The term frontotemporal dementia (FTD) refers to a heterogeneous group of neurodegenerative disorders affecting the frontal and temporal lobes. Cognitively, impairment of executive function and social cognition predominates across the FTD spectrum, although other domains can be affected. Traditionally, cognition is tested through standard ‘pen and paper’ tasks in FTD. However, recent attempts have been made across other neurodegenerative disorders such as Alzheimer’s disease to develop computerised batteries that allow more accurate and sensitive detection of cognitive impairment.
This paper describes the development of a novel battery of tests for a tablet computer, particularly focused on FTD. It consists of 12 different tasks which aim to tap into information processing speed, various aspects of executive function, social cognition, semantic knowledge, calculation and visuospatial skills. Future studies will focus on validating the battery in a healthy control cohort, comparing it against a standard ‘pen and paper’ psychometric battery, and finally testing it within an FTD cohort, including those with genetic forms of FTD where we will be able to assess its ability to detect very early cognitive deficits prior to the onset of symptoms.
Normative data will be produced in the initial validation study (approved by the UCL Ethics Committee, project ID 17691/002) and will be made available online.
by Courtney P. Williams, Gabrielle B. Rocque, Nicole E. Caston, Kathleen D. Gallagher, Rebekah S. M. Angove, Eric Anderson, Janet S. de Moor, Michael T. Halpern, Anaeze C. Offodile II, Risha Gidwani
Uninsured or underinsured individuals with cancer are likely to experience financial hardship, including forgoing healthcare or non-healthcare needs such as food, housing, or utilities. This study evaluates the association between health insurance coverage and financial hardship among cancer survivors during the COVID-19 pandemic. This cross-sectional analysis used Patient Advocate Foundation (PAF) survey data from May to July 2020. Cancer survivors who previously received case management or financial aid from PAF self-reported challenges paying for healthcare and non-healthcare needs during the COVID-19 pandemic. Associations between insurance coverage and payment challenges were estimated using Poisson regression with robust standard errors, which allowed for estimation of adjusted relative risks (aRR). Of 1,437 respondents, 74% had annual household incomesThis meta-review aimed to appraise and synthesise findings from existing systematic reviews that measured the impact of compression therapy on venous leg ulcers healing. We searched five databases to identify potential papers; three authors extracted data, and a fourth author adjudicated the findings. The AMSTAR-2 tool was used for quality appraisal and the certainty of the evidence was appraised using GRADEpro. Data analysis was undertaken using RevMan. We identified 12 systematic reviews published between 1997 and 2021. AMSTAR-2 assessment identified three as high quality, five as moderate quality, and four as low quality. Seven comparisons were reported, with a meta-analysis undertaken for five of these comparisons: compression vs no compression (risk ratio [RR]: 1.55; 95% confidence interval [CI] 1.34-1.78; P < .00001; moderate-certainty evidence); elastic compression vs inelastic compression (RR: 1.02; 95% CI: 0.96-1.08; P < .61 moderate-certainty evidence); four layer vs <four-layer bandage systems (RR: 1.07; 95% CI: 0.82-1.40; P < .63; moderate-certainty evidence); comparison between different four-layer bandage systems (RR: 1.08; 95% CI: 0.93-1.25; P = .34; moderate-certainty evidence); compression bandage vs compression stocking (RR 0.95; 95% CI 0.87-1.03; P = .18; moderate-certainty evidence). The main conclusion from this review is that there is a statistically significant difference in healing rates when compression is used compared with no compression, with moderate-certainty evidence. Otherwise, there is no statistically different difference in healing rates using elastic compression vs inelastic compression, four layer vs <four-layer bandage systems, different four-layer bandage systems, or compression bandages vs compression stockings.
Wounds continue to be of a global concern. Therefore, a more focussed, evidence-based approach to wound assessment and management is required. The WOUND COMPASS™ Clinical Support App (CSA) is designed to support the health care professional with wound assessment and management at the point of care. This real-world pilot study aimed to determine the utility of the CSA during routine wound management, in multiple care settings. A non-interventional, real-world pilot programme of the CSA was conducted at four sites. Patients received routine wound management. The CSA was programmed to replicate the site's formulary for evidence-based wound management. Anonymised pre- and post-pilot clinician opinion surveys on useability and impact of the CSA were collected and reported. Wound Specialists (n = 7 [100%]) and Non-Wound Specialists (NWS) (n = 58 [82%]) indicated that competence and confidence in wound assessment were enhanced with use of the CSA (100%; 82%). Furthermore, practice variation was reduced because of a greater compliance to their local formulary (n = 7 [100%]; 79% [54%]). This real-world pilot shows the positive impact of the CSA, and the improvements that can be potentially realised via reduction in practice variation, improvement in NWSs confidence when managing wounds and increased formulary compliance.
Sub-Saharan Africa shoulders the highest burden of global sepsis and associated mortality. In high HIV and tuberculosis (TB) prevalent settings such as sub-Saharan Africa, TB is the leading cause of sepsis. However, anti-TB therapy is often delayed and may not achieve adequate blood concentrations in patients with sepsis. Accordingly, this multisite randomised clinical trial aims to determine whether immediate and/or increased dose anti-TB therapy improves 28-day mortality for participants with HIV and sepsis in Tanzania or Uganda.
This is a phase 3, multisite, open-label, randomised controlled clinical 2x2 factorial superiority trial of (1) immediate initiation of anti-TB therapy and (2) sepsis-specific dose anti-TB therapy in addition to standard of care antibacterials for adults with HIV and sepsis admitted to hospital in Tanzania or Uganda. The primary endpoint is 28-day mortality. A sample size of 436 participants will provide 80% power for testing each of the main effects of timing and dose on 28-day mortality with a two-sided significance level of 5%. The expected main effect for absolute risk reduction is 13% and the expected OR for risk reduction is 1.58.
This clinical trial will determine the optimal content, dosing and timing of antimicrobial therapy for sepsis in high HIV and TB prevalent settings. The study is funded by the National Institutes of Health in the US. Institutional review board approval was conferred by the University of Virginia, the Tanzania National Institute for Medical Research, and the Uganda National Council for Science and Technology. Study results will be published in peer-reviewed journals and in the popular press of Tanzania and Uganda. We will also present our findings to the Community Advisory Boards that we convened during study preparation.
ClinicalTrials.gov (NCT04618198).
High use of CT scanning has raised concern due to the potential ionising radiation exposure. This study examined trends of CT during admission to tertiary hospitals and its associations with length of stay (LOS), readmission and mortality.
Retrospective observational study from 2003 to 2015.
West Australian linked administrative records at individual level.
2 375 787 episodes of tertiary hospital admission in adults aged 18+ years.
LOS, 30-day readmissions and mortality stratified by CT use status (any, multiple (CTs to multiple areas during episode), and repeat (repeated CT to the same area)).
Multivariable regression models were used to calculate adjusted rate of CT use status. The significance of changes since 2003 in the outcomes (LOS, 30-day readmission and mortality) was compared among patients with specific CT imaging status relative to those without.
Between 2003 and 2015, while the rate of CT increased 3.4% annually, the rate of repeat CTs significantly decreased –1.8% annually and multiple CT showed no change. Compared with 2003 while LOS had a greater decrease in those with any CT, 30-day readmissions had a greater increase among those with any CT, while the probability of mortality remained unchanged between the any CT/no CT groups. A similar result was observed in patients with multiple and repeat CT scanning, except for a significant increase in mortality in the recent years in the repeat CT group.
The observed pattern of increase in CT utilisation is likely to be activity-based funding policy-driven based on the discordance between LOS and readmissions. Meanwhile, the repeat CT reduction aligns with a more selective strategy of use based on clinical severity. Future research should incorporate in-hospital and out-of-hospital CT to better understand overall CT trends and potential shifts between settings over time.
Evidence suggests a role for Central nervous system glia in pain transmission and in augmenting maladaptive opioid effects. Identification of drugs that modulate glia has guided the evaluation of glial suppression as a pain management strategy. This planned systematic review will describe evidence of the efficacy and adverse effects of glial-modulating drugs in pain management.
A detailed search will be conducted on the Cochrane Central Register of Controlled Trials, Medline, and Embase from their inception until the date the final searches are run to identify relevant randomised controlled trials. The reference lists of retrieved studies, as well as online trial registries, will also be searched. English language, randomised, double-blind trials comparing various glial-modulating drugs with placebo and/or other comparators, with participant-reported pain assessment, will be included. Two reviewers will independently evaluate studies for eligibility, extract data and assess trial quality and potential bias. Risk of bias will be assessed using criteria outlined in the Cochrane Handbook for Systematic Review of Interventions. Primary outcomes for this review will include any validated measure of pain intensity and/or pain relief. Dichotomous data will be used to calculate risk ratio and number needed to treat or harm. The quality of evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation.
This systematic review does not require formal ethics approval. The findings will be disseminated through peer-reviewed publications and conference presentations.
CRD42021262074.
by Mathangi Janakiraman, Shin-Young Na, Gurumoorthy Krishnamoorthy
T cells express co-receptors CD4 and CD8, which are involved in the recognition of antigen presented to T cell receptors. The expression of CD4 in thymic hematopoietic cells is crucial for the thymic development and selection of T cells. In this study, we identified a novel CD4 mutant allele that emerged spontaneously in our mouse colony. The frameshift mutation led to a truncated CD4 protein which failed to reach the plasma membrane resulting in impaired development of CD4+ helper T cells. The CRISPR mediated correction of mutant allele restored the membrane CD4 expression. Further, using an adoptive transfer of T cells, we show that this model is an ideal recipient mouse for the study of CD4+ T cells.Sex and gender are independently important in health and disease but have been incompletely explored in neurology. This is in part contributed to by the pre-existing male bias in scientific literature that results in fewer females being included in clinical research and the often interchangeable use of sex and gender in the literature. This scoping review intends to identify the advances as well as under-explored aspects of this field to provide a road map for future research. This paper outlines the methods for a scoping review of published, peer-reviewed literature on sex and gender differences in four subspecialty areas of neurology: demyelination, stroke, epilepsy and headache.
A detailed search strategy will be used to search five databases pertaining only to sex differences. Specific inclusion and exclusion criteria will be applied to capture relevant literature published from 2014 to 2020. Data will be collected and synthesised to provide an overview of information retrieved, a narrative synthesis of each subspecialty area and map of results.
Research ethics board approval was not required for this study. This study will aid in mapping recent trends in sex differences in four major neurological conditions and will help identify areas for further research. A manuscript will be compiled for publication and presentations of findings.
The final protocol is registered with the Open Science Framework (https://osf.io/n937x/).
The Banned Drinker Register (BDR) was reintroduced in the Northern Territory (NT) in September 2017. The BDR is a supply reduction measure and involves placing people who consume alcohol at harmful levels on a register prohibiting the purchase, possession and consumption of alcohol. The current study aims to evaluate the impacts of the reintroduction of the BDR, in the context of other major alcohol policy initiatives introduced across the NT such as Police Auxiliary Liquor Inspectors and a minimum unit price for alcohol of US$1.30 per standard drink.
The Learning from Alcohol (policy) Reforms in the Northern Territory project will use a mixed-methods approach and contain four major components: epidemiological analysis of trends over time (outcomes include health, justice and social welfare data); individual-level data linkage including those on the BDR (outcomes include health and justice data); qualitative interviews with key stakeholders in the NT (n≥50); and qualitative interviews among people who are, or were previously, on the BDR, as well as the families and communities connected to those on the BDR (n=150). The impacts of the BDR on epidemiological data will be examined using time series analysis. Linked data will use generalised mixed models to analyse the relationship between outcomes and exposures, utilising appropriate distributions. Qualitative data will be analysed using thematic analysis.
Ethics approvals have been obtained from NT Department of Health and Menzies School of Health Research Human Research Ethics Committee (HREC), Central Australia HREC and Deakin University HREC. In addition to peer-reviewed publications, we will report our findings to key organisational, policy, government and community stakeholders via conferences, briefings and lay summaries.
By subsidising access to direct acting antivirals (DAAs) for all people living with hepatitis C (HCV) in 2016, Australia is positioned to eliminate HCV as a public health threat. However, uptake of DAAs has declined over recent years and new initiatives are needed to engage people living with HCV in care. Active follow-up of HCV notifications by the health department to the notifying general practitioner (GP) may increase treatment uptake. In this study, we explore the impact of using hepatitis C notifications systems to engage diagnosing GPs and improve patient access to treatment.
This study is a randomised controlled trial comparing enhanced case management of HCV notifications with standard of care. The intervention includes phone calls from a department of health (DoH) specialist HCV nurse to notifying GPs and offering HCV management support. The level of support requested by the GP was graded in complexity: level 1: HCV information only; level 2: follow-up testing advice; level 3: prescription support including linkage to specialist clinicians and level 4: direct patient contact. The study population includes all GPs in Tasmania who notified HCV diagnosis to the DoH between September 2020 and December 2021. The primary outcome is proportion of HCV cases who initiate DAAs after 12 weeks of HCV notification to the health department. Secondary outcomes are proportion of HCV notifications that complete HCV RNA testing, treatment workup and treatment completion. Multiple logistic regression modelling will explore factors associated with the primary and secondary outcomes. The sample size required to detect a significant difference for the primary outcome is 85 GPs in each arm with a two-sided alpha of 0.05% and 80% power.
The study was approved by University of Tasmania’s Human Research Ethics Committee (Protocol ID: 18418) on 17 December 2019. Results of the project will be presented in scientific meetings and published in peer-reviewed journals.
The study commenced recruitment in September 2020 and end of study expected December 2021.
To explore the various stakeholders’ perspectives on barriers and facilitators for medication adherence among patients with cardiovascular diseases (CVDs) and diabetes mellitus (DM)in India.
Systematic review of qualitative studies.
A comprehensive systematic search was conducted in Medline, Cochrane Library, Science Direct and Google Scholar from January 2010 to July 2020. We included all qualitative peer-reviewed studies, reporting barriers and facilitators of medication adherence, from India, for our current review.
Data extraction was performed by two independent authors who also assessed the quality of included studies using the Critical Appraisal Skills Programme criteria. This qualitative evidence synthesis adhered to the enhancing transparency in reporting the synthesis of qualitative research checklist
In total, 18 studies were included. Major barriers reported were lack of understanding about the disease, complications related to non-adherence, followed by forgetfulness, lack of family support and risk communication. Health system-related barriers such as accessibility, affordability and acceptability were also reported by majority of the studies. Creation of peer support groups, digital reminder systems, integration of native Indian systems of India, physiotherapy and geriatric clinics at the primary healthcare level and innovations in patient care were suggested to counter these barriers in medication adherence.
Such patient-specific targeted interventions need to be developed to achieve better control among patients with CVD and DM.
PROSPERO registration number
CRD42020199529.
Kidney stones are a global healthcare problem. Given high recurrence rates and the morbidity associated with symptomatic stone disease, effective medical prophylaxis is clearly an unmet need. Explanatory analyses of randomised controlled trials with sodium/glucose cotransporter isoform 2 inhibitors indicated a 30%–50% reduced rate of stone events in patients with diabetes. Underlying mechanisms remain unclear. We aim to determine the effect of empagliflozin on urinary supersaturations in non-diabetic kidney stone formers to evaluate their therapeutic potential for recurrence prevention. We will provide first clinical trial evidence on whether urinary supersaturations are affected by empagliflozin in kidney stone formers.
The SWEETSTONE trial is a randomised, double-blind, placebo-controlled, cross-over, exploratory study to assess the impact of empagliflozin on urinary supersaturations of calcium oxalate, calcium phosphate and uric acid in kidney stone formers. We plan to include 46 non-diabetic adults (18–74 years) with ≥1 past kidney stone event and stone composition with ≥80% of calcium or ≥80% of uric acid. Patients with secondary causes of kidney stones or chronic kidney disease will be excluded. Eligible individuals will be randomised in equal proportions to receive either a 14-day treatment with 25 mg empagliflozin followed after the 2–6 weeks wash out period by a 14-day treatment with a matching placebo or the reverse procedure. Secondary outcomes will include electrolyte concentrations, renal function, mineral metabolism and glycaemic parameters, urinary volume and safety.
Results will be presented as effect measures (95% CIs) with p values and hypothesis testing for primary outcomes (significance level 0.02).
The SWEETSTONE trial was approved by the Swiss ethics committee and Swissmedic. First results are expected in the fourth quarter of 2022.
To evaluate the impact of the COVID-19 pandemic on the emotional and spiritual well-being and resilience of a global sample of Advanced Practice Nurses.
A web-based cross-sectional mixed methods study. Survey data were collected from Advanced Practice Nurses globally over a 2-month period ending on 31 August 2020.
The Warwick-Edinburgh Mental Well-being Scale, FACIT-12 Spiritual Well-being Scale and Connor-Davidson Resilience Scale 10 were used to quantify emotional and spiritual well-being and resilience of Advanced Practice Nurses' globally. The survey was distributed internationally using snowball sampling via a secure platform (Qualtrics). Results were analysed using various bivariate tests for associations and group differences.
Nine hundred and twenty-eight Advanced Practice Nurses from 53 countries participated in the study. Study participants reported meaningfully lower scores in resilience and emotional well-being compared with non-pandemic scores. Participants from countries with well-developed Advanced Practice Nurses roles reported lower resilience and well-being scores compared with those from countries where Advanced Practice Nurses roles are still being developed. Each scale revealed significant positive associations with the other scales.
Emotional and spiritual well-being and resilience of Advance Practice Nurses has been significantly impacted during the COVID-19 pandemic. Regardless of their work location, work hours, credential or demographics, the APNs in our study reported lower levels of resilience and mental well-being compared with typical scores on the instruments.
Event-free survival rates at 15 years for paediatric patients with relapsed/refractory acute lymphoblastic leukaemia (ALL) are 30%–50%, with 5-year survival for adult patients only 20%. Many patients with newly diagnosed and relapsed ALL harbour somatic RAS-signalling activation mutations. Induction therapy for ALL involves steroids, with preclinical data suggesting the combination of dexamethasone with the MEK1/2 inhibitor, selumetinib (ARRY-142886) has a synergistic anticancer effect.
The SeluDex trial is an international, parallel-group, dose-finding with expansion, phase I/II trial to assess the selumetinib/dexamethasone combination in adult and paediatric patients with relapsed/refractory, RAS pathway mutant ALL. The Cancer Research UK Clinical Trials Unit at University of Birmingham is the UK Coordinating Centre, with national hubs in Copenhagen, Denmark; Monza, Italy; Münster, Germany; Paris, France; and Utrecht, Netherlands. Patients with morphologically proven relapsed/refractory or progressive B-cell precursor or T-cell ALL, with demonstrated RAS pathway activating mutations are eligible. Adult patients are
Medical ethical committees of all the participating countries have approved the study protocol; initial (UK) ethics approval (17/YH/0123) was granted by Yorkshire & The Humber—Leeds West Research Ethics Committee. Participants are required to provide written informed consent/assent. Results will be disseminated through national and international presentations and peer-reviewed publications.
To investigate socioeconomic, behavioural and healthcare delivery factors that are associated with health outcomes of cancer patients during the COVID-19 pandemic, especially among underserved cancer patients.
Cancer patients are at a higher risk of adverse physical and mental health outcomes during the pandemic than those without cancer.
Cross-sectional online survey. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines in this study.
The sample comprised 322 individuals diagnosed with incident cancer between January 2019 and January 2020. Demographically, 64% were female, 49% had a college degree, 12% were African American, and 88% were White (77% of the Whites were from metropolitan and 23% from nonmetropolitan areas). Descriptive analysis and multivariable regression analyses of global health status, depression and irritability were performed.
After adjusting for demographic variables and comorbidity, the feelings of loneliness, crowded living space, lower confidence in taking preventive measures and less satisfaction with telehealth visits were significantly associated with poorer global health, depression and irritability. Daily exercise was associated with better global health, and difficulty in getting medicine was associated with depression and irritability. Moreover, African Americans who felt lonely reported more depression and irritability and those who had less confidence in taking preventive measures reported more irritability than Whites. Respondents having low income and feeling lonely reported more depression than others.
In this study, socioeconomic factors (e.g. loneliness or crowded living conditions) were as important to health outcomes during the pandemic as behavioural (e.g. prevention and exercises) and quality-of-care factors (e.g. telehealth, access to medicine). Disparity was more pronounced in the mental health of African Americans and those with low incomes.
Healthcare providers should promote social support and physical activity for improving health and reducing mental health disparities among cancer patients.