Dosing strategies for de novo once-daily extended release tacrolimus in kidney transplant recipients based on CYP3A5 genotype

BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression.Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus,but this has not been established for tacrolimus extended-release tablets in the de novo setting.AIM To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.METHODS Single-arm,prospective,single-center,open-label,observational study(ClinicalTrials.gov:NCT037-13645).Life cycle pharma tacrolimus(LCPT)orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight.If weight is more than 120%of ideal body weight,an adjusted body weight was used.LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL.Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.RESULTS Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(6 d vs 13.5 d vs 4.5 d;P=0.025).Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(16 mg vs 16 mg vs 12 mg;P=0.010)(0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg;P=0.018).CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers(7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL;P=00.008).No differences were identified with regards to kidney graft function at 30-d post-transplant.Serious adverse events were reported for 13(36%)patients.CONCLUSION Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacrolimus to achieve target trough concentrations.We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.

Evaluating Vancomycin Clinical Outcomes Using Area under the Curve versus Trough Based Dosing Strategies

Background: The 2020 consensus guidelines recommend AUC guided dosing as the preferred monitoring method for vancomycin. AUC based dosing has shown to reduce incidence of acute kidney injury (AKI), utilize lower daily doses in obese patients, and maintain efficacy. Several institutions have adjusted their protocols to utilize AUC guided dosing. However, there are limited studies comparing the clinical outcomes of AUC versus trough monitoring. Methods: This was a retrospective, observational, single centered study. The primary outcome was to evaluate the clinical success of AUC dosing versus trough based dosing of vancomycin for MRSA infections using a composite outcome of afebrile post treatment ( Results: Forty-seven patients were included in this study, 17 in the AUC group and 30 in the trough group. The primary composite outcome showed a significant benefit of AUC dosing (p = 0.04). The composite component culture clearance showed the largest improvement for the AUC group when compared with the trough group (p = 0.03). More patients achieved therapeutic target attainment and reached the target sooner (3 days versus 4 days, p = 0.2) in the AUC group. Over the study course, 94.1% of patients in the AUC group were considered therapeutic compared to 63.8% in the trough group (p = 0.03). Vancomycin levels were collected less frequently in the AUC group (3 versus 4, p = 0.2). Conclusion: The outcomes of this study may suggest AUC guided dosing as a beneficial alternative to trough based dosing. AUC based dosing may improve clinical success which can be further explored in larger prospective clinical trials.

Optimal dosing time of acid algaecide for restraining algal growth

Restraining algal growth by algaecide has been studied by many researchers, but the dosing time has not yet been studied. In this study, we examined the appropriate dosing time of algaecide through a series of experiments. In the experiments, the pH value of water is significantly affected by Microcystis aeruginosa, and the variation of the pH value is in favor of the growth of the alga. Therefore, using acid algaecide in the period with maximum pH values, i.e., the stable phase, would change the acidity-alkalinity of the water significantly, and would negatively affect algal growth. Acid algaecide does not eliminate the alga effectively if the acid algaecide is dosed in the logarithmic growth phase. Using acid algaecide in the decline phase after algal bloom not only is unfavorable for eliminating the alga, but also prolongs the decline phase, and even brings about next larger algal bloom.

Dynamic Flow Control Strategies of Vehicle SCR Urea Dosing System

Selective Catalyst Reduction（SCR）Urea Dosing System（UDS）directly affects the system accuracy and the dynamic response performance of a vehicle.However,the UDS dynamic response is hard to keep up with the changes of the engine＇s operating conditions.That will lead to low NO_χconversion efficiency or NH_3 slip.In order to optimize the injection accuracy and the response speed of the UDS in dynamic conditions,an advanced control strategy based on an air-assisted volumetric UDS is presented.It covers the methods of flow compensation and switching working conditions.The strategy is authenticated on an UDS and tested in different dynamic conditions.The result shows that the control strategy discussed results in higher dynamic accuracy and faster dynamic response speed of UDS.The inject deviation range is improved from being between-8%and 10%to-4%and 2%and became more stable than before,and the dynamic response time was shortened from 200 ms to 150 ms.The ETC cycle result shows that after using the new strategy the NH_3 emission is reduced by 60%,and the NO_χemission remains almost unchanged.The trade-off between NO_χconversion efficiency and NH_3 slip is mitigated.The studied flow compensation and switching working conditions can improve the dynamic performance of the UDS significantly and make the UDS dynamic response keep up with the changes of the engine＇s operating conditions quickly.

Application of FTA Method to Reliability Analysis of Vacuum Resin Shot Dosing Equipment

Faults of vacuum resin shot dosing equipment are studied systematically and the fault tree of the system is constructed by using the fault tree analysis(FTA) method. Then the qualitative and quantitative analysis of the tree is carried out, respectively, and according to the results of the analysis, the measures to improve the system are worked out and implemented. As a result, the reliability of the equipment is enhanced greatly.

Enoxaparin dosing errors in the emergency department

BACKGROUND:The study aimed to determine the frequency of enoxaparin dosing errors for patients who had a measured emergency department(ED)weight compared to those who did not have a measured ED weight,and to determine if demographic variables(e.g.,weight,height,age,Englishspeaking,race)impact the likelihood of receiving an inappropriate dose.METHODS:This is a retrospective,electronic chart review of patients who received a dose of enoxaparin in the ED between January 1,2008 and July 1,2013.We identified all patients>18 years who received a dose of enoxaparin while in the ED,were admitted,and had at least one inpatient weight within the first four days of hospitalization.Patients were excluded if they received enoxaparin for prophylaxis or a dose of more than 1.25mg/kg.RESULTS:A total of 1,944 patients were included.Patients were more likely to experience an error if they did not have a measured ED weight.Over-doses of>10mg were more likely to occur in patients without a measured ED weight.Patients with no documented ED weight or with a staffestimated ED weight were more likely to experience a dosing error than those with a patient-stated weight.Patients were more likely to experience an error if their first inpatient weight was more than 96kg,they were more than 175-cm tall,or were English speaking.CONCLUSION:Dosing errors are more likely to occur when patients are not weighed in the ED.Modifications to current workflows to incorporate weighing those patients who receive weightdosed medications may be warranted.

婴儿选择: Yo-Yoing 糖尿病控制或十分之一单位胰岛素 dosing？

While the incidence of toddlers’ diabetes is soaring,their mainstay insulins were withdrawn,namely the weak 10% or 20% insulin mixtures (WIM),which were injected only once or twice daily.Consequently,toddlers are coerced to use an insulin pump,multi-dose insulin regime (MuDIR),mix or dilute insulins.This paper highlights the difficulties and proposes a simple solution.While an insulin pump is the best available option,it is not readily available for everyone.Mixing insulins is not sufficiently precise in small doses.Although diluting insulin would allow precise dosing and reduce the dose variability secondary to dribbling after injections,it,like insulin mixing,deprives children from using the pen and related child-friendly accessories.In MuDIR,we inject 4-5 small doses of insulin instead of 1-2 daily larger doses of WIM.Thus,on using a half unit (unit) insulin pen,a dose of 0.5,1,1.5 and 2 units are adjusted in steps of 100%,50%,33% or 25%;unlike the advisable 5%-20%.This does not easily match the tiny erratic meals of grazing toddlers.Maternal anxiety peaks on watching yo-yoing glycemia.Carers have to accept either persistently high sugar or wild fluctuation.The risks of such poor glycemic pattern are increasingly recognized.Using insulin U20 in a unit disposable pen allows deci-unit dosing,with 5%-20% dose-tuning,greater accuracy on delivering small doses and reduction of dose variability from dribbling.Deci-unit dosing may help avoid wide glycemic swings and provide the affordable alternative to insulin pumps for toddlers.Deci-unit pen materializes the Human Rights of Children,a safer and effective treatment.

The PLC Control System of Vacuum Resin Shot Dosing Equipment

The principle and working process of Vacuum Resin Shot Dosing Equipment(VRSDE) are analyzed and the characteristics of IP1612-220PLC (Programmable Logical Controller) areintroduced briefly at first. Then the authors discuss the flow of program, the assignment of PLCI/O ports, the wiring diagram, and the ladder logic program of the PLC control system of VRSDE indetail. Some application issues of the system are accounted for in addition. Finally, according tothe information acquired from users, the authors draw the conclusion: this system owns a highreliability and a-vailability and greatly improves the automatic degree of VRDE.

Anti-Malarial Targeting and Dosing Practices among Health Workers at Lower Level Health Facilities in Uganda

Background: Health worker shortages remain a significant challenge to delivery of health care services globally. Moving tasks, where appropriate, to less specialized health workers is recommended by the World Health Organization as a strategy to address this challenge. However, this concept is feared to raise specific quality concerns. This research aimed at assessing the performance of health workers to correctly prescribe (target) appropriate antimalarial treatment. Methods: We conducted a cross sectional study at three public health centre IVs in Uganda, with varying malaria transmission intensities (Kihihi-low, Kasambya-medium and Nagongera-high). We categorized prescribers into two groups: specialized prescribers (doctors and clinical officers) and less specialized prescribers (nurses and midwives). At each site, 100 records of patients seen between September and November 2011 and prescribed an antimalarial were retrieved for each group of prescribers. Correctness of the antimalarial drug prescribed and dose given were assessed for each group and compared to the 2005 Uganda national malaria treatment guidelines which recommend Artemether Lumefantrine (AL) for treatment of uncomplicated malaria and Quinine for complicated malaria. Results: Findings of the study showed that specialized health workers were more likely to target correctly as compared to the less specialized health workers [OR = 1.49 (1.00 - 2.22), p = 0.046]. Appropriateness of dosing was higher among specialized prescribers compared to less specialized prescribers however this was not significant [OR = 1.58 (0.77 - 3.25), p = 0.206]. Age of the participants, history of fever, diagnosis of malaria and prescription experience were not associated with correct targeting. Conclusion: This study shows that task shifting at the targeting level is not suitable;however, there is inadequate evidence to show that this also applies to anti-malarial dosing. Task shifting for the treatment of Malaria in Uganda should be investigated further using larger studies if it is to be considered as an option for solving the health worker shortages especially in regions with few specialized health workers but high malaria burden.

Novel Approach to Chemotherapy and Administration Selection with Metronomic/Fractionated Dosing

Metronomic dosing of chemotherapy was introduced in the early 2000s and has since gained recognition as a potential game changer in the manner of which chemotherapy can be administered. There are several known candidates for metronomic dosing of chemotherapy with the potential for many more to be elucidated in the future. Minimized overall side effects, longer durations of treatment, potential minimization of multidrug resistance (MDR) mutations, potential less refractory responses, and the potential to safely use more than one chemotherapy treatments also make metronomic dosing of chemotherapy attractive. Metronomic dosing reduces common side effects and has the potential to reduce neutropenia, lymphocytopenia, and cognitive changes associated with maximum tolerated dosages (MTD). Methods of enhancing chemotherapy including fasting and administration of insulin are also discussed. Metronomic dosing combined with a patient’s molecular profile derived from biomarkers is particularly exciting. It holds significant potential with regard to administrating the most relevant chemotherapies and offers maximal beneficial results.

A Fuzzy Mathematics Based Fault Auto-diagnosis System for Vacuum Resin Shot Dosing Equipment

On the basis of the analysis of faults and their causes of vacuum resin shot dosing equipment, the fuzzy model of fault diagnosis for the equipment is constructed, and the fuzzy relationship matrix, the symptom fuzzy vector, the fuzzy compound arithmetic operator, and the diagnosis principle of the model are determined. Then the fault auto-diagnosis system for the equipment is designed , and the functions for real-time monitoring its operation condition and for fault auto diagosis are realized. Finally, the experiments of fault auto-diagnosis are conducted in practical production and the veracity of the system is verified.

Comparison of split-dosing vs non-split(morning) dosing regimen for assessment of quality of bowel preparation for colonoscopy

AIM: To compare(using the Ottawa Bowel Preparation Scale) the efficacy of split-dose vs morning administration of polyethylene glycol solution for colon cleansing in patients undergoing colonoscopy, and to assess the optimal preparation-to-colonoscopy interval.METHODS: Single-centre, prospective, randomized, investigator-blind stud in an academic tertiarycare centre. Two hundred patients requiring elective colonoscopy were assigned to receive one of the two preparation regimens(split vs morning) prior to colonoscopy. Main outcome measurements were bowel preparation quality and patient tolerability.RESULTS: Split-dose regimen resulted in better bowel preparation compared to morning regimen [Ottawascore mean 5.52(SD 1.23) vs 6.02(1.34); P = 0.017]. On subgroup analysis, for afternoon procedures, both the preparations were equally effective(P = 0.756). There was no difference in tolerability and compliance between the two regimens.CONCLUSION: Overall, previous evening- same morning split-dosing regimen results in better bowel cleansing for colonoscopy compared to morning preparation. For afternoon procedures, both schedules are equally effective; morning preparation may be more convenient to the patient.

Treatment Outcome of Pharmacokinetics-Based Dosing of Docetaxel and Fluorouracil in Advanced Head and Neck Cancer Patients

Introduction: Docetaxel, Cisplatin and 5-Fluorouracil (DPF) became the standard induction chemotherapy in advanced Head and Neck Cancer (HNC) but associated with high toxicity rate. Several studies reported higher response rates with better tolerability when chemotherapy dose is calculated based on Pharmacokinetics (PK) versus conventional Body Surface Area (BSA). Patients and Methods: Thirty nine patients with stage III and IV HNC who received induction DPF were included in the study. Dose of cycle 1 was BSA-based then Docetaxel and 5-FU doses were PK-adjusted starting from cycle 2 whereas Cisplatin dose was BSA-based throughout the study. Results: After median follow up period of 14 months the median overall survival (OS) and progression free survival (PFS) were 15.1 and 10.6 months respectively. Twenty nine patients were available for response assessment. Seven patients (24.1%) achieved complete response while partial response encountered in 19 patients (65.5%) with and Overall response rate of 89.6%. Both treatment related side effects and mortality significantly decreased after the application of PK dose adjustments (p-value 0.007 and 0.01 respectively). Conclusion: PK-guided dose adjustments of 5-FU and Docetaxel in DPF regimen can significantly decrease the treatment related side effects and mortality without compromising the tumor response rate. A randomized clinical trial is needed to compare the PK-guided dose adjustment with the standard BSA based protocol.

Immunogenicity and Safety of Homologous Booster Doses of CoronaVac COVID-19 Vaccine in Elderly Individuals Aged 60 Years and Older:A Dosing Interval Study—Yunnan Province,China,2021–2022

Summary What is already known about this topic?Neutralization levels induced by inactivated vaccines rapidly wane after primary immunization,and a homologous booster can recall specific immune memory,resulting in a remarkable increase in antibody concentration.The optimal interval between primary and booster doses has yet to be determined.

Effects of silver nanoparticles with different dosing regimens and exposure media on artificial ecosystem

Due to the wide use of silver nanoparticles(AgNPs) in various fields, it is crucial to explore the potential negative impacts on the aquatic environment of AgNPs entering into the environment in different ways. In this study, comparative experiments were conducted to investigate the toxicological impacts of polyvinylpyrrolidone-coated silver nanoparticles(PVP-AgNPs) with two kinds of dosing regimens, continuous and one-time pulsed dosing, in different exposure media(deionized water and XiangJiang River water). There were a number of quite different experimental results(including 100% mortality of zebrafish,decline in the activity of enzymes, and lowest number and length of adventitious roots) in the one-time pulsed dosing regimen at high PVP-AgNP concentration exposure(HOE)compared to the three other treatments. Meanwhile, we determined that the concentration of leached silver ions from PVP-AgNPs was too low to play a role in zebrafish death. Those results showed that HOE led to a range of dramatic ecosystem impacts which were more destructive than those of other treatments. Moreover, compared with the continuous dosing regimen, despite the fact that higher toxicity was observed for HOE, there was little difference in the removal of total silver from the aquatic environment for the different dosing regimens. No obvious differences in ecological impacts were observed between different water columns under low concentration exposure. Overall, this work highlighted the fact that the toxicity of Ag NPs was impacted by different dosing regimens in different exposure media, which may be helpful for assessments of ecological impacts on aquatic environments.

Town-scale microbial sewer community and H2S emissions response to common chemical and biological dosing treatments

Controlling hydrogen sulfide(H2S)odors and emissions using a single,effective treatment across a town-scale sewer network is a challenge faced by many water utilities.Implementation of a sewer diversion provided the opportunity to compare the effectiveness of magnesium hydroxide(Mg(OH)2)and two biological dosing compounds(Bioproducts A and B),with different modes of action(MOA),in a field-test across a large sewer network.Mg(OH)2 increases sewer p H allowing suppression of H2S release into the sewer environment while Bioproduct A acts to disrupt microbial communication through quorum sensing(QS),reducing biofilm integrity.Bioproduct B reduces H2S odors by scouring the sewer of fats,oils and grease(FOGs),which provide adhesion points for the microbial biofilm.Results revealed that only Mg(OH)2 altered the microbial community structure and reduced H2S emissions in a live sewer system,whilst Bioproducts A and B did not reduce H2S emissions or have an observable effect on the composition of the microbial community at the dosed site.Study results recommend in situ testing of dosing treatments before implementation across an operational system.

Decontamination of alachlor herbicide wastewater by a continuous dosing mode ultrasound/Fe^(2+)/H_2O_2 process

We used a ultrasound/Fe2＋/H2O2 process in continuous dosing mode to degrade the alachlor. Experimental results indicated that lower pH levels enhanced the degradation and mineralization of alachlor. The maximum alachlor degradation （initial alachlor concentration of 50 mg/L） was as high as 100% at pH 3 with ultrasound of 100 Watts, 20 mg/L of Fe2＋, 2 mg/min of H2O2 and 20℃ within 60 min reaction combined with 46.8% total organic carbon removal. Higher reaction temperatures inhibited the degradation of alachlor. Adequate dosages of Fe2＋ and H2O2 in ultrasound/Fe2＋/H2O2 process not only enhance the degradation efficiency of alachlor but also save the operational cost than the sole ultrasound or Fenton process. A continuous dosing mode ultrasound/Fe2＋/H2O2 process was proven as an effective method to degrade the alachlor.

Accurate models and nutritional strategies for specific oxidative stress factors: Does the dose matter in swine production?

Oxidative stress has been associated with a number of physiological problems in swine,including reduced production efficiency.Recently,although there has been increased research into regulatory mechanisms and antioxidant strategies in relation to oxidative stress-induced pig production,it remains so far largely unsuccessful to develop accurate models and nutritional strategies for specific oxidative stress factors.Here,we discuss the dose and dose intensity of the causes of oxidative stress involving physiological,environmental and dietary factors,recent research models and the antioxidant strategies to provide theoretical guidance for future oxidative stress research in swine.

Association of Thyroid Nodules with Various Elements in Urine and Blood Serum: A Case-Control Study

Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid nodules but also the severity of disease in humans[1].The environment is awash with elements,and all mineral elements,including heavy metals and trace elements,are considered potentially toxic.A significantly higher incidence of thyroid cancer has been reported in populations exposed to low doses of metallic elements in volcanic areas over a long period[2].As research on thyroid disorders continues,it is becoming clear that abnormalities in trace elements in the body can affect the development of thyroid-related disorders.

Total ionizing dose effect modeling method for CMOS digital-integrated circuit

Simulating the total ionizing dose(TID)of an electrical system using transistor-level models can be difficult and expensive,particularly for digital-integrated circuits(ICs).In this study,a method for modeling TID effects in complementary metaloxide semiconductor(CMOS)digital ICs based on the input/output buffer information specification(IBIS)was proposed.The digital IC was first divided into three parts based on its internal structure:the input buffer,output buffer,and functional area.Each of these three parts was separately modeled.Using the IBIS model,the transistor V-I characteristic curves of the buffers were processed,and the physical parameters were extracted and modeled using VHDL-AMS.In the functional area,logic functions were modeled in VHDL according to the data sheet.A golden digital IC model was developed by combining the input buffer,output buffer,and functional area models.Furthermore,the golden ratio was reconstructed based on TID experimental data,enabling the assessment of TID effects on the threshold voltage,carrier mobility,and time series of the digital IC.TID experiments were conducted using a CMOS non-inverting multiplexer,NC7SZ157,and the results were compared with the simulation results,which showed that the relative errors were less than 2%at each dose point.This confirms the practicality and accuracy of the proposed modeling method.The TID effect model for digital ICs developed using this modeling technique includes both the logical function of the IC and changes in electrical properties and functional degradation impacted by TID,which has potential applications in the design of radiation-hardening tolerance in digital ICs.