Use of the energy waveform electrocardiogram to detect subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND: Recent guidelines propose N-terminal pro-B-type natriuretic peptide (NT-proBNP) for recognition of asymptomatic left ventricular (LV) dysfunction (Stage B Heart Failure, SBHF) in type 2 diabetes mellitus (T2DM). Wavelet Transform based signal-processing transforms electrocardiogram (ECG) waveforms into an energy distribution waveform (ew)ECG, providing frequency and energy features that machine learning can use as additional inputs to improve the identification of SBHF. Accordingly, we sought whether machine learning model based on ewECG features was superior to NT-proBNP, as well as a conventional screening tool-the Atherosclerosis Risk in Communities (ARIC) HF risk score, in SBHF screening among patients with T2DM. METHODS: Participants in two clinical trials of SBHF (defined as diastolic dysfunction [DD], reduced global longitudinal strain [GLS ≤ 18%] or LV hypertrophy [LVH]) in T2DM underwent 12-lead ECG with additional ewECG feature and echocardiography. Supervised machine learning was adopted to identify the optimal combination of ewECG extracted features for SBHF screening in 178 participants in one trial and tested in 97 participants in the other trial. The accuracy of the ewECG model in SBHF screening was compared with NT-proBNP and ARIC HF. RESULTS: SBHF was identified in 128 (72%) participants in the training dataset (median 72 years, 41% female) and 64 (66%) in the validation dataset (median 70 years, 43% female). Fifteen ewECG features showed an area under the curve (AUC) of 0.81 (95% CI 0.787-0.794) in identifying SBHF, significantly better than both NT-proBNP (AUC 0.56, 95% CI 0.44-0.68, p < 0.001) and ARIC HF (AUC 0.67, 95%CI 0.56-0.79, p = 0.002). ewECG features were also led to robust models screening for DD (AUC 0.74, 95% CI 0.73-0.74), reduced GLS (AUC 0.76, 95% CI 0.73-0.74) and LVH (AUC 0.90, 95% CI 0.88-0.89). CONCLUSIONS: Machine learning based modelling using additional ewECG extracted features are superior to NT-proBNP and ARIC HF in SBHF screening among patients with T2DM, providing an alternative HF screening strategy for asymptomatic patients and potentially act as a guidance tool to determine those who required echocardiogram to confirm diagnosis. Trial registration LEAVE-DM, ACTRN 12619001393145 and Vic-ELF, ACTRN 12617000116325.

Evaluating a new emergency department avoidance service for older people: patient and relative experiences.

BACKGROUND: High emergency department (ED) usage by older individuals for non-emergencies is a global concern. ED avoidance initiatives have proven effective in addressing this issue. To specifically cater to individuals aged 65 and above, the Southern Adelaide Local Health Network introduced an innovative ED avoidance service. This study assessed the acceptability of the service among its users. METHOD: The Complex And RestorativE (CARE) Centre is a six-bed unit staffed by a multidisciplinary geriatric team. Patients are transported directly to CARE after calling for an ambulance and being triaged by a paramedic. The evaluation took place between September 2021 and September 2022. Semi-structured interviews were conducted with patients and relatives who had accessed the service. Data analysis was performed using a six-step thematic analysis. RESULTS: Seventeen patients and 15 relatives were interviewed, who described the experience of 32 attendances to the urgent CARE centre between them. Patients accessed the service for several reasons but over half were associated with falls. There was a hesitation to call emergency services for several reasons, the primary being long wait times in ED and/or the prospect of an overnight stay in hospital. Some individuals attempted to contact their General Practitioner (GP) for the presenting problem but were unable to get a timely appointment. Most participants had previously attended a local ED and had a negative experience. All individuals reported favouring the CARE centre over the traditional ED for numerous reasons including a quieter and safer environment and specially trained geriatric staff who were less rushed than ED staff. Several participants would have appreciated a standardised follow-up process after discharge. CONCLUSION: Our findings suggest that ED admission avoidance programmes may be an acceptable alternative treatment for older people requiring urgent care, potentially benefiting both public health systems and user experience.

Association of biomarkers and risk scores with subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND: Subclinical LV dysfunction (LVD) identifies heart failure (HF) risk in type 2 diabetes mellitus (T2DM). We sought the extent to which clinical scores (ARIC-HF, WATCH-DM), natriuretic peptides (NTpBNP) and troponin (hs-TnT) were associated with subclinical LV dysfunction (LVD). These associations could inform the ability of these tests to identify which patients should undergo echocardiography. METHODS: Participants with T2DM were prospectively recruited from three community-based populations. ARIC-HF risk at 4 years and WATCH-DM scores were calculated from clinical data. NTpBNP and hs-TnT were measured using an electro-chemiluminescence assay. All underwent a comprehensive echocardiogram. We calculated the sensitivity and specificity of clinical scores and biomarkers to identify abnormal global longitudinal strain (GLS ≥ -16%)), diastolic function (E/e' ≥ 14 or e' < 8 cm/s), left atrial volume index (LAV > 34 ml/m2) and LV hypertrophy (LV mass index > 88 g/m2 (F) > 102 g/m2(M)). RESULTS: Of 804 participants (median age 69 years [inter-quartile range (IQR) 65-73], 36% female), clinical scores suggested significant HF risk (median ARIC-HF 8% [IQR 4-12]; WATCH-DM 10 points [IQR 8-12]), and the median NTpBNP was 50 pg/mL [IQR 25-101] and hs-TnT 9.6 pg/mL [IQR 6.8-13.6]. Abnormal GLS was present in 126 (17%), elevated E/e' in 114 (15%), impaired e' in 629 (78%), increased LAV in 351 (44%) and LV hypertrophy in 113 (14%). After adjustments for age, body-mass index, and renal function, each standard deviation increase in NTpBNP was associated with a GLS increase of 0.32 (p < 0.001) and hs-TnT increase by 0.26 (p < 0.001). Similar trends were observed with ARIC-HF (standardised ß = 0.22, p < 0.001) and WATCH-DM (standardised ß = 0.22, p < 0.001) in univariable analyses. However, none of the risk assessment tools provided satisfactory discrimination for abnormal GLS (AUC 63%), diastolic indices (e' AUC 54-61%) or LV mass (AUC 59-67%). At a sensitivity of 90%, there was an unacceptably low (< 50%) specificity. CONCLUSION: Although risk assessment based on clinical scores or biomarkers would be desirable to stratify HF risk in people with T2DM, they show a weak relationship with subclinical LVD.

Understanding the contribution of general medical services to acute inpatient care in Victorian public hospitals.

BACKGROUND: General medicine is an integral part of health services, yet there is little data highlighting their contribution to acute hospital care in Australia. AIMS: To utilise the Victorian Department of Health's administrative dataset for hospital admissions to evaluate the relative contribution and trends over time of general medical services to acute multiday inpatient hospital separations in the Victorian public healthcare system. METHODS: A retrospective time-series study of general medical activity compared to other major specialties using hospital-level data provided by the Department of Health: (i) extrapolation from diagnosis-related group (DRG) activity data (2011-2021) and, (ii) directly reported discharge unit-based activity (available from 2018). Acute multiday separations of all patients aged ≥18 years from all metropolitan and rural Victorian public hospitals were included. RESULTS: Using the DRG-based data, general medicine ranked as the largest care provider of all specialties studied, accounting for 12.1% of separations. Despite the largest increase at a rate of 2831 separations/year (0.336%/year of total, P < 0.001) compared to others, mean length of stay declined by 0.08 days/year (P < 0.001). These findings were significant for metropolitan and rural hospitals. The use of directly reported discharge unit-based data also ranked general medicine as the largest care provider accounting for 32.9% of total separations, with rural hospital general medical services contributing nearly 50% of all multiday separations. CONCLUSIONS: Both DRG-based data and discharge unit-based data indicate that general medicine is the largest provider of acute multiday inpatient care in Victorian hospitals. The estimate of contribution of general medicine differed between the two datasets as DRG data likely over-represents the role of other specialties possibly due to assumptions regarding specialty management of varying groups of diagnoses.

Research activities in general medicine: a scoping survey by the Internal Medicine Society of Australia and New Zealand.

BACKGROUND: In developing an effective framework for a collaborative research network (RN) that supports members involved in research, the Internal Medicine Society of Australia and New Zealand (IMSANZ) required a better understanding of the current level of research activity and engagement by general physicians, and factors influencing such engagement. AIMS: To explore the current research landscape amongst general physicians in Australia and Aotearoa New Zealand. METHODS: A questionnaire exploring research participation, scope, research enablers and barriers was disseminated to IMSANZ members over a 3-month period. Core functions of IMSANZ-RN, research priorities, potential solutions to perceived barriers and required level of support were also evaluated. RESULTS: A total of 82 members, mostly senior medical staff (74.4%), responded to the survey (11.8% response rate). More than 70% were involved in impactful research across multiple disciplines, encompassing a wide range of research themes and topics. However, there is limited support and resources available to conduct research, with most projects being self-instigated and self-funded. There is overwhelming support to increasing the profile of research in general medicine through the establishment of IMSANZ-RN, whose principal purposes, as identified by respondents, are to foster collaboration, promote research, provide research education and training, and share information among general physicians. Quality improvement studies (56.1%) and clinical trials (41.5%) were also identified as priority research types. CONCLUSIONS: This study has profiled the constraints faced by general physicians in conducting high-quality collaborative research and provides insights into what is needed to support greater research engagement, through development of a discipline-specific clinical RN.

Cognitive Dysfunction in Heart Failure: Pathophysiology and Implications for Patient Management.

PURPOSE OF REVIEW: There is increasing recognition of the prevalence and impact of cognitive dysfunction (CD) in heart failure (HF) patients. This contemporary review appraises the evidence for epidemiological association, direct pathophysiological links and emerging pharmacological and non-pharmacological interventions. Furthermore, we present evidence for care models that aim to mitigate the morbidity and poor quality of life associated with these dual processes and propose future work to improve outcomes. RECENT FINDINGS: CD disproportionately affects heart failure patients, even accounting for known comorbid risk factors, and this may extend to subclinical left ventricular dysfunction. Neuroimaging studies now provide evidence of anatomical and functional differences which support previously postulated mechanisms of reduced cerebral blood flow, micro-embolism and systemic inflammation. Interventions such as multidisciplinary ambulatory HF care, education and memory training improve HF outcomes perhaps to a greater degree in those with comorbid CD. Additionally, optimisation of standard heart failure care (cardiac rehabilitation, pharmacological and device therapy) may lead to additional cognitive benefits. Epidemiological, neuroimaging and intervention studies provide evidence for the causal association between HF and CD, although evidence for Alzheimer's dementia is less certain. Specific reporting of cognitive outcomes in HF trials and evaluation of targeted interventions is required to further guide care provision.

Association between socioeconomic status and incident atrial fibrillation.

BACKGROUND: Low socioeconomic status is associated with cardiovascular diseases, and an association with atrial fibrillation (AF) could guide screening. AIM: To investigate if indices of advantage/disadvantage (IAD), index of education/occupation (IEO) and index of economic resources were associated with incident AF, independent of risk factors and cardiac function. METHODS: We studied community-based participants aged ≥65 years with AF risk factors (n = 379, age 70 ± 4 years, 45% men). The CHARGE-AF score (a well validated AF risk score) was used to assess 5-year risk of developing AF. Participants also had baseline echocardiograms. IAD, IEO and index of economic resources were obtained from the 2011 Socio-Economic Indexes for Areas score, in which higher decile ranks indicate more advantaged areas. Patients were followed up for incident AF (median 21 (range 5-31) months), with AF diagnosed by clinical review, including 12-lead electrocardiogram (ECG), as well as single-lead portable ECG monitoring used to record 60 s ECG tracings five times/day for 1 week. Cox proportional hazards models were used to assess the association between socioeconomic status and incident AF. RESULTS: Subjects with AF (n = 50, 13%) were more likely to be male (64 vs 42%, P = 0.003) and had higher CHARGE-AF score (median 7.1% (5.2-12.8%) vs 5.3% (3.3-8.6%), P < 0.001). Areas with lower socioeconomic status (IAD and IEO) had a higher risk of incident AF independent of LV function and CHARGE-AF score (hazard ratio for IAD 1.16, 95% confidence interval 1.05-1.29, P = 0.005 and hazard ratio for IEO 1.18, 95% confidence interval 1.07-1.30, P = 0.001). CONCLUSION: Regional socioeconomic status is associated with risk of incident AF, independent of LV function and clinical risk. This association might permit better regional targeting of prevention.

Development and Characterization of Monoclonal Antibodies Specific for Mouse and Human Fcγ Receptors.

FcγRs are key regulators of the immune response, capable of binding to the Fc portion of IgG Abs and manipulating the behavior of numerous cell types. Through a variety of receptors, isoforms, and cellular expression patterns, they are able to fine-tune and direct appropriate responses. Furthermore, they are key determinants of mAb immunotherapy, with mAb isotype and FcγR interaction governing therapeutic efficacy. Critical to understanding the biology of this complex family of receptors are reagents that are robust and highly specific for each receptor. In this study, we describe the development and characterization of mAb panels specific for both mouse and human FcγR for use in flow cytometry, immunofluorescence, and immunocytochemistry. We highlight key differences in expression between the two species and also patterns of expression that will likely impact on immunotherapeutic efficacy and translation of therapeutic agents from mouse to clinic.

Fcγ receptor dependency of agonistic CD40 antibody in lymphoma therapy can be overcome through antibody multimerization.

Immunomodulatory mAbs, led by the anti-CTLA4 mAb ipilimumab, are an exciting new class of drugs capable of promoting anticancer immunity and providing durable control of some tumors. Close analysis of a number of agents has revealed a critical yet variable role for Fcγ receptors in their efficacy. In this article, we reveal that agonistic anti-CD40 mAbs have an absolute requirement for cross-linking by inhibitory FcγRIIB when used systemically to treat established BCL1 syngeneic lymphoma, and therapy is lost when using a mouse IgG2a mAb not cross-linked by FcγRIIB. Furthermore, in FcγRIIB-deficient mice the lymphoma itself can provide FcγRIIB to cross-link anti-CD40 on neighboring cells, and only when this is blocked does therapy fail. The dependence on FcγRIIB for immunostimulatory activity was not absolute, however, because when anti-CD40 mAbs were administered systemically with the TLR3 agonist polyinosinic:polycytidylic acid or were given subcutaneously, activatory FcγR could also provide cross-linking. Using this mechanistic insight, we designed multimeric forms of anti-CD40 mAb with intrinsic FcγR-independent activity that were highly effective in the treatment of lymphoma-bearing mice. In conclusion, FcγR-independent anti-CD40 activation is a viable strategy in vivo. These findings have important translational implications, as humans, unlike mice, do not have IgG that binds strongly to FcγRIIB; therefore FcγR-independent derivatives represent an attractive therapeutic option.

A novel coronary angiography index (DILEMMA score) for prediction of functionally significant coronary artery stenoses assessed by fractional flow reserve: A novel coronary angiography index.

BACKGROUND: Angiographic evaluation of diameter stenosis has modest predictive value for functionally significant coronary artery stenoses as assessed by fractional flow reserve (FFR). Lesion length and assessment of area of myocardium at risk (Bypass Angioplasty Revascularization Investigation [BARI] Myocardial Jeopardy Index [MJI]) subtended by the stenotic coronary arteries are also predictors of functionally significant coronary artery stenoses. We sort to assess the diagnostic accuracy of DILEMMA score, which combines minimal lumen diameter (MLD), lesion length, and BARI MJI in prediction of significantly reduced FFR (≤0.8). METHODS: We assessed patients who underwent coronary angiography and FFR. Lesion length and MLD were assessed by quantitative coronary angiography. Estimation of area of myocardium at risk subtended by coronary stenoses was performed using the BARI MJI. RESULTS: A total of 296 patients (age 64 ± 10.6 years, 68% male, 497 vessels) were included. DILEMMA score was significantly higher in vessels with significant FFR, 6.09 ± 3.23 versus 3.84 ± 2.99 (P < .001). In the derivation cohort, the optimism-adjusted Harrell c statistic for DILEMMA score was 0.82 compared with 0.76 for BARI MJI, 0.75 for lesion length, and 0.7 for MLD. In the validation cohort, the c-statistic for DILEMMA score, BARI MJI, lesion length, and MLD was 0.88, 0.77, 0.81, and 0.72, respectively. The DILEMMA score was a better predictor of FFR ≤0.8 compared with MLD, lesion length, and BARI MJI individually (P < .001, P < .02, and P < .045, respectively) on Bonferroni-adjusted pairwise comparison. CONCLUSIONS: DILEMMA score, taking into account MLD, lesion length, and BARI MJI, may have incremental predictive value beyond the individual indices alone for detecting functionally significant coronary artery stenoses.

Investigation of fatty acid conjugates of 3,5-bisarylmethylene-4-piperidone derivatives as antitumor agents and human topoisomerase-IIα inhibitors.

A series of five 3,5-bisarylidene-4-piperidones designed as analogs of curcumin and their twenty five fatty acid conjugates were synthesized as candidate anticancer agents. The fatty acid conjugates were designed for efficient delivery of these compounds at the targeted cancer sites. The cytostatic potential of these compounds was evaluated against three representative cancer cell lines namely murine leukemic L1210 cells, and human T-lymphocyte CEM cells and cervical HeLa cells. Most compounds were found to exhibit significant anti-cancer activity in vitro. QSAR studies indicated electrophilicity of these compounds towards cellular nucleophiles may have a key role to play in their cytostatic activity. Representative compounds were also tested for topoisomerase IIα inhibitory potential, which indicated strong catalytic inhibition of the enzyme in vitro. The data showed that the fatty acid conjugates also possessed robust antioxidant activity in multiple analyses. This study also indicated that these compounds prompted significantly lower cellular damage in human fibroblasts than a currently used cancer drug sorafenib in vitro. The wide spectrum of anticancer action, supplemented with antioxidant potential along with non-toxic manifestations, certainly augment the anticancer candidacy of the novel fatty acid conjugates.

Use of Clinical and Echocardiographic Evaluation to Assess the Risk of Heart Failure.

BACKGROUND: Clinical and echocardiographic features predict incident heart failure (HF), but the optimal strategy for combining them is unclear. OBJECTIVES: This study sought to define an effective means of using echocardiography in HF risk evaluation. METHODS: The same clinical and echocardiographic evaluation was obtained in 2 groups with HF risk factors: a training group (n = 926, followed to 7 years) and a validation group (n = 355, followed to 10 years). Clinical risk was categorized as low, intermediate, and high using 4-year ARIC (Atherosclerosis Risk In Communities) HF risk score cutpoints of 9% and 33%. A risk stratification algorithm based on clinical risk and echocardiographic markers of stage B HF (SBHF) (abnormal global longitudinal strain [GLS], diastolic dysfunction, or left ventricular hypertrophy) was developed using a classification and regression tree analysis and was validated. RESULTS: HF developed in 12% of the training group, including 9%, 18%, and 73% of low-, intermediate-, and high-risk patients. HF occurred in 8.6% of stage A HF and 19.4% of SBHF (P < 0.001), but stage A HF with clinical risk of ≥9% had similar outcome to SBHF. Abnormal GLS (HR: 2.92 [95% CI: 1.95-4.37]; P < 0.001) was the strongest independent predictor of HF. Normal GLS and diastolic function reclassified 61% of the intermediate-risk group into the low-risk group (HF incidence: 12%). In the validation group, 11% developed HF over 4.5 years; 4%, 17%, and 39% of low-, intermediate-, and high-risk groups. Similar results were obtained after exclusion of patients with known coronary artery disease. The echocardiographic parameters also provided significant incremental value to the ARIC score in predicting new HF admission (C-statistic: 0.78 [95% CI: 0.71-0.84] vs 0.83 [95% CI: 0.77-0.88]; P = 0.027). CONCLUSIONS: Clinical risk assessment is adequate to classify low and high HF risk. Echocardiographic evaluation reclassifies 61% of intermediate-risk patients.

CDKN2B expression in adipose tissue of familial combined hyperlipidemia patients.

The purpose of this study was to determine the core biological processes perturbed in the subcutaneous adipose tissue of familial combined hyperlipidemia (FCHL) patients. Annotation of FCHL and control microarray datasets revealed a distinctive FCHL transcriptome, characterized by gene expression changes regulating five overlapping systems: the cytoskeleton, cell adhesion and extracellular matrix; vesicular trafficking; lipid homeostasis; and cell cycle and apoptosis. Expression values for the cell-cycle inhibitor CDKN2B were increased, replicating data from an independent FCHL cohort. In 3T3-L1 cells, CDKN2B knockdown induced C/EBPα expression and lipid accumulation. The minor allele at SNP site rs1063192 (C) was predicted to create a perfect seed for the human miRNA-323b-5p. A miR-323b-5p mimic significantly reduced endogenous CDKN2B protein levels and the activity of a CDKN2B 3'UTR luciferase reporter carrying the rs1063192 C allele. Although the allele displayed suggestive evidence of association with reduced CDKN2B mRNA in the MuTHER adipose tissue dataset, family studies suggest the association between increased CDKN2B expression and FCHL-lipid abnormalities is driven by factors external to this gene locus. In conclusion, from a comparative annotation analysis of two separate FCHL adipose tissue transcriptomes and a subsequent focus on CDKN2B, we propose that dysfunctional adipogenesis forms an integral part of FCHL pathogenesis.

Amyloid positron emission tomography with (18)F-flutemetamol and structural magnetic resonance imaging in the classification of mild cognitive impairment and Alzheimer's disease.

OBJECTIVE: To evaluate the contributions of amyloid-positive (Am+) and medial temporal atrophy-positive (MTA+) scans to the diagnostic classification of prodromal and probable Alzheimer's disease (AD). METHODS: (18)F-flutemetamol-labeled amyloid positron emission tomography (PET) and magnetic resonance imaging (MRI) were used to classify 10 young normal, 15 elderly normal, 20 amnestic mild cognitive impairment (aMCI), and 27 AD subjects. MTA+ status was determined using a cut point derived from a previous study, and Am+ status was determined using a conservative and liberal cut point. RESULTS: The rates of MRI scans with positive results among young normal, elderly normal, aMCI, and AD subjects were 0%, 20%, 75%, and 82%, respectively. Using conservative cut points, the rates of Am+ scans for these same groups of subjects were 0%, 7%, 50%, and 93%, respectively, with the aMCI group showing the largest discrepancy between Am+ and MTA+ scans. Among aMCI cases, 80% of Am+ subjects were also MTA+, and 70% of amyloid-negative (Am-) subjects were MTA+. The combination of amyloid PET and MTA data was additive, with an overall correct classification rate for aMCI of 86%, when a liberal cut point (standard uptake value ratio = 1.4) was used for amyloid positivity. INTERPRETATION: (18)F-flutemetamol PET and structural MRI provided additive information in the diagnostic classification of aMCI subjects, suggesting an amyloid-independent neurodegenerative component among aMCI subjects in this sample.

Echocardiographic detection of heart valve disease in a community cohort of asymptomatic Australians > 65 years with cardiovascular risk factors.

BACKGROUND: Valvular heart disease is becoming an increasingly prevalent with population ageing. We sought to define the current prevalence of valvular heart disease in Australia. METHODS: The TasELF and VicELF studies prospectively recruited 962 asymptomatic participants ≥65 years, with at least one cardiovascular risk factor, from the Tasmanian and Victorian communities. People were excluded if they had a previous diagnosis of heart failure, or a life expectancy <1 year. All underwent baseline echocardiography. Those with moderate or severe valvular disease were identified. The current prevalence of clinically significant valve disease was applied to the Australian Bureau of Statistics population projections. RESULTS: Echocardiograms were interpretable in 943 participants (98%). Clinically significant valve disease was present in 5% of the population, and mitral regurgitation was the most common overall valvular lesion, present in 36% of the population. The projected numbers of people with clinically significant valvular disease is expected to increase significantly across all age groups by the year 2060. CONCLUSIONS: Clinically significant yet asymptomatic valvular disease was prevalent in a large community cohort of participants with at least one risk factor. The total burden of valvular heart disease is expected to increase dramatically over the coming decades.

'Put in a room and left': a qualitative study exploring the lived experiences of COVID-19 isolation and quarantine among rehabilitation inpatients.

BACKGROUND: The SARS-CoV-2 (COVID-19) pandemic has resulted in significant changes to health care delivery and the patient's experience in hospital. Changes for those who contracted COVID-19 or were close contacts included isolation and quarantine, visitor restrictions and changes to usual models of care to reduce viral transmission. Traditional models of inpatient rehabilitation utilise communal spaces (e.g. shared gyms and dining rooms) and involve a multidisciplinary team interacting with the patient daily. OBJECTIVES: To report the experience of COVID-19 related isolation and quarantine among rehabilitation inpatients and their family members who experienced a nosocomial outbreak and to make recommendations for rehabilitation units. METHODS: A qualitative phenomenological methodology using semi-structured telephone interviews. RESULTS: 19 semi-structured interviews were conducted comprising of 13 general rehabilitation inpatients and 6 family members. Five themes were established: (1) the impact of social and physical isolation; (2) boredom and limited access to therapy; (3) the impact of technology; (4) inadequate information sharing and (5) positive experiences and things done well. Several novel insights were identified including: the desire for increased social interaction from staff to compensate for a lack of visitors; the impact of physical and cognitive deficits on a patient's ability to reach basic items around their room or call for help, and the unique impact of isolation and quarantine on individuals who have a history of trauma, discrimination or mental illness. CONCLUSIONS: This study establishes key areas that should be considered by rehabilitation units globally to adjust traditional models which are not suitable in this pandemic. Strategies to mitigate the impact of isolation include providing training to increase use of technologies such as tablet devices, increased staff social engagement to reduce isolation and tailoring the environment to suit specific patient groups.KEY MESSAGESCOVID-19 related isolation and quarantine has a significant and unique impact on patients with cognitive and physical impairments such as those in inpatient rehabilitation. Patients who are required to isolate in inpatient settings expressed a desire for compensatory increased social interaction from staff and required specific assistance with basic daily tasks while isolated. The study makes key recommendations for other rehabilitation units to integrate into their approach for managing patients required to isolate or quarantine.

Facilitators and barriers to employment for persons with chronic spinal cord injury or disorder: A qualitative study framed by the person-environment-occupation model.

CONTEXT/OBJECTIVE: Prolonged unemployment is common for people living with a spinal cord injury or disorder (SCI/D) and can impact negatively on quality of life. The present study examines stakeholder perspectives and experiences with the job search process in order to identify service gaps and return-to-work solutions. DESIGN: In-depth semi-structured interviews were thematically analysed, with questions focused on factors that can help or hinder efforts to gain employment. Generated themes were then applied to the Person-Environment-Occupation (PEO) systems model of participation. SETTING: Community-based disability service provider in South Australia. PARTICIPANTS: Purposive sample of persons with SCI/D (n = 8) and rehabilitation professionals (n = 4). RESULTS: Person-centred themes were strongly endorsed by both groups and focused on incentives of, and motivation for, employment. Equally important to the job search process were individual expectations and attitudes, particularly job readiness. Environmental facilitators included employers' positive attitude, although workplace discrimination remained a concern. Occupation-based barriers, rather than opportunities, were identified - namely, difficulties in SCI/D self-management, the need for timely functional assessments, and more opportunities for education, upskilling and retraining. CONCLUSIONS: The PEO model provides a broad framework to better understand the complex return-to-work process for people with a SCI/D and, potentially, uncover tangible solutions. The suggestion is that vocational rehabilitation should go beyond skills training and include motivational support to enhance job readiness. This must be done on a case-by-case basis. There is also a need for active and covert discrimination to be addressed through employment policies. The findings will be used to develop intervention targets for a newly established vocational rehabilitation service.

Comparing new templates and atlas-based segmentations in the volumetric analysis of brain magnetic resonance images for diagnosing Alzheimer's disease.

BACKGROUND: The segmentation of brain structures on magnetic resonance imaging scans for calculating regional brain volumes, using automated anatomic labeling, requires the use of both brain atlases and templates (template sets). This study aims to improve the accuracy of volumetric analysis of hippocampus (HP) and amygdala (AMG) in the assessment of early Alzheimer's disease (AD) by developing template sets that correspond more closely to the brains of elderly individuals. METHODS: Total intracranial volume and HP and AMG volumes were calculated for elderly subjects with no cognitive impairment (n = 103), with amnestic mild cognitive impairment (n = 68), or with probable AD (n = 46) using the following: (1) a template set consisting of a standard atlas (atlas S), drawn on a young adult male brain, and the widely used Montreal Neurological Institute template (MNI template set); (2) a template set (template S set) in which the template is based on smoothing the image from which atlas S is derived; and (3) a new template set (template E set) in which the template is based on an atlas (atlas E) created from the brain of an elderly individual. RESULTS: Correspondence to HP and AMG volumes derived from manual segmentation was highest with automated segmentation by template E set, intermediate with template S set, and lowest with the MNI template set. The areas under the receiver operating curve for distinguishing elderly subjects with no cognitive impairment from elderly subjects with amnestic mild cognitive impairment or probable AD and the correlations between HP and AMG volumes and cognitive and functional scores were highest for template E set, intermediate for template S set, and lowest for the MNI template set. CONCLUSIONS: The accuracy of automated anatomic labeling and the diagnostic value of the derived volumes are improved with template sets based on brain atlases closely resembling the anatomy of the to-be-segmented brain magnetic resonance imaging scans.

Cognitive and structural magnetic resonance imaging features of Lewy body dementia and Alzheimer's disease.

OBJECTIVE: To assess medial temporal atrophy (MTA) and atrophy adjacent to the third ventricle (Peri-IIIVent) on brain magnetic resonance images as biomarkers for the diagnosis of Alzheimer's disease (AD) and Lewy body dementia (LBD), and to assess the relationship between biomarkers and clinical and functional measures. METHODS: Subjects diagnosed with no cognitive impairment (n = 30), AD (n = 30), or LBD (n = 31) were evaluated with the Mini-Mental State Examination, Multiple Delayed Recall Test, Category Fluency Test, Clinical Dementia Rating Sum of Boxes score, Functional Assessment Questionnaire, and the Unified Parkinson's Disease Rating Scale. A validated visual rating system was used to rate MTA, and volumetric studies were performed to measure total intracranial and hippocampal volumes. Additionally, linear measurements of third ventricle width, Peri-IIIVent height, and Peri-IIIVent width were performed. RESULTS: Subjects with AD and those with LBD were equivalent with respect to age and levels of cognitive impairment. Atrophy in medial temporal and Peri-IIIVent regions was greater among both patients with AD and those with LBD compared with subjects with no cognitive impairment. The best discriminators of AD from LBD were the severity of MTA, using visual rating, and the severity of memory impairment. Only subjects with LBD showed significant correlations between Unified Parkinson's Disease Rating Scale scores and Peri-IIIVent atrophy measures. CONCLUSIONS: Mild AD could be distinguished from mild LBD by the severity of MTA and memory impairment. The severity of parkinsonism was associated with the severity of atrophy in the third ventricular region, but was not a good discriminator between AD and LBD.