Treatment of nausea in hospitalized patients with acute illness.

Evidence suggests that available antiemetics are equal to intravenous fluid treatment against acute nausea of other causes than motion sickness, pregnancy, anaesthesia, chemo- or radiation therapy. Each antiemetic is associated with adverse effects, which include movement disorders, sedation, and QT prolongation. Intravenous fluid and treatment directed against underlying pathology is recommended as a first-line treatment against nausea in these patients. If an antiemetic is clinically warranted, ondansetron has the most favourable ratio between side effects and price, as argued in this review.

The prophylactic antiemetic therapies in management of differentiated thyroid cancer patients with radioactive iodine therapy: a single-center, non-randomized clinical trial.

Objective: The present study was to investigate three different single-drug regimens to show which was more effective to reduce radioactive iodine therapy (RAI) associated nausea and vomiting, and to compare the occurrence of long-term gastrointestinal diseases after RAI therapy. Method: We performed a single-center, non-randomized clinical trial among patients who underwent RAI therapy from March 2016 to July 2022. Enrolled patients were divided into four cohorts based on the date of the treatment. cohort 1, with no preventive antiemetics; cohort 2, received 20 mg of pantoprazole per day for 3 days; cohort 3, received a 10 mg metoclopramide tablet two times daily for 3 days; cohort 4, oral ondansetron, 8 mg, twice daily for 3 days. The primary endpoints were proportion of patients who experience vomiting episodes and nausea during the 7-day hospital period. Secondary end points included Functional Living Index Emesis (FLIE) quality-of life questionnaires and the occurrence of gastrointestinal diseases. Results: A total of 1755 patients were analyzed, comprised of 1299 (74.0%) women and 456 (26.0%) men, with a median age of 44 years (range 18-78 years). The characteristics of patient were similar within the four groups. 465 (26.4%) patients developed RAI-associated nausea, and 186 (14.4%) patients developed RAI-associated vomiting. The rate of nausea was significantly decreased in the patients who were taking ondansetron when compared with the other cohorts (P<0.05), while the rate of vomiting (≥6 episodes) was slightly lower. As secondary endpoint, FLIE measures ondansetron scored highly compared to other cohorts, from baseline (mean score of 110.53 ± 17.54) to day 7 (mean score of 105.56 ± 12.48). In addition, 48 (2.7%) patients were found to be with gastrointestinal diseases at the end of one year follow up. Multiple RAI therapy and higher dose of I-131 per body weight revealed a significantly independent risk factors of developing gastrointestinal disorders. Conclusions: In conclusion, the present study demonstrated that short-term ondansetron could be an effective prophylactic agent in controlling RAI-associated nausea and vomiting. Furthermore, the risk of developing gastrointestinal disorders was significantly higher for patients with multiple RAI therapy and higher dose of I-131 per body weight.

Gastro-Intestinal Symptoms in Palliative Care Patients.

This review of the palliation of various gastro-intestinal (GI) symptoms encountered in cancer patients is by no means exhaustive. Frequent symptoms such as constipation, nausea and vomiting, bowel obstructions, ascites and bleeds will be discussed, focusing on their assessment and most importantly, how to control the associated symptoms. All of these symptoms and GI complications can significantly impact patients' quality of life (QOL) and should be treated as quickly and aggressively as possible.

Meal related symptoms in youth with chronic abdominal pain: Relationship to anxiety, depression, and sleep dysfunction.

OBJECTIVE: The objective of the current study was to describe meal-related symptoms in youth with chronic abdominal pain fulfilling criteria for a disorder of gut-brain interaction (DGBI) and their associations with anxiety, depression, and sleep disturbances. METHODS: This was a retrospective evaluation of 226 consecutive patients diagnosed with an abdominal pain-associated DGBI. As part of routine care, all had completed a standardized symptom history, the Sleep Disturbances Scale for Children (utilized to assess for disorders of initiation and maintenance of sleep and excessive daytime somnolence) and the Behavior Assessment System for Children-Third Edition (utilized to assess for anxiety and depression). Four meal related symptoms were assessed: early satiety, postprandial bloating, postprandial abdominal pain, and postprandial nausea. RESULTS: Overall, 87.6% of patients reported at least one meal related symptom and the majority reported at least three symptoms. All meal related symptoms were significantly related to each other. Postprandial pain and nausea were more often reported by females. Early satiety, postprandial bloating, and postprandial nausea, but not postprandial pain demonstrated significant though variable associations with anxiety, depression, disorders of initiation and maintenance of sleep, and disorders of excessive somnolence, but only in adolescents. CONCLUSIONS: Meal related symptoms are very common in youth with abdominal pain-associated DGBIs. Early satiety, bloating, and postprandial nausea demonstrate variable associations with anxiety, depression, and disordered sleep while increased postprandial pain was not associated with psychologic or sleep dysfunction, suggesting a different pathway for symptom generation.

Nausea and Vomiting as Initial Manifestations of Pediatric NMOSD.

Intractable nausea and vomiting are commonly attributed to gastrointestinal (GI) conditions but can sometimes be a symptom of an underlying central nervous system disease. One potentially overlooked neurologic cause of intractable nausea and vomiting that is refractory to antiemetics is area postrema syndrome (APS). APS is a condition characterized by lesions of the dorsal caudal medulla and is considered a core clinical feature of neuromyelitis optica spectrum disorder (NMOSD). APS is present in up to 30% of patients ultimately diagnosed with NMOSD and can be the first presenting symptom of NMOSD in 12% of patients, as our case illustrates. Importantly, APS is highly responsive to immunotherapy. We present the case of a 14-year-old female with a history of migraines who presented to the emergency department multiple times for persistent nausea, vomiting, and hiccups. Multiple GI diagnoses were considered until she developed additional neurologic symptoms that prompted further workup and revealed the final diagnosis of NMOSD-APS. We posit that NMOSD-APS should be considered in the differential diagnosis for patients with intractable nausea and vomiting, especially in patients with a negative GI workup result and poor response to antiemetics.

Nausea-induced suppression of feeding is mediated by central amygdala Dlk1-expressing neurons.

The motivation to eat is suppressed by satiety and aversive stimuli such as nausea. The neural circuit mechanisms of appetite suppression by nausea are not well understood. Pkcδ neurons in the lateral subdivision of the central amygdala (CeA) suppress feeding in response to satiety signals and nausea. Here, we characterized neurons enriched in the medial subdivision (CeM) of the CeA marked by expression of Dlk1. CeADlk1 neurons are activated by nausea, but not satiety, and specifically suppress feeding induced by nausea. Artificial activation of CeADlk1 neurons suppresses drinking and social interactions, suggesting a broader function in attenuating motivational behavior. CeADlk1 neurons form projections to many brain regions and exert their anorexigenic activity by inhibition of neurons of the parabrachial nucleus. CeADlk1 neurons are inhibited by appetitive CeA neurons, but also receive long-range monosynaptic inputs from multiple brain regions. Our results illustrate a CeA circuit that regulates nausea-induced feeding suppression.

Under-reporting of subjective symptoms and its prognostic value: a pooled analysis of 12 cancer clinical trials.

BACKGROUND: Oncologists tend to under-report subjective symptoms during cancer treatment. This study describes the under-reporting rate of selected symptoms and explores its association with overall survival (OS). A secondary aim is to test the association of patient-reported symptoms with OS. PATIENTS AND METHODS: This is a post hoc analysis on data pooled from 12 randomized trials, promoted by the National Cancer Institute of Naples (Italy), enrolling patients between 2002 and 2019, with published primary analyses. Occurrence and grade of six side-effects (anorexia, nausea, vomiting, constipation, diarrhea and fatigue) reported by physicians were compared with corresponding symptoms reported by patients in quality-of-life (QoL) questionnaires. Under-reporting was defined as the rate of cases reported grade 0 by the physician while grade ≥1 by the patient. Prognostic value was tested in a multivariable model stratified by trial, including age, sex and performance status as confounders. A landmark threshold was defined for OS analyses. RESULTS: 3792 patients with advanced lung, ovarian, pancreatic, breast or colorectal cancer were pooled; 2603 (68.6%) were eligible having at least one toxicity assessment and one QoL questionnaire, before the first planned disease restaging. Concordance between physicians' and patients' reporting was low with Cohen's k coefficients ranging from 0.03 (fatigue) to 0.33 (vomiting). Under-reporting ranged from 52.7% (nausea) to 80.5% (anorexia), and was not associated with OS. Patient-reported anorexia, vomiting and fatigue ('a little' or more) were significantly associated with shorter OS. CONCLUSIONS: Under-reporting of treatment side-effects is frequent, but it does not affect OS. Patients' reported symptoms should be used for prognostic evaluation.

The Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum (Green-top Guideline No. 69).

An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be used to classify the severity of NVP and HG. [Grade C] Ketonuria is not an indicator of dehydration and should not be used to assess severity. [Grade A] There are safety and efficacy data for first line antiemetics such as anti (H1) histamines, phenothiazines and doxylamine/pyridoxine (Xonvea®) and they should be prescribed initially when required for NVP and HG (Appendix III). [Grade A] There is evidence that ondansetron is safe and effective. Its use as a second line antiemetic should not be discouraged if first line antiemetics are ineffective. Women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG. [Grade B] Metoclopramide is safe and effective and can be used alone or in combination with other antiemetics. [Grade B] Because of the risk of extrapyramidal effects metoclopramide should be used as second-line therapy. Intravenous doses should be administered by slow bolus injection over at least 3 minutes to help minimise these. [Grade C] Women should be asked about previous adverse reactions to antiemetic therapies. If adverse reactions occur, there should be prompt cessation of the medications. [GPP] Normal saline (0.9% NaCl) with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration. [Grade C] Combinations of different drugs should be used in women who do not respond to a single antiemetic. Suggested antiemetics for UK use are given in Appendix III. [GPP] Thiamine supplementation (either oral 100 mg tds or intravenous as part of vitamin B complex (Pabrinex®)) should be given to all women admitted with vomiting, or severely reduced dietary intake, especially before administration of dextrose or parenteral nutrition. [Grade D] All therapeutic measures should have been tried before considering termination of pregnancy. [Grade C].

The Etiology and Outcome of Area Postrema Syndrome in Childhood: Two Cases and a Literature Review.

BACKGROUND: Area postrema syndrome (APS), a rare childhood condition, manifests as intractable nausea and hiccups. APS has high diagnostic significance in neuromyelitis optica syndrome spectrum disorders (NMOSD) and can be the initial presentation of other critical diseases, including brainstem glioma. METHODS: We described two representative cases of unrelated Japanese patients with APS. An etiologic evaluation, including a detailed intracranial neuroradiological examination and autoantibodies assessment, was performed. We also reviewed the literature focusing on the prognosis of pediatric APS symptoms. RESULTS: A 14-year-old girl with aquaporin-4 antibody-positive NMOSD showed a good prognosis with immunotherapy, whereas another nine-year-old girl with irresectable medullary low-grade glioma had persistent symptoms for more than 10 years. All reported children aged >12 years were diagnosed with NMOSD, and patients aged <13 years showed heterogeneous etiologies. CONCLUSIONS: Distinctive time courses and neuroimaging features were key clinical findings for the diagnostic and therapeutic processes in these patients. This literature review highlights the wide spectrum and prognosis of pediatric-onset APS.

Hemorrhagic Complications Following Ultrasound-Guided Breast Biopsy: A Prospective Patient-Centered Study.

OBJECTIVE: We aimed to evaluate the clinical and imaging factors associated with hemorrhagic complications and patient discomfort following ultrasound (US)-guided breast biopsy. MATERIALS AND METHODS: We prospectively enrolled 94 patients who were referred to our hospital between June 2022 and December 2022 for US-guided breast biopsy. After obtaining informed consent, two breast radiologists independently performed US-guided breast biopsy and evaluated the imaging findings. A hemorrhagic complication was defined as the presence of bleeding or hematoma on US. The patients rated symptoms of pain, febrile sensation, swelling at the biopsy site, and dyspnea immediately, 20 minutes, and 2 weeks after the procedure on a visual analog scale, with 0 for none and 10 for the most severe symptoms. Additional details recorded included those of nausea, vomiting, bleeding, bruising, and overall satisfaction score. We compared the clinical symptoms, imaging characteristics, and procedural features between patients with and those without hemorrhagic complications. RESULTS: Of 94 patients, 7 (7%) developed hemorrhagic complications, while 87 (93%) did not. The complication resolved with 20 minutes of manual compression, and no further intervention was required. Vascularity on Doppler examination (P = 0.008), needle type (P = 0.043), and lesion location (P < 0.001) were significantly different between the groups. Patients with hemorrhagic complications reported more frequent nausea or vomiting than those without hemorrhagic complications (29% [2/7] vs. 2% [2/87], respectively; P = 0.027). The overall satisfaction scores did not differ between the two groups (P = 0.396). After 2 weeks, all symptoms subsided, except bruising (50% 2/4 in the complication group and 25% [16/65] in the no-complication group). CONCLUSION: US-guided breast biopsy is a safe procedure with a low complication rate. Radiologists should be aware of hemorrhagic complications, patient discomfort, and overall satisfaction related to this procedure.

The Role of Liposomal Bupivacaine in Multimodal Pain Management Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis: Faster and Farther With Less Opioids.

STUDY DESIGN: Retrospective controlled cohort. OBJECTIVE: To evaluate the effect of intraoperative liposomal bupivacaine (LB) infiltration on postsurgical pain management in adolescent idiopathic scoliosis (AIS) patients by analyzing postoperative opioid consumption, ambulation, and length of stay (LOS). SUMMARY OF BACKGROUND DATA: Optimal postoperative pain control for AIS patients undergoing posterior spinal fusion (PSF) is challenging. Multimodal pain management protocols provide adequate analgesia while decreasing opioid consumption. LB was recently approved for pediatric patients; however, use in AIS patients is understudied. METHODS: 119 consecutive patients with AIS who underwent PSF were included. Patients were divided into 2 groups: patients who received LB as erector spinae block in addition to the standard postoperative pain management protocol (Group A), and patients who received only the standard postoperative pain protocol (Group B). Oral morphine equivalents, intravenous opioid and valium consumption, pain scores (VAS), nausea/vomiting, ambulation distance and LOS were assessed. RESULTS: Group A experienced significantly lower total opioid consumption compared to Group B (44.5 mg vs. 70.2 mg). Morphine use was lower in Group A on postoperative day (POD) 0, and oxycodone use was lower in Group A on PODs 1 and 2. There was a higher proportion of patients who used only oral opioids in Group A (81% vs. 41%). Of patients requiring any intravenous opioids, 79% did not receive LB. A significantly higher proportion of LB patients were discharged on POD 2 (55% vs. 27%); therefore, LOS was shorter for Group A. Group A ambulated further postoperatively. There were no differences in pain scores, valium requirements or nausea/vomiting. CONCLUSIONS: LB was associated with decreased total opioid use, shorter LOS, and improved ambulation in AIS patients undergoing PSF. Including LB in multimodal pain management protocols proved effective in reducing opioid use while increasing mobilization in the immediate postoperative period. LEVEL OF EVIDENCE: 3.

Visceral symptoms in patients with anterior cutaneous nerve entrapment syndrome (ACNES): expression of viscerosomatic reflexes?

PURPOSE: Anterior cutaneous nerve entrapment (ACNES) is characterized by neuropathic pain in a predictable, circumscript abdominal area. The diagnostic delay is long, with half of ACNES-affected individuals reporting nausea, bloating, or loss of appetite mimicking visceral disease. The aim of this study was to describe these phenomena and to determine whether treatment could successfully reverse the visceral symptoms. METHODS: This prospective observational study was conducted between July 2017 and December 2020 at SolviMáx, Center of Excellence for Chronic Abdominal Wall and Groin Pain, Máxima Medical Center, Eindhoven. Adult patients who fulfilled published criteria for ACNES and reported at least one visceral symptom at intake were eligible for the study. A self-developed Visceral Complaints ACNES Score (VICAS) questionnaire that scores several visceral symptoms (minimum 1 point, maximum 9 points) was completed before and after therapy. The success of treatment was defined as at least 50% reduction in pain. RESULTS: Data from 100 selected patients (86 females) aged 39 ± 5 years were available for analysis. Frequently reported symptoms were abdominal bloating (78%), nausea (66%) and altered defecation (50%). Successful treatment significantly reduced the number of visceral symptoms, with a VICAS before of 3 (range 1-8) and after of 1 (range 0-6) (p < 0.001). A low baseline VICAS was associated with successful treatment outcome (OR 0.738, 95% CI 0.546-0.999). CONCLUSION: Patients with ACNES may report a variety of visceral symptoms. Successful treatment substantially reduces these visceral symptoms in selected patients.

A Phase 1 Study of the DNA-PK Inhibitor Peposertib in Combination With Radiation Therapy With or Without Cisplatin in Patients With Advanced Head and Neck Tumors.

PURPOSE: DNA-dependent protein kinase (DNA-PK) plays a key role in the repair of DNA double strand breaks via nonhomologous end joining. Inhibition of DNA-PK can enhance the effect of DNA double strand break inducing anticancer therapies. Peposertib (formerly "M3814") is an orally administered, potent, and selective small molecule DNA-PK inhibitor that has demonstrated radiosensitizing and antitumor activity in xenograft models and was well-tolerated in monotherapy. This phase 1 trial (National Clinical Trial 02516813) investigated the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, and tolerability of peposertib in combination with palliative radiation therapy (RT) in patients with thoracic or head and neck tumors (arm A) and of peposertib in combination with cisplatin and curative-intent RT in patients with squamous cell carcinoma of the head and neck (arm B). METHODS AND MATERIALS: Patients received peposertib once daily in ascending dose cohorts as a tablet or capsule in combination with palliative RT (arm A) or in combination with intensity modulated curative-intent RT and cisplatin (arm B). RESULTS: The most frequently observed treatment-emergent adverse events were radiation skin injury, fatigue, and nausea in arm A (n = 34) and stomatitis, nausea, radiation skin injury, and dysgeusia in arm B (n = 11). Based on evaluations of dose-limiting toxicities, tolerability, and pharmacokinetic data, RP2D for arm A was declared as 200 mg peposertib tablet once daily in combination with RT. In arm B (n = 11), 50 mg peposertib was declared tolerable in combination with curative-intent RT and cisplatin. However, enrollment was discontinued because of insufficient exposure at that dose, and the RP2D was not formally declared. CONCLUSIONS: Peposertib in combination with palliative RT was well-tolerated up to doses of 200 mg once daily as tablet with each RT fraction. When combined with RT and cisplatin, a tolerable peposertib dose yielded insufficient exposure.

Nutrition outcomes and treatment toxicities in patients with head and neck cancer receiving helical intensity-modulated radiotherapy.

BACKGROUND: Helical intensity-modulated radiotherapy (H-IMRT) provides excellent limitation of dose to tissues not requiring treatment, although acute toxicity still occurs. The present study aimed to determine how treatment-related acute toxicities affect nutrition outcomes in patients with head and neck cancer. METHODS: A prospective observational study was conducted in 194 patients undergoing curative intent H-IMRT with or without other treatment modalities. Weight outcomes (kg) and acute toxicity and dysphagia data were collected during treatment using Common Toxicity Criteria for Adverse Effects (CTCAE), version 4.0. RESULTS: Significant weight loss (> 10%) was observed in 30% of high nutritional risk patients and 7% of low nutritional risk patients. Nausea, adjusted for baseline dysphagia, in high nutritional risk patients and nausea, dysphagia and pharyngeal mucositis in low nutritional risk patients were significant factors in explaining the percentage loss in baseline weight to treatment completion. CONCLUSIONS: Significant weight loss remains an issue during treatment, despite improvements in radiotherapy technology and high-level multidisciplinary care.

Symptom Adverse Events and Quality of Life of Children With Advanced Cancer: Results From a Longitudinal Study Using the Pediatric Patient-Reported Outcomes-Common Terminology Criteria for Adverse Events.

Background: The presence of poorly controlled symptoms negatively impacts the quality of life (QoL) throughout cancer treatment. The purpose of this multisite study was to explore the relationship between QoL and symptom adverse events (AEs) in children with advanced cancer over 6 months. Method: A prospective and longitudinal descriptive study design was used to collect QoL and symptom AE data from children aged 2 to 18 with advanced cancer. QoL was measured using the Pediatric Quality of Life Inventory (PedsQLTM) Cancer Module 3.0 and symptom AEs were measured using the Pediatric Patient-Reported Outcome-Common Terminology Criteria for AEs (PRO-CTCAEs®). Descriptive statistics were used to describe QoL and symptom AE data. Correlational analyses and generalized linear mixed models were used to examine the relationship between symptom AEs and QoL. Results: Forty-nine children participated in the study. The mean total PedsQLTM score was 73.86 for the sample across all time points. Children diagnosed with a central nervous system (CNS) tumor reported poorer QoL compared to children diagnosed with a hematologic malignancy or non-CNS solid tumor. Symptom frequency AEs of anxiety, pain, nausea, insomnia, hot flashes, and fatigue severity demonstrated the strongest and most significant negative correlation with total QoL scores. Analyses of the relationship between QoL and symptom AEs over time revealed time-specific significant differences with children who experienced frequency AEs of nausea, and anxiety reporting poorer QoL at time point 4 (week 8). Discussion: The Ped PRO-CTCAE® and PedsQLTM can be used to evaluate the relationship between symptom AEs and QoL in practice and in future research.