Dementia praecox redux: A systematic review of the nicotinic receptor as a target for cognitive symptoms of schizophrenia

Most individuals with schizophrenia suffer some cognitive dysfunction: such deficits are predictive of longer-term functioning; and current dopamine-blocking antipsychotics have made little impact on this domain. There is a pressing need to develop novel pharmacological agents to tackle this insidious but most disabling of problems. The acetylcholinergic system is involved in cognitive and attentional processing, and its metabotropic and nicotinic receptors are widespread throughout the brain. Deficits in acetylcholinergic functioning occur in schizophrenia, and high rates of tobacco smoking have been posited to represent a form of self-medication. The nicotinic acetylcholine receptor (nAChR) has emerged as a putative target to improve cognitive deficits in schizophrenia, and this study systematically reviewed the emerging data. Nineteen studies were identified, covering three compound classes: agonists at the α7 and α 4β2 nAChRs, and positive allosteric modulators. Overall data are underwhelming: some studies showed significant improvements in cognition but as many studies had negative findings. It remains unclear if this represents drug limitations or nascent study methodology problems. The literature is particularly hindered by variability in inclusion of smokers, generally small sample sizes, and a lack of consensus on cognitive test batteries. Future work should evaluate longer-term outcomes, and, particularly, the effects of concomitant cognitive training.

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The Influence of Genetic Variants on Striatal Dopamine Transporter and D2 Receptor Binding after TB

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.87 ◽

2014 ◽

Vol 34 (8) ◽

pp. 1328-1339 ◽

Cited By ~ 38

Author(s):

Amy K Wagner ◽

Joelle M Scanion ◽

Carl R Becker ◽

Anne C Ritter ◽

Christian Niyonkuru ◽

...

Keyword(s):

Genetic Variants ◽

Ventral Striatum ◽

D2 Receptor ◽

Variable Number ◽

Small Sample ◽

Post Injury ◽

Positron Emission ◽

Small Sample Sizes ◽

Future Work

Dopamine (DA) neurotransmission influences cognition and recovery after traumatic brain injury (TBI). We explored whether functional genetic variants affecting the DA transporter (DAT) and D2 receptor (DRD2) impacted in vivo dopaminergic binding with positron emission tomography (PET) using [11C]βCFT and [11C]raclopride. We examined subjects with moderate/severe TBI ( N = 12) ~1 year post injury and similarly matched healthy controls ( N = 13). The variable number of tandem repeat polymorphism within the DAT gene and the Taql restriction fragment length polymorphism near the DRD2 gene were assessed. TBI subjects had age-adjusted DAT-binding reductions in the caudate, putamen, and ventral striatum, and modestly increased D2 binding in ventral striatum versus controls. Despite small sample sizes, multivariate analysis showed lower caudate and putamen DAT binding among DAT 9-allele carriers and DRD2 A2/A2 homozygotes with TBI versus controls with the same genotype. Among TBI subjects, 9-allele carriers had lower caudate and putamen binding than 10/10 homozygotes. This PET study suggests a hypodopaminergic environment and altered DRD2 autoreceptor DAT interactions that may influence DA transmission after TBI. Future work will relate these findings to cognitive performance; future studies are required to determine how DRD2/DAT1 genotype and DA-ligand binding are associated with neurostimulant response and TBI recovery.

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Interventions in an Ambulatory Setting to Prevent Progression to Severe Disease in Patients With COVID-19: A Systematic Review

Annals of Pharmacotherapy ◽

10.1177/10600280211028242 ◽

2021 ◽

pp. 106002802110282

Author(s):

Eamon O Murchu ◽

Susan Spillane ◽

Paula Byrne ◽

Michelle O’Neill ◽

Patricia Harrington ◽

...

Keyword(s):

Systematic Review ◽

Data Extraction ◽

Severe Disease ◽

Small Sample ◽

Ambulatory Setting ◽

Absolute Difference ◽

Published Data ◽

Pharmacological Agents ◽

Study Selection ◽

Small Sample Sizes

Objective: To conduct a systematic review on the effectiveness and safety of pharmacological and nonpharmacological interventions, in the ambulatory setting, aimed at preventing severe disease in patients with COVID-19. Data Sources: Electronic databases (PubMed, EMBASE, and EuropePMC) were searched on January 6, 2021. Study Selection and Data Extraction: A systematic review was conducted, adhering to PRISMA guidelines. The quality of individual trials was assessed using the Cochrane Risk-of-Bias Tool 2, and the certainty of evidence was assessed using GRADE. Data Synthesis: The collective search retrieved 3818 citations. Eight trials relating to 9 pharmacological interventions were identified. No evidence for nonpharmacological interventions was identified. Low certainty evidence of effectiveness in preventing severe disease was found for fluvoxamine (absolute difference: −8.7%; 95% CI: −1.8% to −16.4%) and bamlanivimab plus etesevimab (absolute difference: −4.9%; 95% CI: −0.8% to −8.9%). Both trials were limited by small sample sizes and short durations of follow-up. In addition, very low certainty evidence of effect was found for ivermectin plus doxycycline and sulodexide. Based on published data, insufficient evidence of effect was found for bamlanivimab (monotherapy), casirivimab plus imdevimab, ivermectin (monotherapy), nitazoxanide, and peginterferon lambda. Relevance to Patient Care and Clinical Practice: This review assessed all ambulatory treatments for COVID-19 that may improve patient outcomes and reduce hospitalizations. Conclusion: Recent trials have shown promising results for a number of pharmacological agents to treat COVID-19 in the ambulatory setting. However, larger, more robust trials are needed to support the routine use of these agents outside of monitored clinical trials.

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Comparative Evaluation of a Novel Concept Design Method

Volume 12: Systems and Design ◽

10.1115/imece2013-63769 ◽

2013 ◽

Author(s):

Damian Rogers ◽

Filippo A. Salustri

Keyword(s):

Design Method ◽

Statistical Significance ◽

Small Sample ◽

Design Methods ◽

Concept Design ◽

Sample Sizes ◽

Pilot Experiment ◽

Small Sample Sizes ◽

Novel Concept ◽

Future Work

Based on their previous work in creating a new method of design, termed the “Design by DNA” method, the authors are now experimentally validating the method against other, known methods. The goal of the experiment is to determine if Design by DNA promotes creative designs. Specifically, the authors are seeking to measure and compare creativity resulting from the use of Design by DNA and from other, known design methods. However, few have conducted empirical experiments in the past, and further, the literature on comparatively evaluating creativity of different design methods is relatively sparse. Therefore, the authors are developing a framework for defining and executing meaningful experiments that can accommodate various design methods, including Design by DNA, and also provide meaningful data to comparatively evaluate those methods, with the goal of determining whether Design by DNA impacts creativity in design. The experimental framework is described, and results of a pilot experiment are given. In that framework, creativity was characterized by novelty, usefulness, and cohesion. Due to small sample sizes, confidence in the results is not particularly high. Even so, some results do indicate several points of interest. An analysis of the results suggests that Design by DNA can offer advantages in engineering design, ranking higher in both the ‘usefulness’ and ‘cohesion’ categories of the creativity assessment. Hypotheses are given to explain why the experimental results show the slightly lower score in the ‘novelty’ category. Experiment participants were also evaluated on the NASA Task Loading Index (TLX) to evaluate how taxed they were using the different design methods and results are shown. Here, the Design by DNA method accrues better scores in 5 of the 6 NASA TLX categories, suggesting that it was less strenuous on the participants than the other methods. Statistical analysis of both the creativity scores and the TLX document shows confidence levels of between 65% and 96%, which is acceptable for very low populations. As this was a pilot experiment, the authors foresee future work to improve the results presented here. First, larger sample sizes are needed to improve statistical significance of our conclusions. Secondly, the authors wish to set out a series of experiments whereby each test is run by pitting one specific design method against the Design by DNA method, to better show a 1-on-1 comparison between the methods and highlight the strengths and weaknesses of each.

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Are the Biological and Biomechanical Properties of Meniscal Scaffolds Reflected in Clinical Practice? A Systematic Review of the Literature

International Journal of Molecular Sciences ◽

10.3390/ijms20030632 ◽

2019 ◽

Vol 20 (3) ◽

pp. 632 ◽

Cited By ~ 2

Author(s):

Chanuka Ranmuthu ◽

Charindu Ranmuthu ◽

Jodie Russell ◽

Disha Singhania ◽

Wasim Khan

Keyword(s):

Clinical Practice ◽

Articular Cartilage ◽

Clinical Outcome ◽

Clinical Outcomes ◽

Biomechanical Properties ◽

Small Sample ◽

Histological Evaluation ◽

Study Methodology ◽

Small Sample Sizes ◽

The Ideal

The aim of this PRISMA review was to assess whether the CMI and Actifit scaffolds, when used in clinical practice, improve clinical outcomes and demonstrate the ideal biological and biomechanical properties of scaffolds: being chondroprotective, porous, resorbable, able to mature and promote regeneration of tissue. This was done by only including studies that assessed clinical outcome and used a scale to assess both integrity of the scaffold and its effects on articular cartilage via MRI. A search was performed on PubMed, EMBASE, Scopus and clinicaltrials.gov. 2457 articles were screened, from which eight studies were selected: four used Actifit, three used CMI and one compared the two. All studies reported significant improvement in at least one clinical outcome compared to baseline. Some studies suggested that the scaffolds appeared to show porosity, mature, resorb and/or have possible chondroprotective effects, as assessed by MRI. The evidence for clinical translation is limited by differences in study methodology and small sample sizes, but is promising in terms of improving clinical outcomes in the short to mid-term. Higher level evidence, with MRI and histological evaluation of the scaffold and articular cartilage, is now needed to further determine whether these scaffolds exhibit these useful properties.

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Touchless computer interfaces in hospitals: A review

Health Informatics Journal ◽

10.1177/1460458217748342 ◽

2018 ◽

Vol 25 (4) ◽

pp. 1325-1342 ◽

Cited By ~ 3

Author(s):

Seán Cronin ◽

Gavin Doherty

Keyword(s):

User Interfaces ◽

Small Sample ◽

Hospital Environment ◽

Major Theme ◽

Computer Interfaces ◽

Use Of Technology ◽

Touchless Interaction ◽

Image Navigation ◽

Small Sample Sizes ◽

Future Work

The widespread use of technology in hospitals and the difficulty of sterilising computer controls has increased opportunities for the spread of pathogens. This leads to an interest in touchless user interfaces for computer systems. We present a review of touchless interaction with computer equipment in the hospital environment, based on a systematic search of the literature. Sterility provides an implied theme and motivation for the field as a whole, but other advantages, such as hands-busy settings, are also proposed. Overcoming hardware restrictions has been a major theme, but in recent research, technical difficulties have receded. Image navigation is the most frequently considered task and the operating room the most frequently considered environment. Gestures have been implemented for input, system and content control. Most of the studies found have small sample sizes and focus on feasibility, acceptability or gesture-recognition accuracy. We conclude this article with an agenda for future work.

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Are Persons With Intellectual and Developmental Disabilities Being Embraced in Healthy Aging Interventions?

Innovation in Aging ◽

10.1093/geroni/igab046.868 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 226-226

Author(s):

Johanna Zurek ◽

Matthew Janicki ◽

Flavia Santos

Keyword(s):

Social Inclusion ◽

Healthy Aging ◽

Small Sample ◽

Healthy Ageing ◽

Intellectual And Developmental Disabilities ◽

Nutrition And Health ◽

Education And Health ◽

Negative Findings ◽

Small Sample Sizes

Abstract We carried out a systematic review of healthy ageing interventions for adults with IDD. Twenty-three prospective studies including 2,398 men and women [average age: 44.3 years old] were found worldwide. Among them were only five RCTs. The designs usually were within or between subjects involving small sample sizes (ranging from 8 to 379 participants), mostly non-randomised or without follow up. We identified four thematic areas: Physical activity - nutrition and health (n = 10); Health education and health exams (n = 6); Social inclusion and community participation (n = 3); and Multi-components (n = 4). Overall, studies found effective outcomes, such as loss of body weight and improvement in nutritional habits, despite a few negative findings. We conclude that healthy ageing initiatives for people with IDD continue to be scarce, incipient, and sporadic. More research should embrace health promotion in people with IDD as a programme practice and public policy.

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Prospective Memory After Stroke: A Scoping Review

Brain Impairment ◽

10.1017/brimp.2016.12 ◽

2016 ◽

Vol 17 (2) ◽

pp. 123-142 ◽

Cited By ~ 3

Author(s):

Christy Hogan ◽

Jennifer Fleming ◽

Petrea Cornwell ◽

David Shum

Keyword(s):

Prospective Memory ◽

Memory Impairment ◽

Methodological Quality ◽

Intervention Studies ◽

Small Sample ◽

Self Report ◽

Retrospective Memory ◽

Single Item ◽

Study Methodology ◽

Small Sample Sizes

The aim of this paper was to review the limited, but growing, literature on prospective memory (PM) following stroke using a scoping study methodology. Multiple databases were systematically searched and yielded 11 studies that were classified as observational (n = 7) or intervention studies (n = 4) and reviewed for quality. PM impairment after stroke was more commonly identified using behavioural measures compared to self-report measures. There were mixed findings regarding the extent and nature of PM impairment poststroke; however, more studies reported impairment for time-based PM, compared to both event- and activity-based PM. Studies examining rehabilitative techniques for PM resulted in mixed findings and were limited as most were case studies of poor methodological quality. Overall previous research in this area was limited as most studies were often underpowered due to small sample sizes, or used single-item measures which may not be robust enough to reliably measure PM impairment. Additionally, the methods used to measure PM were varied and many studies did not control for retrospective memory impairment, which could impact the results, as PM has both a retrospective (remembering both the action and when it needs to be completed) and prospective component (remembering to perform the action when appropriate). In conclusion, PM impairment is apparent poststroke, specifically for time-based PM. However, more research is needed to determine why PM impairment occurs, and how it can be improved.

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Sweet Taste as a Predictor of Dietary Intake: A Systematic Review

Nutrients ◽

10.3390/nu11010094 ◽

2019 ◽

Vol 11 (1) ◽

pp. 94 ◽

Cited By ~ 23

Author(s):

Sze-Yen Tan ◽

Robin M. Tucker

Keyword(s):

Systematic Review ◽

Dietary Intake ◽

Food Choice ◽

Sweet Taste ◽

Small Sample ◽

Taste Perception ◽

Hedonic Evaluation ◽

Small Sample Sizes ◽

Future Work ◽

Degree Of Heterogeneity

Taste is frequently cited as an important factor in food choice, and while a number of studies have attempted to identify relationships between taste function and dietary intake, a systematic review of these studies has been lacking. This review identified studies that examined associations between taste function or taste perception and dietary intake. The purpose was to determine which taste measure was most closely associated with dietary intake in healthy adults. Studies that measured some component of dietary intake, either acutely or longer-term, were eligible for inclusion. Studies were grouped into three categories: those that measured sensitivity (thresholds), intensity, or hedonic responses to sweet stimuli. Sensitivity and intensity studies demonstrated little association with dietary intake measures. Hedonic measurements were more likely to be associated with dietary intake, especially if sweet likers were analyzed separately from sweet dislikers, but the degree of heterogeneity among stimulus concentrations and dietary measures as well as small sample sizes likely obscured more consistent relationships between hedonic evaluation and dietary intake. Due to the potential for within-day and between-day variability in both taste function and dietary intake, future work should explore obtaining more than one taste measurement before comparing results to longer-term dietary assessments and attempts to standardize methods.

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