Cross-Cultural Applicability of the Montreal Cognitive Assessment (MoCA): A Systematic Review

The Montreal Cognitive Assessment (MoCA) is widely used to screen for mild cognitive impairment (MCI). While there are many available versions, the cross-cultural validity of the assessment has not been explored sufficiently. We aimed to interrogate the validity of the MoCA in a cross-cultural context: in differentiating MCI from normal controls (NC); and identifying cut-offs and adjustments for age and education where possible. This review sourced a wide range of studies including case-control studies. In addition, we report findings for differentiating dementias from NC and MCI from dementias, however, these were not considered to be an appropriate use of the MoCA. The subject of the review assumes heterogeneity and therefore meta-analyses was not conducted. Quality ratings, forest plots of validated studies (sensitivity and specificity) with covariates (suggested cut-offs, age, education and country), and summary receiver operating characteristic curve are presented. The results showed a wide range in suggested cutoffs for MCI cross-culturally, with variability in levels of sensitivity and specificity ranging from low to high. Poor methodological rigor appears to have affected reported accuracy and validity of the MoCA. The review highlights the necessity for cross-cultural considerations when using the MoCA, and recognizing it as a screen and not a diagnostic tool. Appropriate cutoffs and point adjustments for education are suggested

Cyclodextrin-siRNA conjugates as versatile gene silencing agents

Functional siRNAs (luciferase and PLK1) have been conjugated to β-cyclodextrin and the ability of the conjugates to retain gene knockdown activity has been assessed by delivery to cancer cell lines using various formulations. Initially two formulations used complexation with polycations, namely Lipofectamine 2000 and an amphiphilic polycationic cyclodextrin. Gene knockdown results for human glioblastoma cells (U87) and prostate cancer cells (PC3, DU145) showed that conjugation to the cyclodextrin did not reduce gene silencing by the RNA. A third mode of delivery involved formation of targeted nanoparticles in which the conjugate was first complexed with adamantyl-PEG-ligands (targeting ligand RVG peptide or dianisamide) by adamantyl inclusion in the cyclodextrin cavities of the conjugates, followed by charge neutralisation with the cationic polymer chitosan. Enhanced knockdown was achieved by these ligand-targeted formulations. In summary, while this study illustrated the gene silencing efficacy of a simple cyclodextrin-siRNA conjugate it is envisaged that future studies will explore the use of conjugates with a modified cyclodextrin which would be self-delivering. Detailed data such as stability, lysosomal escape etc. will then be reported for each conjugate, since this will be appropriate for conjugates which are intended to exploit, rather than merely demonstrate, the concept. The present paper was intended to demonstrate the viability and generality of this novel concept

Continuous cardiac autonomic and haemodynamic responses to isometric exercise in females

Purpose: Hypertension is associated with impaired haemodynamic control mechanisms and autonomic dysfunction. Isometric exercise (IE) interventions have been shown to improve autonomic modulation and reduce blood pressure (BP) in predominantly male participants. The physiological responses to IE are under explored in female populations; therefore, this study investigated the continuous cardiac autonomic and haemodynamic response to a single bout of IE in a large female population. Methods: Forty physically inactive females performed a single, individually prescribed isometric wall squat training session. Total power spectral density of heart rate variability (HRV) and associated low frequency (LF) and high-frequency (HF) power spectral components, were recorded in absolute (ms2) and normalised units (nu) pre, during and post an IE session. Heart rate (HR) was recorded via electrocardiography and baroreceptor reflex sensitivity (BRS) via the sequence method. Continuous blood pressure was recorded via the vascular unloading technique and stroke volume via impedance cardiography. Total peripheral resistance (TPR) was calculated according to Ohm’s Law. Results: During IE, there were significant reductions in HRV (p<0.001) and BRS (p<0.001), and significant increases in heart rate (p<0.001), systolic, mean and diastolic BP (p<0.001 for all). In recovery following the IE session, cardiac autonomic parameters returned to baseline (p=0.974); however, total peripheral vascular resistance significantly reduced below baseline (p<0.001). This peripheral vascular response was associated with significant reductions in systolic (-17.3±16.5 mmHg, p<0.001), mean (-18.8±17.4 mmHg, p<0.001) and diastolic BP (-17.3±16.2 mmHg, p<0.001), below baseline. Conclusion: A single IE session is associated with improved haemodynamic cardiovascular responses in females. Cardiac autonomic responses return to baseline values, which suggests alternative mechanisms are responsible for the post exercise haemodynamic improvements in females. Future mechanistic research is required to investigate the acute and chronic effects of IE in female populations with different resting BP profiles

HOw patients view extended half‐life products: impressions from real‐world experience (The HOPE study)

Introduction Extended half‐life (EHL) clotting factors have been shown to offer people with haemophilia (PwH) protection from bleeding with fewer infusions, which might reduce treatment burden. Aim The HOw Patients view Extended half‐life products (HOPE) study aimed to explore, understand and describe patient expectations around the prophylactic use of EHL products and to establish whether these expectations were met through individual follow‐up analysis. Methods The HOPE study was a prospective, qualitative cohort study conducted among PwH who had switched to Fc fusion protein EHL products in routine clinical care and who had not been recruited to clinical trials of these products. Semi‐structured audio‐recorded interviews were undertaken over two time points; transcripts were analysed to systematically generate theory from data that contains both inductive and deductive thinking. Results Forty‐three interviews were conducted with 25 participants. Most participants were positive about EHL treatment and intended to continue using them. Reduced frequency of infusions meant lives were less disrupted or dominated by haemophilia, and there was less perceived stress on overused veins. For those PwH who did not reduce infusion frequency, there were other perceived benefits from EHLs with respect to greater protection with higher trough levels and fewer bleeds. Conclusion Patients switching to EHL treatments believe these products will result in fewer infusions and less disruption of everyday life, leaving them feeling more protected with fewer bleeds and increased activity levels, as well as enhanced well‐being and mental health. Understanding patient expectation and experience around using products adds real‐world data to clinical trial experience

Are senior nurses on clinical commissioning groups in England inadvertently supporting the devaluation of their profession?: A critical integrative review of the literature

This paper discusses the role of senior nurses who sit on clinical commissioning groups that now plan and procure most health services in England. These nurses are expected to bring a nursing view to all aspects of clinical commissioning group business (National Health Service England 2014a; Olphert 2014). The role is a senior level appointment and requires experience of strategic commissioning. However little is known about how nurses function in these roles. Following Barrientos’ methodology (1998), published policy and literature were analysed to investigate these roles and NHS England’s claim that nursing can influence and advance a nursing perspective in clinical commissioning groups. Drawing on work by Berg et al (2008, 2014) on ‘new public management’ we discuss how nurses on clinical commissioning groups work at the alignment of the interests of biomedicine and managerialism. We propose that the way this nursing role is being implemented might paradoxically offer further evidence of the devaluing of nursing (Latimer 2014) rather than the emergence of a strong professional nursing voice at the level of strategic commissioning

Profiles and trajectories of mental health service utilisation during early intervention in psychosis

Background: Early intervention in psychosis services (EIS) support individuals experiencing a first episode of psychosis. Support required will vary in response to the remittance and reoccurrence of symptoms, including relapses. Characterising individuals who will need more intensive support can inform care planning. This study explores service utilisation profiles and their trajectories of service use in a sample of individuals referred to EIS. Method: We analysed service utilisation during the 3 years following referral to EIS (n = 2363) in West London between 2011 and 2020. Mental health service utilisation data were submitted to model-based clustering. Latent growth models were then estimated for identified profiles. Profiles were compared regarding clinical and demographic characteristics and onward pathways of care. Results: Analyses revealed 5 profiles of individuals attending EIS based on their service utilisation over 3 years. 55.5% of the sample were members of a low utilisation and less clinically severe profile. The distinct service use patterns of these profiles were associated with Health of the Nations Outcome Scale scores at treatment initiation (at total, subscale, and individual item level), along with age and gender. These patterns of use were also associated with onward care and ethnicity. Conclusions: Profiles and trajectories of service utilisation call for development of integrated care pathways and use of more personalised interventions. Services should consider patient symptoms and characteristics when making clinical decisions informing the provision of care. The profiles represent typical patterns of service use, and identifying factors associated with these subgroups might help optimise EIS support

Do governing body and CSU nurses on clinical commissioning groups really lead a nursing agenda? Findings from a 2015 Survey of the Commissioning Nurse Leaders’ Network Membership

Aims This paper presents findings from a 2015 survey of the Commissioning Nurse Leaders’ Network (CNLN) aiming to understand how governing body nurses (GBNs), perceive their influence and leadership on clinical commissioning groups (CCGs). Methods An online survey method was used with a census sample of 238 GBNs and nurses working in CSUs, who were members of the CNLN. The response rate was 40.7% (n=97). Results While most GBNs felt confident in their leadership role, this was less so for non-executive GBNs and nurses in CSUs were much less positive than GBNs about their influence on CCGs. Conclusions Despite GBNs’ satisfaction with their impact on CCGs, there is no reliable evidence of this impact. The purpose of such roles to "represent nursing, and ensure the patient voice is heard” (NHSCC 2016:9) may be a flawed aspiration, conflating nursing leadership and patient voice. Implications for Nursing Management This is the first study to explicitly explore differences between executive and non-executive GBNs and CSUs. Achieving CCG goals, including developing and embedding nursing leadership roles in CCGs, may be threatened if the contributions of GBNs, and other nurses supporting, CCGS, go unrecognised or if GPs or other CCG executive members dominate decision-making

Can non-viral technologies knockdown the barriers to siRNA delivery and achieve the next generation of cancer therapeutics?

Cancer is one of the most wide-spread diseases of modern times, with an estimated increase in the number of patients diagnosed worldwide, from 11.3 million in 2007 to 15.5 million in 2030 (www.who.int). In many cases, due to the delay in diagnosis and high increase of relapse, survival rates are low. Current therapies, including surgery, radiation and chemotherapy, have made significant progress, but they have many limitations and are far from ideal. Although immunotherapy has recently offered great promise as a new approach in cancer treatment, it is still very much in its infancy and more information on this approach is required before it can be widely applied. For these reasons effective, safe and patient-acceptable cancer therapy is still largely an unmet clinical need. Recent knowledge of the genetic basis of the disease opens up the potential for cancer gene therapeutics based on siRNA. However, the future of such gene-based therapeutics is dependent on achieving successful delivery. Extensive research is ongoing regarding the design and assessment of non-viral delivery technologies for siRNA to treat a wide range of cancers. Preliminary results on the first human Phase I trial for solid tumours, using a targeted non-viral vector, illustrate the enormous therapeutic benefits once the issue of delivery is resolved. In this review the genes regulating cancer will be discussed and potential therapeutic targets will be identified. The physiological and biochemical changes caused by tumours, and the potential to exploit this knowledge to produce bio-responsive ‘smart’ delivery systems, will be evaluated. This review will also provide a critical and comprehensive overview of the different non-viral formulation strategies under investigation for siRNA delivery, with particular emphasis on those designed to exploit the physiological environment of the disease site. In addition, a section of the review will be dedicated to pre-clinical animal models used to evaluate the stability, safety and efficacy of the delivery systems

Centre of pressure, vertical ground reaction forces and neuromuscular responses of special-forces soldiers to 43km load carriage in the field

The primary purpose of this study was to examine lateral deviations in centre of pressure as a result of an extreme duration load carriage task, with particular focus on heel contact. Twenty (n=17 males, n=3 females) soldiers from a Special Operation Forces unit (body mass: 80.72±21.49kg; stature:178.25±8.75cm; age: 26±9yrs) underwent gait plantar pressure assessment and vertical jump testing before and after a 43km load carriage event (duration 817.02[32.66]min) carrying a total external load of 29.80 (1.05)kg. Vertical jump height decreased by 18.62%±16.85% (0.30±0.08m to 0.24±0.07m) p<.001. Loading peak and mid stance force minimum were significantly increased after load carriage (2.59±0.51BW vs. 2.81±0.61BW; p=.035; dGlass=0.44 and 1.28±0.40BW vs. 1.46±0.41BW; p=.015 dGlass=0.45, respectively) and increases in lateral centre of pressure displacement were observed as a result of the load carriage task 14.64±3.62mm to 16.97 ±3.94mm p<.029. In conclusion, load carriage instigated a decrease in neuromuscular function alongside increases in ground reaction forces associated with injury risk and centre of pressure changes associated with ankle sprain risk. Practitioners should consider that possible reduction in ankle stability remains even once the load had been removed, suggesting soldiers are still at increased risk of injury even once the load has been removed