Risk factors associated with nausea and vomiting in children with cancer receiving chemotherapy.

INTRODUCTION: Despite treatment with antiemetic medications, nausea remains uncontrolled for many children receiving chemotherapy. One reason is that risk factors for nausea in children remain poorly explored. The purpose of this study was to identify risk factors for chemotherapy-induced nausea (CIN) in children. METHODS: Prospective, observational study including 101 children (median age 6.4 years, range 0.8-17.9) with cancer receiving moderately or highly emetogenic chemotherapy. Primary endpoints were complete control of acute and delayed CIN, defined as no nausea in the acute phase 0-24 h after chemotherapy and in the delayed phase starting after the acute phase and ending 5 days later. Multivariable analyses included age, sex, cancer type, susceptibility to motion sickness, chemotherapy duration, numbers of antiemetics, co-administration with opioids or tricyclic antidepressants, and previously uncontrolled nausea or vomiting. RESULTS: Acute CIN was associated with susceptibility to motion sickness (odds ratio [OR] 5.73, 95% confidence interval [CI] 1.36-33.7) and older age (OR 4.19, 95% CI 1.30-14.7), comparing age group 8-18 years with 0-3 years. Delayed CIN was associated with uncontrolled acute nausea or vomiting (OR 10.3, 95% CI 2.65-50.9), highly emetogenic chemotherapy (OR 8.26, 95% CI 1.17-76.8), and having a hematologic cancer type (OR 7.81, 95% CI 1.05-79.2). CONCLUSIONS: Susceptibility to motion sickness and age can influence the risk of acute CIN. More research is needed on how best to integrate risk information in preventive antiemetic strategies. Sufficient acute nausea and vomiting control are crucial to prevent delayed CIN.

[The efficacy and safety of proton pump inhibitors in infants with reflux].

Proton pump inhibitors (PPIs) are widely used in Denmark as a treatment for gastrooesophageal reflux disease (GERD) in infants under 12 months of age. In this review, we investigated the efficacy and safety of treatment with PPI against GERD in infants. We found that PPIs increased ventricular pH in infants but without a decline in symptoms of GERD compared with placebo. More frequent and serious adverse effects were observed after PPI treatment than after placebo. The available published evidence indicates that PPIs cannot be recommended as a treatment for GERD in infants.

Safety of rapid intravenous paracetamol infusion in paediatric patients.

PURPOSE: Paracetamol is recommended as a first-line treatment for pain and fever in paediatric patients. Intravenous (IV) infusions are recommended to be administered as a 15-min infusion to minimize local tissue trauma and related pain. The purpose of this study was to demonstrate that IV paracetamol could be administered during 5 â€‹min or less in paediatric patients without causing related adverse reactions. METHODS: Prospective, observational safety study including children aged <18 years who received IV paracetamol. Pain scores before and after the paracetamol infusions were obtained using VAS, FLACC, COMFORT neo, or COMFORT behaviour scales with scores from 0 to 10 representing no pain to worst pain. Further, objective signs of inflammation at the infusion site were registered. FINDINGS: We included 44 patients (median age 2.8 years, range 0.01-17.0 years) who received paracetamol in a peripheral venous catheter (n â€‹= â€‹22) or central venous catheter (n â€‹= â€‹22). In total, the 93 paracetamol infusions had a median infusion time of 3:00 â€‹min, range 0:40 to 5:00 â€‹min. After infusions, pain scores were lower, compared to before infusions (mean change -0.26, 95% confidence interval -0.45 to -0.07, P â€‹= â€‹0.007), and no objective signs of inflammation were reported. IMPLICATIONS: This safety study indicates that IV paracetamol can be administered in paediatric patients with a shorter infusion time than recommended without causing adverse reactions. The results may contribute to a more efficient workflow at paediatric departments.

Background sensitivity to chemotherapy-induced nausea and vomiting and response to antiemetics in paediatric patients: a genetic association study.

Chemotherapy-induced nausea and vomiting (CINV) remains a common adverse effect for children with cancer. In children, chemotherapy emetogenicity and patient factors such as susceptibility to motion sickness and age group determine a patient's risk of CINV. Besides known risk factors, genetic factors may play a role in interindividual variation in the occurrence of CINV. We investigated the influence of candidate gene polymorphisms on the efficacy of antiemetics and on the background sensitivity to CINV in children. This prospective study included 100 children with cancer (median age 6.4 years, range 0.8-17.9) who received moderately to highly emetogenic chemotherapy. Participants registered nausea and vomiting episodes in a mobile app. Genotypes were determined by whole-genome sequencing (n = 79) or Sanger sequencing (n = 21) for 71 genetic polymorphisms involved in motion sickness and antiemetic pathways. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate associations between acute CINV and genotypes adjusting for susceptibility to motion sickness and age group. Rs3782025 in the 5-hydroxytryptamine type 3 (5-HT3) receptor gene (HTR3B) [minor allele frequency (MAF): 0.48] affected response to 5-HT3 receptor antagonists; acute CINV occurred in 76% of patients with GA/AA genotypes and in 41% of patients with GG genotype (OR 5.59; 95% CI 1.74-17.9, dominant genetic model). Rs2975226 in the dopamine transporter gene (SLC6A3) (MAF: 0.54) was associated with acute CINV (OR 5.79; 95% CI 1.09-30.67, recessive genetic model). Polymorphisms in HTR3B and SLC6A3 may contribute to the variability in response to antiemetic prophylaxis for CINV in children.

Smartphone App to Self-Monitor Nausea During Pediatric Chemotherapy Treatment: User-Centered Design Process.

BACKGROUND: Nausea and vomiting are common and distressing side effects for children receiving chemotherapy. Limited evidence is available to guide antiemetic recommendations; therefore, prospective and reliable evaluation of antiemetic efficacy is needed. Smartphone apps can be used to effortlessly and precisely collect patient-reported outcomes in real time. OBJECTIVE: Our objective was to develop a smartphone app to monitor nausea and vomiting episodes in pediatric cancer patients aged 0 to 18 years and to test its usability and adherence to its use. METHODS: We used a user-centered design process and the evolutionary prototype model to develop and evaluate the app. Multidisciplinary group discussions and several rounds of patient feedback and modification were conducted. We translated the validated Pediatric Nausea Assessment Tool to assess nausea severity in children aged 4 to 18 years. The child's own term for nausea was interactively incorporated in the nausea severity question, with response options expressed as 4 illustrative faces. Parent-reported outcomes were used for children aged 0 to 3 years. Reminders were sent using push notifications in order to ensure high response rates. Children aged 0 to 18 years who were undergoing chemotherapy were recruited from the Department of Pediatric Oncology at Copenhagen University Hospital Rigshospitalet to evaluate the app. RESULTS: The app's most important function was to record nausea severity in children. After assistance from a researcher, children aged 4 to 18 years were able to report their symptoms in the app, and parents were able to report symptoms for their children aged 0 to 3 years. Children (n=20, aged 2.0-17.5 years) and their parents evaluated the app prospectively during a collective total of 60 chemotherapy cycles. They expressed that the app was user-friendly, intuitive, and that the time spent on data entry was fair. The response rates were on average 92%, 93%, and 80% for the day before, the first day of, and the next 3 days after chemotherapy, respectively. Researchers and clinicians were able to obtain an overview of the patient's chemotherapy dates and responses through a secure and encrypted web-based administrative portal. Data could be downloaded for further analysis. CONCLUSIONS: The user-friendly app could be used to facilitate future pediatric antiemetic trials and to refine antiemetic treatment during chemotherapy.

Pharmacogenetics of antiemetics for chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis.

A substantial proportion of cancer patients experience chemotherapy-induced nausea and vomiting (CINV) despite the use of antiemetic drugs. Prevalent genetic polymorphisms involved in antiemetic drug metabolism, drug transport and receptor pathways likely affect the effectiveness of antiemetics. Knowledge on which polymorphisms to integrate into individualised clinical care is needed. We did a systematic review evaluating the association between polymorphisms and effectiveness of antiemetics in cancer patients receiving moderately to highly emetogenic chemotherapy. Twenty studies n = 2331 evaluated eight polymorphisms in five candidate genes involved in 5-HT3 antagonist pathways. HTR3C C1214G increased the risk of acute chemotherapy-induced vomiting in the dominant model (odds ratio (OR) = 2.67, 95 % confidence interval (CI): 1.08-6.63). ABCB1 C3435T reduced the risk of acute CINV in the recessive model (OR = 0.60, 95 % CI: 0.44-0.81). Future studies should evaluate candidate genes that affect pharmacogenetics of other antiemetics beside 5-HT3 antagonists.

Real-world effectiveness and safety of pharmacological thromboprophylaxis in patients undergoing primary total hip and knee arthroplasty: A narrative review.

In this narrative review of the real-world effectiveness and safety of pharmacological thromboprophylaxis following primary total hip and knee arthroplasty, a total of 12 non-interventional observational studies were included. Pharmacological thromboprophylaxis included warfarin, heparins, dabigatran, rivaroxaban, apixaban, acetylsalicylic acid, and fondaparinux. The absolute risks varied across the included studies. These variations can be explained by differences in patient populations, drug exposure, follow-up time, and definition of outcomes, which makes it a challenge to compare the risk estimates. These findings emphasize the need for a large population-based real-world study to provide comparable risk estimates associated with different pharmacological thromboprophylaxis.

[Insufficient evidence in prophylactic therapy of chemotherapy-induced nausea and vomiting in children and adolescents].

Nausea and vomiting are burdensome side effects of chemotherapy. Vomiting is observed in up to 60% of treated children. An appropriate and effective antiemetic regimen has the potential to eradicate or reduce the symptoms. Differences in local guidelines characterise the antiemetic treatment across the four Danish paediatric oncology departments because the overall knowledge of the most effective antiemetics is incomplete. There is an unmet need for research, which can promote evidence-based guidelines. The impact of host genome polymorphisms should be included in the research.

Neurological diseases and risk of suicide attempt: a case-control study.

INTRODUCTION: Neurological diseases have a profound impact on quality of life. We investigated the risk of suicide attempt in ten neurological diseases. METHODS: Case-control study. Cases were identified from the Danish Poison Information Centre database in the period 2006-2013. The prevalence of ten neurological diagnoses was compared with the prevalence in a randomly sampled age- and gender-matched control group. RESULTS: We identified 8974 cases of suicidal attempt and 89,740 controls. We found an association between suicide attempt in nine of ten neurological diseases and disease groups, including stroke [odds ratio (OR) 3.1, 95% confidence interval (CI) (2.8-3.6)], Huntington's disease [OR 8.8, 95% CI (3.2-24.1)], amyotrophic lateral sclerosis [OR 5.0, 95% CI (1.7-14.6)], Parkinson's disease [OR 2.9, 95% CI (1.8-4.6)], Alzheimer's disease and other degenerative diseases [OR 4.8, 95% CI (3.1-7.5)], multiple sclerosis [OR 1.5, 95% CI (1.1-2.1)], epilepsy [OR 4.5, 95% CI (4.1-5.0)], hereditary and idiopathic neuropathy [OR 2.2, 95% CI (1.1-4.3)] and myasthenia gravis [OR 4.3, 95% CI (2.0-9.4)]. CONCLUSION: Nine out of ten chronic neurological diseases were associated with an increased risk of suicide attempt. These data must be considered for clinicians treating this vulnerable group of patients.