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[PMID]:29362796
[Au] Autor:Bouillon K; Bertrand M; Bader G; Lucot JP; Dray-Spira R; Zureik M
[Ad] Endereço:Department of Epidemiology of Health Products, French National Agency for Medicines and Health Products Safety (ANSM), Saint-Denis, France.
[Ti] Título:Association of Hysteroscopic vs Laparoscopic Sterilization With Procedural, Gynecological, and Medical Outcomes.
[So] Source:JAMA;319(4):375-387, 2018 01 23.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Safety of hysteroscopic sterilization has been recently questioned following reports of general symptoms such as allergy, tiredness, and depression in addition to associated gynecological results such as pelvic pain, perforation of fallopian tubes or uterus, and unwanted pregnancy. Objective: To compare the risk of reported adverse events between hysteroscopic and laparoscopic sterilization. Design, Setting, and Participants: French nationwide cohort study using the national hospital discharge database linked to the health insurance claims database. Women aged 30 to 54 years receiving a first hysteroscopic or laparoscopic sterilization between 2010 and 2014 were included and were followed up through December 2015. Exposures: Hysteroscopic sterilization vs laparoscopic sterilization. Main Outcomes and Measures: Risks of procedural complications (surgical and medical) and of gynecological (sterilization failure that includes salpingectomy, second sterilization procedure, or pregnancy; pregnancy; reoperation) and medical outcomes (all types of allergy; autoimmune diseases; thyroid disorder; use of analgesics, antimigraines, antidepressants, benzodiazepines; outpatient visits; sickness absence; suicide attempts; death) that occurred within 1 and 3 years after sterilization were compared using inverse probability of treatment-weighted Cox models. Results: Of the 105 357 women included (95.5% of eligible participants; mean age, 41.3 years [SD, 3.7 years]), 71 303 (67.7% ) underwent hysteroscopic sterilization, and 34 054 (32.3%) underwent laparoscopic sterilization. During the hospitalization for sterilization, risk of surgical complications for hysteroscopic sterilization was lower: 0.13% for hysteroscopic sterilization vs 0.78% for laparoscopic sterilization (adjusted risk difference [RD], -0.64; 95% CI, -0.67 to -0.60) and was lower for medical complications: 0.06% vs 0.11% (adjusted RD, -0.05; 95% CI, -0.08 to -0.01). During the first year after sterilization, 4.83% of women who underwent hysteroscopic sterilization had a higher risk of sterilization failure than the 0.69% who underwent laparoscopic sterilization (adjusted hazard ratio [HR], 7.11; 95% CI, 5.92 to 8.54; adjusted RD, 4.23 per 100 person-years; 95% CI, 3.40 to 5.22). Additionally, 5.65% of women who underwent hysteroscopic sterilization required gynecological reoperation vs 1.76% of women who underwent laparoscopic sterilization (adjusted HR, 3.26; 95% CI, 2.90 to 3.67; adjusted RD, 4.63 per 100 person-years; 95% CI, 3.38 to 4.75); these differences persisted after 3 years, although attenuated. Hysteroscopic sterilization was associated with a lower risk of pregnancy within the first year of the procedure but was not significantly associated with a difference in risk of pregnancy by the third year (adjusted HR, 1.04; 95% CI, 0.83-1.30; adjusted RD, 0.01 per 100 person-years; 95% CI, -0.04 to 0.07). Risks of medical outcomes were not significantly increased with hysteroscopic sterilization compared with laparoscopic sterilization. Conclusions and Relevance: Among women undergoing first sterilization, the use of hysteroscopic sterilization was significantly associated with higher risk of gynecological complications over 1 year and over 3 years than was laparoscopic sterilization. Risk of medical outcomes was not significantly increased over 1 year or over 3 years. These findings do not support increased medical risks associated with hysteroscopic sterilization.
[Mh] Termos MeSH primário: Histeroscopia/efeitos adversos
Laparoscopia/efeitos adversos
Complicações Pós-Operatórias/etiologia
Esterilização Tubária/métodos
[Mh] Termos MeSH secundário: Adulto
Estudos de Coortes
Feminino
França
Seres Humanos
Meia-Idade
Complicações Pós-Operatórias/epidemiologia
Gravidez
Gravidez não Planejada
Reoperação/estatística & dados numéricos
Esterilização Tubária/efeitos adversos
Falha de Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.21269


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Registro de Ensaios Clínicos
Registro de Ensaios Clínicos
Registro de Ensaios Clínicos
Registro de Ensaios Clínicos
Registro de Ensaios Clínicos
Registro de Ensaios Clínicos
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[PMID]:29318278
[Au] Autor:Atri A; Frölich L; Ballard C; Tariot PN; Molinuevo JL; Boneva N; Windfeld K; Raket LL; Cummings JL
[Ad] Endereço:Ray Dolby Brain Health Center, California Pacific Medical Center, San Francisco.
[Ti] Título:Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease: Three Randomized Clinical Trials.
[So] Source:JAMA;319(2):130-142, 2018 01 09.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: New therapeutic approaches for Alzheimer disease (AD) are needed. Objective: To assess whether idalopirdine, a selective 5-hydroxytryptamine-6 receptor antagonist, is effective for symptomatic treatment of mild to moderate AD. Design, Setting, and Participants: Three randomized clinical trials that included 2525 patients aged 50 years or older with mild to moderate AD (study 1: n = 933 patients at 119 sites; study 2: n = 858 at 158 sites; and study 3: n = 734 at 126 sites). The 24-week studies were conducted from October 2013 to January 2017; final follow-up on January 12, 2017. Interventions: Idalopirdine (10, 30, or 60 mg/d) or placebo added to cholinesterase inhibitor treatment (donepezil in studies 1 and 2; donepezil, rivastigmine, or galantamine in study 3). Main Outcomes and Measures: Primary end point in all 3 studies: change in cognition total score (range, 0-70; a lower score indicates less impairment) from baseline to 24 weeks measured by the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog); key secondary end points: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale and 23-item Activities of Daily Living Inventory scores. Dose group efficacy required a significant benefit over placebo for the primary end point and 1 or more key secondary end points. Safety data and adverse event profiles were recorded. Results: Among 2525 patients randomized in the 3 trials (mean age, 74 years; mean baseline ADAS-Cog total score, 26; between 62% and 65% of participants were women), 2254 (89%) completed the studies. In study 1, the mean change in ADAS-Cog total score between baseline and 24 weeks was 0.37 for the 60-mg dose of idalopirdine group, 0.61 for the 30-mg dose group, and 0.41 for the placebo group (adjusted mean difference vs placebo, 0.05 [95% CI, -0.88 to 0.98] for the 60-mg dose group and 0.33 [95% CI, -0.59 to 1.26] for the 30-mg dose group). In study 2, the mean change in ADAS-Cog total score between baseline and 24 weeks was 1.01 for the 30-mg dose of idalopirdine group, 0.53 for the 10-mg dose group, and 0.56 for the placebo group (adjusted mean difference vs placebo, 0.63 [95% CI, -0.38 to 1.65] for the 30-mg dose group; given the gated testing strategy and the null findings at the 30-mg dose, statistical comparison of the 10-mg dose was not performed). In study 3, the mean change in ADAS-Cog total score between baseline and 24 weeks was 0.38 for the 60-mg dose of idalopirdine group and 0.82 for the placebo group (adjusted mean difference vs placebo, -0.55 [95% CI, -1.45 to 0.36]). Treatment-emergent adverse events occurred in between 55.4% and 69.7% of participants in the idalopirdine groups vs between 56.7% and 61.4% of participants in the placebo groups. Conclusions and Relevance: In patients with mild to moderate AD, the use of idalopirdine compared with placebo did not improve cognition over 24 weeks of treatment. These findings do not support the use of idalopirdine for the treatment of AD. Trial Registration: clinicaltrials.gov Identifiers: NCT01955161, NCT02006641, and NCT02006654.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Benzilaminas/uso terapêutico
Inibidores da Colinesterase/uso terapêutico
Indóis/uso terapêutico
Antagonistas da Serotonina/uso terapêutico
[Mh] Termos MeSH secundário: Acidentes por Quedas
Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/psicologia
Benzilaminas/administração & dosagem
Benzilaminas/efeitos adversos
Inibidores da Colinesterase/efeitos adversos
Cognição/efeitos dos fármacos
Relação Dose-Resposta a Droga
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Galantamina/uso terapêutico
Seres Humanos
Indanos/uso terapêutico
Indóis/administração & dosagem
Indóis/efeitos adversos
Masculino
Meia-Idade
Piperidinas/uso terapêutico
Rivastigmina/uso terapêutico
Antagonistas da Serotonina/administração & dosagem
Antagonistas da Serotonina/efeitos adversos
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 ((2-(6-fluoro-1H-indol-3-yl)-ethyl)-(3-(2,2,3,3-tetrafluoropropoxy)benzyl)amine); 0 (Benzylamines); 0 (Cholinesterase Inhibitors); 0 (Indans); 0 (Indoles); 0 (Piperidines); 0 (Serotonin Antagonists); 0D3Q044KCA (Galantamine); 8SSC91326P (donepezil); PKI06M3IW0 (Rivastigmine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180111
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.20373


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[PMID]:29467153
[Au] Autor:Le Couteur DG; Bateman B; Brayne C
[Ad] Endereço:Centre for Education and Research on Ageing, Concord Hospital and University of Sydney, Sydney, Australia.
[Ti] Título:Idalopirdine: another disappointment for people with dementia.
[So] Source:BMJ;360:k753, 2018 02 21.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Benzilaminas/uso terapêutico
Demência/tratamento farmacológico
Indóis/uso terapêutico
Antagonistas da Serotonina/uso terapêutico
[Mh] Termos MeSH secundário: Ensaios Clínicos como Assunto
Seres Humanos
Falha de Tratamento
[Pt] Tipo de publicação:EDITORIAL
[Nm] Nome de substância:
0 ((2-(6-fluoro-1H-indol-3-yl)-ethyl)-(3-(2,2,3,3-tetrafluoropropoxy)benzyl)amine); 0 (Benzylamines); 0 (Indoles); 0 (Serotonin Antagonists)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180223
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.k753


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[PMID]:29252031
[Au] Autor:Schlabe S; Rockstroh JK
[Ad] Endereço:a Department of Internal Medicine I , University Hospital Bonn , Bonn , Germany.
[Ti] Título:Advances in the treatment of HIV/HCV coinfection in adults.
[So] Source:Expert Opin Pharmacother;19(1):49-64, 2018 Jan.
[Is] ISSN:1744-7666
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Direct-acting antivirals (DAA) have revolutionized the modern treatment of chronic hepatitis C (HCV). These highly efficacious, well-tolerated, all-oral HCV regimens allow cure of HCV in over 95% of HCV-monoinfected as well as HIV/HCV-coinfected patients with short treatment durations of 8-12 weeks. Areas covered: This review will address recent developments of DAA-therapy in HIV/HCV-coinfected patients in clinical trials and real life cohorts and evaluate remaining challenges, particularly resistance, drug-drug interactions, acute HCV infection and liver transplantation focusing on HIV/HCV-coinfected patients. Expert opinion: Indeed, all available data have shown that HIV/HCV-coinfection has no impact on HCV-treatment outcome. Management, indication of therapy and follow-up of HCV-infection are now the same for both patient populations. HIV/HCV-coinfected patients however, require careful evaluation of potential drug-drug-interactions between HCV drugs and HIV antiretroviral therapy, medication for substance abuse and other comedications. The few remaining gaps in DAA-therapy in particular treatment of cirrhotic treatment-experienced genotype 3 infections, decompensated cirrhosis, chronic kidney disease and patients with prior DAA treatment failure have mostly been overcome by the development of new HCV agents recently licensed. Clearly, the biggest challenge globally remains the access to treatment and the inclusion of all patient populations affected in particular people who inject drugs (PWID).
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Infecções por HIV/tratamento farmacológico
Hepatite C Crônica/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Coinfecção
Interações Medicamentosas
Genótipo
Seres Humanos
Cirrose Hepática/tratamento farmacológico
Transplante de Fígado
Insuficiência Renal Crônica/tratamento farmacológico
Falha de Tratamento
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiviral Agents)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171219
[St] Status:MEDLINE
[do] DOI:10.1080/14656566.2017.1419185


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[PMID]:29357819
[Au] Autor:Kodama-Takahashi A; Fukuda M; Sugioka K; Kobayashi A; Shimomura Y
[Ad] Endereço:Department of Ophthalmology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama City, Osaka, 589-8511, Japan. akodama@med.kindai.ac.jp.
[Ti] Título:Spontaneous reattachment of dislocated endothelial graft after non-Descemet stripping automated endothelial keratoplasty: a case report.
[So] Source:BMC Ophthalmol;18(1):14, 2018 Jan 22.
[Is] ISSN:1471-2415
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Graft detachment is a complication of non-Descemet stripping automated endothelial keratoplasty (nDSAEK). We report a case of spontaneous reattachment of an extensively dislocated graft after nDSAEK. CASE PRESENTATION: A 54-year-old male underwent penetrating keratoplasty (PKP) for keratoconus in his left eye in 2001. Following graft opacity due to rejection, a second PKP was implemented in May 2014. The graft was kept in good condition after the reoperation and yet, visual acuity (VA) declined due to cataract. PEA+IOL was then performed in May 2015. Because edema appeared in the graft 6 months after the PEA+IOL, nDSAEK was carried out in May 2016. Although the donor graft well attached immediately after the nDSAEK, the graft was almost completely dislocated 3 h later except a temporal part. Air was reinjected into the anterior chamber on the following day and the detachment was resolved. Despite of the treatment, about 1/5 of the graft remained detached and the detachment deteriorated to 3/4 of the graft 9 days later. Because the patient could not decide whether to undergo another operation immediately, we decided to follow him up first and found that the partially detached graft reattached spontaneously 1 month later during the follow-up. Although the cornea had a mild edema remaining in the superior temporal area, his BCVA improved to 1.0. Three months later, the graft remained in position and the cornea kept its transparency. CONCLUSIONS: Spontaneous reattachment was observed during the follow-up in a case that had shown a comparatively extensive graft dislocation after nDSAEK.
[Mh] Termos MeSH primário: Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos
Sobrevivência de Enxerto
Ceratocone/cirurgia
Complicações Pós-Operatórias/diagnóstico
[Mh] Termos MeSH secundário: Câmara Anterior
Seguimentos
Seres Humanos
Masculino
Meia-Idade
Remissão Espontânea
Estudos Retrospectivos
Falha de Tratamento
Acuidade Visual
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180124
[St] Status:MEDLINE
[do] DOI:10.1186/s12886-018-0684-7


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[PMID]:29336009
[Au] Autor:Sim EH; Yang IA; Wood-Baker R; Bowman RV; Fong KM
[Ad] Endereço:GenesisCare Radiation Oncology, 1 Medical Place, Urraween, Queensland, Australia, 4655.
[Ti] Título:Gefitinib for advanced non-small cell lung cancer.
[So] Source:Cochrane Database Syst Rev;1:CD006847, 2018 01 16.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The role of gefitinib for the treatment of advanced non-small cell lung cancer (NSCLC) is evolving. We undertook a systematic review to evaluate the available evidence from all randomised trials. OBJECTIVES: To determine the effectiveness and safety of gefitinib as first-line, second-line or maintenance treatment for advanced NSCLC. SEARCH METHODS: We performed searches in CENTRAL, MEDLINE and Embase from inception to 17 February 2017. We handsearched relevant conference proceedings, clinical trial registries and references lists of retrieved articles. SELECTION CRITERIA: We included trials assessing gefitinib, alone or in combination with other treatment, compared to placebo or other treatments in the first- or successive-line treatment of patients with NSCLC, excluding compassionate use. DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodology. Two authors independently assessed the search results to select those with sound methodological quality. We carried out all analyses on an intention-to-treat basis. We recorded the following outcome data: overall survival, progression-free survival, toxicity, tumour response and quality of life. We also collected data for the following subgroups: Asian ethnicity and positive epidermal growth factor receptor (EGFR) mutation. MAIN RESULTS: We included 35 eligible randomised controlled trials (RCTs), which examined 12,089 patients.General populationGefitinib did not statistically improve overall survival when compared with placebo or chemotherapy in either first- or second-line settings. Second-line gefitinib prolonged time to treatment failure (TTF) (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90, P < 0.0001) when compared with placebo. Maintenance gefitinib improved progression-free survival (HR 0.70, 95% CI 0.53 to 0.91, P = 0.007) after first-line therapy.Studies in patients of Asian ethnicity or that conducted subgroup analysesSecond-line gefitinib prolonged overall survival over placebo (HR 0.66, 95% CI 0.48 to 0.91, P = 0.01). In the first-line setting, progression-free survival was improved with gefitinib over chemotherapy alone (HR 0.65, 95% CI 0.43 to 0.98, P = 0.04, moderate quality of evidence). Gefitinib given in combination with a chemotherapy regimen improved progression-free survival versus either gefitinib alone or chemotherapy alone (HR 0.69, 95% CI 0.49 to 0.96, P = 0.03; HR 0.69, 95% CI 0.62 to 0.77, P < 0.00001, respectively). In the second-line setting, progression-free survival was superior in patients given gefitinib over placebo or chemotherapy (HR 0.69, 95% CI 0.52 to 0.91, P = 0.009; HR 0.71, 95% CI 0.57 to 0.88, P = 0.002; moderate quality of evidence, respectively). Combining gefitinib with chemotherapy in the second-line setting was superior to gefitinib alone (HR 0.65, 95% CI 0.43 to 0.97, P = 0.04). As maintenance therapy, gefitinib improved progression-free survival when compared with placebo (HR 0.42, 95% CI 0.33 to 0.54, P < 0.00001).Patients with EGFR mutation-positive tumoursStudies in patients with EGFR mutation-positive tumours showed an improvement in progression-free survival in favour of gefitinib over first-line and second-line chemotherapy (HR 0.47, 95% CI 0.36 to 0.61, P < 0.00001; HR 0.24, 95% CI 0.12 to 0.47, P < 0.0001, respectively). Gefitinib as maintenance therapy following chemotherapy improved overall and progression-free survival (HR 0.39, 95% CI 0.15 to 0.98, P = 0.05; HR 0.17, 95% CI 0.07 to 0.41, P < 0.0001, respectively) in one phase III study when compared to placebo.Toxicities from gefitinib included skin rash, diarrhoea and liver transaminase derangements. Toxicities from chemotherapy included anaemia, neutropenia and neurotoxicity.In terms of quality of life, gefitinib improved Functional Assessment of Cancer Therapy-Lung (FACT-L) (standardised mean difference (SMD) 10.50, 95% CI 9.55 to 11.45, P < 0.000001), lung cancer subscale (SMD 3.63, 95% CI 3.08 to 4.19, P < 0.00001) and Trial Outcome Index (SMD 9.87, 95% CI 1.26 to 18.48, P < 0.00001) scores when compared with chemotherapy. AUTHORS' CONCLUSIONS: This systematic review shows that gefitinib, when compared with standard first- or second-line chemotherapy or maintenance therapy, probably has a beneficial effect on progression-free survival and quality of life in selected patient populations, particularly those with tumours bearing sensitising EGFR mutations.Patients with EGFR mutations lived longer when given maintenance gefitinib than those given placebo.One study conducted subgroup analysis and showed that gefitinib improved overall survival over placebo in the second-line setting in patients of Asian ethnicity. All other studies did not detect any benefit on overall survival. The data analysed in this review were very heterogenous. We were limited in the amount of data that could be pooled, largely due to variations in study design. The risk of bias in most studies was moderate, with some studies not adequately addressing potential selection, attrition and reporting bias. This heterogeneity may have an impact on the applicability of the resultsCombining gefitinib with chemotherapy appears to be superior in improving progression-free survival to either gefitinib or chemotherapy alone, however further data and phase III studies in these settings are required.Gefitinib has a favourable toxicity profile when compared with current chemotherapy regimens. Although there is no improvement in overall survival, gefitinib compares favourably with cytotoxic chemotherapy in patients with EGFR mutations with a prolongation of progression-free survival and a lesser side effect profile.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Neoplasias Pulmonares/tratamento farmacológico
Quinazolinas/uso terapêutico
[Mh] Termos MeSH secundário: Antineoplásicos/efeitos adversos
Carcinoma Pulmonar de Células não Pequenas/etnologia
Carcinoma Pulmonar de Células não Pequenas/genética
Intervalo Livre de Doença
Genes erbB-1
Seres Humanos
Neoplasias Pulmonares/etnologia
Neoplasias Pulmonares/genética
Mutação
Qualidade de Vida
Quinazolinas/efeitos adversos
Ensaios Clínicos Controlados Aleatórios como Assunto
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Quinazolines); S65743JHBS (gefitinib)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD006847.pub2


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[PMID]:29260224
[Au] Autor:Gerber JS; Ross RK; Bryan M; Localio AR; Szymczak JE; Wasserman R; Barkman D; Odeniyi F; Conaboy K; Bell L; Zaoutis TE; Fiks AG
[Ad] Endereço:Center for Pediatric Clinical Effectiveness, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
[Ti] Título:Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections.
[So] Source:JAMA;318(23):2325-2336, 2017 12 19.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment. Objective: To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children. Design, Setting, and Participants: A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts. Exposures: Broad-spectrum antibiotics vs narrow-spectrum antibiotics. Main Outcomes and Measures: In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events. Results: Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3% [95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868 (35%) were prescribed broad-spectrum antibiotics. Broad-spectrum antibiotics were associated with a slightly worse child quality of life (score of 90.2 for broad-spectrum antibiotics vs 91.5 for narrow-spectrum antibiotics; score difference for full matched analysis, -1.4% [95% CI, -2.4% to -0.4%]) but not with other patient-centered outcomes. Broad-spectrum treatment was associated with a higher risk of adverse events documented by the clinician (3.7% for broad-spectrum antibiotics vs 2.7% for narrow-spectrum antibiotics; risk difference for full matched analysis, 1.1% [95% CI, 0.4% to 1.8%]) and reported by the patient (35.6% for broad-spectrum antibiotics vs 25.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 12.2% [95% CI, 7.3% to 17.2%]). Conclusions and Relevance: Among children with acute respiratory tract infections, broad-spectrum antibiotics were not associated with better clinical or patient-centered outcomes compared with narrow-spectrum antibiotics, and were associated with higher rates of adverse events. These data support the use of narrow-spectrum antibiotics for most children with acute respiratory tract infections.
[Mh] Termos MeSH primário: Antibacterianos/efeitos adversos
Otite Média/tratamento farmacológico
Qualidade de Vida
Infecções Respiratórias/tratamento farmacológico
[Mh] Termos MeSH secundário: Doença Aguda
Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos
Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico
Antibacterianos/uso terapêutico
Cefalosporinas/efeitos adversos
Cefalosporinas/uso terapêutico
Criança
Pré-Escolar
Feminino
Seres Humanos
Macrolídeos/efeitos adversos
Macrolídeos/uso terapêutico
Masculino
Faringite/tratamento farmacológico
Atenção Primária à Saúde
Estudos Retrospectivos
Sinusite/tratamento farmacológico
Infecções Estreptocócicas/tratamento farmacológico
Streptococcus pyogenes
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Cephalosporins); 0 (Macrolides); 74469-00-4 (Amoxicillin-Potassium Clavulanate Combination)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.18715


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[PMID]:28463162
[Au] Autor:Helou J; Thibault I; Poon I; Chiang A; Jain S; Soliman H; Erler D; Yeung L; Cheung P
[Ad] Endereço:Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
[Ti] Título:Stereotactic Ablative Radiation Therapy for Pulmonary Metastases: Histology, Dose, and Indication Matter.
[So] Source:Int J Radiat Oncol Biol Phys;98(2):419-427, 2017 06 01.
[Is] ISSN:1879-355X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To assess the association between colorectal cancer (CRC) histology, dose, and local failure (LF) after stereotactic ablative radiation therapy (SABR) for pulmonary metastases, and to describe subsequent cancer progression, change of systemic therapy (CST), survival, and their association with treatment indications. METHODS AND MATERIALS: From a prospective SABR cohort, 180 pulmonary metastases in 120 patients were identified. Treatment indications were single metastasis, oligometastases, oligoprogression, and dominant areas of progression. Doses of 48 to 52 Gy/4 to 5 fractions were delivered. Since 2010 the dose for peripheral CRC metastases was increased to 60 Gy/4 fractions. Cumulative incidence function (CIF) was used to report LF, progression probability, and CST. The Kaplan-Meier method estimated overall survival (OS). Univariate and multivariable analyses to assess variable associations were conducted. RESULTS: Median follow-up was 22 months (interquartile range, 14-33 months). At 24 months, the CIF of LF was 23.6% (95% confidence interval [CI] 15.1%-33.3%) and 8.3% (95% CI 2.6%-18.6%), respectively, for CRC and non-CRC metastases (P<.001). This association remained significant after adjusting for confounders (subdistribution hazard ratio [SHR] 13.6, 95% CI 4.2-44.1, P<.001). Among CRC metastases, 56 and 45 received <60 Gy and 60 Gy, respectively. Delivering 60 Gy was independently associated with a lower hazard of LF (SHR 0.271, 95% CI 0.078-0.940, P=.040). At 12 months the CIF of progression was 41.67% (95% CI 21.69%-60.56%), 42.51% (95% CI 29.09%-55.29%), 62.96% (95% CI 41.25%-78.53%), and 78.57% (95% CI 42.20%-93.48%), respectively, for patients treated for single metastasis, oligometastases, oligoprogression, and dominant area of progression (P<.001). A CST was observed, respectively, in 4 (17%), 17 (31%), 12 (44%), and 10 (71%) patients with a median time of 13.1, 11.1, 8.4, and 8.4 months. CONCLUSION: Colorectal cancer lung metastases are associated with a higher hazard of LF and require higher SABR doses. Outcomes for patients with oligometastases and oligoprogression treated with SABR seem favorable. Prospective clinical trials are needed to confirm these benefits.
[Mh] Termos MeSH primário: Neoplasias Colorretais/patologia
Neoplasias Pulmonares/radioterapia
Neoplasias Pulmonares/secundário
Radiocirurgia/métodos
[Mh] Termos MeSH secundário: Idoso
Análise de Variância
Progressão da Doença
Fracionamento de Dose
Feminino
Seguimentos
Tomografia Computadorizada Quadridimensional
Seres Humanos
Estimativa de Kaplan-Meier
Neoplasias Pulmonares/diagnóstico por imagem
Neoplasias Pulmonares/mortalidade
Masculino
Probabilidade
Radiocirurgia/efeitos adversos
Planejamento da Radioterapia Assistida por Computador/métodos
Fatores de Tempo
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:29265182
[Au] Autor:Shah NN; Szabo A; Huntington SF; Epperla N; Reddy N; Ganguly S; Vose J; Obiozor C; Faruqi F; Kovach AE; Costa LJ; Xaiver AC; Okal R; Kanate AS; Ghosh N; Kharfan-Dabaja MA; Strelec L; Hamadani M; Fenske TS; Calzada O; Cohen JB; Chavez J; Svoboda J
[Ad] Endereço:Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
[Ti] Título:R-CHOP versus dose-adjusted R-EPOCH in frontline management of primary mediastinal B-cell lymphoma: a multi-centre analysis.
[So] Source:Br J Haematol;180(4):534-544, 2018 02.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is an uncommon subtype of non-Hodgkin lymphoma (NHL) that presents with a mediastinal mass and has unique clinicopathological features. Historically, patients with PMBCL were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy ± involved field radiation. Since a phase II trial, published in April 2013, demonstrated excellent results using dose-adjusted (DA) R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), this treatment has gained popularity. We performed a retrospective, multicentre analysis of patients aged ≥18 years with PMBCL since January 2011. Patients were stratified by frontline regimen, R-CHOP versus DA-R-EPOCH. 132 patients were identified from 11 contributing centres (56 R-CHOP and 76 DA-R-EPOCH). The primary outcome was overall survival. Secondary outcomes included progression-free survival, complete response (CR) rate, and rates of treatment-related complications. Demographic characteristics were similar in both groups. DA-R-EPOCH use increased after April 2013 (79% vs. 45%, P < 0·001), and there was less radiation use after DA-R-EPOCH (13% vs. 59%, P < 0·001). While CR rates were higher with DA-R-EPOCH (84% vs. 70%, P = 0·046), these patients were more likely to experience treatment-related toxicities. At 2 years, 89% of R-CHOP patients and 91% of DA-R-EPOCH patients were alive. To our knowledge, this represents the largest series comparing outcomes of R-CHOP to DA-R-EPOCH for PMBCL.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Linfoma de Células B/tratamento farmacológico
Neoplasias do Mediastino/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Anticorpos Monoclonais Murinos/efeitos adversos
Anticorpos Monoclonais Murinos/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Terapia Combinada
Ciclofosfamida/efeitos adversos
Ciclofosfamida/uso terapêutico
Gerenciamento Clínico
Doxorrubicina/efeitos adversos
Doxorrubicina/uso terapêutico
Etoposídeo/efeitos adversos
Etoposídeo/uso terapêutico
Feminino
Seres Humanos
Linfoma de Células B/diagnóstico
Linfoma de Células B/mortalidade
Masculino
Neoplasias do Mediastino/diagnóstico
Neoplasias do Mediastino/mortalidade
Meia-Idade
Gradação de Tumores
Estadiamento de Neoplasias
Prednisona/efeitos adversos
Prednisona/uso terapêutico
Recidiva
Estudos Retrospectivos
Rituximab/administração & dosagem
Falha de Tratamento
Resultado do Tratamento
Vincristina/efeitos adversos
Vincristina/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Murine-Derived); 0 (R-CHOP protocol); 4F4X42SYQ6 (Rituximab); 5J49Q6B70F (Vincristine); 6PLQ3CP4P3 (Etoposide); 80168379AG (Doxorubicin); 8N3DW7272P (Cyclophosphamide); VB0R961HZT (Prednisone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.15051


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[PMID]:28467359
[Au] Autor:Yoshida K; Hai H; Tamori A; Teranishi Y; Kozuka R; Motoyama H; Kawamura E; Hagihara A; Uchida-Kobayashi S; Morikawa H; Enomoto M; Murakami Y; Kawada N
[Ad] Endereço:Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan. m2028081@med.osaka-cu.ac.jp.
[Ti] Título:Long-Term Follow-Up of Resistance-Associated Substitutions in Hepatitis C Virus in Patients in Which Direct Acting Antiviral-Based Therapy Failed.
[So] Source:Int J Mol Sci;18(5), 2017 May 03.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:We evaluated the transition of dominant resistance-associated substitutions (RASs) in hepatitis C virus during long-term follow-up after the failure of DAAs (direct acting antivirals)-based therapy. RASs in non-structure (NS)3/4A, NS5A, NS5B, and deletions in NS5A from 20 patients who failed simeprevir/pegylated-interferon/ribavirin (SMV/PEG-IFN/RBV) and 25 patients who failed daclatasvir/asunaprevir (DCV/ASV) treatment were examined by direct sequencing. With respect to SMV/PEG-IFN/RBV treatment, RAS was detected at D168 in NS3/4A but not detected in NS5A and NS5B at treatment failure in 16 of 20 patients. During the median follow-up period of 64 weeks, the RAS at D168 became less dominant in 9 of 16 patients. Among 25 DCV/ASV failures, RASs at D168, L31, and Y93 were found in 57.1%, 72.2%, and 76.9%, respectively. NS5A deletions were detected in 3 of 10 patients treated previously with SMV/PEG-IFN/RBV. The number of RASs in the breakthrough patients exceeded that in relapsers (mean 3.9 vs. 2.7, < 0.05). RAS at D168 in NS3/4A became less dominant in 6 of 15 patients within 80 weeks. Y93H emerged at the time of relapse, then decreased gradually by 99% at 130 weeks post-treatment. Emerged RASs were associated with the clinical course of treatment and could not be detected during longer follow-up.
[Mh] Termos MeSH primário: Farmacorresistência Viral/genética
Hepacivirus/genética
Hepatite C Crônica/tratamento farmacológico
Serina Proteases/genética
Proteínas não Estruturais Virais/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Antivirais/farmacologia
Antivirais/uso terapêutico
Quimioterapia Combinada
Feminino
Seguimentos
Hepacivirus/efeitos dos fármacos
Hepatite C Crônica/virologia
Seres Humanos
Imidazóis/farmacologia
Imidazóis/uso terapêutico
Interferon-alfa/uso terapêutico
Isoquinolinas/farmacologia
Isoquinolinas/uso terapêutico
Masculino
Meia-Idade
Polietilenoglicóis/uso terapêutico
Inibidores de Proteases/farmacologia
Inibidores de Proteases/uso terapêutico
Proteínas Recombinantes/uso terapêutico
Ribavirina/farmacologia
Ribavirina/uso terapêutico
Simeprevir/farmacologia
Simeprevir/uso terapêutico
Sulfonamidas/farmacologia
Sulfonamidas/uso terapêutico
Fatores de Tempo
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (BMS-790052); 0 (Imidazoles); 0 (Interferon-alpha); 0 (Isoquinolines); 0 (NS-5 protein, hepatitis C virus); 0 (Protease Inhibitors); 0 (Recombinant Proteins); 0 (Sulfonamides); 0 (Viral Nonstructural Proteins); 30IQX730WE (Polyethylene Glycols); 49717AWG6K (Ribavirin); 9WS5RD66HZ (Simeprevir); EC 3.4.- (NS3-4A serine protease, Hepatitis C virus); EC 3.4.- (Serine Proteases); G8RGG88B68 (peginterferon alfa-2b); S9X0KRJ00S (asunaprevir)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE



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