Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials

Abstract Background Cachexia is a multisystem syndrome characterized by weight loss, anorexia, loss of muscle mass, systemic inflammation, insulin resistance, and functional decline. Management of cachexia involves addressing multiple underlying biological mechanisms. Previous review on pharmacological management of cancer cachexia identified progestins and corticosteroids as effective agents for treatment of cachexia. However, to date no consensus exists on a single effective or standard treatment for management of cachexia. The aim of this systematic review is to determine the effectiveness of pharmacological treatments used to manage cachexia among adult cancer patients. Methods We performed literature searches of PubMed (NLM), Embase (Ovid), and Medline(Ovid) to identify clinical trials focused on pharmacological management of cancer cachexia among adult cancer patients from 2004 to 2018. Three reviewers screened a random selection of abstracts to measure for interrater reliability. After this step, each screener screened two-thirds of all abstracts and 177 studies were identified for full text review. The primary outcome was impact of pharmacological management on change in either weight or lean body mass in cancer patients. Results We identified 19 articles (representing 20 RCTs) that focused on pharmacological management of cancer cachexia. Agents showing promising results included Anamorelin and Enobosarm. Anamorelin at 50 or 100 mg per day for 12 weeks showed a consistent benefit across all studies and resulted in significant improvement in weight as compared to baseline among cancer patients. Enobosarm at 1 and 3 mg per day was also effective in improving lean body mass and QOL symptoms among advancer stage cancer patients. Finally, use of combination agents provide evidence for targeting multiple pathways underlying cachexia mechanism to achieve maximum benefit. No agents showed functional improvement in cancer patients. Conclusion Anamorelin as a single agent shows promising results in improving cachexia related weight loss among cancer patients. Further research on combination therapies may be helpful to address critical gaps in cachexia management

Effects of Music Participation for Mild Cognitive Impairment and Dementia: A Systematic Review and Meta‐analysis

Objectives: To examine randomized controlled trials with active music‐making interventions, in which older adults with probable mild cognitive impairment (MCI) or dementia physically participate in music, and their effects on cognitive functioning, emotional well‐being, and social engagement. Participating in music‐making is engaging and has shown diverse benefits. Additionally, this review categorized the music activities of each intervention. Design: Systematic review and meta‐analysis. Setting: Long‐term care facilities, day centers, specialty outpatient units, and community. Methods: Published randomized controlled trials of active music‐making interventions to support older adults with probable MCI or dementia were identified (to March 15, 2021) using searches on Medline (Ovid), APA PsycInfo (Ovid), CINAHL (Ebsco), and Embase (Elsevier). The outcomes were cognitive functioning, emotional well‐being, and social engagement, including self‐ and clinician‐reported measures such as the Mini‐Mental State Examination, Positive and Negative Affect Schedule, and the Beck Depression Inventory. Studies were critically appraised and studies with similar methodology were meta‐analyzed. Participants: Older adults with probable MCI and mild or moderate dementia. Results: A total of 21 studies with 1472 participants were analyzed for potential effect sizes and intervention activities. Of the 21 studies, nine studies recruiting a total of 495 participants were used to produce a random‐effects meta‐analytic model for cognitive functioning. Music showed a small, positive effect on cognitive functioning; the combined standard mean difference for the experimental and control group was 0.30 (95% confidence interval [CI] 0.10, 0.51). There was low study heterogeneity, with an I² of 24% (p = 0.004). Individual studies for emotional well‐being in terms of quality of life and mood showed positive effect sizes, d = 1.08 and d = 1.74, respectively. [Corrections added on July 8, 2021, after first online publication: The preceding sentences were revised from: \u27… control group was 0.31 (95% confidence interval [CI] 0.10,0.52). There was low study heterogeneity, with an I2 of 25% (p = 0.004).\u27] Conclusion: This review shows that music‐making has a small but statistically significant effect on cognitive functioning for older adults with probable MCI or dementia. Future music interventions can benefit from rigorous intervention protocols that isolate specific activities. (PsycInfo Database Record (c) 2021 APA, all rights reserved

Patient-report and caregiver-report measures of rehabilitation service use following acquired brain injury: a systematic review

Objective To review patient-report/caregiver-report measures of rehabilitation service use following acquired brain injury (ABI).Data sources Medline, APA PsycINFO, Embase and CINAHL were searched on November 2021 and November 2022. Authors were contacted if measures were not included in manuscripts/appendices.Study selection Included articles were empirical research or a research protocol, available in English and described measures of patient report/caregiver report of rehabilitation service use post-ABI via quantitative or qualitative methods. Two reviewers independently screened 5290 records using DistillerSR. Discrepancies were resolved by team adjudication.Data extraction Data extraction was piloted with high levels of agreement (k=.94). Data were extracted by a single member with team meetings to seek guidance as needed. Data included administration characteristics (reporter, mode of administration, recall period), psychometric evidence and dimensions assessed (types of services, setting, frequency, duration, intensity, qualitative aspects).Data synthesis One hundred and fifty-two measures were identified from 85 quantitative, 56 qualitative and 3 psychometric studies. Psychometric properties were reported for four measures, all of which focused on satisfaction. Most measures inquired about the type of rehabilitation services used, with more than half assessing functional (eg, physical therapy) and behavioural health rehabilitation services, but fewer than half assessing community and academic reintegration (eg, special education, vocational rehabilitation) or cognitive (eg, neuropsychology) services. Fewer than half assessed qualitative aspects (eg, satisfaction). Recall periods ranged from 1 month to ‘since the ABI event’ or focused on current use. Of measures that could be accessed (n=71), many included a limited checklist of types of services used. Very few measures assessed setting, frequency, intensity or duration.Conclusions Despite widespread interest, the vast majority of measures have not been validated and are limited in scope. Use of gold-standard psychometric methods to develop and validate a comprehensive patient-report/caregiver-report measure of rehabilitation service use would have wide-ranging implications for improving rehabilitation research in ABI

Clinical, Pathological, and Molecular Characteristics of CpG Island Methylator Phenotype in Colorectal Cancer: A Systematic Review and Meta-analysis

BACKGROUND: CpG island methylator phenotype (CIMP) tumors, comprising 20% of colorectal cancers, are associated with female sex, age, right-sided location, and BRAF mutations. However, other factors potentially associated with CIMP have not been robustly examined. This meta-analysis provides a comprehensive assessment of the clinical, pathologic, and molecular characteristics that define CIMP tumors. METHODS: We conducted a comprehensive search of the literature from January 1999 through April 2018 and identified 122 articles, on which comprehensive data abstraction was performed on the clinical, pathologic, molecular, and mutational characteristics of CIMP subgroups, classified based on the extent of DNA methylation of tumor suppressor genes assessed using a variety of laboratory methods. Associations of CIMP with outcome parameters were estimated using pooled odds ratio or standardized mean differences using random-effects model. RESULTS: We confirmed prior associations including female sex, older age, right-sided tumor location, poor differentiation, and microsatellite instability. In addition to the recognized association with BRAF mutations, CIMP was also associated with PIK3CA mutations and lack of mutations in KRAS and TP53. Evidence of an activated immune response was seen with high rates of tumor-infiltrating lymphocytes (but not peritumoral lymphocytes), Crohn-like infiltrates, and infiltration with Fusobacterium nucleatum bacteria. Additionally, CIMP tumors were associated with advance T-stage and presence of perineural and lymphovascular invasion. CONCLUSION: The meta-analysis highlights key features distinguishing CIMP in colorectal cancer, including molecular characteristics of an active immune response. Improved understanding of this unique molecular subtype of colorectal cancer may provide insights into prevention and treatment