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1.
Medicine (Baltimore) ; 100(4): e23753, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530174

RESUMO

ABSTRACT: To evaluate the utility of low-concentration nitrous oxide (N2O) anesthesia in ptosis surgeryThis study was a retrospective consecutive case series that included 54 successive patients with blepharoptosis who underwent bilateral levator aponeurosis advancement and on whom skin resection performed by the same surgeon between August 2016 and July 2017. Among these patients, 27 were operated with a local anesthesia injection (air group) and 27 with a local anesthesia injection and low-concentration N2O anesthesia (N2O group). All N2O cases used a total of 6 L of gas comprising 70% oxygen and 30% N2O. Preoperative and postoperative blood pressure (BP) and heart rate (HR) and intraoperative pain, anxiety, nausea, and memory were measured immediately after surgery using visual analog scale score (VASS). Additionally, perioperative side effects were examined.There was no significant difference in age, sex, and preoperative and postoperative margin reflex distance (MRD) between the 2 groups (all P > .05). The intraoperative mean peripheral oxygen saturation was significantly higher (97.5% ±â€Š1.6% vs 99.5% ±â€Š.6%, P < .001), intraoperative HR was significantly lower (78.2 ±â€Š12.8 vs 70.7 ±â€Š11.6 bpm, P = .02), and operation time was significantly shorter (33.1 ±â€Š8.1 vs 29.4 ±â€Š10.3 minutes, P = .03) in the N2O group than in the air group.Difference between intraoperative and preoperative systolic BP (BPs) (+15.8 ±â€Š18.0 vs + 3.1 ±â€Š21.7 mm Hg, P = .02), diastolic BP (BPd) (+7.0 ±â€Š17.4 vs -2.3 ±â€Š13.6 mm Hg, P = .04), and HR (3.2 ±â€Š8.5 vs -3.9 ±â€Š9.4 bpm, P = .01) was significantly lower in the N2O group than in the air group.VASS of intraoperative pain was significantly lower in the N2O group than in the air group (49.5 ±â€Š24.7 vs 22.6 ±â€Š14.9, P < .001), whereas intraoperative anxiety and memory did not present significant differences between the groups (P = .09 and P = .45, respectively). Intraoperative nausea score was 0 for all cases in both groups. There was no other side effect.Ptosis surgery with anesthesia using 30% N2O may effectively suppress intraoperative BP and HR along with pain and shorten the operation time without side effects such as nausea.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/efeitos adversos , Blefaroplastia/métodos , Blefaroptose/cirurgia , Óxido Nitroso/administração & dosagem , Óxido Nitroso/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Anestésicos Locais/administração & dosagem , Ansiedade/prevenção & controle , Pressão Sanguínea/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Período Intraoperatório , Masculino , Memória/efeitos dos fármacos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Duração da Cirurgia , Manejo da Dor , Estudos Retrospectivos , Sinais Vitais
2.
Support Care Cancer ; 29(1): 213-222, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32338316

RESUMO

PURPOSE: To compare rates of complete response (no emesis, retching, or rescue antiemetics) in the late phase (days 4-7 post-chemotherapy) of cycle 1 between transdermal granisetron and oral ondansetron in cervical, endometrial, or vaginal cancer survivors undergoing chemoradiation at The University of Texas MD Anderson Cancer Center and LBJ Hospital in Houston, TX. METHODS: In this non-blinded parallel design trial, eligible patients received a granisetron patch replaced every 7 days or 8 mg of ondansetron thrice daily continued for 72 h after chemotherapy completion. Data were collected on medication compliance, episodes of chemotherapy-induced nausea and vomiting (CINV), use of rescue antiemetics, and effects of CINV on quality of life. RESULTS: Seventy-five survivors receiving chemoradiation for cervical (n = 61), endometrial (n = 12), or vaginal (n = 2) cancer were electronically randomized to transdermal granisetron (n = 41) or oral ondansetron (n = 34). In the late phase of cycle 1, the rate of complete response was 49.8% (95% CI, 35.2-64.3%) for transdermal granisetron and 39.7% (95% CI, 24.4-56.1%) for oral ondansetron. The posterior probability that transdermal granisetron achieved a higher success rate in controlling late-onset CINV compared with oral ondansetron was 82%. During the acute phase (day 1 post-chemotherapy) of cycles 2 and 3, transdermal granisetron patients used more rescue antiemetics than oral ondansetron patients (p = 0.006 and p = 0.003, respectively). Otherwise, no between-group differences in CINV events were observed. Medication compliance and the effect of CINV on quality of life were similar between groups. CONCLUSION: Transdermal granisetron was 82% more like to control CINV than oral ondansetron in the late phase of cycle 1 and performed similarly to oral ondansetron in all other cycles. Transdermal granisetron should be considered an option as prophylactic antiemetic therapy for gynecologic cancer survivors undergoing chemoradiation.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Granisetron/uso terapêutico , Náusea/prevenção & controle , Ondansetron/uso terapêutico , Vômito/prevenção & controle , Administração Cutânea , Adulto , Antineoplásicos/uso terapêutico , Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Granisetron/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Ondansetron/administração & dosagem , Qualidade de Vida/psicologia , Indução de Remissão , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias Vaginais/tratamento farmacológico , Vômito/induzido quimicamente , Vômito/tratamento farmacológico
3.
Support Care Cancer ; 29(1): 255-261, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32346798

RESUMO

PURPOSE: The purpose of this study is to evaluate the prevalence over time of the measured side effects using a self-assessment questionnaire in normal clinical practice. METHODS: The prevalence of symptoms reported by patients on the questionnaire was evaluated over two 1-year periods: from 1 June 2006 to 31 May 2007 and from 1 July 2013 to 30 June 2014. Descriptive statistics were used to describe population. The 2006-2007 and 2013-2014 datasets were compared with each other using the chi-squared test for equality of proportion, Pearson's chi-squared test, and chi-squared test for trend in proportion. RESULTS: We analyzed 1974 questionnaires from 283 patients in 2006-2007 and 2619 questionnaires from 403 patients in 2013-2014. The most frequently encountered symptom in both periods was fatigue; nausea and constipation decreased in 2013-2014 compared with 2006-2007, while alopecia increased. CONCLUSIONS: Using the self-assessment questionnaire in normal clinical practice has allowed us to carry out an accurate prevalence survey on symptoms in patients receiving chemotherapy that takes into account not only reports of the presence of symptoms but also of their absence. Between 2006-2007 and 2013-2014, there was an increase in patients treated at the Oncological Day Hospital of the Biella Hospital, whose characteristics were comparable in the two periods, except for the type of therapies carried out. Some symptoms were in decline: fatigue, nausea, and constipation.


Assuntos
Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Neoplasias/tratamento farmacológico , Autoavaliação , Adulto , Idoso , Idoso de 80 Anos ou mais , Alopecia/induzido quimicamente , Alopecia/epidemiologia , Antineoplásicos/uso terapêutico , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/epidemiologia , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/epidemiologia , Pacientes , Prevalência , Inquéritos e Questionários , Adulto Jovem
4.
N Engl J Med ; 383(26): 2526-2537, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33369355

RESUMO

BACKGROUND: Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor. METHODS: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Patients who were 55 years of age or older, were in complete remission with or without complete blood count recovery, and were not candidates for hematopoietic stem-cell transplantation were randomly assigned to receive CC-486 (300 mg) or placebo once daily for 14 days per 28-day cycle. The primary end point was overall survival. Secondary end points included relapse-free survival and health-related quality of life. RESULTS: A total of 472 patients underwent randomization; 238 were assigned to the CC-486 group and 234 were assigned to the placebo group. The median age was 68 years (range, 55 to 86). Median overall survival from the time of randomization was significantly longer with CC-486 than with placebo (24.7 months and 14.8 months, respectively; P<0.001). Median relapse-free survival was also significantly longer with CC-486 than with placebo (10.2 months and 4.8 months, respectively; P<0.001). Benefits of CC-486 with respect to overall and relapse-free survival were shown in most subgroups defined according to baseline characteristics. The most common adverse events in both groups were grade 1 or 2 gastrointestinal events. Common grade 3 or 4 adverse events were neutropenia (in 41% of patients in the CC-486 group and 24% of patients in the placebo group) and thrombocytopenia (in 22% and 21%, respectively). Overall health-related quality of life was preserved during CC-486 treatment. CONCLUSIONS: CC-486 maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo among older patients with AML who were in remission after chemotherapy. Side effects were mainly gastrointestinal symptoms and neutropenia. Quality-of-life measures were maintained throughout treatment. (Supported by Celgene; QUAZAR AML-001 ClinicalTrials.gov number, NCT01757535.).


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Quimioterapia de Manutenção , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Quimioterapia de Manutenção/efeitos adversos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Qualidade de Vida , Indução de Remissão , Análise de Sobrevida
5.
PLoS One ; 15(12): e0242710, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362248

RESUMO

INTRODUCTION: The use of patient-reported outcomes (PROs) to systematically quantify adverse events (AE) will assist in the improvement of medical care and the QoL of patients living with HIV (PLWH). The aim of this study was to investigate the associations between self-reported side effects and other PROs, demographics and laboratory data, and further evaluate the Health Questionnaire (HQ) as a tool for following trends in patient-reported side effects over time in relation to trends in prescribed third agent in ART. MATERIALS AND METHODS: The Swedish National Registry InfCareHiv includes an annual self-reported nine-item HQwhich is used in patient-centered HIV care in all Swedish HIV units. In this study, the experience of side effects was addressed. We analyzed 9,476 HQs completed by 4,186 PLWH together with details about their prescribed ART and relevant biomarkers collected during 2011-2017. Data were analyzed using descriptive statistics, Pearson's correlation coefficient and mixed logistic regression. RESULTS: The cross-sectional analysis of the HQs showed that the frequency of reported side effects decreased from 32% (2011) to 15% (2017). During the same period, there was a shift in ART prescription from efavirenz (EFV) to dolutegravir (DTG) (positive correlation coefficient r = 0.94, p = 0.0016). Further, PLWH who reported being satisfied with their physical health (OR: 0.47, p = <0.001) or psychological health (OR: 0.70, p = 0.001) were less likely to report side effects than those less satisfied. CONCLUSIONS: Self-reported side effects were found to have a close relationship with the patient's ratings of their overall health situation and demonstrated a strong correlation with the sharp decline in use of EFV and rise in use of DTG, with reported side effects being halved. This study supports the feasibility of using the HQ as a tool for longitudinal follow up of trends in PROs.


Assuntos
Alquinos/efeitos adversos , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Benzoxazinas/efeitos adversos , Ciclopropanos/efeitos adversos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Oxazinas/efeitos adversos , Piperazinas/efeitos adversos , Piridonas/efeitos adversos , Qualidade de Vida/psicologia , Sistema de Registros , Adulto , Alquinos/administração & dosagem , Fármacos Anti-HIV/administração & dosagem , Artralgia/induzido quimicamente , Artralgia/diagnóstico , Artralgia/fisiopatologia , Benzoxazinas/administração & dosagem , Estudos Transversais , Ciclopropanos/administração & dosagem , Disfunção Erétil/induzido quimicamente , Disfunção Erétil/diagnóstico , Disfunção Erétil/fisiopatologia , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/fisiopatologia , Infecções por HIV/psicologia , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/diagnóstico , Náusea/fisiopatologia , Oxazinas/administração & dosagem , Medidas de Resultados Relatados pelo Paciente , Piperazinas/administração & dosagem , Piridonas/administração & dosagem , Suécia
6.
Rev Saude Publica ; 54: 106, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33175025

RESUMO

OBJECTIVE: To estimate the incidence and to evaluate risk factors for antineoplastic nausea and vomiting with high and moderate emetogenic chemotherapy in adult patients in the first treatment cycle. METHODS: Prospective cohort study with follow-up of 269 adults during the first cycle of antineoplastic chemotherapy. The incidence of nausea and vomiting was evaluated in the acute phase (0-24 hours), in the late phase (24 hours-5th day) and in the total phase (0-5th day). RESULTS: In total, 152 patients underwent high emetogenic chemotherapy and 117 moderate emetogenic chemotherapy. The relative frequency of nausea was higher when compared with vomiting in the acute phase (p < 0.001) and in the late phase (p < 0.001). The risk factors identified were: age group ≤ 49 years (odds ratio = 0.47; 95%CI 0.23-0.95) and 50-64 years (odds ratio = 0.45; 95%CI 0.23-0.87), tobacco use (odds ratio = 0.35; 95%CI 0.14-0.88), and high emetogenic chemotherapy (odds ratio 0.55; 95%CI 0.31-0.95). CONCLUSION: The incidence of nausea was higher than that of vomiting, and adverse effects were more frequent in the late phase. The results suggest the risk factors for chemotherapy-induced nausea and vomiting are tobacco, age (young adults), and high emetogenic chemotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Náusea/induzido quimicamente , Neoplasias/tratamento farmacológico , Vômito/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antieméticos/uso terapêutico , Antineoplásicos/uso terapêutico , Brasil/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológico , Náusea/epidemiologia , Estudos Prospectivos , Fatores de Risco , Vômito/tratamento farmacológico , Vômito/epidemiologia
7.
Cochrane Database Syst Rev ; 10: CD013750, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084020

RESUMO

BACKGROUND: In a previous Cochrane Review, we found that for women with metastatic breast cancer unselected for triple-negative disease, there is little or no survival benefit and excess toxicity from platinum-based regimens. In subgroup analyses, however, we found preliminary low-quality evidence of a survival benefit from platinum-based regimens for women with metastatic triple-negative breast cancer (mTNBC). This review updates the evidence from the mTNBC subgroup analyses in the previous Cochrane Review. OBJECTIVES: To assess the effects of platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with mTNBC. SEARCH METHODS: We obtained relevant studies published prior to 2015 and their extracted results from the mTNBC subgroup analysis in the previous Cochrane Review. We searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov between 2015 and 27 September 2019. We identified further potentially relevant studies from previous trial reports, systematic reviews, and meta-analyses. SELECTION CRITERIA: Randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with mTNBC. Individual trials could compare one or more platinum-based regimens to one or more non-platinum regimens; hence there could be more 'treatment-comparisons' (i.e. platinum regimen versus non-platinum regimen comparison) than trials. Trial participants may have been purposely selected for mTNBC or inadvertently selected as a subgroup. DATA COLLECTION AND ANALYSIS: At least two independent reviewers assessed studies for eligibility and quality, and extracted all relevant data from each study. We derived hazard ratios (HRs) for time-to-event outcomes, where possible, and used fixed-effect models for meta-analyses. We analysed objective tumour response rates (OTRRs) and toxicities as binary (dichotomous) outcomes with risk ratios (RRs) used as measures of effects. We extracted quality of life data, if available. We used GRADE to rate the quality of evidence for time-to-event and tumour response outcomes. MAIN RESULTS: This review includes 13 treatment-comparisons involving 1349 women from 10 studies. Twelve of the 13 treatment-comparisons were included in one or more meta-analyses. Of the 13 treatment-comparisons, six and eight had published or provided time-to-event data on overall survival (OS) or progression-free survival/time to progression (PFS/TTP), respectively, that could be included in meta-analyses. Ten treatment-comparisons published or provided OTRR data that could be included in meta-analyses. Eight of the 13 treatment-comparisons were from studies that selected participants on the basis of mTNBC status, while the other five treatment-comparisons were from studies that reported mTNBC results as part of subgroup analyses. Analysis of six treatment-comparisons indicated that platinum-containing regimens may have provided a small survival benefit to mTNBC patients (HR 0.85, 95% CI 0.73 to 1.00; 958 women; moderate-quality evidence) with no evidence of heterogeneity (P = 0.41; I2 = 1%). Data from eight treatment-comparisons showed that platinum regimens may improve PFS/TTP (HR 0.77, 95% CI 0.68 to 0.88; 1077 women; very low-quality evidence). There was marked evidence of heterogeneity (P < 0.0001; I2 = 80%). There was also low-quality evidence of better tumour response for platinum recipients (RR 1.40, 95% CI 1.22 to 1.59; 1205 women) with some evidence of heterogeneity (P = 0.01; I2 = 58%). The observed heterogeneity for the PFS/TTP and OTRR outcomes may reflect between-study differences and general difficulties in assessing tumour response, as well as the varying potencies of the comparators. Compared with women receiving non-platinum regimens: rates of grade 3 and 4 nausea/vomiting were higher for platinum recipients (RR 4.77, 95% CI 1.93 to 11.81; 655 women; low-quality evidence) and rates of grade 3 and 4 anaemia were higher for platinum recipients (RR 3.80, 95% CI 2.25 to 6.42; 843 women; low-quality evidence). In general, however, relatively few intervention-comparisons could be included in meta-analyses for adverse events. None of the studies reported quality of life. AUTHORS' CONCLUSIONS: For women with mTNBC, there was moderate-quality evidence of a small survival benefit from platinum-based regimens compared to non-platinum regimens. This finding is consistent with findings of a PFS/TTP benefit and improved tumour response from platinum-based regimens. These potential benefits, however, should be weighed against previously identified excess toxicities from platinum-based regimens, particularly regimens containing cisplatin. Further randomised trials of platinum-based regimens among women with mTNBC are required.


Assuntos
Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Oxaliplatina/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/efeitos adversos , Viés , Carboplatina/efeitos adversos , Cisplatino/efeitos adversos , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Náusea/induzido quimicamente , Oxaliplatina/efeitos adversos , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Vômito/induzido quimicamente
9.
Medicine (Baltimore) ; 99(33): e21559, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872006

RESUMO

OBJECTIVE: To systematically evaluate the efficacy and safety of antiemetic regimen with aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) and provide updated information for clinical practice. METHODS: Pubmed, Embase, the Cochrane Library, and 3 Chinese literature databases were systematically searched. Randomized controlled trials comparing standard regimen (5-hydroxytryptamine-3 receptor antagonist and glucocorticoid) with aprepitant triple regimen (aprepitant plus the standard regimen) for preventing CINV were screened. Literature selection, data extraction, and quality evaluation were performed by 2 reviewers independently. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the meta-analysis using RevMan 5.3 software. RESULTS: A total of 51 randomized controlled trials were finally included in the systematic review. Compared with the standard regimen, the aprepitant triple regimen significantly improved the complete response in the overall (OR 1.88, 95% CI 1.71-2.07), acute (OR 1.96, 95% CI 1.65-2.32) and delayed (OR 1.96, 95% CI 1.70-2.27) phases, regardless of emetogenic risk of chemotherapy. Aprepitant could also significantly enhance the proportions of patients who have no emesis, nausea, or use of rescue medication respectively in the overall, acute and/or delayed phases. Aprepitant was found to be associated with decreased risk of constipation (OR 0.85, 95% CI 0.74-0.97), but increased the incidence of hiccup (OR 1.26, 95% CI 1.05, 1.51). There were no statistically significant differences between the 2 groups on other safety outcomes. CONCLUSION: The aprepitant triple regimen is effective for the prevention of CINV in patients being treated with moderately or highly emetogenic chemotherapy, and has a significant tendency to reduce the risk of constipation and increase the incidence of hiccup.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Aprepitanto/uso terapêutico , Náusea/prevenção & controle , Vômito/prevenção & controle , Humanos , Náusea/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Vômito/induzido quimicamente
10.
N Engl J Med ; 383(10): 944-957, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32877583

RESUMO

BACKGROUND: Among patients with non-small-cell lung cancer (NSCLC), MET exon 14 skipping mutations occur in 3 to 4% and MET amplifications occur in 1 to 6%. Capmatinib, a selective inhibitor of the MET receptor, has shown activity in cancer models with various types of MET activation. METHODS: We conducted a multiple-cohort, phase 2 study evaluating capmatinib in patients with MET-dysregulated advanced NSCLC. Patients were assigned to cohorts on the basis of previous lines of therapy and MET status (MET exon 14 skipping mutation or MET amplification according to gene copy number in tumor tissue). Patients received capmatinib (400-mg tablet) twice daily. The primary end point was overall response (complete or partial response), and the key secondary end point was response duration; both end points were assessed by an independent review committee whose members were unaware of the cohort assignments. RESULTS: A total of 364 patients were assigned to the cohorts. Among patients with NSCLC with a MET exon 14 skipping mutation, overall response was observed in 41% (95% confidence interval [CI], 29 to 53) of 69 patients who had received one or two lines of therapy previously and in 68% (95% CI, 48 to 84) of 28 patients who had not received treatment previously; the median duration of response was 9.7 months (95% CI, 5.6 to 13.0) and 12.6 months (95% CI, 5.6 to could not be estimated), respectively. Limited efficacy was observed in previously treated patients with MET amplification who had a gene copy number of less than 10 (overall response in 7 to 12% of patients). Among patients with MET amplification and a gene copy number of 10 or higher, overall response was observed in 29% (95% CI, 19 to 41) of previously treated patients and in 40% (95% CI, 16 to 68) of those who had not received treatment previously. The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%); these events were mostly of grade 1 or 2. CONCLUSIONS: Capmatinib showed substantial antitumor activity in patients with advanced NSCLC with a MET exon 14 skipping mutation, particularly in those not treated previously. The efficacy in MET-amplified advanced NSCLC was higher in tumors with a high gene copy number than in those with a low gene copy number. Low-grade peripheral edema and nausea were the main toxic effects. (Funded by Novartis Pharmaceuticals; GEOMETRY mono-1 ClinicalTrials.gov number, NCT02414139.).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imidazóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Triazinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Edema/induzido quimicamente , Éxons , Feminino , Dosagem de Genes , Humanos , Imidazóis/efeitos adversos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-met/genética , Triazinas/efeitos adversos
11.
Medicine (Baltimore) ; 99(38): e22150, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957337

RESUMO

BACKGROUND: Nausea and vomiting are the most common complications after chemotherapy, which cannot be completely controlled even with commonly prescribed antiemetic drugs, particularly in patients receiving highly emetogenic chemotherapy Acupuncture therapy is an effective replacement method for chemotherapy-induced nausea and vomiting (CINV), which effectiveness and safety have been observed by many clinicians. However, different acupuncture treatments have various effectiveness. Based on enough clinical researches, the study aims to uses Bayesian network meta-analysis (NMA) to evaluate the effectiveness of different acupuncture therapies used for preventing CINV. METHODS: Authors will search PubMed/Medline, Cochrane library, Web of Science, Ebsco, Ovid/Embase, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine from setup time to July 2020. All randomized control trails meet the standard will be included. Quality evaluation of included studies will be implemented with Cochrane risk-of-bias tool. STATA 14.0 will be used to perform pairwise meta-analysis. Addis 1.16.8 (University Medical Center Groningen (UMCG), Groningen, NL) and OpenBUGS 3.2.3 (Medical Research Council (MRC), London, UK) will be used to conduct NMA. RESULTS: The results of this review will generate a comprehensive review of current evidence and be published on a peer-reviewed journal. CONCLUSION: The result of this systematic review and Bayesian NMA may offer better options for patients in relieving CINV.Systematic review registration number: INPLASY202070070.


Assuntos
Terapia por Acupuntura/métodos , Antineoplásicos/efeitos adversos , Náusea/prevenção & controle , Projetos de Pesquisa , Vômito/prevenção & controle , Teorema de Bayes , Humanos , Náusea/induzido quimicamente , Metanálise em Rede , Revisões Sistemáticas como Assunto , Vômito/induzido quimicamente
12.
PLoS Med ; 17(8): e1003203, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32822347

RESUMO

BACKGROUND: Artemisinin resistance is threatening malaria control. We aimed to develop and test a human model of artemisinin-resistant (ART-R) Plasmodium falciparum to evaluate the efficacy of drugs against ART-R malaria. METHODS AND FINDINGS: We conducted 2 sequential phase 1, single-centre, open-label clinical trials at Q-Pharm, Brisbane, Australia, using the induced blood-stage malaria (IBSM) model, whereby healthy participants are intravenously inoculated with blood-stage parasites. In a pilot study, participants were inoculated (Day 0) with approximately 2,800 viable P. falciparum ART-R parasites. In a comparative study, participants were randomised to receive approximately 2,800 viable P. falciparum ART-R (Day 0) or artemisinin-sensitive (ART-S) parasites (Day 1). In both studies, participants were administered a single approximately 2 mg/kg oral dose of artesunate (AS; Day 9). Primary outcomes were safety, ART-R parasite infectivity, and parasite clearance. In the pilot study, 2 participants were enrolled between April 27, 2017, and September 12, 2017, and included in final analyses (males n = 2 [100%], mean age = 26 years [range, 23-28 years]). In the comparative study, 25 participants were enrolled between October 26, 2017, and October 18, 2018, of whom 22 were inoculated and included in final analyses (ART-R infected participants: males n = 7 [53.8%], median age = 22 years [range, 18-40 years]; ART-S infected participants: males n = 5 [55.6%], median age = 28 years [range, 22-35 years]). In both studies, all participants inoculated with ART-R parasites became parasitaemic. A total of 36 adverse events were reported in the pilot study and 277 in the comparative study. Common adverse events in both studies included headache, pyrexia, myalgia, nausea, and chills; none were serious. Seven participants experienced transient severe falls in white cell counts and/or elevations in liver transaminase levels which were considered related to malaria. Additionally, 2 participants developed ventricular extrasystoles that were attributed to unmasking of a predisposition to benign fever-induced tachyarrhythmia. In the comparative study, parasite clearance half-life after AS was significantly longer for ART-R infected participants (n = 13, 6.5 hours; 95% confidence interval [CI] 6.3-6.7 hours) compared with ART-S infected participants (n = 9, 3.2 hours; 95% CI 3.0-3.3 hours; p < 0.001). The main limitation of this study was that the ART-R and ART-S parasite strains did not share the same genetic background. CONCLUSIONS: We developed the first (to our knowledge) human model of ART-R malaria. The delayed clearance profile of ART-R parasites after AS aligns with field study observations. Although based on a relatively small sample size, results indicate that this model can be safely used to assess new drugs against ART-R P. falciparum. TRIAL REGISTRATION: The studies were registered with the Australian New Zealand Clinical Trials Registry: ACTRN12617000244303 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372357) and ACTRN12617001394336 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373637).


Assuntos
Anti-Infecciosos/uso terapêutico , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/sangue , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/metabolismo , Adolescente , Adulto , Animais , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/farmacologia , Antimaláricos/efeitos adversos , Antimaláricos/farmacologia , Artemisininas/efeitos adversos , Artemisininas/farmacologia , Artesunato/efeitos adversos , Artesunato/farmacologia , Artesunato/uso terapêutico , Austrália/epidemiologia , Feminino , Cefaleia/induzido quimicamente , Voluntários Saudáveis , Humanos , Malária Falciparum/epidemiologia , Masculino , Náusea/induzido quimicamente , Parasitos/metabolismo , Projetos Piloto , Adulto Jovem
13.
Cochrane Database Syst Rev ; 8: CD012977, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32767571

RESUMO

BACKGROUND: Asthma is an illness that commonly affects adults and children, and it serves as a common reason for children to attend emergency departments. An asthma exacerbation is characterised by acute or subacute worsening of shortness of breath, cough, wheezing, and chest tightness and may be triggered by viral respiratory infection, poor compliance with usual medication, a change in the weather, or exposure to allergens or irritants. Most children with asthma have mild or moderate exacerbations and respond well to first-line therapy (inhaled short-acting beta-agonists and systemic corticosteroids). However, the best treatment for the small proportion of seriously ill children who do not respond to first-line therapy is not well understood. Currently, a large number of treatment options are available and there is wide variation in management. OBJECTIVES: Main objective - To summarise Cochrane Reviews with or without meta-analyses of randomised controlled trials on the efficacy and safety of second-line treatment for children with acute exacerbations of asthma (i.e. after first-line treatments, titrated oxygen delivery, and administration of intermittent inhaled short-acting beta2-agonists and oral corticosteroids have been tried and have failed) Secondary objectives - To identify gaps in the current evidence base that will inform recommendations for future research and subsequent Cochrane Reviews - To categorise information on reported outcome measures used in trials of escalation of treatment for acute exacerbations of asthma in children, and to make recommendations for development and reporting of standard outcomes in future trials and reviews - To identify relevant randomised controlled trials that have been published since the date of publication of each included review METHODS: We included Cochrane Reviews assessing interventions for children with acute exacerbations of asthma. We searched the Cochrane Database of Systematic Reviews. The search is current to 28 December 2019. We also identified trials that were potentially eligible for, but were not currently included in, published reviews. We assessed the quality of included reviews using the ROBIS criteria (tool used to assess risk of bias in systematic reviews). We presented an evidence synthesis of data from reviews alongside an evidence map of clinical trials. Primary outcomes were length of stay, hospital admission, intensive care unit admission, and adverse effects. We summarised all findings in the text and reported data for each outcome in 'Additional tables'. MAIN RESULTS: We identified 17 potentially eligible Cochrane Reviews but extracted data from, and rated the quality of, 13 reviews that reported results for children alone. We excluded four reviews as one did not include any randomised controlled trials (RCTs), one did not provide subgroup data for children, and the last two had been updated and replaced by subsequent reviews. The 13 reviews included 67 trials; the number of trials in each review ranged from a single trial up to 27 trials. The vast majority of comparisons included between one and three trials, involving fewer than 100 participants. The total number of participants included in reviews ranged from 40 to 2630. All studies included children; 16 (24%) included children younger than two years of age. Most of the reviews reported search dates older than four years. We have summarised the published evidence as outlined in Cochrane Reviews. Key findings, in terms of our primary outcomes, are that (1) intravenous magnesium sulfate was the only intervention shown to reduce hospital length of stay (high-certainty evidence); (2) no evidence suggested that any intervention reduced the risk of intensive care admission (low- to very low-certainty evidence); (3) the risk of hospital admission was reduced by the addition of inhaled anticholinergic agents to inhaled beta2-agonists (moderate-certainty evidence), the use of intravenous magnesium sulfate (high-certainty evidence), and the use of inhaled heliox (low-certainty evidence); (4) the addition of inhaled magnesium sulfate to usual bronchodilator therapy appears to reduce serious adverse events during hospital admission (moderate-certainty evidence); (5) aminophylline increased vomiting compared to placebo (moderate-certainty evidence) and increased nausea and nausea/vomiting compared to intravenous beta2-agonists (low-certainty evidence); and (6) the addition of anticholinergic therapy to short-acting beta2-agonists appeared to reduce the risk of nausea (high-certainty evidence) and tremor (moderate-certainty evidence) but not vomiting (low-certainty evidence). We considered 4 of the 13 reviews to be at high risk of bias based on the ROBIS framework. In all cases, this was due to concerns regarding identification and selection of studies. The certainty of evidence varied widely (by review and also by outcome) and ranged from very low to high. AUTHORS' CONCLUSIONS: This overview provides the most up-to-date evidence on interventions for escalation of therapy for acute exacerbations of asthma in children from Cochrane Reviews of randomised controlled trials. A vast majority of comparisons involved between one and three trials and fewer than 100 participants, making it difficult to assess the balance between benefits and potential harms. Due to the lack of comparative studies between various treatment options, we are unable to make firm practice recommendations. Intravenous magnesium sulfate appears to reduce both hospital length of stay and the risk of hospital admission. Hospital admission is also reduced with the addition of inhaled anticholinergic agents to inhaled beta2-agonists. However, further research is required to determine which patients are most likely to benefit from these therapies. Due to the relatively rare incidence of acute severe paediatric asthma, multi-centre research will be required to generate high-quality evidence. A number of existing Cochrane Reviews should be updated, and we recommend that a new review be conducted on the use of high-flow nasal oxygen therapy. Important priorities include development of an internationally agreed core outcome set for future trials in acute severe asthma exacerbations and determination of clinically important differences in these outcomes, which can then inform adequately powered future trials.


Assuntos
Antiasmáticos/uso terapêutico , Asma/terapia , Broncodilatadores/uso terapêutico , Progressão da Doença , Revisões Sistemáticas como Assunto , Doença Aguda , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Aminofilina/administração & dosagem , Aminofilina/efeitos adversos , Antiasmáticos/administração & dosagem , Antibacterianos/uso terapêutico , Asma/tratamento farmacológico , Viés , Broncodilatadores/administração & dosagem , Criança , Pré-Escolar , Antagonistas Colinérgicos/uso terapêutico , Hélio , Humanos , Lactente , Tempo de Internação , Antagonistas de Leucotrienos/uso terapêutico , Sulfato de Magnésio/administração & dosagem , Sulfato de Magnésio/efeitos adversos , Sulfato de Magnésio/uso terapêutico , Náusea/induzido quimicamente , Náusea/prevenção & controle , Oxigênio/administração & dosagem , Respiração com Pressão Positiva , Ensaios Clínicos Controlados Aleatórios como Assunto , Vômito/induzido quimicamente , Trabalho Respiratório/efeitos dos fármacos
14.
J Vasc Interv Radiol ; 31(8): 1292-1299, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32654960

RESUMO

PURPOSE: To assess the use of opioid analgesics and/or antiemetic drugs for pain and nausea following selective chemoembolization with doxorubicin-based conventional (c)-transarterial chemoembolization versus drug-eluting embolic (DEE)-transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From October 2014 to 2016, 283 patients underwent 393 selective chemoembolization procedures including 188 patients (48%) who underwent c-transarterial chemoembolization and 205 (52%) who underwent DEE-transarterial chemoembolization. Medical records for all patients were retrospectively reviewed. Administration of postprocedural opioid and/or antiemetic agents were collated. Time of administration was stratified as phase 1 recovery (0-6 hours) and observation (6-24 hours). Logistic regression model was used to investigate the relationship of transarterial chemoembolization type and use of intravenous and/or oral analgesic and antiemetic medications while controlling for other clinical variables. RESULTS: More patients treated with DEE-transarterial chemoembolization required intravenous analgesia in the observation (6-24 hours) phase (18.5%) than those treated with c-transarterial chemoembolization (10.6%; P = .033). Similar results were noted for oral analgesic agents (50.2% vs. 31.4%, respectively; P < .001) and antiemetics (17.1% vs. 7.5%, respectively; P = .006) during the observation period. Multivariate regression models identified DEE-transarterial chemoembolization as an independent predictor for oral analgesia (odds ratio [OR], 1.84; P = .011), for intravenous and oral analgesia in opioid-naïve patients (OR, 2.46; P = .029) and for antiemetics (OR, 2.56; P = .011). CONCLUSIONS: Compared to c-transarterial chemoembolization, DEE-transarterial chemoembolization required greater amounts of opioid analgesic and antiemetic agents 6-24 hours after the procedure. Surgical data indicate that a persistent opioid habit can develop even after minor surgeries, therefore, caution should be exercised, and a regimen of nonopiate pain medications should be considered to reduce postprocedural pain after transarterial chemoembolization.


Assuntos
Analgésicos Opioides/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica , Neoplasias Hepáticas/tratamento farmacológico , Dor/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/efeitos adversos , Antieméticos/administração & dosagem , Antieméticos/efeitos adversos , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/prevenção & controle , Dor/diagnóstico , Dor/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Vômito/induzido quimicamente , Vômito/prevenção & controle
15.
Int J Hematol ; 112(4): 577-583, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32656635

RESUMO

Post-transplantation cyclophosphamide (PTCy) is a new method to prevent graft-versus-host disease after allogeneic hematopoietic cell transplantation. Although the use of dexamethasone is recommended as prophylaxis against chemotherapy-induced nausea and vomiting (CINV) for patients who receive high-dose cyclophosphamide, corticosteroids cannot be used during PTCy administration to exploit depletion of alloreactive T cells. Thus, CINV may not be adequately controlled in this situation. We retrospectively examined antiemetic efficacy of the combination of a 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA) and a NK1 receptor antagonist (NK1 RA) in 36 patients who received PTCy, and compared this efficacy with that of the same combination together with dexamethasone in 27 patients conditioned with cyclophosphamide and total body irradiation (CY/TBI). The proportion of patients who had no vomiting during the acute phase of PTCy administration was 81%, and was lower than 100% in the CY/TBI group (p = 0.02). Our results suggest that prevention of CINV using 5-HT3 RA and NK1 RA during PTCy administration is suboptimal and that addition of antiemetic is necessary in patients who receive PTCy.


Assuntos
Ciclofosfamida/efeitos adversos , Náusea/induzido quimicamente , Náusea/prevenção & controle , Antagonistas do Receptor de Neuroquinina-1/uso terapêutico , Cuidados Pós-Operatórios/efeitos adversos , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Vômito/induzido quimicamente , Vômito/prevenção & controle , Adulto , Antieméticos/administração & dosagem , Dexametasona/uso terapêutico , Quimioterapia Combinada , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Adulto Jovem
17.
Support Care Cancer ; 28(10): 5031-5036, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32601854

RESUMO

PURPOSE: People with cancer face an elevated risk of infection and severe sequelae from COVID-19. Dexamethasone is commonly used for antiemetic prophylaxis with systemic therapy for cancer. However, dexamethasone is associated with increased risk of viral and respiratory infections, and causes lymphopenia, which is associated with worse outcomes during COVID-19 infections. Our purpose was to minimize dexamethasone exposure during antiemetic prophylaxis for systemic therapy for solid tumors during the COVID-19 pandemic, while maintaining control of nausea and emesis. METHODS: We convened an expert panel to systematically review the literature and formulate consensus recommendations. RESULTS: No studies considered the impact of dexamethasone-based antiemetic regimens on the risk and severity of COVID-19 infection. Expert consensus recommended modifications to the 2019 Cancer Care Ontario Antiemetic Recommendations. CONCLUSION: Clinicians should prescribe the minimally effective dose of dexamethasone for antiemetic prophylaxis. Single-day dexamethasone dosing is recommended over multi-day dosing for regimens with high emetogenic risk excluding high-dose cisplatin, preferably in combination with palonosetron, netupitant, and olanzapine. For regimens with low emetogenic risk, 5-HT3 antagonists are recommended over dexamethasone.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Betacoronavirus , Infecções por Coronavirus , Dexametasona/uso terapêutico , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Pandemias , Pneumonia Viral , Vômito/prevenção & controle , Antineoplásicos/uso terapêutico , Infecções por Coronavirus/epidemiologia , Humanos , Náusea/induzido quimicamente , Ontário , Pneumonia Viral/epidemiologia , Guias de Prática Clínica como Assunto , Vômito/induzido quimicamente
18.
Cochrane Database Syst Rev ; 7: CD007783, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32609387

RESUMO

BACKGROUND: This is an update of the Cochrane Review first published in 2010; it includes one additional study. Primary generalised tonic-clonic seizures are a type of generalised seizure. Other types of seizures include: absence, myoclonic, and atonic seizures. Effective control of tonic-clonic seizures reduces the risk of injury and death, and improves quality of life. While most people achieve seizure control with one antiepileptic drug, around 30% do not, and require a combination of antiepileptic drugs. OBJECTIVES: To assess the effectiveness and tolerability of add-on lamotrigine for drug-resistant primary generalised tonic-clonic seizures. SEARCH METHODS: For the latest update, we searched these databases on 19 March 2019: Cochrane Register of Studies (CRS) Web, MEDLINE Ovid, and the WHO International Clinical Trials Registry Platform (ICTRP). The CRS includes records from the Cochrane Epilepsy Group Specialized Register, CENTRAL, Embase, and ClinicalTrials.gov. We imposed no language restrictions. We also contacted GlaxoSmithKline, manufacturers of lamotrigine. SELECTION CRITERIA: Randomised controlled parallel or cross-over trials of add-on lamotrigine for people of any age with drug-resistant primary generalised tonic-clonic seizures. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology; two review authors independently assessed trials for inclusion, evaluated risk of bias, extracted relevant data, and GRADE-assessed evidence. We investigated these outcomes: (1) 50% or greater reduction in primary generalised tonic-clonic seizure frequency; (2) seizure freedom; (3) treatment withdrawal; (4) adverse effects; (5) cognitive effects; and (6) quality of life. We used an intention-to-treat (ITT) population for all analyses, and presented results as risk ratios (RRs) with 95% confidence intervals (CIs); for adverse effects, we used 99% CIs to compensate for multiple hypothesis testing. MAIN RESULTS: We included three studies (total 300 participants): two parallel-group studies and one cross-over study. We assessed varied risks of bias across studies; most limitations arose from the poor reporting of methodological details. We meta-analysed data extracted from the two parallel-group studies, and conducted a narrative synthesis for data from the cross-over study. Both parallel-group studies (270 participants) reported all dichotomous outcomes. Participants taking lamotrigine were almost twice as likely to attain a 50% or greater reduction in primary generalised tonic-clonic seizure frequency than those taking a placebo (RR 1.88, 95% CI 1.43 to 2.45; low-certainty evidence). The results between groups were inconclusive for the likelihood of seizure freedom (RR 1.55, 95% CI 0.89 to 2.72; very low-certainty evidence); treatment withdrawal (RR 1.20, 95% CI 0.72 to 1.99; very low-certainty evidence); and individual adverse effects: ataxia (RR 3.05, 99% CI 0.05 to 199.36); dizziness (RR 0.91, 99% CI 0.29 to 2.86; very low-certainty evidence); fatigue (RR 1.02, 99% CI 0.13 to 8.14; very low-certainty evidence); nausea (RR 1.60, 99% CI 0.48 to 5.32; very low-certainty evidence); and somnolence (RR 3.73, 99% CI 0.36 to 38.90; low-certainty evidence). The cross-over trial (26 participants) reported that 7/14 participants with generalised tonic-clonic seizures experienced a 50% or greater reduction in seizure frequency with add-on lamotrigine compared to placebo. The authors reported four treatment withdrawals, but did not specify during which treatment allocation they occurred. Rash (seven lamotrigine participants; zero placebo participants) and fatigue (five lamotrigine participants; zero placebo participants) were the most frequently reported adverse effects. None of the included studies measured cognition. One parallel-group study (N = 153) evaluated quality of life. They reported inconclusive results for the overall quality of life score between groups (P = 0.74). AUTHORS' CONCLUSIONS: This review provides insufficient information to inform clinical practice. Low-certainty evidence suggests that lamotrigine reduces the rate of generalised tonic-clonic seizures by 50% or more. Very low-certainty evidence found inconclusive results between groups for all other outcomes. Therefore, we are uncertain to very uncertain that the results reported are accurate, and suggest that the true effect could be grossly different. More trials, recruiting larger populations, over longer periods, are necessary to determine lamotrigine's clinical use.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Tônico-Clônica/tratamento farmacológico , Lamotrigina/uso terapêutico , Anticonvulsivantes/efeitos adversos , Quimioterapia Adjuvante/métodos , Tontura/induzido quimicamente , Erupção por Droga/etiologia , Exantema/induzido quimicamente , Fadiga/induzido quimicamente , Humanos , Lamotrigina/efeitos adversos , Náusea/induzido quimicamente , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sonolência
19.
J Headache Pain ; 21(1): 66, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503415

RESUMO

BACKGROUND: Migraine has been recognized as one of common diseases in the world whose current treatment options are not ideal. Lasmiditan, an oral 5-hydroxytryptamine (HT)1F receptor agonist, appears more promising for the acute treatment of migraine because of considerably better effect profiles with no severe adverse events (AEs). This review aimed to systematically evaluate the efficacy and safety of lasmiditan from the results of randomized controlled trials (RCTs). METHODS: PubMed, Cochrane Library, Embase were searched on lasmiditan for the acute treatment of migraine from inception of the databases to Feb 1, 2020. Pain free and pain relief, global impression (very much/much better), and no/mild disability at 2 h in efficacy; total treatment-emergent adverse events (TEAEs), dizziness, nausea, fatigue, paraesthesia and somnolence in safety were extracted from the included studies. A systematic review and meta-analysis was performed using Review Manager Software version 5.3 (RevMan 5.3). RESULTS: Four RCTs with a total of 4960 subjects met our inclusion criteria. The overall effect estimate showed that lasmiditan was significantly superior to placebo in terms of pain free (RR 1.71, 95% CI 1.55-1.87), pain relief (RR 1.40, 95% CI 1.33-1.47), global impression (very much/much better) (RR 1.55, 95% CI 1.44-1.67), and no/mild disability (RR 1.15, 95% CI 1.10-1.20) at 2 h. For the safety, significant number of patients experienced TEAEs with lasmiditan than with placebo (RR 2.77, 95% CI 2.53-3.03), most TEAEs were central nervous system (CNS)-related and included dizziness (RR 5.81, 95% CI 4.72-7.14), nausea (RR 2.58, 95% CI 1.87-3.57), fatigue (RR 5.38, 95% CI 3.78-7.66), paraesthesia (RR 4.48, 95% CI 3.33-6.02), and somnolence (RR 2.82, 95% CI 2.18-3.66). CONCLUSIONS: This meta-analysis suggests that lasmiditan is effective for the acute treatment of migraine with a higher incidence of CNS-related adverse reactions compared with placebo. Long-term, open-label, multi-dose trials are required to verify the current findings.


Assuntos
Benzamidas/uso terapêutico , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/tratamento farmacológico , Piperidinas/uso terapêutico , Piridinas/uso terapêutico , Receptores de Serotonina/fisiologia , Agonistas do Receptor de Serotonina/uso terapêutico , Benzamidas/efeitos adversos , Tontura/induzido quimicamente , Humanos , Náusea/induzido quimicamente , Piperidinas/efeitos adversos , Piridinas/efeitos adversos , Agonistas do Receptor de Serotonina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Vertigem/induzido quimicamente
20.
Expert Opin Pharmacother ; 21(12): 1407-1418, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32486875

RESUMO

INTRODUCTION: Sufentanil is a selective µ-opioid agonist, used intravenously and intrathecally for moderate to severe acute pain. Sublingual sufentanil nanotablets have been developed; 15 mcg tablet for a patient-controlled analgesia device and 30-mcg tablet for a single-dose device administered by a healthcare professional. Dosing interval is a minimum of 20 min for a 15 mcg tablet and a treatment duration of up to 72 hours. The single 30-mcg nanotablet dosing interval is 1 hour. Mean plasma elimination half-life is 13 hours and bioavailability 47-57% after the first sublingual sufentanil tablet. AREAS COVERED: This review focuses on the effectiveness, safety, and feasibility of sublingual sufentanil 30-mcg single dose suspended by a healthcare professional for the management of moderate to severe acute pain. A few Phase 4 studies concerning the sublingual sufentanil tablet system containing 15-mcg nanotablets are also reviewed. EXPERT OPINION: Sufentanil sublingual 30-mcg nanotablets provide effective pain relief in various acute moderate to severe pain states. The safety profile of sublingual sufentanil 30 mcg is typical to opioids nausea, vomiting, and sedation being the most common ones. Sublingual sufentanil 30-mcg nanotablet has the potential for efficient moderate to severe pain management in supervised healthcare facilities.


Assuntos
Dor Aguda/tratamento farmacológico , Analgésicos Opioides/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Sufentanil/administração & dosagem , Dor Aguda/sangue , Administração Sublingual , Analgesia Controlada pelo Paciente , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Disponibilidade Biológica , Duração da Terapia , Feminino , Humanos , Náusea/induzido quimicamente , Medição da Dor , Dor Pós-Operatória/sangue , Sufentanil/efeitos adversos , Sufentanil/uso terapêutico , Comprimidos
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