Frontotemporal dementia (FTD) remains challenging to diagnose owing to the marked clinical heterogeneity associated with the disease. This heterogeneity stems from the complex interplay of various clinical phenotypes, genetic mutations and underlying neuropathologies, such as TDP-43 and tau proteinopathies. Currently, there is no single confirmed biomarker that can reliably diagnose disease, specifically disease stage, disease subtype and underlying neuropathology. Recent research has indicated that neuroimaging techniques hold the most promise for the discovery of FTD biomarkers. We propose a protocol for a systematic review and meta-analysis to identify MRI and fluorodeoxyglucose positron emission tomography (FDG-PET) biomarkers associated with clinical, genetic and pathological subtypes of FTD. We aim to address the following research questions: can regional MRI volumetry and FDG-PET hypometabolism differentiate (1) FTD patients from healthy controls; (2) sporadic cases of FTD from healthy controls; (3) genetic cases of FTD (MAPT, GRN, and C9orf72 mutations); and (4) underlying neuropathology, specifically discriminating between tau- and TDP-43-based FTD?
Literature searches will be performed across three databases: Ovid Medline, Ovid Embase and Web of Science. Publications that have fewer than five participants, are non-human-based, not written in the English language or contain unpublished data will be excluded. Two independent investigators will screen and subsequently evaluate which publications to include. Should any disagreements arise, a third investigator will settle the discrepancy. After the random-effects meta-analysis has been used to extract and pool the data, I2 analysis will be used to quantify heterogeneity.
Ethics approval will not be required for this research. On completion, the systematic review and meta-analysis will be published in a peer-reviewed journal.
CRD42024545302.
Growing evidence points towards the integral role of both central and peripheral inflammation across all neurodegenerative diseases, including dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). The immune alterations observed in these diseases may occur long before the onset of clinical and cognitive symptoms; however, the exact timing and role of inflammation in the pathogenesis of neurodegenerative disease remains unclear. Findings to date are conflicting, with most work focused on AD rather than other dementias and most studies from single sites and cross-sectional. Through longitudinally examining detailed phenotypes of the peripheral immune system using mass cytometry, the Immune Profiling in Early Cognitive Disorders study aims to uncover specific immune signatures in early AD and DLB, how these signatures change over time and how they relate to disease progression and cognitive changes.
Blood, cerebrospinal fluid, saliva and urine samples will be collected from a cohort of participants with either prodromal (mild cognitive impairment) or early dementia due to Lewy bodies or AD (MCI-LB and DLB; and MCI-AD and AD), alongside healthy controls. Through immunophenotyping with mass cytometry, detailed immune fingerprints will be identified for these groups. We will assess which key combinations of immune cell clusters are predictive of disease phenotype, cognitive decline and progression to dementia. Samples will also be evaluated with novel techniques to measure markers of degenerative pathology and inflammation.
This study was approved by the Preston North West Research Ethics committee (21/NW/0314) and is registered with the ISRCTN registry (ISRCTN62392656). The study is ongoing (since June 2022). Baseline visits are being undertaken, and follow-up visits have started for some participants. Full data analyses will be completed and submitted for publication upon conclusion of the study.
Leishmaniasis poses a significant public health problem in Kenya, where effective case management and treatment rely on accurate diagnosis. This review aims to summarise the research landscape on leishmaniasis diagnostics in Kenya and identify gaps.
This scoping review expands a previously published scoping review on leishmaniasis in Kenya to further analyse studies focusing on diagnostics. The field of diagnostics was chosen because of recent pushes for novel tools and because of the role timely diagnosis plays in disease elimination. A comprehensive search of PubMed, Embase via Embase.com, Web of Science Core Collection, the Cochrane Library, ClinicalTrials.gov, WHO ICTRP and the Pan African Clinical Trials Registry was conducted, covering studies up to 5 January 2024.
After dual, blind screening with conflict resolution by a third reviewer, 41 studies were included in the review. These studies examined a range of diagnostic tools; however most were assessed in one or few studies, and none evaluated real-time PCR. Additional gaps in the research landscape include a lack of diagnostics for cutaneous leishmaniasis and post-kala-azar dermal leishmaniasis in Kenya, outdated literature surrounding the Direct Agglutination Test and randomised trials for any diagnostic tool.
Future research should focus on solidifying the validity and reliability of diagnostic tools in the Kenyan context and updating previous work.
Vector control is imperative for eliminating leishmaniasis as a public health problem in Kenya. As elimination efforts expand in East Africa, it is crucial to understand the current research landscape. To address that need and identify gaps, a scoping review was conducted to characterise the landscape of leishmaniasis vector research in Kenya.
Building on a previously published scoping review by this team, we updated database searches in PubMed, Embase via Embase.com, Web of Science Core Collection, the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) and the Pan African Clinical Trials Registry to incorporate literature up to 4 January 2024 and focused on vector-related papers. Studies classified as ‘prevention’ in the original scoping review were included due to overlapping definitions.
A total of 95 studies were included in the analysis. Although a wide range of sandfly species have been documented, most of the research is outdated, having taken place 20–40 years ago. Existing studies are mostly epidemiological with little focus on basic and clinical research. There are also no studies on post-kala-azar dermal leishmaniasis despite its potential contribution to the disease transmission cycle. The geographical scope of the research is largely limited to traditional transmission foci with little attention to new disease hotspots such as North Eastern Kenya.
These research gaps need to be addressed to better inform the country’s leishmaniasis prevention and vector control strategy.
The Episodic Disability Questionnaire (EDQ) was developed to measure the presence, severity and episodic nature of disability experienced among persons with chronic conditions. Our aim was to assess the sensibility, utility and implementation considerations of the EDQ among older adults with complex health needs.
Cross-sectional measurement study involving quantitative and qualitative methods of data collection.
We recruited community-dwelling older adults (65 years of age or older) living with complex health needs receiving care from a primary healthcare team in Toronto, Canada.
We administered the EDQ, sensibility questionnaire (assessing face and content validity, and ease of usage, with each item scored from 0 to 7 with greater scores indicating greater sensibility) and demographic questionnaire, followed by a semi-structured interview in the home or clinical setting. Using an interview guide, we asked participants about their perspectives on utility, format and implementation of the EDQ in clinical practice. We considered the EDQ sensible if the median score on the sensibility questionnaire was ≥5/7 for ≥80% of items and if none of the items had a median score of ≤3/7. We conducted a team-based directed content analysis of the interview transcripts.
The median age of the 11 participants in this study was 83 years of age. All participants reported living with two or more chronic health conditions, with osteoarthritis (n=5) and diabetes (n=4) most frequently reported. The EDQ met the criterion for sensibility as measured by the sensibility questionnaire. Interview data from participants (n=10) indicated that the EDQ represents the health-related challenges among this sample of older adults with complex health needs, captures the episodic nature of disability and was easy to use. Utility of the EDQ included providing clinicians with a holistic understanding of health challenges older adults face, aiding in intervention planning and measuring changes in disability over time. Six of the participants also expressed uncertainty as to how the EDQ specifically could be used by clinicians in their care. Considerations for implementation included mode of administration (paper or electronic) and the importance of communicating EDQ scores with older adults based on individual preferences.
The EDQ possesses sensibility and utility for use among this sample of older adults living with complex health needs in home or clinical care settings.
The COVID-19 pandemic dramatically affected schools. However, there are insufficient data on the chronic physical and mental health consequences of the pandemic in school workers.
To determine the prevalence and the functional and mental health impact of pandemic-related chronic health symptoms among school workers towards the end of the COVID-19 pandemic.
Cross-sectional analysis of health questionnaires and serology testing data (nucleocapsid, N antibodies) collected between January and April 2023, within a cohort of school workers.
Three large school districts (Vancouver, Richmond, Delta) in the Vancouver metropolitan area, Canada (representing 186 elementary and secondary schools in total).
Active school staff employed in these three school districts.
COVID-19 infection history by self-reported viral and/or nucleocapsid antibody testing.
Self-reported, new-onset pandemic-related chronic health symptoms that started within the past year, lasting at least 3 months, after a positive viral test among those with a known infection.
Of 1128 school staff enrolled from 185/186 (99.5%) schools, 1086 (96.3%) and 998 (88.5%) staff completed health questionnaires and serology testing, respectively. The N-seroprevalence adjusted for clustering by school and test sensitivity and specificity was 84.7% (95% Credible Interval (95% CrI): 79.2% to 91.8%) compared with 85.4% (95% CrI: 81.6% to 90.3%) in a community-matched sample of blood donors. Overall, 31.1% (95% CI: 28.4% to 34.0%) staff reported new-onset chronic symptoms. These symptoms were more frequently reported in staff with viral test-confirmed infections (38.0% (95% CI: 34.3% to 41.9%)) compared with those with positive serology who were unaware that they had COVID-19 (14.3% (95% CI: 7.6% to 23.6%); p
The pandemic had major health impacts on school workers. To our knowledge, this study is among the first to concurrently quantify a broad range of chronic physical and mental health impacts, highlighting the need for further research and targeted health programmes to address this significant burden.
Amoxicillin is recommended for children with uncomplicated severe acute malnutrition (SAM). However, some trials have shown no difference in amoxicillin for nutritional recovery in children with SAM compared with placebo. In addition, amoxicillin treatment requires two times per day dosing for 7 days, which may influence adherence. Azithromycin is a broad-spectrum antibiotic that can be provided as a single dose and has reduced mortality in children aged 1–59 months when provided by mass drug administration. The AMOUR trial is designed to assess amoxicillin, azithromycin and placebo as part of outpatient treatment of uncomplicated SAM.
This double-masked randomised controlled trial will enrol 3000 children over 3 years in an individually randomised 1:1:1 allocation to azithromycin, amoxicillin or placebo arms and follow them for 12 months. Children eligible to enrol in the study will be aged 6–59 months and have uncomplicated non-oedematous SAM as defined by weight-for-height Z-score
Ethical approval was obtained from the Institutional Review Board at the University of California, San Francisco (Protocol 23–39411) and the Comité d’Ethique pour la Recherche en Santé in Ouagadougou, Burkina Faso (Protocol 2024-01-08). The results of this study will be disseminated to the Ministry of Health, community stakeholders and via peer-reviewed publications and academic conferences.