ABSTRACT
BACKGROUND: The co-design of health care enables patient-centredness by partnering patients, clinicians and other stakeholders together to create services. METHODS: We conducted a systematic review of co-designed health interventions for people living with multimorbidity and assessed (a) their effectiveness in improving health outcomes, (b) the co-design approaches used and (c) barriers and facilitators to the co-design process with people living with multimorbidity. We searched MEDLINE, EMBASE, CINAHL, Scopus and PsycINFO between 2000 and March 2022. Included experimental studies were quality assessed using the Cochrane risk of bias tool (ROB-2 and ROBINS-I). RESULTS: We screened 14,376 reports, with 13 reports meeting the eligibility criteria. Two reported health and well-being outcomes: one randomised clinical trial (n = 134) and one controlled cohort (n = 1933). Outcome measures included quality of life, self-efficacy, well-being, anxiety, depression, functional status, healthcare utilisation and mortality. Outcomes favouring the co-design interventions compared to control were minimal, with only 4 of 17 outcomes considered beneficial. Co-design approaches included needs assessment/ideation (12 of 13), prototype (11 of 13), pilot testing (5 of 13) (i.e. focus on usability) and health and well-being evaluations (2 of 13). Common challenges to the co-design process include poor stakeholder interest, passive participation, power imbalances and a lack of representativeness in the design group. Enablers include flexibility in approach, smaller group work, advocating for stakeholders' views and commitment to the process or decisions made. CONCLUSIONS: In this systematic review of co-design health interventions, we found that few projects assessed health and well-being outcomes, and the observed health and well-being benefits were minimal. The intensity and variability in the co-design approaches were substantial, and challenges were evident. Co-design aided the design of novel services and interventions for those with multimorbidity, improving their relevance, usability and acceptability. However, the clinical benefits of co-designed interventions for those with multimorbidity are unclear.
Subject(s)
Multimorbidity , Quality of Life , Humans , Outcome Assessment, Health CareABSTRACT
In several long-lived Caenorhabditis elegans strains, such as insulin/IGF-1 receptor daf-2 mutants, enhanced proteostatic mechanisms are accompanied by elevated intestinal lipid stores, but their role in longevity is unclear. Here, while determining the regulatory network of the selective autophagy receptor SQST-1/SQSTM1, we uncovered an important role for lipid droplets in proteostasis and longevity. Using genome-wide RNAi screening, we identified several SQST-1 modulators, including lipid droplets-associated and aggregation-prone proteins. Expansion of intestinal lipid droplets by silencing the conserved cytosolic triacylglycerol lipase gene atgl-1/ATGL enhanced autophagy, and extended lifespan. Notably, a substantial amount of ubiquitinated proteins were found on lipid droplets. Reducing lipid droplet levels exacerbated the proteostatic collapse when autophagy or proteasome function was compromised, and significantly reduced the lifespan of long-lived daf-2 animals. Altogether, our study uncovered a key role for lipid droplets in C. elegans as a proteostatic mediator that modulates ubiquitinated protein accumulation, facilitates autophagy, and promotes longevity.
ABSTRACT
Altered nucleolar and ribosomal dynamics are key hallmarks of aging, but their regulation remains unclear. Building on the knowledge that the conserved nuclear export receptor Exportin 1 (XPO-1/XPO1) modulates proteostasis and life span, we systematically analyzed the impact of nuclear export on protein metabolism. Using transcriptomic and subcellular proteomic analyses in nematodes, we demonstrate that XPO-1 modulates the nucleocytoplasmic distribution of key proteins involved in nucleolar dynamics and ribosome function, including fibrillarin (FIB-1/FBL) and RPL-11 (RPL11). Silencing xpo-1 led to marked reduction in global translation, which was accompanied by decreased nucleolar size and lower fibrillarin levels. A targeted screen of known proteostatic mediators revealed that the autophagy protein LGG-1/GABARAP modulates nucleolar size by regulating RPL-11 levels, linking specific protein degradation to ribosome metabolism. Together, our study reveals that nucleolar size and life span are regulated by LGG-1/GABARAP via ribosome protein surveillance.
ABSTRACT
OBJECTIVE: The incidence of young-onset (<50 years) colorectal cancer (CRC) has been increasing internationally. The psychosocial experience of younger cancer patients is vastly different from older patients, especially in domains such as financial toxicity, body image, and sexual dysfunction. What is unknown is the cancer type-specific experience. The aim of the current scoping review was to examine (1) the psychosocial factors and/or outcomes associated with young-onset CRC and (2) other determinants that influences these outcomes. METHODS: A systematic search was conducted on four databases (PubMed, CINAHL, Scopus and PsycINFO) from inception to December 2020 using key terms and combinations. Primary literature that examined the psychosocial (e.g., quality-of-life, emotional, social, sexual) impact of young-onset CRC were included. RESULTS: A total of 1389 records were assessed by four reviewers, with a total of seven studies meeting inclusion criteria (n = 5 quantitative, n = 1 qualitative and n = 1 case series). All studies indicated there was significant psychosocial impact in younger CRC patients, including emotional impact, social impact, physical burden, sexual impact, work impact, unmet needs, financial impact and global quality of life. Three studies explored other determinants that influenced the psychosocial experience and found that socioeconomic background (e.g., being female, lower education), CRC treatment (e.g., chemotherapy) and health status were associated with worse psychosocial impact. CONCLUSIONS: Young-onset CRC patients face severe psychosocial impact unique to this age group, such as self-image and sexual impact. Social support services and resources needs to be uniquely tailored. More empirical investigations are required to understand its long-term impact and influence of other psychosocial domains.
