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Randomised controlled trial combining vitamin E-functionalised chocolate with physical exercise to reduce the risk of protein-energy malnutrition in predementia aged people: study protocol for Choko-Age

Por: Pedrinolla · A. · Isanejad · M. · Antognelli · C. · Bartolini · D. · Borras · C. · Cavedon · V. · Di Sante · G. · Migni · A. · Mas-Bargues · C. · Milanese · C. · Baschirotto · C. · Modena · R. · Pistilli · A. · Rende · M. · Schena · F. · Stabile · A. M. · Telesa · N. V. · Tortorella · S.
Objective

Protein–energy malnutrition and the subsequent muscle wasting (sarcopenia) are common ageing complications. It is knowing to be also associated with dementia. Our programme will test the cytoprotective functions of vitamin E combined with the cortisol-lowering effect of chocolate polyphenols (PP), in combination with muscle anabolic effect of adequate dietary protein intake and physical exercise to prevent the age-dependent decline of muscle mass and its key underpinning mechanisms including mitochondrial function, and nutrient metabolism in muscle in the elderly.

Methods and analysis

In 2020, a 6-month double-blind randomised controlled trial in 75 predementia older people was launched to prevent muscle mass loss, in respond to the ‘Joint Programming Initiative A healthy diet for a healthy life’. In the run-in phase, participants will be stabilised on a protein-rich diet (0.9–1.0 g protein/kg ideal body weight/day) and physical exercise programme (high-intensity interval training specifically developed for these subjects). Subsequently, they will be randomised into three groups (1:1:1). The study arms will have a similar isocaloric diet and follow a similar physical exercise programme. Control group (n=25) will maintain the baseline diet; intervention groups will consume either 30 g/day of dark chocolate containing 500 mg total PP (corresponding to 60 mg epicatechin) and 100 mg vitamin E (as RRR-alpha-tocopherol) (n=25); or the high polyphenol chocolate without additional vitamin E (n=25). Muscle mass will be the primary endpoint. Other outcomes are neurocognitive status and previously identified biomolecular indices of frailty in predementia patients. Muscle biopsies will be collected to assess myocyte contraction and mitochondrial metabolism. Blood and plasma samples will be analysed for laboratory endpoints including nutrition metabolism and omics.

Ethics and dissemination

All the ethical and regulatory approvals have been obtained by the ethical committees of the Azienda Ospedaliera Universitaria Integrata of Verona with respect to scientific content and compliance with applicable research and human subjects’ regulation. Given the broader interest of the society toward undernutrition in the elderly, we identify four main target audiences for our research activity: national and local health systems, both internal and external to the project; targeted population (the elderly); general public; and academia. These activities include scientific workshops, public health awareness campaigns, project dedicated website and publication is scientific peer-review journals.

Trial registration number

NCT05343611.

Medium-term storage of calf beddings affects bacterial community and effectiveness to inactivate zoonotic bacteria

by Delphine Rapp, Colleen Ross, Vanessa Cave, Paul Maclean, Ruy Jauregui, Gale Brightwell

Land-spreading of animal faecal wastes -such as animal beddings- can introduce zoonotic enteropathogens into the food system environment. The study evaluated the effectiveness of animal beddings naturally contaminated by calf manure to reduce E. coli O157:H7 or Salmonella enterica. The two pathogens were introduced separately as a four strains-cocktail and at high (>6.5 Log10 g-1) concentration into bedding materials, and their inactivation over a 10 weeks-period was monitored by using a Most Probable Number (MPN) enumeration method. Inactivation of E. coli O157:H7 was more effective in the bedding inoculated immediately after collection from calf pens than in the beddings inoculated after a 2 months-pre-storage period: E. coli O157:H7 levels were reduced by 6.6 Log10 g-1 in unstored bedding (0.5 Log10 g-1 recovered; 95%CI: 0.0–1.2), and by 4.9 Log10 g-1 in pre-stored bedding (2.2 Log10 g-1 recovered; 95%CI: 1.5–2.8) with a significant (pS. enterica was inactivated less effectively as counts were reduced by one order of magnitude, with no significant difference in inactivation between unstored and pre-stored beddings. Low levels of naturally occurring E. coli O157 and Salmonella spp. were detected in the non-inoculated beddings, as well as in the straw prior to use in the animal facility. To better understand the possible biological processes involved, the bacterial community present in the beddings was characterised by short-read 16S rRNA sequencing. Pre-storage of the bedding affected the composition but not the diversity of the bacterial community. Analyses of the key bacterial phyla suggested that the presence of a diverse and stable bacterial community might facilitate inactivation of the introduced pathogens, and a possible role of bacterial orders associated with lignocellulolytic resources. Overall, the study contributed to the understanding of the fate of zoonotic bacteria introduced in animal beddings during storage and identified bedding storage practices pre-and post-use in animal facilities that could be important to prevent the risk of zoonosis dissemination to the environment or to the dairy herds.

Young carers perspectives on navigating the healthcare system and co-designing support for their caring roles: a mixed-methods qualitative study

Por: Saragosa · M. · Hahn-Goldberg · S. · Lunsky · Y. · Cameron · J. I. · Caven · I. · Bookey-Bassett · S. · Newman · K. · Okrainec · K.
Objectives

Despite young carers (YCs) providing regular and significant care that exceeds what would normally be associated with an adult caregiver, we need to learn more about their experience interacting with the healthcare system. The primary study aims were to (1) describe YC experiences in interacting with the healthcare system and (2) identify types of support YC recognise as potentially helpful to their caring role.

Design and setting

A mixed-methods qualitative study was conducted between March 2022 and August 2022, comprising two phases of (1) semi-structured interviews and focus groups with YCs living in the community to confirm and expand earlier research findings, and (2) a co-design workshop informed by a generative research approach. We used findings from the interviews and focus groups to inform the brainstorming process for identifying potential solutions.

Results

Eight YCs completed either a focus group or an interview, and four continued the study and participated in the co-design activity with 12 participants. Phase 1 resulted in three overarching themes: (1) navigating the YC role within the healthcare system; (2) being kept out of the loop; and (3) normalising the transition into caregiving. Phase 2 identified two categories: (1) YC-focused supports and (2) raising awareness and building capacity in the healthcare system.

Conclusion

Study findings revealed the critical role that YCs play when supporting their families during pivotal interactions in the healthcare system. Like their older caregiver counterparts, YCs struggle to navigate, coordinate and advocate for their family members while juggling their needs as they transition from adolescence to adulthood. This study provides important preliminary insights into YCs encountering professionals, which can be used to design and implement national support structures.

Evaluating niraparib versus active symptom control in patients with previously treated mesothelioma (NERO): a study protocol for a multicentre, randomised, two-arm, open-label phase II trial in UK secondary care centres

Por: Fennell · D. · Griffiths · D. · Eminton · Z. · Morgan-Fox · A. · Hill · K. · Ewings · S. · Stuart · C. · Johnson · L. · Mallard · K. · Nye · M. · Darlison · L. · Dulloo · S. · Cave · J. · Luo · J.-L. · Taylor · P. · Spicer · J. · Poile · C. · Bzura · A. · Griffiths · G.
Background

Malignant mesothelioma is a rapidly lethal cancer that has been increasing at an epidemic rate over the last three decades. Targeted therapies for mesothelioma have been lacking. A previous study called MiST1 (NCT03654833), evaluated the efficacy of Poly (ADP-ribose) polymerase (PARP) inhibition in mesothelioma. This study met its primary endpoint with 15% of patients having durable responses exceeding 1 year. Therefore, there is a need to evaluate PARP inhibitors in relapsed mesothelioma patients, where options are limited. Niraparib is the PARP inhibitor used in NERO.

Methods

NERO is a multicentre, two-arm, open-label UK randomised phase II trial designed to evaluate the efficacy of PARP inhibition in relapsed mesothelioma. 84 patients are being recruited. NERO is not restricted by line of therapy; however, eligible participants must have been treated with an approved platinum based systemic therapy. Participants will be randomised 2:1, stratified according to histology and response to prior platinum-based chemotherapy, to receive either active symptom control (ASC) and niraparib or ASC alone, for up to 24 weeks. Participants will be treated until disease progression, withdrawal, death or development of significant treatment limiting toxicity. Participants randomised to niraparib will receive 200 or 300 mg daily in a 3-weekly cycle. The primary endpoint is progression-free survival, where progression is determined by modified Response Evaluation Criteria in Solid Tumors (mRECIST) or RECIST 1.1; investigator reported progression; or death from any cause, whichever comes first. Secondary endpoints include overall survival, best overall response, 12-week and 24 week disease control, duration of response, treatment compliance and safety/tolerability. If NERO shows niraparib to be safe and biologically effective, it may lead to future late phase randomised controlled trials in relapsed mesothelioma.

Ethics and dissemination

The study received ethical approval from London-Hampstead Research Ethics Committee on 06-May-2022 (22/LO/0281). Data from all centres will be analysed together and published as soon as possible.

Trial registration number

ISCRTN16171129; NCT05455424.

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