METHODS: A crude methanol extract of the aerial parts of Isodon rugosus (Ir.Cr.) was used for both in vitro and in vivo experiments. The plant extract was tested on isolated rabbit jejunum preparations for possible presence of spasmolytic activity. Moreover, isolated rabbit tracheal and aorta preparations were used to ascertain the relaxant effects of the extract. Acetylcholinesterase and butyrylcholinesterase inhibitory activities of Ir.Cr were also determined as well as its antioxidant activity. The in vivo antiemetic activity of the extract was evaluated by using the chick emesis model, while the analgesic and antipyretic activities were conducted on albino mice.
RESULTS: The application of the crude extract of I. rugosus to isolated rabbit jejunum preparations exhibited relaxant effect (0.01-0.3 mg/ml). The Ir.Cr also relaxed K+(80 m M)-induced spastic contractions in isolated rabbit jejunum preparations and shifted the Ca+2 concentration response curves towards right (0.01-0.3 mg/ml). Similarly, the extract, when applied to the isolated rabbit tracheal preparations relaxed the carbachol (1 μM)--as well as K+ (80 mM)-induced contractions in a concentration range of 0.01-1.0 mg/ml. Moreover, it also relaxed (0.01-3.0 mg/ml) the phenylephrine (1 μM)- and K+ (80 mM)-induced contractions in isolated rabbit aorta preparations. The Ir.Cr (80 mg/kg) demonstrated antipyretic activity on pyrogen-induced pyrexia in rabbits as compared to aspirin as standard drug. The Ir.Cr also exhibited anti-oxidant as well as inhibitory effect on acetyl- and butyryl-cholinesterase and lipoxygenase (0.5 mg/ml).
CONCLUSIONS: The observed relaxant effect on isolated rabbit jejunum, trachea and aorta preparations caused by Ir.Cr is possibly to be mediated through Ca+2 channel blockade and therefore may provided scientific basis to validate the folkloric uses of the plant in the management of gastrointestinal, respiratory and cardiovascular ailments. The observed antioxidant activity as well as the lipoxygenase inhibitory activity may validate its traditional use in pain and inflammations.
RECENT FINDINGS: The cause of hyperemesis is continuing to be elaborated. Recent data attest to the effectiveness of the oral doxylamine-pyridoxine in NVP. Follow-up data of children exposed in early pregnancy to doxylamine-pyridoxine for NVP are reassuring. Evidence is increasing for ginger as an effective herbal remedy for NVP. Metoclopramide is effective in NVP and hyperemesis gravidarum, with a good balance of efficacy and tolerability. A recent large-scale study on first trimester exposure to metoclopramide is reassuring of its safety. Evidence is emerging for the treatment of acid reflux to ameliorate NVP. The role of corticosteroids for hyperemesis gravidarum remains controversial. Transpyloric feeding may be warranted for persistent weight loss, despite optimal antiemetic therapy.
SUMMARY: Women with significant NVP should be identified so that they can be safely and effectively treated.
METHODS: In three double-blind phase 3 studies, patients receiving HEC or MEC were randomized 1:1 to receive oral rolapitant 180 mg or placebo prior to chemotherapy plus 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone therapy. Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included FLIE total score, nausea and vomiting domain scores, and the proportion of patients with no impact on daily life (total score >108 [range 18-126]). We performed a prespecified analysis of the MEC/anthracycline-cyclophosphamide (AC) study and a post hoc analysis of two pooled cisplatin-based HEC studies.
RESULTS: In the pooled HEC studies, rolapitant significantly improved the FLIE total score (114.5 vs 109.3, p
METHODS: Plasma SPM were measured in samples obtained from two double-blind controlled interventions. The first, included 51 women mean age 53 ± 1.5 years, undergoing breast surgery allocated to either intravenous saline, or dexamethasone (4 mg or 8 mg) after induction of anaesthesia. The second study included 31 women of mean age 44 ± 0.5 years undergoing laparoscopic gynecological surgery that were allocated to either saline, or dexamethasone (4 mg). SPM (18-HEPE, 17-HDHA, RvE2, RvD1 17R-RvD1 and RvD2) were measured in plasma collected prior to induction of anaesthesia and at 24 h, and 6 weeks post-surgery. Pain was assessed using a verbal analogue scale at discharge from the post-anaesthesia recovery unit. The data from each study was combined to examine the effect of dexamethasone on plasma SPM. The relationship between pain score and SPM was examined using ordinal logistic regression.
RESULTS: The SPM 18-HEPE, 17-HDHA, RvE2, RvD1 17R-RvD1 and RvD2 were detectable in all plasma samples. There was no significant difference in any SPM due to dexamethasone over the duration of the study. There was a fall in 17-HDHA between baseline and 24 h in both the dexamethasone and saline groups (P = 0.003) but no change in the downstream SPM (RvD1, 17R-RvD1 and RvD2) or 18-HEPE and RvE2. Pain score was negatively related to levels of RvE2 measured prior to induction of anaesthesia (rho = -0.2991, P = 0.006) and positively related to BMI (rho = 0.279, P = 0.011). In ordinal logistic regression the odds ratio for RvE2 was 0.931 (CI 0.880, 0.986; P = 0.014); after adjusting for the effect of BMI indicating that an increase in RvE2 of 1 pg/ml would result in a 6.9 % fall in pain score. Allocation to a dexamethasone group did not influence the pain score or the relationship between RvE2 and pain score.
CONCLUSION: Dexamethasone administered as an anti-emetic does not affect plasma SPM levels. An elevated RvE2 level prior to surgery is predictive of a lower perceived pain score post-anaesthesia.
MATERIALS AND METHODS: This cost evaluation refers to 2011, the year in which the observation was conducted. Direct costs incurred by hospitals including the drug acquisition, materials and time spent for clinical activities from prescribing to dispensing of home medications were evaluated (MYR 1=$0.32 USD). As reported to be significantly different between two regimens (96.1% vs 81.0%; p=0.017), the complete response rate of acute emesis which was defined as a patient successfully treated without any emesis episode within 24 hours after LEC was used as the main indicator for effectiveness.
RESULTS: Antiemetic drug acquisition cost per patient was 40.7 times higher for the granisetron-based regimen than for the standard regimen (MYR 64.3 vs 1.58). When both the costs for materials and clinical activities were included, the total cost per patient was 8.68 times higher for the granisetron-based regimen (MYR 73.5 vs 8.47). Considering the complete response rates, the mean cost per successfully treated patient in granisetron group was 7.31 times higher (MYR 76.5 vs 10.5). The incremental cost-effectiveness ratio (ICER) with granisetron-based regimen, relative to the standard regimen, was MYR 430.7. It was found to be most sensitive to the change of antiemetic effects of granisetron-based regimen.
CONCLUSIONS: While providing a better efficacy in acute emesis control, the low incidence of acute emesis and high ICER makes use of granisetron as primary prophylaxis in LEC controversial.
MATERIALS AND METHODS: This was a single-centre, prospective cohort study. A total of 96 patients receiving LEC (52 with and 42 without granisetron) were randomly selected from the full patient list generated using the e-Hospital Information System (e-His). The rates of complete control (no CINV from days 1 to 5) and complete response (no nausea or vomiting in both acute and delayed phases) were identified through patient diaries which were adapted from the MASCC Antiemesis Tool (MAT). Selected covariates including gender, age, active alcohol consumption, morning sickness and previous chemotherapy history were controlled using the multiple logistic regression analyses.
RESULTS: Both groups showed significant difference with LEC regimens (p<0.001). No differences were found in age, gender, ethnic group and other baseline characteristics. The granisetron group indicated a higher complete response rate in acute emesis (adjusted OR: 0.1; 95%CI 0.02-0.85; p=0.034) than did the non-granisetron group. Both groups showed similar complete control and complete response rates for acute nausea, delayed nausea and delayed emesis.
CONCLUSIONS: Granisetron injection used as the primary prophylaxis in LEC demonstrated limited roles in CINV control. Optimization of the guideline-recommended antiemetic regimens may serve as a less costly alternative to protect patients from uncontrolled acute emesis.
OBJECTIVE: The aim of this study was to determine the impact of CINV (i.e., acute and delayed) on breast cancer patients QOL and to discern opinions related with antiemetic guidelines used dependent on the three main races in Malaysia (Malay, Chinese, Indian).
METHODS: In this longitudinal prospective observational study, 158 breast cancer patients treated with chemotherapy were interviewed and valid questionnaires (MANE and ONEM) were used to report the impact of CINV on their QOL within the first 24 hours and after 3 to 5 days of chemotherapy treatment.
RESULTS: The main result was that delayed CINV has an impact on QOL greater than acute CINV. The impact of nausea was reportedly higher than that of vomiting. Also differences in race i.e., genetic polymorphisms (pharmacogenomics) influenced the utility of antiemetic treatments and patients opinions.
CONCLUSION: Based on the results of our study a new guideline for antiemetic treatment should be used to reduce the impact of CINV on QOL, taking into account variation in genetic polymorphisms among the three races in Malaysia.
AIMS: To investigate the effect of intraperitoneal administration of ondansetron for postoperative pain management as an adjuvant to intravenous acetaminophen in patients undergoing laparoscopic cholecystectomy.
METHODS: Patients scheduled for elective laparoscopic cholecystectomy were randomized into two groups (n = 25 each) to receive either intraperitoneal ondansetron or saline injected in the gall bladder bed at the end of the procedure. The primary outcome was the difference in pain from baseline to 24-h post-operative assessed by comparing the area under the curve of visual analog score between the two groups.
RESULTS: The derived area under response curve of visual analog scores in the ondansetron group (735.8 ± 418.3) was 33.97% lower than (p = 0.005) that calculated for the control group (1114.4 ± 423.9). The need for rescue analgesia was significantly lower in the ondansetron (16%) versus in the control group (54.17%) (p = 0.005), indicating better pain control. The correlation between the time for unassisted mobilization and the area under response curve of visual analog scores signified the positive analgesic influence of ondansetron (rs =0.315, p = 0.028). The frequency of nausea and vomiting was significantly lower in patients who received ondansetron than that reported in the control group (p = 0.023 (8 h), and 0.016 (24 h) respectively).
CONCLUSIONS: The added positive impact of ondansetron on postoperative pain control alongside its anti-emetic effect made it a unique novel option for patients undergoing laparoscopic cholecystectomy.