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1.
AIDS ; 33(14): 2197-2203, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31689263

RESUMO

OBJECTIVES: Drug-drug interactions limit current antiretroviral treatment options for HIV-infected children with tuberculosis (TB). Rifampicin (RIF) induces UDP-glucuronosyltransferase activity, accelerating the clearance of raltegravir (RAL). We sought to establish an optimal and well tolerated dose of RAL when administered with RIF to HIV and TB co-infected children. DESIGN: P1101 is a phase I/II open-label dose-finding study of RAL with RIF for children 2 to less than 12 years of age beginning treatment for HIV and active TB. SETTING: Four sites in South Africa. METHODS: Chewable RAL was given at 12 mg/kg per dose twice daily (twice the usual pediatric dose) with two nucleoside reverse transcriptase inhibitors. Intensive RAL pharmacokinetic sampling was conducted 5 to 8 days after antiretroviral therapy was initiated; a fourth antiretroviral agent was then added. RESULTS: Children were recruited into two age-defined groups: cohort 1 (2 to <6 years old) and cohort 2 (6 to <12 years old). Pharmacological targets [geometric mean (GM) AUC12 h of 14-45 µmol/l h and GM C12 h ≥75 nmol/l) were reached in both cohort 1 (28.8 µmol/l h and 229 nmol/l) and cohort 2 (38.8 µmol/l h and 228 nmol/l). The RAL-based ART was well tolerated by most participants: one participant discontinued treatment because of grade 4 hepatitis that was possibly treatment-related. At week 8, 22 of 24 participants (92%) had HIV RNA concentrations below 400 copies/ml; 19 of 24 (79%) were below 50 copies/ml. CONCLUSION: Giving 12 mg/kg twice daily of the chewable RAL formulation achieved pharmacokinetic targets safely in HIV-infected children receiving RIF for TB.

2.
N Engl J Med ; 381(14): 1333-1346, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31577875

RESUMO

BACKGROUND: The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown. METHODS: In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years. RESULTS: A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], -4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, -0.39; 95% CI, -1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, -0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9). CONCLUSIONS: The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038.).


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Isoniazida/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Tuberculose/prevenção & controle , Adolescente , Adulto , Antituberculosos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Isoniazida/efeitos adversos , Testes de Função Hepática , Período Pós-Parto , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Adulto Jovem
3.
FP Essent ; 474: 20-27, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30427649

RESUMO

Menopause is the cessation of menstruation due to loss of ovarian function and is diagnosed retrospectively after 12 consecutive months of amenorrhea. The average age of onset in the United States is 51 years but symptoms can be present for many years before and after. Vasomotor and genitourinary symptoms are the most common. Hormone replacement therapy (HRT) is the most effective management. Given the possible risks of cardiovascular disease and breast cancer, recommendations for HRT after the Women's Health Initiative study are to limit HRT to the lowest dose and shortest duration to relieve symptoms. Based on more recent data, women younger than 60 years and less than 10 years from menopause onset appear to be at lower risk of these factors when initiating HRT. Dosing, type of HRT, administration route, and duration of use are individualized. Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, gabapentin, and clonidine are alternative nonhormonal options with high-quality evidence supporting their use for symptom relief. However, these management options are less effective than HRT. Local vaginal therapy is effective and recommended for management of isolated vulvovaginal symptoms. Decisions to discontinue HRT should be based on symptoms and risk factors, not age.


Assuntos
Menopausa , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Idoso , Clonidina/uso terapêutico , Doenças do Sistema Endócrino , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Feminino , Gabapentina/uso terapêutico , Terapia de Reposição Hormonal/métodos , Fogachos/tratamento farmacológico , Fogachos/etiologia , Fogachos/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Captação de Serotonina/uso terapêutico
4.
FP Essent ; 474: 28-32, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30427650

RESUMO

Incidentally discovered adrenal masses, referred to as adrenal incidentalomas, are fairly common given the routine use of imaging as part of clinical care in a variety of settings. Adrenal incidentalomas most frequently are benign and hormonally inactive tumors. However, approximately 11% to 15% are hormonally active, which can lead to diagnosis of clinically relevant conditions that affect morbidity and mortality. Thus, all adrenal incidentalomas should be tested for production of hormones at initial diagnosis. A 1-mg dexamethasone suppression test is the initial screening test. Patients then should be referred for appropriate treatment. Among the adrenal mass subtypes, pheochromocytomas are associated with the highest risk of mortality. Every effort should be made to exclude the presence of these tumors. Patients with hypertension and adrenal incidentalomas should be evaluated for aldosterone excess with an aldosterone to renin ratio. Primary malignancy represents a low percentage of adrenal incidentalomas. A minority of adrenal malignancies are primary adrenocortical tumors, which are associated with a poor prognosis and for which management often is palliative.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Achados Incidentais , Neoplasias das Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Idoso , Aldosterona/sangue , Biópsia , Catecolaminas/sangue , Catecolaminas/urina , Dexametasona/sangue , Doenças do Sistema Endócrino , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Metanefrina/sangue , Metanefrina/urina , Renina/sangue , Tomógrafos Computadorizados
5.
FP Essent ; 474: 33-38, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30427651

RESUMO

Interest in slowing or reversing the process of aging continues to grow and has encouraged the growth of an entire anti-aging industry. However, there is a dearth of data based on randomized trials in humans to support proposed therapies to address the various complex processes involved in aging. Hormonal therapies, in particular, have little data to support safe use and are associated with some degree of risk. Experimental data in animal models suggest possible molecular targets but their use in clinical medicine is far in the future. Observational data guide the current recommendations to maintain a healthy lifestyle, including consumption of a healthful diet and achieving adequate sleep, toward the goal of slowing the aging process. Patients may ask their physicians to offer opinions about treatments they hope will increase their health span. To counsel patients effectively, it is important for physicians to understand the basic principles of anti-aging science. Maintenance of supportive, nonjudgmental therapeutic relationships with patients is critical to avoid harmful and costly treatments while trying to present reliable evidence for available anti-aging therapies.


Assuntos
Envelhecimento/fisiologia , Antioxidantes , Suplementos Nutricionais , Estilo de Vida Saudável/fisiologia , Terapia de Reposição Hormonal , Homeostase do Telômero/fisiologia , Idoso , Envelhecimento/efeitos dos fármacos , Animais , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/metabolismo , Sistema Endócrino/fisiologia , Feminino , Humanos , Masculino
6.
J Prim Health Care ; 3(3): 210-7, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21892423

RESUMO

INTRODUCTION: Information about the impact of addiction on New Zealand (NZ) families is scarce. A good understanding of the nature and extent of family problems is essential to help families become more resilient and minimise the consequences. This study aimed to explore experiences of NZ families living with addiction, identify impacts on non-addicted family members, their coping strategies and barriers to help seeking. METHODS: Literature and key stakeholder interviews informed the development of an interview schedule for 29 family participants recruited through health and social services. Interviews were recorded for analysis of central themes and critical elements that underpin those. Key stakeholders and informal informants were again consulted to discuss findings and interpretation. FINDINGS: Addiction has widespread effects on NZ families. The coping strategies described by the participants in this project lacked the positive connotations of resilience, namely positive adaptation under significant adversity. CONCLUSION: Family impacts of addiction are complex, and similar family problems arise regardless of the substance(s) involved. This small exploratory study indicates that the implications for NZ families deserve further investigation. Future research is also required to further characterise the impact of behavioural addictions on families, addiction in particular ethnic groupings and the implications of the findings for clinical practice, other social and health services, and for public health and social policy.


Assuntos
Adaptação Psicológica , Família/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Nova Zelândia , Resiliência Psicológica , Apoio Social , Serviço Social
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