Multiple Impairments Research Articles

Creutzel-Jakob disease mimics a Richardson syndrome, spectrum of supranuclear progressive palsy

The clinical spectrum of Creutzeld-Jakob disease (CJD) is extensive. CJD in the sporadic variant could be debut as prominent ataxic (10%) o thalamic (2%) of cases) symptoms. In a patient with rapidly cognitive impairment in less than six months, the probability of diagnosis is high. We presented a man with six months of evolution con cerebellar syndrome, ocular supraversion limited and symmetrical parkinsonism with multiple cognitive impairments that simulated a Richardson spectrum of Supranuclear progressive Palsy.

Multidisciplinary outpatient rehabilitation of physical and neurological sequelae and persistent symptoms of covid-19: a prospective, observational cohort study

Purpose This prospective, observational cohort study investigated the effects of multidisciplinary rehabilitation of post Covid-19 sequelae and persistent symptoms and their impact on patients’ functioning and quality of life. Methods From 58 patients referred for neurorehabilitation, 43 were eligible for and participated in the present study. Before and after 8 weeks of rehabilitation, patients underwent physical, neuropsychological and respiratory evaluations and assessment of functional independence, impact of fatigue and quality of life. Results Forty of 43 individuals (52 ± 11.4 years, 24 male) completed the rehabilitation program. Fatigue (87.5%), dyspnea and/or shortness of breath (62.5%), and cognitive impairment (37.5%) were reported by both previously hospitalized and home-confined patients. Neurological sequelae (35.5%) were present only in hospitalized patients. After 8 weeks of rehabilitation, patients reported significant improvements in motor functional independence, upper and lower limb functionality, impact of fatigue on daily activities, respiratory muscle strength, cognitive performance, and quality of life. Conclusions Post Covid-19 patients present with heterogeneous neurological, physical, and respiratory impairments requiring a multidisciplinary rehabilitation approach to reduce disability and improve functionality and quality of life. A comprehensive assessment of clinical profiles and responses to rehabilitation may facilitate the identification of rehabilitation candidates and help to design effective rehabilitation interventions. Implication for rehabilitation Post Covid-19 patients present multiple, heterogeneous neurological, physical and respiratory impairments that are observed in both previously hospitalized and home-confined patients. Eight weeks of multidisciplinary rehabilitation may significantly reduce disability and improve functionality and quality of life. A comprehensive assessment of their clinical profile and response to rehabilitation may facilitate the identification of rehabilitation candidates and help to design more effective rehabilitation interventions.

Exploring the Complexity of Aphasia With Network Analysis.

Purpose Aphasia is a complex, neurogenic language disorder, with different aphasia syndromes hallmarked by impairment in fluency, auditory comprehension, naming, and/or repetition. Broad, standardized assessments of language domains and specific language and cognitive assessments provide a holistic impairment profile of a person with aphasia. While many recognize the correlations between assessments, there remains a need to continue understanding the complexity of relationships between assessments for the purpose of better characterization of language impairment profiles of persons with aphasia. We explored the use of network analysis to identify the complex relationships between a variety of language assessments. Method We computed a regularized partial correlation network and a directed acyclic graph network to estimate the relations between different aphasia assessments in 128 persons with aphasia. Results Western Aphasia Battery-Revised Comprehension subtest was the most central assessment in the aphasia symptom network, whereas the Philadelphia Naming Test had the most putative causal influence on other assessments. Additionally, the language assessments segregated into three empirically derived communities denoting phonology, semantics, and syntax. Furthermore, several assessments, including the Philadelphia Naming Test, belonged to multiple communities, suggesting that certain assessments may capture multiple language impairments. Conclusion We discuss the implications of using a network analysis approach for clinical intervention and driving forward novel questions in the field of clinical aphasiology. Supplemental Material https://doi.org/10.23641/asha.16620229.

Let them go! Compassionate release for disabled prisoners with chronic health conditions during the COVID-19 public health emergency

Inmates with disabilities are at high risk of serious illness and death from COVID-19 due to crowded and unsanitary conditions. The punishment for serious crimes is incarceration—not exposure to a dangerous, contagious virus. Prisoners have human rights, notwithstanding the loss of most of their civic rights. Critical Disability Studies draws attention to multiple and overlapping injustices and oppressions. Prisoners with disabilities often suffer from race and ethnic discrimination, poverty, trauma, multiple physical impairments, mental illness, and/or cognitive limitations. This essay calls for action to accelerate compassionate release of disabled inmates, many of whom are at high risk for COVID-19, and offers recommendations for improving conditions of confinement for disabled inmates who remain incarcerated.

Increased Asymmetry of Trunk, Pelvis, and Hip Motion during Gait in Ambulatory Children with Spina Bifida

Spina bifida (SB) is caused by incomplete neural tube closure and results in multiple impairments, including muscle weakness. The severity of muscle weakness depends on the neurologic lesion level. Though typically symmetric, there can be asymmetries in neurologic lesion level, motor strength, skeletal structures, and body composition that affect patients’ gait and function. Using body segment and joint motion obtained through 3D computerized motion analysis, we evaluated asymmetry and range of motion at the hip, pelvis, and trunk in the frontal and transverse planes during gait in 57 ambulatory children with SB and 48 typically developing controls. Asymmetry and range of hip, pelvis, and trunk motion in the frontal and transverse planes were significantly greater for patients with mid-lumbar and higher level lesions compared with those having sacral/low-lumbar level lesions and controls without disability (p ≤ 0.01). Crutch use decreased asymmetry of trunk rotation in mid-lumbar level patients from 10.5° to 2.6° (p ≤ 0.01). Patients with asymmetric involvement (sacral level on one side and L3-4 on the other) functioned similarly to sacral level patients, suggesting that they may be better categorized using their stronger side rather than their weaker side as is traditional. The information gained from this study may be useful to clinicians when assessing bracing and assistive device needs for patients with asymmetric SB involvement.

Hippocampal atrophy and levels of posterior cingulate cortex (PCC) metabolites in Alzheimer's disease, vascular dementia and normal cognitive

Introduction: Dementia defined as an acquired condition marked by multiple cognitive impairments. The most prevalent type is Alzheimer's disease, followed by vascular dementia. Studies have examined hippocampal atrophy and its relationship to aging and dementia. This study aimed to calculate the amount of hippocampal volume loss associated with dementia, also a,nxto examine the possible role of proton magnetic resonance spectroscopy (1H-MRS) in common type of dementia.Methods: This study compared hippocampal volume measures and metabolites level in posterior cingulate cortex (PCC) between Alzheimer's disease patients, vascular dementia patients, and controls using volumetric-based MR and 1H-MR spectroscopy. Metabolite levels were calculated from the peak integral value of the metabolite N-Acetyl Aspartate (NAA) (2 ppm), Myo-inositol (MI) (3.5 ppm), Cholin (Cho) (3.2 ppm), and Creatin (Cr) (3 ppm), then a comparison was made to the levels of brain metabolites in the form of: NAA / Cr, Cho / Cr, and MI / Cr.Results: Between Alzheimer's disease and control, a significant difference was observed in the total volume of the hippocampus of 20.45 % (p = 0.004). The comparison of brain metabolite levels in PCC patients with Alzheimer's disease, vascular dementia, and control subjects revealed no statistically significant differences in the levels of Cholin, Creatine, NAA, MyoInositol, Cho / Cr, NAA / Cr, and mI/ Cr for any of the metabolites.Conclusion: There was a significant difference in the mean total size of the hippocampus between patients with Alzheimer's disease and controls, but not in the PCC metabolites measured by MR spectroscopy.

Multiple immune function impairments in diabetic patients and their effects on COVID-19.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, poses a significant threat to public health worldwide, and diabetes is considered a risk factor for the rapid progression and poor prognosis of COVID-19. Limited immune function is a clinical feature of COVID-19 patients, and diabetes patients have defects in innate and adaptive immune functions, which may be an important reason for the rapid progression and poor prognosis of COVID-19 in patients with diabetes. We review the possible multiple effects of immune impairment in diabetic patients on the immune responses to COVID-19 to provide guidance for the diagnosis and treatment of diabetic patients with COVID-19.

Physical function and frailty in elderly patients with acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by grants from CIBER CV, Madrid, Spain [grant number 16/11/00420] and Instituto de Salud Carlos III-FEDER, Madrid, Spain. Background Frailty is described a complex clinical syndrome of increased vulnerability to stressors that places the individual at increased risk of adverse health outcomes. It results from multiple impairments (among others, in physical functioning) and its severity ranges from mild to severe. In older cardiac patients, frailty is reported to be a significant and an independent predictor of functional decline. Purpose To analyze the relationship between physical functioning and frailty of elderly patients with an Acute Coronary Syndrome (ACS). Methods A cross-sectional study was carried out. A total of 110 patients, aged ³ 70 years and hospitalized for ACS were included. Frailty status was determined by using the Fried scale. The Short Physical Performance Battery (SPPB), which includes three timed tasks (balance, walking and leg strength), was used to assess physical functioning. The SPPB total score and the partial scores of its different dimensions were compared between frail and pre-frail patients. Results Sample characteristics and results are shown in table 1. There were differences between groups for all the studied variables (p<.01). Pre-frail patients achieved higher total and partial scores in the SPPB. Conclusion Our results showed that, in elderly patients with ACS, those in a pre-frail status showed better physical function (SPPB total score and partial scores of its dimensions) than those who were frail. Due to unbalanced groups size, these results must be interpreted with caution requiring future research with larger samples.

From Deafblindness to Multiple Sensory Impairment: a few explanatory notes on definition, terminology, and historical context

In deafblindness (DB), the consequences of visual and hearing impairments are not additive, but multiplicative creating unique problems in information, communication and mobility, hence the need to recognize it as a distinct disability. There are three types of approaches that depend on several factors, taking into account the structure of educational and support services for people with DB/MSI and the nature of human, technological and financial resources. In our country, according to the law, the broadest approach is promoted, meaning the inclusion of other disabilities in addition to sight and/or hearing. In other countries there are other names that, depending on the context or user, are synonymous with DB. The huge variability of DB/MSI cases causes some specialists to refer to a spectrum disability in which there are different weights and different degrees of sensory loss, cognitive deficit, language impairments and/or somatic pathologies. All this individual “puzzle” generates a state of multi-handicap, which is reflected both in a specific pattern of learning and communication difficulties, and in the emergence of derived disabilities that hinder or obstruct the overall somatic and psychological development through restrictions on using the remaining hearing and sight.

Association of diabetes with severity and mortality in hospitalized patients with COVID-19 in Wuhan, China: a single-centered, retrospective study.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. The aim this study was to investigate the association of diabetes with severity and mortality among hospitalized patients with COVID-19 in Wuhan, China. This retrospective, single-center case study enrolled a total of 564 patients diagnosed with COVID-19 at the Seventh Hospital of Wuhan City, between January 20 and March 15, 2020. Among the 564 patients with confirmed COVID-19, 509 (85.1%) were discharged and 55 (9.8%) died. The median age was 59 years (range, 10-93 years). A total of 85 (15.1%) patients were diagnosed with diabetes on admission (median age, 65.0 [range, 34-91] years). Patients with diabetes had significantly higher proportions of critical cases (24 [28.2%] vs. 66 [13.8%]) and in-hospital mortality (17 [20%] vs. 38 [7.9%]). Moreover, patients with diabetes presented abnormal levels of multiple indicators concerning lymphopenia, inflammation, heart, liver, kidney, and lung function on admission, while diabetic patient group still display higher troponin T (TnT) levels when approaching discharge. The Kaplan-Meier survival curve indicated a trend toward poorer survival in diabetic patients compared to non-diabetic patients, also evidenced by abnormal laboratory biomarker changes regarding multiple system impairments among COVID-19 patients with diabetes with in-hospital death. The detailed clinical investigation of 564 hospitalized patients with COVID-19 indicated a considerable association between diabetes and COVID-19 severity or mortality. Thus, more intensive treatment may be considered for COVID-19 patients with diabetes, especially regarding to cardiac injury.

COVID-19-New challenges in dysphagia and respiratory therapy

Eine COVID-19-Erkrankung kann zu schweren Krankheitsverläufen mit multiplen Organbeteiligungen und respiratorischen und neurologischen Funktionseinschränkungen führen. Schluckstörungen (Dysphagien) können in dieser Patientengruppe durch primäre Schädigungen des zentralen und peripheren neuronalen Netzwerkes der Schluckfunktion entstehen, aber auch bedingt durch die häufig längere intensivmedizinische Behandlung und Beatmung. Erste klinische Befunde zeigen persistierende Dysphagien im Rahmen des Post-COVID-Syndroms („Long-COVID“), sodass die Patienten auch längerfristige Maßnahmen zur Rehabilitation einer sicheren und suffizienten oralen Nahrungsaufnahme benötigen. Daher sollte in die Behandlung von COVID-19-Patienten ein strukturiertes erkrankungsspezifisches Monitoring in Bezug auf Dysphagiesymptome integriert werden, und atemtherapeutische Maßnahmen zur Regulation von Husteneffektivität und Atem-Schluck-Koordination sollten auch bei diesen Patienten essenzieller Bestandteil des Dysphagiemanagements sein. Herausforderungen ergeben sich dabei einerseits durch die erforderlichen Anpassungen etablierter Behandlungsstandards an den Infektionsschutz. Zudem müssen Auswahl und Durchführungsintensität therapeutischer Maßnahmen an die Kapazitäten und die spezifische Pathophysiologie der COVID-19- und Long-COVID-Patienten angepasst werden, um weitere funktionelle Verschlechterungen zu vermindern.

Efficacy and Safety Of Lenalidomide Plus Low-Dose Dexamethasone In Chinese Patients With Relapsed and Refractory Multiple Myeloma (RRMM) and Renal Impairment: MM-021 Subgroup Analysis

BackgroundIn China, the combination of lenalidomide (LEN) and low-dose dexamethasone (LoDEX) is approved for the treatment of RRMM patients (pts) who have received at least 1 prior therapy, based on data from the MM-021 China registration study. In RRMM pts, impaired renal function is a leading cause of comorbidity and early death. In addition, in RRMM pts renal impairment (RI) is associated with poor ECOG performance scores. In this MM-021 subgroup analysis, efficacy and safety of LEN + LoDEX (Rd) were evaluated in pts with RI. As LEN excretion is predominantly renal, LEN plasma concentrations are higher and LEN half-life is longer in pts with RI. Consequently, lower starting doses of LEN are needed for pts with RI in order to ensure adequate safety while maintaining therapeutic efficacy. MethodsMM-021 was a phase 2, multicenter, single-arm, open-label study. Pts with RRMM received LEN (25 mg/day on days 1–21) and LoDEX (40 mg/day on days 1, 8, 15, and 22) in 28-day treatment cycles until disease progression or discontinuation. Pts included in the pharmacokinetics cohort did not receive LoDEX on day 1, cycle 1. The LEN starting dose was adjusted according to baseline creatinine clearance (CrCl): 25 mg/day for pts with normal renal function (CrCl ≥ 60 mL/min), 10 mg/day for pts with moderate RI (CrCl 30 to < 60 mL/min), or 15 mg every other day for pts with severe RI (CrCl < 30 mL/min). All pts received thromboprophylaxis during the study. The primary end-point was best overall response rate (ORR), defined as percentage of pts who achieved a best response of partial response or better. Time to progression, progression-free survival, overall survival and safety were evaluated as secondary end-points. ResultsAt the data cut-off (January 4, 2013; median follow-up 17.6 mos), 199 pts (intent-to-treat population) were evaluable for safety and 187 pts for efficacy. At the cut-off date, 42 pts had completed their treatment, and 157 had discontinued treatment. At baseline, 27.1% ( n= 54) of pts had moderate RI, 7% (n = 14) had severe RI, and 65.8% (n = 131) had normal renal function. ORR was higher in pts with normal renal function compared with those with moderate or severe RI (Table 1). In pts with normal renal function or moderate RI, the rates of grade 3-4 neutropenia (26% and 20.4%, respectively), anemia (21.4% and 29.6%, respectively), and thrombocytopenia (10.7% and 13.0%, respectively) were similar and comparable to the overall population. In pts with severe RI, rates of grade 3-4 neutropenia, anemia, and thrombocytopenia were higher (35.7%, 57.1%, and 57.1%, respectively). There were 2 reports of grade 3-4 peripheral neuropathy. Discontinuation of Rd due to adverse events was reported in 5.3% of pts with normal renal function, 13% of those with moderate RI, and 28.6% of pts with severe RI. ConclusionsAdjusting the starting dose of LEN in RRMM pts with moderate or severe RI did not compromise treatment efficacy. ORR was highest in pts with normal renal function but pts with moderate and severe RI still achieved high ORRs and Rd was well tolerated. [Display omitted] Disclosures:Zhang:Celgene Corporation: Employment, Equity Ownership. Wortman-Vayn:Celgene Corporation: Employment, Equity Ownership. Mei:Celgene: Employment, Equity Ownership. Hou:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; J & J: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Outcome of abusive head trauma in children less than 2 years: A single center study from a middle-income country

BackgroundAbusive head trauma (AHT) is a severe manifestation of physical abuse in young children. This study examines the outcome of AHT in children under 2 years and features associated with mortality and disability. MethodsRetrospective chart review of 72 children under 2 years diagnosed to have AHT between 2011 and 2018 at a tertiary teaching hospital in Malaysia. Demographic variables, clinical features, results of neuroimaging and their associations with outcome were explored. ResultsThe median age at presentation was 4 months, 78% were six months or younger and 68% were male. Two-thirds became unwell in the care of an alternative caregiver. Subdural hemorrhage was present in 98%. Mortality was 10%. Forty-nine survivors returned with median interval of 16 months (IQR 5–44 months) between discharge and last follow-up. At least 35% of 65 survivors were disabled with 29% having multiple disabilities. Multiple disabilities (61.1% versus 25.8%) and cognitive impairment (61.1% versus 22.6%) were significantly higher in children 3 years or older at last follow-up (p < 0.05). Signs of brainstem dysfunction at presentation, requirement for ventilation and hypoxic-ischemic injury on neuroimaging were associated with mortality. Needing ventilation, cerebral edema and neurological or visual impairment at discharge were associated with disability. ConclusionsOutcomes of death or disability in 42% make prevention of AHT a public health priority. Survivors require long-term multi-disciplinary follow-up for coordination of rehabilitation and educational support. Prevention should be directed at improving resources and services to support families in the care of young infants under 6 months.

Visual Function and Ophthalmological Findings in CHARGE Syndrome: Revision of Literature, Definition of a New Clinical Spectrum and Genotype Phenotype Correlation.

CHARGE syndrome (CS) is a rare genetic disease causing multiple anatomical defects and sensory impairment. Visual function is usually reported by caregivers and has never been described with a structured behavioral assessment. Our primary objective was to describe ocular abnormalities, visual function and genotype–ocular-phenotype correlation in CS. A prospective monocentric cohort study was performed on 14 children with CS carrying pathogenic CHD7 variants. All children underwent ophthalmological evaluation and structured behavioral assessment of visual function. The VISIOCHARGE questionnaire was administered to parents. Colobomas were present in 93% of patients. Genotype–phenotype correlation documented mitigated features in a subset of patients with intronic pathogenic variants predicted to affect transcript processing, and severe features in patients with frameshift/nonsense variants predicting protein truncation at the N-terminus. Abnormal visual function was present in all subjects, with different degrees of impairment. A significant correlation was found between visual function and age at assessment (p-value = 0.025). The present data are the first to characterize visual function in CS patients. They suggest that hypomorphic variants might be associated with milder features, and that visual function appears to be related to age. While studies with larger cohorts are required for confirmation, our data indicate that experience appears to influence everyday use of visual function more than ocular abnormalities do.

Multiple Myeloma and Renal Impairment: Analysis of Induction Therapy Strategies and Outcome after Autologous Stem Cell Transplantation

Introduction: Multiple Myeloma (MM) is frequently accompanied by renal impairment (RI) at diagnosis. As MM-specific therapeutic strategies have evolved drastically within the past decades, we aimed at delivering a re-evaluation of applied treatments and outcomes according to renal function at diagnosis.Methods: In this multicenter, retrospective cohort analysis, we analyzed 366 patients who were diagnosed with MM between 1997-2016 and subsequently underwent autologous stem cell transplantation (ASCT). RI at diagnosis was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2. We carried out statistical analysis of patient groups stratified by renal function with regard to induction therapy defined as conventional chemotherapy (CT) versus immuno-chemotherapy (ICT) including either a proteasome inhibitor and/or an immunomodulator. Further, overall and progression-free survival (OS, PFS) were analyzed in the defined subgroups.Results: Of 366 patients, 287 received ICT versus 79 who had CT alone. The choice of the applied treatment strategy was highly dependent on diagnosis date, as all patients diagnosed before the year 2000 received chemotherapy alone, while all but 4 patients diagnosed after 2006 received ICT. Patients with renal impairment were just as likely to receive ICT as those without (75.9 vs. 79.5%, p=0.259). On OS analysis in the patient groups A) normal renal function/ICT (n=202), B) normal renal function/CT (n=52), C) impaired renal function/ICT (n=85), D) impaired renal function/CT (n=27), a longer survival was observed in groups A and B; however without statistical significance (p=0.080; Figure 1). On analysis of PFS, no differences were observed (p=0.784; Figure 2).Conclusions: Impaired renal function confers only a slight and statistically insignificant OS disadvantage in newly diagnosed MM patients receiving ASCT. On analysis of treatment strategy, however, it is evident that ICT attains better OS outcomes compared to CT alone. Therefore, while renal impairment remains common in patients with MM, an interdisciplinary mode of action between hemato/oncologists and nephrologists concerning the optimal induction therapy prior to ASCT is of pivotal clinical importance. The application of an adequate immuno-chemotherapy should conquer the fear of the negative impact of renal failure on outcome in patients with MM. [Display omitted] DisclosuresGisslinger:Janssen Cilag: Honoraria; Shire: Honoraria; PharmaEssentia: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; AOP Orphan Pharmaceuticals AG: Consultancy, Honoraria; Takeda: Honoraria. Krauth:Takeda: Honoraria; Janssen Cilag: Honoraria; Novartis: Honoraria; Amgen: Honoraria; AOP Orphan Pharmaceuticals AG: Honoraria; Celgene: Honoraria; BMS: Honoraria.

The Nexus of Sensory Loss, Cognitive Impairment, and Functional Decline in Older Adults: A Scoping Review.

The prevalence of cognitive impairment and sensory loss in hearing or vision increases with age. Based on the Information Processing Model, cognitive impairment coupled with sensory loss may exacerbate disability in late life. Yet this issue has not been systematically studied. The purpose of this scoping review was to examine the literature that studied the relationship between cognitive impairment, sensory loss, and activities of daily living in older adults. Two reviewers independently screened 1,410 studies identified from 5 electronic databases (Medline, EMBASE, PsycINFO, CINHAL, and Web of Science). The search was completed in June 2020. A study was eligible if it included measurements of cognitive function, vision or hearing, and activities of daily living. Additionally, the data analyses must address how cognitive impairment and sensory loss are related to the performance of activities of daily living. The final review included 15 studies. Findings show an additive effect of cognitive impairment and sensory loss on the activities of daily living. Cognitive impairment or vision loss independently relates to the decline in activities of daily living. Hearing loss relates to the decline only when the loss is severe, or if the daily task is hearing - specific. Older adults with coexisting sensory loss and cognitive impairment have the highest risk or prevalence of disability, comparing to cognitive impairment or sensory loss alone. This finding highlights the importance of developing interventions to reduce the risk of disability for older adults experiencing multiple impairments.

Multi-Component Intervention Program on Habitual Physical Activity Parameters and Cognitive Function in Patients with Mild Cognitive Impairment: A Randomized Controlled Trial.

Age-related dementia refers to a state in which someone experiences multiple cognitive function impairment due to degenerative brain disease, and which causes difficulties in their daily life or social life. Dementia is the most common and serious obstacle in later life. Early intervention in the case of patients who are in the mild cognitive impairment (MCI) stage among the high-risk group can maintain and improve their cognitive function. The purpose of the current trial is aimed at investigating the association between a multi-component (exercise with cognitive) intervention program and habitual physical activity parameters on cognitive functions in MCI patients. Neuropsychological cognitive and depression assessments were performed by neuropsychologists according to normalized methods, including the Korean mini-mental State examination (K-MMSE) and modified Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog) and cognitive assessment tool (attention, processing speed), and the Korean version of the geriatric depression scale (SGDS-K), both at baseline and at a 12 weeks follow-up. The 12-week multi-component intervention improved cognitive function and habitual physical activity parameters in patients with MCI relative to controls. A multi-component intervention program for patients with MCI is considered to be an effective method of dementia prevention by improving global (ADAS-Cog) and frontal (trail-making test, digit symbol substitution test) cognition and habitual physical activity parameters such as moderate to vigorous physical activity and step count. In addition, it is important to encourage habitual physical activities to ensure that exercise intervention strategies are carried out at the duration and intensity required for improving physical and cognitive wellbeing and obtaining health benefits.

A Novel Hierarchical Deep Learning Framework for Diagnosing Multiple Visual Impairment Diseases in the Clinical Environment.

Early detection and treatment of visual impairment diseases are critical and integral to combating avoidable blindness. To enable this, artificial intelligence–based disease identification approaches are vital for visual impairment diseases, especially for people living in areas with a few ophthalmologists. In this study, we demonstrated the identification of a large variety of visual impairment diseases using a coarse-to-fine approach. We designed a hierarchical deep learning network, which is composed of a family of multi-task & multi-label learning classifiers representing different levels of eye diseases derived from a predefined hierarchical eye disease taxonomy. A multi-level disease–guided loss function was proposed to learn the fine-grained variability of eye disease features. The proposed framework was trained for both ocular surface and retinal images, independently. The training dataset comprised 7,100 clinical images from 1,600 patients with 100 diseases. To show the feasibility of the proposed framework, we demonstrated eye disease identification on the first two levels of the eye disease taxonomy, namely 7 ocular diseases with 4 ocular surface diseases and 3 retinal fundus diseases in level 1 and 17 subclasses with 9 ocular surface diseases and 8 retinal fundus diseases in level 2. The proposed framework is flexible and extensible, which can be inherently trained on more levels with sufficient training data for each subtype diseases (e.g., the 17 classes of level 2 include 100 subtype diseases defined as level 3 diseases). The performance of the proposed framework was evaluated against 40 board-certified ophthalmologists on clinical cases with various visual impairment diseases and showed that the proposed framework had high sensitivity and specificity with the area under the receiver operating characteristic curve ranging from 0.743 to 0.989 in identifying all identified major causes of blindness. Further assessment of 4,670 cases in a tertiary eye center also demonstrated that the proposed framework achieved a high identification accuracy rate for different visual impairment diseases compared with that of human graders in a clinical setting. The proposed hierarchical deep learning framework would improve clinical practice in ophthalmology and broaden the scope of service available, especially for people living in areas with a few ophthalmologists.

Public health utility of cause of death data: applying empirical algorithms to improve data quality

BackgroundAccurate, comprehensive, cause-specific mortality estimates are crucial for informing public health decision making worldwide. Incorrectly or vaguely assigned deaths, defined as garbage-coded deaths, mask the true cause distribution. The Global Burden of Disease (GBD) study has developed methods to create comparable, timely, cause-specific mortality estimates; an impactful data processing method is the reallocation of garbage-coded deaths to a plausible underlying cause of death. We identify the pattern of garbage-coded deaths in the world and present the methods used to determine their redistribution to generate more plausible cause of death assignments.MethodsWe describe the methods developed for the GBD 2019 study and subsequent iterations to redistribute garbage-coded deaths in vital registration data to plausible underlying causes. These methods include analysis of multiple cause data, negative correlation, impairment, and proportional redistribution. We classify garbage codes into classes according to the level of specificity of the reported cause of death (CoD) and capture trends in the global pattern of proportion of garbage-coded deaths, disaggregated by these classes, and the relationship between this proportion and the Socio-Demographic Index. We examine the relative importance of the top four garbage codes by age and sex and demonstrate the impact of redistribution on the annual GBD CoD rankings.ResultsThe proportion of least-specific (class 1 and 2) garbage-coded deaths ranged from 3.7% of all vital registration deaths to 67.3% in 2015, and the age-standardized proportion had an overall negative association with the Socio-Demographic Index. When broken down by age and sex, the category for unspecified lower respiratory infections was responsible for nearly 30% of garbage-coded deaths in those under 1 year of age for both sexes, representing the largest proportion of garbage codes for that age group. We show how the cause distribution by number of deaths changes before and after redistribution for four countries: Brazil, the United States, Japan, and France, highlighting the necessity of accounting for garbage-coded deaths in the GBD.ConclusionsWe provide a detailed description of redistribution methods developed for CoD data in the GBD; these methods represent an overall improvement in empiricism compared to past reliance on a priori knowledge.

Sex- and subtype-specific adaptations in excitatory signaling onto deep-layer prelimbic cortical pyramidal neurons after chronic alcohol exposure.

Long-term alcohol use results in behavioral deficits including impaired working memory, elevated anxiety, and blunted inhibitory control that is associated with prefrontal cortical (PFC) dysfunction. Preclinical observations demonstrate multiple impairments in GABAergic neurotransmission onto deep-layer principal cells (PCs) in the prelimbic cortex that suggest dependence-related cortical dysfunction is the product of elevated excitability in these cells. Despite accumulating evidence showing alcohol-induced changes in interneuron signaling onto PCs differ between sexes, there is limited data explicitly evaluating sex-specific ethanol effects on excitatory signaling onto deep-layer PCs that may further contribute to deficits in PFC-dependent behaviors. To address this, we conducted electrophysiological and behavioral tests in both male and female Sprague-Dawley rats to evaluate the effects of chronic ethanol exposure. Among our observations, we report a marked enhancement in glutamatergic signaling onto deep-layer PCs in male, but not female, rats after alcohol exposure. This phenomenon was furthermore specific to a sub-class of PC, sub-cortically projecting Type-A cells, and coincided with enhanced anxiety-like behavior, but no observable deficit in working memory. In contrast, female rats displayed alcohol-induced facilitation in working memory performance with no change in expression of anxiety-like behavior. Together, these results suggest fundamental differences in alcohol effects on cell activity, cortical sub-circuits, and PFC-dependent behaviors across male and female rats.