Risk for Mortality in High versus Low Antiparkinsonian Therapy Dose During the First Year of Parkinson's Disease: A Real-World Study.

INTRODUCTION: Early, simple predictors for long-term survival in Parkinson's disease (PD) may help identify patients at elevated risk and are crucial for more personalized treatment. METHODS: This large, retrospective study examined whether higher levodopa equivalent daily dose (LEDD) a year after diagnosis predicts long-term survival. RESULTS: Mortality risk was increased among 292 patients receiving ≥ 600 mg LEDD versus 2233 patients receiving < 600 mg LEDD (hazard ratio 1.5; 95% confidence interval 1.3-1.7), particularly among patients aged < 75 years (1.8; 1.4-2.4). CONCLUSION: In PD, higher LEDD can be an early risk marker of increased mortality, probably because it reflects more severe disease.

Discrepancies among equations to estimate the glomerular filtration rate for drug dosing decision making in aged patients: a cross sectional study.

BACKGROUND: Patients often require adjustments to drug doses due to impaired renal function. Glomerular filtration rate (GFR) estimation using various equations can result in discrepancies, potentially leading to different dose adjustment recommendations. AIM: To determine the clinical significance of discrepancies observed between different equations used to estimate GFR for drug dose adjustments in a real-world group of patients over 65 years in primary care. METHOD: The Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Berlin Initiative Study 1 equations were applied to estimate GFR in a group of patients over 65 years old attending a primary care center. Results were compared using Bland-Altman plots, and limits of agreement (LoA) and overall bias were calculated. Regression analyses were conducted to identify the null difference GFR and the slope of differences for each pairwise comparison. RESULTS: A total of 1886 patients were analyzed. Differences between patient-adjusted and body surface area (BSA)-normalized versions of the equations were not clinically relevant for dose adjustments, with LoAs below 20 mL/min. However, discrepancies among the original versions of several equations presented LoAs over 30 mL/min. Greater differences were found between CG and MDRD or CKD-EPI equations. CONCLUSION: Clinically relevant differences in GFR estimation were observed among different equations, potentially impacting drug dose adjustments. However, discrepancies were not considered significant when comparing patient-adjusted and BSA-normalized versions of the equations, particularly for patients with BSA close to the average.

Application status and prospect of Indocyanine green in radical prostatectomy / 国际外科学杂志

Prostate cancer is a common malignant tumor in male genitourinary system, and radical prostatectomy is one of the important methods to treat prostate cancer. Indocyanine green is a non-radioactive, water-soluble compound, which can help identify anatomical structures and visualize blood vessels through near-infrared fluorescence. The role and injection techniques of Indocyanine green in radical prostatectomy in sentinel lymph node identification, pelvic lymph node dissection and neurovascular bundle preservation are reviewed, so as to provide a reference for improving the surgical effect, reducing the difficulty of surgery, and prolonging the survival period of patients, and evaluate the potential research field of this technology in the future.

Modelos farmacocinéticos poblacionales de sirólimus en pacientes trasplantados renales: Revisión sistemática / Population pharmacokinetics models of sirolimus in renal transplant patients: A systematic review

Objetivo: Sirólimus es un fármaco utilizado en los esquemas terapéuticos inmunosupresores en pacientes con trasplante renal. La elevada variabilidad farmacocinética de sirólimus hace que la monitorización farmacocinética y la individualización posológica de la terapia inmunosupresorasea un proceso crucial para conseguir mejores resultados de eficacia. Ladisponibilidad de un modelo farmacocinético poblacional permite realizar un mejor ajuste farmacocinético de las concentraciones plasmáticasde sirólimus y así conseguir un mayor beneficio clínico.Método: Se realizó un análisis sistemático de la literatura disponible enlas bases de datos Medline, Embase y Scopus para identificar y posteriormente analizar los modelos farmacocinéticos poblacionales de sirólimusadministrado por vía oral en pacientes adultos con trasplante renal. Seutilizaron como descriptores MeSH: kidney transplantation, pharmacokinetic y sirolimus. De cada artículo seleccionado se evaluó: la poblacióna estudio, el esquema de tratamiento inmunosupresor, los tiempos demuestreo de las extracciones de sangre, las covariables analizadas, eltipo de modelo farmacocinético, el programa informático utilizado, losparámetros farmacocinéticos estimados, la variabilidad interindividual de los parámetros farmacocinéticos, la variabilidad residual y las ecuacionesmatemáticas del modelo farmacocinético.Resultados: Se obtuvieron un total de 548 resultados, excluyendo175 registros tras identificarse en más de una base de datos. Finalmentese seleccionaron siete artículos que cumplían los criterios de inclusión.La mayoría de los modelos farmacocinéticos encontrados siguen unmodelo bicompartimental. Covariables como edad, peso, función hepática, exposición y dosis de ciclosporina, dosis de sirólimus, polimorfismosgenéticos del CYP3A5, creatinina sérica y tratamiento concomitante explican la variabilidad interindividual de sirólimus. (AU)

Objective: Sirolimus is used in the immunosuppressive therapeutictreatment of kidney transplant patients. The high pharmacokinetic variability of sirolimus makes pharmacokinetic monitoring and dosage individualization of immunosuppressive therapy a key process to achieve betterefficacy results. The availability of a population pharmacokinetic modelcan be used to provide better pharmacokinetic adjustment of plasma concentrations of sirolimus and thus achieve greater clinical benefit.Method: We conducted a systematic review of the literature availablein the Medline, Embase, and Scopus databases to identify and subsequently analyze population pharmacokinetic models of orally administered sirolimus in adult patients after kidney transplant. The descriptorsused MeSH were kidney transplantation, pharmacokinetics, and sirolimus.The following variables from the selected studies were assessed: studypopulation, immunosuppressive treatment, blood sampling times, covariates analyzed, type of pharmacokinetic model, computer software used,estimated pharmacokinetic parameters, interindividual variability of pharmacokinetic parameters, residual variability and mathematical equationsof the pharmacokinetic model. Results: A total of 548 results were obtained, excluding 175 records thatwere identified in more than one database. Finally, seven articles that met theinclusion criteria were selected. Most of the pharmacokinetic models foundfit a two-compartment model. The interindividual variability of sirolimus wasexplained by covariates such as age, weight, liver function, cyclosporineexposure and dose, sirolimus doses, CYP3A5 genetic polymorphisms, serumcreatinine, and concomitant treatment. (AU)

Software de contenido farmacocinético para la monitorización terapéutica de fármacos: Protocolo de revisión exploratoria / Pharmacokinetic software for therapeutic drug monitoring: A scoping review protoco

Objetivo: Los nomogramas, ecuaciones y software de contenido farmacocinético se consideran las principales herramientas disponibles para la monitorización farmacocinética clínica. Debido a su gran aplicabilidad en numerososgrupos de fármacos, el empleo de software se encuentra ampliamente extendido en la práctica clínica. Generalmente, el objetivo principal de los estudiosque incluyen el uso de estos software no es la descripción de los mismos, porlo que la información disponible es escasa y, además, no se dispone de unarevisión que aúne toda la información disponible referente a este tipo de softwareEl objetivo de este estudio será sintetizar la evidencia disponible sobre losdistintos software de aplicación en la monitorización farmacocinética parafacilitar a los usuarios su identificación, evaluación y selección.Método: Se realizará una revisión exploratoria de la literatura cuyo protocolo se describe en este artículo, de acuerdo con las recomendacionesPRISMA para la elaboración de revisiones exploratorias y publicaciónde protocolos. Se realizará una búsqueda bibliográfica en las bases dedatos Medline, Embase, OpenAire y Bielefeld Academic Search Engine.Se incluirán en el estudio aquellos software detectados de los que se disponga de la siguiente información: nombre del software, desarrollador/comercializador, tipo de análisis farmacocinético y fármacos incluidos.Resultados: En este estudio se espera realizar una síntesis de lascaracterísticas más relevantes en la práctica clínica de los software decontenido farmacocinético disponibles en el mercado. Se realizará una síntesis narrativa crítica de las fuentes de información utilizadas. Además,se llevará a cabo, si es posible, una comparación de los mismos parafacilitar la evaluación y selección por parte de los usuarios. (AU)

Objective: Nomograms, equations and pharmacokinetic software areconsidered the main tools available for therapeutic drug monitoring. Dueto its great applicability to various groups of drugs, the use of software iswidely extended in clinical practice. The main goals of the studies usingthis type of software do not normally include the description of its features,therefore, the information about its characteristic is scarce. Moreover, noreview of the literature has been published that brings together all theinformation available about these software. The present study aimed tosynthesize the available evidence regarding software applied to therapeutic drug monitoring to facilitate its identification, evaluation and selectionby users.Method: This article describe a scoping review protocol, developedfollowing the PRISMA-P and PRISMA-ScR guidelines. An electronic literature search was performed in MEDLINE, EMBASE, OpenAire and BASE(Bielefeld Academic Search Engine) databases. Only those software forwhich the following information was available were included: name of thesoftware, developer/marketer, type of pharmacokinetic analysis allowed,and drugs included in the analysis.Results: In this study we will synthesized the most relevant characteristics for the clinical practice of the pharmacokinetic software available.A critical appraisal of the sources if information will be included. Also,if it is possible, a comparison of the available tools will be carried out in order to facilitate the evaluation and selection of pharmacokineticsoftware. (AU)

Preformulation of a liquid dosage formulation of captopril for pediatric use: drug-excipient compatibility and stability studies

Currently, medications used in children are typically modified from pharmaceutical dosage forms designed for adults. Captopril is widely adapted to liquid formulations for use in hospitals. Its stability in the aqueous medium is reduced since it undergoes oxidation producing captopril disulfide (its main metabolite). The aim of this formulation study was to suggest favorable conditions for the development of a stable captopril formulation. The compatibility between the drug and excipients was evaluated by differential scanning calorimetry analysis (DSC). For studies in solution, different formulations were prepared according to a factorial design varying EDTA concentration, water purity and pH. The resultant formulations were stored at 60°C and analyzed over a twelve-day period using HPLC. The DSC curves obtained suggested, although not conclusive to elucidation, interactions of captopril with citric acid and sucralose. The stability study of these solutions revealed that the variables significantly influenced captopril content, which degraded at zero order kinetics and rates differing by a factor of up to 7 times, where pH proved the most influential factor. Interactions between variables were observed. Therefore, development of a stable captopril formulation is feasible provided EDTA and a buffering agent is used at suitable concentrations (0.08% and pH 3.85).

Comparison of effect and safety of different dosages of alteplase in the treatment of elderly patients with acute cerebral infarction / 中国基层医药

Objective To compare the effect of different dosages of alteplase in the treatment of elderly patients with acute cerebral infarction,as well to evaluate the safety.Methods From January 2016 to June 2017,82 patients with acute cerebral infarction in the Hospital of Changping District were chosen in this study.The patients were randomly divided into 2 groups according to the digital table:41 patients in study group (0.6 mg/kg alteplase) and 41 patients in control group (0.9mg/kg alteplase).The effective rate and incidence of hemorrhage were compared between the two groups.Results The effective rate of the study group was 95.13％ (39/41),which of the control group was 100.00％ (41/41),the difference was not statistically significant (Z =4.982,P ＞ 0.05).The incidence rate of hemorrhage in the study group was 7.32％ (3/41),which in the control group was 24.39％ (10/41),the difference was statistically significant (x2 =6.248,P ＜ 0.05).Conclusion The effect of different dosages of alteplase demonstrates no significant difference in the treatment of elderly patients,and the safety of low dose is more reliable.

Volume de dipirona para via oral versus tipo de conta-gotas, temperatura e ângulos de gotejamento / The volume of dipyrone for oral use versus dropper type, temperature and drip angles / Volumen de dipirona (metamizol) para vía oral versus tipo cuentagotas, temperatura y ángulo de goteo

Objetivo: determinar as diferenças entre volume e número de gotas de dipirona (via oral) por mililitro controlando algumas variáveis. Método: trata-se de um estudo experimental, com abordagem quantitativa, que foi realizado a partir de dados obtidos em experimentos realizados em laboratório, com dois tipos de conta-gotas, temperaturas de 5o e 35o Celsius, além da temperatura ambiente (30o Celsius), de laboratório e os ângulos de 90°, 60° e 45° utilizados para dispensar dipirona. Resultados: com base nos dados coletados, considerou-se que o ângulo de maior confiança para atingir o volume de 20 gotas por cada ml é o ângulo de 90o com o conta-gotas de vidro; em relação à temperatura, a maior confiança no volume de gotas desejado foi alcançada no intervalo de 5o e 30oCelsius. Conclusão: os resultados indicam a necessidade de seguir rigorosamente as orientações do fabricante para que se possa atingir a dose certa na administração de medicamento.

Objective: to determine the differences between volume and number of drops of dipyrone (oral) per milliliter, while controlling some variables. Method: this study applied quantitative analysis to data obtained in laboratory experiments with two types of droppers, temperatures of 5o and 35o Celsius, in addition to ambient temperature (30o Celsius), and the 90°, 60° and 45° angles used to dispense dipyrone. Results: based on the data collected, it was considered that, with the glass dropper, the angle of greatest confidence to achieve the volume of 20 drops per ml is 90o. In relation to temperature, the highest confidence in the desired volume of drops was achieved in the 5o to 30o Celsius interval. Conclusion: the results indicate the need to follow manufacturer's guidelines strictly, so as to achieve the correct dose for drug administration.

Objetivo: determinar las diferencias entre volumen y número de gotas de dipirona (vía oral) por mililitro controlando algunas variables. Método: se trata de un estudio experimental, con enfoque cuantitativo realizado con datos obtenidos en experimentos realizados en laboratorio, con dos tipos de cuentagotas, temperaturas de 5o y 35o Celsius, temperatura ambiente (30° Celsius) de laboratorio y los ángulos de 90°, 60° y 45° para gotear dipirona. Resultados: con base en los datos recolectados, se consideró que el ángulo de mayor confianza para alcanzar el volumen de 20 gotas por cada ml es el ángulo de 90o con el cuentagotas de vidrio. Respecto a la temperatura, la mayor confianza en el volumen de gotas deseado fue alcanzada en el intervalo de 5o y 30o Celsius. Conclusión: los resultados indican la necesidad de seguir rigurosamente las orientaciones del fabricante para alcanzar la dosis correcta en la administración de medicamentos.

Efficacy and safety of tacrolimus for patients with refractory IgA nephropathy / 第二军医大学学报

Objective To evaluate the efficacy and safety of tacrolimus (TAC) therapy in patients with refractory IgA nephropathy. Methods Nine IgA nephropathy patients were included in this study were treated from Jun. 2008 tc Sep. 2013 in Changzheng Hospital of Second Military Medical University. All patients received TAC therapy after the renin-angiotensin system (RAS) blockade therapy and steroid therapy failed. The main outcome was complete or partial remission. Secondary outcomes included the time required to remission, the frequency of recurrence, TAC dosage and adverse events. Results The initial dosage of TAC" was (1. 89 + 0. 33) mg/d. After treatment with TAC for 6 months, 6 patients achieved complete remission, 2 partial remission and 1 treatment resistance, and most of the remission patients achieved remission during the first 2 months of TAC therapy. The urine protein level of enrolled patients was significantly decreased ([3. 05 ± 1. 35] g/24 h vs [0. 85±1. 54] g/24 h. P<0. 05) and the serum album level of all patients was significantly improved ([27. 00±8. 37] g/L vs [37. 33±8. 08] g/L. P<0. 05). One patient receiving TAC" therapy presented worsened hypertension, and no other adverse event was observed in this study. Three of 8 proteinuria remission patients had relapses find achieved remission by adjusting the dosages of steroids and tacrolimus. Conclusion TAC ear improve proteinuria in patients with refractory IgA nephropathy, with less adverse reactions.

Serum levels of vancomycin: is there a prediction using doses in mg/kg/day or m2/day for neonates?

Abstract Coagulase-negative Staphylococcus has been identified as the main nosocomial agent of neonatal late-onset sepsis. However, based on the pharmacokinetics and erratic distribution of vancomycin, recommended empirical dose is not ideal, due to the inappropriate serum levels that have been measured in neonates. The aim of this study was to evaluate serum levels of vancomycin used in newborns and compare the prediction of adequate serum levels based on doses calculated according to mg/kg/day and m2/day. This is an observational reprospective cohort at a referral neonatal unit, from 2011 to 2013. Newborns treated with vancomycin for the first episode of late-onset sepsis were included. Total dose in mg/kg/day, dose/m2/day, age, weight, body surface and gestational age were identified as independent variables. For predictive analysis of adequate serum levels, multiple linear regressions were performed. The Receiver Operating Characteristic curve for proper serum vancomycin levels was also obtained. A total of 98 patients received 169 serum dosages of the drug, 41 (24.3%) of the doses had serum levels that were defined as appropriate. Doses prescribed in mg/kg/day and dose/m2/day predicted serum levels in only 9% and 4% of cases, respectively. Statistical significance was observed with higher doses when the serum levels were considered as appropriate (p < 0.001). A dose of 27 mg/kg/day had a sensitivity of 82.9% to achieve correct serum levels of vancomycin. Although vancomycin has erratic serum levels and empirical doses cannot properly predict the target levels, highest doses in mg/kg/day were associated with adequate serum levels.

Prospective validation of a novel dosing scheme for intravenous busulfan in adult patients undergoing hematopoietic stem cell transplantation

The objective of this study was to externally validate a new dosing scheme for busulfan. Thirty-seven adult patients who received busulfan as conditioning therapy for hematopoietic stem cell transplantation (HCT) participated in this prospective study. Patients were randomized to receive intravenous busulfan, either as the conventional dosage (3.2 mg/kg daily) or according to the new dosing scheme based on their actual body weight (ABW) (23×ABW(0.5) mg daily) targeting an area under the concentration-time curve (AUC) of 5924 µM·min. Pharmacokinetic profiles were collected using a limited sampling strategy by randomly selecting 2 time points at 3.5, 5, 6, 7 or 22 hours after starting busulfan administration. Using an established population pharmacokinetic model with NONMEM software, busulfan concentrations at the available blood sampling times were predicted from dosage history and demographic data. The predicted and measured concentrations were compared by a visual predictive check (VPC). Maximum a posteriori Bayesian estimators were estimated to calculate the predicted AUC (AUC(PRED)). The accuracy and precision of the AUC(PRED) values were assessed by calculating the mean prediction error (MPE) and root mean squared prediction error (RMSE), and compared with the target AUC of 5924 µM·min. VPC showed that most data fell within the 95% prediction interval. MPE and RMSE of AUCPRED were -5.8% and 20.6%, respectively, in the conventional dosing group and −2.1% and 14.0%, respectively, in the new dosing scheme group. These fi ndings demonstrated the validity of a new dosing scheme for daily intravenous busulfan used as conditioning therapy for HCT.

A case control study on risk factors for dose wearing off in Parkinson's disease patients / 中华老年心脑血管病杂志

Objective To study the risk factors for dose wearing off (WO)in PD patients .Methods One hundred and thirty-three PD patients were recruited in this study according to the UKPDBB criteria .Their dose WO was diagnosed according to the Wo questionnaire 9 (WOQ-9) .The pa-tients were divided into WOQ-9 (+ ) group (n=111) and WOQ-9 (-) group (n=22) .The pa-tients in WOQ-9 (+) group were further divided int WO (+ ) group (n=59) and WO (-) group (n=52) .The difference in their clinical and therapeutic parameters was compared .Results The dose WO was observed in 83 .5% of the 133 PD patients ,53 .2% of which accorded with the dose WO clinical definition .T he disease onset age ,disease course ,maximal levodopa daily dose and ac-cumulated levodopa dose differed greatly in WOQ-9 (+ ) group and WOQ-9 (-) group (P<005) . The disease course ,H-Y stage ,UPDRS score ,tetany score ,maximal levodopa daily dose ,levodopa dose per body weight and accumulated drug use time differed greatly in WOQ-9 (+ ) group and WOQ-9 (-) group (P< 0 .01) .The major risk of dose WO was the levodopa dose per body weight (OR=1.364 ,P<0 .05) .Conclusion Dose WO is related with the progress of disease and the use of levodopa .Levodopa dose per body weight is an independent risk factor for dose WO .

Effect of esomeprazole with different dosage and usage on intragastric pH of healthy volunteers / 中华消化杂志

Objective To evaluate the effect of csomeprazole with different dosage and usage regimes on intragastric pH of healthy volunteers. Methods It was a randomized, open-label, three-way crossover study. Fifteen healthy volunteers received esomeprazole with 3 different dosages (20 mg or 40 mg once daily or 20 mg twice daily) with 5 days each. Twenty-four continuous ambulatory intragastric pH was recorded at day 5 of each regime. Results The mean time of intragastric pH above 4 was higher in regime of 20 mg twice daily [(21.16 ±2.45) hours ] than that in regimes of 20 mg once daily [(18. 70±4.19) hours] and 40 mg once daily [(19.27±2.68 ) hours] (P<0.05). The percentages of the sleeping and active period that pH remained above 3,4,5 were significantly higher in regime of 20 mg twice daily(day time:95.0%±7.5% ,92.0%±10.6% ,86.7% ± 14.5% ;night time:93.2%± 13.1% ,87.8%±20.3% ,78.6%±28. 9 % )compared with regimes of 40 mg once daily(day time:87.9%±9.5% ,83.5%±11.7%,75.6%±15.50%, night time:75. 7%±20. 8%,66. 9%±23. 8%,53. 3%±30. 3%) and 20 mg once daily(day time: 85.1 % ± 16.3 %, 81.1 %± 18. 1%, 71.5 % ± 20.3 % ; night time: 72.9 % ± 30.5 %,67.2 % ± 31.9 %, 55.7 % ± 31.8 % ) (P< 0.05 ). Esomeprazole maintained intragastric pH above these pH thresholds for a similar propotion of sleeping and active periods with 40 mg once daily and 20 mg once daily.Conclusions Esomeprazole has strong inhibitory effect on intragastric acid. The regime of 20 mg twice daily is superior to 40 mg once daily and 20 mg once daily in both day and night time acid inhibition.There is no difference between esomeprazole 40 mg once daily and 20 mg once daily.