OBJECTIVE: Combined spinal-epidural analgesia (CSEA) is effective but not sufficient for labor pain. This study was conducted to assess the real-time analgesic efficacy, side effects of anesthetic drug dosage, and maternal satisfaction in labor to provide reference for the optimization of labor analgesia.
METHODS: This was a prospective, cohort, single-center study that included 3020 women who received CSEA for labor analgesia. The visual analogue scale (VAS) for labor pain, real-time anesthetic drug dosage, side effects, adverse labor outcomes, factors influencing average drug dosage, and maternal satisfaction with CSEA were assessed.
RESULTS: Overall, the VAS labor pain score was lowest at the first hour after the anesthesia was given. After 4 h for primiparas and 3 h for multiparas, the VAS score was greater than 3 but the anesthetic drug dosage did not reach the maximum allowed dosage at the same time. The average anesthetic drug dosage was positively correlated with fever, urinary retention, uterine atony, prolonged active phase, prolonged second stage, assisted vaginal delivery, and postpartum hemorrhage. The average anesthetic drug dosage was the highest in women ≤ 20 years old, those with a body mass index (BMI) ≥ 24.9 kg/m2, and those with a primary or secondary education level.
CONCLUSIONS: Appropriate age guidance and emphasis on education of labor analgesia, weight management during pregnancy, and real-time anesthetic dosage adjustment during labor based on VAS pain score may have positive effects on the satisfaction of labor analgesia.
BACKGROUND: Clinicaltrials.gov (ChiCTR2100051809).

OBJECTIVE: Cenobamate is an antiseizure medication (ASM) associated with high rates of seizure freedom and acceptable tolerability in patients with focal seizures. To achieve the optimal cenobamate dose for maximal potential effectiveness while avoiding or minimizing drug-related adverse events (AEs), the administration of cenobamate with other ASMs must be managed through concomitant ASM load reduction. A panel of Spanish epilepsy experts aimed to provide a Spanish consensus on how to adjust the dose of concomitant ASMs in patients with drug-resistant epilepsy (DRE) in order to improve the effectiveness and tolerability of adjunctive cenobamate.
METHODS: A three-stage modified Delphi consensus process was undertaken, including six Spanish epileptologists with extensive experience using cenobamate. Based on current literature and their own expert opinion, the expert panel reached a consensus on when and how to adjust the dosage of concomitant ASMs during cenobamate titration.
RESULTS: The expert panel agreed that tailored titration and close follow-up are required to achieve the best efficacy and tolerability when initiating cenobamate in patients receiving concomitant ASMs. When concomitant clobazam, phenytoin, phenobarbital, and sodium channel blockers are taken at high dosages, or when the patient is receiving two or more sodium channel blockers, dosages should be proactively lowered during the cenobamate titration period. Other concomitant ASMs should be reduced only if the patient reports a moderate/severe AE at any stage of the titration period.
CONCLUSIONS: Cenobamate is an effective ASM with a dose-dependent effect. To maximize effectiveness while maintaining the best tolerability profile, co-medication management is needed. The recommendations included herein provide practical guidance for proactive and reactive management of co-medication in cenobamate-treated patients with DRE and a high drug load.
CONCLUSIONS: Patients with epilepsy may continue to have seizures even after treatment with several different antiseizure medications (ASMs). Cenobamate is an ASM that can reduce seizures in these patients. In this study, six Spanish experts in epilepsy discussed the best way to use cenobamate in drug-resistant epilepsy. They provide practical guidance on when and how the dose of other ASMs might be adjusted to reduce side effects and optimize the use of cenobamate.

Renal failure in the course of rheumatoid arthritis (RA) is a consequence of many factors, including drug-induced nephrotoxicity, comorbidities and chronic inflammation. Contemporary treatment strategies have reduced the incidence of renal failure in the population of RA patients. However, it remains a problem for approximately 25% of patients. Therefore, special attention should be paid to the potential need for dosage modifications of administered medications. Many drugs used in the therapy of rheumatic diseases have not been thoroughly studied for their safety in patients with reduced glomerular filtration, resulting in limited data in this area. The establishment of precise, transparent, and consistent dosage recommendations for antirheumatic drugs in chronic kidney disease would significantly facilitate the care of patients with RA. The following review provides a general summary of the available knowledge regarding the dosage of rheumatic medications in renal insufficiency and aims to highlight the need for further research in this area.

Dilated cardiomyopathy (DCM) has brought great damage to the patients\' health and social economy. The number of patients with recovered dilated cardiomyopathy (recDCM) has increased over the years as treatment progresses. However, there is a lack of relevant evidence to support the clinical management of patients with recDCM, thereby, the recommendations in guidelines remains sparse. Accordingly, the exploration of recDCM is important to improve patient prognosis and reduce societal burden. This is an open-label, randomized controlled, prospective study that will compare the safety and efficacy of original dose and halved dose of neurohumoral blockades for patients with recDCM.
UNASSIGNED: An open-label, randomized controlled, prospective study will be conducted among eligible patients with recDCM. During the pilot study phase, we will recruit 50 patients. The primary endpoint is hospitalization for heart failure or heart failure relapse within 12 months. Secondary endpoint is major adverse cardiovascular events, including cardiovascular mortality, myocardial infarction, stroke, sustained atrial tachycardia, or ventricular tachycardia. The results will be analyzed using intention-to-treatment analysis.
UNASSIGNED: The study will provide important evidence of whether it is safe and effective to halve the dosage of neurohumoral blockades in recDCM patients.
UNASSIGNED: ChiCTR2100054051 (www.chictr.org.cn).

Although many different designed air-assisted sprayers can be used for pesticide application in apple orchards, the lack of adequate adjustments according to specific crop characteristics leads to application inefficiencies and failures. To evaluate the spray coverage and biological efficacy of different application techniques combined with an alternative dosage adjustment based on tree row volume (TRV), field tests with five different techniques were carried out at three crop stages on a commercial apple orchard. The results showed that conventional mist-blower with a high application volume (800 L ha-1) exhibited an excessive coverage with a high risk of contamination at the early crop stage (BBCH19), whereas other treatments using different application techniques, with a reduced volume rate and pesticide dose of 75%, were equivalent with good uniformity, revealing the great importance of suitable adjustment for the sprayers. For the middle and late stages (BBCH64 and 75), the orchard sprayer equipped with vertical booms provided the maximum coverage, and the pneumatic sprayer achieved significantly higher impacts density, which revealed their advantages and high efficiency for dense apple trees. The newly developed multi-fan sprayer and pneumatic sprayer achieved consistent coverage during the entire crop stage, independent of the changes in canopy structure (TRV). This indicates that a suitable setting and adjustment of the sprayer can contribute to a consistent spray quality. In general, benefiting from these new spraying technologies, an average reduction of 60.7% in pesticide dose and volume rate were achieved within the entire season, maintaining the same threshold of pest and disease control as that of the higher reference dose normally applied. These results demonstrate the importance of an alternative dose adjustment method to meet the requirements of the Farm to Fork strategy.

OBJECTIVE: To optimize the dosing regimen in patients with severe renal impairment based on population pharmacokinetic (PPK)/pharmacodynamic analysis.
METHODS: The pharmacokinetics and safety of nemonoxacin was evaluated in a single-dose, open-label, nonrandomized, parallel-group study after single oral dose of a 0.5-g nemonoxacin capsule in 10 patients with severe renal impairment and 10 healthy controls. Both blood and urine samples were collected within 72 hours after admission and determined the concentrations. A PPK model was built using nonlinear mixed effects modelling. The probability of target attainment and the cumulative fraction of response against Streptococcus pneumoniae and Staphylococcus aureus was calculated by Monte Carlo simulation.
RESULTS: The data best fitted a 2-compartment model, from which the PPK parameters were estimated, including clearance (8.55 L/h), central compartment volume (80.8 L) and peripheral compartment volume (50.6 L). The accumulative urinary excretion was 23.4 ± 6.5% in severe renal impairment patients and 66.1 ± 16.8% in healthy controls. PPK/pharmacodynamic modelling and simulation of 4 dosage regimens found that nemonoxacin 0.5 g every 48 hours (q48h) was the optimal dosing regimen in severe renal impairment patients, evidenced by higher probability of target attainment (92.7%) and cumulative fraction of response (>99%) at nemonoxacin minimum inhibitory concentration ≤ 1 mg/L against S. pneumoniae and S. aureus. The alternative regimens (0.25 g q24h; loading dose 0.5 g on Day 1 followed by 0.25 g q24h) were insufficient to cover the pathogens even if minimum inhibitory concentration = 1 mg/L.
CONCLUSIONS: An extended dosing interval (0.5 g q48h) may be appropriate for optimal efficacy of nemonoxacin in case of severe renal impairment.

BACKGROUND: Management of breast cancer patients undergoing hemodialysis (HD) is difficult because of a lack of evidence about drug selection, dose adjustment, and surgical procedures. We herein present a case of metastatic breast cancer in a patient undergoing HD.
METHODS: A 58-year-old Japanese woman with breast cancer undergoing HD underwent total mastectomy of the left breast and left axillary dissection. Histopathological examination revealed invasive ductal carcinoma, and the diagnosis was pT2N3cM0 Stage ⅢC. Immunostaining of the resected specimen indicated that the tumor was estrogen receptor-positive, progesterone receptor-negative, human epithelial growth factor receptor 2-positive, and the Ki-67 labeling index was 70%. A postoperative positron emission tomography/computed tomography (PET/CT) scan indicated fluorodeoxyglucose uptake in the supraclavicular nodes. She received adjuvant therapy of epirubicin and cyclophosphamide followed by docetaxel, trastuzumab (T-mab) and radiation therapy. However, she developed multiple liver metastases during adjuvant T-mab and hormone therapy. Therefore, her regimen was changed to trastuzumab emtansine (T-DM1) as first-line therapy, T-mab, pertuzumab (P-mab), and eribulin as second-line therapy, and T-mab, P-mab, and weekly paclitaxel as third-line therapy. Eventually, she was administered fourth-line treatment of T-mab, P-mab, and vinorelbine because of adverse events. She has survived more than 25 months after the initial detection of recurrence of breast cancer and maintained quality of life.
CONCLUSIONS: We report a case of breast cancer in a patient undergoing HD. It is very difficult to identify the appropriate drugs and dosages in patients undergoing HD to improve survival and quality of life.

Background Renal dosage adjustment for patients with reduced kidney function is a common function of clinical pharmacy service. Assessment of pharmacist\'s intervention in the aspect of quality and economic impact should be conducted to evaluate the benefit of this service. Objective This study aimed to assess the quality and cost saving of clinical pharmacists\' recommendation on renal dosage adjustment among patients with reduced kidney function. Setting Eight medical wards of the Siriraj Hospital, a tertiary-care hospital in Bangkok, Thailand. Method A retrospective study was conducted using medical records and clinical pharmacist\'s intervention database. All patients admitted to the study wards whose estimated creatinine clearance were less than 60 mL/min or presented with acute kidney injury on admission during October 2016-December 2017 were included. The targeted medications were antimicrobial agents. Main outcome measure Percentage of the concordance between pharmacists\' recommendation compared to standard dosing references and related cost saving. Results Among 158 patients, pharmacists provided 190 recommendations, including 151 (79.1%) dose reduction, 17 (8.9%) dose increase and 22 (11.5%) recommendations to provide supplemental dose after dialysis. These recommendations were 90.5% consistent with standard references. Physician accepted and complied with 89.5% of pharmacists\' recommendations. Average direct cost saving was €5,114.11 while cost avoidance was €863.47. Conclusion Trained clinical pharmacists were able to provide high-quality recommendation on dosage adjustment in these patients in accordance to standard dosing guidelines. In addition, dosage adjustment also led to a significant direct cost saving and cost avoidance from prevention of adverse drug reactions.

Background and aims: Medication dosage adjustments for renally impaired patients have not been studied in Botswana. This study was conducted to determine prescribing practices among patients with renal impairment in medical wards to improve future patient care.Methods: We conducted a retrospective study involving medical charts of patients admitted at a tertiary level hospital in Gaborone Botswana. Study participants included all patients admitted between August and October 2016 who were hospitalized for ≥24 h. \'Drug prescribing in renal failure: dosing guidelines for adults and children\'. was used to determine the extent of dosage adjustments. A logistic regression model was used to assess which patient factors were associated with inappropriate dosage adjustment.Results: Twenty-nine percent (233/804) of patients had renal impairment. Of these, 184 patients with renal impairment were included in the final analysis. There were 1143 prescription entries, of which 20.5% (n = 234) required dosage adjustment for renal function but only 45.7% (n = 107) were adjusted correctly. Of note, 112 patients were prescribed at least one drug that required dosage adjustment and only 30.4% (n = 34) patients had all of their medications appropriately adjusted. Patient factors associated with inappropriate dosage adjustment included a higher number of medicines being prescribed. Mortality among patients with renal impairment was independently associated with higher scores of the Charlson comorbidity index and hospital stay duration of 1-7 days.Conclusion: The renal function status of patients was not sufficiently taken into account when prescribing medicines especially in patients with severely impaired kidney function in Botswana. Continuous medical education needs to be encouraged to address this, which is being implemented. We will be following this up in future studies.

Ten percent of the world\'s population is affected by chronic kidney disease that can lead to kidney failure. In France, nearly three million people are concerned, half of whom are undiagnosed, 85,000 people are on dialysis or waiting for a kidney transplant. Each year, 11,000 new diagnoses of severe renal failure are made, one third of which had not been treated before. Kidney failure is constantly increasing due to the aging of the population and the resurgence of chronic diseases, including obesity and cardiovascular diseases such as high blood pressure and diabetes, two conditions that impair renal function. The pharmacist, a local actor, is well placed to help patients adhere to their treatment and manage it to the best of their quality of life. It is up to the pharmacist to check the dosages according to the degree of renal involvement, ideally noted on the prescription or, failing that, by asking the patient the results of his recent biological examinations. The consultation of the pharmaceutical file and, ultimately, the shared medical file, will make it possible, in a concerted management of the patient\'s care pathway, to also detect possible drug interactions. By dispensing the prescribed drugs, the pharmacist can also warn against those known to be known for their nephrotoxicity, especially nonsteroidal anti-inflammatory drugs. In the case of over-the-counter products, the pharmacist may discourage a person at risk from taking certain drugs containing nonsteroidal anti-inflammatory drugs, including aspirin and ibuprofen. Because of their potential renal toxicity, the pharmacist is competent to alert, especially on certain food supplements, herbal products, and is legitimate to participate in screening campaigns.