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Aims: Information on breastfeeding and safety of biologics in infants is lacking due to difficulties in case collection. We evaluated methods for determining the concentration of biologics in breast milk using a dry filter method that can simplify the collection, storage and transport of breast milk. Methods: To generate dried filter paper (DFP) samples, approximately 30 μL of breast milk was placed onto a Whatman 903 card and punched out. After extraction, the supernatant was measured using an enzyme‐linked immunosorbent assay. Three concentrations of each drug were prepared in liquid breast milk (LBM) and DFP samples to determine their stability up to 28 days after storage at 2–8°C or −20°C for LBM and 25 ± 5°C for DFP. LBM and DFP samples were also provided by nursing mothers using biologics during lactation, and drug concentrations in both samples were compared. The agreement between the two measurement methods was confirmed by Bland–Altman analysis. Results: Breast milk was provided by 12 mothers who used biologics (tocilizumab, abatacept, etanercept, golimumab, sarilumab and belimumab). The coefficients of variation for within‐run and between‐run precision for the six drugs were within 15% for both LBM and DFP, and accuracy was within 90%–110% of the quality controls. After 28 days, concentrations remained at more than 90%. The difference between the values obtained by each method was within the acceptable range of error (−12.1 to +16.6 ng/mL). Conclusions: A method for determining the concentration of biologics using DFP is expected to help improve pharmacotherapy for lactating women. [ABSTRACT FROM AUTHOR]

A neonatal patient with Herpes simplex virus type-2 meningoencephalitis was treated by high-dose intravenous acyclovir therapy. Serum and cerebrospinal fluid (CSF) concentrations were measured retrospectively, showing that the CSF-to-serum concentration ratio was 0.67–0.71, which was higher than the previously reported values in other age groups. [ABSTRACT FROM AUTHOR]

Introduction: Areas displaying reduced bipolar voltage are defined as low‐voltage areas (LVAs). Moreover, left atrial (LA) LVAs after pulmonary vein isolation (PVI) have been reported as a predictor of recurrent atrial fibrillation (AF). In this study, we compared grid mapping catheter (GMC) with PentaRay catheter (PC) for LA voltage mapping on Ensite Precision mapping system. Methods: Twenty‐six consecutive patients with LVAs and border zone within the LA were enrolled. After achieving PVI, voltage mapping under high right atrial pacing for 600 ms was performed twice using each catheter type (GMC first, PC next). Furthermore, LVA was defined as a region with a bipolar voltage of <0.50, and border zone was defined as a region with a bipolar voltage of <1.0, or <1.5 mV. Results: Compared with PC, using GMC, voltage mapping contained more mapping points (20 242 [15 859, 26 013] vs. 5589 [4088, 7649]; p <.0001), and more mapping points per minute(1428 [1275, 1803] vs. 558 [372, 783]; p <.0001). In addition, LVA and border zone size using GMC was significantly less than that reported using PC: <1.0 mV (5.9 cm2 [2.9, 20.2] vs. 13.9 cm2 [6.3, 24.1], p =.018) and <1.5 mV voltage cutoff (10.6 cm2 [6.6, 27.2] vs. 21.6 cm2 [12.6, 35.0], p =.005). Conclusion: Bipolar voltage amplitude estimated by GMC was significantly larger than that estimated by PC on Ensite Precision mapping system. GMC may be able to find highly selective identification of LVAs with lower prevalence and smaller LVA and border zone size. [ABSTRACT FROM AUTHOR]

What is known and objective: Statins are associated with improved pregnancy outcomes in patients with preeclamptic antiphospholipid syndrome (APS) and intrauterine foetal death. Several studies showed that statins are not teratogenic. However, data characterizing placental transfer and excretion of pravastatin into breast milk are limited. Case summary: We experienced two patients diagnosed with APS received 10 mg of pravastatin from the first trimester until delivery to prevent pre‐eclampsia. Pravastatin concentrations in maternal serum, infant serum and cord blood were evaluated. The estimated maternal‐foetal transfer ratios of pravastatin in the two patients were 25.5% and 23.8% respectively. Pravastatin was eliminated from neonatal serum within 2 days. Both infants developed normally with no drug‐related adverse effects. Pravastatin was not detected in either patient's breast milk at 3 days after the last dose. What is new and conclusion: The infants delivered from the mothers who were treated with pravastatin during pregnancy had no apparent adverse effects. [ABSTRACT FROM AUTHOR]

Safety information on diazoxide for pregnant and lactating women with hypoglycemia is limited. In this case report, we assessed diazoxide concentrations in maternal and infant blood, cord blood, and breast milk. We described a 30-year-old pregnant woman diagnosed with hypoglycemia due to nesidioblastosis at 4 months of age. Before becoming pregnant, she was treated with oral diazoxide (75–375 mg). All medications were discontinued after she was discovered to be pregnant. During gestational week 25, diazoxide treatment was resumed at 150–175 mg daily for repeated hypoglycemic episodes. Diazoxide administration was continued in combination with diet treatment until delivery. Glucose levels were well controlled. During gestational week 40, a male infant weighing 3069 g was delivered via spontaneous vaginal delivery with no pregnancy or neonatal complications. Diazoxide concentrations detected in maternal serum at 2.5–11.6 h after oral treatment ranged from 12.4 to 32.7 µg/mL. In cord blood, the diazoxide concentration was 18.5 µg/mL at 7.2 h after the last dose. During lactation, no hypoglycemia or hyperglycemia was observed. The approximate calculated ratio of diazoxide in breast milk and maternal serum was 0.09. The calculated daily infant dose was 0.47 mg/kg/day. The relative infant dose via breast milk ranged from 3.1% to 5.9%. Diazoxide transferred from maternal blood to the fetus across the placenta. It also transferred into breast milk, but there were no harmful effects on the infant. [ABSTRACT FROM AUTHOR]

Compounding of medications, such as crushing tablets and dispersing the contents of capsules, is a common practice in pharmacies and hospitals worldwide and is often done to provide age-appropriate formulations for oral use in pediatric patients. In the present study, a retrospective, descriptive, questionnaire-based survey was conducted to clarify the current status of drug compounding for pediatric patients in Japan. An electronic questionnaire was distributed to 740 hospitals in Japan with pediatric beds, and 208 (28.1%) of these hospitals responded. The total instances of compounding numbered 14,864 (9.6% of the total pediatric oral prescriptions) and comprised 266 active pharmaceutical ingredients (APIs), one-third of which (98 APIs) were compounded even though flexible dosage forms were available. The three most frequently compounded drugs were dantrolene sodium capsules (1152 prescriptions), ramelteon tablets (726 prescriptions), and hydrocortisone tablets (652 prescriptions), all of which were prescribed and administered in powder form. Although compounding of medications frequently varied by the patients' age, steroids such as prednisolone, dexamethasone, and hydrocortisone were commonly compounded in all age groups. To ensure the quality and safety of these compounded medications, developing a standard protocol for compounding methods is urgently needed in Japan. [ABSTRACT FROM AUTHOR]

The demand for tocilizumab is increasing in women who wish to bear children and who have active rheumatoid arthritis. Described here is a woman with rheumatoid arthritis who discontinued her tocilizumab therapy at the end of the first trimester and resumed it after delivery and where tocilizumab levels in maternal serum, infant serum, and the breast milk were measured. Tocilizumab was not detected in maternal serum just before delivery, or in umbilical cord blood or infant serum after birth. Tocilizumab levels in colostrum after intravenous injection were 0.57% of those in serum. Tocilizumab treatment in the first trimester was not associated with a significant drug level in the fetus at delivery and no fetal complications were noted. [ABSTRACT FROM AUTHOR]

We report on an 8‐year‐old girl with Wilson disease who developed three episodes of peritonitis due to extended‐spectrum beta‐lactamase‐producing Escherichia coli after liver transplantation. Massive ascites were thought to account for low meropenem concentrations with standard dosing. Extending the infusion achieved higher troughs, greater time above minimum inhibitory concentration. [ABSTRACT FROM AUTHOR]

Aims: Tocilizumab (TCZ), a humanized anti‐interleukin‐6 receptor monoclonal antibody, is used to treat rheumatic diseases. There is limited information about the administration of TCZ during lactation. The dried spot method, a simple technique for processing biological samples which involves placement of a drop of specimen onto filter paper, has been used in clinical pharmacology to determine various drug concentrations. This study examined the feasibility of sample collection using the dried milk spot (DMS) method for obtaining data about the transfer of TCZ into breast milk. Methods: Concentrations of TCZ determined using DMSs prepared by patients were compared with those using liquid breast milk. Results: In an enzyme‐linked immunosorbent assay of TCZ in DMSs, the accuracy ranged from 93.0% to 113.8% and the precision ranged from 0.3% to 8.4%. All concentrations of TCZ were within 15% of the reference value when analyzed on separate days. TCZ in DMSs at room temperature, 4°C, and −20°C were stable for 28 days. Extracted TCZ concentrations from patient‐prepared DMSs were strongly correlated with those of liquid samples (r = 0.996). In a pharmacokinetic study, the median (range) maximum and minimum concentrations were 113 ng/mL (68‐205) and 8.5 ng/mL (4.8‐13.4), respectively. The milk‐to‐serum ratio at the trough TCZ concentration of 3 lactating mothers were 0.0015, 0.00082 and 0.0014. Conclusions: The DMS method for measuring TCZ transfer into breast milk may be reliable and feasible, and should contribute to evaluating the safety of breast‐fed infants whose mothers receive TCZ during lactation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Appropriate calcium and phosphate supplementation is essential for bone growth in preterm infants. Using Rehabix‐K2™ (AY Pharmaceuticals, Tokyo, Japan) and Pleamin‐P Injection™ (Fuso Pharmaceutical Industries, Osaka, Japan) as the total parenteral nutrition (TPN) and amino acid solution, respectively, we investigated ways of maximizing calcium and phosphate in the TPN solution. Methods: Rehabix‐K2, Pleamin‐P, calcium gluconate, sodium phosphate, 50% glucose, and water were mixed in varying proportions to create 16 formulations. Precipitation assessment was done three times for each of the 16 formulations, and was based on the Japanese Pharmacopeia. Result: Precipitation was observed 24 h after mixing when the calcium and phosphate were 60 mEq/L and 30 mmol/L or 80 mEq/L and 40 mmol/L, respectively. No precipitation was observed when the calcium and phosphate were 20 mEq/L and 10 mmol/L, respectively. Precipitation was observed once out of three times, when the calcium and phosphate were 40 mEq/L and 20 mmol/L, respectively, and the amino acids were 2% and 3% (mean pH, 6.13 and 6.26, respectively). No precipitation was observed, however, when the calcium and phosphate were 40 mEq/L and 20 mmol/L, respectively, and the amino acids were 0% and 1% (mean pH, 5.88 and 6.05, respectively). Conclusion: Not only the concentration of calcium and phosphate, but also the pH of the TPN solution, are crucial factors for precipitation. Based on these results, a well‐balanced TPN solution maximizing calcium and phosphate availability will be able to be formulated. [ABSTRACT FROM AUTHOR]

The article discusses a study that measured abatacept concentrations in the breast milk of a 41-year-old nursing mother with rheumatoid arthritis and examined the safety of her breastfed infant. Highlights include the approval of the study by the ethics committee of the National Center for Child Health and Development, her treatment with tocilizumab and certolizumab pegol before switching to abatacept treatment, and the infant Apgar scores at one and five minutes.

The article discusses research which investigated safety of tocilizumab use during pregnancy and lactation. Topics explored include the intravenous tocilizumab dosage administered to a pregnant woman with adult-onset Still's disease (AOSD), measurement of tocilizumab concentrations in maternal serum, cord blood, and breast milk, and the health condition of the infant following exposure to tocilizumab.

The infant dose I via i breast milk was 0.95% of the maternal daily dose, that was considered to be acceptable,8 even though the drug information states that etizolam use should be avoided during breastfeeding.5 To clarify more accurate information about etizolam excretion into breastmilk, a detailed etizolam concentration profile including maximum concentration in breastmilk following oral etizolam administration will be required. Anxiety disorders may require pharmacological treatment, and it has been estimated that 10% to 26% of pregnant women with these disorders are prescribed benzodiazepines or benzodiazepine-like hypnotic drugs.1,2 These medications cross the placental and blood-brain barriers, may affect fetal growth and development,3 and have been associated with increased risks of preterm birth, low Apgar score, neonatal intensive care unit admission, and neonatal respiratory distress syndrome.4 Etizolam, a benzodiazepine-class anxiolytic, is prescribed for the treatment and management of agitation, tension, insomnia and anxiety.5 Due to the limited market distribution and use of etizolam worldwide, only one report from Japan published the information on etizolam transfer into breast milk.6 Furthermore, the information on etizolam transfer into the fetal circulation is limited. Benzodiazepine concentrations in the breast milk and plasma of nursing mothers: Estimation of relative infant dose. [Extracted from the article]

Abstract: Degradation and recovery of electrode performance during the operation of polymer electrolyte fuel cells (PEFCs) with sulfonated polyimide (SPI-8) and Nafion® membranes were evaluated by changes in cell voltage (E cell), mass activity (MA), Tafel slope (TS), and electrochemical surface area (ECA) of the Pt catalyst. During continuous cell operation, values of E cell, MA and ECA decreased, but TS increased. It was found by ion chromatography combined with mass spectrometry (IC/MS) that the drain water contained, as decomposition products, bisulfate and several other ionic compounds derived from the side chain of SPI-8. These ionic compounds were found to adsorb on the surface of the Pt cathode catalyst and to suppress oxygen adsorption, resulting in increases in the overpotential for the oxygen reduction reaction (ORR). The cathode performance was able to recover by potential cycling under high humidity conditions, as the ionic compounds were removed from the Pt surface. [Copyright &y& Elsevier]

Abstract: A novel sulfonated polyimide membrane containing triazole groups (SPI-8) was subjected to long-term fuel cell operation. Excellent durability of the SPI-8 membrane was confirmed by single cell operation for 5000h at 80°C. Open circuit voltage and hydrogen crossover through the membrane showed only minor changes during cell operation, indicating a lack of catastrophic damage for the SPI-8 membrane. It was found by post-test analyses of the membrane that the ion exchange capacity (IEC) decreased only slightly, but the molecular weight decreased to 1/10, resulting in a loss of mechanical strength. It was concluded that the major degradation mode of the sulfonated polyimide membrane involves the ring-opening of the imide linkages via hydrolysis, while a certain degree of side chain degradation occurs as a result of oxidative attack by radical species. [Copyright &y& Elsevier]

Hydrocortisone has been utilized in the management of adrenal insufficiency. For pediatric patients, the commercially available enteral form of hydrocortisone tablets (Cortoril®) is administered in powder form after being compounded by a pharmacist. However, the stability and quality of compounded hydrocortisone powder have not been verified. In this study, we formulated a 20 mg/g oral hydrocortisone powder by adding lactose monohydrate to crushed and filtered hydrocortisone tablets and assessed the stability and physical properties of this compounded product in polycarbonate amber bottles or coated paper packages laminated with cellophane and polyethylene. Stability was examined over 120 days in three storage conditions: closed bottle, in-use bottle, and laminated paper. Drug dissolution and powder X-ray diffraction analysis were conducted to assess its physicochemical stabilities. Validated liquid chromatography-diode array detection was used to detect and quantify hydrocortisone and its degradation products. Although impurity B (cortisone) and G (hydrocortisone-21-aldehyde) were found after 120 days of storage, no crystallographic and dissolution changes were noted. Hydrocortisone content was maintained between 90% and 110% of initial contents for 120 days at 25 ± 2 °C and 60 ± 5% relative humidity in all packaging conditions. [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI) is a common health care-associated adverse event and the leading nosocomial complication following pediatric urological surgery. While continuous antimicrobial prophylaxis effectively reduces the risk of UTI following such a surgery, non-adherence is common and represents a distinct clinical entity that is associated with renal scarring. Acceptability is likely to have a significant impact on patient adherence. Herein we used a validated data-driven approach—the ClinSearch acceptability score test (CAST)—to investigate the acceptability of cefaclor, an oral antibiotic widely used for the prevention of pediatric UTI in Japan. Standardized observer reports were collected for 58 intakes of cefaclor 10% fine granules in patients aged from 0 to 17 years. The medicine was classified as positively accepted on the acceptability reference framework. According to the percentage of the prescribed dose taken reported at the end of the treatment, patients exhibited good adherence to this well-accepted medicine. Nonetheless, requirements for greater dosing frequency or poor acceptability in certain patients could affect adherence. Acceptability should be established to ensure patient adherence to medicines used for long-term prophylaxis and consequently guarantee the safety and efficacy of the treatment. [ABSTRACT FROM AUTHOR]

Background: Neonatal hemochromatosis (NH) is a rare but serious disease causing fulminant hepatic failure. The recurrence rate of NH in a subsequent infant of a mother with an affected infant is 70-90%. Recently, antenatal maternal high-dose intravenous immunoglobulin (IVIG) treatment has been reported to be effective for preventing NH recurrence. However, data on the IgG concentrations during this treatment are limited.Objective: We report a Japanese experience and present a pharmacokinetic simulation model of IgG during IVIG treatment.Methods: Women with histories of pregnancy diagnosed with NH were treated with IVIG weekly from the second trimester until the end of gestation. Serum IgG levels during treatment were collected frequently and pharmacokinetics were simulated by a two-compartment model.Results: Six women were included during eight pregnancies. None experienced severe adverse events. Three out of eight infants showed temporary liver dysfunction, but none required any treatment. A simulation study showed that the estimated trough and peak levels of IgG concentrations during IVIG were 2000-3000 and 4000-5000 mg/dl, respectively.Conclusion: This treatment prevented the recurrence of NH in siblings in Japanese women. We examined the details of serum IgG concentrations and introduced a new pharmacokinetic simulation model of IgG concentrations during IVIG treatment. [ABSTRACT FROM AUTHOR]

Background and Objective: High variability in vancomycin exposure in neonates requires advanced individualized dosing regimens. Achieving steady-state trough concentration (C0) and steady-state area-under-curve (AUC0–24) targets is important to optimize treatment. The objective was to evaluate whether machine learning (ML) can be used to predict these treatment targets to calculate optimal individual dosing regimens under intermittent administration conditions. Methods: C0 were retrieved from a large neonatal vancomycin dataset. Individual estimates of AUC0–24 were obtained from Bayesian post hoc estimation. Various ML algorithms were used for model building to C0 and AUC0–24. An external dataset was used for predictive performance evaluation. Results: Before starting treatment, C0 can be predicted a priori using the Catboost-based C0-ML model combined with dosing regimen and nine covariates. External validation results showed a 42.5% improvement in prediction accuracy by using the ML model compared with the population pharmacokinetic model. The virtual trial showed that using the ML optimized dose; 80.3% of the virtual neonates achieved the pharmacodynamic target (C0 in the range of 10–20 mg/L), much higher than the international standard dose (37.7–61.5%). Once therapeutic drug monitoring (TDM) measurements (C0) in patients have been obtained, AUC0–24 can be further predicted using the Catboost-based AUC-ML model combined with C0 and nine covariates. External validation results showed that the AUC-ML model can achieve an prediction accuracy of 80.3%. Conclusion: C0-based and AUC0–24-based ML models were developed accurately and precisely. These can be used for individual dose recommendations of vancomycin in neonates before treatment and dose revision after the first TDM result is obtained, respectively. [ABSTRACT FROM AUTHOR]

This single-centre prospective feasibility study (UMIN000030232) evaluated whether zinc supplementation was safe and effective for improving outcomes among patients with acute myocardial infarction (AMI). Within 24 h after successful primary percutaneous coronary intervention, consenting patients with AMI were randomly assigned 1:1 to receive conventional treatment (conventional treatment group) or conventional treatment plus zinc acetate supplementation (zinc supplementation group). The two groups were compared in terms of major adverse cardiovascular events (MACE), and scar size, which was evaluated using cardiac magnetic resonance imaging (CMR) at 4 weeks after discharge. A total of 56 patients underwent randomization (with 26 assigned to the zinc supplementation group and 27 to the conventional treatment group). The two groups had generally similar laboratory findings and clinical characteristics. The two groups also had similar lengths of hospital stay and rates of MACE. Forty of the 53 patients underwent CMR and it revealed that % core zone was numerically lower in the zinc supplementation group than in the conventional treatment group (9.3 ± 6.9% vs. 14.2 ± 9.1%, P = 0.07). This small single-centre study failed to detect a significant reduction in mid-term MACE after AMI among patients who received zinc supplementation. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA) are non-coding small RNA that regulate gene expression. MiR-328 is reported to influence breast cancer resistance protein (BCRP) expression in cancer cells. As a large inter-individual difference in BCRP levels is observed in various human tissues, the contribution of miR-328 to these differences is of interest. We hypothesized that DNA methylation in the miR-328 promoter region is responsible for the difference in miR-328 levels, leading to inter-individual variability in BCRP levels in human placenta. The association between placental miR-328 and BCRP levels was analyzed, and then DNA methylation in the miR-328 5'-flanking region and regulatory mechanisms causing inter-individual differences in miR-328 and BCRP levels were examined. MiR-328 expression was significantly correlated with BCRP mRNA (Rs = -0.560, P < 0.01) and protein (Rs = -0.730, P < 0.01) levels. It was also up-regulated by the demethylating agent 5-aza-2’-deoxycytidine in BCRP-expressing cells. Luciferase assays with differentially methylated reporter constructs indicated that methylation in the miR-328 5’-flanking region including a predicted CpG island remarkably decreased transcriptional activity compared to that in unmethylated constructs. We selected CCAAT/enhancer binding protein α (C/EBPα), located within the predicted CpG island, by in silico analysis. To elucidate the role of C/EBPα in miR-328 expression, a chromatin immunoprecipitation assay, promoter deletion analysis, and electrophoretic mobility shift assay (EMSA) were performed. C/EBPα-binding site-truncated constructs showed significantly decreased promoter activity, and EMSA indicated that the C/EBPα-binding sites were located in the CpG island. Finally, the methylation patterns of several CpG dinucleotides proximal to two C/EBPα-binding sites in the miR-328 5’-flanking region were correlated negatively with miR-328 levels, and positively with BCRP levels in human placental samples. These results suggest that methylation patterns in the miR-328 5’-flanking region are involved in the inter-individual difference in BCRP levels in human placenta. [ABSTRACT FROM AUTHOR]

This study aimed to determine the optimal cut-off value of the early drop in systolic blood pressure (SBP) for worsening renal function (WRF) in hospitalized patients with heart failure (HF) and analyze predictors of WRF and the early drop in SBP at that threshold. We retrospectively enrolled 396 patients with acute decompensated HF. The early drop in SBP was defined as the difference between baseline and SBP measured 24 h after hospitalization. We performed receiver operating characteristic (ROC) analysis to determine the optimal cut-off value of the early drop in SBP for WRF and evaluated the effect of the early drop in SBP on in-hospital mortality by multivariate logistic regression analyses. The mean age of the patients was 73.4 ± 14.7 years, and 61.2% were men. A 14.0% drop in SBP was identified as the optimal cut-off value for WRF from the ROC curve analysis. An early drop in SBP ≥ 14.0% was associated with WRF in multivariate logistic regression analysis (odds ratio 7.84; 95% confidence interval 4.06–15.14; P < 0.0001). The dose of intravenous furosemide within 24 h of admission was one of the predictors of the early drop in SBP ≥ 14.0%, while no early drop in SBP was a predictor of in-hospital mortality in multivariate logistic regression models. In conclusion, the optimal cut-off value for WRF in patients with HF was a 14.0% drop in SBP within 24 h of admission. The early drop in SBP ≥ 14.0% was one of the predictors of WRF in patients with HF. However, no early drop in SBP was associated with in-hospital mortality. This study was registered with the University Hospital Medical Information Network in Japan (UMIN000035989). [ABSTRACT FROM AUTHOR]

Antibiotics are among the most commonly prescribed drugs in children. Adherence to the treatment with these drugs is of the utmost importance to prevent the emergence of resistant bacteria, a global health threat. In children, medicine acceptability is likely to have a significant impact on compliance. Herein we used a multivariate approach, considering simultaneously the many aspects of acceptability to explore the drivers of oral antibiotic acceptability in children under twelve, especially in toddlers and in preschoolers. Based on 628 real-life observer reports of the intake of 133 distinct medicines, the acceptability reference framework highlighted the influence of many factors such as age and sex of patients, previous exposure to treatment, place of administration, administration device, flavor agent in excipients and active pharmaceutical ingredient. These findings from an international observational study emphasize the multidimensional nature of acceptability. Therefore, it is crucial to consider all these different aspects for assessing this multi-faceted concept and designing or prescribing a medicine in order to reach adequate acceptability in the target population. [ABSTRACT FROM AUTHOR]

Objectives: In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates.Methods: A 'meta-model' with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0-24 of 400 mg·h/L at steady-state in at least 80% of neonates.Results: A two-compartment model best fitted the data. Current weight, postmenstrual age (PMA) and serum creatinine were the significant covariates for CL. After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg q12h if <35 weeks PMA and 15 mg/kg q8h if ≥35 weeks PMA) achieved the AUC0-24 target earlier than a standard 'Blue Book' dosage regimen in >89% of the treated patients.Conclusions: The results of a population meta-analysis of vancomycin data have been used to develop a new dosing regimen for neonatal use and to assist in the design of the model-based, multinational European trial, NeoVanc. [ABSTRACT FROM AUTHOR]

Introduction: There were few studies that investigated the association between serum zinc concentration and acute myocardial infarction (AMI) in percutaneous coronary intervention era. Objective: We assessed the relationships between serum zinc concentration, complications, and prognosis in AMI patients after primary percutaneous coronary intervention. Methods: We conducted a single-center, prospective, observational study including 50 patients with AMI. We divided patients into two groups (High-zinc group and Low-zinc group) by median serum zinc concentration and compared two groups about clinical outcomes up to 1 year follow up. Results: The mean age of patients was 66.2 ± 11.8 years old. Patients in the Low-zinc group had ST-segment elevation more frequently than those in the High-zinc group (96.0% vs. 72.0%, P = 0.02). All-cause mortality at 1 year was similar in both groups (P (log-rank) = 0.33). However, the lengths of hospital stay and in coronary care unit were longer in patients in the Low-zinc group than in those in the High-zinc group (15.6 ± 9.2 days vs. 11.9 ± 2.9 days, P = 0.06; 3.9 ± 2.8 days vs. 2.3 ± 0.8 days, P = 0.01). Multivariate regression analysis showed that low serum zinc concentration was associated with the use of cardiac or respiratory assist devices (adjusted odds ratio, 17.79; 95% CI 1.123 to 1216.5; P = 0.04). Conclusions: Although there was no significance difference in mortality in Low-zinc and High-zinc groups, low serum zinc concentration was associated with longer stay in the coronary care unit, and was one of the independent predictors for the use of cardiac or respiratory assist devices. [ABSTRACT FROM AUTHOR]

Minitablets have garnered interest as a new paediatric formulation that is easier to swallow than liquid formulations. In Japan, besides the latter, fine granules are frequently used for children. We examined the swallowability of multiple drug-free minitablets and compared it with that of fine granules and liquid formulations in 40 children of two age groups (n = 20 each, aged 6–11 and 12–23 months). We compared the percentage of children who could swallow minitablets without chewing with that of children who could swallow fine granules or liquid formulations without leftover. The children who visited the paediatric department of Showa University Hospital were enrolled. Their caregivers were allowed to choose the administration method. In total, 37 out of 40 caregivers dispersed the fine granules in water. Significantly more children (80%, 95% CI: 56–94%) aged 6–11 months could swallow the minitablets than those who could swallow all the dispersed fine granules and liquid formulations (22%, 95% CI: 6–47% and 35%, 95% CI: 15–59%, respectively). No significant differences were observed in children aged 12–23 months. Hence, minitablets may be easier to swallow than dispersed fine granules and liquid formulations in children aged 6–11 months. [ABSTRACT FROM AUTHOR]

Objective: Cardiovascular disease is an important contributor to the mortality rate of patients with systemic lupus erythematosus (SLE), which is related to SLE disease activity. Fragmented QRS (fQRS) complexes, defined by additional spikes in the QRS complex, are useful for identifying myocardial scars on electrocardiography and can be an independent predictor of cardiac events. We aimed to assess the relationship between disease activity in patients with SLE and fQRS at the time of diagnosis. Methods: Forty-four patients with SLE were included. Patients with cardiac diseases, other rheumatic diseases, and prior treatment at the time of electrocardiography measurement were excluded. The appearance of fQRS represented exposure. The primary outcome was SLE Disease Activity Index 2000 (SLEDAI-2K). Multiple regression analysis was conducted to assess the association between fQRS and SLEDAI-2K adjusted for age, sex, and time from the estimated onset date to the date of diagnosis. Results: Among patients with SLE at diagnosis, 26 (59.1%) had fQRS. The median SLEDAI-2K was 18 (interquartile range [IQR], 12–22) and 9 (IQR, 8–15) in the fQRS(+) and fQRS(-) groups, respectively. SLEDAI-2K was significantly higher in the fQRS(+) group than in the fQRS(-) group (regression coefficient, 2.69; 95% confidence interval, 0.76–4.61; p = 0.008). Conclusion: Our results suggested that fQRS(+) patients with SLE had high disease activity. fQRS could likely detect subclinical myocardial involvement in patients with SLE and predict long-term occurrence of cardiac events. [ABSTRACT FROM AUTHOR]