Influence of Virtual Reality Devices on Pain and Anxiety in Patients Undergoing Cystoscopy Performed under Local Anaesthesia

Background: Bladder cancer is one of the most common malignancies. Its diagnosis is based on transurethral cystoscopy. Virtual reality (VR) is a three-dimensional world generated through the projection of images, the emission of sounds and other stimuli. VR has been proven to be a very effective “distractor” and, thus, a useful tool in managing pain. The aim of this study was to determine whether the use of VR sets is technically feasible during the cystoscopy and whether the use of VR devices would reduce the degree of ailments associated with the procedure; Methods: The study prospectively included both men and women who qualified for rigid cystoscopy due to both primary and follow-up diagnostics. The study group underwent rigid cystoscopy with the VR set and the control group underwent the procedure without the VR set. Patients enrolled in both groups were subjected to blood pressure, heart rate and saturation measurements before, during and after the procedure. Additionally, the patients were asked to describe the severity of fear, pain sensations and nausea associated with the procedure. Non-verbal pain manifestations were assessed using the adult adjusted Faces, Legs, Activity, Cry and Consolability (FLACC) scale; Results: The study population included 103 patients (74M/29F; mean age 64.4 years). Pain intensity differed significantly between the groups, reaching lower values in the VR group. In all analyzed subgroups the use of the VR set was associated with higher levels of nausea. The mean FLACC score reached higher values for patients without the VR set. Blood pressure as well as heart rate increased during the procedure and decreased afterwards. The increase in systolic blood pressure and pulse rate was statistically higher in the control group; Conclusions: This study confirmed that cystoscopy is associated with considerable preprocedural fear and severe pain. Blood pressure and heart rate rise significantly during the cystoscopy. VR sets can lower pain perception during cystoscopy, but they may cause moderate nausea.

Effect of Lavender Oil on Nausea, Vomiting, and Anxiety in Pregnant Women: A Randomized Clinical Trial

Objective: The present study was performed to determine whether lavender oil affects nausea-vomiting and anxiety in pregnant women.Methodology: In a quasi-experimental study, sixty-six pregnant women in the 6th to 16th week of pregnancy with a range of mild to moderate nausea and vomiting were randomized into two groups; a Lavender and a control group (n = 33 for each group). Twice a day (before rest in the afternoon and night sleep) for a week, samples in the intervention and control group inhaled Lavender and sesame oil, respectively. Every night before sleeping, the Rhodes nausea-vomiting questionnaire was completed by the subjects. In addition, Maternal State Anxiety (MSA) in mothers of two groups was measured by using the state anxiety scale before and on the seventh day of the intervention. Results: Seven days after inhalation of Lavender oil, the overall mean score of Rhodes index and the severity of nausea and vomiting (p = 0.008, p = 0.032, respectively), also the mean scores and severity of MSA in mothers of the Lavender group were significantly lower than the control group (p = 0.012 and p = 0.027, respectively). According to the repeated measures analysis, the mean score of the Rhodes index was significantly decreased in the Lavender and control groups during one week (p = 0.0001 and 0.004, respectively).Conclusion: This study presented evidence that Lavender aromatherapy could decrease nausea, vomiting, and anxiety in pregnant women. The findings can guide healthcare workers in providing aromatherapy to women throughout pregnancy.

VERU-111, an oral cytoskeleton disruptor, to treat men with metastatic castration-resistant prostate cancer (mCRPC) who failed an androgen receptor targeting agent.

5056 Background: VERU-111 is an oral cytoskeletal disruptor that disrupts microtubules supporting the cytoskeleton and has no affinity for multidrug resistance proteins. A phase 1b/2 clinical study has been conducted to establish the maximum tolerated dose (MTD) and evaluate the preliminary efficacy in men with mCRPC also resistant to androgen receptor targeting agents. Methods: In the phase 1b component of the study, a 3+3 design with escalating oral dosing of 4.5 mg to 81 mg (7 days on drug/14 days off per 21-day cycle) was utilized. The schedule was also expanded to continuous dosing/cycle. The phase 2 portion utilized 63 mg daily dosing to evaluate efficacy in approximately 40 taxane-naïve men with mCRPC that have failed at least one androgen receptor targeting agent. Results: In the phase 1b portion of the study, 30 taxane-naïve men with mCRPC and a median age of 76 (61-92) were enrolled. 8 had received prior enzalutamide, 12 abiraterone and 10 both. 8 men had bone mets, 5 lymph node, 5 mixed and 1 had soft tissue metastases at study entry. The MTD of VERU-111 is 72mg (3/11 men had grade 3 diarrhea) and the recommended phase 2 dose is 63mg. Grade 3 diarrhea was not observed at doses ≤ 63mg per day and the most common non-dose limiting AEs were mild to moderate nausea, vomiting, diarrhea, and fatigue, with no observed neurotoxicity or neutropenia. Efficacy was assessed by PSA and bone/CT scans. In men treated for ≥ 4 continuous 21-day cycles, 6/10 (60%) had PSA declines, 4(40%) men had ≥ 30% declines and 2(20%) ≥ 50% declines compared to their 21-day cycle baseline PSA. Median PFS is currently 12 months (6-23+ months) with 3 patients continuing on study, 2 of which have been on study for approximately 2 years. In patients receiving at least a single dose of ≥ 63 mg daily (n=19), objective tumor responses were seen in 3 men (16%). The median rPFS in these patients is currently 12.4 months. In the phase 2 portion of the study, 55% of the patients had bone only metastases, 11% had nodal only, 32% had mixed bone and nodal disease and 3% had visceral disease at study entry. 6/32 (19%) were previously treated with abiraterone alone, 12/32 (38%) with enzalutamide alone, and 14/32 (44%) had abiraterone in combination with enzalutamide, proxalutamide or apalutamide. The phase 2 portion of the study is ongoing and objective tumor responses have been observed including a CR and PRs and PSA decreases >50%. Patients have been on study as long as 9 months. Conclusions: This phase 1b/2 clinical trial, demonstrates that oral daily dosing of VERU-111 has a favorable safety profile and that chronic dosing is feasible. The recommended phase 2 dose of 63mg daily has significant durable antitumor activity. These data support a potential prominent role of VERU 111 for the treatment of men with mCRPC who previously failed an androgen receptor targeting agent and prior to the administration of intravenous chemotherapy. Clinical trial information: NCT03752099.

Predicting Individual Susceptibility to Visually Induced Motion Sickness by Questionnaire

Background: The introduction of new visual technologies increases the risk of visually induced motion sickness (VIMS). The aim was to evaluate the 6-item Visually Induced Motion Sickness Susceptibility Questionnaire (VIMSSQ; also known as the VIMSSQ-short) and other predictors for individual susceptibility to VIMS.Methods: Healthy participants (10M + 20F), mean age 22.9 (SD 5.0) years, viewed a 360° panoramic city scene projected in the visual equivalent to the situation of rotating about an axis tilted from the vertical. The scene rotated at 0.2 Hz (72° s−1), with a ‘wobble’ produced by superimposed 18° tilt on the rotational axis, with a field of view of 83.5°. Exposure was 10 min or until moderate nausea was reported. Simulator Sickness Questionnaire (SSQ) was the index of VIMS. Predictors/correlates were VIMSSQ, Motion Sickness Susceptibility Questionnaire (MSSQ), migraine (scale), syncope, Social & Work Impact of Dizziness (SWID), sleep quality/disturbance, personality (“Big Five” TIPI), a prior multisensory Stepping-Vection test, and vection during exposure.Results: The VIMSSQ had good scale reliability (Cronbach’s alpha = 0.84) and correlated significantly with the SSQ (r = 0.58). Higher MSSQ, migraine, syncope, and SWID also correlated significantly with SSQ. Other variables had no significant relationships with SSQ. Regression models showed that the VIMSSQ predicted 34% of the individual variation of VIMS, increasing to 56% as MSSQ, migraine, syncope, and SWID were incorporated as additional predictors.Conclusion: The VIMSSQ is a useful adjunct to the MSSQ in predicting VIMS. Other predictors included migraine, syncope, and SWID. No significant relationship was observed between vection and VIMS.

Effectiveness of the Use of Acupressure Wristband at Neiguan Point (P6) Towards Postoperative Nausea Vomiting (PONV) in Orthopedic Surgical Patients

Postoperative nausea and vomiting (PONV) is one of the most common causes of patient discomfort after undergoing surgery. The emergence of PONV allows the emergence of various complications including dehydration, electrolyte imbalance, slowing the wound healing process, the emergence of problems related to nutritional fulfillment to pneumonia aspiration. Pharmacological treatment has been done but it has not been effective and there are side effects of drugs used so that we need a complementary therapy that works synergistically with antiemetic therapy, namely acupressure. This study aimed at determine the effectiveness of the use of acupressure wristband at neiguan point (p6) towards postoperative nausea vomiting (ponv) in orthopedic surgical patients at BIMC Hospital Kuta. The study design was a pre-experimental with non-randomized uncontrolled trial with pretest-posttest without control group design, with a total of 19 research subjects included in the inclusion criteria. The research instrument consisted of two questionnaires namely the patient information form and the RINVR questionnaire (Rhodes Index of Nausea Vomiting and Retching). The results showed that the incidence of PONV before being given an intervention was obtained by 12 people (63.2%) had mild nausea and vomiting 7 people (36, 8%) experience moderate nausea and vomiting. Whereas after being given the intervention obtained as many as 6 people (31.6%) did not experience nausea, vomiting, 12 people (63.2%) experienced mild nausea, and 1 (5.3%) experienced moderate nausea and vomiting. Wilcoxon test results showed there is the effect of the use of acupressure wristband at neiguan point (p6) towards postoperative nausea vomiting (PONV) in orthopedic surgical patients at BIMC Hospital Kuta

Objective and subjective responses to motion sickness: the group and the individual

We investigated and modeled the temporal evolution of motion sickness in a highly dynamic sickening drive. Slalom maneuvers were performed in a passenger vehicle, resulting in lateral accelerations of 0.4 g at 0.2 Hz, to which participants were subjected as passengers for up to 30 min. Subjective motion sickness was recorded throughout the sickening drive using the MISC scale. In addition, physiological and postural responses were evaluated by recording head roll, galvanic skin response (GSR) and electrocardiography (ECG). Experiment 1 compared external vision (normal view through front and side car windows) to internal vision (obscured view through front and side windows). Experiment 2 tested hypersensitivity with a second exposure a few minutes after the first drive and tested repeatability of individuals’ sickness responses by measuring these two exposures three times in three successive sessions. An adapted form of Oman’s model of nausea was used to quantify sickness development, repeatability, and motion sickness hypersensitivity at an individual level. Internal vision was more sickening compared to external vision with a higher mean MISC (4.2 vs. 2.3), a higher MISC rate (0.59 vs. 0.10 min−1) and more dropouts (66% vs. 33%) for whom the experiment was terminated due to reaching a MISC level of 7 (moderate nausea). The adapted Oman model successfully captured the development of sickness, with a mean model error, including the decay during rest and hypersensitivity upon further exposure, of 11.3%. Importantly, we note that knowledge of an individuals’ previous motion sickness response to sickening stimuli increases individual modeling accuracy by a factor of 2 when compared to group-based modeling, indicating individual repeatability. Head roll did not vary significantly with motion sickness. ECG varied slightly with motion sickness and time. GSR clearly varied with motion sickness, where the tonic and phasic GSR increased 42.5% and 90%, respectively, above baseline at high MISC levels, but GSR also increased in time independent of motion sickness, accompanied with substantial scatter.

Irinotecan combined with oxaliplatin and S-1 in patients with metastatic pancreatic adenocarcinoma: a single-arm, three-centre, prospective study

Objective: To study the efficacy and toxicity of irinotecan combined with oxaliplatin and S-1 in patients with metastatic pancreatic adenocarcinoma. Patients and methods: Previously untreated patients with cytologically or histologically confirmed metastatic pancreatic adenocarcinoma underwent a treatment regimen consisting of an intravenous infusion of irinotecan 165 mg/m2 and oxaliplatin 85 mg/m2 on day 1, and oral S-1 40 mg/m2 twice daily on days 1–14, repeating the regimen every 21 days until one of the following occurred: disease progression, intolerable toxicity, or patient death. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), response rate, toxicity, and quality of life. This ongoing study had been registered on ClinicalTrials.gov, NCT03726021. Results: A total of 41 patients were enrolled in this study, 18 men and 23 women. The median PFS was 4.33 months [95% confidence interval (CI): 2.83–5.88] and the median OS was 11.00 months (95% CI: 9.16–12.84). There were no instances of a complete response; the partial response, stable disease, and disease progression rates were 39.02% (16/41), 29.27% (12/41), and 31.71% (13/41), respectively. The most common adverse side effects were mild to moderate nausea, vomiting, neutropenia, and thrombocytopenia. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 29.27% (12/41) and 12.20% (5/41) of the patients, respectively. No treatment-related death was observed. Conclusion: Irinotecan combined with oxaliplatin and S-1 is a safe and effective treatment for metastatic pancreatic adenocarcinoma, and any toxicities are mild to moderate and tolerable. A larger study population is needed for further evaluation.

Chemoradiotherapy (Gemox Plus Helical Tomotherapy) for Unresectable Locally Advanced Pancreatic Cancer: A Phase II Study

The aim of the study was to evaluate the safety and efficacy of a new chemo-radiotherapy regimen for patients with locally advanced pancreatic cancer (LAPC). Patients were treated as follows: gemcitabine 1000 mg/m2 on day 1, and oxaliplatin 100 mg/m2 on day 2, every two weeks (GEMOX regimen) for 4 cycles, 15 days off, hypofractionated radiotherapy (35 Gy in 7 fractions in 9 consecutive days), 15 days off, 4 additional cycles of GEMOX, restaging. From April 2011 to August 2016, a total of 42 patients with non resectable LAPC were enrolled. Median age was 67 years (range 41–75). Radiotherapy was well tolerated and the most frequently encountered adverse events were mild to moderate nausea and vomiting, abdominal pain and fatigue. In total, 9 patients underwent surgical laparotomy (5 radical pancreatic resection 1 thermoablation and 3 explorative laparotomy), 1 patient became operable but refused surgery. The overall resectability rate was 25%, while the R0 resection rate was 12.5%. At a median follow-up of 50 months, the median progression-free survival and overall survival were 9.3 (95% CI 6.2–14.9) and 15.8 (95% CI 8.2–23.4) months, respectively. The results demonstrate the feasibility of a new chemo-radiotherapy regimen as a potential treatment for unresectable LAPC.

1387. Phase I Study to Evaluate the Safety and Pharmacokinetics (PK) of Single and Multiple Ascending Doses (SAD/MAD) of Intravenous (IV) Minocycline in Healthy Adult Subjects

Background Carbapenem-resistant Acinetobacter baumannii infections are defined by the WHO as a critical threat. IV minocycline is approved in the United States for treatment of Acinetobacter infections at doses up to 200 mg BID. This study investigated safety and PK of single and multiple doses of IV minocycline, including doses higher than approved in the United States. Methods This was a randomized, double blind, placebo-controlled, SAD/MAD study of 6 doses (100–600 mg) of IV minocycline. Healthy adult subjects received a single dose of minocycline or placebo on Day 1, and 15 doses BID starting on Day 4. Safety was assessed throughout the study. Serial blood and urine samples were collected for PK assessment. Results Sixty-nine healthy subjects were randomized, 49 were included in the PK analysis. No serious adverse events (AEs) occurred; 55 subjects (79.9%) reported study drug-related AEs; dizziness 40 (58.0%) and nausea 34 (49.3%) were the most common. All related AEs were mild except for seven subjects with moderate nausea and/or dizziness. Dosing in the 400 mg cohort was discontinued due to AEs, therefore MAD escalation was stopped. Subsequent cohorts were escalated for SAD and loading dose only. Conclusion Single IV doses of minocycline up to 600 mg were tolerated reasonably well, but the maximum tolerated multi-dose was 300 mg BID. Most common AEs were mild nausea and dizziness with evidence of increasing incidence but not increasing severity with increasing dose. Exposure increased in a dose proportional fashion with exception of the 500 mg dose. The dosage regimen selected for further studies will be a 600 mg loading dose followed by 300 mg BID. Disclosures O. A. Cornely, Innovative Medicines Initiative Joint Undertaking: Grant Investigator, Grant recipient. A. MacGowan, Merck: Commercial grant, Research support; Paratek: Commercial grant, Research support; VenatoRx: Commercial grant, Research support; Bayer: Commercial grant, Research support; Achaogen: Commercial grant, Research support; AiCuris: Collaborator and Commercial grant, Grant recipient and Research support; Polyphor: Commercial grant, Research support; Pfizer: Commercial grant, Research support; Roche: Commercial grant, Research support; Melinta: Industrial partner, Research support; MedImmune (AZ): Industrial partner (IMI), Research support; NIHR England: Grant Investigator, Grant recipient; MRC (UK): Grant Investigator, Grant recipient; Innovate UK: Grant Investigator, Grant recipient. Newton Fund (FCO): Grant Investigator, Grant recipient. S. K. Cammarata, Melinta Therapeutics, Inc.: Employee, Salary. K. Fusaro, Melinta Therapeutics: Employee, Salary. J. S. Loutit, The Medicines Company: Employee and Shareholder, Salary

Implementing standardised rhodes index to measure the efficacy of ginger extract (Zingiber officinale) in pregnancy induced nausea and vomiting

Background: Although nausea and vomiting are natural signs of pregnancy affecting about half the pregnant women during their first trimester of pregnancy, it is unpleasant and difficult symptom to deal with. Considering the fact that medication during pregnancy is not advised, we decided to study the efficacy of a natural product to control nausea and vomiting during early pregnancy. Our study was directed to estimate the efficacy of ginger extract (Zingiber officinale) in pregnancy induced nausea and vomiting.Methods: A total of 30 women with pregnancy of 4-16 weeks, suffering from nausea and vomiting were included in this study (n=30). Subjects were given ginger extract 250mg, to be taken 3 times a day half an hour before food for 1 week. Severity of vomiting was assessed by Rhodes Index of Nausea and Vomiting by the patients. Baseline scores were compared with the score at the end of 7 day. The findings were analysed statistically.Results: Effect with the ginger extract in pregnancy induced nausea and vomiting was assessed at the end of treatment (day 7) and compared with the baseline values. Four patients reported symptoms of heartburn. Otherwise, there were no other reports of any adverse effects. The results showed significance (p <0.005).Conclusions: Ginger extract (Zingiber officinale) helps in reducing severity and frequency of pregnancy induced nausea and vomiting. Therefore, we conclude that ginger extract can be used for mild to moderate nausea and vomiting induced by pregnancy during first trimester.