Clinical utility of cerebrospinal fluid biomarkers in the evaluation of cognitive impairment: a systematic review and meta-analysis

BACKGROUND: The analytical and clinical validity of cerebrospinal (CSF) biomarkers has been extensively researched in dementia. Further work is needed to assess the ability of these biomarkers to improve diagnosis, management and health outcomes in the clinical setting OBJECTIVES: To assess the added value and clinical utility of CSF biomarkers in the diagnostic assessment of cognitively impaired patients under evaluation for Alzheimer's disease (AD). METHODS: Systematic literature searches of Medline, EMBASE, PsycINFO and Web of Science research databases were conducted on 17 December 2022. Data from relevant studies were extracted and independently screened for quality using a tool for bias. Clinical utility was measured by clinicians' changes in diagnosis, diagnostic confidence and patient management (when available), after their examination of patients' CSF biomarkers. Cost-effectiveness was assessed by consideration of additional cost per patient and quality-adjusted life years. RESULTS: Searches identified 17 studies comprising 2090 patient participants and 593 clinicians. The meta-analysis revealed that clinicians' use of CSF biomarkers resulted in a pooled percentage change in diagnosis of 25% (95% CI 14 to 37), an increase in diagnostic confidence of 14% (95% CI 9 to 18) and a pooled proportion of patients whose management changed of 31% (95% CI 12 to 50). CSF biomarkers were deemed cost-effective, particularly in memory services, where pre-test AD prevalence is higher compared with a primary care setting. CONCLUSIONS: CSF biomarkers can be a helpful additional diagnostic tool for clinicians assessing patients with cognitive impairment. In particular, CSF biomarkers consistently improved clinicians' confidence in diagnosing AD and influenced on diagnostic change and patient management. Further research is needed to study the clinical utility of blood-based biomarkers in the clinical setting

Regenerable DNA-Functionalized Hydrogels for Ultrasensitive, Instrument-Free Mercury(II) Detection and Removal in Water

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see Dave, N., Chan, M. Y., Huang, P.-J. J., Smith, B. D., & Liu, J. (2010). Regenerable DNA-Functionalized Hydrogels for Ultrasensitive, Instrument-Free Mercury(II) Detection and Removal in Water. Journal of the American Chemical Society, 132(36), 12668–12673. https://doi.org/10.1021/ja106098jMercury is a highly toxic environmental pollutant with bioaccumulative properties. Therefore, new materials are required to not only detect but also effectively remove mercury from environmental sources such as water. We herein describe a polyacrylamide hydrogel-based sensor functionalized with a thymine-rich DNA that can simultaneously detect and remove mercury from water. Detection is achieved by selective binding of Hg2+ between two thymine bases, inducing a hairpin structure where, upon addition of SYBR Green I dye, green fluorescence is observed. In the absence of Hg2+, however, addition of the dye results in yellow fluorescence. Using the naked eye, the detection limit in a 50 mL water sample is 10 nM Hg2+. This sensor can be regenerated using a simple acid treatment and can remove Hg2+ from water at a rate of ∼1 h−1. This sensor was also used to detect and remove Hg2+ from samples of Lake Ontario water spiked with mercury. In addition, these hydrogel-based sensors are resistant to nuclease and can be rehydrated from dried gels for storage and DNA protection. Similar methods can be used to functionalize hydrogels with other nucleic acids, proteins, and small molecules for environmental and biomedical applications.University of Waterloo || Natural Sciences and Engineering Research Council |

Advisory panel review on the feasibility of three intervention programmes for children with autism spectrum disorder

Introduction: The prevalence of children with autism spectrum disorder is increasing each year. Intervention programmes towards improving the occupational needs such as daily activities of these children are limited. This study aimed to collect opinions from advisory panel for the content validation of the three developed intervention programmes to be implemented among children with autism spectrum disorder aged between 6 to 12 years. The intervention programmes are; i) self-regulated learning, ii) sensory integration intervention and iii) activity-based intervention. Methods: A cross-sectional study was conducted. Twenty occupational therapists with more than three years’ experience working with children with autism spectrum disorders were recruited as advisory panel members. Re-searchers-developed questionnaire was used. The questionnaire consists of nine to eleven items. Each item consists of a five-point Likert scale for quantitative responses and open-ended questions for qualitative responses. Results: Advisory panel ratings of ‘Good’ to ‘Excellent’ was reported across most items in all three intervention programmes. Overall results suggested that the intervention programmes content was rated to be suitable for children with autism spectrum disorder. Constructive comments were adopted to clarify the activities and structure of the intervention programmes. Final development of the intervention programmes is presented. Conclusion: This study provides confidence for the interventions to be incorporated into the future randomised controlled trial

Closing the gap in surveillance and audit of invasive mold diseases for antifungal stewardship using machine learning

Clinical audit of invasive mold disease (IMD) in hematology patients is inefficient due to the difficulties of case finding. This results in antifungal stewardship (AFS) programs preferentially reporting drug cost and consumption rather than measures that actually reflect quality of care. We used machine learning-based natural language processing (NLP) to non-selectively screen chest tomography (CT) reports for pulmonary IMD, verified by clinical review against international definitions and benchmarked against key AFS measures. NLP screened 3014 reports from 1 September 2008 to 31 December 2017, generating 784 positives that after review, identified 205 IMD episodes (44% probable-proven) in 185 patients from 50,303 admissions. Breakthrough-probable/proven-IMD on antifungal prophylaxis accounted for 60% of episodes with serum monitoring of voriconazole or posaconazole in the 2 weeks prior performed in only 53% and 69% of episodes, respectively. Fiberoptic bronchoscopy within 2 days of CT scan occurred in only 54% of episodes. The average turnaround of send-away bronchoalveolar galactomannan of 12 days (range 7-22) was associated with high empiric liposomal amphotericin consumption. A random audit of 10% negative reports revealed two clinically significant misses (0.9%, 2/223). This is the first successful use of applied machine learning for institutional IMD surveillance across an entire hematology population describing process and outcome measures relevant to AFS. Compared to current methods of clinical audit, semi-automated surveillance using NLP is more efficient and inclusive by avoiding restrictions based on any underlying hematologic condition, and has the added advantage of being potentially scalable

Development and feasibility of first- and third-person motor imagery for people with stroke living in the community

Background: Impairment of arm movement occurs in up to 85% of people post-stroke, affecting daily living activities, and quality of life. Mental imagery effectively enhances hand and daily function in people with stroke. Imagery can be performed when people imagine themselves completing the movement or imagine another person doing it. However, there is no report on the specific use of first-person and third-person imagery in stroke rehabilitation. Aims: To develop and assess the feasibility of the First-Person Mental Imagery (FPMI) and the Third-Person Mental Imagery (TPMI) programs to address the hand function of people with stroke living in the community. Methods: This study comprises phase 1—development of the FPMI and TPMI programs, and phase 2—pilot-testing of the intervention programs. The two programs were developed from existing literature and reviewed by an expert panel. Six participants with stroke, living in the community, participated in the pilot-testing of the FPMI and TPMI programs for 2 weeks. Feedback collected included the suitability of the eligibility criteria, therapist’s and participant’s adherence to intervention and instructions, appropriateness of the outcome measures, and completion of the intervention sessions within the specified time. Results: The FPMI and TPMI programs were developed based on previously established programs and included 12 hand tasks. The participants completed four 45-min sessions in 2 weeks. The treating therapist adhered to the program protocol and completed all the steps within the specified time frame. All hand tasks were suitable for adults with stroke. Participants followed the instructions given and engaged in imagery. The outcome measures selected were appropriate for the participants. Both programs showed a positive trend towards improvement in participants’ upper extremity and hand function and self-perceived performance in activities of daily living. Conclusions: The study provides preliminary evidence that these programs and outcome measures are feasible for implementation with adults with stroke living in the community. This study outlines a realistic plan for future trials in relation to participant recruitment, training of therapists on the intervention delivery, and the use of outcome measures

A semantic-based cognitive training programme on everyday activities : a feasibility and acceptability study among cognitively healthy older adults

Background. During the normal ageing process, a person’s cognitive functions and memory gradually decline, which can affect their ability to perform everyday activities including cooking, cleaning, managing finances, and shopping. Semantic memory encoding strategies benefit older adults’ cognitive and functional performance. Such strategies can be taught by an accessible, cost-effective, and flexible app-based programme. Currently, no studies examine such an app-based programme focussed on everyday activities. Objectives. To determine if an app-based programme constructed on the principles of semantic memory encoding strategies, targeted towards older adults, called Enhancing Memory in Daily Life (E-MinD Life) is (1) feasible by examining acceptance, engagement, and attendance and (2) acceptable by examining the perceived effectiveness, relevancy, clarity, and convenience. Methods. Eleven participants were recruited to a nine-week (18 sessions) programme using E-MinD Life. Feasibility was measured by collecting data on recruitment and retention rates, attendance, and duration of sessions. Acceptability was measured via a Likert scale questionnaire and free comments. Likert scale responses were analysed using descriptive statistics; open-ended responses were categorised qualitatively via constant comparative approach. Results. Nine participants completed the programme. Overall, most participants found the programme relevant, convenient, logical, and easy to understand and perceived it to be effective to address functional cognitive problems impacting performance of everyday activities. The results from the qualitative analysis showed that participants found the programme enjoyable and the interaction with the research team throughout the intervention beneficial. Conclusion. E-MinD Life shows promise as the focus of further research to determine the effectiveness of the programme and sematic-based cognitive strategies in maintaining cognition and performance in everyday activities among older adults with and without cognitive impairment

The feasibility and acceptability of an app-based cognitive strategy training programme for older people

Background Increasing numbers of people are living with mild cognitive impairment in later life and seeking therapy to maintain cognition to remain as independent as possible in daily life. Based on a review of the literature, an app-based programme using perceptual-encoding strategies called Enhancing Memory in Daily Life (E-MinD Life) was developed. An expert panel reviewed the programme’s appropriateness for older people with and without mild cognitive impairment. As part of the design process, the feasibility and acceptability of the E-MinD Life programme were then assessed in relation to its use by healthy older adults, with fndings informing the application of the programme to older people with mild cognitive impairment in the future. Methods Phase 1: The E-MinD Life programme was reviewed by an expert panel of occupational therapists. Experts rated the programme on a Likert scale and answered open-ended questions in relation to feasibility, clarity, and relevancy. Phase 2 involved feld-testing the 9-week programme with a sample of nine healthy older people. Participants rated the acceptability of the programme on a Likert scale questionnaire. Data on recruitment rates and retention, and adherence and duration of sessions were collected to determine the feasibility of the programme. Responses to the Likert scale were analysed using descriptive statistics. Open-ended responses were categorised qualitatively using a constant comparative approach. Results Phase 1: Experts indicated that the E-MinD Life programme was feasible and included relevant activities for community living. Although experts felt that an older user with mild NCD would be able to independently complete the programme, the qualitative analysis suggests formatting changes in future iterations of the programme to enhance visual clarity. Phase 2: All participants completed the 9-week programme. The average number of selfadministered sessions attempted over the 9-week period was 13.44 (SD=6.73) out of 18 scheduled sessions. Overall, most participants found the programme relevant, logical and easy to understand, and perceived it to be efective for functional cognitive problems. Conclusion The E-MinD Life programme shows promise for inclusion into trial designs to determine the efectiveness of the cognitive strategy programme for older people with and without cognitive impairment. Trial registration ClinicalTrials.gov, NCT03430401. Registered 1 February 2018

Efficacy of cognitive remediation on activities of daily living in individuals with mild cognitive impairment or early-stage dementia : a systematic review and meta-analysis

Introduction: Instrumental activities of daily living are essential for ageing well and independent living. Little is known about the effectiveness of cognitive remediation on instrumental activities of daily living performance for individuals with mild cognitive impairment or early-stage dementia. The objective of this study was to evaluate the immediate and long-term carryover effects of cognitive remediation on improving or maintaining instrumental activities of daily living performance in older adults with mild cognitive impairment and early-stage dementia. Methods: Randomized controlled trials published from 2009 to 2022 were identified in OvidSP versions of MEDLINE and Embase, EBSCO versions of CINAHL and PsycINFO, and the Cochrane Central Register of Controlled Trials. A narrative synthesis of the findings was reported on the outcomes of the included studies. Relevant data was extracted and analysed using R software’s ‘metafor’ package with a random effect model with 95% CI. Results: Thirteen studies, totalling 1414 participants, were identified in the narrative analysis. The results of meta-analysis, inclusive of 11 studies, showed that cognitive remediation elicited a significant improvement in the instrumental activities of daily living performance (SMD: 0.17, 95% CI 0.03–0.31). There was insufficient evidence of any lasting effect. Discussion: Cognitive remediation is effective in improving instrumental activities of daily living performance immediately post-intervention in older adults with mild cognitive impairment and early-stage dementia. It appears that individualized interventions with a short duration, such as 10 hours, might be beneficial. Systematic review registration: PROSPERO CRD4201604236

Effectiveness of action observation and motor imagery on relearning upper extremity function after stroke : a systematic review and meta-analysis

The effectiveness of action observation (AO) and motor imagery (MI) in high-quality studies with less risk of bias is rarely reported together. This systematic review evaluates the effectiveness of AO and MI on improving upper extremity function among people after stroke by combining evidence of studies with high methodological quality. Randomised controlled trials, with a score of 6 or above in the PEDro Scale, that examined the effects of AO or MI for people with stroke were selected. A narrative analysis and meta-analysis were conducted using the PRISMA guidelines. Ten randomised controlled trials from 11 articles met the inclusion criteria. The results of meta-analysis showed that AO had a small to moderate statistically significant effect on improving upper extremity motor function (standardized mean difference, SMD=0.34; confidence interval, CI=0.08, 0.59; P=0.35; I2=0.00%) and no significant effect on MI (SMD=0.08; CI=-0.26, 0.42; P=0.65; I2=0.00%) when compared with the control intervention. Evidence was found in support of AO and it is recommended for people with acute or sub-acute stroke