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1.
Rev Med Suisse ; 15(666): 1802-1806, 2019 Oct 09.
Artigo em Francês | MEDLINE | ID: mdl-31599521

RESUMO

Discovered in 1977, Hepatitis D is the most severe form of chronic hepatitis, with rapid development of cirrhosis, hepatic failure and hepatocellular carcinoma. Despite all this, it is still largely underdiagnosed and there is no standardised management. The current treatment options are scarce and bear frequent side-effects, but the early diagnosis and an optimal follow-up with identification of the patients suitable for treatment improve significantly their survival rate and quality of life. Moreover, new promising treatments are entering phase III trials and offer new perspectives for our patients.


Assuntos
Hepatite D/terapia , Carcinoma Hepatocelular/virologia , Ensaios Clínicos Fase III como Assunto , Hepatite D/diagnóstico , Humanos , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Taxa de Sobrevida
2.
Rinsho Ketsueki ; 60(9): 1100-1107, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597833

RESUMO

In 2017, The British Society of Haematology published new guidelines for the diagnosis and management of autoimmune hemolytic anemia (AIHA). Usually this is diagnosed using a combination of clinical and laboratory findings of hemolysis using the direct antiglobulin test (DAT). The revised guidelines propose several steps to evaluate and diagnose patients with unexplained hemolysis and a negative DAT, and they recommend screening for cold agglutinin disease (CAD) using a direct agglutination test (DAggT) before evaluating the cold agglutinin titer. Rituximab is becoming the preferred second-line choice for steroid-refractory warm AIHA and the first-line choice for primary CAD. Rituximab is an off-label drug for use in AIHA treatment in Japan, but in future will be used as standard therapy. Anti-C1s antibody is a new drug for CAD that has entered phase 3 trials.


Assuntos
Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/terapia , Testes de Aglutinação , Ensaios Clínicos Fase III como Assunto , Hemólise , Humanos , Uso Off-Label , Guias de Prática Clínica como Assunto , Rituximab/uso terapêutico
3.
Rinsho Ketsueki ; 60(9): 1176-1185, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31597841

RESUMO

Although the Janus kinase (JAK) inhibitor ruxolitinib has long been the only drug licensed for treatment of the classic Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms, years of drug development efforts have begun to bear fruit with the recent approval of a novel monopegylated interferon alfa-2b, ropeginterferon alfa, for patients with polycythemia vera without symptomatic splenomegaly in Europe. Several newer JAK inhibitors (fedratinib, pacritinib, momelotinib) have shown activity in phase 3 trials in patients with myelofibrosis but have, for various reasons, not yet received regulatory approval; all these agents, however, remain in active clinical development. Many other agents with diverse mechanisms of action are being explored in clinical trials in patients with myelofibrosis, both as single agents and in combination with ruxolitinib. Besides splenomegaly and symptoms, improvement of anemia has become a new focus of drug development in myelofibrosis. Ruxolitinib appears promising also in chronic neutrophilic leukemia, where mutations in CSF3R are common. Pemigatinib, a potent and selective inhibitor of fibroblast growth factor receptor (FGFR), has shown impressive efficacy in a small registration-directed trial in patients with FGFR1-rearranged myeloid/lymphoid neoplasms. Finally, avapritinib, a highly potent and selective inhibitor of KITD816V, has demonstrated unprecedented response rates in patients with advanced systemic mastocytosis.


Assuntos
Transtornos Mieloproliferativos/terapia , Mielofibrose Primária/terapia , Ensaios Clínicos Fase III como Assunto , Europa (Continente) , Humanos , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Policitemia Vera , Polietilenoglicóis/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Esplenomegalia
4.
Cancer Radiother ; 23(6-7): 496-499, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471251

RESUMO

Stereotactic radiotherapy of oligometastases, mono- or hypofractionated, represents a fundamental change in the practice of the specialty as it was developed for a century. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Four main phase II and III trials are underway in France. Future research concerns the association of stereotactic radiotherapy with immunotherapy or different conventional chemotherapy protocols, the identification of the best clinical presentations, and optimization of fractionation and biological dose for poor prognosis localizations.


Assuntos
Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Neoplasias/radioterapia , Radiocirurgia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Terapia Combinada/métodos , Previsões , França , Humanos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Metástase Neoplásica , Neoplasias/patologia , Neoplasias/terapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
5.
Cancer Radiother ; 23(6-7): 503-509, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471253

RESUMO

There are many treatment options for localized prostate cancers, including active surveillance, brachytherapy, external beam radiotherapy, and radical prostatectomy. Quality of life remains a primary objective in the absence of superiority of one strategy over another in terms of specific survival with similar long-term biochemical control rates. Despite a significant decrease in digestive and urinary toxicities thanks to IMRT and IGRT, external radiotherapy remains a treatment that lasts approximately 2 months or 1.5 months, when combined with a brachytherapy boost. Given the specific radiosensitivity of this tumor, several randomized studies have shown that a hypofractionated scheme is not inferior in terms of biochemical control and toxicities, allowing to divide the number of fractions by a factor 2 to 8. Given that SBRT becomes a validated therapeutic option for a selected population of patients with localized prostate cancer, extreme hypofractionation is becoming a strong challenger of conventional external radiotherapy or brachytherapy.


Assuntos
Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Hipofracionamento da Dose de Radiação , Braquiterapia , Ensaios Clínicos Fase III como Assunto , Estudos de Equivalência como Asunto , Humanos , Irradiação Linfática/métodos , Masculino , Seleção de Pacientes , Cuidados Pós-Operatórios , Qualidade de Vida , Hipofracionamento da Dose de Radiação/normas , Tolerância a Radiação , Radioterapia Guiada por Imagem , Radioterapia de Intensidade Modulada , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Drugs ; 79(12): 1337-1348, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31372959

RESUMO

Manufacturing influenza virus vaccines using a mammalian cell line rather than embryonated chicken eggs may carry certain advantages. A quadrivalent inactivated influenza virus vaccine produced using the Madin Darby canine kidney cell line has been approved in the EU (Flucelvax® Tetra) and USA (Flucelvax Quadrivalent®; QIVc hereafter) for the prevention of influenza in adults and children. The clinical development of QIVc has built upon that of a cell-based trivalent influenza virus vaccine (TIVc) manufactured using the same processes; the additional influenza B strain contained in QIVc reduces the risk of the strain in the vaccine not matching that in circulation. Pivotal phase III clinical trials in adult and paediatric participants have demonstrated the immunogenicity of QIVc to be noninferior to that of TIVc formulations against shared strains and superior against the influenza B strain absent from each TIVc formulation. Protective efficacy data for TIVc is considered foundational for QIVc and, in a phase III clinical trial, TIVc was effective in protecting adults against antigenically matched influenza strains. Large real-world studies from the 2017/2018 US influenza season further support the prophylactic effectiveness of QIVc, with possible benefits over egg-based vaccines. QIVc was generally well tolerated in clinical trials. In adult and paediatric QIVc recipients, the most common solicited adverse reactions were injection site pain and headache. Reactogenicity was comparable to that of TIVc; no safety signals unique to QIVc emerged. Through circumventing concerns around egg adaptation, QIVc has the potential to be more effective than currently available egg-based quadrivalent vaccines.


Assuntos
Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adulto , Animais , Criança , Ensaios Clínicos como Assunto , Ensaios Clínicos Fase III como Assunto , Cães , Aprovação de Drogas , Europa (Continente) , Humanos , Vacinas contra Influenza/efeitos adversos , Células Madin Darby de Rim Canino , Estados Unidos , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia
8.
Cancer Radiother ; 23(6-7): 572-575, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31422001

RESUMO

Along with the surgeon, the gastroenterologist and the general practitioner, the radiation oncologist is involved in the follow-up of patients with rectal cancer treated by radiation. Post-treatment follow-up is recommended by major professional expert groups and consists of clinical examination, monitoring of carcinoembryonic antigen, colonoscopy and computed tomography of the abdomen and pelvis. Three recent large phase III randomized trials demonstrated a lack of survival benefit from intensive follow-up strategies in comparison with minimal follow-up. However, a follow-up program is not only important for the detection of an early disease relapse but it can be also used for the identification and the management of long-term toxicity and sequalae related to rectal cancer treatment.


Assuntos
Assistência ao Convalescente/métodos , Recidiva Local de Neoplasia/diagnóstico , Segunda Neoplasia Primária/prevenção & controle , Papel do Médico , Radio-Oncologistas , Neoplasias Retais/diagnóstico , Neoplasias Retais/radioterapia , Ensaios Clínicos Fase III como Assunto , Feminino , Seguimentos , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Expert Rev Pharmacoecon Outcomes Res ; 19(5): 505-508, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31379219

RESUMO

Introduction: The analysis was conducted to assess a cost-efficacy analysis of new antiemetic drugs (netupitant plus palonosetron (NEPA)) for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in highly and moderately emetogenic chemotherapy for cancer treatment. Areas covered:The present evaluation was restricted to pivotal phase III randomized controlled trials (RCTs) of NEPA versus (vs.) palonosetron for the prophylaxis of CINV. We calculated the pharmacological costs necessary to get the benefit in complete response (CR), for each trial. Our analysis evaluated 2 RCTs, including 1720 patients. Referring to both highly and moderately emetogenic chemotherapy, NEPA plus DEX was economic superior to palonosetron (PALO) plus DEX, with 13 312 € and 7885 € gain in medical costs every 100 patients treated, respectively. The cost-effectiveness ratios (CERs) (€/CR) in highly emetoge nic risk were 1.24 and 13.23 for the NEPA and PALO group, respectively and 1.49 and 15.20 for the same groups in moderately emetogenic risk. The incremental cost-effectiveness ratio (ICER) between the groups was 1016.18 €/CR and 1024.03 €/CR in highly and moderately emetogenic risk, respectively. Expert opinion:The combination of NEPA plus DEX is cost-effective for preventing CINV in highly and moderately (AC-based) emetogenic cancer treatment.


Assuntos
Antieméticos/administração & dosagem , Palonossetrom/administração & dosagem , Piridinas/administração & dosagem , Antieméticos/economia , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Análise Custo-Benefício , Dexametasona/administração & dosagem , Dexametasona/economia , Humanos , Náusea/induzido quimicamente , Náusea/economia , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Palonossetrom/economia , Piridinas/economia , Ensaios Clínicos Controlados Aleatórios como Assunto , Vômito/induzido quimicamente , Vômito/economia , Vômito/prevenção & controle
10.
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.
Zhonghua Gan Zang Bing Za Zhi ; 27(6): 415-419, 2019 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-31357755

RESUMO

Main indication of nonalcoholic steatohepatitis (NASH) progression is hepatic fibrosis. The extent of fibrosis correlates negatively with long-term comorbidity and survival of NASH patients. Clinical screening for hepatic fibrosis extent higher than F2 is a main criterion for high risk NASH patients. Currently on-going phase III clinical trials for potential pharmacotherapeutics recruit NASH patients with F2-3, and whether tested pharmacotherapeutics block hepatic fibrosis is one of main end-points for assessment of clinical efficacy. Therefore, understanding molecular mechanisms and identifying potential targets are critical for intervention of NASH progression.


Assuntos
Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Fibrose , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Cirrose Hepática/terapia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/terapia
12.
Drugs ; 79(12): 1349-1354, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31301033

RESUMO

Volanesorsen (Waylivra®), an antisense oligonucleotide inhibitor of apolipoprotein CIII (apoCIII) mRNA, is being developed by Ionis Pharmaceuticals through its subsidiary company, Akcea Therapeutics, to treat familial chylomicronemia syndrome (FCS), hypertriglyceridemia and familial partial lipodystrophy (FPL). In May 2019, volanesorsen was approved in the EU for the treatment of adult patients with FCS based on positive results from the multinational, phase III APPROACH and COMPASS studies. Other clinical trials are ongoing to assess its utility in hypertriglyceridemia, FPL and partial lipodystrophy. This article summarizes the milestones in the development of volanesorsen leading to this first approval as an adjunct to diet in adult patients with genetically confirmed FCS and at high risk for pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate.


Assuntos
Apolipoproteína C-III/antagonistas & inibidores , Oligonucleotídeos Antissenso/uso terapêutico , Oligonucleotídeos/uso terapêutico , Apolipoproteína C-III/genética , Apolipoproteína C-III/metabolismo , Ensaios Clínicos Fase III como Assunto , Aprovação de Drogas , Europa (Continente) , Humanos , Hiperlipoproteinemia Tipo I/tratamento farmacológico , Hipertrigliceridemia/tratamento farmacológico , Lipodistrofia Parcial Familiar/tratamento farmacológico , Lipodistrofia Parcial Familiar/genética , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/efeitos adversos , Oligonucleotídeos Antissenso/administração & dosagem , Oligonucleotídeos Antissenso/efeitos adversos
13.
Drugs ; 79(11): 1241-1247, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31267482

RESUMO

Naldemedine [Symproic® (Japan; USA); Rizmoic® (EU)], an orally available peripherally acting µ-opioid receptor antagonist (PAMORA), is approved in several countries for the treatment of opioid-induced constipation. In phase III trials, naldemedine was more effective than placebo at increasing the frequency of bowel movements in patients with constipation induced by opioid treatment for cancer pain or chronic non-cancer pain. Naldemedine was also associated with improvements in patient-rated constipation-related symptoms and quality of life. Naldemedine was generally well tolerated, including over the longer term. Because naldemedine specifically targets opioid receptors in the gastrointestinal (GI) tract and does not cross the blood-brain barrier, it does not cause opioid withdrawal symptoms or interfere with centrally mediated opioid analgesia. Consistent with its mechanism of action, the most commonly reported adverse events were GI in nature. In conclusion, current data indicate that naldemedine is an effective and generally well-tolerated treatment option for opioid-induced constipation in patients with cancer pain or chronic non-cancer pain, with the convenience of once-daily oral dosing.


Assuntos
Analgésicos Opioides/efeitos adversos , Constipação Intestinal/tratamento farmacológico , Naltrexona/análogos & derivados , Antagonistas de Entorpecentes/uso terapêutico , Dor do Câncer/tratamento farmacológico , Dor Crônica/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Constipação Intestinal/induzido quimicamente , Humanos , Naltrexona/uso terapêutico , Qualidade de Vida
14.
Anticancer Res ; 39(7): 3961-3965, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262928

RESUMO

BACKGROUND/AIM: Immune check point inhibitors (ICIs) are changing cancer treatment in several malignancies, including non-small cell lung cancer (NSCLC). The introduction of these active new agents is associated with a relevant increase of costs and it is, therefore, important to create a balance between the costs of treatment and the added value represented by the improvement of the clinical parameters of interest such as overall survival (OS). This analysis was conducted to assess the pharmacological costs of first- and second-line treatments with ICIs (pembrolizumab, nivolumab and atezolizumab) for metastatic NSCLC. MATERIALS AND METHODS: The present evaluation was restricted to phase III randomized controlled trials (RCTs). We calculated the pharmacological costs necessary to get the benefit in OS. RESULTS: Six phase III RCTs were evaluated. Concerning first-line, the lowest cost per month of OS-gain was associated with the use of pembrolizumab at 2,734 €. Concerning second-line, the lowest cost per month of OS-gain was associated with the use of atezolizumab at 3,724 €. CONCLUSION: Pembrolizumab and atezolizumab are cost-effective in both first and second-line treatment for metastatic NSCLC, respectively.


Assuntos
Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais/economia , Antineoplásicos Imunológicos/economia , Carcinoma Pulmonar de Células não Pequenas/economia , Neoplasias Pulmonares/economia , Nivolumabe/economia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Anticancer Res ; 39(7): 3971-3973, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262930

RESUMO

BACKGROUND/AIM: Biosimilar agents are biologic products that have no clinically meaningful differences in terms of quality, efficacy, safety and immunogenicity compared to an already approved reference biological product, with the potential to reduce the costs of biologics. Considering the increasing numbers of oncology biosimilars, it is important to calculate the economic impact of biosimilars in oncology and hemathology, considering trastuzumab and rituximab as examples, with their greatest budgetary impact in Oncology and Hematology Units, respectively. The present analysis was conducted to assess the pharmacological costs of trastuzumab and rituximab originator versus the corresponding approved biosimilars. MATERIALS AND METHODS: Pivotal phase III randomized controlled trials (RCTs) were considered for the approved indications in neoadiuvant breast cancer (BC) and in first-line treatment for advanced follicular lymphoma. Pharmacological costs necessary to get the benefit in the cancer outcomes: i) time to treatment failure (TTF) and ii) pathological complete response (pCR) in biosimilars and originators were calculated. The costs of drugs are at the Pharmacy of our Hospital and are expressed in euros (€). RESULTS: Our analysis evaluated 5 phase III RCTs, including 2,362 patients. The economic advantage of biosimilars versus (vs.) originator is 274 € (rituximab) and from 3,283 € to 6,310 € (trastuzumab) per month for TTF (about 40% less than the originator). CONCLUSION: Combining pharmacological costs of drugs with the measure of efficacy represented by TTF and pCR, biosimilars of rituximab and trastuzumab are cost-effective treatments for advanced follicular lymphoma and breast cancer.


Assuntos
Antineoplásicos Imunológicos/economia , Medicamentos Biossimilares/economia , Rituximab/economia , Trastuzumab/economia , Antineoplásicos Imunológicos/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Hematologia/economia , Humanos , Oncologia/economia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/uso terapêutico , Trastuzumab/uso terapêutico
16.
BMC Infect Dis ; 19(1): 484, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146698

RESUMO

BACKGROUND: Network meta-analyses (NMAs) provide comparative treatment effects estimates in the absence of head-to-head randomized controlled trials (RCTs). This NMA compared the efficacy and safety of dolutegravir (DTG) with other recommended or commonly used core antiretroviral agents. METHODS: A systematic review identified phase 3/4 RCTs in treatment-naïve patients with HIV-1 receiving core agents: ritonavir-boosted protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), or integrase strand inhibitors (INSTIs). Efficacy (virologic suppression [VS], CD4+ cell count change from baseline) and safety (adverse events [AEs], discontinuations, discontinuation due to AEs, lipid changes) were analyzed at Week 48 using Bayesian NMA methodology, which allowed calculation of probabilistic results. Subgroup analyses were conducted for VS (baseline viral load [VL] ≤/> 100,000copies/mL, ≤/> 500,000copies/mL; baseline CD4+ ≤/>200cells/µL). Results were adjusted for the nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) combined with the core agent (except subgroup analyses). RESULTS: The NMA included 36 studies; 2 additional studies were included in subgroup analyses only. Odds of achieving VS with DTG were statistically superior to PIs (odds ratios [ORs] 1.78-2.59) and NNRTIs (ORs 1.51-1.86), and similar but numerically higher than other INSTIs. CD4+ count increase was significantly greater with DTG than PIs (difference: 23.63-31.47 cells/µL) and efavirenz (difference: 34.54 cells/µL), and similar to other core agents. INSTIs were more likely to result in patients achieving VS versus PIs (probability: 76-100%) and NNRTIs (probability: 50-100%), and a greater CD4+ count increase versus PIs (probability: 72-100%) and NNRTIs (probability: 60-100%). DTG was more likely to result in patients achieving VS (probability: 94-100%), and a greater CD4+ count increase (probability: 53-100%) versus other core agents, including INSTIs (probability: 94-97% and 53-93%, respectively). Safety outcomes with DTG were generally similar to other core agents. In patients with baseline VL > 100,000copies/mL or ≤ 200 CD4+cells/µL (18 studies), odds of achieving VS with DTG were superior or similar to other core agents. CONCLUSION: INSTI core agents had superior efficacy and similar safety to PIs and NNRTIs at Week 48 in treatment-naïve patients with HIV-1, with DTG being among the most efficacious, including in patients with baseline VL > 100,000copies/mL or ≤ 200 CD4+cells/µL, who can be difficult to treat.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/classificação , Teorema de Bayes , Benzoxazinas/uso terapêutico , Contagem de Linfócito CD4 , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase IV como Assunto/estatística & dados numéricos , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Adulto Jovem
17.
Gynecol Oncol ; 154(3): 539-546, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31230821

RESUMO

OBJECTIVE: Low-grade epithelial ovarian cancers (EOC), constitute the minority among all epithelial cancers. Our study objective was to focus on low-grade recurrent EOC and compare the survival with high-grade disease, as well as in regard to "platinum-sensitive" and "-resistant" recurrences according to platinum-free interval. METHODS: This is an exploratory analysis within the North-Eastern German Society of Gynecological Oncology (NOGGO) database including five randomized phase II/III trials comparing different chemotherapy regimens in recurrent EOC. We conducted survival analyses and cox-proportional regression models. RESULTS: Out of 1050 patients having the first recurrence, 42 (4%) patients had low-grade and 1008 (96%) patients had high-grade disease. In the subgroup of platinum-sensitive recurrences, progression-free survival (PFS) (8.7 m vs 9.7 m, p = 0.7) and overall survival (OS) (23.9 m vs 24.8 m, p = 0.9) did not differ between low-grade and high-grade diseases. In platinum-resistant recurrences, patients with low-grade ovarian cancer had significantly better PFS (7.6 m vs 3.6 m, p = 0.03) and OS (41.9 m vs 9.5 m p = 0.002) in comparison to those with high-grade cancer. At low-grade EOC, there were no significant PFS (p = 0.91) and OS (p = 0.25) differences between platinum-sensitive and -resistant recurrences. Patients with low-grade non-serous histology had lower PFS with compared to those with low-grade serous histology (p = 0.004). At cox regression analysis presence of ascites and residual disease after secondary cytoreductive surgery were independently associated with poor PFS within low-grade recurrent EOC. CONCLUSION: Our study indicates, platinum-free interval does not have any prognostic significance at recurrent low-grade EOC and non-serous histology is associated with poorer outcome in recurrence. Secondary surgical cytoreduction to no-gross residual disease and ascites are independently associated with disease progression.


Assuntos
Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Compostos Organoplatínicos/administração & dosagem , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Topotecan/administração & dosagem , Adulto Jovem
18.
Drugs Aging ; 36(7): 625-638, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31066015

RESUMO

In patients with osteoporosis and severely reduced bone mass and/or recurring fractures, antiresorptive therapy may not be the optimal first-line treatment. Two recent clinical trials comparing bone-forming treatment with antiresorptive therapy have demonstrated that bone-forming treatment is superior in reducing the fracture risk in patients with severe osteoporosis. All of the currently available bone-forming agents-teriparatide, abaloparatide, and romosozumab-increase bone mineral density (BMD) and reduce the fracture risk; however, the effect wears off with time and treatment is therefore only transient. Thus, a bone-forming therapy should be followed by antiresorptive treatment with a bisphosphonate or denosumab. The BMD response to bone-forming treatment is reduced in patients previously treated with antiresorptive drugs; however, based on the findings of the VERO trial, the anti-fracture efficacy of bone-forming treatment in comparison with antiresorptives seems to be preserved. This review provides an overview of the existing bone-forming therapies for osteoporosis including considerations of sequential and combination therapy.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Quimioterapia Combinada , Humanos , Osteogênese/efeitos dos fármacos , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Teriparatida/uso terapêutico
19.
Medicine (Baltimore) ; 98(22): e15522, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145273

RESUMO

BACKGROUND: The N-methyl-N'-nitroso-guanidine human osteosarcoma transforming gene (MET) inhibitors show a surprising survival benefit in the treatment of numerous tumors especially in MET-high tumor. Besides their impressive efficacy, fatigue reduced by MET inhibitors is still the safety issue during treatment. Thus, an understanding of this risk in the context of expanding MET-inhibitors use is an important cost and patient safety issue. METHODS: We searched PubMed, Embase, and the Cochrane Library databases for relevant studies up to October 2017. Eligibility criteria included phase II/III trials of MET inhibitors that reported adequate safety profiles of fatigue. The principal summary measures were incidence and relative risk (RR) of all-grade (grade 1-4) and high-grade (grade 3-4) fatigue, respectively. Random-effects model was applied to consider within-study and between-study variation. RESULTS: A total of 5028 patients from 17 clinical trials were identified. The results revealed that the incidences of MET inhibitors-associated all-grade and high-grade fatigue were 41.9% and 9.6%, respectively. The RR of high-grade fatigue was (RR = 1.37; 95% confidence interval, 1.14-1.66; P = .0009), whereas the RR of all-grade fatigue was (RR = 1.02; 95% confidence interval, 0.91-1.15; P = .71). CONCLUSION: Our meta-analysis has demonstrated that MET inhibitors-based treatment is associated with an increased risk of high-grade fatigue compared with control.


Assuntos
Fadiga/induzido quimicamente , Fadiga/epidemiologia , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Incidência , Risco
20.
Future Microbiol ; 14: 563-580, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31091978

RESUMO

Protection by meningococcal group A, C, W and Y (MenACWY) vaccines against four meningococcal disease-causing serogroups is increasingly important because of changing epidemiologic patterns of meningococcal disease, including recent meningococcal serogroup W outbreaks/disease clusters. The MenACWY vaccine conjugated to tetanus toxoid (MenACWY-TT) has been extensively evaluated across the age spectrum (age ≥6 weeks) in randomized Phase II and III and in postmarketing studies. Results support the robust immunogenicity of MenACWY-TT across ages and coadministration with other vaccines. The safety profile is similar regardless of age, primary versus booster vaccination, or concomitant administration; local (swelling, pain, redness) and systemic (fever, fatigue, headache, drowsiness, loss of appetite, irritability) reactogenicity events are most common. These data support use of MenACWY-TT to protect against MenACWY disease.


Assuntos
Infecções Meningocócicas/imunologia , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Toxoide Tetânico/imunologia , Vacinas Conjugadas/imunologia , Antígenos de Bactérias/imunologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Imunogenicidade da Vacina , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/efeitos adversos , Neisseria meningitidis/patogenicidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Sorogrupo , Vacinação , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/efeitos adversos
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