The effectiveness of cinacalcet: a randomized, open label study in chronic hemodialysis patients with severe secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is associated with high incidences of cardiovascular disease, bone fracture, and mortality. This study was conducted to demonstrate the effectiveness of cinacalcet treatment on chronic kidney disease-mineral bone disorder (CKD-MBD) markers in chronic hemodialysis patients with severe SHPT. METHODS: In phase 1, 30 adult HD patients were randomized to cinacalcet or control groups for 12 weeks to explore the achievement of >30% reduction of iPTH. In phase 2, 45 patients were participated to further explore the effect of cinacalcet on CKD-MBD parameters for 24-week follow up and 12 additional weeks after cinacalcet discontinuation. RESULTS: In phase 1, the baseline serum iPTH levels were not different [1374 (955, 1639) pg/mL in the control group vs. 1191 (1005, 1884) pg/mL in the cinacalcet group], the percentage of patients achieving iPTH target were significantly higher in the treatment group [80% vs. 13%, p = .001]. In phase 2, the significant reductions of iPTH, FGF-23, tartrate-resistant acid phosphatase 5b, and slightly decreased size of parathyroid gland and stabilized vascular calcification were observed at 24-week follow up and markedly rebounded after discontinuation of cinacalcet. CONCLUSIONS: The effectiveness of cinacalcet were still obviously demonstrated even in chronic HD patients with severe SHPT. In addition, the improvements of bone markers and FGF-23, and stabilization of vascular calcification were observed. Therefore, cinacalcet can provide salutary effects on CKD-MBD in severe SHPT and might be an initially effective PTH-lowering therapy prior to surgical parathyroidectomy as well as an alternative treatment in the patients unsuitable for surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02056730. Date of registration: February 4, 2014.

ChatGPT vs pharmacy students in the pharmacotherapy time-limit test: A comparative study in Thailand.

OBJECTIVES: ChatGPT is an innovative artificial intelligence designed to enhance human activities and serve as a potent tool for information retrieval. This study aimed to evaluate the performance and limitation of ChatGPT on fourth-year pharmacy student examination. METHODS: This cross-sectional study was conducted on February 2023 at the Faculty of Pharmacy, Chiang Mai University, Thailand. The exam contained 16 multiple-choice questions and 2 short-answer questions, focusing on classification and medical management of shock and electrolyte disorders. RESULTS: Out of the 18 questions, ChatGPT provided 44% (8 out of 18) correct responses. In contrast, the students provided a higher accuracy rate with 66% (12 out of 18) correctly answered questions. The findings of this study underscore that while AI exhibits proficiency, it encounters limitations when confronted with specific queries derived from practical scenarios, on the contrary with pharmacy students who possess the liberty to explore and collaborate, mirroring real-world scenarios. CONCLUSIONS: Users must exercise caution regarding its reliability, and interpretations of AI-generated answers should be approached judiciously due to potential restrictions in multi-step analysis and reliance on outdated data. Future advancements in AI models, with refinements and tailored enhancements, offer the potential for improved performance.

Comparison of Tacrolimus Intra-Patient Variability during 6-12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers.

A high intra-patient variability (IPV) of tacrolimus exposure is associated with poor long-term kidney transplantation outcomes. To assess the influence of cytochrome P450 (CYP) 3A5 genetic polymorphisms on tacrolimus IPV, 188 clinically stable kidney transplant recipients, who had received an immediate-release tacrolimus-based immunosuppressive regimen, were enrolled in this retrospective cohort study. Genotyping of CYP3A5*3 (rs776746) was performed and 110 (58.5%) were identified as CYP3A5 expressers and 78 (41.5%) as nonexpressers. Whole blood tacrolimus concentrations were analyzed by chemiluminescent microparticle immunoassay. Dose-adjusted trough tacrolimus concentrations (C0/D) measured at months 6, 9, and 12 were used to determine IPV. There were no significant differences in the IPV estimated by the coefficient of variation, the IPV calculated by mean absolute deviation method, and the proportions of recipients with the IPV estimated by the coefficient of variation of 30% or more between CYP3A5 expressers and nonexpressers (p = 0.613, 0.686, and 0.954, respectively). Tacrolimus C0/D in CYP3A5 expressers was approximately half of those in nonexpressers, overall (p < 0.001). In both CYP3A5 expressers and nonexpressers, tacrolimus C0/D increased gradually from month 6 to month 12 (p = 0.021). There was no evidence that the CYP3A5 polymorphisms significantly influence tacrolimus IPV during the 6 to 12 months after kidney transplantation.

Treatment Costs for Patients with Chronic Kidney Disease Who Received Multidisciplinary Care in a District Hospital in Thailand.

AIM: To estimate direct medical treatment costs in patients with pre-dialysis chronic kidney disease (CKD) in a district hospital and to analyze the factors that affected the treatment costs. PATIENTS AND METHODS: Data were retrospectively retrieved from the hospital database in the period from January 2015 to December 2017. Patients who were diagnosed with CKD and had visited ambulatory care services at least two times during the index year (January to December 2015) were included. Patients' data were excluded if they had cancer, had received renal replacement therapy, or had been referred to receive treatment at other hospitals. Treatment costs based on the providers' perspectives in the first and second years after the index year were assessed. Descriptive statistics were used to analyze patients' characteristics, and multiple linear regression was used to analyze the factors in the cost model. RESULTS: Data of 212 patients with CKD stage G3a, G3b, or G4 who met inclusion and exclusion criteria were included for analysis. Average costs for treatment in year 1 and year 2 were not statistically different. Total cost was 5701.34 Thai Baht (THB) per year. The total cost for patients with CKD stage G4 was two times greater than for patients with CKD stage G3. Costs were increased for longer hospitalization, more frequent ambulatory visits, having diabetes mellitus or dyslipidemia as a comorbidity, and uncontrolled fasting blood glucose (FBG). A cost model with R 2=0.906 was provided. Significant predictors were length of stay, ambulatory visits, diabetes mellitus, dyslipidemia, serum creatinine, FBG, and body mass index. CONCLUSION: Total annual treatment costs for the 2 years were not different. A more advanced stage of CKD, having diabetes mellitus or dyslipidemia as comorbidities, and uncontrolled FBG were significantly associated with increased costs for treatment in patients with pre-dialysis CKD.

Meropenem dosing recommendations for critically ill patients receiving continuous renal replacement therapy.

PURPOSES: To gather available meropenem pharmacokinetics and define drug dosing regimens for Asian critically ill patients receiving CRRT. METHODS: All necessary pharmacokinetic and pharmacodynamic data from Asian population were gathered to develop mathematic models with first order elimination. Meropenem concentration-time profiles were calculated to evaluate efficacy based on the probability of target attainment (PTA) of 40%fT>4MIC. A group of 5000 virtual patients was created and tested using Monte Carlo simulations for each dose in the models. The optimal dosing regimens were defined as the doses achieved at least 90% of the PTA. RESULTS: The recommended meropenem dosing regimen for Asian critically ill patients receiving CRRT with standard (20-25 mL/kg/h) and high (35 mL/kg/h) effluent rates was 750 mg q 8 h to manage Gram negative infections with expected MIC < 2 mg/L in virtual Asian patients. Some meropenem dosages from available clinical resources could not achieve the aforementioned target. The volume of distribution, body weights and nonrenal clearance significantly contributed to drug dosing adaptation especially in the specific population. CONCLUSIONS: A meropenem regimen of 750 mg q 8 h was recommended for Asian critically ill patients receiving 2 different CRRT modalities with standard and high effluent rates. Clinical validation of these results is needed.

The effect of direct hemoperfusion with polymyxin B immobilized cartridge on meropenem in critically ill patients requiring renal support.

PURPOSE: To evaluate the effect of direct hemoperfusion with polymyxin B immobilized cartridge (DHP-PMX) on meropenem pharmacokinetics in critically ill patients with sepsis requiring continuous venovenous hemofiltration (CVVH). MATERIAL AND METHODS: After intravenous infusion of 1 g meropenem over 3 h repeated every 8 h for at least 3 doses, 2 serial blood and ultrafiltration fluid samples were collected: one over a dose interval of meropenem with DHP-PMX therapy; and the other on the following day over a dose interval of meropenem with no DHP-PMX therapy. Meropenem concentrations were measured by high performance liquid chromatography. Pharmacokinetic parameters of meropenem and extraction ratio of DHP-PMX were calculated. RESULTS: Mean AUC0-8 of meropenem on DHP-PMX day was comparable to that of the DHP-PMX free day (285.2 ±â€¯138.2 vs 297.8 ±â€¯130.2 mg ∗ h/L; paired t-test, p = .618). No statistical significance of peak and trough concentrations, volume of distribution, sieving coefficient, or half-life were found. Extraction ratio of DHP-PMX on meropenem was 0 [0-0.03] and clearance by DHP-PMX was 0.04 [0-0.2] L/h which was not considered clinically significant. CONCLUSIONS: No significant effect of DHP-PMX on meropenem pharmacokinetics was observed among severe sepsis/septic shock patients during CVVH treatment. TRIAL REGISTRATION: Clinical Trial Registry detail: NCT registry: 02413541 (First registered March 3, 2015, last update October 16, 2017).