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3.
Int J Antimicrob Agents ; 56(4): 106144, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32853673

RESUMO

Hydroxychloroquine (HCQ) has been largely used and investigated as therapy for COVID-19 across various settings at a total dose usually ranging from 2400 mg to 9600 mg. In Belgium, off-label use of low-dose HCQ (total 2400 mg over 5 days) was recommended for hospitalised patients with COVID-19. We conducted a retrospective analysis of in-hospital mortality in the Belgian national COVID-19 hospital surveillance data. Patients treated either with HCQ monotherapy and supportive care (HCQ group) were compared with patients treated with supportive care only (no-HCQ group) using a competing risks proportional hazards regression with discharge alive as competing risk, adjusted for demographic and clinical features with robust standard errors. Of 8075 patients with complete discharge data on 24 May 2020 and diagnosed before 1 May 2020, 4542 received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%) and 957/3533 (27.1%), respectively. In the multivariable analysis, mortality was lower in the HCQ group compared with the no-HCQ group [adjusted hazard ratio (aHR) = 0.684, 95% confidence interval (CI) 0.617-0.758]. Compared with the no-HCQ group, mortality in the HCQ group was reduced both in patients diagnosed ≤5 days (n = 3975) and >5 days (n = 3487) after symptom onset [aHR = 0.701 (95% CI 0.617-0.796) and aHR = 0.647 (95% CI 0.525-0.797), respectively]. Compared with supportive care only, low-dose HCQ monotherapy was independently associated with lower mortality in hospitalised patients with COVID-19 diagnosed and treated early or later after symptom onset.


Assuntos
Antimaláricos/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/patogenicidade , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Progressão da Doença , Cálculos da Dosagem de Medicamento , Reposicionamento de Medicamentos , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Segurança do Paciente , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Linfócitos T/patologia , Linfócitos T/virologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
4.
Eur J Endocrinol ; 183(4): 357-368, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32621587

RESUMO

Context: Accurate hydrocortisone dosing in children with adrenal insufficiency is important to avoid the risks of over and under treatment including iatrogenic Cushing's syndrome and adrenal crisis. Objective: To establish a population pharmacokinetic model of hydrocortisone in children and use this to refine hydrocortisone replacement regimens. Design and methods: Pharmacokinetic study of hydrocortisone granules, available in 0.5, 1, 2 and 5 mg dose strengths, in 24 children with adrenal insufficiency aged 2 weeks to 6 years. Cortisol concentrations quantified by LC-MS/MS were used to refine an adult pharmacokinetic model to a paediatric population model which was then used to simulate seven different hydrocortisone treatment regimens. Results: Pre-dose cortisol levels were undetectable in 54% of the 24 children. The developed pharmacokinetic model had good predictive performance. Simulations for the seven treatment regimens using either three- or four-times daily dosing showed treatment regimens delivered an AUC0-24h within the 90% reference range for healthy children except in neonates where two regimens had an AUC below the 5th percentile. Cortisol concentrations at individual time points in the 24 h were outside the 90% reference range for healthy individuals in 50%, 55-65% and 70-75% for children, infants and neonates, respectively, with low cortisol levels being most prevalent. Conclusions: Current paediatric hydrocortisone treatment regimens based on either three- or four-times daily administration replicate cortisol exposure based on AUC0-24h, but the majority of cortisol levels are above or below physiological cortisol levels with low levels very common before the next dose.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Insuficiência Adrenal/metabolismo , Cálculos da Dosagem de Medicamento , Hidrocortisona/administração & dosagem , Hidrocortisona/farmacocinética , Administração Oral , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/metabolismo , Insuficiência Adrenal/epidemiologia , Fatores Etários , Idade de Início , Área Sob a Curva , Pesos e Medidas Corporais , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Terapia de Reposição Hormonal/métodos , Terapia de Reposição Hormonal/normas , Humanos , Lactente , Recém-Nascido , Masculino , Modelos Teóricos
6.
Clin Immunol ; 218: 108517, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32585295

RESUMO

Approximately 15% of patients with coronavirus disease 2019 (COVID-19) experience severe disease, and 5% progress to critical stage that can result in rapid death. No vaccines or antiviral treatments have yet proven effective against COVID-19. Patients with severe COVID-19 experience elevated plasma levels of pro-inflammatory cytokines, which can result in cytokine storm, followed by massive immune cell infiltration into the lungs leading to alveolar damage, decreased lung function, and rapid progression to death. As many of the elevated cytokines signal through Janus kinase (JAK)1/JAK2, inhibition of these pathways with ruxolitinib has the potential to mitigate the COVID-19-associated cytokine storm and reduce mortality. This is supported by preclinical and clinical data from other diseases with hyperinflammatory states, where ruxolitinib has been shown to reduce cytokine levels and improve outcomes. The urgent need for treatments for patients with severe disease support expedited investigation of ruxolitinib for patients with COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Citocinas/antagonistas & inibidores , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Betacoronavirus/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Citocinas/genética , Citocinas/imunologia , Cálculos da Dosagem de Medicamento , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 1/genética , Janus Quinase 1/imunologia , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/genética , Janus Quinase 2/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Inibidores de Proteínas Quinases/farmacocinética , Pirazóis/farmacocinética , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos
7.
Int J Hematol ; 112(3): 369-376, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32529585

RESUMO

Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) is one of the standard regimens for indolent B-cell non-Hodgkin's lymphoma (NHL). It is unclear whether the prednisolone (PSL) dosage affects the therapeutic effect or the adverse event profile. We retrospectively examined 48 patients with indolent B-cell NHL who were treated with R-CHOP (PSL 50 mg/m2/day for 5 days) at our institute between 2006 and 2016. We compared them with 149 patients with indolent B-cell lymphoma who were treated with R-CHOP (PSL 100 mg for 5 days) in the JCOG 0203 trial. The proportions of patients with bulky disease, extranodal involvement, and increased nodal sites were higher at our institute. Nevertheless, there was no difference in the CR rate, PFS, OS or the frequency of adverse events, except for peripheral neuropathy, between the two treatment groups. In our institute, there was no difference in the CR rate, PFS, OS or adverse event profile between patients who received PSL at 60-80 mg/day and at 81-100 mg/day. Patients who received PSL at 60-80 mg/day included many female and light-weight patients. In conclusion, the PSL dose adjusted based on body surface area appeared to be appropriate in terms of efficacy and safety.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Prednisolona/administração & dosagem , Rituximab/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Superfície Corporal , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Linfoma Folicular/mortalidade , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisolona/efeitos adversos , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
8.
JAMA Pediatr ; 174(10): e202422, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32501511

RESUMO

Importance: Children of all ages appear susceptible to severe acute respiratory syndrome coronavirus 2 infection. To support pediatric clinical studies for investigational treatments of coronavirus disease 2019 (COVID-19), pediatric-specific dosing is required. Objective: To define pediatric-specific dosing regimens for hydroxychloroquine and remdesivir for COVID-19 treatment. Design, Setting, and Participants: Pharmacokinetic modeling and simulation were used to extrapolate investigated adult dosages toward children (March 2020-April 2020). Physiologically based pharmacokinetic modeling was used to inform pediatric dosing for hydroxychloroquine. For remdesivir, pediatric dosages were derived using allometric-scaling with age-dependent exponents. Dosing simulations were conducted using simulated pediatric and adult participants based on the demographics of a white US population. Interventions: Simulated drug exposures following a 5-day course of hydroxychloroquine (400 mg every 12 hours × 2 doses followed by 200 mg every 12 hours × 8 doses) and a single 200-mg intravenous dose of remdesivir were computed for simulated adult participants. A simulation-based dose-ranging study was conducted in simulated children exploring different absolute and weight-normalized dosing strategies. Main Outcomes and Measures: The primary outcome for hydroxychloroquine was average unbound plasma concentrations for 5 treatment days. Additionally, unbound interstitial lung concentrations were simulated. For remdesivir, the primary outcome was plasma exposure (area under the curve, 0 to infinity) following single-dose administration. Results: For hydroxychloroquine, the physiologically based pharmacokinetic model analysis included 500 and 600 simulated white adult and pediatric participants, respectively, and supported weight-normalized dosing for children weighing less than 50 kg. Geometric mean-simulated average unbound plasma concentration values among children within different developmental age groups (32-35 ng/mL) were congruent to adults (32 ng/mL). Simulated unbound hydroxychloroquine concentrations in lung interstitial fluid mirrored those in unbound plasma and were notably lower than in vitro concentrations needed to mediate antiviral activity. For remdesivir, the analysis included 1000 and 6000 simulated adult and pediatric participants, respectively. The proposed pediatric dosing strategy supported weight-normalized dosing for participants weighing less than 60 kg. Geometric mean-simulated plasma area under the time curve 0 to infinity values among children within different developmental age-groups (4315-5027 ng × h/mL) were similar to adults (4398 ng × h/mL). Conclusions and Relevance: This analysis provides pediatric-specific dosing suggestions for hydroxychloroquine and remdesivir and raises concerns regarding hydroxychloroquine use for COVID-19 treatment because concentrations were less than those needed to mediate an antiviral effect.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Antivirais/farmacocinética , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/farmacocinética , Pneumonia Viral/tratamento farmacológico , Terapias em Estudo/métodos , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/farmacocinética , Adolescente , Adulto , Alanina/administração & dosagem , Alanina/farmacocinética , Criança , Pré-Escolar , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Modelos Biológicos , Pandemias , Simulação de Paciente , Adulto Jovem
9.
Ther Adv Cardiovasc Dis ; 14: 1753944720924255, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32449469

RESUMO

BACKGROUND: Recombinant factor VIIa (rFVIIa) (Novoseven®) is utilized for the reversal of anticoagulation-associated bleeding and refractory bleeding in cardiac surgery. In August 2015, rFVIIa was transferred from the blood bank to the pharmacy at New York University (NYU) Langone Health. Concordantly, an off-label dosing guideline was developed. The objective of this study was to describe utilization and cost of rFVIIa and assess compliance to our dosing guideline. METHODS: We performed a retrospective, observational review of rFVIIa administrations post-implementation of an off-label dosing guideline. All patients who received rFVIIa between September 2015 and June 2017 were evaluated. For each rFVIIa administration, anticoagulation and laboratory values, indications for use, dosing, ordering and administration times, concomitant blood products, and adverse events were collected. Adverse events included venous thromboembolism, stroke, myocardial infarction, and death due to systemic embolism and mortality. The primary endpoint was the utilization of rFVIIa in accordance with the off-label dosing guideline. Secondary endpoints included hemostatic efficacy of rFVIIa, adverse events, blood products administered, and cost-effectiveness of rFVIIa transition to pharmacy. RESULTS: A total of 63 patients [pediatric (n = 6), adult (n = 57)] received rFVIIa, with the majority of use for refractory bleeding after cardiac surgery. The utilization of rVIIa decreased after development of the off-label dosing guideline and transition from blood bank to pharmacy. The total incidence of thromboembolic events within 30 days was 19.6%; 17.6% arterial and 2% venous; 70% of patients with an adverse event were over 70 years of age. Use of rFVIIa reduced the median number of units of blood products administered. CONCLUSION: Administration of rFVIIa for cardiac surgery appears to be effective for hemostasis. Transitioning rFVIIa from the blood bank to pharmacy and implementation of a dosing guideline appears to have reduced utilization. Patients receiving rFVIIa should be monitored for thromboembolic events. Elderly patients may be at higher risk for thromboembolic events.


Assuntos
Centros Médicos Acadêmicos , Anticoagulantes/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Fator VIIa/administração & dosagem , Hemorragia/prevenção & controle , Hemostáticos/administração & dosagem , Padrões de Prática Médica , Centros Médicos Acadêmicos/economia , Idoso , Procedimentos Cirúrgicos Cardíacos/economia , Criança , Pré-Escolar , Custos de Medicamentos , Cálculos da Dosagem de Medicamento , Revisão de Uso de Medicamentos , Fator VIIa/efeitos adversos , Fator VIIa/economia , Feminino , Hemorragia/induzido quimicamente , Hemorragia/economia , Hemostáticos/efeitos adversos , Hemostáticos/economia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Uso Off-Label , Padrões de Prática Médica/economia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/economia , Estudos Retrospectivos , Fatores de Risco , Tromboembolia/induzido quimicamente , Resultado do Tratamento
10.
Clin Transl Sci ; 13(4): 646-648, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32441462

RESUMO

The global response to finding therapeutics for coronavirus disease 2019 (COVID-19) is chaotic even if well intentioned. There is an opportunity, but more importantly, an obligation for the global clinical and quantitative pharmacology community to come together and use our state-of-the-art tools and expertise to help society accelerate therapeutics to fight COVID-19. This brief commentary is a call to action and highlights how the global pharmacology community should contribute to the COVID-19 pandemic and prepare for future pandemics.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Aprovação de Drogas/organização & administração , Desenvolvimento de Medicamentos/organização & administração , Descoberta de Drogas/organização & administração , Farmacologia Clínica/organização & administração , Pneumonia Viral/tratamento farmacológico , Antivirais/efeitos adversos , Antivirais/farmacocinética , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Humanos , Pandemias , Segurança do Paciente , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Fatores de Tempo , Fluxo de Trabalho
11.
Internist (Berl) ; 61(6): 565-572, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32394073

RESUMO

BACKGROUND: The central circadian pacemaker in the suprachiasmatic nucleus and interaction of clock genes with the hypothalamus pituitary adrenal axis are responsible for very distinct cortisol concentrations. Unphysiologically high doses of glucocorticoids that do not follow the circadian rhythm lead to increased rates of morbidity, mortality and reduced quality of life. OBJECTIVES: Does a switch to modified-release hydrocortisone in multimorbid elderly patients offer benefits compared to a conventional therapy regime? METHODS: Evaluation, analysis and discussion of statistics, recent research results and expert advice. RESULTS: Overdosage and unphysiological timing of cortisol administration result in higher incidences of obesity, hypertension, hyperglycemia, coronary heart disease and cardiac events. Body weight, body mass index and HbA1c decline with Plenadren® (Shire Pharmaceuticals Ireland Limited, Dublin, Ireland) treatment compared to conventional therapy. CD16+ natural killer cells and natural killer cytotoxycity are reduced, and the incidence of respiratory-tract infections is increased, with conventional therapy compared to Plenadren®. Cortisol influences sleep pattern and sleep quality by its circadian secretion. CONCLUSION: Novel modified-release hydrocortisone preparations offer diverse benefits with regard to their effect on metabolism, cardiovascular risk, immunity and sleep, which might be beneficial in particular in multimorbid elderly.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Ritmo Circadiano/fisiologia , Glucocorticoides/uso terapêutico , Terapia de Reposição Hormonal/métodos , Hidrocortisona/uso terapêutico , Insuficiência Adrenal/metabolismo , Idoso , Relação Dose-Resposta a Droga , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Glucocorticoides/administração & dosagem , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/metabolismo , Qualidade de Vida , Resultado do Tratamento
12.
J Pharmacokinet Pharmacodyn ; 47(3): 189-198, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32435882

RESUMO

To face SARS-CoV-2 pandemic various attempts are made to identify potential effective treatments by repurposing available drugs. Among them, indomethacin, an anti-inflammatory drug, was shown to have potent in-vitro antiviral properties on human SARS-CoV-1, canine CCoV, and more recently on human SARS-CoV-2 at low micromolar range. Our objective was to show that indomethacin could be considered as a promising candidate for the treatment of SARS-CoV-2 and to provide criteria for comparing benefits of alternative dosage regimens using a model-based approach. A multi-stage model-based approach was developed to characterize % of recovery and viral load in CCoV-infected dogs, to estimate the PK of indomethacin in dog and human using published data after administration of immediate (IR) and sustained-release (SR) formulations, and to estimate the expected antiviral activity as a function of different assumptions on the effective exposure in human. Different dosage regimens were evaluated for IR formulation (25 mg and 50 mg three-times-a-day, and 25 mg four-times-a-day), and SR formulation (75 mg once and twice-a-day). The best performing dosing regimens were: 50 mg three-times-a-day for the IR formulation, and 75 mg twice-a-day for the SR formulation. The treatment with the SR formulation at the dose of 75 mg twice-a-day is expected to achieve a complete response in three days for the treatment in patients infected by the SARS-CoV-2 coronavirus. These results suggest that indomethacin could be considered as a promising candidate for the treatment of SARS-CoV-2 whose potential therapeutic effect need to be further assessed in a prospective clinical trial.


Assuntos
Antivirais/administração & dosagem , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Cálculos da Dosagem de Medicamento , Indometacina/administração & dosagem , Indometacina/uso terapêutico , Modelos Biológicos , Pneumonia Viral/tratamento farmacológico , Animais , Antivirais/farmacocinética , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/virologia , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/uso terapêutico , Cães , Humanos , Indometacina/farmacocinética , Pandemias , Pneumonia Viral/virologia , Carga Viral/efeitos dos fármacos
14.
Clin Pharmacol Ther ; 108(5): 921-923, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32445484

RESUMO

Potential treatments for coronavirus disease 2019 (COVID-19) are being investigated at unprecedented speed, and successful treatments will rapidly be used in tens or hundreds of thousands of patients. To ensure safe and effective use in all those patents it is essential also to develop, at unprecedented speed, a means to provide frequently updated, optimal dosing information for all patient subgroups. Success will require immediate collaboration between drug developers, academics, and regulators.


Assuntos
Antivirais , Infecções por Coronavirus , Relação Dose-Resposta a Droga , Desenvolvimento de Medicamentos , Reposicionamento de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Pandemias , Pneumonia Viral , Antivirais/farmacocinética , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Disponibilidade Biológica , Biomarcadores Farmacológicos/análise , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Desenvolvimento de Medicamentos/métodos , Desenvolvimento de Medicamentos/normas , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos/normas , Reposicionamento de Medicamentos/métodos , Reposicionamento de Medicamentos/normas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Cooperação Internacional , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Resultado do Tratamento
15.
Ann Endocrinol (Paris) ; 81(5): 500-506, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32445637

RESUMO

INTRODUCTION: Euthyroid patients show decreased TSH level following sleeve gastrectomy. However, studies of levothyroxine absorption after bariatric surgery reported contradictory results and data on levothyroxine dose adjustment according to weight are sparse. The aim of this study was to evaluate levothyroxine dose adjustment during weight loss following sleeve surgery. METHOD: This retrospective study assessed change in levothyroxine dose in patients undergoing sleeve gastrectomy at the university hospital center of Nîmes (France) between January 2010 and March 2016. Patients were receiving standard bariatric surgery follow-up with levothyroxine therapy for hypothyroidism. RESULTS: Fifty-two of the 271 patients who underwent sleeve gastrectomy (19.2%) were being treated with levothyroxine. Among these patients, 31 were followed up for 12 months, including 12 who were followed up for 24 months. Mean weight loss was 35±11kg at 12 months and 41.8±10.2 kg at 24 months. Daily levothyroxine dose decreased from 108 [88-144] µg/day to 94 [63-125] µg/day at 12 months and 69 [44-134] µg/day at 24 months, with positive correlation between dose and weight loss at 12 months (P=0.03). Weight-adjusted dose was 1.04 [0.81-1.24] µg/kg/day at baseline, 1.14 [0.85-1.66] µg/kg/day at 12 months, and 0.85 [0.53-2.10] µg/kg/day at 24 months, showing no correlation with weight loss. Median TSH level dropped to 1.30 [0.63-2.27] mIU/l at 12 months and 1.48 [1.08-2.42] mIU/l at 24 months. CONCLUSION: Despite a decrease in daily levothyroxine dose correlating with weight loss at 12 months, the absence of correlation with weight-adjusted dose suggests the involvement of confounding factors such as poor levothyroxine absorption or altered thyroid function. Further studies are required to elucidate the absorption of levothyroxine.


Assuntos
Gastrectomia/efeitos adversos , Hipotireoidismo/tratamento farmacológico , Síndromes de Malabsorção , Obesidade Mórbida/cirurgia , Tiroxina/administração & dosagem , Perda de Peso/fisiologia , Adulto , Cirurgia Bariátrica/efeitos adversos , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Feminino , França , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/complicações , Hipotireoidismo/cirurgia , Síndromes de Malabsorção/sangue , Síndromes de Malabsorção/tratamento farmacológico , Síndromes de Malabsorção/etiologia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Obesidade Mórbida/tratamento farmacológico , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/tratamento farmacológico , Período Pós-Operatório , Estudos Retrospectivos , Hormônios Tireóideos/sangue , Tireotropina/sangue
19.
Ann Palliat Med ; 9(2): 537-541, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32233628

RESUMO

Opioids are an important tool in the management of acute and chronic (cancer and non-cancer) pain. Pain and palliative care practitioners are frequently called upon to switch a patient from one opioid regimen to a different regimen either to gain better pain control, to minimize opioid-related adverse effects, to overcome opioid tolerance, or due to a change in patient status. To this end, equianalgesic tables have been published to guide practitioners in making these calculations. Despite being built on the best data available, equianalgesic tables do not tell the whole story, requiring the practitioner to thoroughly consider the patient's situation, and unknown variables. A five-step process is presented in this article that espouse a safe and effective way to switch from one opioid regimen to another. Directions for the future include better refinement of the data that informs the equianalgesic table, and perhaps inclusion of opioid utility data.


Assuntos
Analgésicos Opioides/uso terapêutico , Dor/tratamento farmacológico , Uso Indevido de Medicamentos sob Prescrição/prevenção & controle , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Humanos , Metadona/uso terapêutico , Morfina/uso terapêutico , Epidemia de Opioides/prevenção & controle , Manejo da Dor/métodos
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