9ORF72
Clinical series.
Tertiary care academic medical center.
The members of the family affected by the mutation with features of FTD and/or ALS.
Main Outcome Measures
Clinical, neuropsychological, and neuroimaging assessments.
All three examined subjects had the hexanucleotide expansion detected in C9ORF72. All had personality/behavioral changes early in the course of the disease. One case had levodopa-unresponsive parkinsonism, and one had ALS. MRI showed symmetric bilateral frontal, temporal, insular and cingulate atrophy.
This report highlights the clinical and neuroimaging characteristics of a family with c9FTD/ALS. Further studies are needed to better understand the phenotypical variability and the clinico-neuroimaging-neuropathologic correlations.
PMCID: PMC3625860  PMID: 22637471
5.  Underlying Neurobiology and Clinical Correlates of Mania Status-Post Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s disease: A Review of the Literature 
Deep brain stimulation (DBS) is a novel and effective surgical intervention for refractory Parkinson’s disease (PD).
We review the current literature to identify the clinical correlates associated with STN DBS-induced hypomania/mania in PD patients.
Ventromedial electrode placement has been most consistently implicated in the induction of STN DBS-induced mania. There is some evidence of symptom amelioration when electrode placement is switched to a more dorsolateral contact. Additional clinical correlates may include unipolar stimulation, higher voltage (>3 V), male patients and/or early onset PD.
STN DBS-induced psychiatric adverse events emphasize the need for comprehensive psychiatric presurgical evaluation and follow-up in PD patients. Animal studies and prospective clinical research, combined with advanced neuroimaging techniques, are needed to identify clinical correlates and underlying neurobiological mechanism(s) of STN DBS-induced mania. Such working models would serve to further our understanding of the neurobiological underpinnings of mania and contribute valuable new insight towards development of future DBS mood stabilization therapies.
PMCID: PMC3570815  PMID: 22450620
Parkinson’s disease; mania; subthalamic nucleus (STN); deep brain stimulation (DBS)
6.  Clinical Characterization of a Kindred with a Novel Twelve Octapeptide Repeat Insertion in the Prion Protein Gene 
Archives of Neurology  2011;68(9):1165-1170.
To report the clinical, electroencephalographic, and neuroradiologic findings in a kindred with a novel insertion in the prion protein gene (PRNP).
Clinical description of a kindred.
Mayo Clinic Alzheimer’s Disease Research Center (Rochester).
Two pathologically-confirmed cases and their relatives.
Main outcome measures
Clinical features, electroencephalographic patterns, magnetic resonance imaging abnormalities, genetic analyses and neuropathological features.
The proband presented with clinical and neuroimaging features of atypical frontotemporal dementia (FTD) and ataxia. Generalized tonic-clonic seizures developed later in her course, and electroencephalography revealed spike and wave discharges but no periodic sharp wave complexes. Her affected sister and father also exhibited FTD-like features, and both experienced generalized tonic-clonic seizures and gait ataxia late in their course. Genetic analyses in the proband identified a novel defect in PRNP with one mutated allele carrying a 288 base pair insertion (BPI) consisting of 12 octapeptide repeats. Neuropathologic examination of the sister and proband revealed PrP-positive plaques and widespread tau-positive tangles.
This kindred has a unique combination of clinical and neuropathologic features associated with the largest BPI identified to date in PRNP, and underscores the need to consider familial prion disease in the differential diagnosis of a familial FTD-like syndrome.
PMCID: PMC3326586  PMID: 21911696
frontotemporal dementia; FTD; nonfluent aphasia; Gerstmann–Straüssler–Scheinker syndrome (GSS); Creutzfeldt-Jakob disease (CJD); prion; PRNP
7.  Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72 
Brain  2012;135(3):765-783.
Numerous kindreds with familial frontotemporal dementia and/or amyotrophic lateral sclerosis have been linked to chromosome 9, and an expansion of the GGGGCC hexanucleotide repeat in the non-coding region of chromosome 9 open reading frame 72 has recently been identified as the pathogenic mechanism. We describe the key characteristics in the probands and their affected relatives who have been evaluated at Mayo Clinic Rochester or Mayo Clinic Florida in whom the hexanucleotide repeat expansion were found. Forty-three probands and 10 of their affected relatives with DNA available (total 53 subjects) were shown to carry the hexanucleotide repeat expansion. Thirty-six (84%) of the 43 probands had a familial disorder, whereas seven (16%) appeared to be sporadic. Among examined subjects from the 43 families (n = 63), the age of onset ranged from 33 to 72 years (median 52 years) and survival ranged from 1 to 17 years, with the age of onset <40 years in six (10%) and >60 in 19 (30%). Clinical diagnoses among examined subjects included behavioural variant frontotemporal dementia with or without parkinsonism (n = 30), amyotrophic lateral sclerosis (n = 18), frontotemporal dementia/amyotrophic lateral sclerosis with or without parkinsonism (n = 12), and other various syndromes (n = 3). Parkinsonism was present in 35% of examined subjects, all of whom had behavioural variant frontotemporal dementia or frontotemporal dementia/amyotrophic lateral sclerosis as the dominant clinical phenotype. No subject with a diagnosis of primary progressive aphasia was identified with this mutation. Incomplete penetrance was suggested in two kindreds, and the youngest generation had significantly earlier age of onset (>10 years) compared with the next oldest generation in 11 kindreds. Neuropsychological testing showed a profile of slowed processing speed, complex attention/executive dysfunction, and impairment in rapid word retrieval. Neuroimaging studies showed bilateral frontal abnormalities most consistently, with more variable degrees of parietal with or without temporal changes; no case had strikingly focal or asymmetric findings. Neuropathological examination of 14 patients revealed a range of transactive response DNA binding protein molecular weight 43 pathology (10 type A and four type B), as well as ubiquitin-positive cerebellar granular neuron inclusions in all but one case. Motor neuron degeneration was detected in nine patients, including five patients without ante-mortem signs of motor neuron disease. While variability exists, most cases with this mutation have a characteristic spectrum of demographic, clinical, neuropsychological, neuroimaging and especially neuropathological findings.
PMCID: PMC3286335  PMID: 22366793
frontotemporal dementia; amyotrophic lateral sclerosis; motor neuron disease; TDP-43; neurogenetics; chromosome 9
8.  Atherosclerosis Risk Factors in American Indians With Alzheimer Disease 
Factors predisposing to and associated with atherosclerosis may impact the onset and progression of Alzheimer disease (AD). The high prevalence of atherosclerosis and associated risk factors in American Indians makes them ideal subjects to test this association. We compared frequency of history of hypertension, myocardial infarction, stroke, diabetes, and high cholesterol in 34 American Indians with AD with 34 age-matched American Indian controls, and 34 age-matched whites with probable AD. We also measured waist size, height, and weight, and acquired blood for determination of plasma homocysteine and apolipoprotein E genotype. The 3 groups did not differ significantly in age or sex. History of hypertension and diabetes was significantly more common among American Indian AD patients than Indian controls or whites with AD. The 3 groups did not differ in history of stroke or myocardial infarction. Body mass index was significantly greater in both Indian groups than the white AD group. Plasma homocysteine levels were greater, but not significantly so, in the Indian AD than the Indian control group. Thus, there is preliminary evidence of a modest association between history of hypertension and diabetes and AD in a small sample of American Indians. This suggests that changes in lifestyle factors could influence the expression of AD in American Indians.
PMCID: PMC3176329  PMID: 18580594
atherosclerosis; hypertension; diabetes; homocysteine; Alzheimer disease
9.  Is race medically relevant? A qualitative study of physicians' attitudes about the role of race in treatment decision-making 
The role of patient race in medical decision-making is heavily debated. While some evidence suggests that patient race can be used by physicians to predict disease risk and determine drug therapy, other studies document bias and stereotyping by physicians based on patient race. It is critical, then, to explore physicians' attitudes regarding the medical relevance of patient race.
We conducted a qualitative study in the United States using ten focus groups of physicians stratified by self-identified race (black or white) and led by race-concordant moderators. Physicians were presented with a medical vignette about a patient (whose race was unknown) with Type 2 diabetes and untreated hypertension, who was also a current smoker. Participants were first asked to discuss what medical information they would need to treat the patient. Then physicians were asked to explicitly discuss the importance of race to the hypothetical patient's treatment. To identify common themes, codes, key words and physician demographics were compiled into a comprehensive table that allowed for examination of similarities and differences by physician race. Common themes were identified using the software package NVivo (QSR International, v7).
Forty self-identified black and 50 self-identified white physicians participated in the study. All physicians - regardless of their own race - believed that medical history, family history, and weight were important for making treatment decisions for the patient. However, black and white physicians reported differences in their views about the relevance of race. Several black physicians indicated that patient race is a central factor for choosing treatment options such as aggressive therapies, patient medication and understanding disease risk. Moreover, many black physicians considered patient race important to understand the patient's views, such as alternative medicine preferences and cultural beliefs about illness. However, few white physicians explicitly indicated that the patient's race was important over-and-above medical history. Instead, white physicians reported that the patient should be treated aggressively regardless of race.
This investigation adds to our understanding about how physicians in the United States consider race when treating patients, and sheds light on issues physicians face when deciding the importance of race in medical decision-making.
PMCID: PMC3167748  PMID: 21819597
10.  Annualized Functional Change in Alzheimer's Disease Participants and Normal Controls 
The Clinical neuropsychologist  2008;22(5):801-806.
The rate of functional change in persons with mild Alzheimer's disease (AD) was compared to that of cognitively normal elderly control subjects. A comparison of annualized rates of change on the Test of Everyday Functional Abilities (TEFA) was carried out, along with a brief measure of instrumental activities of daily living skills, in persons with mild AD (Mini-Mental State Exam score > 20) and cognitively normal elderly controls. Persons with AD (N = 30) showed an 8.5 % (3.5 point) annualized decline in TEFA scores over an average of 1.2 years; there was no decline in a group of elderly normal controls (N = 20) over an average of 1.5 years. Persons with mild AD showed functional changes over the course of a year on a direct measure of instrumental activities of daily living; a comparable group of normally aging persons did not.
PMCID: PMC2566778  PMID: 18609317
Alzheimer's disease; Direct measure; Functional abilities
11.  Modeling the impact of COPD on the brain 
Previous studies have shown that COPD adversely affects distant organs and body systems, including the brain. This pilot study aims to model the relationships between respiratory insufficiency and domains related to brain function, including low mood, subtly impaired cognition, systemic inflammation, and brain structural and neurochemical abnormalities. Nine healthy controls were compared with 18 age- and education-matched medically stable COPD patients, half of whom were oxygen-dependent. Measures included depression, anxiety, cognition, health status, spirometry, oximetry at rest and during 6-minute walk, and resting plasma cytokines and soluble receptors, brain MRI, and MR spectroscopy in regions relevant to mood and cognition. ANOVA was used to compare controls with patients and with COPD subgroups (oxygen users [n = 9] and nonusers [n = 9]), and only variables showing group differences at p ≤ 0.05 were included in multiple regressions controlling for age, gender, and education to develop the final model. Controls and COPD patients differed significantly in global cognition and memory, mood, and soluble TNFR1 levels but not brain structural or neurochemical measures. Multiple regressions identified pathways linking disease severity with impaired performance on sensitive cognitive processing measures, mediated through oxygen dependence, and with systemic inflammation (TNFR1), related through poor 6-minute walk performance. Oxygen desaturation with activity was related to indicators of brain tissue damage (increased frontal choline, which in turn was associated with subcortical white matter attenuation). This empirically derived model provides a conceptual framework for future studies of clinical interventions to protect the brain in patients with COPD, such as earlier oxygen supplementation for patients with desaturation during everyday activities.
PMCID: PMC2629981  PMID: 18990971
oxygen desaturation; frontal choline; cognition; mood; SGRQ; cytokines

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