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1.
Reumatol. clín. (Barc.) ; 16(6): 437-446, nov.-dic. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-194661

RESUMO

OBJETIVO: Generar las recomendaciones para la atención de pacientes con enfermedades reumáticas que reciben terapias inmunomoduladoras e inmunosupresoras (fármacos convencionales, biológicos y moléculas pequeñas) durante la pandemia por COVID-19. MATERIALES Y MÉTODOS: Las recomendaciones se realizaron utilizando el método Delphi como herramienta de acuerdo. Se conformó un panel de expertos con trayectoria académica y experiencia en investigación en reumatología. Se realizó la búsqueda de la literatura y se generó el cuestionario del ejercicio Delphi conformado por 42 preguntas. El grado de acuerdo se logró con el 80% de aprobación de los participantes. RESULTADOS: Se conformó un grupo de 11 reumatólogos de 7 ciudades del país. La tasa de respuesta fue del 100% para las 3 rondas de consulta. En la primera ronda se logró acuerdo en 35 preguntas, en la segunda ronda 37 y en la tercera ronda se logró el acuerdo de las 42 preguntas. CONCLUSIÓN: La recomendación para la mayoría de los tratamientos inmunomoduladores utilizados en reumatología es continuar con las terapias en pacientes que no tengan la infección y suspenderlas en aquellos con diagnóstico de SARS-CoV-2/COVID-19


OBJECTIVE: To produce recommendations for patients with rheumatological diseases receiving immunomodulatory and immunosuppressive therapies (conventional drugs, biologicals, and small molecules) during the COVID-19 pandemic. MATERIALS AND METHODS: The recommendations were determined using the Delphi method as an agreement tool. A panel of experts was formed, with academic backgrounds and research experience in rheumatology. A literature search was conducted and 42 questions were generated. The level of agreement was made with 80% of approval by the participants. RESULTS: A group of eleven rheumatologists from 7 cities in the country participated. The response rate was 100% for the three consultation rounds. In the first round, agreement was reached on 35 questions, on 37 in the second round, and on 42 questions in the third round. CONCLUSION: The recommendation for the majority of the pharmacological treatments used in rheumatology is to continue with immunomodulatory or immunosuppressive therapies in patients who do not have the infection, and to suspend it in patients with a diagnosis of SARS-CoV-2/COVID-19


Assuntos
Humanos , Doenças Reumáticas/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Antirreumáticos/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Doenças Reumáticas/complicações , Padrões de Prática Médica , Suspensão de Tratamento/tendências , Infecções por Coronavirus/epidemiologia , Pandemias/estatística & dados numéricos
2.
Medicine (Baltimore) ; 99(40): e22572, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019469

RESUMO

RATIONALE: Atorvastatin is the most common drug used in therapy for cardiovascular diseases. The most common adverse side effects associated with statins are myopathy and hypertransaminasemia. Here, we report a rare case of gamma glutamyl transpeptidase (GGT) elevation induced by atorvastatin. PATIENT CONCERNS: A 47-year-old male was admitted to our hospital with dyslipidemia, he had been taking pitavastatin 2 mg/day for 2 months. The levels of total cholesterol (265.28 mg/dL) and low-density lipoprotein-cholesterol (LDL) (179.15 mg/dL) were also high. DIAGNOSIS: Blood lipid test showed mixed dyslipidemia. INTERVENTION: Atorvastatin 10 mg/day was given to the patient. OUTCOMES: The patient came back to our hospital for blood tests after 4 weeks. Although no symptoms were detectable, the patient's GGT level was markedly elevated (up to 6-fold over normal level) with less marked increases in alkaline phosphatase (ALP) and alanine aminotransferase (ALT). The serum GGT level returned to normal within 6 weeks of cessation of atorvastatin. LESSONS: This is a case of GGT elevation without hyperbilirubinemia, hypertransaminasemiam, or serum creatine phosphokinase (CPK) abnormalities despite an atorvastatin regimen. This case highlights GGT elevation caused by atorvastatin, a rare but serious condition. Clinicians should be aware of these possible adverse effects and monitor liver function tests in patients on statin therapy.


Assuntos
Atorvastatina/efeitos adversos , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Quinolinas/efeitos adversos , gama-Glutamiltransferase/efeitos dos fármacos , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Atorvastatina/administração & dosagem , Atorvastatina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/diagnóstico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Suspensão de Tratamento , gama-Glutamiltransferase/sangue
3.
Medicine (Baltimore) ; 99(40): e22620, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019484

RESUMO

RATIONALE: Low-dose mitotane has been widely used for many decades in patients with advanced adrenocortical carcinoma (ACC), which exhibited good safety profiles compared with the high-dose regimen. The clinical efficacy and toxicity of mitotane are closely related to its plasma concentration, and therapeutic drug monitoring (TDM) is recommended. Until now, no severe adverse drug reaction (ADR) related to the toxic plasma level after a short-term treatment of low-dose mitotane has been published. PATIENT CONCERNS: A 50-year-old Chinese female presented with severe neurological adverse events related to a toxic plasma levels of 42.8 mg/L after 4 months treatment of low-dose mitotane. DIAGNOSES: During the course of therapy, no other medication could cause neurological adverse events. Therefore, we suspected a high sensitivity to the side effect of mitotane related to a toxic plasma level. INTERVENTIONS: Treatment of mitotane was stopped. OUTCOMES: The trough plasma concentration of mitotane decreased to 18.7 mg/mL after one and a half months, and the neurological symptoms gradually improved after drug discontinuance. LESSONS: The present case provides the first report of severe neurological adverse events induced by the short-term use of low-dose mitotane for adjuvant treatment in a patient with ACC, indicating that potentially severe ADR can also occur when using low-dose regimen in the early stage of treatment. TDM and early recognition could result in a favorable outcome.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/tratamento farmacológico , Antineoplásicos Hormonais/toxicidade , Mitotano/toxicidade , Doenças do Sistema Nervoso/induzido quimicamente , Antineoplásicos Hormonais/sangue , Antineoplásicos Hormonais/uso terapêutico , Grupo com Ancestrais do Continente Asiático/etnologia , Monitoramento de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Mitotano/sangue , Mitotano/uso terapêutico , Síndromes Neurotóxicas , Resultado do Tratamento , Suspensão de Tratamento
4.
Lancet Glob Health ; 8(11): e1418-e1426, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33069302

RESUMO

BACKGROUND: Few studies have been done of patterns of treatment during mass drug administration (MDA) to control neglected tropical diseases. We used routinely collected individual-level treatment records that had been collated for the Tuangamize Minyoo Kenya Imarisha Afya (Swahili for Eradicate Worms in Kenya for Better Health [TUMIKIA]) trial, done in coastal Kenya from 2015 to 2017. In this analysis we estimate the extent of and factors associated with the same individuals not being treated over multiple rounds of MDA, which we term systematic non-treatment. METHODS: We linked the baseline population of the TUMIKIA trial randomly assigned to receive biannual community-wide MDA for soil-transmitted helminthiasis to longitudinal records on receipt of treatment in any of the four treatment rounds of the study. We fitted logistic regression models to estimate the association of non-treatment in a given round with non-treatment in the previous round, controlling for identified predictors of non-treatment. We also used multinomial logistic regression to identify factors associated with part or no treatment versus complete treatment. FINDINGS: 36 327 participants were included in our analysis: 16 236 children aged 2-14 years and 20 091 adults aged 15 years or older. The odds of having no treatment recorded was higher if a participant was not treated during the previous round of MDA (adjusted odds ratio [OR] 3·60, 95% CI 3·08-4·20 for children and 5·58, 5·01-6·21 for adults). For children, school attendance and rural residence reduced the odds of receiving part or no treatment, whereas odds were increased by least poor socioeconomic status and living in an urban or periurban household. Women had higher odds than men of receiving part or no treatment. However, when those with pregnancy or childbirth in the previous 2 weeks were excluded, women became more likely to receive complete treatment. Adults aged 20-25 years were the age group with the highest odds of receiving part (OR 1·41, 95% CI 1·22-1·63) or no treatment (OR 1·81, 95% CI 1·53-2·14). INTERPRETATION: Non-treatment was associated with specific sociodemographic groups and characteristics and did not occcur at random. This finding has important implications for MDA programme effectiveness, the relevance of which will intensify as disease prevalence decreases and infections become increasingly clustered. FUNDING: Bill & Melinda Gates Foundation, Joint Global Health Trials Scheme of the Medical Research Council, UK Department for International Development, Wellcome Trust, Children's Investment Fund Foundation, and London Centre for Neglected Tropical Diseases.


Assuntos
Helmintíase/prevenção & controle , Administração Massiva de Medicamentos/estatística & dados numéricos , Solo/parasitologia , Suspensão de Tratamento/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Helmintíase/epidemiologia , Helmintíase/transmissão , Humanos , Quênia/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Fatores Socioeconômicos , Adulto Jovem
6.
BMJ ; 371: m3734, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087345

RESUMO

OBJECTIVE: To assess whether reshaping of the immune balance by infusion of autologous natural regulatory T cells (nTregs) in patients after kidney transplantation is safe, feasible, and enables the tapering of lifelong high dose immunosuppression, with its limited efficacy, adverse effects, and high direct and indirect costs, along with addressing several key challenges of nTreg treatment, such as easy and robust manufacturing, danger of over immunosuppression, interaction with standard care drugs, and functional stability in an inflammatory environment in a useful proof-of-concept disease model. DESIGN: Investigator initiated, monocentre, nTreg dose escalation, phase I/IIa clinical trial (ONEnTreg13). SETTING: Charité-University Hospital, Berlin, Germany, within the ONE study consortium (funded by the European Union). PARTICIPANTS: Recipients of living donor kidney transplant (ONEnTreg13, n=11) and corresponding reference group trial (ONErgt11-CHA, n=9). INTERVENTIONS: CD4+ CD25+ FoxP3+ nTreg products were given seven days after kidney transplantation as one intravenous dose of 0.5, 1.0, or 2.5-3.0×106 cells/kg body weight, with subsequent stepwise tapering of triple immunosuppression to low dose tacrolimus monotherapy until week 48. MAIN OUTCOME MEASURES: The primary clinical and safety endpoints were assessed by a composite endpoint at week 60 with further three year follow-up. The assessment included incidence of biopsy confirmed acute rejection, assessment of nTreg infusion related adverse effects, and signs of over immunosuppression. Secondary endpoints addressed allograft functions. Accompanying research included a comprehensive exploratory biomarker portfolio. RESULTS: For all patients, nTreg products with sufficient yield, purity, and functionality could be generated from 40-50 mL of peripheral blood taken two weeks before kidney transplantation. None of the three nTreg dose escalation groups had dose limiting toxicity. The nTreg and reference groups had 100% three year allograft survival and similar clinical and safety profiles. Stable monotherapy immunosuppression was achieved in eight of 11 (73%) patients receiving nTregs, while the reference group remained on standard dual or triple drug immunosuppression (P=0.002). Mechanistically, the activation of conventional T cells was reduced and nTregs shifted in vivo from a polyclonal to an oligoclonal T cell receptor repertoire. CONCLUSIONS: The application of autologous nTregs was safe and feasible even in patients who had a kidney transplant and were immunosuppressed. These results warrant further evaluation of Treg efficacy and serve as the basis for the development of next generation nTreg approaches in transplantation and any immunopathologies. TRIAL REGISTRATION: NCT02371434 (ONEnTreg13) and EudraCT:2011-004301-24 (ONErgt11).


Assuntos
Imunossupressão/métodos , Imunossupressores/administração & dosagem , Transplante de Rim/métodos , Linfócitos T Reguladores/transplante , Tacrolimo/administração & dosagem , Adulto , Aloenxertos/imunologia , Estudos de Viabilidade , Feminino , Alemanha , Sobrevivência de Enxerto/imunologia , Humanos , Infusões Intravenosas , Rim/imunologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Resultado do Tratamento , Suspensão de Tratamento
7.
Med Klin Intensivmed Notfmed ; 115(8): 649-653, 2020 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-33001219

RESUMO

The development of intensive care medicine started over more than 50 years. Effective organ system support for ventilation initially and subsequently for circulation, nutrition and renal function resulted in improved outcomes in patients with a variety of severe medical conditions. One of the unfortunate consequences of this development was that it did not allow dying or prolonged the dying process and without the possibility of recovery to a quality of life acceptable to the patients. The early realization of this dilemma ultimately led to broad ethical discussions concerning withholding and withdrawal of curative therapies in intensive care units, and introducing palliative care.


Assuntos
Qualidade de Vida , Assistência Terminal , Cuidados Críticos , Tomada de Decisões , Ética Médica , Humanos , Unidades de Terapia Intensiva , Cuidados Paliativos , Suspensão de Tratamento
8.
Medicine (Baltimore) ; 99(43): e22901, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120841

RESUMO

INTRODUCTION: Chemotherapeutic agents of direct cell damage play a role in initiating thrombotic microangiopathy (TMA), however still being underdiagnosed. Decitabine (DAC) is a pyrimidine analogue of the nucleoside cytidine, which can lead to injury to endothelium. Biopsy-proven DAC-induced kidney injury is rare. PATIENT CONCERNS: A 47-year-old Chinese man with membranous nephropathy presented recurrent edema and acute kidney injury after a 3-day course of low dose DAC infusion because of cyclophosphamide-relating thrombocytopenia. DIAGNOSIS: Laboratory data revealed nephrotic syndrome, hematuria, renal glycosuria and hypokalemia with hyperchloridemia. Renal pathological findings revealed TMA with secondary glomerular crescents formation (28%), partial foot process effacement and acute tubular necrosis. A diagnosis of DAC-induced renal TMA was considered. INTERVENTIONS: As DAC had been timely discontinued before admission, the patient only received supportive treatment. OUTCOMES: The patient achieved rapid remission of acute kidney injury after DAC withdrawal, and his serum creatinine further decreased to normal level after 6 months. CONCLUSION: Careful monitoring of renal function especially serum creatinine should be emphasized during DAC treatment.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Decitabina/efeitos adversos , Glomérulos Renais/patologia , Rim/patologia , Microangiopatias Trombóticas/induzido quimicamente , Lesão Renal Aguda/etiologia , Tratamento Conservador , Ciclofosfamida/efeitos adversos , Glomerulonefrite Membranosa/patologia , Humanos , Imunossupressores/efeitos adversos , Rim/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Trombocitopenia/induzido quimicamente , Suspensão de Tratamento
9.
Medicine (Baltimore) ; 99(43): e22924, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120846

RESUMO

RATIONALE: Polymyxin B has been used to treat extensively drug-resistant gram-negative bacteria and shown a better antibacterial effect in the clinic at present. Meanwhile, polymyxin B is associated with several adverse effects. However, there is a lack of awareness that polymyxin B can cause rhabdomyolysis. In this study, we firstly report a case of polymyxin B-induced rhabdomyolysis during antiinfection therapy. PATIENT CONCERNS: A 70-year-old woman suffering from rheumatic heart disease underwent aortic and mitral valve replacement at our institute. Subsequently, she developed bacteremia and pneumonia caused by extensively drug resistance-acinetobacter baumannii. Polymyxin B was administered for 5 days. During treatment, the patient complained of muscle pain and limb weakness, and her serum creatine phosphokinase and myoglobin levels rose. DIAGNOSIS: The clinical symptoms and laboratory examination confirmed rhabdomyolysis, and polymyxin B-induced rhabdomyolysis was considered. INTERVENTION: We ceased polymyxin B treatment and monitored the patient daily. OUTCOMES: Serum creatine phosphokinase levels returned to normal, myoglobin levels decreased, and muscle pain was significantly alleviated after cessation of polymyxin B. We identified this as a case of polymyxin B-induced rhabdomyolysis. LESSONS: Here, we report the first reported case of rhabdomyolysis induced by polymyxin B administration. The awareness of rare adverse reaction helps ensure the clinical safety of polymyxin B treatment.


Assuntos
Antibacterianos/efeitos adversos , Polimixina B/efeitos adversos , Rabdomiólise/induzido quimicamente , Acinetobacter baumannii/isolamento & purificação , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Conscientização , Bacteriemia/tratamento farmacológico , Creatina Quinase/sangue , Feminino , Humanos , Debilidade Muscular/etiologia , Mialgia/etiologia , Mioglobina/sangue , Pneumonia/tratamento farmacológico , Pneumonia/microbiologia , Polimixina B/administração & dosagem , Polimixina B/uso terapêutico , Rabdomiólise/diagnóstico , Suspensão de Tratamento
10.
Value Health ; 23(11): 1423-1426, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33127011

RESUMO

It is expected that the coronavirus disease 2019 (COVID-19) pandemic will leave large deficits in the budgets of many jurisdictions. Funding for other treatments, in particular new treatments, may become more constrained than previously expected. Therefore, a robust health technology assessment (HTA) system is vital. Many clinical trials carried out during the pandemic may have been temporarily halted, while others may have had to change their protocols. Even trials that continue as normal may experience external changes as other aspects of the healthcare service may not be available to the patients in the trial, or the patients themselves may contract COVID-19. Consequently, many limitations are likely to arise in the provision of robust HTAs, which could have profound consequences on the availability of new treatments. Therefore, the National Centre for Pharmacoeconomics Review Group wishes to discuss these issues and make recommendations for applicants submitting to HTA agencies, in ample time for these HTAs to be prepared and assessed. We discuss how the pandemic may affect the estimation of the treatment effect, costs, life-years, utilities, discontinuation rates, and methods of evidence synthesis and extrapolation. In particular, we note that trials conducted during the pandemic will be subject to a higher degree of uncertainty than before. It is vital that applicants clearly identify any parameters that may be affected by the pandemic. These parameters will require considerably more scenario and sensitivity analyses to account for this increase in uncertainty.


Assuntos
Comitês Consultivos , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Avaliação da Tecnologia Biomédica , Betacoronavirus , Orçamentos , Infecções por Coronavirus/tratamento farmacológico , Farmacoeconomia , Humanos , Pneumonia Viral/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento , Suspensão de Tratamento
12.
PLoS One ; 15(9): e0239253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32946479

RESUMO

PURPOSE: To examine the psychological impact of fertility treatment suspensions resulting from the COVID-19 pandemic and to clarify psychosocial predictors of better or worse mental health. METHODS: 92 women from Canada and the United States (ages 20-45 years) whose fertility treatments had been cancelled were recruited via social media. Participants completed a battery of questionnaires assessing depressive symptoms, perceived mental health impact, and change in quality of life related to treatment suspensions. Potential predictors of psychological outcomes were also examined, including several personality traits, aspects of social support, illness cognitions, and coping strategies. RESULTS: 52% of respondents endorsed clinical levels of depressive symptoms. On a 7-point scale, participants endorsed a significant decline in overall quality of life (M(SD) = -1.3(1.3), p < .0001) as well as a significant decline in mental health related to treatment suspensions on a scale from -5 to +5 (M(SD) = -2.1(2.1), p < .001). Several psychosocial variables were found to positively influence these outcomes: lower levels of defensive pessimism (r = -.25, p < .05), greater infertility acceptance (r = .51, p < .0001), better quality social support (r = .31, p < .01), more social support seeking (r = .35, p < .001) and less avoidance of infertility reminders (r = -.23, p = .029). CONCLUSION: Fertility treatment suspensions have had a considerable negative impact on women's mental health and quality of life. However, these findings point to several protective psychosocial factors that can be fostered in the future to help women cope.


Assuntos
Betacoronavirus , Infecções por Coronavirus/psicologia , Infertilidade/tratamento farmacológico , Pneumonia Viral/psicologia , Suspensão de Tratamento , Adulto , Canadá/epidemiologia , Feminino , Fármacos para a Fertilidade Feminina/provisão & distribução , Fármacos para a Fertilidade Feminina/uso terapêutico , Humanos , Infertilidade/psicologia , Saúde Mental , Pessoa de Meia-Idade , Pandemias , Qualidade de Vida/psicologia , Inquéritos e Questionários , Estados Unidos/epidemiologia , Adulto Jovem
13.
G Ital Cardiol (Rome) ; 21(10): 750-756, 2020 Oct.
Artigo em Italiano | MEDLINE | ID: mdl-32968307

RESUMO

BACKGROUND: During the COVID-19 pandemic, non-urgent outpatient activities were temporarily suspended. The aim of this study was to assess the impact of this measure on the management of the heart failure outpatient clinic at our institution. METHODS: We analyzed the clinical outcome of 110 chronic heart failure patients (mean age 73 ± 9 years) whose follow-up visit had been delayed. RESULTS: At their last visit before the lockdown, 80.9% was in NYHA class II, had an ejection fraction of 37 ± 7%, and B-type natriuretic peptide level was moderately elevated (266 ± 138 pg/ml). All patients received loop diuretics, 97.2% beta-blockers, 64.9% an aldosterone antagonist, 60.9% sacubitril/valsartan (S/V), and 72.2% of the remaining patients were on angiotensin-converting enzyme inhibitor or valsartan therapy. Patients were contacted by phone during and at the end of the lockdown period to fix a new appointment and underwent a structured interview to assess their clinical conditions and ongoing therapy and to verify whether they had contracted SARS-CoV-2 infection. Twelve patients (13.2%) contracted COVID-19. None was hospitalized for worsening heart failure or reported defibrillator shocks and none changed autonomously the prescribed therapy. Overall, 75% of patients reported stable or improved general well-being from the last in-person visit, while 25% described subjective worsening due to the social effect of the pandemic. Unchanged body weight and blood pressure values were reported by 86% and 78.4% of patients, respectively. Lower blood pressure values compared to baseline were recorded in 15.2% of patients on conventional renin-angiotensin system inhibition vs 21% of those on S/V, one of whom had to down-titrate S/V for persistent but asymptomatic hypotension; 4 patients up-titrated S/V to 200 mg/day following phone indications. CONCLUSIONS: Cancellation of scheduled follow-up visits during 3 months did not have significant negative effects in a cohort of stable patients with chronic heart failure on optimized medical therapy. Telephone support was effective in keeping connections with the patients during the lockdown, allowing appropriate management and implementation of drug therapy. In particular, patients who received S/V were not affected by delays in scheduled visits, confirming the tolerability and safety of this novel therapy in terms of both clinical and biohumoral parameters.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Insuficiência Cardíaca/tratamento farmacológico , Pneumonia Viral/epidemiologia , Quarentena , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Instituições de Assistência Ambulatorial , Aminobutiratos/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Doença Crônica , Continuidade da Assistência ao Paciente/organização & administração , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/psicologia , Assistência à Saúde , Progressão da Doença , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/psicologia , Humanos , Itália/epidemiologia , Masculino , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Peptídeo Natriurético Encefálico/sangue , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/psicologia , Recidiva , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Volume Sistólico , Telefone , Tetrazóis/uso terapêutico , Suspensão de Tratamento
14.
J Bras Nefrol ; 42(2 suppl 1): 47-48, 2020 Aug 26.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32877500

RESUMO

This position statement of the Department of Hypertension of the Brazilian Society of Nephrology (SBN) addresses the controversy surrounding the use or suspension/replacement of the renin-angiotensin-aldosterone system blockers (particularly inhibitors of the angiotensin-converting enzyme or angiotensin II AT1 receptor blockers) prophylactically in individuals using these drugs, due to the possibility of allegedly worsening the prognosis of hypertensive patients infected with SARS-CoV-2. The SBN Hypertension Department recommends individualizing treatment and maintaining these medications until better scientific evidence is available.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Hipertensão/tratamento farmacológico , Pneumonia Viral/epidemiologia , Brasil , Humanos , Nefrologia , Pandemias , Suspensão de Tratamento
15.
Medicine (Baltimore) ; 99(39): e22301, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991436

RESUMO

RATIONALE: Cardiotoxicity related to osimertinib, including cardiac failure, QT prolongation, and atrial fibrillation, has been reported as an extremely rare incidence in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the occurrence of osimertinib-induced cardiomyopathy. PATIENT CONCERNS: A 76-year old woman was treated with afatinib (40 mg/day) as the 1st line treatment due to recurrence after surgical resection for pulmonary adenocarcinoma. However, she experienced recurrence with positive T790 M, and osimertinib (80 mg/day) was administered as the 2nd line therapy. DIAGNOSIS: Four months after osimertinib initiation, she complained of fever and progressive dyspnea, and a diagnostic endomyocardial biopsy confirmed non-specific cardiomyopathy, indicating osimertinib-induced cardiomyopathy. INTERVENTIONS AND OUTCOMES: She was treated with furosemide, carvedilol, and enalapril, and her cardiac function, her symptoms, and condition improved 3 weeks after the withdrawal of osimertinib. LESSONS: Physicians should be alert of the cardiomyopathy-causing potential of osimertinib in advanced NSCLC patients.


Assuntos
Acrilamidas/efeitos adversos , Compostos de Anilina/efeitos adversos , Cardiomiopatias/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Acrilamidas/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Afatinib/uso terapêutico , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Anilina/uso terapêutico , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/fisiopatologia , Carvedilol/uso terapêutico , Diuréticos/uso terapêutico , Enalapril/uso terapêutico , Feminino , Furosemida/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Recidiva , Resultado do Tratamento , Suspensão de Tratamento
16.
Crit Care ; 24(1): 536, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867803

RESUMO

BACKGROUND: In critically ill children, omitting early use of parenteral nutrition (late-PN versus early-PN) reduced infections, accelerated weaning from mechanical ventilation, and shortened PICU stay. We hypothesized that fasting-induced ketogenesis mediates these benefits. METHODS: In a secondary analysis of the PEPaNIC RCT (N = 1440), the impact of late-PN versus early-PN on plasma 3-hydroxybutyrate (3HB), and on blood glucose, plasma insulin, and glucagon as key ketogenesis regulators, was determined for 96 matched patients staying ≥ 5 days in PICU, and the day of maximal 3HB-effect, if any, was identified. Subsequently, in the total study population, plasma 3HB and late-PN-affected ketogenesis regulators were measured on that average day of maximal 3HB effect. Multivariable Cox proportional hazard and logistic regression analyses were performed adjusting for randomization and baseline risk factors. Whether any potential mediator role for 3HB was direct or indirect was assessed by further adjusting for ketogenesis regulators. RESULTS: In the matched cohort (n = 96), late-PN versus early-PN increased plasma 3HB throughout PICU days 1-5 (P < 0.0001), maximally on PICU day 2. Also, blood glucose (P < 0.001) and plasma insulin (P < 0.0001), but not glucagon, were affected. In the total cohort (n = 1142 with available plasma), late-PN increased plasma 3HB on PICU day 2 (day 1 for shorter stayers) from (median [IQR]) 0.04 [0.04-0.04] mmol/L to 0.75 [0.04-2.03] mmol/L (P < 0.0001). The 3HB effect of late-PN statistically explained its impact on weaning from mechanical ventilation (P = 0.0002) and on time to live PICU discharge (P = 0.004). Further adjustment for regulators of ketogenesis did not alter these findings. CONCLUSION: Withholding early-PN in critically ill children significantly increased plasma 3HB, a direct effect that statistically mediated an important part of its outcome benefit.


Assuntos
Corpos Cetônicos/biossíntese , Nutrição Parenteral , Suspensão de Tratamento , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Resultado do Tratamento
17.
PLoS Pathog ; 16(8): e1008791, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32841299

RESUMO

During antiretroviral therapy (ART) that suppresses HIV replication to below the limit-of-quantification, virions produced during ART can be detected at low frequencies in the plasma, termed residual viremia (RV). We hypothesized that a reservoir of HIV-infected cells actively produce and release virions during ART that are potentially infectious, and that following ART-interruption, these virions can complete full-cycles of replication and contribute to rebound viremia. Therefore, we studied the dynamics of RV sequence variants in 3 participants who initiated ART after ~3 years of infection and were ART-suppressed for >6 years prior to self-initiated ART-interruptions. Longitudinal RV C2V5env sequences were compared to sequences from pre-ART plasma, supernatants of quantitative viral outgrowth assays (QVOA) of cells collected during ART, post-ART-interruption plasma, and ART-re-suppression plasma. Identical, "putatively clonal," RV sequences comprised 8-84% of sequences from each timepoint. The majority of RV sequences were genetically similar to those from plasma collected just prior to ART-initiation, but as the duration of ART-suppression increased, an increasing proportion of RV variants were similar to sequences from earlier in infection. Identical sequences were detected in RV over a median of 3 years (range: 0.3-8.2) of ART-suppression. RV sequences were identical to pre-ART plasma viruses (5%), infectious viruses induced in QVOA (4%) and rebound viruses (5%) (total n = 21/154 (14%) across the 3 participants). RV sequences identical to ART-interruption "rebound" sequences were detected 0.1-7.4 years prior to ART-interruption. RV variant prevalence and persistence were not associated with detection of the variant among rebound sequences. Shortly after ART-re-suppression, variants that had been replicating during ART-interruptions were detected as RV (n = 5). These studies show a dynamic, virion-producing HIV reservoir that contributes to rekindling infection upon ART-interruption. The persistence of identical RV variants over years suggests that a subpopulation of HIV-infected clones frequently or continuously produce virions that may resist immune clearance; this suggests that cure strategies should target this active as well as latent reservoirs.


Assuntos
Antirretrovirais/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Plasma/virologia , Viremia/epidemiologia , Replicação Viral , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Incidência , Plasma/efeitos dos fármacos , Plasma/imunologia , Estudos Retrospectivos , Estados Unidos/epidemiologia , Carga Viral , Viremia/virologia , Latência Viral , Suspensão de Tratamento
18.
Am Surg ; 86(8): 933-936, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32856933

RESUMO

BACKGROUND: Several studies have described the population of adult trauma patients who undergo withdrawal of life-sustaining treatments (WLST); however, no study has looked specifically at trauma patients who undergo WLST following surgery. METHODS: This was a retrospective chart review of all trauma patients who underwent surgery at our trauma center between January 1 and December 31, 2017. Demographics were collected along with injury patterns and advance directives. Charts of all patients who died or who were discharged to hospice were analyzed to determine whether WLST occurred. Statistics included Fisher's exact test and Mann-Whitney U test. RESULTS: Three thousand and twenty-five adult trauma patients received care and 1495 (49.4%) had operations. Thirty (2.0%) patients underwent WLST, 15 (50.0%) of whom died in the hospital and 15 (50.0%) of whom were discharged to hospice. Twenty-six (86.7%) patients had a palliative care consult and 12 (40.0%) had prior advance directives. The most common injuries were femur fractures and subdural hematomas. Adjusting for age, white race, and age-adjusted CCI, femur fracture patients had, on average, 8.8 more hours between presentation and surgery (95% CI 2.1-15.4, P = .01) and 39 fewer hours between surgery and WLST (95% CI -107-29, P = .26) than traumatic brain injury patients. DISCUSSION: The short time between surgery and WLST in this cohort of patients may demonstrate that surgery was not aligned with patients' goals of care. A patient-centered approach that includes surgeon-driven palliative care discussions may help avoid nonbeneficial surgery in the last few days of life.


Assuntos
Cuidados Paliativos/estatística & dados numéricos , Conforto do Paciente/estatística & dados numéricos , Assistência Centrada no Paciente/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios , Suspensão de Tratamento/estatística & dados numéricos , Ferimentos e Lesões/terapia , Adulto , Diretivas Antecipadas/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Cuidados Paliativos na Terminalidade da Vida/estatística & dados numéricos , Humanos , Masculino , Futilidade Médica , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Estudos Retrospectivos , Ferimentos e Lesões/mortalidade
20.
Pediatrics ; 146(Suppl 1): S3-S8, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32737225

RESUMO

One of the earliest controversies in the modern history of bioethics was known at the time as "the Hopkins Mongol case," involving an infant with Trisomy 21 and duodenal atresia whose parents declined to consent to surgery. Fluids and feeding were withheld, and the infant died of dehydration after 15 days. The child's short life had a profound impact on the author's career and that of several others and ultimately led to changes in the care of children and adults with disabilities and the way difficult end-of-life decisions are made in US hospitals today. It also contributed to the growth of the modern bioethics movement and scholarship focused on pediatric bioethics issues.


Assuntos
Temas Bioéticos , Tomada de Decisão Clínica/ética , Síndrome de Down/terapia , Pediatria/ética , Suspensão de Tratamento/ética , Comitês Consultivos/ética , Temas Bioéticos/história , Temas Bioéticos/legislação & jurisprudência , Crianças com Deficiência/legislação & jurisprudência , Síndrome de Down/história , Atresia Esofágica/história , Atresia Esofágica/terapia , Fundações , História do Século XX , Humanos , Recém-Nascido , Consentimento dos Pais/ética , Consentimento dos Pais/legislação & jurisprudência , Pais , Pediatria/legislação & jurisprudência , Assistência Terminal/ética , Suspensão de Tratamento/legislação & jurisprudência
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