AIM: The present study was conducted to investigate the possible mechanism of actions underlying the systemic antinociception activity of the essential oil of Zingiber zerumbet (EOZZ) in chemical-induced nociception tests in mice.
MATERIALS AND METHODS: Acetic acid-induced abdominal constriction, capsaicin-, glutamate- and phorbol 12-myristate 13-acetate-induced paw licking tests in mice were employed in the study. In all experiments, EOZZ was administered systemically at the doses of 50, 100, 200 and 300 mg/kg.
RESULTS: It was shown that EOZZ given to mice via intraperitoneal and oral routes at 50, 100, 200 and 300 mg/kg produced significant dose dependent antinociception when assessed using acetic acid-induced abdominal writing test with calculated mean ID(50) values of 88.84 mg/kg (80.88-97.57 mg/kg) and 118.8 mg/kg (102.5-137.8 mg/kg), respectively. Likewise, intraperitoneal administration of EOZZ at similar doses produced significant dose dependent inhibition of neurogenic pain induced by intraplantar injection of capsaicin (1.6 μg/paw), glutamate (10 μmol/paw) and phorbol 12-myristate 13-acetate (1.6μg/paw) with calculated mean ID(50) of 128.8 mg/kg (118.6-139.9 mg/kg), 124.8 mg/kg (111.4-139.7 mg/kg) and 40.29 (35.39-45.86) mg/kg, respectively. It was also demonstrated that pretreatment with l-arginine (100mg/kg, i.p.), a nitric oxide precursor significantly reversed antinociception produced by EOZZ suggesting the involvement of l-arginine/nitric oxide pathway. In addition, methylene blue (20mg/kg, i.p.) significantly enhanced antinociception produced by EOZZ. Administration of glibenclamide (10mg/kg, i.p.), an ATP-sensitive K(+) channel antagonist significantly reversed antinociceptive activity induced by EOZZ.
CONCLUSION: Together, the present results suggested that EOZZ-induced antinociceptive activity was possibly related to its ability to inhibit glutamatergic system, TRPV1 receptors as well as through activation of l-arginine/nitric oxide/cGMP/protein kinase C/ATP-sensitive K(+) channel pathway.
METHODS: Patients (n = 94) scheduled for gynaecological laparotomy received i.v. fentanyl infusion (3 μg/kg/h) after induction of general anaesthesia. Post-operative fentanyl requirements were quantified by using a patient-controlled analgesia and the number of i.v. fentanyl rescue analgesia required were recorded. Pain control was assessed using visual analogue scores (VAS) and fentanyl's adverse effects were documented. CYP3A4*4, CYP3A4*5 and CYP3A4*18 alleles of cytochrome P450 3A4 were identified by polymerase chain reaction-restriction fragment length polymorphism. Differences in fentanyl requirements, VAS scores and adverse effects among the various genotypes were compared.
RESULTS AND DISCUSSION: No CYP3A4*4 and CYP3A4*5 alleles were detected. Eighty-nine patients (94·7%) were wild-type, five (5·3%) were heterozygous and none was homozygous. No significant difference was demonstrated between the genotype groups in terms of fentanyl consumption, pain control and adverse effects.
WHAT IS NEW AND CONCLUSION: CYP3A4*4 and CYP3A4*5 are rare in the Malaysian Malay population. Genetic polymorphism of CYP3A4*18 may not play an important role in influencing postoperative fentanyl requirements.
METHODS: Ninety-seven patients with adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion surgery at a single tertiary institution from March 2019 until June 2020 were enrolled in this retrospective study. Anesthesia was maintained using a target-controlled infusion of remifentanil combined with volatile anesthetic desflurane in 92 patients, while five patients received it as part of total intravenous anesthesia. Intravenous ketamine, paracetamol, and fentanyl were administered as multimodal analgesia. All patients received patient-controlled analgesia (PCA) morphine postoperatively. Pain scores at rest and on movement, assessed using the numerical rating scale, and the cumulative PCA morphine consumption were collected at a six-hourly interval for up to 48 h. According to the median intraoperative remifentanil dose usage of 0.215 µg/kg/min, patients were divided into two groups: low dose and high dose group.
RESULTS: There were no significant differences in the pain score and cumulative PCA morphine consumption between the low and high dose remifentanil group. The mean duration of remifentanil infusion was 134.9 ± 22.0 and 123.4 ± 23.7 min, respectively.
CONCLUSION: Intraoperative use of remifentanil as an adjuvant in AIS patients undergoing posterior spinal fusion surgery was not associated with postoperative hyperalgesia.
DESIGN: Single-site, parallel, two-arm randomised controlled feasibility trial.
SETTING: A UK tertiary centre hospital.
PARTICIPANTS: Patients aged ≥70 years who were ambulating pre-injury requiring hospital admission (within 28 days of injury) with a type 1 lateral compression PFF.
INTERVENTIONS: The intervention group received sacral fracture fixation (cement augmentation±screw fixation) within 7 days of randomisation. Routine preoperative and postoperative care followed each surgical intervention. The control group received usual care consisting of analgesia, and regular input from the medical and therapy team.
PRIMARY AND SECONDARY OUTCOME MEASURES: The feasibility outcomes were the number of eligible patients, willingness to be randomised, adherence to allocated treatment, retention, data on the completeness and variability of the proposed definitive trial outcome measures, and reported adverse events.
RESULTS: 241 patients were screened. 13 (5.4%) were deemed eligible to participate. Among the eligible participants, nine (69.2%) were willing to participate. Five participants were randomised to the intervention group and four to the control group. The clinicians involved were willing to allow their patients to be randomised and adhere to the allocated treatment. One participant in the intervention group and two participants in the control group received their allocated treatment. All participants were followed up until 12 weeks post-randomisation, and had an additional safety follow-up assessment at 12 months. Overall, the proportion of completeness of outcome measures was at least 75%. No adverse events were directly related to the trial.
CONCLUSIONS: There were significant challenges in recruiting sufficient participants which will need to be addressed prior to a definitive trial.
TRIAL REGISTRATION NUMBER: ISRCTN16719542.
OBJECTIVE: This review aimed to answer the following research question: 'Does pulpotomy (partial or full) (I) result in better patient and clinical reported outcomes (O), compared with RCT (C) in permanent teeth with pulpitis characterized by spontaneous pain (P) evaluated at various time intervals?' (T).
METHODS: Two authors independently performed study selection, data extraction and risk of bias assessment. The literature search was conducted in the following electronic databases: Clarivate Analytics' Web of Science, Scopus, PubMed and Cochrane Central Register of Controlled Trials. English language clinical trials comparing the patient and clinical reported outcomes between RCT and pulpotomy were included. The meta-analysis was performed on a fixed-effect model and the quality of evidence assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.
RESULTS: Two randomized clinical trials were included. Amongst two trials, one has published four reports at different time points involving the same cohorts. The meta-analysis revealed no difference in postoperative pain (Day 7) between RCT and pulpotomy (OR = 0.99, 95% CI 0.63-1.55, I2 = 0%) and quality of evidence was graded as 'High'. Clinical success was high at year 1, 98% for both interventions, however, decreased over time to 78.1% (pulpotomy) and 75.3% (RCT) at 5 years.
DISCUSSION: Pulpotomy is a definitive treatment modality that is as effective as RCT. This could have a significant impact on treatment of such patients affording the advantages of retaining a vital pulp and preventing the need for RCT.
CONCLUSION: This review could only include two trials, hence there is insufficient evidence to draw robust conclusions. The clinical data accumulated so far suggests no difference in pain between RCT and pulpotomy at Day 7 postoperatively and a single randomized control trial suggests that the clinical success rate for both treatment modalities is similar long term. There is a need for more well-designed trials by different research groups to develop a stronger evidence base in this area.
REGISTRATION: PROSPERO database (CRD42021259744).
METHODS: A discrete choice experiment was developed to include 7 attributes valued in cancer management: physical, psychological and social functioning, pain control, survival, place of death, and cost. Patients were recruited via convenience sampling from 2 Malaysian public hospitals. The survey questionnaire was administered to patients within 6 months of their cancer diagnosis with a follow-up 3 months later. Conditional logit regression was used to estimate the preference weight, relative attribute importance, and willingness to pay.
RESULTS: One hundred valid responses were collected at baseline and 45 at follow-up. Respondents placed higher values on QoL improvements from severe to moderate or mild levels and to achieve home death over survival extension from 6 to 18 months. However, additional improvements (from moderate to mild) in some of the QoL outcomes were not valued as highly as life extension from 12 to 18 months, showing that it was vital for patients to avoid being in "severe" health dysfunction. Improving physical dysfunction from severe to mild yielded 3 times as much value as additional 1-year survival. After 3 months, the respondents' preferences changed significantly, with increased relative attribute importance of physical functioning, pain control, and cost.
CONCLUSIONS: As QoL outcomes are valued more than survival, palliative care should be introduced as early as possible to alleviate suffering related to advanced cancer.
OBJECTIVE: To report two cases of malignant melanoma in the eye, one in the conjunctiva and the other in the choroid.
CASES: The first case was in a 49-year-old lady who presented with a swelling on the inner side of left upper eyelid. The vision was 6/6. On everting the eyelid, multiple, pigmented, nodular swellings were noted on the tarsal conjunctiva. Excision biopsy confirmed the diagnosis of malignant melanoma of the conjunctiva. A pigmented nodular swelling occurred on the lower bulbar conjunctiva in the same eye one-and-a-half years after the first presentation. There were no secondary nodules in the body. Excision biopsy confirmed malignant melanoma of the conjunctiva. The second case was in a 72-year-old lady who presented with pain and bleeding in the right eye. There was no perception of light. The cornea was hazy and the details behind it could not be seen. There was micro perforation of the cornea with oozing of blood and secondary glaucoma. B-scan ultrasonography of the right eye revealed an intraocular tumour. The histopathology of the enucleated eyeball confirmed the diagnosis of malignant melanoma of the choroid.
CONCLUSION: In the case of conjunctival melanoma, the occurrence of tumour at multiple sites and absence of recurrence at the original site suggests the possibility of de novo origin of the tumour. Secondary glaucoma and bleeding may be the presenting features of melanoma in the choroid.