Refractory Nausea Research Articles

Efficacy of Olanzapine for Symptom Relief in Cancer Patients

Olanzapine is an atypical antipsychotic and is widely used for prophylaxis of chemotherapy-induced nausea and vomiting in cancer patients. Previous studies have suggested its potential efficacy for the relief of various symptoms in cancer patients, especially gastrointestinal and psychiatric symptoms. We retrospectively reviewed the prescription of olanzapine to cancer patients at our hospital. Between 2008 and 2020, olanzapine was prescribed to 41 patients for relief of symptoms associated with cancer other than prophylaxis of chemotherapy-induced nausea and vomiting. Of those patients, symptom relief was seen in 53.7%. Notably, olanzapine was effective in 13 of 14 patients with chemotherapy-induced nausea and vomiting refractory to guideline-recommended prophylaxis. Of 16 patients in whom this symptom was not relieved by olanzapine, 13 (81.3%) continued taking olanzapine even after it was judged ineffective. No treatment-related adverse events were seen in this study. Our observation implies good efficacy of olanzapine for refractory chemotherapy-induced nausea and vomiting and a tendency to continue olanzapine even in those for whom it was ineffective.

A prospective study of intrapyloric botulinum toxin and EndoFLIP in children with nausea and vomiting.

Intrapyloric botulinum toxin injection (IPBI) is used to treat nausea and vomiting in children, but no prospective pediatric studies exist. The aims of the current study were to assess the efficacy of IPBI in children with refractory nausea or vomiting and to use EndoFLIP as a biomarker of IPBI response. This was a prospective observational cohort study of pediatric patients undergoing IPBI for refractory nausea, vomiting, or feeding difficulties at a tertiary center. Patients completed validated questionnaires at baseline and 1, 2, and 3 months after IPBI. A subset of patients >10 years old underwent pyloric EndoFLIP at the time of IPBI. Symptoms were compared pre- and post-IPBI, and EndoFLIP measurements were assessed in relation to baseline characteristics and response to IPBI. Forty-five patients (mean age 14.2 ± 6.0 years) received IPBI, and 23 of those patients underwent EndoFLIP. Twenty-nine patients (64%) had symptomatic improvement at 1-month follow-up, including improvements in overall GI symptoms (p=0.003), nausea and vomiting (p=0.009), and discomfort when eating (p=0.006). Symptomatic improvements lasted up to 3 months. There was a trend towards lower pyloric distensibility in patients with delayed versus normal gastric emptying (4.5 ± 3.8 mm² /mmHg in delayed vs. 8.9 ± 6.6 mm² /mmHg in normal, p=0.09), though there were no differences in EndoFLIP measurements between IPBI responders and non-responders (p > 0.05). The majority of patients responded to IPBI, with significant improvements seen in nausea, vomiting, and discomfort. Pyloric EndoFLIP tended to distinguish baseline delays in gastric emptying, but it did not predict IPBI response in this patient cohort.

Bowel recovery after intra- vs extra-corporeal anastomosis for oncologic laparoscopic right hemicolectomy within an ERAS protocol: a retrospective study.

Restoring bowel continuity after laparoscopic right hemicolectomy with an intra-corporeal (IC) rather than an extra-corporeal (EC) ileocolic anastomosis may offer advantages in post-operative recovery. The aim of this study was to compare bowel function recovery between these two techniques, in a context of complete mesocolic excision within an enhanced recovery after surgery (ERAS) protocol. All consecutive patients who underwent oncologic laparoscopic right hemicolectomy from January 2012 to February 2021 in our institution were included in the study. Data were gathered from the prospectively maintained official ERAS (EIAS) database and completed through our institution's electronic health records. The primary endpoint was prolonged post-operative ileus (PPOI), defined as the need to insert a nasogastric tube, or refractory nausea VAS > 4, on or after the third post-operative day. Secondary endpoints were post-operative pain, morbidity and length of hospital stay (LoS). Groups were compared before and after propensity score matching based on age, gender, ASA score, use of epidural analgesia and post-operative complications. A total of 108 patients met the inclusion criteria, 36 (30%) had IC and 72 (70%) EC anastomosis. In the unmatched population, baseline characteristics were similar except for more frequent use of epidural analgesia in the EC group (62 (72.9%) vs. 17 (47.2), p = 0.007). PSM analysis was carried out. Operative time was longer in the IC group (197min (176-223) vs. 160 (140-189), p < 0.001). The rate of PPOI was similar (2 (5.6%) patients in the IC group vs. 10 (11.6%) in the EC group (p = 0.306)), but time to frist passage of flatus and stool was shorter in the IC group. There was no difference in morbidity but patients after IC anastomosis had lower pain VAS scores at 24h (p = 0.004) and a trend for a shorter LoS (6 (5-8) days vs 7 (5-10) in the EC group, p = 0.054). After PSM, there were 36 patients in each group. PPOI, time to first flatus and stool, morbidity and LoS were not significantly different although there was a trend for better recovery outcomes in the IC group. Patients in the IC group had significantly longer operative times but less pain at 24h. Although IC anastomosis was not significantly associated to lower rates of PPOI, it showed trends of faster recovery and significantly less post-operative pain at the expense of longer operating times.

Bowel recovery after intra vs extracorporeal anastomosis for oncologic laparoscopic right hemicolectomy within an ERAS protocol: A retrospective study

Abstract Objective Restoring bowel continuity after laparoscopic right hemicolectomy with an intra-corporeal (IC) rather than an extracorporeal (EC) ileocolic anastomosis, may offer advantages in post-operative recovery. The aim of this study was to compare bowel function recovery between these two techniques, in a context of complete mesocolic excision within an enhanced recovery after surgery (ERAS) protocol. Methods All consecutive patients who underwent oncologic laparoscopic right hemicolectomy from January 2012 until February 2021 in our institution were included in the study. Data were gathered from the prospectively maintained official ERAS (EIAS) database and completed through our institution's electronic health records. The primary endpoint was Prolonged Postoperative Ileus (PPOI), defined as the need to insert a nasogastric tube, or refractory nausea VAS &amp;gt; 4, on or after the third postoperative day. Secondary endpoints were postoperative morbidity and length of hospital stay (LoS). Results 122 patients met the inclusion criteria, 36 (30%) had IC, and 86 (70%) EC anastomosis. Baseline characteristics were similar. Operative time was longer in the IC group (197 min (176–223) vs. 160 min (140–189, p&amp;lt;0.001). There was no difference in post-operative morbidity between groups. PPOI occurred in 2 (5.6%) patients in the IC group vs. 10 (11.6%) in the EC group (p=0.306). Patients in the IC group had an earlier first passage of gas (1.5 days (1–2) vs. 2 days (1–3), p=0.035) and stool (2 days (2–4) vs. 3 days (2–4), p=0.029). Upon multivariate analysis, pain VAS scores at 24 h, age and complications Clavien-Dindo &amp;gt;III, but not the anastomotic technique were independent predictors of slower bowel function recovery. IC anastomosis was an independent predictor of lower pain VAS scores at 24 h (OR 0.341, 95%CI [0.151–0.767], p=0.009) and shorter LoS (OR 0.346, 95%CI [0.132–0.910], p=0.031). Conclusion Although IC anastomosis was not significantly associated to lower rates of PPOI, it conferred advantages in terms of less post-operative pain, a trend for faster bowel recovery and shorter LoS at the expense of longer operating times.

Duodenal adenocarcinoma presenting as duodenal cystic dystrophy

A 79-year-old woman presented with refractory nausea, vomiting, and weight loss. EGD showed mucosal erythema and edema of the second part of the duodenum with lumen narrowing, leading to gastric outlet obstruction (GOO) (A). Endoscopic biopsy specimens showed mild focal nonspecific duodenitis. Subsequent EUS demonstrated a 23-mm (largest diameter) cystic structure in the duodenum arising from the muscularis propria (B). Specimens obtained by EUS-guided core needle biopsy showed atypical epithelium in the duodenal mucosa with acute inflammation and reactive changes.

Routes of administration, reasons for use, and approved indications of medical cannabis in oncology: a scoping review

IntroductionSome patients diagnosed with cancer use medical cannabis to self-manage undesirable symptoms, including nausea and pain. To improve patient safety and oncological care quality, the routes of administration for use of medical cannabis, patients’ reasons, and prescribed indications must be better understood.MethodsBased on the Joanna Briggs Institute guidelines, a scoping review was conducted to map the current evidence regarding the use of medical cannabis in oncological settings based on the experiences of patients diagnosed with cancer and their healthcare providers. A search strategy was developed with a scientific librarian which included five databases (CINAHL, Web of Science, Medline, Embase, and PsycINFO) and two grey literature sources (Google Scholar and ProQuest). The inclusion criteria were: 1) population: adults aged 18 and over diagnosed with cancer; 2) phenomena of interest: reasons for cannabis use and/or the prescribed indications for medical cannabis; 3) context: oncological setting. French- or English-language primary empirical studies, knowledge syntheses, and grey literature published between 2000 and 2021 were included. Data were extracted by two independent reviewers and subjected to a thematic analysis. A narrative description approach was used to synthesize and present the findings.ResultsWe identified 5,283 publications, of which 163 met the eligibility criteria. Two main reasons for medical cannabis use emerged from the thematic analysis: limiting the impacts of cancer and its side effects; and staying connected to others. Our results also indicated that medical cannabis is mostly used for three approved indications: to manage refractory nausea and vomiting, to complement pain management, and to improve appetite and food intake. We highlighted 11 routes of administration for medical cannabis, with oils and oral solutions the most frequently reported.ConclusionFuture studies should consider the multiple routes of administration for medical cannabis, such as inhalation and edibles. Our review highlights that learning opportunities would support the development of healthcare providers’ knowledge and skills in assessing the needs and preferences of patients diagnosed with cancer who use medical cannabis.

Sick sinus syndrome as the initial manifestation of neuromyelitis optica spectrum disorder: a case report

BackgroundSick sinus syndrome (SSS) is known to occur due to lesions in the medulla oblongata. Although medullary lesions have occurred in patients with neuromyelitis optica spectrum disorder (NMOSD), there are few reports of SSS associated with NMOSD. We report a patient with NMOSD who developed refractory nausea, vomiting and SSS as the initial manifestation.Case presentationA 77-year-old female developed refractory nausea and frequent episodes of syncope. The patient was diagnosed with SSS because sinus pauses lasting five to six seconds were observed, and pacemaker implantation was performed. Two months later, she was referred to our hospital because of limb weakness and sensory impairment that progressed over a month. The patient was confirmed to have muscle weakness; manual muscle testing revealed grade 4 in the upper extremities and grade 3 in the lower extremities. Tendon reflexes were diminished, while no pathological reflexes were present. Thermal and pain sensations were impaired in the upper and lower extremities, and vibration sensation was impaired in both lower extremities. Bladder and rectal disturbances were also noted. Optic neuritis was not detected. T2-weighted magnetic resonance imaging (MRI) showed high-intensity lesions in the dorsal part of the medulla oblongata and C3–6 cervical cord. Her serum was positive for antibodies against aquaporin 4, and a diagnosis of NMOSD was made. She was treated with two courses of an intravenous methylprednisolone pulse and one course of plasma exchange. Then, she was transferred to another hospital for rehabilitation.ConclusionsBecause SSS is a life-threatening complication, clinicians should be aware of the possibility that medullary lesions in NMOSD can cause SSS as the initial manifestation.

34-Year-Old Woman With Human Immunodeficiency Virus and Chronic Diarrhea

A 34-year-old woman with a history of human immunodeficiency virus (HIV) treated with antiretroviral therapy (ART) for 1 year, chronic hepatitis B, latent tuberculosis, and treated Helicobacter pylori infection was transferred to our institution for the evaluation of refractory abdominal pain, nausea, vomiting, and diarrhea. She experienced about 10 to 12 daily episodes of Bristol type 7 stool associated with abdominal bloating and cramping for a year with intermittent episodes requiring hospital admission for failure to thrive.

Implementation of a clinical pharmacist-led service to optimize management of refractory chemotherapy-induced nausea and vomiting in adult hematology/oncology clinic.

Chemotherapy-induced nausea and vomiting (CINV) is a common and potentially debilitating adverse effect of chemotherapy. Refractory CINV can be particularly difficult to control. This report provides details on the implementation and evaluation of a pharmacist-led program for the management of refractory CINV in hematology and oncology clinics. A pharmacist-led program open to adult outpatients with refractory CINV was implemented at University of Wisconsin. Pharmacists conducted baseline and follow-up assessments, provided patient education, and started, discontinued, and/or adjusted antiemetics as clinically necessary for all enrolled patients. Retrospective chart review was used to describe the proportion of patients whose CINV improved through pharmacist intervention, effect of the program on antiemetic adherence, categorization of pharmacist interventions, and duration of patient enrollment. Forty-six patients were enrolled between February 2019 and January 2020. Forty-one patients (89.1%) had an overall reduction in their nausea and vomiting from baseline. Eleven patients (23.9%) met criteria for nonadherence to prescribed antiemetics at baseline; all patients were adherent at unenrollment. A total of 111 pharmacist interventions were made. The most common intervention was addition of new breakthrough antiemetic. The least common intervention was dose escalation of a previously prescribed antiemetic. The average number of interventions made per patient was 2.5. On average, patients were enrolled in the program for 16.6 days and met with a pharmacist three times. Implementation of this program standardized and streamlined pharmacist involvement with refractory CINV. Enrollment resulted in a measurable reduction in nausea and/or vomiting for patients with refractory CINV.

Haloperidol Use in the Emergency Department for Gastrointestinal Symptoms: Nausea, Vomiting, and Abdominal Pain.

INTRODUCTION:Haloperidol (HL) has successfully been used for nausea and abdominal pain in emergency departments (EDs). This study examines outcomes and predictive factors for clinical improvement of patients presenting to an ED with gastrointestinal (GI) symptoms (nausea, vomiting, and abdominal pain) who received HL.METHODS:Review of patients' records who presented to our ED between August 2016 and March 2019 with GI symptoms and received HL. International Classification of Diseases, Tenth Revision codes were used to identify patients.RESULTS:In all, 281 patients (410 encounters) presented to the ED with GI symptoms and received HL for their symptoms: 66% were women, 32% had diabetes, 68% used marijuana, and 27% used chronic opioids. Patients received HL 1.1 ± 0.3 times with dose 2.5 ± 3.0 mg, mostly intravenously (84.6%). Total ED length of stay was 7.5 ± 3.9 hours (3.2 ± 2.1 hours before HL and 4.4 ± 3.4 hours after). Approximately 4.4% of patients developed side effects to HL, including 2 patients with dystonia which improved with medication before discharge. Most patients (56.6%) were discharged home while 43.2% were admitted to hospital mostly because of refractory nausea or vomiting (70.1%). Receiving HL as the only medication in the ED led to lower hospital admission (odds ratio = 0.25, P < 0.05). Diabetes, cannabinoid use, anxiety, male sex, and longer ED stay were associated with increased hospital admissions.DISCUSSION:Most patients treated in our ED with HL for GI symptoms, particularly nausea, vomiting, and/or abdominal pain, were successfully treated and discharged home. HL use seemed relatively safe and, when used as the only medication, led to less frequent hospital admissions.

Long-Term Daily Administration of Aprepitant for the Management of Intractable Nausea and Vomiting in Children With Life-Limiting Conditions: A Case Series

BackgroundNausea and vomiting is a common symptom in children through their end of life journey. Aprepitant, a NK-1 antagonist, has become a potent weapon in the fight against chemo-induced nausea and vomiting. However, its use in palliative care for refractory nausea and vomiting has been limited due to limited experience or evidence of continuous use. Emerging evidence suggests that continuous use is not only safe, but also effective in patients with nausea and vomiting refractory to multiple lines of antiemetic therapy. MethodsWe conducted a single centre retrospective chart review of children receiving care from a specialist palliative care team who were given continuous daily aprepitant for nausea and vomiting and were unresponsive to at least two prior lines of antiemetic therapy. Parental reports of the impact of nausea on mobility and feeding were used as proxy efficacy markers. Duration of effect and toxicity was also evaluated. ResultsTen children (eight with cancer as a primary diagnosis and two with noncancer diagnoses) received continuous aprepitant and all showed resolution of nausea and vomiting and an increased ability to mobilize and tolerate feeds. No adverse events noted. ConclusionOur review suggests a role for aprepitant in management of refractory nausea and vomiting, demonstrating safety and efficacy. This case series is the first report of aprepitant use in this manner in the paediatric palliative care setting.

Bowel function recovery after laparoscopic transverse colectomy within an ERAS program: a comparison to right and left colectomy

It is known that functional recovery of the bowel is slower after right colectomy (RC) compared to left colectomy (LC), but very little has been reported on transverse colectomy (TC). The aim of this study was to compare the clinical and early functional outcomes of TC, a more infrequent operation, to RC, and LC for colorectal cancer. Between December 2011 and December 2017, all patients undergoing elective colon resection in our institution were treated according to a standardized ERAS protocol and entered in a prospective database. We included in the study patients undergoing laparoscopic TC, RC, or LC for cancer with curative intent. The primary endpoint was prolonged postoperative ileus (PPOI), defined as need to insert a nasogastric tube, or refractory nausea VAS > 4 on or after the third postoperative day. Secondary endpoints were postoperative morbidity and length of hospital stay (LoS). Out of 286 patients, 126 met the inclusion criteria: 20 underwent TC, 65 RC, and 41 LC. Patients in LC group were younger than in TC and RC groups; other baseline demographics were similar. PPOI was observed in 5 (25%), 26 (40%), and 10 (24%) patients in TC, RC, and LC groups, respectively (p= 0.417). In single group comparisons, the incidence of PPOI in the TC group was significantly lower in comparison to the RC group (OR for RC: 4.255, 95% CI 1.092-16.667, p= 0.037) and similar to the LC group. No significant differences in terms of postoperative complications or LoS stay were observed. The incidence of PPOI after segmental laparoscopic colectomy for cancer within an ERAS program appears as infrequent in TC as in LC and lower than after RC. It may be reasonable to consider a slower oral intake after RC, as it represents an independent predictor of PPOI.

Treatment of Cannabinoid Hyperemesis Syndrome-Associated Nausea with Haloperidol: A Case Report

Introduction: Because of the rising prevalence of cannabis abuse, cannabinoid hyperemesis syndrome (CHS) was recognized as a new medical diagnosis in 2004. Despite the syndrome’s growing prevalence, many providers are unfamiliar with its diagnosis and treatment, and there is little data to back up clinical knowledge and treatment recommendations. For many years, haloperidol has been widely used as an antiemetic, despite a lack of evidence-based clinical data on efficacy and side effects. We present the case of a female who presented to the emergency room with suspected CHS and was treated with haloperidol. Case: A 34-year-old African-American woman with diabetes and a history of marijuana use presented to the emergency department with refractory nausea and vomiting. Her urine drug screen came back positive for THC, but she denied using marijuana prior to this admission. She stated that she was following her current medication regimen. She denied drinking alcohol and smoking cigarettes. Multiple doses of ondansetron, promethazine, scopolamine, and metoclopramide had no effect on the patient. After two days of treatment with haloperidol 5 mg by mouth every 8 hours, nausea and vomiting subsided. Discussion: Haloperidol was able to control nausea and vomiting in six previous case reports of CHS. However, haloperidol was administered intravenously in five of the reports, and the route of administration was not specified in the sixth. To the best of our knowledge, we are the first to demonstrate the benefit of oral haloperidol for CHS. Conclusion: Although cessation of marijuana use is required for long-term resolution of CHS, our case and six others show the benefit of using IV haloperidol for acute management and oral for relapse prevention. More extensive clinical trials are needed to confirm haloperidol’s therapeutic role in patients presenting with CHS symptoms.

Gastrointestinal: Franseen-tip transmural fine-needle biopsy for localized gastric linitis plastica.

A 59-year-old male patient presented with refractory nausea and vomiting. Esophagogastroduodenoscopy revealed a concentric, malignant-appearing stricture in the distal antrum (Fig. 1a). Of note, despite the clinical picture of functional outlet obstruction, endoscopic passage into the duodenum was maintained. However, two extensive rounds of conventional mucosal biopsies (each > 12) did not yield a malignant histology. While a thoracoabdominal computed tomography scan excluded distant metastases, endoscopic ultrasound (EUS) revealed marked, diffusely hypoechogenic wall thickening up to 30 mm with irregular margins and fusion of layers, highly suggestive of gastric linitis plastica (GLP) (Fig. 1b, linear probe: Pentax, EG38J10UT). Final locoregional staging was determined uT3N0, and transmural EUS fine-needle biopsy (FNB) using a novel FNB-dedicated 22G Franseen-tip needle was performed (Acquire, Boston Scientific) (Fig. 1c). Relative to more established EUS-FNB needle, such as the Procore needle, the specific design of the needle with its stabilizing three-point tip allows for improved tissue capture and reduced fragmentation. EUS-FNB was performed in the slow pull technique with extensive fanning through the lesion, resulting in a macroscopically excellent yield (Fig. 1d). Pathology assessment indicated atypical epithelial cells with a prominent desmoplastic stroma within the muscularis propria (Fig. 1e, top). There was faint granular positivity in the periodic acid-Schiff staining, albeit a clear-cut signet ring morphology was absent. Ancillary immunohistochemistries were positive for CK-20 (Fig. 1e, lower left), CDX-2 (Fig. 1e, lower right), and (not shown) carcinoembryonic antigen, while p53 remained negative. In conjunction with clinical characteristics, a final diagnosis of poorly differentiated adenocarcinoma underlying linitis plastica was entertained. After an unremarkable ileocolonoscopy, the patient underwent diagnostic laparoscopy, excluding peritoneal carcinomatosis and providing an enteral nutrition access, and perioperative chemotherapy using FLOT4 (fluorouracil plus leucovorin, oxaliplatin, and docetaxel) was recommended prior to surgical gastrectomy. EUS-based tissue acquisition of either the gastric wall and/or suspicious lymph nodes is instrumental in confirming the malignant nature of gastric wall thickening, albeit the distinct benefit of newer FNB-dedicated needles, such as with a Franseen-tip design, considered to translate into improved maintenance of tissue architecture, is yet to be better determined in systematic, GLP-exclusive analyses.

Impact of Gastric Electrical Stimulation on Economic Burden of Refractory Vomiting: A French Nationwide Multicentre Study

Medico-economic data of patients suffering from chronic nausea and vomiting are lacking. In these patients, gastric electrical stimulation (GES) is an effective, but costly treatment. The aim of this study was to assess the efficacy, safety and medico-economic impact of Enterra therapy in patients with chronic medically refractory nausea and vomiting. Data were collected prospectively from patients with medically refractory nausea and/or vomiting, implanted with an Enterra device and followed for two years. Gastrointestinal quality of life index (GIQLI) score, vomiting frequency, nutritional status and safety were evaluated. Direct and indirect expenditure data were prospectively collected in diaries. Complete clinical data were available for142 patients (60 diabetic, 82 non-diabetic) and medico-economic data were available for 96 patients (36 diabetic, 60 non-diabetic), 24 months after implantation. GIQLI score increased by 12.1 ± 25.0 points (p < .001), with a more significant improvement in non-diabetic than in diabetic patients (+15.8 ± 25.0 points, p < .001 versus 7.3 ± 24.5 points, p = .027, respectively). The proportion of patients vomiting less than once per month increased by 25.5% (p < .001). Hospitalisations, time off work and transport were the main sources of costs. Enterra therapy decreased mean overall healthcare costs from 8873 US$ to 5525 US$ /patient/year (p= .001), representing a saving of 3348 US$ per patient and per year. Savings were greater for diabetic patients (4096 US$ /patient/year) than for non-diabetic patients (2900 US$ /patient/year). Enterra therapy is an effective, safe and cost-effective option for patients with refractory nausea and vomiting. gov Identifier: NCT00903799.

S0473 Domperidone Is Superior Compared With Metoclopramide in Improving Gastroparesis Symptoms: A Systematic Review and Meta-Analysis

INTRODUCTION: Gastroparesis (GP) is a syndrome presenting with refractory nausea, vomiting, early satiety, and bloating in the setting of delayed gastric emptying (GE) in the absence of mechanical obstruction. Medical management of GP is difficult, and the outcome is often poor. Metoclopramide (MCP) and domperidone are antiemetics and prokinetics with antidopaminergic activities. They produce their antiemetic effects through the chemoreceptor trigger zone, and they function as prokinetics by blocking dopamine in the stomach and proximal duodenum. Unlike domperidone, MCP is permeable to the blood-brain barrier and has a “black box” warning for tardive dyskinesia. However, domperidone is only prescribed under an Investigational New Drug protocol in the United States, mainly due to scattered reports of cardiac events related to prolonged QTc interval. In this meta-analysis, the authors sought to compare the effects of MCP and domperidone for improving GP symptoms. METHODS: A search in PubMed, Embase, American College of Gastroenterology, and Digestive Disease Week abstracts database was performed to find trials on MCP and domperidone in GP. Direct and indirect comparisons of GP symptom and GE improvement with MCP and domperidone were pooled and were reported as mean (standard deviation). Random effects model was used in this meta-analysis to overcome limitations related to heterogeneity. RESULTS: Response to MCP (3-6 weeks treatment), domperidone (4 weeks to 4 years), and domperidone vs MCP (4 weeks treatment) were examined in 5, 10, and 1 (Patterson 1999) published studies, respectively. Overall, 99 and 421 GP patients received MCP and domperidone, respectively. MCP had an overall symptom improvement rate of 48.8 (95% CI: 38.8–58.70) compared with 63.6 (95% CI: 55.1–71.7) (P < 0.05) improvement in domperidone-treated groups (Figures 1 and 2). MCP and domperidone improved GE by 19.7 (SD: 6.6) and 30.7% (SD: 13.9), respectively (P > 0.05) involving different methodologies. No major adverse events, including acute coronary syndrome, serious arrhythmias, or cardiac death were reported with domperidone. Most recent studies provided QTc values which did not show any clinically significant QTc prolongation. CONCLUSION: Domperidone demonstrates significant superiority compared to MCP. It is safe and effective in GP when administered under monitored conditions. Promotility effects of domperidone are complemented by its powerful antiemetic properties providing a clinically valuable symptom control in GP patients.Figure 1.: Pooled overall gastroparesis symptom improvement rate after metoclopramide treatment.Figure 2.: Pooled overall gastroparesis symptom improvement rate after domperidone treatment.

Improvement of Cardiac Structure And Function In Hereditary Transthyretin Amyloidosis Cardiomyopathy With Inotersen: A Case Report

Introduction Hereditary transthyretin amyloidosis (hATTR) is a progressive, fatal disease caused by systemic deposition of misfolded transthyretin (TTR) fibrils resulting in cardiomyopathy (CM) and polyneuropathy (PN). Treatment options include stabilizers (tafamidis) to prevent TTR tetramer dissociation, silencers (inotersen, patisiran) that inhibit hepatic TTR synthesis, or liver transplantation. Silencers have favorable outcomes in PN, with limited data on CM. This case highlights improvement in hATTR-CM in a patient treated with inotersen. Patient Case A 68 year old female with a family history of hATTR presented for evaluation as a heterozygous carrier of the p.T80A (T60A) TTR mutation. She experienced refractory nausea, vomiting, diarrhea alternating with constipation, weight loss (10 kg) over the preceding 6 months, and 2 months of new onset exertional dyspnea and was in NYHA Class 2 heart failure. ECHO showed severe concentric hypertrophy (septal and posterior walls, 2.1 cm and 1.9 cm), moderate reduction in left ventricular systolic function with a left ventricular ejection fraction (LVEF) of 32%, and moderate pericardial effusion. BNP and troponin I levels were 532 pg/mL and 0.05 ng/mL. Diffuse 4-chamber delayed gadolinium enhancement was noted on cardiac MRI (A). Nerve conduction studies confirmed sensorimotor neuropathy with an estimated neuropathy impairment score of 10. Furosemide and spironolactone resulted in a 6.4 kg diuresis with improved dyspnea. Right heart catheterization showed right atrial pressure of 6 mm Hg, pulmonary artery pressure of 39/16 mm Hg, and pulmonary capillary wedge pressure of 10 mm, with a cardiac index of 2. Episodic orthostatic hypotension precluded initiation of beta blockers and vasodilators. She was initiated on inotersen for symptoms of neuropathy. After 6 months, LVEF increased to 45% and diastolic function improved from stage 2 to 1. The pericardial effusion resolved. Six minute walk distance showed an increasing trend over 10 months (B). BNP levels were 108 pg/mL after 1 year on inotersen, and modified BMI stabilized. Conclusion Inotersen was associated with improvements in cardiac function in this patient with hATTR-CM who could not be treated with guideline-directed heart failure therapy. For hATTR-CM with no convincing benefit from conventional therapy beyond symptom control, inotersen may offer a treatment option to alter the natural history of this fatal disease.

Efficacy of gastric electrical stimulation in intractable nausea and vomiting at 10 years: A retrospective analysis of prospectively collected data.

Gastric electrical simulation has been shown to relieve nausea and vomiting in medically refractory patients. Efficacy of gastric electrical stimulation has been reported mostly in short-term studies, but none has evaluated its efficacy beyond 10years after implantation. Patients implanted at our center for medically refractory severe and chronic nausea and/or vomiting were evaluated before and over 10years after implantation using symptomatic scale and quality of life (GIQLI) score. Improvement was defined as a reduction of more than 50% in vomiting frequency. A total of 50 patients were implanted from January 1998 to December 2009. Among them, 7 were explanted due to a lack of efficacy and/or side effects, 2 died, and 4 were lost to follow-up. Mean follow-up was 10.5±3.7years. In intention-to-treat analysis, 27/50 (54%) patients reported an improvement. Beyond 10years, an improvement in early satiety (3.05 vs 1.76, <0.001), bloating (2.51 vs 1.70, P=.012), nausea (2.46 vs 1.35, P=.001), and vomiting (3.35 vs 1.49 P<.001) scores were observed. Quality of life improved over 10years (GIQLI score: 69.7 vs. 86.4, P=.005) and body mass index (BMI: 23.4 vs. 26.2kg/m2 ; P=.048). Gastric electrical simulation is effective in the long-term in patients with medically refractory nausea and vomiting, with an efficacy of 54% at 10years on an intention-to-treat analysis. Other long-term observational studies are warranted to confirm these results.

The role of diet in the treatment of eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic immuno- or antigen-mediated condition leading to eosinophilic inflammation of the esophagus. As a result, esophageal dysfunction develops, presenting in adults mainly with dysphagia and heartburn. In children, the main symptoms are abdominal pain, refractory reflux complaints, nausea and vomiting. Treatment with oral topical corticosteroids and proton-pump inhibitors are well-established therapeutic tools. Dietary restrictions have a proven beneficial effect on clinical symptoms. Elimination diets are not without risk and can impact nutritional status, eating pleasure and quality of life. With adequate selection and balance, dietary therapy can be effective and the adverse effects on lifestyle can be minimized. The review presents a brief overview of the possibilities and guidance for dietary therapy of this increasingly recognizable disease.

Dronabinol Prescribing and Exposure Among Children and Young Adults Diagnosed with Cancer.

Purpose: The therapeutic utility of Cannabis in cancer is a topic of intense interest. Dronabinol is synthetic Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of Cannabis sativa, and is approved for treating refractory chemotherapy-induced nausea and vomiting. Little is known about dronabinol prescribing in children and young adults, and no published concentration data are available. This study evaluated national level dronabinol use and assessed concentrations of THC and its primary metabolites in patients with cancer <27 years of age prescribed dronabinol. Methods: Observational review of records from the Pediatric Health Information System (PHIS) and a regional network of hospitals in the Intermountain West, including a tertiary care children's hospital, Primary Children's Hospital (PCH), for inpatients <27 years of age prescribed dronabinol. Prospective blood samples were collected from children with cancer at PCH. Results: Across PHIS institutions, overall dronabinol prescribing aligned with the pharmacy records for those with cancer (p < 0.0001), and of these, 10.4% received dronabinol as inpatients. Blood collected within 72 hours of dronabinol administration was available from 10 children with a median age of 12.5 (range 6-17) years. Quantifiable concentrations were found in 4 (13%), 6 (20%), and 1 (3%) samples assayed for THC, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (COOH-THC), and 11-hydroxy-Δ9-tetrahydrocannabinol (OH-THC), respectively. THC concentrations ranged between 0.100 and 0.128 ng/mL and were not associated with dose. Conclusion: Dronabinol prescribing appears exclusive to patients diagnosed with cancer, and its use has increased steadily in the past decade. In a small sample of children administered dronabinol, THC and metabolite concentrations were consistently low or undetectable.