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.

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.

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.

The effect of oral nutrition supplements and appetite stimulants on weight status among pediatric cancer patients: A systematic review.

The objective of this study was to identify the use and impact of oral nutrition supplements (ONSs) and appetite stimulants on weight status among pediatric patients diagnosed with malignancy. We performed a literature search of trials using Medline PubMed, CINAHL, Web of Science Core Collection, Scopus, and Cochrane Database of Systematic Reviews and included all prospective studies except review articles and case-reports/series that assessed ONSs or appetite stimulants among patients (0-20 years old) diagnosed with a pediatric malignancy. Databases were searched through May 17, 2022. There were six trials included with three studies related to ONS and the remaining on appetite stimulants. No studies that compared both ONS and appetite stimulants were found. To assess quality, we used the Risk of Bias in Nonrandomized Studies of Interventions and the Revised Cochrane Risk of Bias Tool for Randomized Trials depending on the study design. The studies all had pediatric patients diagnosed with a variety of malignancy types. All studies demonstrated improvement of weight status in the treatment group across various malignancy types. However, none of the studies addressed nutrition intakes outside of ONS consumption, compliance to ONSs, or frequency of ONS use. Despite the short durations (3-6 months) and significant differences in the timing of intervention initiation (ONS or appetite stimulants), these treatment modalities can improve weight status. Further research is needed to identify the best intervention for improving weight status.

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.

Bedaquiline Effect on QT Interval of Drugs-Resistant Tuberculosis Patients: Real World Data.

BACKGROUND: Bedaquiline (BDQ) is effective as part of treatment regimen for drug-resistant tuberculosis (DR-TB), but the cardiac safety profile of BDQ is not fully elucidated. This study aimed to analyse the cardiac safety of BDQ by examining its effect on the QT interval of DR-TB patients. METHODS: This is a retrospective study cohort conducted in two DR-TB referral hospitals in Indonesia. The QT interval before and after therapy using BDQ was measured manually and corrected using the Fridericia formula (QTcF). The QT interval profile was analysed over time during BDQ treatment. RESULTS: A total of 105 subjects participated in the study. The maximum mean difference (standard deviation) of QTcF after treatment with the baseline (∆QTcF) is 34,06 (52,92) ms after three months of therapy. During BDQ treatment, clinically significant QTcF prolongations was observed in 37.1% subjects with neither arrhythmia nor any other adverse cardiac event occurred. The interval QT prolongation led to BDQ discontinuation in 15.2% subjects temporarily and in 6.7% subjects permanently. There were seven deaths (6.7%) during the treatment. CONCLUSION: During BDQ treatment, maximum QT prolongation was observed after three months of BDQ therapy. Therefore, more intensive cardiac monitoring is recommended during this period and afterwards.

Comparison of Effects of Capromorelin and Mirtazapine on Appetite in New Zealand White Rabbits (Oryctolagus cuniculus).

Inappetence is a welfare concern in rabbits (Oryctolagus cuniculus), as it can lead to potentially fatal gastrointestinal stasis. In other species, inappetence is commonly treated with appetite stimulants; however, few published studies have evaluated the efficacy of appetite stimulants in rabbits. We performed 2 studies to evaluate the effects of capromorelin and mirtazapine on appetite in New Zealand White (NZW) rabbits. In the first study, healthy rabbits ( n = 9) were evaluated using a randomized crossover design and 9 treatments: capromorelin 4 mg/kg oral (PO) once a day (SID), capromorelin 8 mg/kg PO SID, saline control PO SID, capromorelin 4 mg/kg PO twice a day (BID), capromorelin 8 mg/kg PO BID, saline control PO BID, mirtazapine 0.5 mg/kg transdermal (TD) SID, mirtazapine 1 mg/kg TD SID, and saline control TD SID for 3 d with a 1-wk washout period between treatments. Treatment efficacy was assessed by measuring daily feed intake and fecal output and by weighing rabbits twice a week. Overall, feed intake and fecal output were higher for all treatments as compared with controls, except for fecal output in the capromorelin 4 mg/kg and 8 mg/kg PO SID groups. Feed intake and fecal output were significantly higher with mirtazapine as compared with capromorelin. Body weight and erythema/petechia of the pinnae were greater in the mirtazapine 1 mg/kg TD SID group than in the control group. A second study evaluated rabbits that had undergone surgery (castration, n = 7) and then received one of 3 treatments: capromorelin 8 mg/kg PO BID, mirtazapine 1 mg/kg TD SID, or saline PO BID for 3 d postoperatively. Feed intake and fecal output in the postoperative mirtazapine group were not significantly different from those of the capromorelin and control groups. Due to its superior efficacy as compared with capromorelin in healthy NZW rabbits, we recommend considering mirtazapine as a treatment for inappetence in NZW rabbits.

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.

2022 ISFM Consensus Guidelines on Management of the Inappetent Hospitalised Cat.

PRACTICAL RELEVANCE: Inappetence may have many origins and, as a presenting sign or observation in the hospitalised patient, is common in feline practice. Nutritional assessment of every patient is encouraged, to identify the need for, and appropriate type of, intervention indicated. The impact of malnutrition may be significant on the feline patient, perpetuating illness, delaying recovery, slowing wound healing and negatively impacting gut health and immunity. Delayed intervention may result in the cat's deterioration; hence prompt control of contributing factors such as the underlying illness, pain, nausea, ileus and stress is vital to optimise voluntary food intake. Management is multimodal, comprising reduction of stress, medications and assisted nutrition in the form of tube feeding or parenteral nutrition. Use of antiemetic, analgesic, prokinetic and appetite stimulant medications may restore appetite, but placement of feeding tubes should not be delayed. Feeding tubes are generally well tolerated and allow provision of food, water and medication with minimal stress, although clinicians must be aware of complications such as stoma site infections and refeeding syndrome. CLINICAL CHALLENGES: Cats are vulnerable to malnutrition owing to their unique metabolism and specific nutritional requirements. Moreover, their nature as a species means they are susceptible to stress in the hospital environment, which may result in reduced food intake; previous negative experiences may compound the problem. In particular, an inappropriate clinic environment and/or handling may cause or exacerbate inappetence in hospitalised patients, with negative impacts on recovery. Postponing interventions such as feeding tube placement to await improvement, owing to clinician or caregiver apprehension, may hinder recovery and worsen nutritional deficits. EVIDENCE BASE: The 2022 ISFM Consensus Guidelines on Management of the Inappetent Hospitalised Cat have been created by a panel of experts brought together by the International Society of Feline Medicine (ISFM). Information is based on the available literature, expert opinion and the panel members' experience.

Propensity score-matching analysis comparing safety outcomes of appetite-stimulating medications in oncology patients.

PURPOSE: Anorexia and weight loss are common complications in the elderly, advanced cancer population. Appetite stimulants are commonly used therapies for oncology patients with weight loss, yet their safety comparison remains unknown. METHODS: This was a two-center, retrospective, study conducted in New York City at Mount Sinai Beth Israel and New York University Langone from January 2016 to July 2019 in adult patients with histologic evidence of malignancy who were taking either megestrol acetate or mirtazapine as an appetite-stimulating medication. Endpoints included safety concerns of mortality, QTc prolongation, venous thromboembolism, fall, somnolence, xerostomia, and hallucinations. Effectiveness of weight gain or maintenance of weight was not assessed. A propensity score-matching analysis was performed using a logistic regression analysis to assess the two comparable groups. RESULTS: The study included 350 patients (69.56 ± 13.31 years) with the most common malignancies being gastrointestinal, breast, and hematologic with metastasis present in over half the patients. Adverse events were commonly seen in the oncology population. After a propensity score-matched analysis, all safety outcomes associated with mirtazapine compared to megestrol acetate were similar; all-cause mortality (7%, n = 7 vs. 12%, n = 12, p = 0.23), QTc prolongation (31%, n = 31 vs. 31%, n = 31, p = 1.00), thromboembolism (11%, n = 11 vs. 11%, n = 11, p = 1.00), somnolence (29%, n = 30 vs. 22%, n = 23, p = 0.34), xerostomia (27%, n = 28 vs. 18%, n = 19, p = 0.24), and hallucinations (17%, n = 18 vs. 8%, n = 8, p = 0.06), respectfully. CONCLUSION: There were no safety differences seen when evaluating both agents.

Malnutrition identification and management variability: An administrative database study of children with solid tumors.

BACKGROUND: Malnutrition during cancer treatment increases treatment-related morbidity and mortality. Our study better characterizes variability in malnutrition identification and treatment by examining nutrition-related diagnoses and support for children with central nervous system (CNS) and non-CNS solid tumors during therapy. We examined diagnosis of malnutrition, use of tube feeding or parenteral nutrition (PN), and appetite stimulants. METHODS: We retrospectively reviewed 0 to 21-year-old patients in the Pediatric Health Information System from 2015 to 2019. Patients were classified as having (1) billed malnutrition diagnosis, (2) malnutrition diagnosis or using PN and enteral nutrition ("functional malnutrition"), and (3) any previous criteria or prescribed appetite stimulants ("possible malnutrition"), as well as associated risk factors. RESULTS: Among 13,375 unique patients, CNS tumors were most common (24.4%). Overall, 26.5% of patients had malnutrition diagnoses, 45.4% met functional malnutrition criteria, and 56.0% had possible malnutrition. Patients with adrenal tumors had highest billed, functional, and possible malnutrition (36.6%, 64.1%, and 69.4%, respectively) followed by CNS tumors (29.1%, 52.4%, and 64.1%). Patients with adrenal tumors had highest rates of PN use (47.4%) and those with CNS tumors had the highest tube feeding use (26.8%). Hospital admissions with malnutrition had a longer hospital length of stay (LOS) (6 vs 3 days, P < 0.0001), more emergency department admissions (24.4% vs 21.8%, P < 0.0001), and more opioid use (58.6% vs 41.4%, P < 0.0001). CONCLUSIONS: Variability in malnutrition diagnoses hinders clinical care and nutrition research in pediatric oncology. Improving disease-specific recognition and treatment of malnutrition can target nutrition support, ensure appropriate reimbursement, and potentially improve outcomes for children with solid tumors.

Feeding fennel (Foeniculum vulgare) seed as a potential appetite stimulant for Holstein dairy calves: Effects on growth performance and health.

This experiment was conducted to determine the effect of increasing dietary doses of fennel seed powder (FSP) on growth performance and health status in calves. Holstein calves (n = 48; 3 d of age; 36.3 ± 1.06 kg BW; mean ± SE) were allocated randomly to diets containing 0 (FSP0), 1.5 (FSP1.5), or 3 g/d (FSP3) FSP in milk (morning feeding; during the first month) and then in the starter feed (top-dressed; from d 31 until weaning on d 71). The calves remained in the trial until d 81. Weight gain and final BW were greater in FSP-supplemented calves compared with control calves. Heart girth and hip width gained more in FSP-supplemented calves compared with control calves. Body weight gain and frame growth were not affected by calf sex. The calves receiving FSP had a lower chance of having elevated rectal temperature (≥39.4°C) and a lower probability of suffering from diarrhea or pneumonia. The chance of having diarrhea, but not pneumonia, was greater in female calves. The chance of medication occurrence for diarrhea and pneumonia was not affected by FSP and calf sex. The FSP3 calves had shorter days with elevated rectal temperature (≥39.4°C) compared with the FSP1.5 (1.2 d; SEM = 0.10) and FSP0 (2.9 d; SEM = 0.10) calves. Days with diarrhea but not its frequency and medication days was shorter (4 d; SEM = 0.10) in the FSP-supplemented calves. Control calves experienced more days with pneumonia compared with calves fed FSP1.5 (3.1 d; SEM = 0.08) and FSP3 (5.4 d; SEM = 0.08). Calves fed FSP3 experienced shorter days (2.3 d; SEM = 0.08) with pneumonia compared with calves fed FSP1.5. Feeding FSP tended to decrease (1.6 d; SEM = 0.10) medication days for pneumonia compared with control group. The duration (2.2 d; SEM = 0.10) and medication days (1.3 d; SEM = 0.15) for diarrhea were higher in female calves compared with the male calves. Compared with the control calves, feeding 3 g/d of FSP may be more beneficial in improving the weight gain and skeletal growth (heart girth and hip width) and in reducing the susceptibility to and duration of diarrhea and pneumonia in dairy calves.

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.

Efficacy and Tolerability of Cyproheptadine in Poor Appetite: A Multicenter, Randomized, Double-blind, Placebo-controlled Study.

PURPOSE: Cyproheptadine, an antihistamine and antiserotonergic agent, is an appetite stimulant that is efficacious in promoting weight gain in children and adults with poor appetite. Despite numerous studies showing that cyproheptadine achieved positive outcomes, studies documenting its effectiveness on appetite are limited. This study evaluated the efficacy and tolerability of cyproheptadine in adults with poor appetite in South Korea. METHODS: Patients aged 19 to 64 years with poor appetite were randomly assigned to receive either cyproheptadine or placebo for 8 weeks. The primary end point was the difference between the groups in change in appetite, as measured by the Korean version of the Edmonton Symptom Assessment System from the beginning to the end of the study period. The secondary end points included effects on weight, anthropometrics, body composition, Simplified Nutritional Appetite Questionnaire-measured appetite, and toxicities. A total of 375 patients were randomly assigned to the two groups (189 cyproheptadine, 186 placebo). FINDINGS: The cyproheptadine group experienced a mean (SD) change in appetite score of -2.42 (0.12) compared with -2.03 (0.13) in the placebo arm, representing a statistically significant appetite gain in the cyproheptadine group (difference, +0.38 [0.18]; 95% CI, -0.73 to -0.04; P = 0.0307). Patients in the cyproheptadine group experienced significant increases in weight and body mass index. The most common adverse event was somnolence, as predicted. Cyproheptadine was well tolerated, with one serious adverse event (colitis) which was classified as a moderate adverse effect unlikely to be related to the study drug. IMPLICATIONS: We present the largest randomized, double-blind, placebo-controlled clinical trial of cyproheptadine versus placebo in healthy adults with poor appetite using the lowest effective dosage of cyproheptadine. Cyproheptadine is a safe treatment option in patients with poor appetite. Our findings provide important information for the use of cyproheptadine to ameliorate poor appetite in adults. Further randomized studies focused on the effect of cyproheptadine in older populations are needed.

Appetite regulation by plant-derived bioactive peptides for promoting health.

Appetite is closely regulated not only by gut hormonal and neuronal peptides but also by exogenous peptides derived from food proteins. Food proteins are now recognized to contain many thousands of bioactive compounds that provide additional health benefits beyond their nutritional effects. Bioactive peptides are beneficial to the life and/or to regulate physiological functions. Although animal protein products have been widely applied in the food industry, exploring the possibilities of developing functional foods based on plant protein-derived peptides is considered attractive for achieving sustainable development goals. In addition, peptides from plant proteins have the potential to treat numerous diseases or risk factors and may therefore facilitate a healthy life expectancy. In this review, we discuss the identified plant-based bioactive peptides and their appetite regulating effects. Plant-based bioactive peptides may provide new opportunities to discover novel approaches that can improve and prevent diseases in a sustainable environment.

The use of midazolam as an appetite stimulant and anxiolytic in the common marmoset (Callithrix jacchus).

BACKGROUND: Food avoidance secondary to disease or stress can lead to weight loss and rapid deterioration of clinical condition in the common marmoset (Callithrix jacchus). Currently, there are no data supporting the use of any pharmaceuticals as an appetite stimulant in this species; however, benzodiazepines are frequently used for this purpose in other species. METHODS: Six marmosets were used in a crossover study design to evaluate the benzodiazepine midazolam as an appetite stimulant and anxiolytic. Total food intake (TFI) and latency to eat (LTE) were measured following administration of oral and injectable midazolam in non-anxious and anxious states. RESULTS: Injectable midazolam increased TFI and decreased LTE in anxious marmosets, but had no effect in non-anxious animals. Oral midazolam had no effect on appetite in either state. CONCLUSIONS: Injectable midazolam may be an effective treatment for anxiety-induced inappetence in marmosets. Individual response to both oral and injectable midazolam may vary.