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Concept: Nausea

259

Human noroviruses (NoV) are the leading cause of acute gastroenteritis worldwide. Epidemiological studies of outbreaks have suggested that vomiting facilitates transmission of human NoV, but there have been no laboratory-based studies characterizing the degree of NoV release during a vomiting event. The purpose of this work was to demonstrate that virus aerosolization occurs in a simulated vomiting event, and to estimate the amount of virus that is released in those aerosols. A simulated vomiting device was constructed at one-quarter scale of the human body following similitude principles. Simulated vomitus matrices at low (6.24 mPa*s) and high (177.5 mPa*s) viscosities were inoculated with low (108 PFU/mL) and high (1010 PFU/mL) concentrations of bacteriophage MS2 and placed in the artificial “stomach” of the device, which was then subjected to scaled physiologically relevant pressures associated with vomiting. Bio aerosols were captured using an SKC Biosampler. In low viscosity artificial vomitus, there were notable differences between recovered aerosolized MS2 as a function of pressure (i.e., greater aerosolization with increased pressure), although this was not always statistically significant. This relationship disappeared when using high viscosity simulated vomitus. The amount of MS2 aerosolized as a percent of total virus “vomited” ranged from 7.2 x 10-5 to 2.67 x 10-2 (which corresponded to a range of 36 to 13,350 PFU total). To our knowledge, this is the first study to document and measure aerosolization of a NoV surrogate in a similitude-based physical model. This has implications for better understanding the transmission dynamics of human NoV and for risk modeling purposes, both of which can help in designing effective infection control measures.

Concepts: Epidemiology, Microbiology, Virus, Bacteriophage, Vomiting, Gastroenteritis, Norovirus, Nausea

220

Roughly one in three individuals is highly susceptible to motion sickness and yet the underlying causes of this condition are not well understood. Despite high heritability, no associated genetic factors have been discovered. Here, we conducted the first genome-wide association study on motion sickness in 80,494 individuals from the 23andMe database who were surveyed about car sickness. Thirty-five single-nucleotide polymorphisms (SNPs) were associated with motion sickness at a genome-wide-significant level (p<5×10-8). Many of these SNPs are near genes involved in balance, and eye, ear, and cranial development (e.g., PVRL3, TSHZ1, MUTED, HOXB3, HOXD3). Other SNPs may affect motion sickness through nearby genes with roles in the nervous system, glucose homeostasis, or hypoxia. We show that several of these SNPs display sex-specific effects, with up to three times stronger effects in women. We searched for comorbid phenotypes with motion sickness, confirming associations with known comorbidities including migraines, postoperative nausea and vomiting (PONV), vertigo, and morning sickness, and observing new associations with altitude sickness and many gastrointestinal conditions. We also show that two of these related phenotypes (PONV and migraines) share underlying genetic factors with motion sickness. These results point to the importance of the nervous system in motion sickness and suggest a role for glucose levels in motion-induced nausea and vomiting, a finding that may provide insight into other nausea-related phenotypes like PONV. They also highlight personal characteristics (e.g., being a poor sleeper) that correlate with motion sickness, findings that could help identify risk factors or treatments.

Concepts: Central nervous system, DNA, Genetics, Bioinformatics, Vomiting, Nausea, Metoclopramide, Postoperative nausea and vomiting

178

We report information about an unpublished 1970s study (“8-way” Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and dicyclomine in the management of nausea and vomiting during pregnancy. We are publishing the trial’s findings according to the restoring invisible and abandoned trials (RIAT) initiative because the trial was never published.

Concepts: Epidemiology, Randomized controlled trial, ClinicalTrials.gov, Efficacy, The Trial, Nausea, Trial, Morning sickness

149

Hyperemesis gravidarum (HG), or intractable vomiting during pregnancy, is the single most frequent cause of hospital admission in early pregnancy. HG has a major impact on maternal quality of life and has repeatedly been associated with poor pregnancy outcome such as low birth weight. Currently, women with HG are admitted to hospital for intravenous fluid replacement, without receiving specific nutritional attention. Nasogastric tube feeding is sometimes used as last resort treatment. At present no randomised trials on dietary or rehydration interventions have been performed. Small observational studies indicate that enteral tube feeding may have the ability to effectively treat dehydration and malnutrition and alleviate nausea and vomiting symptoms. We aim to evaluate the effectiveness of early enteral tube feeding in addition to standard care on nausea and vomiting symptoms and pregnancy outcomes in HG patients.

Concepts: Nutrition, Obstetrics, Dehydration, Vomiting, Nausea, Hyperemesis gravidarum, Morning sickness

76

Nausea and vomiting during pregnancy have been associated with a reduced risk for pregnancy loss. However, most prior studies enrolled women with clinically recognized pregnancies, thereby missing early losses.

Concepts: Pregnancy, Childbirth, Clinical trial, Abortion, Miscarriage, Human chorionic gonadotropin, Nausea, Morning sickness

68

Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, occurs in 0.3-2% of pregnancies and is associated with maternal and fetal morbidity. The cause of HG remains unknown, but familial aggregation and results of twin studies suggest that understanding the genetic contribution is essential for comprehending the disease etiology. Here, we conduct a genome-wide association study (GWAS) for binary (HG) and ordinal (severity of nausea and vomiting) phenotypes of pregnancy complications. Two loci, chr19p13.11 and chr4q12, are genome-wide significant (p < 5 × 10-8) in both association scans and are replicated in an independent cohort. The genes implicated at these two loci are GDF15 and IGFBP7 respectively, both known to be involved in placentation, appetite, and cachexia. While proving the casual roles of GDF15 and IGFBP7 in nausea and vomiting of pregnancy requires further study, this GWAS provides insights into the genetic risk factors contributing to the disease.

Concepts: Pregnancy, Genetics, Fetus, Genome-wide association study, Vomiting, Nausea, Hyperemesis gravidarum, Morning sickness

47

Nausea and vomiting in early pregnancy (NVEP) is commonly encountered in family medicine. Ginger (Zingiber officinale) is a popular nonpharmacological treatment but consensus of its use is lacking.

Concepts: Vomiting, Nausea, Ginger, Morning sickness, Zingiberaceae, Zingiber, Motion sickness, Seasickness

43

We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy.

Concepts: Chemotherapy, Serotonin, Vomiting, Gastroenteritis, Nausea

36

OBJECTIVE: The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors. STUDY DESIGN: This is a case-control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test. RESULTS: Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p<0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p<0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p<0.0089). Poor outcomes were associated with early start of symptoms (p<0.019), and treatment with methylprednisolone (p<0.0217), promethazine (p<0.0386), and other antihistamines [diphenhydramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p<0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome. CONCLUSION: Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy.

Concepts: Pregnancy, Childbirth, Obstetrics, Antiemetic, Nausea, Hyperemesis gravidarum, Morning sickness, Diphenhydramine

30

The rhizomes of Zingiber officinale (ginger) have been used since ancient times as a traditional remedy for gastrointestinal complaints. The most active ingredients in ginger are the pungent principles, particularly gingerols and shogaols. Various preclinical and clinical studies have evaluated ginger as an effective and safe treatment for nausea and vomiting in the context of pregnancy and as an adjuvant treatment for chemotherapy-induced nausea and vomiting. Here, we provide an update and analysis of ginger use for the prevention of nausea and vomiting, with a focus on the types and presentations of ginger available. We also examine the pharmacokinetic properties of ginger and highlight the type and posology of ginger and its metabolites.

Concepts: Pharmacology, Clinical trial, Effectiveness, Pharmacokinetics, Nausea, Ginger, Morning sickness, Zingiber