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1.
J Neurol ; 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38656620

ABSTRACT

OBJECTIVE: To describe the frequency of neuropsychiatric complications among hospitalized patients with coronavirus disease 2019 (COVID-19) and their association with pre-existing comorbidities and clinical outcomes. METHODS: We retrospectively identified all patients hospitalized with COVID-19 within a large multicenter New York City health system between March 15, 2020 and May 17, 2021 and randomly selected a representative cohort for detailed chart review. Clinical data, including the occurrence of neuropsychiatric complications (categorized as either altered mental status [AMS] or other neuropsychiatric complications) and in-hospital mortality, were extracted using an electronic medical record database and individual chart review. Associations between neuropsychiatric complications, comorbidities, laboratory findings, and in-hospital mortality were assessed using multivariate logistic regression. RESULTS: Our study cohort consisted of 974 patients, the majority were admitted during the first wave of the pandemic. Patients were treated with anticoagulation (88.4%), glucocorticoids (24.8%), and remdesivir (10.5%); 18.6% experienced severe COVID-19 pneumonia (evidenced by ventilator requirement). Neuropsychiatric complications occurred in 58.8% of patients; 39.8% experienced AMS; and 19.0% experienced at least one other complication (seizures in 1.4%, ischemic stroke in 1.6%, hemorrhagic stroke in 1.0%) or symptom (headache in 11.4%, anxiety in 6.8%, ataxia in 6.3%). Higher odds of mortality, which occurred in 22.0%, were associated with AMS, ventilator support, increasing age, and higher serum inflammatory marker levels. Anticoagulant therapy was associated with lower odds of mortality and AMS. CONCLUSION: Neuropsychiatric complications of COVID-19, especially AMS, were common, varied, and associated with in-hospital mortality in a diverse multicenter cohort at an epicenter of the COVID-19 pandemic.

2.
Epilepsia ; 64(10): 2725-2737, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37452760

ABSTRACT

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is associated with mortality in persons with comorbidities. The aim of this study was to evaluate in-hospital outcomes in patients with COVID-19 with and without epilepsy. METHODS: We conducted a retrospective study of patients with COVID-19 admitted to a multicenter health system between March 15, 2020, and May 17, 2021. Patients with epilepsy were identified using a validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)/ICD-10-CM case definition. Logistic regression models and Kaplan-Meier analyses were conducted for mortality and non-routine discharges (i.e., not discharged home). An ordinary least-squares regression model was fitted for length of stay (LOS). RESULTS: We identified 9833 people with COVID-19 including 334 with epilepsy. On univariate analysis, people with epilepsy had significantly higher ventilator use (37.70% vs 14.30%, p < .001), intensive care unit (ICU) admissions (39.20% vs 17.70%, p < .001) mortality rate (29.60% vs 19.90%, p < .001), and longer LOS (12 days vs 7 days, p < .001). and fewer were discharged home (29.64% vs 57.37%, p < .001). On multivariate analysis, only non-routine discharge (adjusted odds ratio [aOR] 2.70, 95% confidence interval [CI] 2.00-3.70; p < .001) and LOS (32.50% longer, 95% CI 22.20%-43.60%; p < .001) were significantly different. Factors associated with higher odds of mortality in epilepsy were older age (aOR 1.05, 95% CI 1.03-1.08; p < .001), ventilator support (aOR 7.18, 95% CI 3.12-16.48; p < .001), and higher Charlson comorbidity index (CCI) (aOR 1.18, 95% CI 1.04-1.34; p = .010). In epilepsy, admissions between August and December 2020 or January and May 2021 were associated with a lower odds of non-routine discharge and decreased LOS compared to admissions between March and July 2020, but this difference was not statistically significant. SIGNIFICANCE: People with COVID-19 who had epilepsy had a higher odds of non-routine discharge and longer LOS but not higher mortality. Older age (≥65), ventilator use, and higher CCI were associated with COVID-19 mortality in epilepsy. This suggests that older adults with epilepsy and multimorbidity are more vulnerable than those without and should be monitored closely in the setting of COVID-19.


Subject(s)
COVID-19 , Epilepsy , Humans , Aged , Cohort Studies , Retrospective Studies , Length of Stay , Epilepsy/epidemiology , Hospitals , Hospital Mortality
3.
Eur J Immunol ; 53(8): e2250228, 2023 08.
Article in English | MEDLINE | ID: mdl-37194443

ABSTRACT

The advent of highly effective disease modifying therapy has transformed the landscape of multiple sclerosis (MS) care over the last two decades. However, there remains a critical, unmet need for sensitive and specific biomarkers to aid in diagnosis, prognosis, treatment monitoring, and the development of new interventions, particularly for people with progressive disease. This review evaluates the current data for several emerging imaging and liquid biomarkers in people with MS. MRI findings such as the central vein sign and paramagnetic rim lesions may improve MS diagnostic accuracy and evaluation of therapy efficacy in progressive disease. Serum and cerebrospinal fluid levels of several neuroglial proteins, such as neurofilament light chain and glial fibrillary acidic protein, show potential to be sensitive biomarkers of pathologic processes such as neuro-axonal injury or glial-inflammation. Additional promising biomarkers, including optical coherence tomography, cytokines and chemokines, microRNAs, and extracellular vesicles/exosomes, are also reviewed, among others. Beyond their potential integration into MS clinical care and interventional trials, several of these biomarkers may be informative of MS pathogenesis and help elucidate novel targets for treatment strategies.


Subject(s)
Multiple Sclerosis , Humans , Multiple Sclerosis/diagnostic imaging , Biomarkers , Prognosis , Magnetic Resonance Imaging/methods , Neurofilament Proteins/cerebrospinal fluid , Glial Fibrillary Acidic Protein/cerebrospinal fluid
4.
Mult Scler ; 28(14): 2157-2159, 2022 12.
Article in English | MEDLINE | ID: mdl-36341515

Subject(s)
Drugs, Generic , Humans
5.
Neurohospitalist ; 12(2): 268-272, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35419149

ABSTRACT

Community-acquired bacterial meningitis (CABM) morbidity and mortality remains high in those infected. Rapid diagnosis and treatment is paramount to reducing mortality and improving outcome. This retrospective cohort study aims to assess the time from presentation to diagnosis and treatment of vaccine preventable CABM as well as identify possible factors associated with delays in diagnosis and antibiotic administration. A retrospective chart review was conducted of individuals who presented to Columbia University Irving Medical Center (CUIMC), Children's Hospital of New York (CHONY), Mount Sinai Medical Center, and Weill Cornell Medical Center with BM due to Haemophilus influenzae type B, Streptococcus pneumoniae, and Neisseria meningitidis between January 1, 2012 and December 31, 2017. Diagnosis was delayed by more than 8 hours in 13 patients (36.1%) and 5 individuals (13.9%) had a delay of 4 hours or more from presentation to the administration of antibiotics with appropriate CNS coverage. All of these patients were also initially misdiagnosed at an outpatient clinic, outside hospital, or emergency department. This retrospective study identified febrile and/or viral infections not otherwise specified and otitis media as the most common misdiagnoses underlying delays from presentation to diagnosis and to antibiotic treatment in those with BM.

6.
Mult Scler ; 28(1): 139-148, 2022 01.
Article in English | MEDLINE | ID: mdl-34787004

ABSTRACT

OBJECTIVE: Assess readmissions for depression or suicide attempt (SA) after MS admission versus other chronic inflammatory illnesses. METHODS: This retrospective cohort study identified MS, asthma, rheumatoid arthritis (RA), depression, and SA in the 2013 National Readmissions Database by International Classification of Diseases codes. Index admissions (MS, n = 7698; asthma, n = 93,590; RA, n = 3685) and depression or SA readmission rates were analyzed. Hazard ratios (HRs) estimated 1-year depression/SA readmission hazard, comparing MS to asthma or RA, adjusting for age, sex, psychiatric comorbidity, substance abuse, tobacco use, income, and index hospitalization characteristics. RESULTS: MS had more baseline depression (24.7%) versus asthma (15.6%) and RA (14.6%). Ninety-day depression readmission rate was higher in MS (0.5%) than asthma (0.3%) and RA (0.03%). Depression readmission HR was higher after MS admission versus asthma (HR = 1.37, 95% confidence interval (CI) = 1.00-1.86, p = 0.0485) and RA (HR = 4.68, 95% CI = 1.60-13.62, p = 0.0047). HR was not different for SA readmission across groups. Depression readmission HR was more than double in MS patients with psychiatric disease or substance abuse versus RA or asthma patients with either comorbidity. CONCLUSION: Depression readmission risk after MS hospitalization was elevated versus asthma/RA. Substance use and baseline psychiatric comorbidity were more strongly associated with depression readmission in MS patients.


Subject(s)
Multiple Sclerosis , Patient Readmission , Chronic Disease , Comorbidity , Depression/epidemiology , Humans , Retrospective Studies , Risk Factors
7.
J Stroke Cerebrovasc Dis ; 30(5): 105659, 2021 May.
Article in English | MEDLINE | ID: mdl-33621823

ABSTRACT

BACKGROUND AND PURPOSE: Prior studies examining sex-related risk of readmission for ischemic stroke (IS) after coronary artery bypass grafting (CABG) did not adjust for preoperative comorbidities and used small study samples that were single-center or otherwise poorly generalizable. We assessed risk of readmission for IS after CABG for females compared to males in a nationwide sample. METHODS: The 2013 Nationwide Readmissions Database contains data on 49% of all U.S. hospitalizations. We used population weighting to determine national estimates. Using all follow-up data up to 1 year after discharge from CABG hospitalization, we estimated Kaplan-Meier cumulative risk of IS, stratified by sex, using the log-rank test for significance. We created Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for IS readmission, with sex as the main independent variable. We ran unadjusted models and models adjusted for age, vascular risk factors, estimated severity of illness and risk of mortality, hospital characteristics, and income quartile of patient's zip code. RESULTS: An estimated 53,270 females and 147,396 males survived index CABG admission in 2013. There was a consistently elevated cumulative risk of readmission for IS after CABG for females versus males (log-rank p-value = 0.0014). In the unadjusted Cox model, the HR of IS in females vs. males was 1.35 (95% CI 1.12-1.62, p = 0.0015). The elevated risk for females remained after adjusting for severity of illness (1.30 [1.08-1.56], p = 0.0056) and risk of mortality (1.28 [1.07-1.54], p = 0.0086). This elevated risk persisted after adjusting for multiple vascular risk factors, hospital characteristics, and income quartile of patient's zip code (1.23 [1.02-1.48], p = 0.03). CONCLUSIONS: We found a 23% increased risk of readmission for IS up to 1 year after CABG for females compared to males in a fully adjusted model utilizing a large, contemporary, nationwide database. Further research would clarify mechanisms of this increased risk among women.


Subject(s)
Coronary Artery Bypass/adverse effects , Coronary Artery Disease/surgery , Ischemic Stroke/epidemiology , Patient Readmission , Aged , Coronary Artery Bypass/mortality , Coronary Artery Disease/mortality , Databases, Factual , Female , Humans , Ischemic Stroke/diagnosis , Ischemic Stroke/mortality , Male , Risk Assessment , Risk Factors , Sex Factors , Time Factors , Treatment Outcome , United States/epidemiology
8.
Epilepsia ; 62(2): 397-407, 2021 02.
Article in English | MEDLINE | ID: mdl-33475161

ABSTRACT

OBJECTIVE: This study aimed to evaluate the proportion of patients with seizures and electroencephalography (EEG) abnormalities in autoimmune encephalitis (AE) and its most common subtypes. METHODS: This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standards and was registered with the International Prospective Register of Systematic Reviews (PROSPERO). We searched Medline All, Embase, and PsychINFO in Ovid from inception to June 2019 for articles pertaining to AE and seizure. Included studies reported seizure and/or EEG data in cohorts of ≥10 AE patients. Patient demographics, antibody type, seizure incidence, and EEG findings were extracted. Review of studies and data extraction were performed in duplicate. In addition to descriptive analysis, quantitative synthesis stratified by autoantibody subtype was performed with logistic regression and chi-square analyses. RESULTS: Our search yielded 3856 abstracts: 1616 were selected for full-text review and 118 studies met eligibility criteria. Of 3722 antibody-positive AE patients, 2601 (69.9%) had clinical seizures during the course of their illness. Of the 2025 patients with antibody-positive AE and available EEG data, 1718 (84.8%) had some EEG abnormality (eg, epileptiform discharges, slowing, and so on). Anti- N-methyl-d-aspartate (NMDA) receptor encephalitis (anti-NMDARE) was the most commonly reported type of AE (1985/3722, 53.3%). Of the anti-NMDARE patients with available seizure or EEG data, 71.8% (n = 1425/1985) had clinical seizures during their illness, and 89.7% (n = 1172/1306) had EEG abnormalities. For all AE patients and in the anti-NMDARE subpopulation, seizures were more common in younger patients (p < .05). SIGNIFICANCE: This systematic review provides an estimate of the proportion of AE patients with seizures, confirming the magnitude of seizure burden in this population. Prospective studies are needed to understand population-based prevalence of seizures, identify factors associated with seizures, and evaluate particular EEG findings as biomarkers of seizures and outcomes in AE.


Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis/physiopathology , Encephalitis/physiopathology , Hashimoto Disease/physiopathology , Seizures/physiopathology , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/immunology , Autoantibodies/immunology , Autoimmune Diseases of the Nervous System/immunology , Autoimmune Diseases of the Nervous System/physiopathology , Electroencephalography , Encephalitis/immunology , Glutamate Decarboxylase/immunology , Hashimoto Disease/immunology , Humans , Receptors, GABA-B/immunology
9.
Neurology ; 96(13): e1804-e1808, 2021 03 30.
Article in English | MEDLINE | ID: mdl-33184229

ABSTRACT

OBJECTIVE: To describe cases presented by junior neurology residents and to evaluate resident diagnostic patterns to help address individual and systemic educational needs. METHODS: For 6 academic years, details of all morning report cases assessed and presented by junior neurology residents were logged, including the resident's independent initial diagnostic impression. Cases were later revisited at subsequent morning reports to "close the loop" on a final diagnosis. We conducted retrospective review to quantify case demographics and to determine resident diagnostic accuracy based on prespecified localization pathways. RESULTS: Demographic analysis included 1,472 cases; of these, 1,301 qualified for accuracy analysis due to diagnostic uncertainty at time of morning report. Non-neurologic etiologies represented 26.0% of cases. CNS etiologies were the majority (86.0%) of neurologic cases. The most frequent diagnoses were ischemic stroke and seizure. Overall resident diagnostic accuracy was 64.0%. Accuracy was similar between central and peripheral etiologies. Of 1,301 cases, 15.3% were overcalled as neurologic, while neurologic disease was rarely mistaken as non-neurologic (5.1%). Most diagnostic errors (49.1%) occurred when determining whether a case was neurologic. Where in the localization pathway errors occurred varied between etiologies. CONCLUSION: Overall diagnostic accuracy for neurology junior residents in our cohort was similar to prior work conducted in smaller samples. Analysis of errors, particularly at the critical "neurologic or non-neurologic" decision point, warrants further investigation. Close the loop methodology is simple to employ and can guide educational and quality initiatives to improve neurology resident clinical acumen.


Subject(s)
Clinical Competence , Diagnostic Errors , Internship and Residency , Nervous System Diseases/diagnosis , Neurology/education , Adolescent , Adult , Aged , Aged, 80 and over , Child , Cohort Studies , Education, Medical, Graduate/methods , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
10.
Stroke ; 51(3): 800-807, 2020 03.
Article in English | MEDLINE | ID: mdl-31951154

ABSTRACT

Background and Purpose- There are few large studies examining comorbidities, outcomes, and acute interventions for patients with retinal artery occlusion (RAO). RAO shares pathophysiology with acute ischemic stroke (AIS); direct comparison may inform emergent treatment, evaluation, and secondary prevention. Methods- The National Readmissions Database contains data on ≈50% of US hospitalizations from 2013 to 2015. We used International Classification of Diseases, Ninth Revision, codes to identify and compare index RAO and AIS admissions, comorbidities, and interventions and Clinical Comorbidity Software codes to identify readmissions causes, using survey-weighted methods when possible. Cumulative risk of all-cause readmission after RAO ≤1 year was estimated by Kaplan-Meier analysis. Results- Among 4871 RAO and 1 239 963 AIS admissions, patients with RAO were less likely (P<0.0001) than patients with AIS to have diabetes mellitus (RAO, 24.3% versus AIS, 36.8%), congestive heart failure (9.1% versus 14.8%), atrial fibrillation (15.5% versus 25.2%), or hypertension (62.2% versus 67.6%) but more likely to have valvular disease (13.3% versus 10.5%) and tobacco usage (38.6% versus 32.9%). In RAO admissions, thrombolysis was administered in 2.9% (5.8% in central RAO subgroup, versus 8.0% of AIS), therapeutic anterior chamber paracentesis in 1.0%, thrombectomy in none; 1.4% received carotid endarterectomy during index admission, 1.6% within 30 days. Nearly 1 in 10 patients with RAO were readmitted within 30 days and were more than twice as likely as patients with AIS to be readmitted for dysrhythmia or endocarditis. Readmission for stroke after RAO was the highest within the first 150 days after index admission, and risk was higher in central RAO than in branch RAO. Conclusions- Patients with RAO had high prevalence of many stroke risk factors, particularly valvular disease and smoking, which can be addressed to minimize subsequent risk. Despite less baseline atrial fibrillation, RAO patients were more likely to be readmitted for atrial fibrillation/dysrhythmias. A variety of interventions was administered. AIS risk is the highest shortly after RAO, emphasizing the importance of urgent, thorough neurovascular evaluation.


Subject(s)
Retinal Artery Occlusion/physiopathology , Retinal Artery Occlusion/therapy , Aged , Brain Ischemia/mortality , Brain Ischemia/physiopathology , Brain Ischemia/therapy , Comorbidity , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Patient Readmission/statistics & numerical data , Prevalence , Retinal Artery Occlusion/mortality , Risk Factors , Smoking/adverse effects , Smoking/epidemiology , Stroke/mortality , Stroke/physiopathology , Stroke/therapy , Survival Analysis , Thrombolytic Therapy , Treatment Outcome
11.
J Neurovirol ; 26(1): 14-22, 2020 02.
Article in English | MEDLINE | ID: mdl-31529280

ABSTRACT

Enteroviruses (EV) are responsible for a large number of meningoencephalitis cases, especially in children. The objective of this study was to identify modes of diagnosis including the significance of respiratory and cerebrospinal fluid samples, associated clinical characteristics, inpatient management, and outcome of individuals with EV infections of the central nervous system (CNS). Electronic medical records of individuals with enterovirus infections of the CNS who presented to the Columbia University Irving Medical Center and Children's Hospital of New York between January 1, 2012 and December 31, 2017 were reviewed retrospectively for demographic, epidemiological, and clinical data. The median age overall was 1.7 months (interquartile range 14 years) and most (62.4%) were male. The majority of CNS infections presented as meningitis (95.7%) and occurred in the summer (45.2%) and fall seasons (37.6%). Eighty-five cases (91.4%) demonstrated EV positivity in cerebrospinal fluid, thirty cases (32.3%) exhibited both cerebrospinal fluid and respiratory positivity, and eight cases (8.6%) exhibited respiratory positivity with coinciding neurological findings. Eighty-nine individuals overall (95.7%) received antibiotics and 37 (39.8%) received antiviral treatment. All surviving individuals had favorable Modified Rankin Scores (MRS) within the zero to two ranges upon discharge. Testing respiratory samples in addition to cerebrospinal fluid was found to be an important diagnostic tool in EV-associated cases. While clinical outcomes were favorable for an overwhelming majority of cases, etiological understanding of CNS infections is essential for identifying ongoing and changing epidemiological patterns and aid in improving the diagnosis and treatment.


Subject(s)
Enterovirus Infections , Meningoencephalitis/virology , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Retrospective Studies
12.
Disabil Rehabil ; 42(17): 2437-2443, 2020 08.
Article in English | MEDLINE | ID: mdl-31006276

ABSTRACT

Objective: This study sought to determine whether parenting styles predict long-term psychosocial outcomes after traumatic brain injury in young children.Methods: The study involved a concurrent cohort, prospective design, with longitudinal assessments up to early adolescence. Participants included 126 children with moderate to severe traumatic brain injury or orthopedic injury, ages 3 to 6 years 11 months, recruited between 2003 and 2006. Parents rated children's pre-injury behavioral adjustment, social competence, and executive functioning shortly after injury, and again 6.8 years post injury. Parents also rated their parenting styles (permissive, authoritarian, authoritative) at both occasions.Results: After controlling for pre-injury functioning, the groups differed significantly on all three outcomes (ΔR2 0.07 to 0.13). Late but not early parenting styles predicted outcomes in all groups (ΔR2 0.06 to 0.17): more permissive parenting predicted worse outcomes in all domains (ß= -0.18, 0.20, 0.27); and more authoritative parenting predicted better social competence and executive functioning (ß= -0.17, 0.46). Severe traumatic brain injury interacted with parenting style for several outcomes, with ineffective parenting exacerbating the negative sequelae.Conclusions: Parenting style predicts children's long-term psychosocial functioning after early childhood injury, and may moderate the effects of early traumatic brain injury.Implications for rehabilitationChildren with traumatic brain injury (especially those with severe injuries) are likely to require long-term monitoring and rehabilitation to address their psychosocial functioning.Interventions that focus on parenting may be an important avenue for promoting better psychosocial outcomes among children with severe traumatic brain injury.


Subject(s)
Brain Injuries, Traumatic , Parenting , Adolescent , Child , Child, Preschool , Cohort Studies , Humans , Parents , Prospective Studies
13.
Psychiatr Serv ; 69(1): 84-99, 2018 01 01.
Article in English | MEDLINE | ID: mdl-29089010

ABSTRACT

OBJECTIVE: Although the negative consequences associated with first-episode psychosis (FEP) have been well investigated, relatively less is known about positive changes that people may experience after FEP. Existing literature is disparate and in need of synthesis. Such a synthesis can inform the design of mental health services that foster strengths, hope, and optimism. The objective of this study was to synthesize the literature on how positive change is experienced after FEP by affected persons and their families and friends and to delineate the individual, social, and structural factors facilitating positive change. METHODS: A librarian-assisted systematic review of quantitative, qualitative, and mixed-methods studies published in English between 1970 and 2015 was conducted. Articles identified from three databases (PubMed, PsycINFO, and Embase) and through additional search strategies were screened. Results sections were open coded and analyzed by using thematic synthesis. RESULTS: Of the 2,777 studies identified, 40 were retained. The synthesis of findings showed that after FEP, service users and their families and friends experienced positive changes at the individual (for example, more insight and clarity), interpersonal (for example, improved relationships), and spiritual levels (for example, greater religiosity). In addition to being facilitated by mental health services, these positive changes were enabled by personal (for example, motivation), social (for example, family support), and spiritual (for example, prayer) factors. CONCLUSIONS: Suffering is a core experience of FEP from which a range of positive changes can follow among service users and their families and friends. It may be beneficial for mental health services to specifically strive to promote these positive changes.


Subject(s)
Early Medical Intervention/statistics & numerical data , Mental Health Services/statistics & numerical data , Posttraumatic Growth, Psychological , Psychotic Disorders , Humans , Psychotic Disorders/epidemiology , Psychotic Disorders/psychology , Psychotic Disorders/rehabilitation
14.
Hear Res ; 343: 72-82, 2017 01.
Article in English | MEDLINE | ID: mdl-27473505

ABSTRACT

Considerable research documents the cross-modal reorganization of auditory cortices as a consequence of congenital deafness, with remapped functions that include visual and somatosensory processing of both linguistic and nonlinguistic information. Structural changes accompany this cross-modal neuroplasticity, but precisely which specific structural changes accompany congenital and early deafness and whether there are group differences in hemispheric asymmetries remain to be established. Here, we used diffusion tensor imaging (DTI) to examine microstructural white matter changes accompanying cross-modal reorganization in 23 deaf adults who were genetically, profoundly, and congenitally deaf, having learned sign language from infancy with 26 hearing controls who participated in our previous fMRI studies of cross-modal neuroplasticity. In contrast to prior literature using a whole-brain approach, we introduce a semiautomatic method for demarcating auditory regions in which regions of interest (ROIs) are defined on the normalized white matter skeleton for all participants, projected into each participants native space, and manually constrained to anatomical boundaries. White-matter ROIs were left and right Heschl's gyrus (HG), left and right anterior superior temporal gyrus (aSTG), left and right posterior superior temporal gyrus (pSTG), as well as one tractography-defined region in the splenium of the corpus callosum connecting homologous left and right superior temporal regions (pCC). Within these regions, we measured fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and white-matter volume. Congenitally deaf adults had reduced FA and volume in white matter structures underlying bilateral HG, aSTG, pSTG, and reduced FA in pCC. In HG and pCC, this reduction in FA corresponded with increased RD, but differences in aSTG and pSTG could not be localized to alterations in RD or AD. Direct statistical tests of hemispheric asymmetries in these differences indicated the most prominent effects in pSTG, where the largest differences between groups occurred in the right hemisphere. Other regions did not show significant hemispheric asymmetries in group differences. Taken together, these results indicate that atypical white matter microstructure and reduced volume underlies regions of superior temporal primary and association auditory cortex and introduce a robust method for quantifying volumetric and white matter microstructural differences that can be applied to future studies of special populations.


Subject(s)
Auditory Pathways/diagnostic imaging , Deafness/diagnostic imaging , Diffusion Magnetic Resonance Imaging , Diffusion Tensor Imaging , Hearing , White Matter/diagnostic imaging , Adult , Anisotropy , Auditory Cortex/diagnostic imaging , Auditory Cortex/physiopathology , Auditory Pathways/physiopathology , Case-Control Studies , Corpus Callosum/diagnostic imaging , Corpus Callosum/physiopathology , Deafness/congenital , Deafness/physiopathology , Deafness/psychology , Female , Genetic Predisposition to Disease , Hearing/genetics , Humans , Male , Neuronal Plasticity , Phenotype , Predictive Value of Tests , Temporal Lobe/diagnostic imaging , Temporal Lobe/physiopathology , White Matter/physiopathology , Young Adult
15.
Biol Blood Marrow Transplant ; 22(12): 2180-2186, 2016 12.
Article in English | MEDLINE | ID: mdl-27596130

ABSTRACT

Myelofibrosis (MF) is a chronic progressive hematologic malignancy with a median overall survival (OS) of approximately 6 years. Allogeneic hematopoietic stem cell transplantation (HSCT) is the sole treatment approach that offers curative potential. The use of reduced-intensity conditioning regimens has expanded the application of HSCT to patients with MF up to age 70 years. Recent retrospective and prospective reports have suggested worse HSCT outcomes for patients with MF receiving an unrelated donor graft compared with those receiving a related donor graft. To identify patient- and HSCT-specific variables influencing outcomes, we conducted a retrospective analysis of 42 patients with chronic and advanced-phase MF who underwent HSCT at our institution. For this cohort, at a median follow-up of 43 months, progression-free survival (PFS) was 15 months and OS was 25 months. In multivariable analysis, the sole clinical variable that negatively influenced outcome was the use of an unrelated donor, with a median PFS and OS both of 11 months versus not yet reached in patients receiving a related donor graft. At 2 years, OS was 38% (95% confidence interval [CI], 20%-56%) and nonrelapse mortality (NRM) was 53% (95% CI, 36%-78%) in the unrelated donor graft group, compared with 75% (95% CI, 46%-90%) and 21% (95% CI, 9%-47%) in the related donor graft group. There was no difference in the rates of grade III-IV acute graft-versus-host disease between the unrelated and related donor groups (38% versus 38%). Despite a more aggressive disease state, 2-year PFS and OS were both 42% (95% CI, 15%-67%) in patients with myeloproliferative neoplasm-blast phase undergoing HSCT. Graft failure rate was higher in patients receiving a mismatched donor graft compared with those receiving a matched donor graft (60% versus 13%; P = .0398). Retransplantation of patients with graft failure resulted in long-term survival. Baseline splenomegaly did not affect transplantation outcomes. Given the particularly poor outcomes seen in the unrelated donor cohort here and elsewhere, a formal exploration of alternative hematopoietic stem cell sources is warranted.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Primary Myelofibrosis/therapy , Adult , Aged , Chronic Disease , Female , Graft vs Host Disease/mortality , Hematopoietic Stem Cell Transplantation/mortality , Histocompatibility , Humans , Male , Middle Aged , Primary Myelofibrosis/mortality , Retreatment/mortality , Retrospective Studies , Survival Analysis , Transplantation Conditioning/methods , Transplantation, Homologous , Treatment Outcome , Unrelated Donors
16.
Cogn Neuropsychiatry ; 20(1): 53-63, 2015.
Article in English | MEDLINE | ID: mdl-25341444

ABSTRACT

INTRODUCTION: Schizotypy is phenologically and genetically related to schizophrenia-spectrum illness. Previous studies find cognitive function to be mildly impaired, but specific impairments and their relationship to functioning are not well understood. In this study, we sought to examine how cognitive load affects performance in schizotypy and to examine whether impairments might manifest in functional capacity and quality of life. METHODS: Undergraduate students were screened for abnormally high levels of schizotypy (N = 72) and compared to those without psychopathology (N = 80) on a standard battery of neuropsychological tests, cognitive tests with varying cognitive load, functional capacity measures and quality of life. RESULTS: The high schizotypy group did not differ from controls on traditional measures of neuropsychological functioning, but an interaction of group by cognitive load was observed, where those with schizotypy manifested a greater decline in performance as information processing load was parametrically increased. Differences in functioning were observed and cognitive impairment was associated with impaired functioning. CONCLUSIONS: Cognitive and functional impairment can be observed in those with high schizotypal traits who are non-treatment seeking. The sensitivity of cognitive tests to impairment in this population might be a function of their ability to parametrically increase cognitive load.


Subject(s)
Cognition , Cognitive Dysfunction/diagnosis , Problem Solving , Quality of Life , Schizotypal Personality Disorder/psychology , Activities of Daily Living , Adolescent , Cognitive Dysfunction/psychology , Female , Humans , Male , Neuropsychological Tests , Psychometrics , Schizophrenia/complications , Self Report , Young Adult
17.
Ethn Dis ; 24(3): 276-82, 2014.
Article in English | MEDLINE | ID: mdl-25065067

ABSTRACT

OBJECTIVES: With an increase and diversity in ethnic populations in Westernized countries, understanding the differences in levels of knowledge surrounding hypertension is important in planning appropriate prevention strategies. The purpose of our study was to assess levels of hypertension knowledge in Chinese, Indian and White populations in a large metropolitan Canadian city. DESIGN: A telephone survey was conducted in English, Chinese (Cantonese and Mandarin) and Indian languages (Hindi, Punjabi and Urdu). Hypertension knowledge was assessed through a 10-item validated instrument; respondents received 1 point for each correct answer. Logistic regression was used to test differences in hypertension knowledge among these three populations. RESULTS: Survey response rates were 68.7% (301) for Chinese, 61.3% (248) for Indian and 69.7% (254) for White populations. The average hypertension knowledge score for Chinese respondents was 7.23 out of 10, 7.11 for Indian respondents and 7.28 for White respondents. Compared to White respondents, Chinese respondents were less likely than White respondents to know high blood pressure can cause heart attacks (adjusted odds ratio [aOR]: .43, 95% confidence interval [CI]: .19-.96] and Indian respondents were less likely to know losing weight usually decreases blood pressure (aOR: .38, 95% CI: .21-.68). CONCLUSIONS: Hypertension knowledge levels among these three ethnic/racial populations were similar and relatively high and varied by content. Low levels of knowledge for Chinese and Indian ethnic populations were on hypertension risk factors, long-term consequences of hypertension and anti-hypertensive medication adherence. Specifically, females, recent immigrants to Canada and Chinese seniors were identified as sub-groups who should be targeted for hypertension knowledge promotion.


Subject(s)
Asian People , Health Knowledge, Attitudes, Practice/ethnology , Health Literacy , Hypertension/ethnology , Hypertension/therapy , White People , Adolescent , Adult , Aged , Canada , China/ethnology , Cross-Sectional Studies , Female , Humans , Hypertension/diagnosis , India/ethnology , Male , Middle Aged , Socioeconomic Factors , Young Adult
18.
Clin Lymphoma Myeloma Leuk ; 14(1): 31-6, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24220620

ABSTRACT

INTRODUCTION: Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), and are characterized by clonal proliferation of hematopoietic cells in the bone marrow. There are numerous case reports and reviews reporting patients with coexisting MPN and plasma-cell disease such as multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). METHODS: We report 15 patients treated at our institution over a 5-year period (January 2008 to December 2012) with a diagnosis of both an MPN and MGUS or MM. We also reviewed and summarized published case reports and studies describing the coexistence of these two disease entities. RESULTS: Most patients (12/15) had an MPN diagnosis made before or at the same time as the MGUS/MM diagnosis. Eventually, 2 patients developed a lymphoid leukemia, 1 patient developed lymphoma, and 1 patient developed acute myeloid leukemia, raising the question of whether patients with coexistence of myeloid- and lymphoid-derived neoplasms are more prone to leukemic or lymphomatous transformation. We did not find any treatment-related effect that could have contributed to the development of coexisting MGUS or MM and MPN. Of the 7 patients with an abnormal karyotype, 3 patients had trisomy 8. CONCLUSION: At present, management strategies are aimed at treating the MPN and regularly monitoring the MGUS for transformation to an overt plasma-cell malignancy. However, for patients who develop overt MM, management is focused more on treating the myeloma and monitoring the MPN. It has not yet been definitively shown that these 2 entities arise from a common-ancestor hematopoietic stem cell.


Subject(s)
Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/pathology , Paraproteinemias/diagnosis , Paraproteinemias/pathology , Humans
19.
FEMS Yeast Res ; 12(6): 637-50, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22594927

ABSTRACT

Using site-directed mutants of ARL1 predicted to alter nucleotide binding, we examined phenotypes associated with the loss of ARL1 , including effects on membrane traffic and K (+) homeostasis. The GTP-restricted allele, ARL[Q72L] , complemented the membrane traffic phenotype (CPY secretion), but not the K (+) homeostasis phenotypes (sensitivity to hygromycin B, steady-state levels of K (+) , and accumulation of (86) Rb (+) ), while the XTP-restricted mutant, ARL1[D130N] , complemented the ion phenotypes, but not the membrane traffic phenotype. A GDP-restricted allele, ARL1[T32N] , did not effectively complement either phenotype. These results are consistent with a model in which Arl1 has three different conformations in vivo. We also explored the relationship between ARL1 and MON2 using the synthetic lethal phenotype exhibited by these two genes and demonstrated that MON2 is a negative regulator of the GTP-restricted allele of ARL1 , ARL1[Q72L] . Finally, we constructed several new alleles predicted to alter binding of Arl1 to the sole GRIP domain containing protein in yeast, Imh1, and found that ARL1[F52G] and ARL1[Y82G] were unable to complement the loss of ARL1 with respect to either the membrane traffic or K (+) homeostasis phenotypes. Our study expands understanding of the roles of Arl1 in vivo.


Subject(s)
Gene Expression Regulation, Fungal , Monomeric GTP-Binding Proteins/biosynthesis , Saccharomyces cerevisiae Proteins/biosynthesis , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/genetics , Vesicular Transport Proteins/biosynthesis , Vesicular Transport Proteins/metabolism , Amino Acid Substitution , Genetic Complementation Test , Models, Biological , Monomeric GTP-Binding Proteins/genetics , Mutagenesis, Site-Directed , Mutant Proteins/biosynthesis , Mutant Proteins/genetics , Mutation, Missense , Potassium/metabolism , Repressor Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/genetics , Vesicular Transport Proteins/genetics
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