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1.
J Comput Assist Tomogr ; 44(1): 7-12, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31939875

RESUMO

OBJECTIVE: The aim of the study was to investigate the feasibility of coronary computed tomography (CT) angiography with a low kilovoltage peak scan and a refined scan timing prediction using a small contrast medium (CM) dose. METHODS: In protocol A, 120-kVp scanning and a standard CM dose were used. The scan timing was fixed. In protocol B, 80 kVp and a 60% CM dose were used. The scan timing was determined according to the interval from the CM arrival to the peak time in the ascending aorta. We measured the CT number and recorded the radiation dose. RESULTS: Higher CT numbers were observed in the left circumflex (proximal, P = 0.0235; middle, P = 0.0007; distal, P < 0.0001) in protocol B compared with protocol A. The radiation dose in protocol B was significantly lower than in protocol A (2.2 ± 0.9 vs 4.3 ± 1.7 mSv). CONCLUSIONS: Low-contrast, low-radiation dose, high-image quality coronary CT angiography can be performed with low kilovoltage peak scanning and a refined scan timing prediction.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Meios de Contraste/administração & dosagem , Doença da Artéria Coronariana/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Idoso , Cálculos da Dosagem de Medicamento , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Estudos Retrospectivos
2.
Medicine (Baltimore) ; 99(2): e18651, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914049

RESUMO

RATIONALE: Heart-valve replacement is one of the main surgical methods for various heart-valve diseases. Warfarin is the only oral anticoagulant used for thrombosis prevention after heart-valve replacement. However, warfarin has a narrow therapeutic window, large differences in efficacy between individuals, and can be affected by drugs, food and disease status. PATIENT CONCERNS: We used the Hamberg model to develop an anticoagulation regimen for a 10-month-old Chinese male after mitral-valve replacement. DIAGNOSES: Echocardiography revealed mitral malformation with severe regurgitation, patent foramen ovale, thickening of the left ventricular wall, enlargement of the left atrium, and the overall systolic function of the left ventricle was lower than normal. INTERVENTIONS: First, the patient was treated with Mitral valvuloplasty plus temporary implantation of a pacing wire. Since this was inadequate, he underwent mitral-valve replacement. Then, we used the Hamberg model to develop an anticoagulation regimen. OUTCOMES: After discharge from hospital, the pharmacist provided anticoagulation management for this pediatric patient using an "Online Anticoagulation Clinic" (OAC). Point-of-care testing could be employed by the boy's mother at home to obtain the International Normalized Ratio. His time to response was 89.6% during the 6 months after hospital discharge, and adverse reactions such as bleeding or thrombosis did not occur. LESSONS: This is the first time the Hamberg model has been employed to design anticoagulation therapy for an Asian infant. His anticoagulation therapy may be managed using the OAC.


Assuntos
Anticoagulantes/administração & dosagem , Cálculos da Dosagem de Medicamento , Implante de Prótese de Valva Cardíaca/métodos , Valva Mitral/cirurgia , Tromboembolia/prevenção & controle , Grupo com Ancestrais do Continente Asiático , Humanos , Lactente , Coeficiente Internacional Normatizado , Masculino , Sistemas Automatizados de Assistência Junto ao Leito
5.
Hosp Pract (1995) ; 47(5): 231-240, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31662005

RESUMO

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


Assuntos
Cálculos da Dosagem de Medicamento , Insuficiência Renal/tratamento farmacológico , Adolescente , Adulto , Idoso , Botsuana , Estudos Transversais , Assistência à Saúde/normas , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Medicamentos sob Prescrição/uso terapêutico , Melhoria de Qualidade , Estudos Retrospectivos , Adulto Jovem
6.
Lancet Haematol ; 6(10): e500-e509, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31420317

RESUMO

BACKGROUND: Rivaroxaban has been shown to be efficacious for treatment of venous thromboembolism in adults, and has a reduced risk of bleeding compared with standard anticoagulants. We aimed to develop paediatric rivaroxaban regimens for the treatment of venous thromboembolism in children and adolescents. METHODS: In this phase 2 programme, we did three studies to evaluate rivaroxaban treatment in children younger than 6 months, aged 6 months to 5 years, and aged 6-17 years. Our studies used a multicentre, single-arm design at 54 sites in Australia, Europe, Israel, Japan, and north America. We included children with objectively confirmed venous thromboembolism previously treated with low-molecular weight heparin, fondaparinux, or a vitamin K antagonist for at least 2 months or, in children who had catheter-related venous thromboembolism for at least 6 weeks. We administered rivaroxaban orally in a bodyweight-adjusted 20 mg-equivalent dose, based on physiologically-based pharmacokinetic modelling predictions and EINSTEIN-Jr phase 1 data in young adults, in either a once-daily (tablets; for those aged 6-17 years), twice-daily (in suspension; for those aged 6 months to 11 years), or three times-daily (in suspension; for those younger than 6 months) dosing regimen for 30 days (or 7 days for those younger than 6 months). The primary aim was to define rivaroxaban treatment regimens that match the target adult exposure range. The principal safety outcome was major bleeding and clinically relevant non-major bleeding. Analyses were per-protocol. The predefined efficacy outcomes were symptomatic recurrent venous thromboembolism, asymptomatic deterioration on repeat imaging at the end of the study treatment period. These trials are registered at ClinicalTrials.gov, numbers NCT02564718, NCT02309411, and NCT02234843. FINDINGS: Between Feb 11, 2013, and Dec 20, 2017, we enrolled 93 children (ten children younger than 6 months; 15 children aged 6 months to 1 year; 25 children aged 2-5 years; 32 children aged 6-11 years; and 11 children aged 12-17 years) into our study. 89 (96%) children completed study treatment (30 days of treatment, or 7 days in those younger than 6 months), and 93 (100%) children received at least one dose of study treatment and were evaluable for the primary endpoints. None of the children had a major bleed, and four (4%, 95% CI 1·2-10·6) of these children had a clinically relevant non-major bleed (three children aged 12-17 years with menorrhagia and one child aged 6-11 years with gingival bleeding). We found no symptomatic recurrent venous thromboembolism in any patients (0%, 0·0-3·9). 24 (32%) of 75 patients with repeat imaging had their thrombotic burden resolved, 43 (57%) patients improved, and eight (11%) patients were unchanged. No patient deteriorated. We confirmed therapeutic rivaroxaban exposures with once-daily dosing in children with bodyweights of at least 30 kg and with twice-daily dosing in children with bodyweights of at least 20 kg and less than 30 kg. Children with low bodyweights (<20 kg, particularly <12 kg) showed low exposures so, for future studies, rivaroxaban dosages were revised for these weight categories, to match the target adult exposure range. 61 (66%) of 93 children had adverse events during the study. Pyrexia was the most common adverse event (ten [11%] events), and anaemia and neutropenia or febrile neutropenia were the most frequent grade 3 or worse events (four [4%] events each). No children died or were discontinued from rivaroxaban because of adverse events. INTERPRETATION: Treatment with bodyweight-adjusted rivaroxaban appears to be safe in children. The treatment regimens that we confirmed in children with bodyweights of at least 20 kg and the revised treatment regimens that we predicted in those with bodyweights less than 20 kg will be evaluated in the EINSTEIN-Jr phase 3 trial in children with acute venous thromboembolism. FUNDING: Bayer AG, Janssen Research and Development.


Assuntos
Anticoagulantes/uso terapêutico , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Adolescente , Anemia/etiologia , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacocinética , Peso Corporal , Criança , Pré-Escolar , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Fator Xa/análise , Feminino , Meia-Vida , Hemorragia/etiologia , Humanos , Lactente , Masculino , Neutropenia/etiologia , Tempo de Protrombina , Rivaroxabana/efeitos adversos , Rivaroxabana/farmacocinética , Resultado do Tratamento , Tromboembolia Venosa/patologia
7.
Nursing ; 49(9): 51-54, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31436723

RESUMO

This article reviews the method of measure known as body surface area (BSA) and discusses when and why BSA calculations are used. Techniques for BSA calculation are also described.


Assuntos
Superfície Corporal , Cálculos da Dosagem de Medicamento , Enfermagem , Índice de Massa Corporal , Humanos
8.
Paediatr Drugs ; 21(5): 357-369, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432433

RESUMO

Obesity rates continue to rise in children, and little guidance exists regarding the need for adjustment away from total body weight-based doses for those prescribing drugs to this population of children. A majority of drugs prescribed to children with obesity result in either sub-therapeutic or supra-therapeutic concentrations, placing these children at risk for treatment failure and drug toxicities. In this review, we highlight available obesity-specific pharmacokinetic and dosing information for the most frequently prescribed drugs to children in the inpatient and outpatient clinical settings. We also comment on available dosing recommendations for drugs prescribed to treat common pediatric obesity-related comorbidities. This review highlights that there is no safe or proven 'rule of thumb,' for dosing drugs for children with obesity, and a striking lack of pharmacokinetic data to support the creation of dosing guidelines for children with obesity for the most commonly prescribed drugs. It is important that those prescribing for children with obesity are aware of these gaps in knowledge and of potential drug treatment failure or adverse events related to drug toxicity as a result of these knowledge gaps. Until more data are available, we recommend close monitoring of drug response and adverse events in children with obesity receiving commonly prescribed drugs.


Assuntos
Cálculos da Dosagem de Medicamento , Prescrições de Medicamentos/normas , Obesidade Pediátrica/tratamento farmacológico , Criança , Comorbidade , Humanos
9.
Ther Adv Cardiovasc Dis ; 13: 1753944719863641, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31364490

RESUMO

BACKGROUND: This analysis aimed to evaluate the impact of rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome (ACS) and to determine whether therapeutic drug monitoring might provide additional information regarding rivaroxaban dose, beyond what patient characteristics provide. METHODS: A post hoc exposure-response analysis was conducted using data from the phase III ATLAS ACS 2 Thrombolysis in Myocardial Infarction (TIMI) 51 study, in which 15,526 randomized ACS patients received rivaroxaban (2.5 mg or 5 mg twice daily) or placebo for a mean of 13 months (maximum follow up: 31 months). A multivariate Cox model was used to correlate individual predicted rivaroxaban exposures and patient characteristics with time-to-event clinical outcomes. RESULTS: For the incidence of myocardial infarction (MI), ischemic stroke, or nonhemorrhagic cardiovascular death, hazard ratios (HRs) for steady-state maximum plasma concentration (Cmax) in the 5th and 95th percentiles versus the median were statistically significant but close to 1 for both rivaroxaban doses. For TIMI major bleeding events, a statistically significant association was observed with Cmax [HR, 1.08; 95% CI, 1.06-1.11 (95th percentile versus median, 2.5 mg twice daily)], sex [HR, 0.56; 95% CI, 0.38-0.84 (female versus male)], and previous revascularization [HR, 0.62; 95% CI, 0.44-0.87 (no versus yes)]. CONCLUSIONS: The shallow slopes of the exposure-response relationships and the lack of a clear therapeutic window render it unlikely that therapeutic drug monitoring in patients with ACS would provide additional information regarding rivaroxaban dose beyond that provided by patient characteristics.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Modelos Biológicos , Rivaroxabana/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Idoso , Isquemia Encefálica/mortalidade , Tomada de Decisão Clínica , Ensaios Clínicos Fase III como Assunto , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/farmacocinética , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Rivaroxabana/farmacocinética , Acidente Vascular Cerebral/mortalidade , Resultado do Tratamento
11.
PLoS Negl Trop Dis ; 13(7): e0007541, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31314753

RESUMO

BACKGROUND: The World Health Organization (WHO) currently recommends height or age-based dosing as alternatives to weight-based dosing for mass drug administration lymphatic filariasis (LF) elimination programs. The goals of our study were to compare these alternative dosing strategies to weight-based dosing and to develop and evaluate new height-based dosing pole scenarios. METHODOLOGY/PRINCIPAL FINDINGS: Age, height and weight data were collected from >26,000 individuals in five countries during a cluster randomized LF clinical trial. Weight-based dosing for diethylcarbamazine (DEC; 6 mg/kg) and ivermectin (IVM; 200 ug/kg) with tablet numbers derived from a table of weight intervals was treated as the "gold standard" for this study. Following WHO recommended age-based dosing of DEC and height-based dosing of IVM would have resulted in 32% and 27% of individuals receiving treatment doses below those recommended by weight-based dosing for DEC and IVM, respectively. Underdosing would have been especially common in adult males, who tend to have the highest LF prevalence in many endemic areas. We used a 3-step modeling approach to develop and evaluate new dosing pole cutoffs. First, we analyzed the clinical trial data using quantile regression to predict weight from height. We then used weight predictions to develop new dosing pole cutoff values. Finally, we compared different dosing pole cutoffs and age and height-based WHO dosing recommendations to weight-based dosing. We considered hundreds of scenarios including country- and sex-specific dosing poles. A simple dosing pole with a 6-tablet maximum for both DEC and IVM reduced the underdosing rate by 30% and 21%, respectively, and was nearly as effective as more complex pole combinations for reducing underdosing. CONCLUSIONS/SIGNIFICANCE: Using a novel modeling approach, we developed a simple dosing pole that would markedly reduce underdosing for DEC and IVM in MDA programs compared to current WHO recommended height or age-based dosing.


Assuntos
Cálculos da Dosagem de Medicamento , Filariose Linfática/prevenção & controle , Filaricidas/administração & dosagem , Administração Massiva de Medicamentos/métodos , Razão Cintura-Estatura , Adolescente , Adulto , Estatura , Peso Corporal , Criança , Estudos de Coortes , Dietilcarbamazina/administração & dosagem , Feminino , Saúde Global , Humanos , Ivermectina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Prevalência , Análise de Regressão , Adulto Jovem
12.
Eur J Pharm Biopharm ; 142: 31-37, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31201856

RESUMO

The rat single-pass intestinal perfusion (SPIP) model is commonly used to investigate gastrointestinal physiology and membrane drug transport. The SPIP model can be used with the intestinal segment inside or outside the abdomen. The rats can also be treated with parecoxib, a selective cycloxygenase-2 inhibitor that has been shown to affect some intestinal functions following abdominal surgery, such as motility, epithelial permeability, fluid flux and ion transport. However, the impact of extra-abdominal placement of the intestinal segment in combination with parecoxib on intestinal drug transport has not been investigated. There is also uncertainty how well intestinal permeability determinations based on luminal drug disappearance and plasma appearance correlate in the rat SPIP model. The main objective of this rat in vivo study was to investigate the effect of intra- vs. extra-abdominal SPIP, with and without, pretreatment with parecoxib. The effect was evaluated by determining the difference in blood-to-lumen 51Cr-EDTA clearance, lumen-to-blood permeability of a cassette-dose of four model compounds (atenolol, enalaprilat, ketoprofen, and metoprolol), and water flux. The second objective was to compare the jejunal permeability values of the model drugs when determined based on luminal disappearance or plasma appearance. The study showed that the placement of the perfused jejunal segment, or the treatment with parecoxib, had minimal effects on membrane permeability and water flux. It was also shown that intestinal permeability of low permeability compounds should be determined on the basis of data from plasma appearance rather than luminal disappearance. If permeability is calculated on the basis of luminal disappearance, it should preferably include negative values to increase the accuracy in the determinations.


Assuntos
Permeabilidade da Membrana Celular/fisiologia , Mucosa Intestinal/metabolismo , Jejuno/metabolismo , Preparações Farmacêuticas/metabolismo , Animais , Transporte Biológico/fisiologia , Cálculos da Dosagem de Medicamento , Absorção Intestinal/fisiologia , Masculino , Perfusão/métodos , Permeabilidade , Ratos , Ratos Wistar
13.
Nurse Educ Pract ; 38: 89-95, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31229942

RESUMO

Safe drug calculation is important in nursing as insufficient skills pose a risk to patient safety. Therefor solid education in mathematics for undergraduate nursing students must be provided. To support nursing students' skills in drug calculation, a web-based learning platform for drug calculation was created. The aim of this study was to investigate nursing students' experiences of a web-based learning platform for drug calculation in terms of usability and learning support. The study was a cross-sectional comparative study. Ninety-five nursing students participated, out of which 46 students were in semester one and 49 students were in semester six. A questionnaire was used to evaluate the nursing students' experiences of a web-based learning platform for drug calculation in terms of usability and learning support. The findings were informed by statistical and thematic analyses. The majority of the participants evaluated the platform positively. The platform was deemed useful, and it was a support for the nursing students' learning. These findings provide that a web-based learning platform for drug calculation can be used as a complement to traditional lectures. Nevertheless, further research is required focusing teaching strategies facilitating different learning styles and level of computer skills.


Assuntos
Cálculos da Dosagem de Medicamento , Bacharelado em Enfermagem/normas , Estudantes de Enfermagem/psicologia , Adulto , Estudos Transversais , Bacharelado em Enfermagem/métodos , Feminino , Humanos , Internet , Acontecimentos que Mudam a Vida , Masculino , Erros de Medicação/prevenção & controle , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Inquéritos e Questionários , Suécia
14.
Eur Arch Otorhinolaryngol ; 276(9): 2559-2564, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31250085

RESUMO

PURPOSE: As the lack of consensus in the initial levothyroxine (LT4) dose titration following total thyroidectomy exists, the aim of this study was to identify and quantify predictive factors for LT4 dose replacement. METHODS: A retrospective analysis of a prospectively gathered data of 234 patients who underwent total-thyroidectomy at two institutions between November 9, 2009 and January 1, 2016 was conducted. Outcome variable was the clinically observed optimal LT4 dose. Linear and polynomial regression methods were used for prediction. Continuous variables were tested for mean differences using Student's t-test and association using Pearson's correlation. RESULTS: We identified Body Surface Area (BSA) as the most significant predictor. We propose a model that titrates LT4 dose based on BSA (1.4 µg /kg/day for BSA > 1.79 m2 vs. 1.7 µg /kg/day for BSA ≤ 1.79 m2; P = 0.00). Men required higher doses than women and no differences were noted based on DM status or pathological diagnosis. CONCLUSIONS: Our analysis shows BSA as an independent predictor of LT4 dose post total thyroidectomy. Despite the possibility of generating different equations for predicting LT4 post total-thyroidectomy, finding a practical and clinically relevant prediction model is yet of limited efficiency.


Assuntos
Terapia de Reposição Hormonal/métodos , Hipotireoidismo , Complicações Pós-Operatórias , Tireoidectomia , Tiroxina/administração & dosagem , Adulto , Idoso , Algoritmos , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/tratamento farmacológico , Estudos Retrospectivos , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Tiroxina/sangue
15.
Methodist Debakey Cardiovasc J ; 15(1): 23-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049146

RESUMO

The discovery of statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) is a consequence of the highly targeted, arduous search for naturally occurring compounds that inhibit cholesterol biosynthesis. An enormous amount of basic scientific, genetic, and clinical research substantiated the role of lipoprotein-derived cholesterol in atherogenesis. Quantifying the impact of lipid lowering on cardiovascular event rates became an issue of utmost urgency. Although a variety of nonstatin drugs had been tested in clinical trials, they found limited utility in the clinical setting due to lack of mortality reduction or tolerability issues. As multiple prospective randomized statin trials began publishing their results, it became clear that reducing atherogenic lipoprotein burden with these drugs was highly efficacious, safe, and generally well tolerated. Statins have been shown to reduce risk for nonfatal MI, ischemic stroke, need for revascularization, and cardiovascular and all-cause mortality. They have also been shown to stabilize and even regress established atherosclerotic plaque. For the first 2 decades of their use, statin dosing was largely determined by risk-stratified low-density lipoprotein cholesterol (LDL-C) goals. More recently, there has been a transition away from LDL-C goal attainment with a focus more on cardiovascular risk and percent LDL-C reduction. Unfortunately, long-term adherence rates with statin therapy remain low and, even when used, they tend to be underdosed.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Cálculos da Dosagem de Medicamento , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
16.
Support Care Cancer ; 27(9): 3195-3207, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31062109

RESUMO

PURPOSE: This systematic literature review examines research into the use of medicinal cannabis in cancer management. The aim was to identify the gaps in knowledge on the dose, dosing schedule and absorption of the administration routes of medicinal cannabis use in oncology. METHODS: A comprehensive search of the literature was conducted across six databases to identify original data reporting the pharmacology of medicinal cannabis in oncology. RESULTS: Eighteen articles were selected for review. Of the selected articles, ten were identified as randomised control trials, two experimental studies, two retrospective cohort studies and four case studies. Four articles reported absorption data and one drug interaction study was identified. CONCLUSIONS: There is little evidence reported in the literature on the absorption of medicinal cannabis in cancer populations. Various reasons are explored for the lack of pharmacokinetic studies for medicinal cannabis in cancer populations, including the availability of assays to accurately assess cannabinoid levels, lack of clinical biomarkers and patient enrolment for pharmacokinetic studies.


Assuntos
Canabinoides/uso terapêutico , Maconha Medicinal/uso terapêutico , Neoplasias/tratamento farmacológico , Analgésicos/uso terapêutico , Antieméticos/uso terapêutico , Antineoplásicos/uso terapêutico , Canabinoides/farmacocinética , Cannabis/química , Antagonistas Colinérgicos/uso terapêutico , Cálculos da Dosagem de Medicamento , Humanos , Maconha Medicinal/farmacocinética , Preparações de Plantas/uso terapêutico , Estudos Retrospectivos
17.
Drug Discov Ther ; 13(2): 89-95, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080208

RESUMO

Basic bronchoscopic diagnostic procedures like Broncho-alveolar lavage (BAL) are often performed without sedation, using lignocaine administered via the working channel of bronchoscope (spray-as-you-go technique) and other routes. Our aim was to evaluate the factors responsible for variation in the total dose of lignocaine administered in individual subjects. We prospectively included consecutive subjects undergoing BAL in an outpatient setting from August 2016 to November 2017 at our centre. The subjects were administered lignocaine via nebulization, nasal gel, oropharyngeal spray before and during bronchoscopy ("spray-as-you-go") as per a predefined protocol. The demographic details, high resolution computerized tomography (HRCT) characteristics, procedural details, doses of lignocaine administered and a visual analogue scale (VAS) for satisfaction with the procedure were recorded. Using lignocaine dose as outcome, variables were assessed for effect by univariate and multivariate regression analysis. 96 subjects were included with a mean age of 40 years and male predominance (60.4%). Cough was the most common presenting symptom (64.6%). Predisposing factors included tuberculosis (47.9%) and smoking (23.2%). Maximum variation in lignocaine dose occurred prior to intubating vocal cords using "spray-as-you-go", which was significantly related to history of past tuberculosis (p = 0.031), obstructive airway disease (p = 0.009), fibrotic sequelae (p = 0.011) and bronchiectasis (p = 0.049). Obstructive airway disease and fibrotic sequelae were also significant on multivariate analysis (p = 0.01 and 0.005 respectively). Obstructive airway disease and architectural distortion due to fibrotic sequelae leads to higher dose requirement for lignocaine during BAL by fibre-optic bronchoscopy. Caution must be maintained during bronchoscopic procedures to avoid exceeding recommended maximum doses in such patients.


Assuntos
Anestésicos Locais/administração & dosagem , Lavagem Broncoalveolar/métodos , Broncoscopia/métodos , Lidocaína/administração & dosagem , Administração Tópica , Adulto , Lavagem Broncoalveolar/efeitos adversos , Broncoscopia/efeitos adversos , Cálculos da Dosagem de Medicamento , Feminino , Géis , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Sprays Orais , Estudos Prospectivos , Irrigação Terapêutica , Escala Visual Analógica
18.
Acta Med Indones ; 51(1): 10-18, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31073101

RESUMO

BACKGROUND: the shifting of minimum inhibitory concentration (MIC) of methicillin-resistant Staphylocuccus aureus (MRSA) strains to the higher value has emerged to worsen clinical outcome to the patients particularly critically ill population.  The aim of this study was to identify the most appropriate dosage regimen of vancomycin to treat infection caused by MRSA with higher MIC in critically ill Thai population. METHODS: 10,000 replications of intermittent vancomycin dosage regimens were performed using Monte Carlo simulation. Pharmacokinetic parameters were derived from a population pharmacokinetic study conducted specifically in Thai population. The probability of target attainment (PTA) and cumulative fraction of response (CFR) of each dosage regimen were calculated. Risk of nephrotoxicity was also calculated and used as a consideration in determining the most appropriate dosage regimen of vancomycin. RESULTS: in order to achieve desired PTA > 80% vancomycin at higher dosing regimens were needed including 3g/day and 4 g/day for MIC 1.5mg/L and 2.0 mg/L, respectively. Highest CFR of 94.40% and 93.57% were from vancomycin 1 g every 6 h and 2 g every 12h. Standard dose of vancomycin and total dose of vancomycin 3 g/day provided approximately 51% and 73% CFR. Risk of nephrotoxicity afforded by giving 1.5g every 12h and 2g every 12h of vancomycin were 26.59% and 31.20%, respectively. CONCLUSION: the result from this study recommended intermittent dosage regimen 1.5g every 12h and 2g every 12h should be implemented as definite antibiotic treatment when considered infection caused by MRSA with MIC 1.5 and 2.0 mg/L, respectively.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/administração & dosagem , Vancomicina/farmacocinética , Simulação por Computador , Estado Terminal , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Tailândia
19.
PLoS One ; 14(5): e0215607, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31075149

RESUMO

BACKGROUND: Shorter, more effective treatments for tuberculosis (TB) are urgently needed. While many TB drugs are available, identification of the best regimens is challenging because of the large number of possible drug-dose combinations. We have found consistently that responses of cells or whole animals to drug-dose stimulations fit a parabolic response surface (PRS), allowing us to identify and optimize the best drug combinations by testing only a small fraction of the total search space. Previously, we used PRS methodology to identify three regimens (PRS Regimens I-III) that in murine models are much more effective than the standard regimen used to treat TB. However, PRS Regimens I and II are unsuitable for treating drug-resistant TB and PRS Regimen III includes an experimental drug. Here, we use PRS methodology to identify from an expanded pool of drugs new highly effective near-universal drug regimens comprising only approved drugs. METHODS AND FINDINGS: We evaluated combinations of 15 different drugs in a human macrophage TB model and identified the most promising 4-drug combinations. We then tested 14 of these combinations in Mycobacterium tuberculosis-infected BALB/c mice and chose for PRS dose optimization and further study the two most potent regimens, designated PRS Regimens IV and V, consisting of clofazimine (CFZ), bedaquiline (BDQ), pyrazinamide (PZA), and either amoxicillin/clavulanate (AC) or delamanid (DLM), respectively. We then evaluated the efficacy in mice of optimized PRS Regimens IV and V, as well as a 3-drug regimen, PRS Regimen VI (CFZ, BDQ, and PZA), and compared their efficacy to PRS Regimen III (CFZ, BDQ, PZA, and SQ109), previously shown to reduce the time to achieve relapse-free cure in mice by 80% compared with the Standard Regimen (isoniazid, rifampicin, PZA, and ethambutol). Efficacy measurements included early bactericidal activity, time to lung sterilization, and time to relapse-free cure. PRS Regimens III-VI all rapidly sterilized the lungs and achieved relapse-free cure in 3 weeks (PRS Regimens III, V, and VI) or 5 weeks (PRS Regimen IV). In contrast, mice treated with the Standard Regimen still had high numbers of bacteria in their lungs after 6-weeks treatment and none achieved relapse-free cure in this time-period. CONCLUSIONS: We have identified three new regimens that rapidly sterilize the lungs of mice and dramatically shorten the time required to achieve relapse-free cure. All mouse drug doses in these regimens extrapolate to doses that are readily achievable in humans. Because PRS Regimens IV and V contain only one first line drug (PZA) and exclude fluoroquinolones and aminoglycosides, they should be effective against most TB cases that are multidrug resistant (MDR-TB) and many that are extensively drug-resistant (XDR-TB). Hence, these regimens have potential to shorten dramatically the time required for treatment of both drug-sensitive and drug-resistant TB. If clinical trials confirm that these regimens dramatically shorten the time required to achieve relapse-free cure in humans, then this radically shortened treatment has the potential to improve treatment compliance, decrease the emergence of drug resistance, and decrease the healthcare burden of treating both drug-sensitive and drug-resistant TB.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose/tratamento farmacológico , Animais , Antituberculosos/farmacologia , Inteligência Artificial , Modelos Animais de Doenças , Aprovação de Drogas , Combinação de Medicamentos , Cálculos da Dosagem de Medicamento , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/efeitos dos fármacos , Células THP-1 , Resultado do Tratamento
20.
Nutrients ; 11(5)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126048

RESUMO

Post-prandial hyperglycemia is still a challenging issue in intensified insulin therapy. Data of 35 T1D patients during a four-week period were analyzed: RT-CGM (real time continuous glucose monitoring) record, insulin doses, diet (including meal photos), energy expenditure, and other relevant conditions. Patients made significant errors in carbohydrate counting (in 56% of cooked and 44% of noncooked meals), which resulted in inadequate insulin doses. Subsequently, a mobile application was programmed to provide individualized advice on prandial insulin dose. When using the application, a patient chooses only the type of categorized situation (e.g., meals with other relevant data) without carbohydrates counting. The application significantly improved postprandial glycemia as normoglycemia was reached in 95/105 testing sessions. Other important findings of the study include: A high intake of saturated fat (median: 162% of recommended intake); a low intake of fiber and vitamin C (median: 42% and 37%, respectively, of recommended intake); an increase in overweight/obesity status (according to body fat measurement), especially in women (median of body fat: 30%); and low physical activity (in 16/35 patients). The proposed individualized approach without carbohydrate counting may help reach postprandial normoglycemia but it is necessary to pay attention to the lifestyle habits of T1D patients too.


Assuntos
Glicemia/efeitos dos fármacos , Telefone Celular , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cálculos da Dosagem de Medicamento , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Estilo de Vida , Aplicativos Móveis , Período Pós-Prandial , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Carboidratos da Dieta/administração & dosagem , Metabolismo Energético , Exercício , Comportamento Alimentar , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudo de Prova de Conceito , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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