Should Cannabis be Used for Anorexia in Patients With Cancer?

Healthcare professionals are frequently asked about the benefits of cannabis for appetite or anorexia-cachexia syndrome. In popular culture, cannabis has a reputation of causing an increased hunger, slang termed "the munchies," so many patients consume this with the hope that it may improve the loss of appetite associated with serious illness such as cancer. There have only been a few randomized, controlled trials studying the controversial question as to if cannabis improves appetite. These studies are small and show no statistically significant benefit for appetite and one small study showed improvement of taste for foods. Due to regulation barriers, the studies have use synthetic products, not the products that represent what is more commonly used in the population, often whole flower smoked, vaporized or oral products. Despite the popularity of cannabis in culture, often touted as a panacea for all maladies, the evidence and education for several adverse effects and potential drug interactions have has yet to catch up with the cultural craze. International cannabis experts in the United States and Australia do not routinely certify patients for medical cannabis off trial for anorexia-cachexia, but one expert in Canada would consider use in selected cancer patients.

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.

Ketamine ameliorates activity-based anorexia of adolescent female mice through changes in GluN2B-containing NMDA receptors at postsynaptic cytoplasmic locations of pyramidal neurons and interneurons of medial prefrontal cortex.

Anorexia nervosa (AN) is a mental illness with high rates of mortality and relapse, and no approved pharmacotherapy. Using the activity-based anorexia (ABA) model of AN, we previously showed that a single sub-anesthetic intraperitoneal injection of ketamine (30 mg/kg-KET, but not 3 mg/kg-KET), has an immediate and long-lasting effect of reducing anorexia-like behavior among adolescent female mice. We also showed previously that excitatory outflow from medial prefrontal cortex (mPFC) engages hunger-evoked hyperactivity, leading to the ABA condition of severe weight loss. Ketamine is known to target GluN2B-containing NMDARs (NR2B). Might synaptic plasticity involving NR2B in mPFC contribute to ketamine's ameliorative effects? We addressed this question through electron microscopic immunocytochemical quantification of GluN2B at excitatory synapses of pyramidal neurons (PN) and GABAergic interneurons (IN) in mPFC layer 1 of animals that underwent recovery from a second ABA induction (ABA2), 22 days after ketamine injection during the first ABA induction. The 30 mg/kg-KET evoked synaptic plasticity that differed for PN and IN, with changes revolving the cytoplasmic reserve pool of NR2B more than the postsynaptic membrane pool. Those individuals that suppressed hunger-evoked wheel running the most and increased food consumption during recovery from ABA2 the most showed the greatest increase of NR2B at PN and IN excitatory synapses. We hypothesize that 30 mg/kg-KET promotes long-lasting changes in the reserve cytoplasmic pool of NR2B that enables activity-dependent rapid strengthening of mPFC circuits underlying the more adaptive behavior of suppressed running and enhanced food consumption, in turn supporting better weight restoration.

Psychiatric Adverse Events of Acetylcholinesterase Inhibitors in Alzheimer's Disease and Parkinson's Dementia: Systematic Review and Meta-Analysis.

BACKGROUND: The acetylcholinesterase inhibitors (AChEIs) donepezil, galantamine, and rivastigmine are commonly used in the management of various forms of dementia. OBJECTIVES: While these drugs are known to induce classic cholinergic adverse events such as diarrhea, their potential to cause psychiatric adverse events has yet to be thoroughly examined. METHODS: We sought to determine the risk of psychiatric adverse events associated with the use of AChEIs through a systematic review and meta-analysis of double-blind randomized controlled trials involving patients with Alzheimer's dementia and Parkinson's dementia. RESULTS: A total of 48 trials encompassing 22,845 patients were included in our analysis. Anorexia was the most commonly reported psychiatric adverse event, followed by agitation, insomnia, and depression. Individuals exposed to AChEIs had a greater risk of experiencing appetite disorders, insomnia, or depression compared with those who received placebo (anorexia: odds ratio [OR] 2.93, 95% confidence interval [CI] 2.29-3.75; p < 0.00001; decreased appetite: OR 1.93, 95% CI 1.33-2.82; p = 0.0006; insomnia: OR 1.55, 95% CI 1.25-1.93; p < 0.0001; and depression: OR 1.59, 95% CI 1.23-2.06, p = 0.0004). Appetite disorders were also more frequent with high-dose versus low-dose therapy. A subgroup analysis revealed that the risk of insomnia was higher for donepezil than for galantamine. CONCLUSIONS: Our findings suggest that AChEI therapy may negatively impact psychological health, and careful monitoring of new psychiatric symptoms is warranted. Lowering the dose may resolve some psychiatric adverse events, as may switching to galantamine in the case of insomnia. CLINICAL TRIAL REGISTRATION: The study was pre-registered on PROSPERO (CRD42021258376).

The efficacy and safety of anamorelin for patients with cancer-related anorexia/cachexia syndrome: a systematic review and meta-analysis.

Cancer-related anorexia/cachexia syndrome (CACS) is characterized by anorexia and loss of body weight. Evidence is insufficient to strongly endorse any pharmacologic agent for the treatment of CACS. In this systematic review, we assessed the efficacy of oral anamorelin treatment for patients with CACS. On July 6, 2022, we systematically searched the following databases for randomized controlled trials (RCTs) of adults with CACS comparing oral anamorelin versus placebo: CENTRAL, PubMed, EMBASE, and ICHUSHI. The primary outcomes were total body weight (TBW), patient-reported quality of life (QOL), and adverse events (AEs). Secondary outcomes included lean body mass (LBM), overall survival (OS), non-dominant hand grip strength (HGS), and appetite. We included seven RCTs with a total of 1944 CACS patients. Anamorelin significantly increased TBW (mean difference (MD) 1.73, 95% confidence interval (CI) 1.34-2.13, p < 0.00001), LBM (MD 1.06, 95% CI 0.30-1.81, p = 0.006), and QOL (standardized mean difference (SMD) 0.16, 95% CI 0.04-0.27, p = 0.006) compared with placebo without a significant difference in all AEs, severe AEs, OS, HGS or appetite. Anamorelin may be an effective treatment for CACS patients; however, further studies are needed to confirm the efficacy and safety of this drug.

Screening study of anti-emetics to improve GDF15-induced malaise and anorexia: Implications for emesis control.

Considerable preclinical and clinical attention has focused on the food intake and body weight suppressive effects of growth differentiation factor 15 (GDF15) and its elevated blood levels as a consequence of disease states and disease treatment therapeutics. We have previously reported that exogenous administration of GDF15 induces anorexia through nausea and emesis in multiple species. Importantly, GDF15 signaling as a meditator of chemotherapy-induced anorexia and emesis has recently been demonstrated in both murine and nonhuman primate models. The mechanism, however, by which GDF15 induces malaise and the utility of existing therapeutic targets to counteract its effects remain largely unknown. Using a dose of GDF15 that mimics stimulated levels following chemotherapy administration and reliably induces malaise, we sought to screen anti-emetics that represent distinct pharmacotherapeutic classes hypothesized to reduce GDF15-induced effects in rats. Strikingly, our results showed that none of the tested compounds were effective at preventing GDF15-induced malaise. These results illustrate the complexity of GDF15 signaling mechanism and may have important implications for medical conditions characterized by elevated GDF15 levels and incomplete symptom control, such as chemotherapy-induced nausea and vomiting.

Phase II, double blind, placebo controlled, multi-site study to evaluate the safety, feasibility and desirability of conducting a phase III study of anamorelin for anorexia in people with small cell lung cancer: A study protocol (LUANA trial).

Anorexia is experienced by most people with lung cancer during the course of their disease and treatment. Anorexia reduces response to chemotherapy and the ability of patients to cope with, and complete their treatment leading to greater morbidity, poorer prognosis and outcomes. Despite the significant importance of cancer-related anorexia, current therapies are limited, have marginal benefits and unwarranted side effects. In this multi-site, randomised, double blind, placebo controlled, phase II trial, participants will be randomly assigned (1:1) to receive once-daily oral dosing of 100mg of anamorelin HCl or matched placebo for 12 weeks. Participants can then opt into an extension phase to receive blinded intervention for another 12 weeks (weeks 13-24) at the same dose and frequency. Adults (≥18 years) with small cell lung cancer (SCLC); newly diagnosed with planned systemic therapy OR with first recurrence of disease following a documented disease-free interval ≥6 months, AND with anorexia (i.e., ≤ 37 points on the 12-item Functional Assessment of Anorexia Cachexia Treatment (FAACT A/CS) scale) will be invited to participate. Primary outcomes are safety, desirability and feasibility outcomes related to participant recruitment, adherence to interventions, and completion of study tools to inform the design of a robust Phase III effectiveness trial. Secondary outcomes are the effects of study interventions on body weight and composition, functional status, nutritional intake, biochemistry, fatigue, harms, survival and quality of life. Primary and secondary efficacy analysis will be conducted at 12 weeks. Additional exploratory efficacy and safety analyses will also be conducted at 24 weeks to collect data over longer treatment duration. The feasibility of economic evaluations in Phase III trial will be assessed, including the indicative costs and benefits of anamorelin for SCLC to the healthcare system and society, the choice of methods for data collection and the future evaluation design. Trial registration. The trial has been registered with the Australian New Zealand Clinical Trials Registry [ACTRN12622000129785] and approved by the South Western Sydney Local Health District Human Research Ethics Committee [2021/ETH11339]. https://clin.larvol.com/trial-detail/ACTRN12622000129785.

Engagement of the brain orexin system in activity-based anorexia behaviour in mice.

While excessive physical activity is common amongst anorexia nervosa (AN) patients, contributing to their low body weight, little is known about the underlying biology and effective treatments targeting the hyperactivity are lacking. Given the role of orexin in arousal, physical activity and energy expenditure, we sought to investigate i) the extent to which orexin neurons are activated during severe anorectic state in the activity-based anorexia (ABA) mouse model, and ii) if the dual orexin receptor antagonist suvorexant can reduce physical activity during ABA. The Fos-TRAP2 technique enable us to visually capture active neurons (Fos expressing) during severe anorectic state in the ABA mouse model, and by immunohistochemistry, determine the extent to which these active neurons are orexin positive. In addition, suvorexant was administered peripherally to ABA mice and running activity was monitored. We found that a large population of orexin neurons in the hypothalamus are activated by ABA and that peripheral administration of suvorexant decreases food anticipatory activity in these mice. We conclude that orexin may be a suitable target to treat hyperactivity in AN and recommend further studies to examine the efficacy of suvorexant in aiding AN patients to control their drive for hyperactivity.

Current advancements in pharmacotherapy for cancer cachexia.

INTRODUCTION: Cancer cachexia is a multifactorial metabolic syndrome associated with a pathophysiology intertwined with increased inflammatory response, anorexia, metabolic dysregulation, insulin resistance, and hormonal alterations, which together generate a negative energy balance in favor of catabolism. The development of therapeutic strategies to treat cancer cachexia has always been related to clinical interventions with increased food intake/supplementation, physical exercise regimens, and/or medication to attenuate catabolism and increase the anabolic response. However, the approval of drugs by regulatory agencies has always been a challenge. AREAS COVERED: This review outlines the main pharmacotherapy findings in cancer cachexia as well as the ongoing clinical trials that have evaluated changes in body composition and muscle function. The National Library of Medicine (PubMed) was used as search tool. EXPERT OPINION: The pharmacological therapy for cachexia should be focused on improving body composition, muscle function, and mortality, although none of the compounds used so far was able to demonstrate positive results beyond increased appetite and improvements in body composition. Ponsegromab (GDF15 inhibitor), a new compound that has just entered a phase II clinical trial, is a promising candidate to treat cancer cachexia and may produce exciting results if the study can be conducted as planned.

Efficacy of antacids for cisplatin-induced gastrointestinal symptoms in the treatment of lung cancer.

OBJECTIVE: Chemotherapy-induced nausea and vomiting (CINV) and chemotherapy-associated dyspepsia syndrome (CADS) are frequently appearing adverse effects of cisplatin (CDDP)-containing chemotherapy. Antiemetic guidelines suggest that the administration of antacids such as proton pump inhibitors (PPIs) or histamine type-2 receptor antagonists be considered for CADS, although their efficacy for treating these symptoms remains unknown. This study aimed to reveal whether antacids attenuate gastrointestinal symptoms in CDDP-containing chemotherapy. MATERIALS AND METHODS: In total, 138 patients with lung cancer who received ≥ 75 mg/m2 CDDP-containing regimens were enrolled in this retrospective study. Patients were divided into an antacid group including patients administered PPIs or vonoprazan during all chemotherapy periods and controls without antacid administration. The primary endpoint was the comparison of anorexia incidence during the first cycle of chemotherapy. Secondary endpoints were CINV evaluation and risk factor analysis for the incidence of anorexia using logistic regression analysis. RESULTS: The incidence of anorexia during the first cycle was 54.4% in the control group and 60.3% in the antacid group, without significant differences (p = 0.60). The incidence of nausea was also similar between the groups (p = 1.00). Multivariate analysis suggested that antacid administration was not associated with anorexia. CONCLUSION: Baseline antacid administration does not affect gastrointestinal symptoms associated with CDDP-containing treatment in lung cancer.

Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer.

PURPOSE: Anorexia occurs in 30%-80% of patients with advanced malignancies, which may be worsened with chemotherapy. This trial assessed the efficacy of olanzapine in stimulating appetite and improving weight gain in patients receiving chemotherapy. METHODS: Adults (≥18 years) with untreated, locally advanced, or metastatic gastric, hepatopancreaticobiliary (HPB), and lung cancers were randomly assigned (double-blind) to receive olanzapine (2.5 mg once a day for 12 weeks) or placebo along with chemotherapy. Both groups received standard nutritional assessment and dietary advice. The primary outcomes were the proportion of patients with weight gain > 5% and the improvement in appetite (assessed by the visual analog scale [VAS] and the Functional Assessment of Chronic Illness Therapy system of Quality-of-Life questionnaires Anorexia Cachexia subscale [FAACT ACS]). Secondary end points were change in nutritional status, quality of life (QOL), and chemotherapy toxicity. RESULTS: We enrolled 124 patients (olanzapine, 63 and placebo, 61) with a median age of 55 years (18-78 years), of whom 112 (olanzapine, 58 and placebo, 54) were analyzable. The majority (n = 99, 80%) had metastatic cancer (gastric [n = 68, 55%] > lung [n = 43, 35%] > HPB [n = 13, 10%]). The olanzapine arm had a greater proportion of patients with a weight gain of > 5% (35 of 58 [60%] v 5 of 54 [9%], P < .001) and improvement in appetite by VAS (25 of 58 [43%] v 7 of 54 [13%], P < .001) and by FAACT ACS (scores ≥37:13 of 58 [22%] v 2 of 54 [4%], P = .004). Patients on olanzapine had better QOL, nutritional status, and lesser chemotoxicity. Side effects attributable to olanzapine were minimal. CONCLUSION: Low-dose, daily olanzapine is a simple, inexpensive, well-tolerated intervention that significantly improves appetite and weight gain in newly diagnosed patients on chemotherapy.

Discovery of the Potent and Selective MC4R Antagonist PF-07258669 for the Potential Treatment of Appetite Loss.

The melanocortin-4 receptor (MC4R) is a centrally expressed, class A GPCR that plays a key role in the regulation of appetite and food intake. Deficiencies in MC4R signaling result in hyperphagia and increased body mass in humans. Antagonism of MC4R signaling has the potential to mitigate decreased appetite and body weight loss in the setting of anorexia or cachexia due to underlying disease. Herein, we report on the identification of a series of orally bioavailable, small-molecule MC4R antagonists using a focused hit identification effort and the optimization of these antagonists to provide clinical candidate 23. Introduction of a spirocyclic conformational constraint allowed for simultaneous optimization of MC4R potency and ADME attributes while avoiding the production of hERG active metabolites observed in early series leads. Compound 23 is a potent and selective MC4R antagonist with robust efficacy in an aged rat model of cachexia and has progressed into clinical trials.

The Latest Treatments for Cancer Cachexia: An Overview.

Cancer cachexia demonstrates the same pathology as cachexia found in patients with disease-associated malnutrition presenting with inflammation. In advanced cancer, a decrease in skeletal muscle mass progresses with an increase in cancer cell mass. Moreover, cancer cachexia causes systemic edema and cachexia, reduces the efficacy of chemotherapy, and negatively affects cancer prognosis. Early nutritional intervention and multidisciplinary care are essential to ensure sufficient nutritional requirements and minimize anabolic resistance factors. In addition, preventive care that minimizes deterioration of nutritional status and loss of skeletal muscle mass is required for the effective treatment of cachexia. Therefore, the current review sought to comprehensively describe the available evidence for the effective pharmaceutical treatment of cancer-associated cachexia. Steroids have traditionally been used for cachexia drug therapy. However, their effects are limited, and it is difficult to radically restore the highly reduced muscle mass inherent to cancer-associated cachexia. Recently, anamorelin hydrochloride, an endogenous ligand for the growth hormone release-promoting factor receptor, which has a similar pharmacological action to that of ghrelin, was developed to treat weight loss accompanied by anorexia. This medication also treats cachexia and was the first drug to be approved for this purpose. Anamorelin hydrochloride is expected to bring new advancements into the field of clinical oncology as an effective therapeutic drug for cancer cachexia, a devastating complication that, so far, has no definitive and effective treatment.

The influence of Chinese herbal medicines on cancer-related pressure ulcer wound, fatigue, constipation, and anorexia: A meta-analysis.

We performed a meta-analysis to evaluate the influence of Chinese herbal medicines on cancer-related pressure ulcer wounds, fatigue, constipation, and anorexia. A systematic literature search up to March 2022 was done and 25 studies included 1777 subjects with cancer-related symptoms at the start of the study; 953 of them were provided with Chinese herbal medicines and 824 were control. They were reporting relationships about the influence of Chinese herbal medicines on cancer-related pressure ulcer wounds, fatigue, constipation, and anorexia. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) to assess the influence of Chinese herbal medicines on cancer-related pressure ulcer wounds, fatigue, constipation, and anorexia using the dichotomous method with a random or fixed-effect model. Chinese herbal medicines had significantly higher effectiveness in treating pressure ulcer wound (OR, 5.94; 95% CI, 3.94-8.95, P < .001), fatigue (OR, 2.81; 95% CI, 1.78-4.41, P < .001), and effectiveness on treating constipation (OR, 2.59; 95% CI, 1.57-4.25, P < .001) compared to control in subjects with cancer-related symptoms. However, Chinese herbal medicines had no significant effect on treating anorexia (OR, 1.69; 95% CI, 0.61-4.66, P = .31) compared to control in subjects with cancer-related symptoms. Chinese herbal medicines had significantly higher effectiveness in treating pressure ulcer wound, treating pressure ulcer wound, fatigue, and constipation compared to control in subjects with cancer-related symptoms. However, Chinese herbal medicines had no significant effect on the effectiveness of treating anorexia compared to control in subjects with cancer-related symptoms. Further studies are required to validate these findings.

Individual differences in the positive outcome from adolescent ketamine treatment in a female mouse model of anorexia nervosa involve drebrin A at excitatory synapses of the medial prefrontal cortex.

Anorexia nervosa (AN) is a mental illness with the highest rates of mortality and relapse, and no approved pharmacological treatment. Using an animal model of AN, called activity-based anorexia (ABA), we showed earlier that a single intraperitoneal injection of ketamine at a dose of 30 mg/kg (30mgKET), but not 3 mg/kg (3mgKET), has a long-lasting effect upon adolescent females of ameliorating anorexia-like symptoms through the following changes: enhanced food consumption and body weight; reduced running and anxiety-like behavior. However, there were also individual differences in the drug's efficacy. We hypothesized that individual differences in ketamine's ameliorative effects involve drebrin A, an F-actin-binding protein known to be required for the activity-dependent trafficking of NMDA receptors (NMDARs). We tested this hypothesis by electron microscopic quantifications of drebrin A immunoreactivity at excitatory synapses of pyramidal neurons (PN) and GABAergic interneurons (GABA-IN) in deep layer 1 of prefrontal cortex (PFC) of these mice. Results reveal that (1) the areal density of excitatory synapses on GABA-IN is greater for the 30mgKET group than the 3mgKET group; (2) the proportion of drebrin A+ excitatory synapses is greater for both PN and GABA-IN of 30mgKET than 3mgKET group. Correlation analyses with behavioral measurements revealed that (3) 30mgKET's protection is associated with reduced levels of drebrin A in the cytoplasm of GABA-IN and higher levels at extrasynaptic membranous sites of PN and GABA-IN; (5) altogether pointing to 30mgKET-induced homeostatic plasticity that engages drebrin A at excitatory synapses of both PN and GABA-IN.

Analysis of adverse events leading to dose reduction/interruption of lenvatinib treatment in patients with Child-Pugh B unresectable hepatocellular carcinoma.

INTRODUCTION: We aimed to compare the safety of lenvatinib as first-line treatment for unresectable hepatocellular carcinoma (HCC) in patients with Child-Pugh A (CP-A) and Child-Pugh B (CP-B) and to determine the adverse events (AEs) that cause dose reduction/interruption of treatment in patients with CP-B. METHODS: Sixty-six patients with lenvatinib as a first-line treatment for HCC at Ogaki Municipal Hospital (Ogaki, Japan) between April 2018 and January 2022 were retrospectively evaluated. We analyzed the treatment duration, AEs, and reasons for dose reduction/interruption associated with lenvatinib treatment in patients with CP-A and CP-B HCC. RESULTS: The CP-B group had significantly more cases of grade ≥ 2 fatigue and anorexia than the CP-A group (p = 0.045 and p = 0.042, respectively). Regarding AEs that caused dose reduction/interruption of treatment, the CP-A group had significantly more cases of proteinuria than the CP-B group (p = 0.015), whereas the CP-B group had significantly more cases of hand-foot syndrome (HFS) than the CP-A group (p = 0.013). CONCLUSION: Patients with CP-B have greater difficulty than patients with CP-A in continuing treatment with repeated dose reductions/interruption of treatment due to intolerable grade ≥ 2 AEs (fatigue and anorexia). HFS is more likely to cause dose reduction/interruption of treatment in CP-B than in CP-A unresectable HCC.

Extensively Drug-Resistant Enteric Fever In Children: Surging Threats Of Antimicrobial Resistance And Possible Solutions.

BACKGROUND: Enteric fever is an infectious disease caused by Salmonella enterica including Salmonella Typhi and Paratyphi A and is associated with potentially serious outcomes, especially in developing countries. The study was conducted with the aim to present the clinical features, laboratory characteristics and antibiotic susceptibility in patients with culture-proven extensively drug-resistant (XDR) enteric fever and to explore drug combinations as a possible solution for the growing problem of antimicrobial resistance. METHODS: This descriptive cross-sectional study was conducted in the Paediatric unit of Ayub teaching hospital. Patients admitted with culture-proven XDR enteric fever were included. Patient characteristics were documented on a predesigned proforma. Response to antimicrobial agents including ceftriaxone and levofloxacin, azithromycin and meropenem and meropenem alone was assessed. Data was entered and analyzed using SPSS version 26. RESULTS: A total of 53 patients participated in this study. The majority of patients 36 (67.9%) were male and above 5 years of age(n=38,71.7%). The mean age of the participants was 7.08±3.02 years. The major presenting features included fever, anorexia and pain abdomen in 53 (100%), 51 (96.2%) and 41 (77.4%) respectively. The mean duration of symptoms prior to hospitalization was 8.92±3.361 days. Of the total patients, 32(60.4%) responded to the initial therapy with ceftriaxone and levofloxacin, 11(20.8%) patients responded to meropenem alone and 10 (18.9%) patients responded to meropenem and azithromycin in combination. There was no statistically significant difference in mean duration to show response in patients receiving either of the treatments (p=0.484). CONCLUSIONS: Paediatric patients with XDR enteric fever mainly presented with fever, anorexia and pain abdomen and showed good response to therapy with the combination of ceftriaxone and levofloxacin inspite of the apparent resistance on blood culture and sensitivity.

Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/consensus guidance on the use of cannabinoids for gastrointestinal symptoms in patients with cancer.

BACKGROUND: Gastrointestinal symptoms are common in patients with cancer, whether related to treatment or a direct effect of the disease itself. Patients may choose to access cannabinoids outside of their formal medical prescriptions to palliate such symptoms. However, clinical guidelines are lacking in relation to the use of such medicines for gastrointestinal symptoms in patients with cancer. METHODS: A systematic review of the evidence for the use of cannabinoids for symptom control in patients with cancer was undertaken. Search strategies were developed for Medline, Embase, PsychINFO, and the Cochrane Central Register of Controlled Trials, including all publications from 1975 up to 12 November 2021. Studies were included if they were randomized controlled trials of cannabinoids compared with placebo or active comparator in adult patients with cancer, regardless of type, stage, or treatment status. Articles for inclusion were agreed by all authors, and data extracted and summarized by two authors. Each study was scored according to the Jadad scale. This review was specifically for the purpose of developing guidelines for the use of cannabis for gastrointestinal symptoms, including chemotherapy-induced nausea and vomiting (CINV), chronic nausea, anorexia-cachexia syndrome, and taste disturbance. RESULTS: Thirty-six randomized controlled trials were identified that met the inclusion criteria for this review of gastrointestinal symptoms: 31 relating to CINV, one to radiotherapy-induced nausea and vomiting, and the remaining four to anorexia-cachexia and altered chemosensory disturbance. The populations for the randomized controlled trials were heterogeneous, and many studies were of poor quality, lacking clarity regarding method of randomization, blinding, and allocation concealment. For CINV, eleven RCTs showed improvement with cannabis compared to placebo, but out of 21 trials where cannabis was compared to other antiemetics for CINV, only 11 favoured cannabis. CONCLUSION: Tetrahydrocannabinol (THC) and nabilone were more effective in preventing CINV when compared to placebo but are not more effective than other antiemetics. For refractory CINV, one study of THC:CBD demonstrated reduced nausea as an add-on treatment to guideline-consistent antiemetic therapy without olanzapine. The MASCC Guideline Committee found insufficient evidence to recommend cannabinoids for the management of CINV, nausea from advanced cancer, cancer-associated anorexia-cachexia, and taste disturbance. High-quality studies are needed to inform practice.