A study protocol to investigate the management of depression and challenging behaviors associated with dementia in aged care settings

Background:&nbsp;The high occurrence and under-treatment of clinical depression and behavioral and psychological symptoms of dementia (BPSD) within aged care settings is concerning, yet training programs aimed at improving the detection and management of these problems have generally been ineffective. This article presents a study protocol to evaluate a training intervention for facility managers/registered nurses working in aged care facilities that focuses on organisational processes and culture as well as knowledge, skills and self-efficacy. Methods. A Randomised Control Trial (RCT) will be implemented across 18 aged care facilities (divided into three conditions). Participants will be senior registered nurses and personal care attendants employed in the aged care facility. The first condition will receive the training program (Staff as Change Agents - Enhancing and Sustaining Mental Health in Aged Care), the second condition will receive the training program and clinical support, and the third condition will receive no intervention. Results: Pre-, post-, 6-month and 12-month follow-up measures of staff and residents will be used to demonstrate how upskilling clinical leaders using our transformational training approach, as well as the use of a structured screening, referral and monitoring protocol, can address the mental health needs of older people in residential care. Conclusions: The expected outcome of this study is the validation of an evidence-based training program to improve the management of depression and BPSD among older people in residential care settings by establishing routine practices related to mental health. This relatively brief but highly focussed training package will be readily rolled out to a larger number of residential care facilities at a relatively low cost.</div

Prediagnostic sex steroid hormones in relation to male breast cancer risk

Purpose Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones. Patients and Methods Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes. Results Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men. Conclusion Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers

The effectiveness of ω-3 polyunsaturated fatty acid interventions during pregnancy on obesity measures in the offspring: an up-to-date systematic review and meta-analysis.

BACKGROUND: The potential role of ω-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy on subsequent risk of obesity outcomes in the offspring is not clear and there is a need to synthesise this evidence. OBJECTIVE: A systematic review and meta-analysis of randomised controlled trials (RCTs), including the most recent studies, was conducted to assess the effectiveness of ω-3 LCPUFA interventions during pregnancy on obesity measures, e.g. BMI, body weight, fat mass in offspring. METHODS: Included RCTs had a minimum of 1-month follow-up post-partum. The search included CENTRAL, MEDLINE, SCOPUS, WHO's International Clinical Trials Reg., E-theses and Web of Science databases. Study quality was evaluated using the Cochrane Collaboration's risk of bias tool. RESULTS: Eleven RCTs, from ten unique trials, (3644 children) examined the effectiveness of ω-3 LCPUFA maternal supplementation during pregnancy on the development of obesity outcomes in offspring. There were heterogeneities between the trials in terms of their sample, type and duration of intervention and follow-up. Pooled estimates did not show an association between prenatal intake of fatty acids and obesity measures in offspring. CONCLUSION: These results indicate that maternal supplementation with ω-3 LCPUFA during pregnancy does not have a beneficial effect on obesity risk. Due to the high heterogeneity between studies along with small sample sizes and high rates of attrition, the effects of ω-3 LCPUFA supplementation during pregnancy for prevention of childhood obesity in the long-term remains unclear. Large high-quality RCTs are needed that are designed specifically to examine the effect of prenatal intake of fatty acids for prevention of childhood obesity. There is also a need to determine specific sub-groups in the population that might get a greater benefit and whether different ω-3 LCPUFA, i.e. eicosapentaenoic (EPA) vs. docosahexanoic (DHA) acids might potentially have different effects

Distal junctional kyphosis in patients with Scheuermann’s disease: a retrospective radiographic analysis

Purpose To investigate the relationship between preoperative and postoperative spinopelvic alignment and occurrence of DJK/DJF. Study design/setting This was a retrospective observational cohort study. Patient sample The sample included 40 patients who underwent posterior correction of SK from January 2006 to December 2014. Outcome measures Correlation analysis between the preoperative and postoperative spinopelvic alignment parameters and development of DJK over the course of the study period were studied. Methods Whole spine X-rays obtained before surgery, 3 months after surgery and at the latest follow-up were analyzed. The following parameters were measured: maximum of thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lower instrumented vertebra (LIV) and LIV plumb line. Development of DJK was considered as the primary end point of the study. The patient population was split into a control and DJK group, with 34 patients and 6 patients, respectively. Statistic analysis was performed using unpaired t test for normal contribution and Mann–Whitney test for skew distributed values. The significance level was set to 0.05. Results DJK occurred in 15% (n = 6) over the study period. There was a significantly lower postoperative TK for the group with DJK (42.4 ± 5.3 vs 49.8 ± 6.7, p = 0.015). LIV plumb line showed higher negative values in the DJK group (−43.6 ± 25.1 vs −2.2 ± 17.8, p = 0.0435). Furthermore, postoperative LL changes were lower for the DJK group (33.84 ± 13.86% vs 31.77 ± 14.05, p < 0.0001.) The age of the patients who developed DJK was also significantly lower than that of the control group (16.8 ± 1.7 vs 19.6 ± 4.9, p = 0.0024.) Conclusions SK patients who developed DJK appeared to have a significantly higher degree of TK correction and more negative LIV plumb line. In addition, there may be a higher risk for DJK in patients undergoing corrective surgery at a younger age

The effectiveness of psychosocial interventions for anxiety in children and adolescents with autism spectrum disorder:a systematic review and meta-analysis

Anxiety is a common problem in children and adolescents with autism spectrum disorder (ASD). This meta-analysis aimed to systematically evaluate the evidence for the use of psychosocial interventions to manage anxiety in this population. Cognitive behavioural therapy (CBT) was the primary intervention modality studied. A comprehensive systematic search and study selection process was conducted. Separate statistical analyses were carried out for clinician-, parent-, and self-reported outcome measures. Sensitivity analyses were conducted by removing any outlying studies and any studies that did not use a CBT intervention. A subgroup analysis was performed to compare individual and group delivery of treatment. Ten randomised control trials involving a total of 470 participants were included. The overall SMD was d = 1.05 (95 % CI 0.45, 1.65; z = 3.45, p = 0.0006) for clinician- reported outcome measures; d = 1.00 (95%CI 0.21, 1.80; z = 2.47, p = 0.01) for parent-reported outcome measures; and d = 0.65 (95%CI -0.10, 1.07; z = 1.63, p = 0.10) for self-reported outcome measures. Clinician- and parent-reported outcome measures showed that psychosocial interventions were superior to waitlist and treatment-as-usual control conditions at post-treatment. However, the results of self-reported outcome measures failed to reach significance. The sensitivity analyses did not significantly change these results and the subgroup analysis indicated that individual treatment was more effective than group treatment. The main limitations of this review were the small number of included studies as well as the clinical and methodological variability between studies

Metabolic alterations during the growth of tumour spheroids

Solid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology and the flux or utilisation of fuels including glucose. The tumour spheroid model was used to characterise the utilisation of glucose and describe alterations to the activity and expression of key glycolytic enzymes during the tissue growth curve. Glucose was avidly consumed and associated with the production of lactate and an acidified medium, confirming the reliance on glycolytic pathways and a diminution of oxidative phosphorylation. The expression levels and activities of hexokinase, phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the glycolytic pathway were measured to assess glycolytic capacity. Similar measurements were made for glucose-6-phosphate dehydrogenase, the entry point and regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate dehydrogenase, a key link to TCA cycle intermediates. The parameters for these key enzymes were shown to undergo considerable variation during the growth curve of tumour spheroids. In addition, they revealed that the dynamic alterations were influenced by both transcriptional and posttranslational mechanisms

Metabolic alterations during the growth of tumour spheroids

Solid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology and the flux or utilisation of fuels including glucose. The tumour spheroid model was used to characterise the utilisation of glucose and describe alterations to the activity and expression of key glycolytic enzymes during the tissue growth curve. Glucose was avidly consumed and associated with the production of lactate and an acidified medium, confirming the reliance on glycolytic pathways and a diminution of oxidative phosphorylation. The expression levels and activities of hexokinase, phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the glycolytic pathway were measured to assess glycolytic capacity. Similar measurements were made for glucose-6-phosphate dehydrogenase, the entry point and regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate dehydrogenase, a key link to TCA cycle intermediates. The parameters for these key enzymes were shown to undergo considerable variation during the growth curve of tumour spheroids. In addition, they revealed that the dynamic alterations were influenced by both transcriptional and posttranslational mechanisms

Transcriptional Activation of c3 and hsp70 as Part of the Immune Response of Acropora millepora to Bacterial Challenges

The impact of disease outbreaks on coral physiology represents an increasing concern for the fitness and resilience of reef ecosystems. Predicting the tolerance of corals to disease relies on an understanding of the coral immune response to pathogenic interactions. This study explored the transcriptional response of two putative immune genes (c3 and c-type lectin) and one stress response gene (hsp70) in the reef building coral, Acropora millepora challenged for 48 hours with bacterial strains, Vibrio coralliilyticus and Alteromonas sp. at concentrations of 106 cells ml-1. Coral fragments challenged with V. coralliilyticus appeared healthy while fragments challenged with Alteromonas sp. showed signs of tissue lesions after 48 hr. Coral-associated bacterial community profiles assessed using denaturing gradient gel electrophoresis changed after challenge by both bacterial strains with the Alteromonas sp. treatment demonstrating the greatest community shift. Transcriptional profiles of c3 and hsp70 increased at 24 hours and correlated with disease signs in the Alteromonas sp. treatment. The expression of hsp70 also showed a significant increase in V. coralliilyticus inoculated corals at 24 h suggesting that even in the absence of disease signs, the microbial inoculum activated a stress response in the coral. C-type lectin did not show a response to any of the bacterial treatments. Increase in gene expression of c3 and hsp70 in corals showing signs of disease indicates their potential involvement in immune and stress response to microbial challenges

Pragmatic Randomised Evaluation of Stable Thoracolumbar fracture treatment Outcomes (PRESTO): Study Protocol for a Randomised Controlled Feasibility Trial combined with a qualitative study and survey

Background A thoracolumbar fracture is the most common fracture of the spinal column. Where the fracture is not obviously stable or unstable, the optimal management is uncertain. There are variations between surgeons, treating centres and within the evidence base as to whether surgical or non-surgical approaches should be used. In addition, the boundaries of this zone of uncertainty for stability are unclear. This study has been designed in response to a NIHR HTA commissioning brief to assess the feasibility of undertaking a large-scale trial to evaluate the effectiveness of surgical and non-surgical treatments for thoracolumbar fractures without neurological deficit. Methods Assessment of feasibility will be addressed through three elements: a randomised external feasibility study, a national survey of surgeons and a qualitative study. The external feasibility study is a pragmatic, parallel group, randomised controlled trial comparing surgical fixation (intervention) versus non-surgical management (control). Recruitment will take place in three secondary care centres in the United Kingdom. The primary outcome is recruitment rate, defined as the proportion of eligible participants who are randomised. Further outcomes related to recruitment, randomisation, drop-out, cross-over, loss to follow-up, completeness of outcome data, study processes and details of the interventions delivered will be collected. The survey of surgeons and qualitative study of clinicians, recruiting staff and patients will enhance the feasibility study, enabling a broad overview of current practice in the field in addition to perceived facilitators and barriers to running a full-scale trial. Discussion PRESTO is a feasibility study which aims to inform methodology for a definitive trial comparing surgical fixation with non-surgical management for patients with stable thoracolumbar fractures. Trial registration The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN 12094890). Date of registration was 22/02/2018 (http://www.isrctn.com/ISRCTN12094890). Keywords Thoracolumbar, fracture, surgical fixation, randomised controlled trial, qualitative, survey, feasibility, pilot