Search

What is Known and Objectives: The initial tacrolimus dose regimen in paediatric lung transplant recipients is unknown. The present study optimized the initial tacrolimus dose regimen for paediatric lung transplant recipients. Methods: This study was based on a published population pharmacokinetic model of tacrolimus in lung transplant recipients and used Monte Carlo simulations to recommend an initial dose regimen of tacrolimus in paediatric lung transplant recipients. Results: Without voriconazole, the tacrolimus doses recommended for paediatric lung transplant recipients who were not CYP3A5*1 carriers were 0.02, 0.03, and 0.04 mg/kg/day, split into two doses, for weights of 10–16, 16–30, and 30–40 kg, respectively. For paediatric lung transplant recipients who were CYP3A5*1 carriers, the tacrolimus doses of 0.03, 0.04, 0.05, and 0.06 mg/kg/day, split into two doses, were recommended for weights of 10–16, 16–25, 25–30, and 30–40 kg, respectively. With voriconazole, the tacrolimus dose recommended for paediatric lung transplant recipients who were not CYP3A5*1 carriers was 0.02 mg/kg/day, split into two doses, for weights of 10–40 kg. For paediatric lung transplant recipients who were CYP3A5*1 carriers, tacrolimus doses of 0.02 and 0.03 mg/kg/day, split and two doses, were recommended for weights of 10–24 and 24–40 kg, respectively. What is New and Conclusions: This study developed tacrolimus dose regimens for the first time for paediatric lung transplant recipients using Monte Carlo simulation and optimized initial dosage in paediatric lung transplant recipients. [ABSTRACT FROM AUTHOR]

What is known and objective: The presence of extracorporeal membrane oxygenation (ECMO) is suggested to further exacerbate the pharmacokinetics (PK) alterations that occur during critical illness. The objectives of this study were to determine the population PK model of polymyxin B in critically ill patients with or without ECMO support investigated the influence of ECMO on PK variability and to identify an optimal dosing strategy. Methods: Forty‐four critically ill patients were enrolled, including eight patients with ECMO support. Eight serial serum samples were collected from each patient at steady state. The population PK was determined using NONMEM and Monte Carlo simulation was performed to evaluate the exposures of different dosing regimens. Results: The PK analyses included 342 steady‐state concentrations and a two‐compartment model was optimal for polymyxin B PK data modelling. In the final model, creatinine clearance (CLCR) was the significant covariate on CL (typical value 1.27 L/h; between‐subject variability 15.1%) and ECMO did not show a significant impact on the polymyxin B PK. Additionally, we found that the PK parameter estimates of patients with and without ECMO support were mostly similar. Based on Monte Carlo simulations, the dose escalation of polymyxin B in patients with increased CLCR improved the probability of achieving required exposure. For patients with CLCR ≤ 120 ml/min, a dosage regimen of 100 mg every 12 h may represent the optimal regimen at an MIC of 1 mg/L. What is new and conclusion: The impact of ECMO on the polymyxin B PK is likely to be minimal. Our study showed a potential relationship between CLCR and polymyxin B CL, and the dose of polymyxin B should be adjusted in patients with increased CLCR. [ABSTRACT FROM AUTHOR]

With the increase of obesity incidence, the development of antiobesity drugs has aroused extensive interest. In this study, a simple and portable personal glucose meter (PGM) method based on the lipase-mediated reaction combined with molecular docking was developed for the screening of lipase inhibitors. Lipase can catalyse the hydrolysis of 4-acetamidophenyl acetate to form acetaminophen, which can directly trigger the reduction of K3[Fe(CN)6] to K4[Fe(CN)6] in the glucose test strips and generate an electrical signal that can be detected by the PGM. When lipase inhibitors exist, the yield of acetaminophen will be reduced and results in a corresponding decrease of the PGM signal. Therefore, the activity of lipase can be measured by the PGM. After optimization of the experimental conditions, the inhibitory activity of fourteen small-molecule compounds and fifteen natural product extracts on lipase were evaluated by the developed PGM method. The results indicate that tannic acid, (-)-epigallocatechin gallate, (-)-epigallocatechin, (-)-epicatechin gallate, and epicatechin have good inhibitory effect on lipase (% of inhibition higher than 40.0%). Besides, the natural product extracts of Galla Chinensis, lemon, and Rhei Radix et Rhizoma have a good inhibitory effect on lipase with % of inhibition of (97.5 ± 0.6)%, (88.1 ± 0.7)%, and (79.1 ± 1.6)%, respectively. Finally, the binding sites and modes of six small-molecule compounds on lipase were investigated by the molecular docking study. The results show that the developed PGM method is an effective approach for the discovery of potential lipase inhibitors. [ABSTRACT FROM AUTHOR]

What Is Known and Objectives: mTOR inhibitors possess narrow therapeutic range and substantial pharmacokinetic variability and the consequences from suboptimal dosing are serious. The aim of this review is to summarize the current knowledge about the factors influencing mTOR inhibitors pharmacokinetics and the possibility of using these relationships in order to improve its therapy individualization in solid organ transplanted patients. Methods: Literature search from Pubmed and Web of Science databases were performed using Boolean search operators in order to identify relevant studies. Results and Discussion: A total of 701 reports were identified from the initial literature search. Out of which 40 studies dealt with relationships between various factors and pharmacokinetics of mTOR inhibitors and with relevance of these associations for dosage optimization. What Is New and Conclusion: The overview of the current covariates for pharmacokinetic variability of mTOR inhibitors has been provided on the level of absorption, distribution and elimination, and consequences of these relationships for dosing optimization has been summarized. [ABSTRACT FROM AUTHOR]

This study combined the use of radiation dosimeteric measurements and a custom-made anthropomorphic phantom in order to evaluate the accuracy of therapeutic dose calculations at the nasopharyngeal air-tissue interface. The doses at the nasopharyngeal air-tissue interface obtained utilizing the Pinnacle and TomoTherapy TPS, which are based on collapsed cone convolution superposition (CCCS) algorithms, were evaluated and measured under single 10 × 10 c m 2 , 2 × 2 c m 2 , two parallel opposed 2 × 2 c m 2 and clinical fields for early stage of nasopharyngeal carcinoma by using EBT3, GR-200F, and TLD 100. At the air-tissue interface under a 10 × 10 c m 2 field, the TPS dose calculation values were in good agreement with the dosimeter measurement with all differences within 3.5%. When measured the single field 2 × 2 c m 2 , the differences between the average dose were measured at the distal interface for EBT3, GR-200F, and TLD-100 and the calculation values were -15.8%, -16.4%, and -4.9%, respectively. When using the clinical techniques such as IMRT, VMAT, and tomotherapy, the measurement results at the interface for all three techniques did not imply under dose. Small-field sizes will lead to dose overestimation at the nasopharyngeal air-tissue interface due to electronic disequilibrium when using CCCS algorithms. However, under clinical applications of multiangle irradiation, the dose errors caused by this effect were not significant. [ABSTRACT FROM AUTHOR]

Objective. Panax ginseng and Atractylodes macrocephala Koidz. (AMK) are widely used in treating various diseases; however, research is insufficient on measuring the relationship that exists by combining this drug pair using the copula function. Methods. In this study, 279 traditional Chinese medicine prescriptions containing the Panax ginseng and AMK drug pair were extracted from the prescription database for three types of screened indications, namely, diabetes mellitus, diarrhea, and insomnia. Following the principle of dose conversion, each dynasty unit was uniformly converted into a modern unit. Then, the kernel density distribution of Panax ginseng and AMK was fitted with their empirical distribution functions. Finally, the optimal copula function was selected from the copula function family as a t-copula function. Results. The empirical distribution and probability density functions of Panax ginseng and AMK were obtained. From the results, their Kendall rank correlation coefficients with indications of diabetes mellitus, insomnia, and diarrhea were 0.8689, 0.7858, and 0.7403, whereas their Spearman rank correlation coefficients were 0.9563, 0.9276, and 0.8958. Results also indicated that the use of the t-copula function can better reflect the correlation between Panax ginseng and AMK doses. Conclusion. From the three indications, the dose between Panax ginseng and AMK was positively correlated. This study, therefore, confirms the medicinal principle of Chinese medicine "combining" from the perspective of mathematical statistics. Results from this study are practical to evaluate the correlation between the drug pair doses, Panax ginseng and AMK, using the copula function model, which provides a new model for the scientific explanation of compatibility for Chinese medicines. This study also provides a methodological basis for more drug measurement studies and clinical medications. [ABSTRACT FROM AUTHOR]

Background/Objectives. To evaluate the efficacy of switching to monthly ranibizumab in neovascular age-related macular degeneration (nAMD) showing an insufficient response to bimonthly aflibercept. Subjects/Methods. A total of 13 nAMD eyes showing an insufficient treatment response to three successive aflibercept injections were enrolled through a retrospective chart review. After switching, three consecutive monthly intravitreal ranibizumab injections were performed. The main outcome measurements included the best-corrected visual acuity (BCVA), central retinal thickness (CRT), presence of intraretinal fluid (IRF), and subretinal fluid (SRF) using optical coherence tomography (OCT) and were measured every month. Results. CRT and logMAR VA were 349.62 ± 223.51 μm and 0.50 ± 0.23 at the baseline and 274.69 ± 148.77 μm and 0.46 ± 0.24, 311.54 ± 192.90 μm and 0.45 ± 0.20 at 1 month after the first and third ranibizumab injections, respectively. The CRT decrease during three ranibizumab injections was statistically significant (38.08 ± 69.52 μm, p = 0.033). Change in VA was not statistically significant. The percentage of eyes with SRF was 100% at baseline and 53.8%, 76.9%, and 69.2% one month after each ranibizumab injections. The percentage of eyes with IRF was 38.5% at baseline and 23.1%, 23.1%, and 15.4%, respectively, after switching. Conclusion. Switching to monthly ranibizumab in nAMD showing an insufficient response to bimonthly aflibercept led to immediate anatomical improvement. It can be considered in countries where the healthcare insurance system limits the minimum injection interval of aflibercept. [ABSTRACT FROM AUTHOR]

Background. The introduction of carbidopa-levodopa extended-release (CD-LD ER) capsules (Rytary®) did not go as smoothly as expected, largely due to difficulty around dose conversion from available immediate-release (IR) levodopa (LD) formulations. The dose conversion table in the CD-LD ER prescribing information was similar to the table used in the pivotal clinical trial and is considered by many prescribing HCPs to be less than optimal. By the end of the dose conversion period in that trial, dosing in 76% of subjects was adjusted for symptom control; roughly 60% of patients required a higher dose and about half required more frequent administration than the recommended TID dosing. Objective. The primary objective of our nationwide (US) survey was to determine the dose conversion strategy most commonly employed by CD-LD ER frequent prescribers. The survey also aimed to explore additional features regarding CD-LD ER use in clinical practice. Methods. A survey consisting of 21 multiple-choice questions was developed and administered to experts in the use of CD-LD ER, based on prescription volume. Results. Of the 394 HCPs who were invited to participate, 90 (23%) HCPs completed the survey. All respondents were aware of the dose conversion table; the largest group did not find the table to be helpful and did not use it to convert patients to CD-LD ER. The most common strategy in calculating the CD-LD ER dose was based on the total daily LD IR dose, with the majority of that group initiating dose conversion by doubling the total daily LD dose from CD-LD IR and administering CD-LD ER one less time per day. Conclusion. Overall, most survey respondents agreed that a good starting point for CD-LD ER conversion could be doubling the daily LD IR dose and administering it one time less frequently. Moreover, rapid patient follow-up after initial dose conversion to allow for further dose adjustments plays a critical role in achieving success. Gaining experience over time is important for satisfactory conversion. [ABSTRACT FROM AUTHOR]

What is known and objective: The drug therapy of critically ill patients requires intensive evaluation and management due to their severity of illness. These patients often require complex medication regimens. This study analysed the pharmaceutical care provided by clinical pharmacists (CPs) in a single medical centre in Taiwan. In addition, we explored the drug‐related problems (DRPs) experienced by patients in intensive care units (ICUs) to determine how to improve the quality and safety of drug therapy. Methods: This retrospective study was conducted from February 2019 to January 2020. The CPs implemented Taiwan's National Health Insurance (NHI) Scheme for Improving Hospital Drug Safety and Quality programme to improve the safety and quality of drug therapy. The CPs included in the study had at least 2 years' clinical experience and had participated in an ICU team for at least 6 consecutive months. They provided individualized drug treatment evaluation and intervention. Content of care was documented in the Clinical Pharmacy Service Record. Results and discussion: A total of 4374 pharmacy care records were evaluated by 12 CPs. The major category of ICU pharmaceutical care was medication reconciliation (n = 2938; 67.2%). Most of the medication interventions were for errors in dosing or dosing frequency (n = 218; 55.8%). Patients with renal dysfunction required more pharmaceutical interventions than did patients with normal renal function (odds ratio = 1.63; 95% confidence interval 1.31‐2.01). The main interventions were related to antimicrobial agents (n = 386; 81.3%). During the study period, 99.2% of interventions were accepted and 90.8% were changed within 24 hours. What is new and conclusion: Increased pharmaceutical interventions for patients with renal dysfunction compared with patients with normal renal function were observed. Most cases of inappropriate frequency of dosing or dosing of antimicrobial agents required intervention. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the efficacy and safety of different dose regimens of intravenous (IV) tranexamic acid (TXA) in adolescent spinal deformity surgery. Methods. Two researchers independently searched multiple databases, including PubMed, Embase, Cochrane Library, and Web of Science to find studies that met the inclusion criteria. A meta-analysis was performed based on the guidelines of the Cochrane Reviewer's Handbook. Results. Six randomized controlled trials (RCTs) and eleven non-RCTs were identified, including 1148 patients. According to different dose regimens of IV TXA, the included studies were divided into the high-dose group and the low-dose group. Compared with placebo, both groups had less total blood loss (TBL) (high dose: WMD = − 1737.55 , 95% CI: (-2247.16, -1227.94), P < 0.001 , I 2 = 0 % ; low dose: WMD = − 528.67 , 95% CI: (-666.06, -391.28), P < 0.001 , I 2 = 0 %), intraoperative blood loss (IBL) (high dose: WMD = − 301.48 , 95% CI: (-524.3, -78.66), P = 0.008 , I 2 = 60.3 % ; low dose: WMD = − 751.14 , 95% CI: (-967.21, -535.08), P < 0.001 , I 2 = 0 %), and blood transfusion rates (high dose: RR = 0.19 , 95% CI: (0.1, 0.37), P < 0.001 , I 2 = 0 % ; low dose: RR = 0.4 , 95% CI: (0.18, 0.91), P = 0.029 , I 2 = 57 %). High-dose IV TXA use was associated with more vertebral fusion segments (WMD = 0.53 , 95% CI: (0.23, 0.82), P < 0.001 , I 2 = 31.2 %). Low-dose IV TXA use was associated with shorter operative time (WMD = − 18.43 , 95% CI: (-26.68, -10.17), P < 0.001 , I 2 = 0 %). Conclusion. High-dose and low-dose IV TXA were effective in reducing TBL, IBL, and blood transfusion rates without increasing complications in adolescent patients undergoing spinal deformity surgery. Low-dose IV TXA was effective in reducing the operative time. Both the high-dose and low-dose groups had similar preoperative and postoperative Hb levels compared to the control group. [ABSTRACT FROM AUTHOR]

What is known and objective: Vancomycin therapeutic guidelines suggest a loading dose of 25‐30 mg/kg for seriously ill patients. However, high‐quality data to guide the use of loading doses are lacking. We aimed to evaluate whether a loading dose (a) achieved a target trough concentration at steady state and (b) improved early clinical response. Methods: Patients with an estimated glomerular filtration rate ≥ 90 mL/min/1.73 m2 were included. A loading dose of 25 mg/kg vancomycin followed by 15 mg/kg twice daily was compared with traditional dosing. A Cmin sample was obtained before the fifth dose. An early clinical response 48‐72 hours after the start of therapy and clinical success at end of therapy (EOT) was evaluated in patients with methicillin‐resistant Staphylococcus aureus (MRSA), methicillin‐resistant coagulase‐negative Staphylococci or Enterococcus faecium. Results: There was no significant difference in Cmin between the regimen with and without a loading dose (median: 10.4 and 10.2 µg/mL, P =.54). Proportions of patients achieving 10‐20 and 15‐20 µg/mL were 56.9% and 5.6%, respectively, in patients with a loading dose. Although there was no significant difference in success rate at EOT between groups, a loading dose was associated with increased early clinical response for all infections (adjusted odds ratio [OR]: 4.588, 95% confidence interval [CI]: 1.373‐15.330) and MRSA infections (OR: 12.065, 95% CI: 1.821‐79.959). Study limitations included no Cmin measurements within 24 hours and the inclusion of less critically ill patients. What is new and conclusion: A loading dose of 25 mg/kg followed by 15 mg/kg twice daily did not achieve the optimal Cmin at steady state in patients with normal renal function. However, more early clinical responses were obtained with a loading dose compared with traditional dosing, possibly because of a prompt albeit temporary achievement of a more effective concentration. [ABSTRACT FROM AUTHOR]

Purpose. It is well known that interstitial photodynamic therapy (iPDT) of large tumors requires effective planning to ensure efficient delivery of therapeutic dose to the target tumors. This should be achieved in parallel with minimal damage to the nearby intact tissues. To that end, clinical iPDT can be attained using cylindrical diffusing optical fibers (CDFs) as light sources. In this work, we optimize output CDF powers in order to deliver a prescribed light dose to a spherical volume such as a tumor node. Methods. Four CDFs are placed vertically inside the tumor node. The fluence rate is calculated using the diffusion equation. Therapeutic target dose is (20-50) J·cm-2. The optical properties ( μ a = 0.085 c m − 1 , μ s ′ = 16 c m − 1 ) of a breast tumor and the treatment time of 150 sec are used to calculate the fluence rate. Results. For four CDFs, the therapeutic target dose (20-50) J·cm-2 is delivered to more than 90%. This is the ratio of the total points that receive the target dose in proportion to the total points in the volume of the node of 3 cm in diameter, whereas, in larger nodes, the ratio is decreased to approximately 67%. Five CDFs are required to improve this ratio by more than 10%. Conclusion. Optimizing delivered powers enables the distribution of the therapeutic dose uniformly in the medium. In addition, this simulation study represents an essential part of a development dosimetry system for measuring and controlling the optical dose in the breast tumors. [ABSTRACT FROM AUTHOR]

Purpose. We developed a mathematic empirical model for describing the small field penumbra in order to analyze the potential dose perturbation caused by overlapping field to avoid the dose calculation errors in linear accelerator-based radiosurgery. Materials and methods. A ball phantom was fabricated for measuring penumbra at 4 different gantry angles in the coplanar plane. A least square root estimation (LSRE) Model was created to fit the measured penumbra dose profile and to predict the penumbra dose profile at any gantry angles. The Sum of Squared Errors (SSE) was used for finding the parameters n and t for the best fitting of the LSRE model. Geometric and mathematical methods were used to derive the model parameters. Results. The results showed that the larger the gantry angle of the field, the more the expansion of the penumbra dose profile. The least square root estimation model for describing small field penumbra is as follows: PenumbraD(š) = T · (1/2) · (1 - (š/√n + š²)) + t where PenumbraD(š) denotes the dose profile D(š) at the penumbra region, T is the penumbra height (usually in scalar 100), n is the parameter for curvature, š = x - Wd/2 (x and š are the values in cm on x-axis), and t is the radiation transmission of the collimator. Geometric analysis establishes the correlation between the penetration depth of the exposure and its effect on the penumbra region in ball phantom. The penumbra caused by an exposure at any arbitrary angles can be geometrically derived by using a one-variable quadratic equation. Conclusion. The dose distribution in penumbra region of small field can be created by the LSRE model and the potential overdosage or underdosage owing to overlapping field perturbation can be estimated. [ABSTRACT FROM AUTHOR]

Background. The study aimed to evaluate inpatient antibiotic use in both the State Second Hospital and State Third Hospital in Mongolia, using the WHO developed and standardized ATC/DDD methodology. Methods. Data were collected from the State Second Hospital and State Third Hospital which are major public hospitals that provide health care for approximately one fifth of the Mongolian population. Antibiotic utilization was monitored retrospectively for five years (2013–2017) using the ATC/DDD methodology and data were presented in DDD/ admission and DDD/100 bed days. Statistical analysis was performed using a Student's t-test for parametric data. A P value of ≤0.05 was considered to be statistically significant. Results. The annual consumption rates in the State Second Hospital were stable over time while in the State Third Hospital consumption rates varied considerately between years. Overall, the total antibiotic consumption rate was very high, but has decreased in both hospitals. The rate of consumption of all antibiotics was approximately twice that in the State Third Hospital (421.7 DDD/100 bed days) between 2013 and 2017 when compared with the State Second Hospital (199.7 DDD/ 100 bed days), P<0.001). The seven most frequently used antibiotics comprised approximately 75% of all DDDs in both hospitals, in the period 2013–2017; being: amoxicillin, cefazolin, cefotaxime, ceftriaxone, clarithromycin, ciprofloxacin, and nitroxoline. However, this was not consistent when considering the individual years, since in 2015 and 2016, these seven active agents represented approximately 50%. Conclusion. This is the first hospital-based study of antibiotic consumption rates reported in Mongolia. In addition to very high consumption rates, large differences occurred between the hospitals investigated. Inappropriate and high levels of antibiotic use lead to increased costs and also increased nosocomial infection rates with potentially resistant species. The Government and health professionals need to take more active roles in improving and promoting quality antibiotic use among inpatients. [ABSTRACT FROM AUTHOR]

What is known and objective: The aim of this study was to evaluate the appropriateness and clinical outcomes of edoxaban use, and to determine the role of clinical pharmacists in improving the efficacy and safety of edoxaban use. Methods: A retrospective study was performed by using an electronic medical record and anticoagulation clinical data from 600 patients who received edoxaban from 1 March 2016 to 16 July 2017 at a tertiary teaching university hospital. The appropriateness of edoxaban use was assessed using eight criteria based on drug use evaluation criteria developed by the American Society of Health‐System Pharmacists drug use evaluation guidelines, details in Korea Food and Drug Administration approval of edoxaban. Clinical outcomes were evaluated between the appropriately prescribed and inappropriately prescribed groups regarding the incidence of thrombosis and bleeding episodes. Results and discussion: After excluding 86 patients due to the inability to assess renal function, 514 were eligible. Appropriate use was found in 294 patients (57.2%). The most frequent inappropriate use of edoxaban was dose adjustment (60.8%) in accordance with the dosing recommendation in patients with renal insufficiency (creatinine clearance [CrCl] of 15‐50 mL/min) and a low body weight of <60 kg. Moreover, there were three cases of edoxaban use in patients with prosthetic heart valves and moderate‐to‐severe mitral stenosis, and 15 cases of non‐valvular atrial fibrillation in patients with CrCl >95 mL/min in whom edoxaban use is not recommended. Furthermore, we found that the factors related to the appropriateness of edoxaban use were <60 kg body weight (adjusted odds ratio [OR]: 0.310; confidence interval [CI]: 0.197‐0.488) and CrCl <50 mL/min (adjusted OR: 0.629; CI: 0.404‐0.980). There were 45 events (8.75%) of any bleeding, 9 (1.8%) of stroke/transient ischaemic attack (TIA) and four events (0.8%) of deep vein thrombosis (DVT)/pulmonary embolism (PE). However, there was no difference between the appropriately prescribed group (294 patients) and inappropriately prescribed group (220 patients) in the incidence of bleeding events (27 [9.2%] vs 18 [8.2%]), stroke/TIA (7 [2.4%] vs 2 [0.9%]) and DVT/PE (2 [0.7%] vs 2 [0.9%]), respectively. What is new and conclusion: Although edoxaban has a broad therapeutic window that does not require routine monitoring, it should be cautiously used in patients with renal insufficiency (CrCl <50 mL/min) and body weight <60 kg. [ABSTRACT FROM AUTHOR]

Summary: What is known and objective: The International Organization for Standardization (ISO) created enteral device specifications to reduce tubing misconnections. The Global Enteral Device Supplier Association (GEDSA) supports a female design: standard and low dose tip (LDT). Concerns include increased complexity of use with adapters, dosing accuracy and workflow. No peer‐reviewed studies have evaluated dosing accuracy of the complete female system with adapters. The objective of this study was to compare dosing accuracy of the female design to legacy syringes. Methods: An in vitro study was conducted at the University of Florida College of Pharmacy pharmaceutics laboratory. Assessments were completed for syringe size, dispense methods and volumes, and adapters when applicable. A gravimetric scale and specific gravity were used to calculate administration volumes. The primary outcome was frequency administration volume exceeded 10% expected amount. Results and discussion: A total of 576 tests were performed. The LDT resulted in significantly higher rates of unacceptable dosing variance compared to legacy (21.2% vs 7.4%, P = 0.003). Variance exceeding 10% occurred more frequently with LDT 0.5 and 1 mL syringes, medication cup dispensing (liquid or tablet) and inappropriate LDT adapter use. Unapproved adapter processes compared to FDA‐approved processes held a higher likelihood of unacceptable dosing variance (28% vs 7.4%, P < 0.001). FDA‐approved use of adapters with prefilled syringes compared to bedside administration may result in higher rates of dosing inaccuracy (18.8% vs 5.6%, P = 0.06). What is new and conclusions: This study raises clinical concerns of dosing inaccuracies with the LDT syringes, particularly with 0.5 and 1 mL sizes. The use of adapters significantly increases the opportunity for inaccurate dosing. [ABSTRACT FROM AUTHOR]

Summary: What is known and objective: Alzheimer's disease (AD) is the most common cause of dementia among the elderly. The exact cause of the disease is not clearly known, and no existing therapies are able to prevent disease progression. Identification of the possible "impaired brain insulin signalling in AD" enriched the scope for "the repurposing of diabetic drugs in AD management." Among the different classes of diabetic drugs, pioglitazone (PIO), a PPARγ agonist classed as an insulin sensitizer, is of the highest interest for AD management. The drug is reported to have direct action on multiple targets involved in AD, independent of insulin signalling. Even though PIO has appeared to be a potent molecule in preclinical trials, limited success was observed in the clinical stage. The tentative reasons for the limited therapeutic success in the clinical stage are not clear. The main focus of the review is to discuss various factors that might limit the therapeutic success of PIO in clinical trials and possible approaches to overcome those limitations. Method: The research articles, review articles, and patents containing information regarding the clinical and preclinical trials of PIO in AD have been reviewed thoroughly using the keywords related to diabetic drugs in AD, PIO for AD management and mechanism of PIO in AD. Literature search was conducted on PubMed, SCOPUS and EMBASE. Results and discussion: Previous studies have indicated that the blood‐brain barrier (BBB) is the biggest challenge to delivering PIO to the brain. Therefore, to attain a therapeutic concentration in the brain, a higher dose is needed, which is also supported by preclinical investigations in AD; however, in clinical studies, scientists have used the usual diabetic doses. This dose is inadequate to attain a therapeutic concentration in the brain and appears to be the primary reason for the limited success of PIO in clinical trials. The stage of drug intervention and the nature of the study population are also influential factors for the therapeutic response. What is new and conclusion: The insufficient concentration of the drug reaching the brain appears to be the crucial factor that limits the therapeutic success of PIO in AD management. Since the administration of higher doses cannot be recommended due to safety issues, the current situation demands the use of novel tools to ensure a therapeutic concentration reaches the brain. [ABSTRACT FROM AUTHOR]

Introduction. All adult medulloblastoma (AMB) patients should be treated with craniospinal irradiation (CSI) postoperatively. Because of the long irradiation range, multiple radiation fields must be designed for conventional radiotherapy technology. CSI can be completed in only one session with helical tomotherapy (HT). We evaluated the dose of HT, volumetric intensity modulated arc therapy (VMAT), and three-dimensional conformal radiotherapy (3D-CRT) of AMB and the results of 5 cases of AMB treated with HT. Methods. Complete craniospinal and posterior cranial fossa irradiation with HT, VMAT, and 3D-CRT and dose evaluation were performed. And results of 5 cases of AMB treated with HT were evaluated. Results. A large volume of tissue was exposed to low dose radiation in the organs at risk (OAR), while a small volume was exposed to high dose radiation with HT. The conformity and uniformity of the targets were good with HT and VMAT, and the volume of targets exposed to high dose with VMAT was larger than that of HT. The uniformity of 3D-CRT was also good, but the dose conformity was poor. The main toxicity was hematologic toxicity, without 4th-degree bone marrow suppression. There was 3rd-degree inhibition in the white blood cells, hemoglobin, and platelets. The three female patients suffered menstrual disorders during the course of radiation. Two female patients with heavy menstruation suffered 3rd-degree anemia inhibition, and 2 patients suffered amenorrhea after radiotherapy. Although menstrual cycle was normal, the third patient was not pregnant. Conclusion. CSI with HT is convenient for clinical practice, and the side effects are mild. With good conformity and uniformity, VMAT can also be used for selection in CSI. For poor conformity, 3D-CRT should not be the priority selection for CSI. In female patients, the ovaries should be protected. [ABSTRACT FROM AUTHOR]

Objective Insulin dose-adjusted hemoglobin A1c (HbA1C, IDAA1c) correlates well with stimulated C-peptide levels, but has not yet been evaluated in a large cohort of patients with Type 1 diabetes (T1D). Methods We investigated prevalence of partial remission (PREM) defined by IDAA1c ≤9 in 3657 in children with new-onset T1D who were continuously followed over 6 years. We evaluated the predictors of PREM using the multicenter database from the DPV (Diabetes Patienten Verlaufsdokumentation) registry. Results PREM occurred in 71% of patients. Median duration was 9 (0-21) months. Compared to children <5 years at T1D onset, those aged 5-10 and ≥10 years had twice the chance of developing PREM (OR: 2.08, CI: 1.67-2.60; P < .001 and OR: 2.16, CI: 1.70-2.75; P < .001). Boys were more likely to develop PREM than girls (OR 1.41, CI: 1.18-1.69; P = .0002). Further predictors for PREM were: ketoacidosis, autoantibodies, and HbA1c at T1D onset. These results were confirmed by quantile regression analysis with duration of PREM as dependent variable. Conclusion This research on a large cohort provides insight into epidemiologic characteristics of PREM in T1D defined by IDAA1c. As IDAA1c does not discriminate between insulin sensitivity and secretion, available data cannot resolve whether the sex-difference in PREM reflects innate higher insulin resistance in girls, or better beta-cell recovery in boys. Further research is needed to clarify the usefulness and performance of IDAA1c in clinical practice. [ABSTRACT FROM AUTHOR]

A newly developed method based on ultrahigh performance liquid chromatography (UHPLC) was optimized for the simultaneous determination of vitamin D3 and menaquinone-7 (MK-7) in tablet formulation in the present study. UHPLC separation of vitamin D3 and MK-7 was performed with ACE Excel 2 C18-PFP column (2 μm, 2.1 × 100 mm) at 0.6 mL min−1 flow rate, whereas the mobile phase consisted of methanol/water (19:1, v/v, phase A) and isopropyl alcohol (99.9%, phase B) containing 0.5% triethylamine. Isocratic separation of both the analytes was performed at 40°C by pumping the mobile phases A and B in the ratio of 50:50 (v/v, pH, 6.0). Both analytes were detected at a wavelength of 265 nm and the injection volume was 1.0 μL. The overall runtime per sample was 4.5 min with retention time of 1.26 and 3.64 min for vitamin D3 and MK-7, respectively. The calibration curve was linear from 5.0 to 100 μg mL−1 for vitamin D3 and MK-7 with a coefficient of determination (R2) ≥ 0.9981, while repeatability and reproducibility (expressed as relative standard deviation) were lower than 1.46 and 2.21%, respectively. The proposed HPLC method was demonstrated to be simple and rapid for the determination of vitamin D3 and MK-7 in tablets. [ABSTRACT FROM AUTHOR]

Purpose. Use of tranexamic acid (TXA) in the setting of arthroplasty of the lower extremity has been previously described. The aim of this study was to evaluate the benefit of a single dose of TXA (500 mg vial) administered intravenously just prior to RTSA in an Asian population. Methods. The records of 48 patients (no TXA, n=24, versus TXA, n=24) that underwent RTSA for cuff tear arthropathy were retrospectively reviewed. All patients had a Hemovac drain positioned for 2 days after surgery. Hemoglobin (Hb) and hematocrit (Hct) were checked on postoperative day 2 and compared with preoperative levels. Results. Hematologic change on postoperative day 2 as determined by Hb level after surgery was statistically lower in the TXA group (2.8±0.8 versus 2.1±0.8 (mg/dL), P=0.006). Mean fall in Hct level was also significantly less in the TXA group (8.0±2.5 versus 6.1±2.6 (L/L), P=0.012). Total Hemovac drainage tended to be lower in the TXA group (263.4±129.3 versus 203.5±84.2 (ml), P=0.064). TXA was found to have no noticeable side effects. Conclusion. The use of a single intravenous dose of TXA immediately prior to RTSA reduces hematologic deterioration postoperatively and the amount of Hemovac drainage. TXA could avoid unnecessary transfusion and its associated medical side effects and cost. [ABSTRACT FROM AUTHOR]

Background. Many studies have demonstrated that a higher radiotherapy dose is associated with improved outcomes in non-small-cell lung cancer (NSCLC). We performed a dosimetric planning study to assess the dosimetric feasibility of intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) in locally advanced NSCLC. Methods. We enrolled twenty patients. Five different dose plans were generated for each patient. All plans were prescribed a dose of 60 Gy to the planning tumor volume (PTV). In the three SIB groups, the prescribed dose was 69 Gy, 75 Gy, and 81 Gy in 30 fractions to the internal gross tumor volume (iGTV). Results. The SIB-IMRT plans were associated with a significant increase in the iGTV dose (P < 0.05), without increased normal tissue exposure or prolonged overall treatment time. Significant differences were not observed in the dose to the normal lung in terms of the V5 and V20 among the four IMRT plans. The maximum dose (Dmax) in the esophagus moderately increased along with the prescribed dose (P < 0.05). Conclusions. Our results indicated that escalating the dose by SIB-IMRT is dosimetrically feasible; however, systematic evaluations via clinical trials are still warranted. We have designed a further clinical study (which is registered with ClinicalTrials.gov, number NCT02841228). [ABSTRACT FROM AUTHOR]

Objectives. To assess the impact of combining low-tube voltage acquisition with iterative reconstruction (IR) techniques on the iodine dose in coronary CTA. Methods. Three minipigs underwent CCTA to compare a standard of care protocol with two alternative study protocols combining low-tube voltage and low iodine dose with IR. Image quality was evaluated objectively by the CT value, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) in the main coronary arteries and aorta and subjectively by expert reading. Statistics were performed by Mann–Whitney U test and Chi-square analysis. Results. Despite reduced iodine dose, both study protocols maintained CT values, SNR, and CNR compared to the standard of care protocol. Expert readings confirmed these findings; all scans were perceived to be of at least diagnostically acceptable quality on all evaluated parameters allowing image interpretation. No statistical differences were observed (all p values > 0.11), except for streak artifacts (p=0.02) which were considered to be more severe, although acceptable, with the 80 kVp protocol. Conclusions. Reduced tube voltage in combination with IR allows a total iodine dose reduction between 37 and 50%, by using contrast media with low iodine concentrations of 200 and 160 mg I/mL, while maintaining image quality. [ABSTRACT FROM AUTHOR]

Gancao-Ganjiang-Tang (GGT) is a traditional Chinese medicine (TCM) prescription and is a representative prescription for recuperating depleted Yang in Treatise on Febrile Diseases. The TCM theory believes that the efficacy of medicinal herbs is decided by the multicompounds which consist of different kinds of chemical constituents with bioactivities, but not by a monomeric constituent. From ancient times until today, GGT have 5 different kinds of compatibilities that can be verified. In this study, a HPLC-DAD method was established for the simultaneous determination of 8 compounds including 6-gingerol, 8-gingerol, 6-shogaol, liquiritin, liquiritigenin, isoliquiritin, isoliquiritigenin, and glycyrrhizic acid in the five GGT. The total contents of the 8 compounds in GGT varied from 555.56 to 956.33 μg/mL. The effects showed that the dosage and compatibility of medicinal herbs have influenced the content of chemical compounds of TCM prescription while the content of chemical compounds has acted on clinical efficacy. Quality evaluation and active essence screening of TCM (including single herb and prescription) should be based on the TCM theory and clinical effectiveness. The method was proven to be suitable for quality control of GGT. [ABSTRACT FROM AUTHOR]

What is known and objective There are many methods for dosing vancomycin. The purpose of this commentary was to compare open-access vancomycin dosing websites with Vancomycin-Calculator.com and describe how body weight can affect their pharmacokinetic ( PK) calculations. Comment A vancomycin dosing website, Vancomycin-Calculator.com, was developed to improve the dosing practice at our health system. Nine other vancomycin dosing calculators were identified, including three open-access websites. Each website uses a different dosing method. Most of the websites calculated similar doses for patients with normal body weight. Vancomycin-Calculator.com was the only website to calculate practical doses for obese patients, and it calculated higher daily doses for underweight patients compared to other websites. What is new and conclusion Vancomycin-Calculator.com is an open-access vancomycin dosing website that was developed using the Bauer PK method. Compared with three other websites, PK calculations resulted in significant differences for underweight and obese patients. [ABSTRACT FROM AUTHOR]

This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson’s disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson’s disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

Objective Retrospective continuous glucose monitoring ( CGM) can guide insulin pump adjustments, however, interpretation of data and recommending new pump settings is complex and subjective. We aimed to compare the safety and glycaemic profiles of children after their diabetologist or a novel algorithm ( PumpTune) adjusted their insulin pump settings. Research design and methods In a randomized cross-over trial of 22 patients aged 6-14 yr with type 1 diabetes with mean Hba1c 7.4% (57 mmol/mol) using CSII, CGM was used over two periods each of 6.5 d to assess percentage time glucose remained within, above and below 3.9-10.0 mmol/L. Before the start of one period pump settings were adjusted by the patient's diabetologist, and before the other insulin pump settings were adjusted by PumpTune. Results A total of 63.4% of the sensor glucose levels were within target range with PumpTune settings and 57.4% were within range with the clinician settings (p = 0.016). The time spent above target range with PumpTune was 26.9% and with clinician settings was 33.5% (p = 0.021). The time spent below target range with PumpTune was 9.7% and with clinician settings was 9.2% (p = 0.77). The mean number of times when a sensor glucose level <2.75 mmol/L was recorded with PumpTune settings was 2.9 compared with 3.7 with clinician settings (p = 0.39). There were no serious adverse outcomes and no difference in parent-assessed satisfaction. Conclusions Automated insulin pump adjustment with PumpTune is feasible and warrants testing in a larger more varied population over a longer time. In this well-controlled group of children, PumpTune achieved a more favorable glucose profile. [ABSTRACT FROM AUTHOR]

CXCL8 displays several tumor-promoting effects. Targeting and/or lowering CXCL8 concentrations within the tumor microenvironment would produce a therapeutic benefit. Aim of this study was to test the effect of IFNγ on the basal and TNFα-stimulated secretion of CXCL8 in TCP-1 and BCPAP thyroid cancer cell lines (harboring RET/PTC rearrangement and BRAF V600e mutation, resp.). Cells were incubated with IFNγ (1, 10, 100, and 1000 U/mL) alone or in combination with TNF-α (10 ng/mL) for 24 hours. CXCL8 and CXCL10 concentrations were measured in the cell supernatants. IFNγ inhibited in a dose-dependent and significant manner both the basal (ANOVA F: 22.759; p<0.00001) and the TNFα-stimulated (ANOVA F: 15.309; p<0.00001) CXCL8 secretions in BCPAP but not in TPC-1 cells (NS). On the other hand, IFNγ and IFNγ + TNF-α induced a significant secretion of CXCL10 in both BCPAP (p<0.05) and TPC-1 (p<0.05) cells. Transwell migration assay showed that (i) CXCL8 increased cell migration in both TPC-1 and BCPAP cells; (ii) IFNγ significantly reduced the migration only of BCPAP cells; and (iii) CXCL8 reverted the effect of IFNγ. These results constitute the first demonstration that IFNγ inhibits CXCL8 secretion and in turn the migration of a BRAF V600e mutated thyroid cell line. [ABSTRACT FROM AUTHOR]

Background. Sepsis-induced immunosuppression may result in higher mortality rates in patients. Methods. We examined the relationship of cytokine responses from stimulated peripheral blood mononuclear cells (PBMCs) and monocyte human leukocyte antigen-DR (HLA-DR) expression (days 1 and 7) with low-dose steroid therapy in 29 septic patients. Patients were treated according to the guidelines. Thirty healthy controls were enrolled for validation. Results. Eighteen patients were prescribed low-dose steroids and 11 were not. Interleukin- (IL-) 12 responses in patients without low-dose steroid therapy on days 1 and 7 were higher than those with low-dose steroid therapy. Compared to day 1, IL-12 responses significantly increased on day 7 in patients without low-dose steroid therapy. After regression analysis, the change in the IL-12 response from day 7 to day 1 was found to be independently associated with the low-dose steroid therapy. There was no difference in monocyte HLA-DR expression between patients treated with and without low-dose steroid on day 1 or 7. No change in monocyte HLA-DR expression from day 7 to day 1 was observed in patients with or without low-dose steroid therapy. Conclusion. Decreased IL-12 response was associated with the low-dose steroid therapy in PBMCs of septic patients. [ABSTRACT FROM AUTHOR]

Purpose. Drug dose recommendations are not well defined in patients undergoing continuous renal replacement therapy (CRRT) due to limited published data. Several guidelines and pharmacokinetic equations have been proposed as tools for CRRT drug dosing. Dose recommendations derived from these methods have yet to be compared or prospectively evaluated. Methods. A literature search of PubMed, Micromedex, and Embase was conducted for 40 drugs commonly used in the ICU to gather pharmacokinetic data acquired from patients with acute and chronic kidney disease as well as healthy volunteers. These data and that obtained from drug package inserts were gathered for use in three published CRRT drug dosing equations. Doses calculated for a model patient using each method were compared to doses suggested in a commonly used dosing text. Results. Full pharmacokinetic data was available for 18, 31, and 40 agents using acute kidney injury, end stage renal disease, and normal patient data, respectively. On average, calculated doses differed by 30% or more from the doses recommended by the renal dosing text for >50% of the medications. Conclusion. Wide variability in dose recommendations for patients undergoing CRRT exists when these equations are used. Alternate, validated dosing methods need to be developed for this at-risk patient population. [ABSTRACT FROM AUTHOR]

Cancer is a class of diseases characterized by out-of-control cells’ growth which affect cells and make them damaged. Many treatment options for cancer exist. Chemotherapy as an important treatment option is the use of drugs to treat cancer. The anticancer drug travels to the tumor and then diffuses in it through capillaries. The diffusion of drugs in the solid tumor is limited by penetration depth which is different in case of different drugs and cancers. The computation of this depth is important as it helps physicians to investigate about treatment of infected tissue. Although many efforts have been made on studying and measuring drug penetration depth, less works have been done on computing this length from a mathematical point of view. In this paper, first we propose phase lagging model for diffusion of drug in the tumor. Then, using this model on one side and considering the classic diffusion on the other side, we compute the drug penetration depth in the solid tumor. This computed value of drug penetration depth is corroborated by comparison with the values measured by experiments. [ABSTRACT FROM AUTHOR]

Capsule Shaqeeqa, Unani formulation, is prescribed for the clinical treatment of diseases like sinusitis, headache, and migraine. The safety evaluation data of it is not available; in order to provide the safety data the present study was carried out. The study was carried out on four groups of rats (n=5). Two groups (one male and one female group) as normal controls were orally given water while the other two groups were orally given daily doses of drug at the dose level of 150 mg/kg of body weight for duration of 90 days. Physiological parameters like body weight, feed consumption, water consumption, and clinical signs were regularly monitored and recorded. Organs were collected, examined, and weighed and specimens were taken for histopathological studies. The results showed that the drug did not alter the physiological parameters. There was no mortality or any morbidity found in drug treated rats. There was no statistical significant change found in any haematological or biochemical parameter of rats orally fed with Shaqeeqa. A statistically insignificant association verified that haematological and biochemical parameters were rendered unaffected by the drug. Moreover histological investigations of essential key organs demonstrated that the drug did not prompt any histopathological change. These observations demonstrate the safety of Capsule Shaqeeqa at the studied dosage levels. [ABSTRACT FROM AUTHOR]

Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model. [ABSTRACT FROM AUTHOR]

What is known and objective Adjustment of drug dosage in patients with end-stage renal disease prevents serious adverse effects, which occur due to the accumulation of drugs or other toxic metabolites. Nevertheless, dosing errors occur most commonly among patients with end-stage renal disease. The aim of this study was to assess the quality of care for end-stage renal disease outpatients using their renal dosing adjustment status. Methods A cross-sectional study was performed using the data collected from 43 South Korean medical institutions via questionnaires. A total of 2428 patients on haemodialysis, who were at least 18 years of age, were included. Among these patients, the study population was confined to patients who were taking medications and required renal dosing adjustments from three therapeutic classes: antihypertensives, antihyperglycaemics and lipid-modifying agents. The study population ( n = 828) was prescribed a total of 1097 drug orders for the target drugs. Determination of appropriate dosage adjustment was based on GFR (glomerular filtration rate) using the Modification of Diet in Renal Disease revised 4-variable equation. The primary outcome was non-adherence to drug dosing requirements for end-stage renal disease patients with consideration to their renal function. Results and discussion Among the study population ( n = 828), 469 haemodialysis patients were identified as having drug orders that were adherent to renal dosing recommendations. There were significant differences between the patient groups who received recommendation-adherent and non-adherent drug orders in the characteristics of the medical institutions they visited, causes of chronic renal failure and prevalence of concurrent diabetes mellitus. The primary factor of non-adherence to renal dosing adjustment recommendations was characteristics of medical institutions. Compared to tertiary hospitals, secondary hospitals and primary care clinics were 1·16 and 1·22 times, respectively, more non-adherent in accordance with the multivariate analysis ( OR: 1·16, 95% CI: 1·02-1·20, OR: 1·22, 95% CI: 1·00-1·36, respectively). What is new and conclusions Dosing error is one of the most common problems among patients with renal failure. To decrease the dosing errors, an improvement needs to be made in medical institutions. This can be accomplished by implementing the clinical decision support systems that educate physicians on appropriate renal dosing and help them prescribe appropriate drug dosages. [ABSTRACT FROM AUTHOR]

Background and objective The insulin requirement for type 1 diabetes during prolonged fasting is unclear. In order to define this for clinical purposes, we investigated the total insulin dose associated with successful completion of a 25 h religious fast. Subjects and methods Questionnaires were filled in during telephone interviews performed before and after 88 fasts in 57 young individuals with type 1 diabetes (age 20.4 ± 5.3, range: 12.3-31.2 yr). Duration of their diabetes was 8.7 ± 6.1 yr (range: 0.5-21.8) and latest HbA1c was 8.5 ± 1.9% (5.7-13.7). Twenty-eight patients fasted using multiple daily injections (MDI) and 30 were on continuous subcutaneous insulin infusion (CSII), including one who fasted in both categories. Subjects were instructed either to act as they had done for previous successful fasts or, for first-time fasts, to inject half their daily basal insulin injection or halve their basal CSII rate throughout the fast. The total daily insulin dose associated with successful completion of the fast was determined. Results Among those who completed the fast, average total insulin was 0.19 ± 0.16 U/kg, patients who discontinued their fast took on average 0.34 ± 0.15 U/kg. Seven MDI patients and 12 CSII patients terminated their fast early, mostly for mild hypoglycemia. No severe hypoglycemia or other serious adverse event occurred during any of the fasts. Conclusions Fasting for 25 h is safe and can be undertaken in individuals with type 1 diabetes. The recommended total daily dose is 0.2 U/kg/day. This recommendation may possibly be used for other situations in which abstention from oral intake is required. [ABSTRACT FROM AUTHOR]

What is known and objective The dofetilide label recommends using actual body weight ( ABW) to calculate the Cockcroft-Gault creatinine clearance (CrCl) for the determination of the initial dose; however, few studies have attempted to evaluate this dosing recommendation in overweight and obese patients. We evaluated whether the current dofetilide dosing recommendation based on ABW is appropriate in overweight and obese patients. Methods This is a retrospective cohort study conducted at two large academic medical centres in the United States on overweight and obese patients (body mass index ≥ 25 kg/m2) who were newly started on dofetilide based on ABW. Patients were categorized into (i) the different-dose group if their CrCl calculated based on the ideal body weight ( IBW) resulted in a lower initial dofetilide dose compared with ABW-based CrCl and (ii) the same-dose group if they would have the same initial dose based on IBW and ABW. The primary outcome was dofetilide dose reduction or discontinuation due to prolongation of the corrected QT interval during the first 3 days of dofetilide therapy. Multivariable logistic regression analysis was performed to identify factors predicting the risk of primary outcome. Results and discussion Of the 132 patients included in the study, 29 (22·0%) were in the different-dose group and 40 (30·3%) had the primary outcome. The per cent of patients with the primary outcome was not statistically significantly different between the different-dose and same-dose groups (37·9% vs. 28·2%; P = 0·31). Diabetes mellitus was a significant predictor for the primary outcome (odds ratio 2·54; 95% confidence interval 1·05-6·15). What is new and conclusion Our study provides the evidence on the safety of the current dofetilide dosing recommendation in overweight and obese populations in clinical practice. Current ABW-based dofetilide dosing is reasonable in overweight and obese patients. [ABSTRACT FROM AUTHOR]

Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1 diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review - based on the experiences of the Hvidoere Study Group (HSG) - is to propose comprehensive definitions for current insulin regimens reflecting current diabetes management in childhood and adolescence. The HSG - founded in 1994 - is an international group representing 24 highly experienced pediatric diabetes centers, from Europe, Japan, North America and Australia. Different benchmarking studies of the HSG revealed a broad variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides the concepts 'conventional' and 'intensified', several other terms for the characterization of insulin regimens are in use: Basal Bolus Concept (BBC), multiple daily injections (MDI), and flexible insulin therapy (FIT) are most frequently used, although none of these expressions is clearly or consistently defined. The proposed new classification for insulin management will be comprehensive, simple, and catchy. Currently available terms were included. This classification may offer the opportunity to compare therapeutic strategies without the currently existing confusion on the insulin regimen. [ABSTRACT FROM AUTHOR]

Objective We aimed to compare hemoglobin A1c (HbA1c), total and basal insulin doses, basal insulin injection frequencies, and body mass index ( BMI) in children with type 1 diabetes mellitus ( T1DM) who are receiving detemir and glargine as basal insulin in a basal-bolus therapy. Method This retrospective study included 117 (53 females) children and adolescents with T1DM older than 4 yr of age, minimum diabetes duration of 2 yr, and receiving basal-bolus insulin regimen (at least 4 injections/d, insulin aspart or lispro as bolus insulin). Comparisons were made for those receiving insulin detemir (n = 32) or glargine (n = 85) as the basal insulin. Results Age, pubertal status, BMI standard deviation scores, and diabetes duration were similar in detemir and glargine groups. Glycemic control was similar in both groups ( HbA1c levels 8.9 ± 2.1% vs. 8.5 ± 1.7% for detemir and glargine, respectively; p = 0.497). Both mean basal insulin (0.52 vs. 0.41 U/kg/d, p < 0.001) and mean total daily insulin (1.11 vs. 0.93 U/kg/d, p < 0.001) doses were higher in the detemir group. Furthermore, higher ratio of twice-daily basal insulin injection was detected in the detemir group (62.5 vs. 32.9% p = 0.004). Subgroup analysis according to pubertal status, or the number of daily basal injections showed similar results. Conclusion Insulin detemir provides similar glycemic control with glargine, but, approximately 27% higher mean basal and 19% higher mean total insulin doses with two-fold more twice-daily basal insulin injection requirement. [ABSTRACT FROM AUTHOR]

What is known and objective For over 50 years, warfarin was the only oral anticoagulant approved in the United States. In 2011, the Food and Drug Administration ( FDA) approved rivaroxaban. Since its introduction, rivaroxaban has served as an alternative to warfarin to minimize drug interactions and avoid drug monitoring. The objective of this study was to evaluate the appropriateness of rivaroxaban dosing, indication and safety in a community hospital and to identify areas for improvement in its use. Methods This single-centre, retrospective review evaluated patients who received at least one dose of rivaroxaban between November 2011 and July 2013. The primary outcome included appropriateness of the first day of therapy based on indication and renal function per FDA-approved dosing recommendations for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation ( NVAF) and for the treatment or prevention of venous thromboembolism ( VTE). The secondary outcome included incidence of major bleeding or non-major clinically relevant bleeding. Results and discussion Of the 445 patients evaluated, 36·9% of patients treated for NVAF and 12·4% treated for VTE were on an inappropriate regimen. Major bleeding within 12 months occurred in 3·5% of patients treated for NVAF, 1·2% for VTE and 0% for off-label indications with a similar trend for non-major clinically relevant bleeding (3·8%, 1·8% and 0%, respectively). What is new and conclusion Though offering potential advantages over warfarin, the use of rivaroxaban should be monitored to increase appropriateness of therapy and improve patient safety. Therapeutic interchanges, pharmacist-directed interventions and other initiatives can be implemented to ensure appropriate use. [ABSTRACT FROM AUTHOR]

What is known and objective Clinical practice in the initiation, prescribing, dosing and monitoring of warfarin in the UK varies, but this has not been adequately documented. The objective was to undertake a survey on current clinical practice in this area, and how it compares with national guidelines that have been developed by the British Committee for Standards in Haematology. Methods A national online survey of anticoagulation clinics was performed using Survey Monkey®. The survey was designed to capture data for prescribing, dosing and monitoring of anticoagulation with warfarin. Results Of 85 clinics who responded to the survey, most were run by secondary care (68%), facilitated by specialist nurses (58%) and followed standard guidelines for the management of warfarin (87%). The majority of clinics indicated their target international normalized ratio (INR) for patients with atrial fibrillation (AF) (69/73; 94·5%) was between 2·0 and 3·0, but the indicated target INR for mechanical heart valves was more variable. Initiation and loading dosing regimens were a major source of variability with uncertainty surrounding individual patient factors such as age, ethnicity and BMI. What is new and conclusions Current practice amongst UK anticoagulation clinics largely follows current national guidelines but better guidance on dosing, taking into account factors that determine interindividual variability in daily warfarin dose requirements would improve and standardize oral anticoagulation with warfarin. [ABSTRACT FROM AUTHOR]

What is known and objective: Vancomycin is administered via intermittent infusion (II) almost exclusively in the United States, whereas continuous infusion (CI) dosing methods are used regularly in many European countries. The purpose of this literature analysis is to review current evidence regarding the advantages and disadvantages of CI vancomycin in relation to II, based on the pharmacokinetic and pharmacodynamic aspects of dosing and monitoring therapy, and to identify current practices of CI vancomycin dosing. Methods: Medline, Cochrane and GoogleScholar databases were searched using vancomycin as a MeSH term, along with continuous and infusion in all fields, which identified 136 citations. A second search added the terms intermittent and survey, producing nine additional articles. All articles that reported an assessment of CI or II vancomycin administration in adult patients, based on clinical, pharmacokinetic, cost or monitoring considerations, were identified. A total of 43 publications were determined to be suitable for final analysis and possible inclusion in the report. Results and discussion: A meta-analysis of six studies concluded that CI vancomycin was associated with a lower relative risk of kidney injury than II therapy, although other studies reported equivocal findings. The results of several clinical studies suggest that CI vancomycin produces clinical outcomes that are comparable to II. Current vancomycin consensus guidelines promote aggressive dosing to achieve trough levels of 10-15 or 15-20 mg/ L, but also include recommendations to target a daily area under the curve (AUC24) to minimum inhibitory concentration (MIC) ratio of at least 400. Because vancomycin is a non-concentrationdependent antibiotic, it might be more prudent to monitor steady-state serum concentrations (Css) during a CI rather than trough concentrations during II, due to the questionable correlation between measured trough concentration and AUC. From a pharmacokinetic/pharmacodynamic perspective, vancomycin dosing and monitoring practices associated with CI offer potentially greater reliability than II. A major disadvantage of CI involves the possibility of having to intravenously coadminister another drug that might not be compatible with vancomycin. [ABSTRACT FROM AUTHOR]

Background Insulin resistance increases during adolescence in those with type 1 diabetes mellitus ( T1DM), complicating glycemic control and potentially increasing cardiovascular disease ( CVD) risk. Metformin, typically used in type 2 diabetes mellitus ( T2DM), is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity. Objective We hypothesized that metformin would improve metabolic parameters in adolescents with T1DM. Design, setting, and participants This randomized, double-blinded, placebo-controlled trial included 74 pubertal adolescents (ages: 13-20 yr) with T1DM. Participants were randomized to receive either metformin or placebo for 6 months. Glycated hemoglobin ( HbA1c), insulin dose, waist circumference, body mass index ( BMI), and blood pressure were measured at baseline, 3 and 6 months, with fasting lipids measured at baseline and 6 months. Results Total daily insulin dose, BMI z-score and waist circumference significantly decreased at 3 and 6 months compared to baseline within the metformin group, even among normal-weight participants. In the placebo group, total insulin dose and systolic blood pressure increased significantly at 3 months and total insulin dose increased significantly at 6 months. No significant change was observed in HbA1c at any time point between metformin and placebo groups or within either group. Conclusions Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose. The decrease in waist circumference indicates that fat distribution is also likely impacted by metformin in T1DM. Further studies with higher metformin doses and more detailed measurements are needed to confirm these results, their underlying mechanisms, and potential impact on CVD in T1DM youth. [ABSTRACT FROM AUTHOR]

A standard protocol of dosimetric measurements is used by the organizations responsible for verifying that the doses delivered in radiation-therapy institutions are within authorized limits. This study evaluated a self-designed simple auditing phantom for use in verifying the dose of radiation therapy; the phantom design, dose audit system, and clinical tests are described. Thermoluminescent dosimeters (TLDs) were used as postal dosimeters, and mailable phantoms were produced for use in postal audits. Correction factors are important for converting TLD readout values from phantoms into the absorbed dose in water. The phantom scatter correction factor was used to quantify the difference in the scattered dose between a solid water phantom and homemade phantoms; its value ranged from 1.084 to 1.031. The energy-dependence correction factor was used to compare the TLD readout of the unit dose irradiated by audit beam energies with 60Co in the solid water phantom; its value was 0.99 to 1.01. The setup-condition factor was used to correct for differences in dose-output calibration conditions. Clinical tests of the device calibrating the dose output revealed that the dose deviation was within 3%. Therefore, our homemade phantoms and dosimetric system can be applied for accurately verifying the doses applied in radiation-therapy institutions. [ABSTRACT FROM AUTHOR]

Radiation pneumonitis (RP) is a common complication for radiotherapy of esophageal cancer and is associated with the low dose irradiated lung volume. This study aims to reduce the mean lung dose (MLD) and the relative lung volume at 20 Gy (V20) and at low dose region using various designs of the fan-shaped complete block (FSCB) in helical tomotherapy. Hypothetical esophageal tumor was delineated on an anthropomorphic phantom. The FSCB was defined as the fan-shaped radiation restricted area located in both lungs. Seven treatment plans were performed with nonblock design and FSCB with different fan angles, that is, from 90° to 140°, with increment of 10°. The homogeneous index, conformation number, MLD, and the relative lung volume receiving more than 5, 10, 15, and 20 Gy (V5, V10, V15, and V20) were determined for each treatment scheme. There was a substantial reduction in the MLD, V5, V10, V15, and V20 when using different types of FSCB as compared to the nonblock design. The reduction of V20, V15, V10, and V5 was 6.3%–8.6%, 16%–23%, 42%–57%, and 42%–66% for FSCB 90°–140°, respectively. The use of FSCB in helical tomotherapy is a promising method to reduce the MLD, V20, and relative lung volume in low dose region, especially in V5 and V10 for esophageal cancer. [ABSTRACT FROM AUTHOR]

What is known and objective Medication errors ( ME) in oncology are known to cause serious iatrogenic complications. However, MEs still occur at each step in the anticancer chemotherapy process, particularly when injections are prepared in the hospital pharmacy. This study assessed whether a ME simulation program would help prevent ME-associated iatrogenic complications. Methods The 5-month prospective study, consisting of three phases, was undertaken in the centralized pharmaceutical unit of a university hospital of Lyon, France. During the first simulation phase, 25 instruction sheets each containing one simulated error were inserted among various instruction sheets issued to blinded technicians. The second phase consisted of activity aimed at raising pharmacy technicians' awareness of risk of medication errors associated with antineoplastic drugs. The third phase consisted of re-enacting the error simulation process 3 months after the awareness campaign. The rate and severity of undetected medication errors were measured during the two simulation (first and third) phases. The potential seriousness of the ME was assessed using the NCC MERP® index. Results and discussion The rate of undetected medication errors decreased from 12 in the first simulation phase (48%) to five in the second simulation phase (20%, P = 0∙04). The number of potential deaths due to administration of a faulty preparation decreased from three to zero. Awareness of iatrogenic risk through error simulation allowed pharmacy technicians to improve their ability to identify errors. What is new and conclusion This study is the first demonstration of the successful application of a simulation-based learning tool for reducing errors in the preparation of injectable anticancer drugs. Such a program should form part of the continuous quality improvement of risk management strategies for cancer patients. [ABSTRACT FROM AUTHOR]

What is known and objective Obesity is a significant burden on the healthcare system in the United States, and determining the appropriate antimicrobial dosing regimen in morbidly obese patients is challenging. Morbidly obese patients have documented differences in pharmacokinetic and pharmacodynamic properties compared to normal-weight patients, which impact antibiotic efficacy and toxicity. The Food and Drug Administration does not recognize obesity as a special population and does not require pharmaceutical companies to perform studies specific to obese patients. However, there are an increasing number of post-approval studies in obese patients, and this manuscript reviews available clinical and pharmacokinetic literature regarding weight-based antimicrobial agents. Additionally, we describe a single-centre approach to optimize dosing in morbidly obese patients. Methods A comprehensive literature search was performed on 15 weight-based antimicrobials in the setting of obesity: acyclovir, aminoglycosides, amphotericin B, cidofovir, colistimethate, daptomycin, flucytosine, foscarnet, ganciclovir, quinupristin/dalfopristin, trimethoprim/sulfamethoxazole, vancomycin and voriconazole. A weight-based antimicrobial dosing guideline for morbidly obese patients was developed. An analysis of guideline compliance and cost analysis were performed following guideline implementation. Results and discussion This review describes the pharmacokinetic changes that occur in obese patients, including increased volume of distribution, altered hepatic metabolism, renal excretion and changes in protein binding. The majority of weight-based antimicrobials result in increased serum concentrations in morbidly obese patients compared to normal-weight patients when the calculated dose is based on actual body weight. What is new and conclusion This review demonstrates different antibiotic pharmacokinetic properties are altered in obese patients that could impact efficacy and toxicity. A single-centre guideline for weight-based antimicrobial dosing in obesity was developed and provides recommendations for using ideal body weight, adjusted body weight or actual body weight when calculating antimicrobial doses. However, more research is needed to better elucidate optimal dosing of weight-based antimicrobials in obesity, with particular focus on efficacy and toxicity. [ABSTRACT FROM AUTHOR]

Objective To validate the partial remission ( PR) definition based on insulin dose-adjusted HbA1c ( IDAA1c). Subjects and methods The IDAA1c was developed using data in 251 children from the European Hvidoere cohort. For validation, 129 children from a Danish cohort were followed from the onset of type 1 diabetes ( T1D). Receiver operating characteristic curve ( ROC) analysis was used to evaluate the predictive value of IDAA1c and age on partial C-peptide remission (stimulated C-peptide, SCP > 300 pmol/L). Results PR ( IDAA1c ≤ 9) in the Danish and Hvidoere cohorts occurred in 62 vs. 61% (3 months, p = 0.80), 47 vs. 44% (6 months, p = 0.57), 26 vs. 32% (9 months, p = 0.32) and 19 vs. 18% (12 months, p = 0.69). The effect of age on SCP was significantly higher in the Danish cohort compared with the Hvidoere cohort (p < 0.0001), likely due to higher attained Boost SCP, so the sensitivity and specificity of those in PR by IDAA1c ≤ 9, SCP > 300 pmol/L was 0.85 and 0.62 at 6 months and 0.62 vs. 0.38 at 12 months, respectively. IDAA1c with age significantly improved the ROC analyses and the AUC reached 0.89 ± 0.04 (age) vs. 0.94 ± 0.02 (age + IDAA1c) at 6 months (p < 0.0004) and 0.76 ± 0.04 (age) vs. 0.90 ± 0.03 (age + IDAA1c) at 12 months (p < 0.0001). Conclusions The diagnostic and prognostic power of the IDAA1c measure is kept but due to the higher Boost stimulation in the Danish cohort, the specificity of the formula is lower with the chosen limits for SCP (300 pmol/L) and IDAA1c ≤9, respectively. [ABSTRACT FROM AUTHOR]

Background While childhood diabetes incidence is rising, especially in toddlers, once or twice-daily toddler-friendly insulin mixtures were withdrawn, imposing four to five miniscule injections, on needle-phobic toddlers. Although more injections may mean more needle-dribbling, such potential dose-loss is unstudied. Objective Study insulin loss in toddlers' dose range if one-drop dribbled during injection from half-unit pens ( SemiPens). Drop-loss is assessed relative to current insulin dose adjustment, and if significant, propose solutions. Methods The SemiPens, New HumaPen Luxura HD® ( HumaPen) and NovoPen Junior® ( NovoPen), with 31G-5 mm BD-MicroFine needles were used to study drop size or dose-fraction lost if one drop dribbled in dose range 0.5-10 units. Results HumaPen and NovoPen produced sizable drops mean standard deviation ( SD) 0.30 (0.05) and 0.36 (0.06) units/drop (p < 0.001). This constituted progressively increasing proportion of the toddlers' doses, 10-fold higher percentage from 6 to 60% or 7.2 to 72%, as the dose gets smaller from 5 to 0.5 units. Discussion Insulin dose-adjustments are usually done therapeutically within 5-20% dose-changes, while one-step reduction by >20% is hardly required. Therefore, the unintentional dosing change if a drop dribbles is clinically important particularly on using multiple doses below 6 units, compared with fewer larger daily injections. We propose using U20 insulin in disposable SemiPens to make DeciPen, with fivefold-reduction in insulin loss if a drop is lost through dribbling or skin-leak. Conclusion The one-drop insulin loss is statistically significant, clinically important, and potentiates glycemic variability. Disposable DeciPen may minimize insulin dribbling and leaking and fivefold improve dose accuracy and precision; and ensure reproducibility without prolonging injection time. [ABSTRACT FROM AUTHOR]

What is known and objective Drug prescribing is an essential part of inpatient care, and prescription errors/omissions have the potential to lead to disastrous consequences. Paediatric inpatient prescribing is particularly sensitive to error due to the weight-adjusted dosing of many medications prescribed in the acute setting. Previous studies have described a high incidence of error in adult drug chart completion, although no studies to date have assessed the error seen in the paediatric setting or accuracy of weight-adjusted dosing. Our objective was to determine the degree of error seen in paediatric drug prescribing for patients admitted under the care of oral and maxillofacial surgery and to explore practical and accessible methods through which error can be reduced. Methods We retrospectively evaluated inpatient drug charts to assess the prescribing practices seen for patients admitted under the care of oral and maxillofacial surgery in an NHS children's hospital and compared these findings against established hospital standards. The study also examined the distribution and variability of weight-adjusted dose prescribing in an attempt to set targets for auditing improvements following the implementation of changes. Results and discussion Prescriptions were completed by a combination of doctors from maxillofacial and anaesthetic teams, with similar error rates seen in both specialties. 13% of drug charts contained one or more errors in frequency prescribing. For weight-adjusted drugs, a median under-dosage of −5·4% was noted, with an IQR of −12 to −0·6. Our study has confirmed that errors are common both in the manual completion of paediatric prescription charts and in the calculation of weight-adjusted doses. What is new and conclusion We conclude that inaccuracies in prescription chart completion are a frequent occurrence and that dosage and frequency-prescribing errors may potentially act synergistically to create a significant disparity between the recommended and actual amount of drug that is delivered. Our study demonstrates a clear bias towards under-prescribing weight-adjusted doses which may be contributing to reduced efficacy of analgesia, among other drugs. Simple methods can be implemented on a specialty basis to improve the accuracy of both drug chart completion and weight-adjusted dosing. [ABSTRACT FROM AUTHOR]

The object of this study is to observe the effects of platycodin D, a saponin purified from Platycodi Radix, on mice collageninduced arthritis (CIA). A daily dose of 200, 100, and 50mg/kg platycodin D was administered orally to male DBA/1J mice for 40 days after initial collagen immunization. To ascertain the effects administering the collagen booster, CIA-related features (including body weight, poly-arthritis, knee and paw thickness, and paw weight increase) was measured from histopathological changes in the spleen, left popliteal lymph node, third digit, and the knee joint regions. CIA-related bone and cartilage damage improved significantly in the platycodin D-administered CIA mice. Additionally, myeloperoxidase (MPO) levels in the paw were reduced in platycodin D-treated CIA mice compared to CIA control groups. The level of malondialdehyde (MDA), an indicator of oxidative stress, decreased in a dose-dependent manner in the platycodin D group. Finally, the production of IL-6 and TNF-α, involved in rheumatoid arthritis pathogenesis, was suppressed by treatment with platycodin D. Taken together, these results suggest that platycodin D is a promising new effective antirheumatoid arthritis agent, exerting anti-inflammatory, antioxidative and immunomodulatory effects in CIA mice. [ABSTRACT FROM AUTHOR]