METHODS: The pharmacy supply database and the medical records of patients with non-valvular atrial fibrillation (NVAF) receiving warfarin, dabigatran or rivaroxaban at two tertiary hospitals were reviewed. Patients who experienced an OAC-associated major or CRB event within 12 months of follow-up, or who have received OAC therapy for at least 1 year, were identified. The BRSs were fitted separately into patient data. The discrimination and the calibration of these BRSs as well as the factors associated with bleeding events were then assessed.
RESULTS: A total of 1017 patients with at least 1-year follow-up period, or those who developed a bleeding event within 1 year of OAC use, were recruited. Of which, 23 patients experienced a first major bleeding event, whereas 76 patients, a first CRB event. Multivariate logistic regression results show that age of 75 or older, prior bleeding and male gender are associated with major bleeding events. On the other hand, prior gastrointestinal bleeding, a haematocrit value of less than 30% and renal impairment are independent predictors of CRB events. All the BRSs show a satisfactory calibration for major and CRB events. Among these BRSs, only HEMORR2 HAGES (C-statistic = 0.71, 95% CI 0.60-0.82, P
PATIENTS AND METHODS: Patients with unequivocal evidence of H. pylori infection based on culture, histology and rapid urease test of both antrum and corpus biopsies were recruited for the study. The study was a randomized, investigator-blind, comparative study. Patients received either omeprazole 20 mg o.m., clarithromycin 250 mg b.d. and amoxycillin 500 mg b.d. (OAC) or omeprazole 20 mg o.m., metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC) for 1 week. Patients were assessed for successful eradication, which was defined as absence of bacteria in all tests (culture, histology and urease test on both antral and corpus biopsies), at least 4 weeks after completion of therapy.
RESULTS: Eighty-two patients were recruited for the study. Eradication rates on intention-to-treat analysis were--OAC: 36/41 (87.8%, 95% CI: 73.8, 95.9); OMC: 33/41 (80.5%, 95% CI: 65.1, 91.2). On per protocol analysis were--OAC: 36/40 (90%, 95% CI: 76.3, 97.2); OMC: 32/38 (84.2%, 95% CI: 68.7, 94.0). All side-effects encountered were mild and no patient discontinued treatment because of intolerance to medications. The most common side-effects were altered taste (OAC 31.7%, OMC 53.7%) and lethargy (OAC 14.6%, OMC 19.5%). Pre-treatment metronidazole resistance was encountered in 34/63 (54.0%) patients. No bacterial strains were found with primary resistance to clarithromycin. Metronidazole resistance did not significantly affect eradication rates. Emergence of resistance to clarithromycin was not seen post-therapy.
CONCLUSIONS: Both the OAC and the OMC regimens were convenient and well-tolerated treatments for H. pylori. However, eradication rates were lower than anticipated.
PURPOSE: The concomitant use of therapeutic drugs may cause potential drug-drug interactions by decreasing or increasing plasma levels of the administered drugs, leading to a suboptimal clinical efficacy or a higher risk of toxicity. Thus, evaluating the inhibitory potential of a new chemical entity, and to clarify the mechanism of inhibition and kinetics in the various CYP enzymes is an important step to predict drug-drug interactions.
STUDY DESIGN: This study was designed to assess the potential inhibitory effects of Alpinia conchigera Griff. rhizomes extract and its active constituent, ACA, on nine c-DNA expressed human cytochrome P450s (CYPs) enzymes using fluorescent CYP inhibition assay.
METHODS/RESULTS: The half maximal inhibitory concentration (IC50) of Alpinia conchigera Griff. rhizomes extract and ACA was determined for CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5. A. conchigera extract only moderately inhibits on CYP3A4 (IC50 = 6.76 ± 1.88µg/ml) whereas ACA moderately inhibits the activities of CYP1A2 (IC50 = 4.50 ± 0.10µM), CYP2D6 (IC50 = 7.50 ± 0.17µM) and CYP3A4 (IC50 = 9.50 ± 0.57µM) while other isoenzymes are weakly inhibited. In addition, mechanism-based inhibition studies reveal that CYP1A2 and CYP3A4 exhibited non-mechanism based inhibition whereas CYP2D6 showed mechanism-based inhibition. Lineweaver-Burk plots depict that ACA competitively inhibited both CYP1A2 and CYP3A4, with a Ki values of 2.36 ± 0.03 µM and 5.55 ± 0.06µM, respectively, and mixed inhibition towards CYP2D6 with a Ki value of 4.50 ± 0.08µM. Further, molecular docking studies show that ACA is bound to a few key amino acid residues in the active sites of CYP1A2 and CYP3A4, while one amino residue of CYP2D6 through predominantly Pi-Pi interactions.
CONCLUSION: Overall, ACA may demonstrate drug-drug interactions when co-administered with other therapeutic drugs that are metabolized by CYP1A2, CYP2D6 or CYP3A4 enzymes. Further in vivo studies, however, are needed to evaluate the clinical significance of these interactions.
METHODS: This retrospective cohort study includes adult patients of two tertiary hospitals in Malaysia. Potential study subjects were identified using pharmacy supply database or novel oral anticoagulant (NOAC) registry. Demographics, clinical data and laboratory test results were extracted from the medical records of the patients or electronic databases. The main outcome measure is the occurrence of a bleeding event. Bleeding events were classified into major bleeding, clinically relevant non-major bleeding, or minor bleeding, according to the International Society on Thrombosis and Haemostasis criteria. We consider clinically relevant non-major bleeding events or major bleeding events as clinically relevant bleeding events. An occurrence of any bleeding event was recorded from the initiation of NOAC therapy until the death of a patient, or the date of permanent discontinuation of NOAC use, or the last day of data collection. The predicted rate of dabigatran-induced bleeding events per 100 patient-years was estimated.
RESULTS: During a median follow-up period of 18 months, 73 patients experienced 90 bleeding events. Among these patients, 25 including 4 fatal cases, experienced major bleeding events. The predicted rate per 100 patient-years of follow-up of any bleeding events was 9.0 [95% CI 6.9 to 11.1]; clinically relevant bleeding events 6.0 [95% CI 4.8 to 8.3], and major bleeding events 3.0 [95% CI 1.9 to 4.2]. The independent risk factor for clinically relevant bleeding events is prior bleeding. While prior bleeding or congestive heart failure is linked with major bleeding events.
CONCLUSIONS: The predicted rate for dabigatran-induced major bleeding episodes is low but these adverse events carry a high fatality risk. Preventive measures should target older patients who have prior bleeding or congestive heart failure. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
METHODS: We recruited 33 (age range from 21 to 72 years) adult patients with a body mass index of 30 kg/m2 and above, who were scheduled for non-cardiac surgeries. Intravenous oxycodone was administered after induction of general anesthesia and blood samples were collected up to 24 h after oxycodone administration. Plasma concentrations of oxycodone were assayed using liquid chromatography-tandem mass spectrometry and 253 concentration-time points were used for pharmacokinetic analysis using nonlinear mixed-effects modeling.
RESULTS: Intravenous oxycodone pharmacokinetics were well described by a two-compartment open model. The estimated total clearance and central volume of distribution of oxycodone are 28.5 l/h per 70 kg and 56.4 l per 70 kg, respectively. Total body weight was identified as a significant covariate of the clearance and central volume of distribution. Dosing simulations based on the final model demonstrate that a starting dose of 0.10 mg/kg of intravenous oxycodone is adequate to achieve a target plasma concentration and repeated doses of 0.02 mg/kg may be administered at 1.5-h intervals to maintain a plasma concentration within an effective analgesic range.
CONCLUSIONS: A population pharmacokinetic model using total body weight as a covariate supports the administration of 0.10 mg/kg of intravenous oxycodone as a starting dose and repeated doses of 0.02 mg/kg at 1.5-h intervals to maintain targeted plasma concentrations for analgesia in the obese adult population.
METHODS: Patients aged 18 years old or above and who were scheduled for gynecology surgery were selected. Three different models with a combination of latent factors were based on a priori hypotheses from previous studies. The root-mean-squared error of approximation, comparative fit index, Tucker-Lewis Index, Chi-squared test, and change in Chi-squared statistic given a change in degrees of freedom between models were used to assess the model fit to the present data.
RESULTS: A total of 302 patients completed the questionnaire. The five-factor model which was based on Gordon's study has an acceptable fit for the data and was superior when compared to the one-factor baseline model. Although the four-factor model, which originated from Botti's study, also demonstrates a good model fit, the "perception of care" construct was excluded in this model. The "perception of care" construct is conceptually important as patient-centered care has become the focus of quality improvement of pain service.
CONCLUSIONS: The APS-POQ-R is easy to administer and is useful for quality evaluation in postoperative pain management. The present study demonstrates that a five-factor structure of the APS-POQ-R is the best fitting model in our patient sample. The results of this study provide further evidence to support the use of APS-POQ-R as a measurement tool for pain management evaluation in acute postoperative patients with a multi-cultural background.
METHODS: We searched PubMed, Embase, and CENTRAL from inception until August 2020 for randomized controlled trials comparing both techniques. The primary outcome was cumulative morphine consumption at 24 h. Secondary pain-related outcomes included pain score at rest and on movement at 2, 6, 12, and 24 h; postoperative nausea and vomiting; and length of hospital stay.
RESULTS: We included 23 studies with a total of 2,178 patients. TAP block is superior to control in reducing opioid consumption at 24 h, improving pain scores at all the time points and postoperative nausea and vomiting. The cumulative opioid consumption at 24 h for IPLA is less than control, while the indirect comparison between IPLA with PSI and control showed a significant reduction in pain scores at rest, at 2 h, and on movement at 12 h, and 24 h postoperatively.
CONCLUSIONS: Transversus abdominis plane block is effective for reducing pain intensity and has superior opioid-sparing effect compared to control. Current evidence is insufficient to show an equivalent analgesic benefit of IPLA to TAP block.
METHODS: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution.
RESULTS: This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non-GFR clearance not associated with normal GFR. All three drugs had GFR clearance estimated as a drug-specific percentage of normal GFR (gentamicin 39%, amikacin 90% and vancomycin 57%). The total clearance (sum of GFR and non-GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% confidence interval [CI] 5.50-5.69) (gentamicin), 7.77 L/h (95% CI 7.26-8.19) (amikacin) and 4.70 L/h (95% CI 4.61-4.80) (vancomycin).
CONCLUSIONS: GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention.