A Critical Review of Multimodal Interventions for Cachexia.
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ABSTRACT:
SUBMITTER: McKeaveney C
PROVIDER: S-EPMC8262513 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and Objectives: The prevalence of cachexia has increased across all of the cancer types and accounts for up to 20% of cancer-related deaths. This paper is a systematic review of nutritional interventions aiming to improve cachexia outcomes in cancer, focusing on weight gain. Materials and Methods: A search in Medline and Elsevier databases for articles up until the 23 January 2022, was conducted. Results: Out of 5732 screened records, 26 publications were included in the final analysis. Four randomized clinical trials showed a significant body weight (BW) increase in patients treated with eicosapentaenoic acid (EPA), β-hydroxy-beta-methyl butyrate (β-HMB), arginine, and glutamine or marine phospholipids (MPL). An upward BW trend was observed in patients treated with L-carnitine, an Ethanwell/Ethanzyme (EE) regimen enriched with ω-3 fatty acids, micronutrients, probiotics, fish oil, a leucine-rich supplement, or total parental nutrition (TPN) with a high dose of a branched-chain amino acid (BCAA). Conclusions: Although clinical trials relating to large numbers of nutritional supplements present promising data, many trials provided negative results. Further studies investigating the underlying mechanisms of action of these nutritional supplements in cancer cachexia are needed. Early screening for cancer cachexia risk and nutritional intervention in cancer patients before aggravating weight loss may stabilize their weight, preventing cachexia syndrome. According to the GRADE methodology, no positive recommendation for these nutritional supplements may be expressed.
| S-EPMC9318456 | biostudies-literature
Project description:Digital health interventions - interventions delivered over digital media to support the health of users - are becoming increasingly prevalent. Utilising an intervention development framework can increase the efficacy of digital interventions for health-related behaviours. This critical review aims to outline and review novel behaviour change frameworks that guide digital health intervention development. Our comprehensive search for preprints and publications used PubMed, PsycINFO, Scopus, Web of Science and the Open Science Framework repository. Articles were included if they: (1) were peer-reviewed; (2) proposed a behaviour change framework to guide digital health intervention development; (3) were written in English; (4) were published between 1/1/19 and 1/8/2021; and (5) were applicable to chronic diseases. Intervention development frameworks considered the user, intervention elements and theoretical foundations. However, the timing and policy of interventions are not consistently addressed across frameworks. Researchers should deeply consider the digital applicability of behaviour change frameworks to improve intervention success.
| S-EPMC10466959 | biostudies-literature
Project description:BackgroundCancer associated cachexia affects the majority of cancer patients during the course of the disease and thought to be directly responsible for about a quarter of all cancer deaths. Current evidence suggests that a pro-inflammatory state may be associated with this syndrome although the molecular mechanisms responsible for the development of cachexia are poorly understood. The purpose of this work was the identification of key drivers of cancer cachexia that could provide a potential point of intervention for the treatment and/or prevention of this syndrome.MethodsGenetically engineered and xenograft tumour models were used to dissect the molecular mechanisms driving cancer cachexia. Cytokine profiling from the plasma of cachectic and non-cachectic cancer patients and mouse models was utilized to correlate circulating cytokine levels with the cachexia phenotype.ResultsUtilizing engineered tumour models we identified MAP3K11/GDF15 pathway activation as a potent inducer of cancer cachexia. Increased expression and high circulating levels of GDF15 acted as a key mediator of this process. In animal models, tumour-produced GDF15 was sufficient to trigger the cachexia phenotype. Elevated GDF15 circulating levels correlated with the onset and progression of cachexia in animal models and in patients with cancer. Inhibition of GDF15 biological activity with a specific antibody reversed body weight loss and restored muscle and fat tissue mass in several cachectic animal models regardless of their complex secreted cytokine profile.ConclusionsThe combination of correlative observations, gain of function, and loss of function experiments validated GDF15 as a key driver of cancer cachexia and as a potential therapeutic target for the treatment and/or prevention of this syndrome.
| S-EPMC4863827 | biostudies-literature
Project description:BackgroundGuidelines recommend implementation of multimodal interventions to help prevent recurrent TIA/stroke. We undertook a systematic review to assess the effectiveness of behavioral secondary prevention interventions.StrategySearches were conducted in 14 databases, including MEDLINE (1980-January 2014). We included randomized controlled trials (RCTs) testing multimodal interventions against usual care/modified usual care. All review processes were conducted in accordance with Cochrane guidelines.ResultsTwenty-three papers reporting 20 RCTs (6,373 participants) of a range of multimodal behavioral interventions were included. Methodological quality was generally low. Meta-analyses were possible for physiological, lifestyle, psychosocial and mortality/recurrence outcomes. Note: all reported confidence intervals are 95%. Systolic blood pressure was reduced by 4.21 mmHg (mean) (-6.24 to -2.18, P = 0.01 I2 = 58%, 1,407 participants); diastolic blood pressure by 2.03 mmHg (mean) (-3.19 to -0.87, P = 0.004, I2 = 52%, 1,407 participants). No significant changes were found for HDL, LDL, total cholesterol, fasting blood glucose, high sensitivity-CR, BMI, weight or waist:hip ratio, although there was a significant reduction in waist circumference (-6.69 cm, -11.44 to -1.93, P = 0.006, I2 = 0%, 96 participants). There was no significant difference in smoking continuance, or improved fruit and vegetable consumption. There was a significant difference in compliance with antithrombotic medication (OR 1.45, 1.21 to 1.75, P<0.0001, I2 = 0%, 2,792 participants) and with statins (OR 2.53, 2.15 to 2.97, P< 0.00001, I2 = 0%, 2,636 participants); however, there was no significant difference in compliance with antihypertensives. There was a significant reduction in anxiety (-1.20, -1.77 to -0.63, P<0.0001, I2 = 85%, 143 participants). Although there was no significant difference in odds of death or recurrent TIA/stroke, there was a significant reduction in the odds of cardiac events (OR 0.38, 0.16 to 0.88, P = 0.02, I2 = 0%, 4,053 participants).ConclusionsThere are benefits to be derived from multimodal secondary prevention interventions. However, the findings are complex and should be interpreted with caution. Further, high quality trials providing comprehensive detail of interventions and outcomes, are required.Review registrationPROSPERO CRD42012002538.
| S-EPMC4368743 | biostudies-literature
Project description:Cancer cachexia is a complex metabolic syndrome characterized by involuntary skeletal muscle loss and is associated with poor clinical outcome, decreased survival and negatively influences cancer therapy. No curative treatments are available for cancer cachexia, but nutritional intervention is recommended as a cornerstone of multimodal therapy. Optimal nutritional care is pivotal in the treatment of cancer cachexia, and the effects of nutrients may extend beyond provision of adequate energy uptake, targeting different mechanisms or metabolic pathways that are affected or deregulated by cachexia. The evidence to support this notion derived from nutritional intervention studies in experimental models of cancer cachexia is systematically discussed in this review. Moreover, experimental variables and readout parameters to determine skeletal muscle wasting and cachexia are methodologically evaluated to allow critical comparison of similar studies. Single- and multinutrient intervention studies including qualitative modulation of dietary protein, dietary fat, and supplementation with specific nutrients, such as carnitine and creatine, were reviewed for their efficacy to counteract muscle mass loss and its underlying mechanisms in experimental cancer cachexia. Numerous studies showed favorable effects on impaired protein turnover and related metabolic abnormalities of nutritional supplementation in parallel with a beneficial impact on cancer-induced muscle wasting. The combination of high quality nutrients in a multitargeted, multinutrient approach appears specifically promising, preferentially as a multimodal intervention, although more studies investigating the optimal quantity and combination of nutrients are needed. During the review process, a wide variation in timing, duration, dosing, and route of supplementation, as well as a wide variation in animal models were observed. Better standardization in dietary design, and the development of experimental models that better recapitulate the etiology of human cachexia, will further facilitate successful translation of experimentally-based multinutrient, multimodal interventions into clinical practice.
| S-EPMC7783418 | biostudies-literature
Project description:BackgroundUp to 80% of pancreatic cancer patients suffer from cachexia, a devastating condition that exacerbates underlying disease, reduces quality of life, and increases treatment complications and mortality. Tumour-induced inflammation is linked to this multifactorial wasting syndrome, but mechanisms and effective treatments remain elusive. Myeloid differentiation factor (MyD88), a key component of the innate immune system, plays a pivotal role in directing the inflammatory response to various insults. In this study, we tested whether MyD88 signalling is essential in the development of pancreatic cancer cachexia using a robust mouse tumour model.MethodsSex, age, and body weight-matched wide type (WT) and MyD88 knockout (MyD88 KO) mice were orthotopically or intraperitoneally implanted with a pancreatic tumour cell line from a syngeneic C57BL/6 KRASG12D/+ P53R172H/+ Pdx-Cre (KPC) mouse. We observed the effects of MyD88 signalling during pancreatic ductal adenocarcinoma progression and the cachexia development through behavioural, histological, molecular, and survival aspects.ResultsBlocking MyD88 signalling greatly ameliorated pancreatic ductal adenocarcinoma-associated anorexia and fatigue, attenuated lean mass loss, reduced muscle catabolism and atrophy, diminished systemic and central nervous system inflammation, and ultimately improved survival. Our data demonstrate that MyD88 signalling plays a critical role in mediating pancreatic cancer-induced inflammation that triggers cachexia development and therefore represents a promising therapeutic target.ConclusionsMyD88-dependent inflammation is crucial in the pathophysiology of pancreatic cancer progression and contributes to high mortality. Our findings implicate the importance of innate immune signalling pathways in pancreatic cancer cachexia and a novel therapeutic target.
| S-EPMC6463469 | biostudies-literature
Project description:ObjectiveTo identify, appraise and synthesise evidence of interventions designed to promote family member involvement in adult critical care units; and to develop a working typology of interventions for use by health professionals and family members.DesignMixed-method systematic review.Data sourcesBibliographic databases were searched without date restriction up to June 2019: MEDLINE, EMBASE and CINAHL; the Cochrane Central Register of Controlled Trials, Joanna Briggs and Cochrane Libraries. Back issues of leading critical care and patient experience journals were manually searched, as were the reference lists of included studies. All evaluation studies of relevant intervention activities were included; all research designs and outcome measures were eligible. Due to heterogeneity in interventions, designs and outcome measures, the synthesis followed a narrative approach. Service users met with the research team termly.ResultsOut of 4962 possible citations, a total of 20 studies were included. The overall evidence base was assessed as moderate to weak. Six categories of interventions were identified: environmental unit changes (n=2), web-based support (n=4), discussion-based support (n=6), multicomponent support (n=4), participation in rounds (n=3) and participation in physical care (n=1). Clinical and methodological heterogeneity across studies hindered meta-analysis, hence a narrative synthesis was pursued. Six main outcomes were identified, grouped under two categories: (i) involvement outcomes: communication (mean difference ranged from 6.39 to 8.83), decision-making (mean difference ranged from -0.8 to 5.85), satisfaction (mean difference ranged from 0.15 to 2.48); and (ii) health outcomes: family trauma (mean difference ranged from -7.12 to 0.9), family well-being (mean difference ranged from -0.7 to -4), patient outcomes (relative risk ranged from 1.27 to 4.91). The findings from the qualitative studies were thematically analysed to identify features of the interventions that participants perceived to influence effectiveness. Synthesised into five overarching categories (practicality, development, interaction, reflexivity and bridging), these can serve as principles to inform the future design and development of more refined family member involvement interventions.ConclusionsFuture interventions should be developed with much closer family member input and designed by considering the key features we identified. We call for future interventions to be multilayered and allow for a greater or lesser level, and different kinds, of involvement for family members. Choice of intervention should be informed by a baseline diagnostic of family members' needs, readiness and preparedness for involvement.Prospero registrationCRD42018086325.
| S-EPMC8031009 | biostudies-literature
Project description:In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia.
| S-EPMC10570071 | biostudies-literature
Project description:Malnutrition is common in heart failure (HF), and it is associated with higher hospital readmission and mortality rates. This review aims to answer the question whether nutritional interventions aiming to increase protein and energy intake are effective at improving outcomes for patients with HF who are malnourished or at risk of malnutrition or cachexia. Systematic searches of four databases (Medline, Embase, CINAHL and Cochrane Central Register of Controlled Trials (CENTRAL)) were conducted on 21 June 2019. Randomized controlled trials (RCTs) or other interventional studies using protein or energy supplementation for adult HF patients who are malnourished or at risk of malnutrition or cachexia were included. Two independent reviewers assessed study eligibility and risk of bias. Five studies (four RCTs and one pilot RCT) met the inclusion criteria. The majority of studies were small and of limited quality. The pooled weighted mean difference (WMD) for body weight showed a benefit from the nutritional intervention by 3.83 kg (95% confidence interval (CI) 0.17 to 7.50, P = 0.04) from three trials with no significant benefit for triceps skinfold thickness (WMD = - 2.14 mm, 95% CI - 9.07 to 4.79, P = 0.55) from two trials. The combination of personalized nutrition intervention with conventional treatment led to a decrease in all-cause mortality and hospital readmission in one study. Findings of this review suggest that nutritional interventions could potentially improve outcomes in HF patients who are malnourished or at risk of malnutrition. However, the strength of the evidence is poor, and more robust studies with a larger number of participants are needed.
| S-EPMC8310486 | biostudies-literature
Project description:"Engagement" with digital behaviour change interventions (DBCIs) is considered important for their effectiveness. Evaluating engagement is therefore a priority; however, a shared understanding of how to usefully conceptualise engagement is lacking. This review aimed to synthesise literature on engagement to identify key conceptualisations and to develop an integrative conceptual framework involving potential direct and indirect influences on engagement and relationships between engagement and intervention effectiveness. Four electronic databases (Ovid MEDLINE, PsycINFO, ISI Web of Knowledge, ScienceDirect) were searched in November 2015. We identified 117 articles that met the inclusion criteria: studies employing experimental or non-experimental designs with adult participants explicitly or implicitly referring to engagement with DBCIs, digital games or technology. Data were synthesised using principles from critical interpretive synthesis. Engagement with DBCIs is conceptualised in terms of both experiential and behavioural aspects. A conceptual framework is proposed in which engagement with a DBCI is influenced by the DBCI itself (content and delivery), the context (the setting in which the DBCI is used and the population using it) and the behaviour that the DBCI is targeting. The context and "mechanisms of action" may moderate the influence of the DBCI on engagement. Engagement, in turn, moderates the influence of the DBCI on those mechanisms of action. In the research literature, engagement with DBCIs has been conceptualised in terms of both experience and behaviour and sits within a complex system involving the DBCI, the context of use, the mechanisms of action of the DBCI and the target behaviour.
| S-EPMC5526809 | biostudies-other