Special issue editorial : The Festival of OCIES 2020

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eHealth and Web-Based Interventions for Informal Carers of People With Dementia in the Community: Umbrella Review

BACKGROUND: The prevalence of dementia is increasing, and there are many associated problems that family members face as informal carers, including emotional, physical, and financial difficulties. There are benefits for a person with dementia to live at home for as long as possible, and therefore, supporting their informal carers is crucial. The growing interest in supporting carers through internet-based interventions is evidenced by the volume of systematic reviews on this topic. It is now appropriate to systematically examine this body of work and provide an overview of the literature. OBJECTIVE: This umbrella review aimed to identify the most effective internet-based intervention content and delivery method to support those caring for someone with dementia living in the community. METHODS: PsycINFO, Web of Science, CINAHL, MEDLINE, Cochrane Library, and PubMed were searched for systematic reviews examining the effectiveness of web-based interventions for informal carers of people with dementia. A total of 3 reviewers extracted data and evaluated the quality of the papers. To ascertain the extent to which the systematic reviews reported on the same evidence, the proportion of overlap between their included studies was calculated. Qualitative research findings were extracted and reported. RESULTS: A total of 21 papers were included in the study. The quality of the review papers was mainly rated as low to moderate, and 10% (2/21) of papers were of high quality. The findings suggest that multicomponent interventions were the most effective in supporting carers. These included combinations of cognitive behavioral therapy and relaxation strategies, educational resources, and online support groups. Interventions that were delivered on the web but included sessions with a personal element, such as telephone contact, showed the best results. When comparing the studies reviewed in all the review papers, a moderate overlap was noted. However, when comparing individual reviews with each other, they showed a high overlap of the included studies. CONCLUSIONS: Mixed delivery methods and intervention content showed the most effective results in supporting those caring for people with dementia. However, many papers do not separate the results for differing intervention contents or delivery; this needs to be considered when drawing conclusions. There was an overlap among the studies included in the reviews. This suggests a lack of current research on the effectiveness of web-based interventions for people caring for a person with dementia. There was also a lack of consistency in the outcome measures across all papers. Future studies can involve updating research on the effectiveness of these interventions while distinguishing between different intervention types, thus creating guidelines for the use of standardized measures to enable comparisons of intervention effects and improve the scientific quality of the overall research. TRIAL REGISTRATION: PROSPERO CRD42021241559; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=24155

Blocking the ZZ domain of sequestosome1/p62 suppresses myeloma growth and osteoclast formation in vitro and induces dramatic bone formation in myeloma-bearing bones in vivo

We reported that p62 (sequestosome 1) serves as a signaling hub in bone marrow stromal cells (BMSCs) for the formation of signaling complexes, including NFκB, p38MAPK and JNK, that are involved in the increased osteoclastogenesis and multiple myeloma (MM) cell growth induced by BMSCs that are key contributors to multiple myeloma bone disease (MMBD), and demonstrated that the ZZ domain of p62 (p62-ZZ) is required for BMSC enhancement of MMBD. We recently identified a novel p62-ZZ inhibitor, XRK3F2, which inhibits MM cell growth and BMSC growth enhancement of human MM cells. In the current study, we evaluate the relative specificity of XRK3F2 for p62-ZZ, characterize XRK3F2's capacity to inhibit growth of primary MM cells and human MM cell lines, and test the in vivo effects of XRK3F2 in the immunocompetent 5TGM1 MM model. We found that XRK3F2 induces dramatic cortical bone formation that is restricted to MM containing bones and blocked the effects and upregulation of tumor necrosis factor alpha (TNFα), an osteoblast (OB) differentiation inhibitor that is increased in the MM bone marrow microenvironment and utilizes signaling complexes formed on p62-ZZ, in BMSC. Interestingly, XRK3F2 had no effect on non-MM bearing bone. These results demonstrate that targeting p62 in MM models has profound effects on MMBD

Protocol for the Rare Dementia Support Impact Study: RDS Impact

OBJECTIVES: The Rare Dementia Support (RDS) Impact study will be the first major study of the value of multicomponent support groups for people living with or supporting someone with a rare form of dementia. The multicentre study aims to evaluate the impact of multicomponent support offered and delivered to people living with a rare form of dementia, comprising the following five Work Packages (WPs): (1) Longitudinal cohort interviews; (2) Theoretical development; (3) Developing measures; (4) Novel interventions; and (5) Economic analysis. METHODS: This is a mixed-methods design, including a longitudinal cohort study (quantitative and qualitative) and a feasibility randomised control trial (RCT). A cohort of >1000 individuals will be invited to participate. The primary and secondary outcomes will be in-part determined through a co-design Nominal Groups Technique pre-study involving caregivers to people living with a diagnosis of a rare dementia. Quantitative analyses of differences and predictors will be based on pre-specified hypotheses. A variety of quantitative (e.g. ANOVA and multiple linear regression techniques), qualitative (e.g. thematic analysis) and innovative analytical methods will also be developed and applied by involving the arts as a research method. RESULTS: The UCL Research Ethics Committee have approved this study. Data collection will begin in Q4 2019. CONCLUSIONS: The study will capture information through a combination of longitudinal interviews, questionnaires and scales, and novel creative data collection methods. The notion of 'impact' in the context of support for rare dementias will involve theoretical development, novel measures and methods of support interventions, and health economic analyses

Rates of Bile Acid Diarrhoea After Cholecystectomy:A Multicentre Audit

Introduction: Bile acid diarrhoea (BAD) can occur due to disruption to the enterohepatic circulation, e.g. following cholecystectomy. Post-cholecystectomy diarrhoea has been reported in 2.1–57.2% of patients; however, this is not necessarily due to BAD. The aim of this study was to determine the rates of bile acid diarrhoea diagnosis after cholecystectomy and to consider investigation practices. Methods: A retrospective analysis of electronic databases from five large centres detailing patients who underwent laparoscopic cholecystectomy between 2013 and 2017 was cross-referenced with a list of patients who underwent 75SeHCAT testing. A 7-day retention time of <15% was deemed to be positive. Patient demographics and time from surgery to investigation were collected and compared for significance (p < 0.05). Results: A total of 9439 patients underwent a laparoscopic cholecystectomy between 1 January 2013 and 31 December 2017 in the five centres. In total, 202 patients (2.1%) underwent investigation for diarrhoea via 75SeHCAT, of which 64 patients (31.6%) had a 75SeHCAT test result of >15%, while 62.8% of those investigated were diagnosed with bile acid diarrhoea (BAD). In total, 133 (65.8%) patients also underwent endoscopy and 74 (36.6%) patients had a CT scan. Median time from surgery to 75SeHCAT test was 672 days (SD ± 482 days). Discussion/Conclusion: Only a small proportion of patients, post-cholecystectomy, were investigated for diarrhoea with significant time delay to diagnosis. The true prevalence of BAD after cholecystectomy may be much higher, and clinicians need to have an increased awareness of this condition due to its amenability to treatment. 75SeHCAT is a useful tool for diagnosis of bile acid diarrhoea

2017 Scientific Consensus Statement: land use impacts on the Great Barrier Reef water quality and ecosystem condition. Chapter 4: management options and their effectiveness

This chapter seeks to answer the following questions: 1. What are the values of the Great Barrier Reef? 2. How effective are better agricultural practices in improving water quality? 3. How can we improve the uptake of better agricultural practices? 4. What water quality improvement can non-agricultural land uses contribute? 5. How can Great Barrier Reef water quality improvement programs be improved? Each section summarises the currently available peer reviewed literature and comments on implications for management and research gaps. This chapter has a wider scope than previous Scientific Consensus Statements, including, for the first time, the social and governance dimensions of management and the management of non-agricultural land uses. These new sections are constrained by a lack of Great Barrier Reef–specific data and information. The relevance of information from other locations must be carefully considered. In comparison, the agricultural practice change and economics sections provide an update on material compiled as part of the 2013 Scientific Consensus Statement. This report has been confined to peer reviewed literature, which is generally published in books and journals or major reports. There is additional evidence in grey literature, such as project and program reports, that has not been included here. Each section of this chapter has been compiled by a writing team and then revised following a series of review processes

Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer

BH3 mimetics such as ABT-263 induce apoptosis in a subset of cancer models. However, these drugs have shown limited clinical efficacy as single agents in small-cell lung cancer (SCLC) and other solid tumor malignancies, and rational combination strategies remain underexplored. To develop a novel therapeutic approach, we examined the efficacy of ABT-263 across >500 cancer cell lines, including 311 for which we had matched expression data for select genes. We found that high expression of the proapoptotic gene Bcl2-interacting mediator of cell death (BIM) predicts sensitivity to ABT-263. In particular, SCLC cell lines possessed greater BIM transcript levels than most other solid tumors and are among the most sensitive to ABT-263. However, a subset of relatively resistant SCLC cell lines has concomitant high expression of the antiapoptotic myeloid cell leukemia 1 (MCL-1). Whereas ABT-263 released BIM from complexes with BCL-2 and BCL-XL, high expression of MCL-1 sequestered BIM released from BCL-2 and BCL-XL, thereby abrogating apoptosis. We found that SCLCs were sensitized to ABT-263 via TORC1/2 inhibition, which led to reduced MCL-1 protein levels, thereby facilitating BIM-mediated apoptosis. AZD8055 and ABT-263 together induced marked apoptosis in vitro, as well as tumor regressions in multiple SCLC xenograft models. In a Tp53; Rb1 deletion genetically engineered mouse model of SCLC, the combination of ABT-263 and AZD8055 significantly repressed tumor growth and induced tumor regressions compared with either drug alone. Furthermore, in a SCLC patient-derived xenograft model that was resistant to ABT-263 alone, the addition of AZD8055 induced potent tumor regression. Therefore, addition of a TORC1/2 inhibitor offers a therapeutic strategy to markedly improve ABT-263 activity in SCLC.United States. Dept. of Defense (Grant W81-XWH-13-1-0323)National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051

A systematic review of the effects of prolonged cow-calf contact on behavior, welfare, and productivity

Separation of calves from cows within hours or days of birth is common on dairy farms. Stakeholders have conflicting perspectives on whether this is harmful or beneficial for the animals’ welfare and production. Our objective was to critically evaluate the scientific evidence for both acute and long-term effects of early separation versus an extended period of cow-calf contact. The outcomes investigated were the behavior, welfare (excluding physical health) and performance (milk yield and growth, respectively) of dairy cows and calves. Primary research papers were found through targeted Web of Science searches, the reference lists of recent reviews for each topic, and the reference lists of papers identified from these sources. Studies were included if they were published in English, the full text was accessible, and they compared treatments with and without contact between dairy cows and calves for a specified period. Early separation (within 24 h post-partum) was found to reduce acute distress responses of cows and calves. However, longer cow-calf contact typically had positive longer-term effects on calves, promoting more normal social behavior, reducing abnormal behavior and sometimes reducing responses to stressors. In terms of productivity, allowing cows to nurse calves generally decreased the volume of milk available for sale during the nursing period, but there was no consistent evidence of reduced milk production over a longer period. Allowing a prolonged period of nursing increased calf weight gains during the milk-feeding period. In summary, extended cow-calf contact aggravates the acute distress responses and reduces the amount of saleable milk while the calves are suckling, but can have positive effects on behaviors relevant to welfare in the longer term and benefit calf growth. The strength of these conclusions is limited, however, given that relatively few studies address most of these effects and that experimental design including timing of contact and observations are often inconsistent across studies. Few studies presented indicators of long-term welfare effects other than abnormal and social behavior of the calves

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients