A taste alteration-related scale assesses megestrol to improve chemotherapy-induced anorexia.

PURPOSE: We evaluated the efficacy of megestrol in improving chemotherapy-related anorexia by analyzing the related scales of taste alteration. METHODS: We conducted the current study on a group of advanced patients with cancer with two or more chemotherapy cycles. The chemotherapy-induced taste alteration scale (CiTAs) scale helped assess the megestrol effects on basic taste perception, aversive taste changes, unpleasant symptoms, and associated concerns. Furthermore, the Short Nutritional Assessment Questionnaire scale (SNAQ) helped measure the impact of megestrol on malnutrition likelihood in patients experiencing chemotherapy-induced anorexia. The World Health Organization Quality of Life (WHOQOL)-BREF Scale was used to evaluate the quality of life of participants, producing scores related to physical health, psychological well-being, environmental factors, and social relationships. RESULTS: The CiTAs scale assessment indicated that administering megestrol significantly enhanced taste perception among advanced patients with cancer undergoing chemotherapy. Notably, the megestrol group patients showed significantly higher Short Nutritional Assessment Questionnaire (SNAQ) scores than the control group. The megestrol group patients also exhibited higher physiological (PHYS) scores than their control group counterparts. However, this distinction was not statistically significant. The study findings indicate that patients who received megestrol demonstrated significantly higher scores in psychological (PSYCH) and environmental(ENVIR) domains than the control group. Furthermore, megestrol administration was associated with significantly elevated SOCIL and ENVIR levels in patients. CONCLUSION: The proficient efficacy evaluation of megestrol in enhancing appetite, mitigating malnutrition likelihood, and improving the quality of life of chemotherapy-induced anorexic patients can be achieved through taste-related scales.

Mirtazapine as Appetite Stimulant in Patients With Non-Small Cell Lung Cancer and Anorexia: A Randomized Clinical Trial.

Importance: Currently there is no standard therapy to improve cancer-related anorexia, hampering survival. Mirtazapine has been suggested as a feasible option in this context. Objectives: To assess the effect of mirtazapine on appetite and energy consumption in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants: This randomized, double-blind, placebo-controlled clinical trial including adults was performed in a tertiary cancer care center from August 2018 to May 2022 with a follow-up of 8 weeks. Overall, 134 patients were screened; 114 were assessed for eligibility and 28 were excluded. Interventions: Patients were randomized in a 1:1 ratio to receive mirtazapine, 15 mg, or placebo for 2 weeks followed by a dose escalation to 30 mg until week 8 or placebo. Both groups received nutritional assessment and dietary advice. Main outcomes and measures: Appetite was assessed by the Anorexia Cachexia Scale and energy intake. Dietary parameters were evaluated at baseline, 4 weeks, and 8 weeks, with a 24-hour dietary recall, and energy quantification based on the Mexican system of nutritional equivalents. Results: A total of 86 patients met the inclusion criteria and were randomized to the placebo (n = 43) or the mirtazapine group (n = 43). The mean (SD) age was 63.5 (11.2) years, 41 were women (57.7%) and had adenocarcinoma, Eastern Cooperative Oncology Group performance status scale score of 1, stage IV NSCLC, and were receiving first-line treatment. Baseline characteristics were similar between groups. There was no difference in appetite scores in patients who received mirtazapine or placebo after 4 and 8 weeks. After 4 weeks, mirtazapine significantly increased energy intake (379.3 kcal; 95% CI, 1382.6-576.1; P < .001) including proteins (22.5 g; 95% CI, 11.5-33.4; P = .001), carbohydrates (43.4 g; 95% CI, 13.1-73.8; P = .006), and fats (13.2 g; 95% CI, 6.0-20.4; P = .006). Fats intake was significantly higher in patients in the mirtazapine group (14.5 g vs 0.7 g; P = .02) after 8 weeks. The mirtazapine group significantly decreased the proportion of patients with sarcopenia (82.8% vs 57.1%, P = .03) at 8 weeks. Patients on mirtazapine tolerated the treatment well, but reported a higher perception of nightmares at 2 weeks based on a 10 cm VAS score (0 [25th-75th percentile, 0-1] vs 0 [25th-75th percentile, 0-0] in the control group; P = .009) but this finding was nonsignificant after 4 and 8 weeks. Conclusion and Relevance: In this randomized clinical trial of patients with advanced NSCLC, there was no difference in appetite scores in all patients who received mirtazapine or placebo, but the mirtazapine group had a significant increase in energy intake through the 4- and 8-week follow-up, mainly in fat intake, which is a better and crucial source of energy. The addition of mirtazapine in the treatment of patients with advanced NSCLC and anorexia may help these patients achieve their energy requirements and improve health-related quality of life, specifically emotional and cognitive functioning. Trial Registration: ClinicalTrials.gov Identifier: NCT04748523.

Addressing cancer anorexia-cachexia in older patients: Potential therapeutic strategies and molecular pathways.

Cancer cachexia (CC) syndrome, a feature of cancer-associated muscle wasting, is particularly pronounced in older patients, and is characterised by decreased energy intake and upregulated skeletal muscle catabolic pathways. To address CC, appetite stimulants, anabolic drugs, cytokine mediators, essential amino acid supplementation, nutritional counselling, cognitive behavioural therapy, and enteral nutrition have been utilised. However, pharmacological treatments that have also shown promising results, such as megestrol acetate, anamorelin, thalidomide, and delta-9-tetrahydrocannabinol, have been associated with gastrointestinal and cardiovascular complications. Emerging evidence on the efficacy of probiotics in modulating gut microbiota also presents a promising adjunct to traditional therapies, potentially enhancing nutritional absorption and systemic inflammation control. Additionally, low-dose olanzapine has demonstrated improved appetite and weight management in older patients undergoing chemotherapy, offering a potential refinement to current therapeutic approaches. This review aims to elucidate the molecular mechanisms underpinning CC, with a particular focus on the role of anorexia in exacerbating muscle wasting, and to propose pharmacological and non-pharmacological strategies to mitigate this syndrome, particularly emphasising the needs of an older demographic. Future research targeting CC should focus on refining appetite-stimulating drugs with fewer side-effects, specifically catering to the needs of older patients, and investigating nutritional factors that can either enhance appetite or minimise suppression of appetite in individuals with CC, especially within this vulnerable group.

Evaluation of the Use of Appetite Stimulants in Pediatric Patients with Cystic Fibrosis.

OBJECTIVE: Poor nutrition in patients with cystic fibrosis (CF) has been associated with lower lung function and increased morbidity and mortality. Conversely, better nutritional status has been associated with improved pulmonary function and fewer CF-associated complications. There is no consensus regarding appetite stimulant therapy in patients with CF (pwCF). The primary objective of this study was to determine if the use of appetite stimulants was associated with weight changes in pediatric pwCF in the ambulatory care setting. METHODS: This was a retrospective study that evaluated 62 pediatric pwCF who received cyproheptadine or mirtazapine for appetite stimulation for at least 6 consecutive months. Weight z scores were collected for each patient at baseline, 3, 6, and 12 months of therapy, if available. RESULTS: Increase in weight z score after 3 months of therapy was statistically significant based on both univariable and multivariable models when evaluating the entire cohort. The adjusted mean difference for change in weight z score was 0.33 ( P < 0.001) from baseline to month 3. There was a statistically significant improvement in pulmonary function after 3 and 6 months of therapy. CONCLUSIONS: Appetite stimulant therapy was associated with improvement in weight z score in the first 3 months of treatment. Appetite stimulant therapy was associated with improvement in pulmonary function in the first 3 months of therapy, which supports the relationship between weight gain and improved pulmonary function in pwCF. These findings suggest that appetite stimulants contribute to weight gain in pediatric pwCF, particularly within the first 3 months of therapy.

A review of the efficacy of appetite stimulating medications in hospitalized adults.

BACKGROUND: The majority of evidence on efficacy of appetite-stimulating medications is limited to specific populations and the outpatient treatment setting. However, hospitalized adults remain at risk for poor appetite and inadequate intake. METHOD: The purpose of this review was to assess recent evidence on the efficacy of dronabinol, megestrol acetate, and mirtazapine (used to stimulate appetite) on promoting change in intake; somatic symptoms, such as appetite and nausea; and weight change during hospital stay. The population was limited to hospitalized adults or adults who demonstrated a need for appetite stimulation during hospitalization. RESULTS: Of the 382 articles screened, four met inclusion criteria (one randomized control trial, two retrospective cohort studies, and one retrospective case series). Based on the studies included, these appetite stimulants have limited efficacy on improving appetite and meal intake. There was no significant change in weight. CONCLUSION: Current data lack standardization, generalizability, and comparability, and higher quality evidence is needed before conclusions can be identified on the efficacy of dronabinol, megestrol acetate, and mirtazapine in the inpatient setting.

Appetite stimulants for people with cystic fibrosis.

BACKGROUND: Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic anorexia attain optimal body mass index (BMI) and nutritional status. However, these may have adverse effects on clinical status. This is an updated version of the original review. OBJECTIVES: To systematically search for and evaluate the evidence on the beneficial effects of appetite stimulants in the management of cystic fibrosis-related anorexia and synthesise reports of any side effects. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register and online trials registries; handsearched reference lists; and contacted local and international experts to identify relevant trials. Last search of the Cystic Fibrosis Trials Register: 23 May 2022. Last search of online trial registries: 10 May 2022. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of appetite stimulants compared to placebo, control, no treatment or different appetite stimulants, or to the same appetite stimulants at different doses or regimens for at least one month in adults and children with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Review authors independently extracted data and assessed risk of bias of the included trials. We used the GRADE approach to assess the certainty of the evidence and performed meta-analyses. MAIN RESULTS: We included four trials (70 participants) comparing appetite stimulants (cyproheptadine hydrochloride and megestrol acetate) to placebo; the numbers of adults or children within each trial were not always reported. We assessed the certainty of evidence as low due to the small number of participants, incomplete or selective outcome reporting, and unclear risk of selection bias.  Regarding our primary outcomes, a meta-analysis of two trials (42 participants) showed that appetite stimulants may produce a larger increase in weight (kg) at three months (mean difference (MD) 1.25 kg, 95% confidence interval (Cl) 0.45 to 2.05), and one trial (17 participants) showed a similar result at six months (MD 3.80 kg, 95% CI 1.27 to 6.33) (both low-certainty evidence). Results also showed that weight z score may increase with appetite stimulants compared to placebo at three months (MD 0.61, 95% CI 0.29 to 0.93; 3 studies; 40 participants; P < 0.001) and at six months (MD 0.74, 95% CI 0.26 to 1.22; 1 trial; 17 participants). There was no evidence of a difference in effect between cyproheptadine hydrochloride and megestrol acetate for either outcome.   Only one trial (25 participants) reported analysable data for body composition (BMI), with results favouring cyproheptadine hydrochloride compared to placebo; a further trial (16 participants) narratively agreed with this result. All four trials reported on lung function at durations ranging from two to nine months. Considering analysable data, two trials (42 participants) found that appetite stimulants may make little or no difference in forced expiratory volume at one second (FEV1) % predicted at three months, and one trial (17 participants) found similar results at six months. Two further three-month trials narratively agreed with these results. Limited information was reported for secondary outcomes. Two trials (23 participants) reported results showing that appetite stimulants may increase appetite compared to placebo at three months (odds ratio 45.25, 95% CI 3.57 to 573.33; low-certainty evidence).  Only one study reported on quality of life, finding that cyproheptadine reduced fatigue in two participants compared with none with placebo. One study (25 participants) found no difference in energy intake between appetite stimulant or placebo at three months. Insufficient reporting of adverse effects prevented a full determination of their impact. Two studies (33 participants) narratively reported similar requirements for additional antibiotics between appetite stimulants and placebo at three months.  AUTHORS' CONCLUSIONS: At six months in adults and children, appetite stimulants improved only two of the outcomes of this review: weight (or weight z score) and subjectively reported appetite. Insufficient reporting of side effects prevented a full determination of their impact. Whilst the data may suggest the potential use of appetite stimulants in treating anorexia in adults and children with cystic fibrosis, this is based upon low-certainty evidence from a small number of trials, therefore firm conclusions cannot be drawn. Clinicians need to be aware of the potential adverse effects of appetite stimulants and actively monitor any individuals prescribed these medications accordingly. Research is required to determine meaningful surrogate measures for appetite and to define what constitutes quality weight gain. Future trials of appetite stimulants should use a validated measure of symptoms including a disease-specific instrument for measuring poor appetite. This review highlights the need for multicentred, adequately powered, and well-designed trials to evaluate agents to safely increase appetite in people with cystic fibrosis and to establish the optimal mode of treatment.

Medical cannabis: Critical points for clinical application / Cannabis medicinal: puntos críticos para su uso clínico.

Since ancient times cannabis has been used for recreational and medicinal purposes. It is a significant source of chemical compounds, most of them called phytocannabinoids. These compounds have several physiological effects and produce their effects primarily by binding to endogenous cannabinoid receptors such as CB1 and CB2, among others. Cannabis has potential therapeutic properties and its preparations have been used as traditional remedies to treat pain and emesis. Synthetic cannabinoids are used clinically as analgesics, antispastics, antiemetics, and appetite stimulants. Significant cannabis toxicity is rare in adults; however, it can produce countless acute and chronic side effects. The quality of the evidence in this field is limited by the short duration of the trials, poor sample sizes, lack of a control group, and the existence of bias in most of the reviewed studies. Therefore, a larger number of studies with better methodological quality is required to support the safe use of this therapy. The decision to include cannabinoids as a treatment for any of the conditions described will depend on the evidence, the use of previous therapies, and the type of patient.

El cannabis se ha utilizado desde la antigüedad con fines recreativos y medicinales. Es una fuente muy rica de compuestos químicos, la mayoría denominados fitocannabinoides, que tienen una variedad de efectos fisiológicos, principalmente por su unión a receptores cannabinoides endógenos como el CB1 y CB2, entre otros. El cannabis tiene propiedades terapéuticas potenciales y sus preparaciones se han utilizado como remedios tradicionales para tratar el dolor y la emesis. Los cannabinoides sintéticos se utilizan clínicamente como analgésicos, antiespasmódico, antieméticos y estimulantes del apetito. La toxicidad significativa del cannabis es poco común en los adultos, sin embargo, puede tener múltiples efectos adversos agudos y crónicos. La calidad de la evidencia en este campo se ha visto limitada por la corta duración de los estudios, los reducidos tamaños de las muestras, la falta de grupos de control y la existencia de sesgos en la mayoría de los estudios revisados. En este contexto, son necesarios más estudios de mejor calidad metodológica para apoyar el uso seguro de esta terapia en otras enfermedades. La decisión de incorporar los cannabinoides como terapia en alguna de las condiciones descritas depende de la evidencia, el uso de terapias previas y el tipo de paciente.

The economic burden of HIV-associated wasting in the era of modern antiretroviral therapy.

BACKGROUND: HIV-associated wasting (HIVAW) is associated with increased morbidity and mortality in people living with HIV (PWH). Evaluating health care resource utilization and cost predictors of HIVAW is important in understanding the overall economic burden of the disease. OBJECTIVE: To evaluate the economic burden and cost predictors associated with HIVAW. METHODS: This analysis of the IBM MarketScan Commercial, Medicare Supplemental, and Medicaid databases included members with a claim for HIV (using International Classification of Diseases, Ninth Revision and Tenth Revision, Clinical Modification codes) between July 2012 and September 2018, with the HIV index date defined as the first HIV diagnosis claim in the dataset. PWH were excluded if they were aged less than 18 years, had any malignancy claim, or had less than 6 months of enrollment data pre-HIV or post-HIV index date. Members were defined as having HIVAW using an algorithm of claims for weight loss-related diagnoses, appetite stimulant or nontestosterone anabolic agents, or enteral/parenteral nutrition at any time post-HIV index. Taking antiretroviral therapy (ART) was defined as having at least 1 pharmacy claim of any ART 12 months post-HIV index. Total all-cause costs were calculated as the sum of payments for hospitalizations, emergency department visits, outpatient visits, and pharmacy use. A multivariate generalized linear model with log-link and γ distribution was used to estimate the impact of HIVAW predictors of total all-cause costs. RESULTS: Among 42,587 members with HIV included in the study (64.6% male; mean age: 44 years; 67.5% insured with Medicaid; and 63.9% taking ART), the overall prevalence of HIVAW was 18.3% during the study period. HIVAW prevalence was 17.9% for those taking ART and 19.1% for those not taking ART. Prevalence by payer type was 7.5% for Commercial ± Medicare Supplemental and 23.5% for Medicaid. Members with HIVAW had more comorbidities and opportunistic infections compared with members without HIVAW. Members with HIVAW were also more than twice as likely to be hospitalized (71.1% vs 32.1%) and had 5 times the number of hospitalizations (1.0 vs 0.2) and twice the number of emergency department visits (3.0 vs 1.3) per year post-index compared with members without HIVAW (P < 0.01). HIVAW was associated with 1.3-times-higher mean annualized total all-cause costs per member (95% CI = 1.26-1.36). CONCLUSIONS: HIVAW remains prevalent despite advances in ART and is associated with additional health care resource utilization and costs. Further research is needed to better understand the relationship between HIVAW and comorbidity burden and ART utilization and payer types. DISCLOSURES: This study was sponsored by EMD Serono, Inc., Rockland, MA, USA (CrossRef Funder ID: 10.13039/100004755). Dr Siddiqui has received consulting and speaking fees from AbbVie, BioFire, Cumberland, EMD Serono, Inc., Rockland, MA, USA, and Merck. Dr Samuel, Ms Hayward, Ms Wirka, Dr Phillips, and Dr Harbour are employees of EMD Serono, Inc., Rockland, MA, USA. Drs Deering and Harshaw are employees of EPI-Q, Inc., which received payment from EMD Serono, Inc., Rockland, MA, USA, for the development and execution of this study.

Appetite stimulants for patients with cancer: current evidence for clinical practice.

The incidence of neoplastic diseases has increased worldwide, with an estimated global burden of 19.3 million incident cases and 10 million deaths in 2020-a considerable increase compared with 9.6 million deaths in 2018. One of the most prevalent problems faced by patients with cancer and their physicians is malnutrition. It is estimated that patients with cancer have important nutritional alterations in 25% to 70% of cases, which directly affects many spheres of patient care and well-being, including quality of life, treatment toxicity, and survival outcomes. Despite the overwhelming need to address this pressing issue, current evidence in terms of pharmacologic interventions for cancer-related anorexia remains inconclusive, and there is no current standard of care for patients with cancer-related anorexia. Nonetheless, international guidelines recommend promoting anabolism through nutritional, physical, and pharmacologic therapies. In this review, the available information is summarized regarding pharmacologic therapies to treat cancer-related anorexia and findings are highlighted from a clinical stance.

The Effect of Cannabis-Based Medicine in the Treatment of Cachexia: A Systematic Review and Meta-Analysis.

Background: Cachexia is a prevalent condition associated with underlying chronic disease. Wasting of skeletal muscle and adipose tissue loss in cachectic patients is associated with higher rates of disability, reduced quality of life (QoL), and worse prognosis. There is a large unmet need to develop strategies to treat cachexia as there are currently no standardized guidelines in the management of cachexia. Activation of endogenous cannabinoid receptors, through exogenous cannabinoids, has demonstrated potential in increasing appetite, reducing catabolism, and has shown anti-inflammatory properties. Since no single pharmacological agent is currently recommended for use in cachexia, the potential of cannabinoids as an appetite stimulant warrants further research and assessment of current evidence. Objective: This review aims to evaluate the evidence for the efficacy of cannabis-based medicinal products, against placebo and other active treatments, in anorexia-cachexia syndrome in improving appetite, weight, and QoL. Methods: A literature search of the Medline, EMBASE, CENTRAL, and the Web of Science Core Collection, for articles published up to February 2020, was conducted. All randomized controlled trials comparing the use of cannabis-based medicine versus placebo/active treatments for patients with cachexia were screened. The quality of evidence in included studies was assessed using the GRADE framework and any risk of bias was judged using the Cochrane risk of bias tool. Results: A total of five studies, encompassing 934 participants, were found to be eligible. The pooled group effect size for change in appetite was -1.79 (95% confidence interval: -3.77 to 0.19) favoring the control group (p=0.08). Additionally, no significant difference for weight change or change in QoL for cannabinoids versus placebo/other treatment was observed. The quality of evidence for all five studies was assessed to be low. Conclusion: There is a lack of high-quality evidence to recommend the use of cannabinoids in the treatment of cachexia. Given the limited available pharmacological options for cachexia and the potential for cannabinoids to increase appetite and alter the immune system, further research is needed before clinical recommendations on the pharmacological management of cachexia can be made.

Appetite Stimulants for Treatment of Protein Energy Wasting of Chronic Kidney Disease.

Nutritional and metabolic abnormalities, or protein energy wasting, is a common complication of chronic kidney disease, leading to significant morbidity and mortality. The cause of these abnormalities is multifactorial, and therefore, difficult to treat. The International Society of Renal Nutrition and Metabolism suggests appetite stimulants, including megestrol, dronabinol, mirtazapine, and cyproheptadine, as adjunctive treatment options in addition to parenteral or oral nutritional supplementation. This article reviews the evidence for use of these drugs as appetite stimulants and discusses their use in patients with chronic kidney disease.

[Avoidant/Restrictive Food Intake Disorder (ARFID): What the pediatrician should know]. / Trastorno de Evitación y Restricción de la Ingesta de Alimentos (ARFID): Lo que el pediatra debe saber.

Feeding problems during childhood have been described over time by various authors. In 2013, Avoi dant/Restrictive Food Intake Disorder (ARFID) was included in the Diagnostic and Statistical Ma nual of Mental Disorders, 5th Edition (DSM-5), as a new diagnosis within the Feeding and Eating di sorders, to describe a group of patients with avoidant or restrictive eating behaviors unrelated to body image disorder or weight loss desire. ARFID may appear as significant weight loss and/or nutritional deficiency and/or a marked interference in psychosocial functioning. There are three forms of pre sentation, which can co-occur or occur independently. The first one includes children with sensory aversions (selective), who reject certain foods due to their taste, texture, smell, or shape; the second one includes those children with poor appetite or limited intake (limited intake); and the third one includes those children who reject certain foods or stop eating as a result of a traumatic event (aversi- ve). Due to the recent incorporation of ARFID into the DSM-5, there is a lack of information regar ding its treatment. The purpose of this review is to clarify diagnostic criteria and to describe targeted management and treatment interventions with a multidisciplinary approach, without deepening on the treatment of organic medical causes.

Cancer cachexia: molecular mechanism and pharmacological management.

Cancer cachexia often occurs in malignant tumors and is a multifactorial and complex symptom characterized by wasting of skeletal muscle and adipose tissue, resulting in weight loss, poor life quality and shorter survival. The pathogenic mechanism of cancer cachexia is complex, involving a variety of molecular substrates and signal pathways. Advancements in understanding the molecular mechanisms of cancer cachexia have provided a platform for the development of new targeted therapies. Although recent outcomes of early-phase trials have showed that several drugs presented an ideal curative effect, monotherapy cannot be entirely satisfactory in the treatment of cachexia-associated symptoms due to its complex and multifactorial pathogenesis. Therefore, the lack of definitive therapeutic strategies for cancer cachexia emphasizes the need to develop a better understanding of the underlying mechanisms. Increasing evidences show that the progression of cachexia is associated with metabolic alternations, which mainly include excessive energy expenditure, increased proteolysis and mitochondrial dysfunction. In this review, we provided an overview of the key mechanisms of cancer cachexia, with a major focus on muscle atrophy, adipose tissue wasting, anorexia and fatigue and updated the latest progress of pharmacological management of cancer cachexia, thereby further advancing the interventions that can counteract cancer cachexia.

Cyproheptadine as an appetite stimulant in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multi-organ genetically inherited disease that leads to progressive lung disease and nutrient malabsorption. The aim of this study was to assess the effectiveness of cyproheptadine (CH) (Periactin®) as an appetite stimulant on improving the nutrition status of paediatric patients with CF. METHODS: We conducted a retrospective study of 15 patients with a suboptimal nutrition status prescribed CH for ≥12 months from 2013 to 2018. Change in Body Mass Index (BMI) z-score and lung function before vs. after treatment with CH were measured as well as dose-response relationship. RESULTS: The mean change in BMI z-score over 12 months of treatment with CH was +0.91 compared to -0.52 in the previous 12 months (p∗∗∗ = 0.0002). There was also a trend towards an improvement in lung function over the 12 months of CH treatment compared to the 12 months prior (+2.79 vs -6.2% (p = 0.07)). No dose-response relationship was observed. CONCLUSION: These results suggest that CH is effective at improving the nutrition status of paediatric CF patients with suboptimal nutrition.

A randomised, double blind, placebo-controlled trial of megestrol acetate or dexamethasone in treating symptomatic anorexia in people with advanced cancer.

This multi-site, double blind, parallel arm, fixed dose, randomised placebo controlled phase III study compared megestrol acetate 480 mg/day with dexamethasone 4 mg/day for their net effects on appetite in people with cancer anorexia. Patients with advanced cancer and anorexia for ≥ 2 weeks with a score ≤ 4 (0-10 numeric rating scale (NRS) 0 = no appetite, 10 = best possible appetite) were recruited. Participants received megestrol 480 mg or dexamethasone 4 mg or placebo daily for up to 4 weeks. Primary outcomes were at day 7. Responders were defined as having a ≥ 25% improvement in NRS over baseline. There were 190 people randomised (megestrol acetate n = 61; dexamethasone n = 67, placebo n = 62). At week 1 (primary endpoint), 79·3% in the megestrol group, 65·5% in the dexamethasone group and 58·5% in the placebo group (p = 0.067) were responders. No differences in performance status or quality of life were reported. Treatment emergent adverse events were frequent (90·4% of participants), and included altered mood and insomnia. Hyperglycemia and deep vein thromboses were more frequent when on dexamethasone than the other two arms. There was no difference in groups between the three arms, with no benefit seen over placebo with anorexia improving in all arms.Trail registration: The trial was registered on 19/08/2008 with the Australian New Zealand Clinical Trials Registry (ACTRN12608000405314).

Randomised placebo-controlled cross-over study examining the role of anamorelin in mesothelioma (The ANTHEM study): rationale and protocol.

INTRODUCTION: Cachexia is common in malignant mesothelioma (MM); half of patients have malnutrition and low skeletal muscle mass. Malnourished patients have worse quality of life (QoL). Weight loss is strongly associated with poor survival. Anamorelin is an oral ghrelin receptor agonist that improves appetite, body weight and QoL in advanced cancer. The aim of this study is to examine the efficacy of anamorelin in improving appendicular skeletal muscle mass (ASM) and patient-reported outcomes in patients with MM with cachexia. METHODS AND ANALYSIS: A single-centre, phase II, randomised, placebo-controlled cross-over pilot study with 28-day treatment periods and 3-day washout. Forty patients will be randomised. Primary outcome is change in ASM relative to height measured by dual energy X-ray absorptiometry at end of period 1. Secondary outcomes include cancer-specific and cachexia-related QoL, objective physical activity, dietary intake and adverse events. Eligible patients will have confirmed MM, Eastern Cooperative Oncology Group 0-2, expected survival >3 months and cachexia (defined as >5% weight loss in 6 months or body mass index <20 kg/m2 with weight loss >2%). ETHICS AND DISSEMINATION: Ethical approval has been granted. Results will be reported in peer-reviewed publications. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (U1111-1240-6828).

Advances in cancer cachexia: Intersection between affected organs, mediators, and pharmacological interventions.

Advanced cancer patients exhibit cachexia, a condition characterized by a significant reduction in the body weight predominantly from loss of skeletal muscle and adipose tissue. Cachexia is one of the major causes of morbidity and mortality in cancer patients. Decreased food intake and multi-organ energy imbalance in cancer patients worsen the cachexia syndrome. Cachectic cancer patients have a low tolerance for chemo- and radiation therapies and also have a reduced quality of life. The presence of tumors and the current treatment options for cancer further exacerbate the cachexia condition, which remains an unmet medical need. The onset of cachexia involves crosstalk between different organs leading to muscle wasting. Recent advancements in understanding the molecular mechanisms of skeletal muscle atrophy/hypertrophy and adipose tissue wasting/browning provide a platform for the development of new targeted therapies. Therefore, a better understanding of this multifactorial disorder will help to improve the quality of life of cachectic patients. In this review, we summarize the metabolic mediators of cachexia, their molecular functions, affected organs especially with respect to muscle atrophy and adipose browning and then discuss advanced therapeutic approaches to cancer cachexia.

Assessment of compounded transdermal mirtazapine as an appetite stimulant in cats with chronic kidney disease.

OBJECTIVES: The aim of this study was to assess the appetite stimulation properties of compounded transdermal mirtazapine (CTM) in cats with chronic kidney disease (CKD). METHODS: Two sequential double-blind placebo-controlled crossover prospective studies were performed in client-owned cats with stable stage 2 or 3 CKD and a history of decreased appetite. In the first study nine CKD cats were randomized to receive 3.75 mg/0.1 ml CTM gel or placebo on the inner pinna every other day for 3 weeks, then, after a 4 day washout period, the cats were crossed over to the alternate 3 week treatment. In a second study, 10 CKD cats were randomized to receive 1.88 mg/0.1 ml CTM or placebo on the same schedule. Physical examination and serum biochemistry were performed before and after each treatment period, and owners kept daily logs of appetite, activity and eating behaviors. Mirtazapine concentrations in CTM gels and steady-state mirtazapine serum concentrations were measured using liquid chromatography/tandem mass spectrometry. RESULTS: Administration of both 3.75 mg and 1.88 mg CTM resulted in a statistically significant increase in weight (P = 0.002 for both), increase in appetite (P = 0.01 and P = 0.005, respectively), and increase in rate of food consumption (P = 0.03 and P = 0.008, respectively). No significant difference in activity or vocalization was seen at either dose; however, individual cats experienced excessive meowing. Median weight increase for the 3.75 mg arm was 0.22 kg (range 0.04-0.44 kg), while median weight increase for the 1.88 mg arm was 0.26 kg (range -0.25 to 0.5 kg). Improvement in body condition score was seen in 5/9 cats in the 3.75 mg arm (P = 0.04) and 6/10 cats in the 1.88 mg arm (P = 0.004). CONCLUSIONS AND RELEVANCE: CTM increased appetite and resulted in weight gain in CKD cats despite significant inconsistencies in compounding, and may benefit cats in countries where an approved product is not available.

A Functional Approach to Feeding Difficulties in Children.

PURPOSE OF REVIEW: This review provides an approach for resolving a variety of feeding difficulties in children, ranging from normal eating behavior that is misperceived as a problem to substantial feeding disorders. RECENT FINDINGS: Criteria to identify pediatric feeding disorders have been thoroughly addressed in the newly established designations of avoidant restrictive food intake disorder (ARFID) and pediatric feeding disorder (PFD). These diagnostic criteria improve the accuracy of identifying, classifying, and managing significant feeding disorders in young children. While recent definitions of feeding difficulties are particularly appropriate in multidisciplinary settings, in this paper, we advocate for a progressive approach of managing feeding problems in all clinical settings. It begins by identifying red flags indicative of serious threats to the child, screening for oral motor dysfunction, stabilizing nutrient intake, and eliminating aversive feeding practices. The next step, if eating behavior does not improve, involves strategies that target specific eating behaviors and parental feeding styles. In severe or resistant cases, referral to specialists or interdisciplinary feeding teams is advised.

The effects of megestrol acetate on nutrition, inflammation and quality of life in elderly haemodialysis patients.

PURPOSE: Malnutrition, inflammation and poor quality of life are prevalent among elderly haemodialysis patients. Megestrol acetate (MA) is a synthetic progestin that is widely used to increase appetite and weight in various clinical settings. MA has been indicated to be effective in improving quality of life in patients with cancers. The aim of the present study was to evaluate the efficacy and safety of MA in treating malnourished elderly haemodialysis patients. METHODS: A randomized controlled study involving 46 hypoalbuminemia haemodialysis patients aged 70 years or older was conducted. The patients in MA-treated group (n = 23) took 160 mg of MA daily, while those in control group (n = 23) were enrolled without any intervention. Anthropometric parameters and laboratory results, including height, dry weight, body mass index, and modified subjective global assessment score as well as serum albumin, triglyceride, total cholesterol, hsCRP, IL-1b and IL-6 concentrations were measured in all patients before and after the intervention. Health-related quality of life was also evaluated using the KDQOL-SF 1.3. RESULTS: In the MA-treated group, a total of 18 patients finished the therapy over a 3-month period. Appetite was reported as improved by 15 patients, and a statistically significant increase was observed in dry weight (53.36 ± 6.15 vs. 54.24 ± 6.32, P < 0.01) and serum albumin concentration (29.05 ± 3.91 vs. 37.67 ± 4.88, P < 0.01) in the MA-treated group compared to those of the control group. The quality of life in both the physical domain (46.73 ± 18.17 vs. 63.37 ± 22.35, P < 0.01) and the mental domain (50.28 ± 20.36 vs. 68.02 ± 25.48, P < 0.01) was also improved in the same group. There was no significant change in the inflammatory marker concentrations after the intervention. No serious or unexpected adverse events were observed except that one patient who withdrew due to excessive fluid gain between haemodialysis sessions. CONCLUSION: Our data suggest that MA can be effective in improving nutritional status and quality of life by increasing appetite in elderly haemodialysis patients with acceptable side effects; however, MA might not ameliorate inflammation.