Music therapy for supporting informal carers of adults with life-threatening illness pre- and post-bereavement; a mixed-methods systematic review.

BACKGROUND: Music therapy interventions with informal carers of individuals with life-threatening illness at pre- and post-bereavement is an increasingly important clinical area. This systematic review is the first to synthesise and critically evaluate the international evidence associated with music therapy with adult informal carers pre- and post-bereavement. Specifically, the objectives were: i) to describe the characteristics and effectiveness of music therapy interventions which aim to improve health-related outcomes for adult informal carers of adults with life-threatening illness (pre- and post-bereavement), and ii) to describe the experience of music therapy for adult informal carers of adults with life-threatening illness (pre- and post-bereavement). METHODS: Eligibility: adult informal carers of adults at end of life or bereaved; music therapy interventions for improving health-related outcomes; qualitative; mixed-method; and quantitative studies including comparators of any other intervention; published in English from 1998 onwards. Six databases were searched up to July 2022. A JBI mixed-methods systematic review approach was followed throughout, including quality appraisal, data extraction and a convergent segregated approach to synthesis and integration. RESULTS: A total of 34 studies were included, published between 2003 and 2022. Most were conducted in North America (n = 13), Australia (n = 10), or Europe (n = 8). No studies were conducted in low- and middle-income countries or in the UK. The majority were qualitative (n = 17), followed by quasi-experimental (n = 8), mixed-methods (n = 7) and two RCTs. The majority focused on carers of individuals with dementia (n = 21) or advanced cancer (n = 7). Seventeen studies were purely quantitative or included a quantitative component. During meta-synthesis, findings were aligned to core outcomes for evaluating bereavement interventions in palliative care and previously identified risk factors for complicated grief. Commonly targeted outcomes in quantitative studies included quality of life and mental wellbeing, showing equivocal effectiveness of music therapy with significant and non-significant results. Twenty-two studies either purely qualitative or with a qualitative component underwent meta synthesis and suggested a diverse range of improved pre- and post-bereavement outcomes for informal carers across all core outcomes, and across all risk and protective factors, including psychological, spiritual, emotional, and social outcomes. CONCLUSIONS: Qualitative studies provide moderate to strong evidence for improved health-related outcomes for adult informal carers of adults with life-threatening illness pre-bereavement. Limited studies including those bereaved negates conclusions for the bereavement phase. Comparisons and explanations for effectiveness across quantitative and qualitative studies are equivocal, with a high risk of bias and small samples in the limited number of quantitative studies, demonstrating a need for high-quality RCTs. SYSTEMATIC REVIEW PRE-REGISTRATION: PROSPERO [CRD42021244859].

Nonpharmacological interventions in dementia and diversity of samples: A scoping review.

BACKGROUND: A public health priority is the increasing number of people with dementia (PwD), and nonpharmacological interventions (NPIs) might offer support. We sought to synthesize types of NPIs tested among PwD and explore sample characteristics. METHODS: This study was a scoping literature review. Eligible articles were identified using the search terms "nonpharmacological intervention" and "dementia". RESULTS: 36 articles were included. Psychosocial NPIs were implemented the most (n=24) and music-based interventions were found to be the most effective. Gender, race, and ethnicity were not consistently reported (n=30, n=24, and n=6, respectively). White PwD had higher representation, with only 62.5% of studies including Black participants and 25% including Hispanic/Latino participants. Women made up a majority (>50%) of the sample in a greater number of studies (n=20). CONCLUSION: Findings suggest that future studies need to be intentional about improving diversity of the sample, particularly with respect to including persons identifying as Black or Hispanic/Latino.

Adjuvant FOLFOX +/- cetuximab in full RAS and BRAF wildtype stage III colon cancer patients.

Background: RAS mutations have been shown to confer resistance to anti- epidermal growth factor receptor (EGFR) treatment. We analysed the results of the PETACC8 trial (cetuximab + FOLFOX vs FOLFOX) in full RAS and BRAF wildtype (WT) patients (pts) with resected stage III colon cancer. Patients and methods: Exons 2, 3 and 4 of KRAS and NRAS, and BRAF exons 11 and 15, were sequenced using the Ampliseq colon-lung cancer panel version 2, in PETACC8 trial pts who consented to translational research. The impact of cetuximab on time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS) was investigated in pts with tumours harbouring RAS and BRAF WT, and RAS mutations. The prognostic value of each individual mutation was also tested. Results: Among the 2559 pts analysed, 745 pts (29%) were known to have KRAS exon 2 mutations and 163 pts (6.4%) the BRAF V600E mutation. Of the remaining 1651 pts, 1054 were assessed by NGS, showing that a further 227 pts (21%) had KRAS exon 2, 3, 4 or NRAS exon 2, 3, 4 mutations, and that 46 pts (4.4%) had a newly diagnosed BRAF mutation. Cetuximab added to FOLFOX did not significantly improve TTR, DFS or OS in pts with RAS WT or RAS and BRAF WT tumours (HR 0.77-1.03, all P > 0.05). Cetuximab addition was not either significantly deleterious in RAS mutant pts or in pts with rare RAS or BRAF mutations. In the overall trial population, NRAS and KRAS codon 61 mutations were the only rare mutations with the same pejorative prognostic value as KRAS exon 2 or BRAF V600E mutations. Conclusion: Though not significant, the clinically relevant 0.76 adjusted HR observed for DFS in favour of adding cetuximab to FOLFOX, in full RAS and BRAF WT stage III colon cancer pts, may justify a new randomized controlled trial testing EGFR inhibitors in this setting. Clinical trial number: This is an ancillary study of the PETACC8 trial: EUDRACT 2005-003463-23.

Antibodies to Glutamate Reversed the Amnesic Effects of Proinflammatory S100A9 Protein Fibrils in Aged C57Bl/6 Mice.

Chronic intranasal administration of fibrillar structures of proinflammatory S100A9 protein impaired passive avoidance learning in old C57Bl/6 mice. Combined treatment with S100A9 fibrils and antibodies to glutamate was followed by an increase in horizontal locomotor activity of animals in the open-field test and did not disturb spatial memory.

Assessing the benefit-risk of new treatments using generalised pairwise comparisons: the case of erlotinib in pancreatic cancer.

BACKGROUND: Efficacy and safety are the two considerations when characterising the effects of a new therapy. We sought to apply an innovative method of assessing the benefit-risk balance using data from a completed randomised controlled trial that compared erlotinib vs placebo added to gemcitabine in patients with advanced pancreatic cancer (NCIC CTG PA.3). METHODS: We applied generalised pairwise comparisons with several prioritised outcome measures (e.g., one or more benefit outcomes and one or more risk outcomes). Here, the first priority outcome was overall survival (OS) time. Differences in OS that exceeded 2 months were considered clinically meaningful. The second priority outcome was toxicity. The overall treatment effect was quantified using the proportion in favour of erlotinib, which can be interpreted as the net proportion of patients who have a better overall outcome with erlotinib as compared with placebo. Sensitivity analyses were performed. RESULTS: In this trial 569 patients were randomly assigned in a 1 : 1 ratio to receive gemcitabine plus either erlotinib or a matched placebo. Overall, the method indicated no statistically significant overall treatment effect in favour of erlotinib; if anything, the point estimate of the net proportion leaned in favour of the placebo group (overall proportion in favour of erlotinib=-3.6%, 95% CI, -14.2- 7.1%; P=0.51). The net proportion was never in favour of the erlotinib group throughout all sensitivity analyses. CONCLUSIONS: Generalised pairwise comparisons make it possible to assess the benefit-risk balance of new treatments using a single statistical test for any number of prioritised outcomes. The benefit-risk assessment was not in favour of adding erlotinib to gemcitabine for the treatment of patients with advanced pancreatic cancer.

Long-term net survival in patients with colorectal cancer in France: an informative contribution of recent methodology.

BACKGROUND: Net survival, the survival that might occur if cancer was the only cause of death, is a major epidemiological indicator. Recent findings have shown that the classical methods used for the estimation of net survival from cancer registry data, referred as to "relative-survival methods," provided biased estimates. OBJECTIVES: The aim of this study was to provide, for the first time, long-term net survival rates for colorectal cancer by using a population-based digestive cancer registry. DESIGN: This study is a population-based cancer registry analysis. The recently proposed unbiased nonparametric Pohar-Perme estimator was used. PATIENTS: Overall, 14,715 colorectal cancers diagnosed between 1976 and 2005 and registered in the population-based digestive cancer registry of Burgundy (France) were included. MAIN OUTCOME MEASURES: The primary outcome measured was cancer net survival, ie, the survival that might occur if all risks of dying of other causes than cancer were removed RESULTS: : Ten-year net survival increased from 31% during the 1976 to 1985 period to 47% during the 1986 to 1995 period and then leveled out (48% during the 1996-2005 period). There was a major improvement in 10-year net survival after resection for cure and for stage I to III. It was striking for stage III cancers, for which 10-year net survival increased from 21% (1976-1985) to 49% (1996-2005). The corresponding net survivals were 70% and 87% for stage I and 49% and 65% for stage II. These trends can be related to the decrease in operative mortality, the increase in the proportion of patients resected for cure, and the improvement in stage at diagnosis. They were mainly seen between 1976 and 1995, explaining why survival leveled out after 1995. LIMITATIONS: The study was limited by its retrospective and population-based nature. CONCLUSIONS: Further improvements for colorectal cancer management can be expected from more effective treatments and from the implementation of organized cancer screening.

Perspectives in adhesion prevention in gynaecological surgery.

Adhesions are a frequent, clinically relevant, and often costly complication of surgery that can develop in any body location regardless of the type of surgical procedure. Adhesions result from surgical trauma inducing inflammatory and coagulation processes and to date cannot be entirely prevented. However, the extent of adhesion formation can be reduced by using good surgical technique and the use of anti-inflammatory drugs, haemostats, and barrier agents. Strategies are needed in the short-, medium- and longer-term to improve the prevention of adhesions. In the short-term, efforts are needed to increase the awareness amongst surgeons and patients about the potential risks and burden of surgically induced adhesions. To aid this in the medium- term, a risk score to identify patients at high risk of adhesion formation is being developed and validated. Furthermore, available potentially preventive measures need to be highlighted. Both clinical and health economic evaluations need to be undertaken to support the broad adoption of such measures. In the longer- term, a greater understanding of the pathogenic processes leading to the formation of adhesions is needed to help identify effective, future treatments to reliably prevent adhesions from forming and lyse existing ones.

[Amyloid-like fibrils forming and fibroblasts destruction in Tenon's capsule in progressive myopia as a result of pigment epithelium derived factor resistance to restricted proteolysis].

We have shown previously the presence of full length (50 kD) and truncated proteolytic form (45 kD) of pigment epithelium derived factor (PEDF) in the eye Tenon's capsule in progressive myopia. The full length PEDF is prevalent in myopia that correlates with breach in collagen fibrils forming. Immunohistochemical analysis of Tenon's capsule with polyclonal antibodies to PEDF revealed PEDF in control group being exclusively inside fibroblasts, whereas in myopia, PEDF was distributed extracellularly as halo around blasted fibroblasts. By means of atomic force microscopy and immunodot analysis with anti amyloid fibrils antibodies the ability was studied of recombinant PEDF fragments to form fibrils. Only full length PEDF was shown to form amyloid like fibril structures, but not the truncated form. Accumulation offibrils results in fibroblasts destruction and might be the cause of changes in biochemical and morphological structure of Tenon's capsule observed in myopia.

Total surgical time in laparoscopic supracervical hysterectomy with laparoscopic in-bag-morcellation compared to laparoscopic supracervical hysterectomy with uncontained morcellation.

Background: A possible solution to the problem of cell dissemination through laparoscopic uncontained morcellation during laparoscopic supracervical hysterectomy (LASH) is the use of laparoscopic in-bag morcellation. One criticism regarding the use of in-bag morcellation is the additional surgical time associated with this procedure. Objectives: In this retrospective study we compared the total surgical time in LASH with laparoscopic in-bag morcellation (107 cases from 2016-2018) and LASH with uncontained morcellation (47 cases from 2015-2017). Materials and Methods: All surgeries were performed in the same department of minimally invasive gynaecological surgery by a total of three experienced surgeons for the indication of bleeding disorder and / or dysmenorrhea. Main outcome measure: We measured and compared total surgical time, surgical outcome, blood loss and complications in LASH with in-bag morcellation and with uncontained morcellation. Results: Total surgical time in both procedures do not show a significant difference. Considering the learning curve in laparoscopic bag use, the total surgical time in LASH with laparoscopic in-bag morcellation is shorter than total surgical time in LASH with uncontained morcellation. Laparoscopic in-bag morcellation consumes time for bag use and handling, but saves time as it eliminates the need for meticulous sampling of lost tissue fragments and the complex lavage of the peritoneal cavity after morcellation. There is no difference between both groups in terms of blood loss, complications and surgical results. Conclusion / What is new?: We conclude that LASH with in-bag morcellation is not related to additional surgical time when compared to LASH with uncontained morcellation.

Beef Quality Assurance national rancher survey: program participation, best management practices, and motivations for joining future sustainability programs.

Till date, with over 137,000 certified members, the most successful rancher educational program has been the Beef Quality Assurance (BQA) program. The BQA program was established in the mid-1990's to improve animal health and welfare with a primary objective to reduce the incidence of injection site lesions by instructing producers to administer injections in the neck only. The present study investigated the drivers of this success to inform future rancher education programs around agricultural sustainability. An online multistate survey was administered to cattle ranchers in collaboration with state cattlemen's associations to better understand rancher motivations for adopting new practices and to gain insight on current involvement in BQA. In total, the survey consisted of 45 questions and was divided into 3 sections: (1) rancher demographics, (2) BQA participation and current best management practice (BMP) application, and (3) willingness to join new rancher educational programs. Data from 842 respondents are including in this study. Of the survey participants, 70% were currently BQA certified or had been BQA certified at one time, and 30% had never been certified. Ranchers who were BQA certified at any time were less likely to administer injections in areas other than the neck compared to ranchers who were not certified (P < 0.05), demonstrating the effectiveness of the BQA program. More than 80% of survey respondents who joined the BQA program stated they believed the BQA program improved animal health and welfare on their operation (n = 617). Among those who had not joined the BQA program, 40% believed BQA practices did not align with their ranching operation, while 38% had not heard of the BQA program (n = 256). The survey indicated that male ranchers, those with more years ranching, those with a larger percent of income coming from ranching, and ranches with larger total acres grazed were more likely to be BQA certified at any time (P < 0.05). Finally, ranchers who were BQA certified at any time were more likely to state that joining a rancher sustainability program would be beneficial to their operation. In conclusion, not only did the survey provide valuable insight into BQA program adoption but highlighted how BQA pedagogy and program structure may be a suitable framework for creating future rancher sustainability programs.