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Frontiers in Pharmacology 2015Although survival rates of breast, colon, and prostate cancers are improving, deaths from these tumors frequently occur due to metastasis. Voltage-gated Na(+) channels... (Review)
Review
Although survival rates of breast, colon, and prostate cancers are improving, deaths from these tumors frequently occur due to metastasis. Voltage-gated Na(+) channels (VGSCs) are membrane proteins, which regulate membrane current and cellular migration during nervous system organogenesis. VGSCs are also expressed in fibroblasts, immune cells, glia, and metastatic cancer cells. VGSCs regulate migration and invasion of breast, bowel, and prostate cancer cells, suggesting that they may be novel anti-metastatic targets. We conducted a systematic review of clinical and preclinical studies testing the effects of VGSC-inhibiting drugs in cancer. Two-hundred and four publications were identified, of which two human, two mouse, and 20 in vitro publications were included. In the clinical studies, the effect of these drugs on survival and metastatic relapse is not clear. The 22 preclinical studies collectively suggest that several VGSC-inhibiting drugs inhibit cancer proliferation, migration, and invasion. None of the human and only six of the preclinical studies directly investigated the effect of the drugs on VGSC activity. Studies were difficult to compare due to lack of standardized methodology and outcome measures. We conclude that the benefits of VGSC inhibitors require further investigation. Standardization of future studies and outcome measures should enable meaningful study comparisons.
PubMed: 26834632
DOI: 10.3389/fphar.2015.00273 -
Archives of Gerontology and Geriatrics 2020The personal and societal impact of age-related cognitive decline supports the development of effective interventions. While some strategies, such as cognitive training,...
The personal and societal impact of age-related cognitive decline supports the development of effective interventions. While some strategies, such as cognitive training, exercise or socio-intellectual engagement, appear beneficial, few studies have examined the association between personality and intervention efficacy. A systematic review was therefore conducted to summarise and synthesise the literature regarding the influence of personality traits on the effectiveness of non-pharmacological interventions for cognitive ageing. A systematic search of PubMed, PsycINFO and Web of Science was carried out. Of the 2100 papers identified by the search strategy, 10 studies were retained that met the relevant criteria (e.g., intervention studies with one or more cognitive outcomes and a measure of personality). Of these, two studies reported that higher levels of Openness to Experience were associated with greater improvement in memory performance after cognitive training interventions. Another found a positive association between Openness and improvement in divergent thinking following a novel group-based problem solving programme. One social intervention study reported positive moderating effects of Conscientiousness and Agreeableness, and mixed effects of Extraversion. Mixed evidence was also found regarding Need for Cognition, with one study reporting a positive association with memory improvement and another reporting less improvement in divergent thinking. Others found no evidence of personality influencing intervention outcomes. Due to the relatively small and heterogeneous sample of studies identified, any conclusions should currently be considered preliminary. These findings highlight the need for further research exploring the role of personality in intervention efficacy, so that interventions might be better tailored to individuals.
Topics: Aged; Cognition; Cognitive Aging; Cognitive Dysfunction; Humans; Memory; Personality
PubMed: 31835190
DOI: 10.1016/j.archger.2019.103992 -
Social Psychiatry and Psychiatric... Oct 2004In view of the plethora of different community-based mental health services, there is a clear need for a classification based on service components rather than labels.... (Review)
Review
BACKGROUND
In view of the plethora of different community-based mental health services, there is a clear need for a classification based on service components rather than labels. Moreover, the sustainability of experimental services beyond their research studies is rarely reported.
METHODS
As part of a systematic review of home treatment for mental health problems, authors of all included studies were followed up for data on service components and sustainability. Associations between components were explored.
RESULTS
There was evidence of a core group of components co-occurring in home treatment services: regularly visiting at home, taking responsibility for health and social care, having smaller caseloads, multidisciplinary teams, integrated psychiatrists and a high proportion of contacts at home. Fifty-four per cent of services no longer existed, of which almost half had ended by the study's publication date. There was a significant association between sustainability and the study's hospitalisation outcome.
CONCLUSIONS
Some of the related service components presented here were associated with reducing hospitalisation. This group cannot, however, be used to provide a new taxonomy of services. It is imperative that future studies prospectively record and report service components to enable better classification. It is of concern that policy is currently predicated on research findings regardless of whether or not the experimental service was sustainable.
Topics: Community Mental Health Services; Home Care Services; Humans; Patient Care Team; Personnel Staffing and Scheduling; Program Evaluation; Statistics, Nonparametric; Workload
PubMed: 15669659
DOI: 10.1007/s00127-004-0818-5 -
Palliative Medicine Jun 2020Despite being a terminal neurodegenerative disease, the role of palliative care is less recognised for motor neurone disease than for other life-limiting conditions....
BACKGROUND
Despite being a terminal neurodegenerative disease, the role of palliative care is less recognised for motor neurone disease than for other life-limiting conditions. Understanding the experiences of, and need for, palliative care for patients and carers is key to configuring optimal policy and healthcare services.
AIM
To explore the experiences of, and need for, palliative care of people with motor neurone disease and their informal carers across the disease trajectory.
DESIGN
A systematic review of qualitative research conducted using Thematic Synthesis - PROSPERO registration CRD42017075311.
DATA SOURCES
Four electronic databases were searched (MEDLINE, CINAHL, PsycINFO, Social Science Citation Index) using terms for motor neurone disease, amyotrophic lateral sclerosis, palliative care, and qualitative research, from inception to November 2018. Included papers were data extracted and assessed for quality.
RESULTS
A total of 41 papers were included, representing the experiences of 358 people with motor neurone disease and 369 caregivers. Analytical themes were developed detailing patients' and carers' experiences of living with motor neurone disease and of palliative care through its trajectory including response to diagnosis, maintaining control, decision-making during deterioration, engaging with professionals, planning for end-of-life care, bereavement.
CONCLUSION
The review identified a considerable literature exploring the care needs of people with motor neurone disease and their carers; however, descriptions of palliative care were associated with the last days of life. Across the disease trajectory, clear points were identified where palliative care input could enhance patient and carer experience of the disease, particularly at times of significant physical change.
Topics: Caregivers; Hospice Care; Humans; Motor Neuron Disease; Palliative Care; Qualitative Research
PubMed: 32286157
DOI: 10.1177/0269216320908775 -
BMC Medicine Apr 2024Various studies have demonstrated gender disparities in workplace settings and the need for further intervention. This study identifies and examines evidence from... (Review)
Review
BACKGROUND
Various studies have demonstrated gender disparities in workplace settings and the need for further intervention. This study identifies and examines evidence from randomized controlled trials (RCTs) on interventions examining gender equity in workplace or volunteer settings. An additional aim was to determine whether interventions considered intersection of gender and other variables, including PROGRESS-Plus equity variables (e.g., race/ethnicity).
METHODS
Scoping review conducted using the JBI guide. Literature was searched in MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, ERIC, Index to Legal Periodicals and Books, PAIS Index, Policy Index File, and the Canadian Business & Current Affairs Database from inception to May 9, 2022, with an updated search on October 17, 2022. Results were reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension to scoping reviews (PRISMA-ScR), Sex and Gender Equity in Research (SAGER) guidance, Strengthening the Integration of Intersectionality Theory in Health Inequality Analysis (SIITHIA) checklist, and Guidance for Reporting Involvement of Patients and the Public (GRIPP) version 2 checklist. All employment or volunteer sectors settings were included. Included interventions were designed to promote workplace gender equity that targeted: (a) individuals, (b) organizations, or (c) systems. Any comparator was eligible. Outcomes measures included any gender equity related outcome, whether it was measuring intervention effectiveness (as defined by included studies) or implementation. Data analyses were descriptive in nature. As recommended in the JBI guide to scoping reviews, only high-level content analysis was conducted to categorize the interventions, which were reported using a previously published framework.
RESULTS
We screened 8855 citations, 803 grey literature sources, and 663 full-text articles, resulting in 24 unique RCTs and one companion report that met inclusion criteria. Most studies (91.7%) failed to report how they established sex or gender. Twenty-three of 24 (95.8%) studies reported at least one PROGRESS-Plus variable: typically sex or gender or occupation. Two RCTs (8.3%) identified a non-binary gender identity. None of the RCTs reported on relationships between gender and other characteristics (e.g., disability, age, etc.). We identified 24 gender equity promoting interventions in the workplace that were evaluated and categorized into one or more of the following themes: (i) quantifying gender impacts; (ii) behavioural or systemic changes; (iii) career flexibility; (iv) increased visibility, recognition, and representation; (v) creating opportunities for development, mentorship, and sponsorship; and (vi) financial support. Of these interventions, 20/24 (83.3%) had positive conclusion statements for their primary outcomes (e.g., improved academic productivity, increased self-esteem) across heterogeneous outcomes.
CONCLUSIONS
There is a paucity of literature on interventions to promote workplace gender equity. While some interventions elicited positive conclusions across a variety of outcomes, standardized outcome measures considering specific contexts and cultures are required. Few PROGRESS-Plus items were reported. Non-binary gender identities and issues related to intersectionality were not adequately considered. Future research should provide consistent and contemporary definitions of gender and sex.
TRIAL REGISTRATION
Open Science Framework https://osf.io/x8yae .
Topics: Male; Female; Humans; Gender Equity; Canada; Workplace; Randomized Controlled Trials as Topic
PubMed: 38581003
DOI: 10.1186/s12916-024-03346-7 -
Systematic Reviews Mar 2014To date no network meta-analysis (NMA) has accounted for baseline variations in viral load when assessing the relative efficacy of interventions for chronic hepatitis B... (Meta-Analysis)
Meta-Analysis Review
The importance of baseline viral load when assessing relative efficacy in treatment-naïve HBeAg-positive chronic hepatitis B: a systematic review and network meta-analysis.
BACKGROUND
To date no network meta-analysis (NMA) has accounted for baseline variations in viral load when assessing the relative efficacy of interventions for chronic hepatitis B (CHB). We undertook baseline-adjusted and unadjusted analyses using the same data to explore the impact of baseline viral load (BVL) on CHB treatment response.
METHODS
We searched Embase, Medline, Medline in Process and the Cochrane CENTRAL databases for randomised clinical trials (RCTs) of monotherapy interventions at licensed doses for use in CHB. Search strategies comprised CHB disease and drug terms (a combination of controlled vocabulary and free text terms) and also a bespoke RCT filter.The NMA was undertaken in WinBUGs using fixed and random effects methods, using data obtained from a systematic review. Individual patient data (IPD) from an entecavir clinical trial were used to quantify the impact of different baseline characteristics (in particular undetectable viral load (UVL) at 1 year) on relative treatment effect. Study level mean baseline values from all identified studies were used. Results were generated for UVL and presented as relative risks (RRs) and 95% credible intervals (CrIs) using entecavir as reference treatment.
RESULTS
Overall, for all eight relevant interventions we identified 3,000 abstracts. Following full text review a total of 35 (including the contents of six clinical study reports) met the inclusion critera; 19 were in hepatitis B e antigen (HBeAg)-positive patients and 14 of the 19 contained outcome information of relevance to the NMA.Entecavir and tenofovir studies had heterogeneous patient populations in terms of BVL (mean values 9.29 and 8.65 log10 copies/ml respectively). After adjusting UVL for BVL using an informative prior based on the IPD analysis, the difference between entecavir and tenofovir was not statistically significant (RR 1.27, 95% CrI 0.96 to 1.47-fixed effects). A similar conclusion was found in all sensitivity analyses. Adjusted tenofovir results were more consistent with observed clinical trial response rates.
CONCLUSIONS
This study demonstrates the importance of adjusting for BVL when assessing the relative efficacy of CHB interventions in achieving UVL. This has implications for both clinical and economic decision making.
Topics: Antiviral Agents; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Treatment Outcome; Viral Load
PubMed: 24602249
DOI: 10.1186/2046-4053-3-21 -
International Journal of Environmental... Aug 2018It has been hypothesised that environmental air pollution, especially airborne particles, is a risk factor for type 2 diabetes mellitus (T2DM) and neurodegenerative...
Exposure to Environmental and Occupational Particulate Air Pollution as a Potential Contributor to Neurodegeneration and Diabetes: A Systematic Review of Epidemiological Research.
It has been hypothesised that environmental air pollution, especially airborne particles, is a risk factor for type 2 diabetes mellitus (T2DM) and neurodegenerative conditions. However, epidemiological evidence is inconsistent and has not been previously evaluated as part of a systematic review. Our objectives were to carry out a systematic review of the epidemiological evidence on the association between long-term exposure to ambient air pollution and T2DM and neurodegenerative diseases in adults and to identify if workplace exposures to particles are associated with an increased risk of T2DM and neurodegenerative diseases. Assessment of the quality of the evidence was carried out using the GRADE system, which considers the quality of the studies, consistency, directness, effect size, and publication bias. Available evidence indicates a consistent positive association between ambient air pollution and both T2DM and neurodegeneration risk, such as dementia and a general decline in cognition. However, corresponding evidence for workplace exposures are lacking. Further research is required to identify the link and mechanisms associated with particulate exposure and disease pathogenesis and to investigate the risks in occupational populations. Additional steps are needed to reduce air pollution levels and possibly also in the workplace environment to decrease the incidence of T2DM and cognitive decline.
Topics: Air Pollutants; Air Pollutants, Occupational; Air Pollution; Cognition; Dementia; Diabetes Mellitus, Type 2; Dust; Environmental Exposure; Epidemiologic Studies; Humans; Incidence; Particulate Matter; Risk Factors
PubMed: 30096929
DOI: 10.3390/ijerph15081704 -
Critical Reviews in Toxicology Mar 2021The use of simulated biological fluids (SBFs) is a promising technique to better understand the release mechanisms and possible behaviour of materials, including...
The use of simulated biological fluids (SBFs) is a promising technique to better understand the release mechanisms and possible behaviour of materials, including fibres, metal-containing particles and nanomaterials. Applications of SBFs in dissolution tests allow a measure of material biopersistence or, conversely, bioaccessibility that in turn can provide a useful inference of a materials biodistribution, its acute and long-term toxicity, as well as its pathogenicity. Given the wide range of SBFs reported in the literature, a review was conducted, with a focus on fluids used to replicate environments that may be encountered upon material inhalation, including extracellular and intracellular compartments. The review aims to identify when a fluid design can replicate realistic biological conditions, demonstrate operation validation, and/or provide robustness and reproducibility. The studies examined highlight simulated lung fluids (SLFs) that have been shown to suitably replicate physiological conditions, and identify specific components that play a pivotal role in dissolution mechanisms and biological activity; including organic molecules, redox-active species and chelating agents. Material dissolution was not always driven by pH, and likewise not only driven by SLF composition; specific materials and formulations correspond to specific dissolution mechanisms. It is recommended that SLF developments focus on biological predictivity and if not practical, on better biological mimicry, as such an approach ensures results are more likely to reflect behaviour regardless of the material under investigation.
Topics: Bodily Secretions; Humans; In Vitro Techniques; Inhalation Exposure; Metals; Nanostructures; Particulate Matter; Reproducibility of Results; Tissue Distribution
PubMed: 33905298
DOI: 10.1080/10408444.2021.1903386 -
Journal of Clinical Psychology in... Sep 2021Romantic attachment rejection (RAR) is a highly prevalent phenomenon among young adults. Rejection by a romantic attachment figure can be a painful and incapacitating...
Romantic attachment rejection (RAR) is a highly prevalent phenomenon among young adults. Rejection by a romantic attachment figure can be a painful and incapacitating experience with lasting negative mental health sequelae, yet the underlying neurobiology of RAR is not well characterized. We systematically reviewed functional neuroimaging studies of adult RAR. Four functional magnetic resonance imaging (fMRI) studies that measured participants' responses to real or imagined RAR and met inclusion criteria were evaluated. These included studies were published between 2004 and 2018. Brain activity in adult participants with an RAR appears to be influenced by the stimulus used to elicit a reaction as well as by attachment styles. Brain regions that show a significant change in activation following a rejection stimulus include cortical regions (cingulate, insular, orbitofrontal, and prefrontal), and subcortical regions (angular gyrus, hippocampus, striatum, tegmental area, and temporal pole) and correspond to (i) pain, distress, and memory retrieval; (ii) reward, romantic love, and dopaminergic circuits; and (iii) emotion regulation and behavioural adaptation. Further neuroimaging studies of adult RAR, as moderated by stimulus and attachment style, are needed to better understand the underlying neurobiology of RAR.
Topics: Brain; Functional Neuroimaging; Humans; Love; Magnetic Resonance Imaging; Reward; Young Adult
PubMed: 33392890
DOI: 10.1007/s10880-020-09757-x -
Ageing Research Reviews Mar 2019Activities running in community-based-settings offer a method of delivering multimodal interventions to older adults beyond cognitive training programmes. This... (Meta-Analysis)
Meta-Analysis
Activities running in community-based-settings offer a method of delivering multimodal interventions to older adults beyond cognitive training programmes. This systematic review and meta-analysis investigated the impact of randomised controlled trials (RCTs) of 'real-world' interventions on the cognitive abilities of healthy older adults. Database searches were performed between October 2016 and September 2018. Forty-three RCTs were eligible for inclusion with 2826 intervention participants and 2234 controls. Interventions to enhance cognitive ability consisted of participation in activities that were physical (25 studies), cognitive (9 studies), or mixed (i.e., physical and cognitive; 7 studies), and two studies used other interventions that included older adults assisting schoolchildren and engagement via social network sites. Meta-analysis revealed that Trail Making Test (TMT) A, p = 0.05, M = 0.43, 95% CI [-0.00, 0.86], digit symbol substitution, p = 0.05, M = 0.30, 95% CI [0.00, 0.59], and verbal fluency, p = 0.04, M = 0.31, 95% CI [0.02, 0.61], improved after specific types of interventions versus the control groups (which were either active, wait-list or passive controls). When comparing physical activity interventions against all control groups, TMT A, p = 0.04, M = 0.25, 95% CI [0.01, 0.48], and digit span forward, p = 0.05, M = 0.91, 95% CI [-0.00, 1.82], significantly improved. Results remained non-significant for all outcomes when comparing cognitive activity interventions against all control groups. Results therefore suggest that healthy older adults are more likely to see cognitive improvements when involved in physical activity interventions. In addition, TMT A was the only measure that consistently showed significant improvements following physical activity interventions. Visuospatial abilities (as measured by TMT A) may be more susceptible to improvement following physical activity-based interventions, and TMT A may be a useful tool for detecting differences in that domain.
Topics: Aged; Aged, 80 and over; Cognition; Cognition Disorders; Cognitive Aging; Exercise; Health Status; Humans; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic
PubMed: 30707947
DOI: 10.1016/j.arr.2019.01.006