Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.009
Filtrar
1.
PLoS Med ; 17(2): e1003038, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32092060

RESUMO

BACKGROUND: HVTN 100 evaluated the safety and immunogenicity of an HIV subtype C pox-protein vaccine regimen, investigating a 12-month booster to extend vaccine-induced immune responses. METHODS AND FINDINGS: A phase 1-2 randomized double-blind placebo-controlled trial enrolled 252 participants (210 vaccine/42 placebo; median age 23 years; 43% female) between 9 February 2015 and 26 May 2015. Vaccine recipients received ALVAC-HIV (vCP2438) alone at months 0 and 1 and with bivalent subtype C gp120/MF59 at months 3, 6, and 12. Antibody (IgG, IgG3 binding, and neutralizing) and CD4+ T-cell (expressing interferon-gamma, interleukin-2, and CD40 ligand) responses were evaluated at month 6.5 for all participants and at months 12, 12.5, and 18 for a randomly selected subset. The primary analysis compared IgG binding antibody (bAb) responses and CD4+ T-cell responses to 3 vaccine-matched antigens at peak (month 6.5 versus 12.5) and durability (month 12 versus 18) timepoints; IgG responses to CaseA2_gp70_V1V2.B, a primary correlate of risk in RV144, were also compared at these same timepoints. Secondary and exploratory analyses compared IgG3 bAb responses, IgG bAb breadth scores, neutralizing antibody (nAb) responses, antibody-dependent cellular phagocytosis, CD4+ polyfunctionality responses, and CD4+ memory sub-population responses at the same timepoints. Vaccines were generally safe and well tolerated. During the study, there were 2 deaths (both in the vaccine group and both unrelated to study products). Ten participants became HIV-infected during the trial, 7% (3/42) of placebo recipients and 3% (7/210) of vaccine recipients. All 8 serious adverse events were unrelated to study products. Less waning of immune responses was seen after the fifth vaccination than after the fourth, with higher antibody and cellular response rates at month 18 than at month 12: IgG bAb response rates to 1086.C V1V2, 21.0% versus 9.7% (difference = 11.3%, 95% CI = 0.6%-22.0%, P = 0.039), and ZM96.C V1V2, 21.0% versus 6.5% (difference = 14.5%, 95% CI = 4.1%-24.9%, P = 0.004). IgG bAb response rates to all 4 primary V1V2 antigens were higher 2 weeks after the fifth vaccination than 2 weeks after the fourth vaccination: 87.7% versus 75.4% (difference = 12.3%, 95% CI = 1.7%-22.9%, P = 0.022) for 1086.C V1V2, 86.0% versus 63.2% (difference = 22.8%, 95% CI = 9.1%-36.5%, P = 0.001) for TV1c8.2.C V1V2, 67.7% versus 44.6% (difference = 23.1%, 95% CI = 10.4%-35.7%, P < 0.001) for ZM96.C V1V2, and 81.5% versus 60.0% (difference = 21.5%, 95% CI = 7.6%-35.5%, P = 0.002) for CaseA2_gp70_V1V2.B. IgG bAb response rates to the 3 primary vaccine-matched gp120 antigens were all above 90% at both peak timepoints, with no significant differences seen, except a higher response rate to ZM96.C gp120 at month 18 versus month 12: 64.5% versus 1.6% (difference = 62.9%, 95% CI = 49.3%-76.5%, P < 0.001). CD4+ T-cell response rates were higher at month 18 than month 12 for all 3 primary vaccine-matched antigens: 47.3% versus 29.1% (difference = 18.2%, 95% CI = 2.9%-33.4%, P = 0.021) for 1086.C, 61.8% versus 38.2% (difference = 23.6%, 95% CI = 9.5%-37.8%, P = 0.001) for TV1.C, and 63.6% versus 41.8% (difference = 21.8%, 95% CI = 5.1%-38.5%, P = 0.007) for ZM96.C, with no significant differences seen at the peak timepoints. Limitations were that higher doses of gp120 were not evaluated, this study was not designed to investigate HIV prevention efficacy, and the clinical significance of the observed immunological effects is uncertain. CONCLUSIONS: In this study, a 12-month booster of subtype C pox-protein vaccines restored immune responses, and slowed response decay compared to the 6-month vaccination. TRIAL REGISTRATION: ClinicalTrials.gov NCT02404311. South African National Clinical Trials Registry (SANCTR number: DOH--27-0215-4796).


Assuntos
Vacinas contra a AIDS/uso terapêutico , Anticorpos Neutralizantes/imunologia , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/prevenção & controle , Proteínas do Vírus da Imunodeficiência Humana/imunologia , Imunização Secundária , Imunoglobulina G/imunologia , Vacinas contra a AIDS/imunologia , Adulto , Artralgia/induzido quimicamente , Método Duplo-Cego , Feminino , Cefaleia/induzido quimicamente , Humanos , Imunogenicidade da Vacina , Reação no Local da Injeção , Injeções Intramusculares , Masculino , África do Sul , Adulto Jovem
2.
JAMA ; 323(5): 432-443, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016310

RESUMO

Importance: Intravenous iron enables rapid correction of iron-deficiency anemia, but certain formulations induce fibroblast growth factor 23-mediated hypophosphatemia. Objective: To compare risks of hypophosphatemia and effects on biomarkers of mineral and bone homeostasis of intravenous iron isomaltoside (now known as ferric derisomaltose) vs ferric carboxymaltose. Design, Setting, and Participants: Between October 2017 and June 2018, 245 patients aged 18 years and older with iron-deficiency anemia (hemoglobin level ≤11 g/dL; serum ferritin level ≤100 ng/mL) and intolerance or unresponsiveness to 1 month or more of oral iron were recruited from 30 outpatient clinic sites in the United States into 2 identically designed, open-label, randomized clinical trials. Patients with reduced kidney function were excluded. Serum phosphate and 12 additional biomarkers of mineral and bone homeostasis were measured on days 0, 1, 7, 8, 14, 21, and 35. The date of final follow-up was June 19, 2018, for trial A and May 29, 2018, for trial B. Interventions: Intravenous administration of iron isomaltoside, 1000 mg, on day 0 or ferric carboxymaltose, 750 mg, infused on days 0 and 7. Main Outcomes and Measures: The primary end point was the incidence of hypophosphatemia (serum phosphate level <2.0 mg/dL) between baseline and day 35. Results: In trial A, 123 patients were randomized (mean [SD] age, 45.1 [11.0] years; 95.9% women), including 62 to iron isomaltoside and 61 to ferric carboxymaltose; 95.1% completed the trial. In trial B, 122 patients were randomized (mean [SD] age, 42.6 [12.2] years; 94.1% women), including 61 to iron isomaltoside and 61 to ferric carboxymaltose; 93.4% completed the trial. The incidence of hypophosphatemia was significantly lower following iron isomaltoside vs ferric carboxymaltose (trial A: 7.9% vs 75.0% [adjusted rate difference, -67.0% {95% CI, -77.4% to -51.5%}], P < .001; trial B: 8.1% vs 73.7% [adjusted rate difference, -65.8% {95% CI, -76.6% to -49.8%}], P < .001). Beyond hypophosphatemia and increased parathyroid hormone, the most common adverse drug reactions (No./total No.) were nausea (iron isomaltoside: 1/125; ferric carboxymaltose: 8/117) and headache (iron isomaltoside: 4/125; ferric carboxymaltose: 5/117). Conclusions and Relevance: In 2 randomized trials of patients with iron-deficiency anemia who were intolerant of or unresponsive to oral iron, iron isomaltoside (now called ferric derisomaltose), compared with ferric carboxymaltose, resulted in lower incidence of hypophosphatemia over 35 days. However, further research is needed to determine the clinical importance of this difference. Trial Registration: ClinicalTrials.gov Identifiers: NCT03238911 and NCT03237065.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Dissacarídeos/efeitos adversos , Compostos Férricos/efeitos adversos , Hematínicos/efeitos adversos , Hipofosfatemia/induzido quimicamente , Maltose/análogos & derivados , Adulto , Anemia Ferropriva/complicações , Biomarcadores/sangue , Biomarcadores/urina , Dissacarídeos/uso terapêutico , Feminino , Compostos Férricos/uso terapêutico , Cefaleia/induzido quimicamente , Hematínicos/uso terapêutico , Humanos , Hipofosfatemia/epidemiologia , Incidência , Masculino , Maltose/efeitos adversos , Maltose/uso terapêutico , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Fosfatos/sangue , Fosfatos/urina
3.
PLoS One ; 15(1): e0227796, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929600

RESUMO

BACKGROUND: Intravenous immunoglobulin (IVIG) therapy is used in the treatment of various diseases, and IVIG-related adverse effects (IVIG-AEs) vary from mild to severe. However, the mechanisms underlying IVIG-AEs and the potential predictive factors are not clear. This study investigated whether certain IVIG-AEs can be predicted before IVIG administration. STUDY DESIGN AND METHODS: This retrospective cohort study at the Division of Neurology, Saitama Children's Medical Center included patients enrolled from 2008 to 2018 who were < 18 years old and received IVIG for the first time. IVIG-AEs were classified according to the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 104 patients fulfilled the inclusion criteria. The rate of IVIG-AEs was 37.5% (39/104). The most frequent IVIG-AEs were fever (41.0% [16/39]) and headache (38.5% [15/39]). AEs were below grade 2 in all except one patient and there were no grade 4 AEs. High serum total protein (TP) level was significantly related to the occurrence of IVIG-AEs (odds ratio, 14.8; 95% confidence interval, 2.4-90.5; P < 0.01). The optimal cutoff TP level was 6.7 g/dL. Although low WBC count and immunoglobulin G level may be predictive risk factors of IVIG-AEs, it was not confirmed in this study. CONCLUSION: IVIG-AEs occurred in 37.5% of cases, and most were mild. TP was the best predictive risk factor of IVIG-AEs before IVIG administration. These results may aid in elucidating the mechanism underlying IVIG-AEs.


Assuntos
Imunoglobulinas Intravenosas/efeitos adversos , Criança , Pré-Escolar , Exantema/induzido quimicamente , Feminino , Febre/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Incidência , Lactente , Masculino , Náusea/induzido quimicamente , Fatores de Proteção , Estudos Retrospectivos , Vômito/induzido quimicamente
4.
J Matern Fetal Neonatal Med ; 33(1): 167-170, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29886797

RESUMO

Purpose: The aim of this study is to evaluate the safety of clinical usage of tadalafil in women with preeclampsia.Materials and methods: Maternal, fetal, and neonatal adverse events were closely examined in eight preeclampsia patients receiving tadalafil treatment.Results: There were no maternal adverse events associated with 10 mg/day of tadalafil. Even at 20 mg/day, only grade 1 headaches in two cases and grade 1 palpitation in one case were observed, which resolved spontaneously within 3 days. At a dose of 40 mg/day, there was only one case of grade 1 headache. All these adverse events were grade 1 and spontaneously resolved within 3 days. There were no fetal adverse events. All observed neonatal adverse events were thought to be caused by prematurity and not related to tadalafil.Conclusion: This study shows that tadalafil treatment for preeclampsia is deemed sufficiently tolerable. Although there was a dose-dependent increase in maternal adverse events, all the adverse events were mild and deemed to be safe for the mother and fetus at all dosages.


Assuntos
Pré-Eclâmpsia/tratamento farmacológico , Tadalafila/administração & dosagem , Tadalafila/efeitos adversos , Adulto , Arritmias Cardíacas/induzido quimicamente , Peso ao Nascer/efeitos dos fármacos , Cesárea/estatística & dados numéricos , Relação Dose-Resposta a Droga , Feminino , Cefaleia/induzido quimicamente , Humanos , Gravidez , Resultado da Gravidez , Resultado do Tratamento
5.
Pediatrics ; 144(6)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31740500

RESUMO

BACKGROUND: The 9-valent human papillomavirus vaccine (9vHPV) was approved for females and males aged 9 to 26 years in 2014. We analyzed postlicensure surveillance reports to the Vaccine Adverse Event Reporting System (VAERS). METHODS: We searched VAERS data for US reports of adverse events (AEs) after 9vHPV from December 2014 through December 2017. We calculated reporting rates and conducted empirical Bayesian data mining to identify disproportional reporting. Physicians reviewed reports for selected prespecified conditions. RESULTS: VAERS received 7244 reports after 9vHPV: 31.2% among females, 21.6% among males, and for 47.2%, sex was not reported. Overall, 97.4% of reports were nonserious. Dizziness, syncope, headache, and injection site reactions were most commonly reported; the most commonly reported AEs were similar between females and males. Two reports of death after 9vHPV were verified; no information in autopsy reports or death certificates suggested a causal relationship with vaccination. Approximately 28 million 9vHPV doses were distributed during the study period; crude AE reporting rates were 259 reports per million 9vHPV doses distributed for all reports and 7 per million doses distributed for serious reports. Syncope (a known AE associated with human papillomavirus vaccination) and several types of vaccine administration errors (eg, administered at wrong age) exceeded the statistical threshold for empirical Bayesian data mining findings. CONCLUSIONS: No new or unexpected safety concerns or reporting patterns of 9vHPV with clinically important AEs were detected. The safety profile of 9vHPV is consistent with data from prelicensure trials and from postmarketing safety data of its predecessor, the quadrivalent human papillomavirus vaccine.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/tendências , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Adolescente , Adulto , Criança , Bases de Dados Factuais/tendências , Tontura/induzido quimicamente , Tontura/epidemiologia , Feminino , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Humanos , Masculino , Estados Unidos/epidemiologia , Adulto Jovem
6.
Rev Lat Am Enfermagem ; 27: e3194, 2019 Oct 14.
Artigo em Português, Inglês, Espanhol | MEDLINE | ID: mdl-31618387

RESUMO

OBJECTIVE: using the urinary cotinine biomarker to verify the occurrence of green tobacco sickness in workers who cultivate Burley tobacco. METHOD: paired case-control study, based on smoking status and on the 1:4 ratio, with participation of 20 case workers and 91 controls. Data collection included household surveys and urine collection for cotinine examination. Student's T-Test, the Mann-Whitney test, Pearson's chi-square or Fisher's exact tests were used. RESULTS: of the 23 suspected cases, 20 showed elevated levels of cotinine, signs and symptoms of headache, skin irritation, nausea, sickness and general malaise, especially in the morning. Most had worked with tobacco that was wet from the morning dew and when the weather was warm. CONCLUSION: there are signs suggestive of green tobacco sickness in Burley tobacco workers. The action of health professionals is necessary for the development of health promotion and preventive actions addressing work-related illness.


Assuntos
Doenças dos Trabalhadores Agrícolas/diagnóstico , Cotinina/urina , Exposição Ocupacional/análise , Adulto , Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Doenças dos Trabalhadores Agrícolas/epidemiologia , Doenças dos Trabalhadores Agrícolas/urina , Biomarcadores/urina , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Cefaleia/induzido quimicamente , Humanos , Indicadores e Reagentes/análise , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Nicotina/envenenamento , Exposição Ocupacional/efeitos adversos , Equipamento de Proteção Individual , Inquéritos e Questionários , Tabaco/envenenamento
7.
N Engl J Med ; 381(10): 933-944, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31483964

RESUMO

BACKGROUND: Pyruvate kinase deficiency is caused by mutations in PKLR and leads to congenital hemolytic anemia. Mitapivat is an oral, small-molecule allosteric activator of pyruvate kinase in red cells. METHODS: In this uncontrolled, phase 2 study, we evaluated the safety and efficacy of mitapivat in 52 adults with pyruvate kinase deficiency who were not receiving red-cell transfusions. The patients were randomly assigned to receive either 50 mg or 300 mg of mitapivat twice daily for a 24-week core period; eligible patients could continue treatment in an ongoing extension phase. RESULTS: Common adverse events, including headache and insomnia, occurred at the time of drug initiation and were transient; 92% of the episodes of headache and 47% of the episodes of insomnia resolved within 7 days. The most common serious adverse events, hemolytic anemia and pharyngitis, each occurred in 2 patients (4%). A total of 26 patients (50%) had an increase of more than 1.0 g per deciliter in the hemoglobin level. Among these patients, the mean maximum increase was 3.4 g per deciliter (range, 1.1 to 5.8), and the median time until the first increase of more than 1.0 g per deciliter was 10 days (range, 7 to 187); 20 patients (77%) had an increase of more than 1.0 g per deciliter in the hemoglobin level at more than 50% of visits during the core study period, with improvement in markers of hemolysis. The response was sustained in all 19 patients remaining in the extension phase, with a median follow-up of 29 months (range, 22 to 35). Hemoglobin responses were observed only in patients who had at least one missense PKLR mutation and were associated with the red-cell pyruvate kinase protein level at baseline. CONCLUSIONS: The administration of mitapivat was associated with a rapid increase in the hemoglobin level in 50% of adults with pyruvate kinase deficiency, with a sustained response during a median follow-up of 29 months during the extension phase. Adverse effects were mainly low-grade and transient. (Funded by Agios Pharmaceuticals; ClinicalTrials.gov number, NCT02476916.).


Assuntos
Anemia Hemolítica Congênita não Esferocítica/tratamento farmacológico , Hemoglobinas/metabolismo , Piperazinas/administração & dosagem , Piruvato Quinase/deficiência , Erros Inatos do Metabolismo dos Piruvatos/tratamento farmacológico , Quinolinas/administração & dosagem , Administração Oral , Adolescente , Adulto , Anemia Hemolítica Congênita não Esferocítica/sangue , Anemia Hemolítica Congênita não Esferocítica/genética , Catecóis , Esquema de Medicação , Feminino , Seguimentos , Cefaleia/induzido quimicamente , Humanos , Masculino , Mutação , Piperazinas/efeitos adversos , Piruvato Quinase/sangue , Piruvato Quinase/genética , Erros Inatos do Metabolismo dos Piruvatos/sangue , Erros Inatos do Metabolismo dos Piruvatos/genética , Quinolinas/efeitos adversos , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Tirfostinas , Adulto Jovem
8.
Medicine (Baltimore) ; 98(33): e16440, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415348

RESUMO

RATIONALE: Consumption of oral contraceptive pills (OCP) is a known risk factor for cerebral venous sinus thrombosis (CVST) among women. Development of dural arteriovenous fistula (dAVF) afterwards was very uncommon. We present a rare chronic complication of development of dAVF after CVST. PATIENT CONCERNS: A 22-year-old woman suffered headache for a week. She was then admitted into our hospital. DIAGNOSIS: Contrast enhanced magnetic resonance venography (MRV) demonstrated the thrombosis of the left transverse-sigmoid sinus the second day. INTERVENTIONS: The intravenous thrombolysis was carried out. As the symptoms improved, the patient was discharged, while the treatment with oral dabigatran continued. However, 3 months after the onset, magnetic resonance imaging (MRI) showed swelling brainstem, and digital subtraction angiography (DSA) confirmed a dAVF. Clipping of the fistula was conducted, and her clinical symptoms improved gradually. OUTCOMES: The patient was transferred to rehabilitation center later, and received follow-up care. LESSONS: When a patient taking OCP and suffering from a sudden headache, a clinical suspicion of possible CVST should always arise to avoid the onset of dAVF as soon as possible.


Assuntos
Malformações Vasculares do Sistema Nervoso Central/induzido quimicamente , Anticoncepcionais Orais/efeitos adversos , Trombose dos Seios Intracranianos/induzido quimicamente , Feminino , Cefaleia/induzido quimicamente , Humanos , Adulto Jovem
9.
Muscle Nerve ; 60(5): 528-537, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31443119

RESUMO

INTRODUCTION: Although intravenous immune globulin (IVIg) is used to treat patients in the outpatient setting, there is limited documentation addressing the safety of this practice. METHODS: Retrospective analysis of 438 patients with neuromuscular diseases receiving IVIg in an outpatient setting. RESULTS: Adverse events (AE) overall occurred in 16.9% of patients. Headache was the most common AE, noted in 11.6% of patients. Serious AEs occurred in 0.91% of patients; aseptic meningitis was the only one noted. Multivariate analyses identified the following risk factors for AEs: first-lifetime course of IVIg, higher dose per course of IVIg, diagnosis of myasthenia gravis, women, and younger age. DISCUSSION: Intravenous immune globulin is generally safe to administer in an outpatient setting. Women, myasthenia gravis patients, and those receiving their first course or a higher total dose of IVIg are at an increased risk of experiencing an AE.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Doenças Neuromusculares/terapia , Adulto , Fatores Etários , Idoso , Assistência Ambulatorial , Exantema/induzido quimicamente , Feminino , Cefaleia/induzido quimicamente , Humanos , Hipertensão/induzido quimicamente , Infusões Intravenosas , Masculino , Meningite Asséptica/induzido quimicamente , Pessoa de Meia-Idade , Análise Multivariada , Miastenia Gravis/terapia , Miosite/terapia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
10.
Acta Neurol Scand ; 140(4): 290-295, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31269227

RESUMO

OBJECTIVES: To identify possible risk factors influencing the incidence of intravenous immunoglobulin (IVIg) treatment-related cephalalgia in neurological diseases. MATERIALS & METHODS: Retrospective chart review of neurological patients receiving IVIg treatment between July 13, 2017, and August 14, 2017. Patients with MS receiving natalizumab in the same setting were observed as a reference group. RESULTS: Patients with headache after IVIg infusion (n = 22 infusions) showed a reduced heart rate (by 6.0 ± 8.5 beats per minute [bpm]), but no significant difference in blood pressure. Patients without headache after IVIg infusion (n = 69 infusions) showed a higher systolic blood pressure increase and a stronger reduction in the heart rate (by 5.7 ± 8.6 bpm), compared to patients with headache after IVIg infusion. The infusion rate was significantly slower and age significantly lower in patients developing headache after IVIg infusion. Body temperature was unchanged in both groups. Binary logistic regression analysis revealed that blood pressure at baseline and age significantly influence the occurrence of cephalalgia. In reference, patients receiving natalizumab (ie, shorter infusions/smaller infusion volume), systolic blood pressure, and heart rate decreased, while body temperature increased. Here, one patient developed headache. CONCLUSIONS: Intravenous immunoglobulin-associated headache is not associated with an increased blood pressure after infusion but with a reduced heart rate, a slower infusion rate, female sex and seems to be influenced by baseline systolic blood pressure and age. A reaction to immunoglobulin aggregates, stabilizers, or vasoactive mediators are possible explanations. The absence of an association with body temperature does not suggest a systemic immune response as a cause for headache.


Assuntos
Cefaleia/induzido quimicamente , Cefaleia/fisiopatologia , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/efeitos adversos , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/fisiopatologia , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Feminino , Cefaleia/diagnóstico , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Infusões Intravenosas/efeitos adversos , Infusões Intravenosas/métodos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento
11.
PLoS One ; 14(7): e0219732, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31339910

RESUMO

BACKGROUND: The number of studies associating the use of sildenafil in gestation is increasing. This drug inhibits phosphodiesterase type 5 (PDE5), an enzyme responsible for degradation of nitric oxide, and its efficacy is greater in the placental territory, as the maternal side of the placenta have more PDE5 than other sites. For this reason, promising results have been observed related to the prevention of preeclampsia and intrauterine growth restriction and to improvement of maternal-fetal morbidity in cases of placental insufficiency. OBJECTIVE: To evaluate the benefits of using sildenafil in pregnancy. SEARCHED STRATEGY: MEDLINE, ClinicalTrials.gov, Embase, LILACS and Cochrane databases were searched through September 2018. There was no restriction in language or year of publication. This study was registered in PROSPERO (CRD42017060288). SELECTION CRITERIA: Randomized clinical trials which used sildenafil for treatment or prevention of obstetric diseases compared with placebo were selected. DATA COLLECTION AND ANALYSIS: The results were obtained using the inverse variance method for continuous variables and Man-Whitney for categorical variables. MAIN RESULTS: Among a population of 598 pregnant women from the seven clinical trials included, 139 had pre-eclampsia, 275 had intrauterine growth restriction, and 184 had oligohydramnios. A significant increase of 222.58 grams [27.75 to 417.41] was observed in the fetal weight at birth of patients taking sildenafil. The other outcomes did not show any statistical significance. This may be due to the small number of patients used in each study and the great heterogeneity between the groups. CONCLUSIONS: Sildenafil could be associated with increasing fetal weight at birth in placental insufficiency despite the limitations of this meta-analysis, even though more studies in this field are needed to introduce this drug into obstetric clinical practice.


Assuntos
Feto/efeitos dos fármacos , Resultado da Gravidez , Citrato de Sildenafila/farmacologia , Peso ao Nascer , Parto Obstétrico , Feminino , Idade Gestacional , Cefaleia/induzido quimicamente , Humanos , Lactente , Mortalidade Infantil , Trabalho de Parto , Gravidez , Viés de Publicação , Risco , Citrato de Sildenafila/efeitos adversos , Artérias Umbilicais/fisiologia
12.
PLoS Med ; 16(6): e1002839, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31233507

RESUMO

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. Recent trials have shown that a single-dose, triple-drug treatment (ivermectin with diethylcarbamazine and albendazole [IDA]) is superior to a two-drug combination (diethylcarbamazine plus albendazole [DA]) that is widely used in LF elimination programs. This study was performed to assess the safety of IDA and DA in a variety of endemic settings. METHODS AND FINDINGS: Large community studies were conducted in five countries between October 2016 and November 2017. Two studies were performed in areas with no prior mass drug administration (MDA) for filariasis (Papua New Guinea and Indonesia), and three studies were performed in areas with persistent LF despite extensive prior MDA (India, Haiti, and Fiji). Participants were treated with a single oral dose of IDA (ivermectin, 200 µg/kg; diethylcarbamazine, 6 mg/kg; plus albendazole, a fixed dose of 400 mg) or with DA alone. Treatment assignment in each study site was randomized by locality of residence. Treatment was offered to residents who were ≥5 years of age and not pregnant. Adverse events (AEs) were assessed by medical teams with active follow-up for 2 days and passive follow-up for an additional 5 days. A total of 26,836 persons were enrolled (13,535 females and 13,300 males). A total of 12,280 participants were treated with DA, and 14,556 were treated with IDA. On day 1 or 2 after treatment, 97.4% of participants were assessed for AEs. The frequency of all AEs was similar after IDA and DA treatment (12% versus 12.1%, adjusted odds ratio for IDA versus DA 1.15, 95% CI 0.87-1.52, P = 0.316); 10.9% of participants experienced mild (grade 1) AEs, 1% experienced moderate (grade 2) AEs, and 0.1% experienced severe (grade 3) AEs. Rates of serious AEs after DA and IDA treatment were 0.04% (95% CI 0.01%-0.1%) and 0.01% (95% CI 0.00%-0.04%), respectively. Severity of AEs was not significantly different after IDA or DA. Five of six serious AEs reported occurred after DA treatment. The most common AEs reported were headache, dizziness, abdominal pain, fever, nausea, and fatigue. AE frequencies varied by country and were higher in adults and in females. AEs were more common in study participants with microfilaremia (33.4% versus 11.1%, P < 0.001) and more common in microfilaremic participants after IDA than after DA (39.4% versus 25.6%, P < 0.001). However, there was no excess of severe or serious AEs after IDA in this subgroup. The main limitation of the study was that it was open-label. Also, aggregation of AE data from multiple study sites tends to obscure variability among study sites. CONCLUSIONS: In this study, we observed that IDA was well tolerated in LF-endemic populations. Posttreatment AE rates and severity did not differ significantly after IDA or DA treatment. Thus, results of this study suggest that IDA should be as safe as DA for use as a MDA regimen for LF elimination in areas that currently receive DA. TRIAL REGISTRATION: Clinicaltrials.gov registration number: NCT02899936.


Assuntos
Antiparasitários/administração & dosagem , Antiparasitários/efeitos adversos , Filariose Linfática/tratamento farmacológico , Administração Massiva de Medicamentos/efeitos adversos , Administração Massiva de Medicamentos/métodos , Adulto , Análise por Conglomerados , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Filariose Linfática/diagnóstico , Filariose Linfática/epidemiologia , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Feminino , Seguimentos , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Medicine (Baltimore) ; 98(22): e15868, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145343

RESUMO

BACKGROUND: Benralizumab, a humanized, anti-interleukin-5 (anti-IL-5) receptor α monoclonal antibody that directly and rapidly depletes eosinophils, has shown significant efficacy in reducing asthma exacerbations and improving lung function in moderate to severe eosinophilic asthma patients. However, there is some controversy regarding the adverse events (AEs) of benralizumab and a comprehensive analysis of these AEs has not been performed. This study aimed to assess the incidence of these AEs in published randomized controlled trials (RCTs). METHODS: We searched for RCTs in the Embase, PubMed and Cochrane databases that compared benralizumab with placebo in moderate to severe eosinophilic asthma patients. The outcome was the incidence of AEs during the observation period. RESULTS: Eight RCTs were analyzed in this study. Patients treated with benralizumab had a lower risk of overall AEs (risk ratio (RR) 0.94; 95% confidence interval (CI) 0.90-0.98), serious adverse events (SAEs) (RR 0.82; 95% CI 0.68-0.98), asthma exacerbation (RR 0.72, 95% CI 0.61-0.85), bronchitis (RR 0.76, 95% CI 0.59-0.96) and sinusitis (RR 0.64, 95% CI 0.48-0.85), but had a higher risk of headache (RR 1.42, 95% CI 1.07-1.87) and pyrexia (RR 2.26, 95% CI 1.32-3.87) than patients treated with placebo. No increased incidence of death, hypersensitivity, injection-site reactions, nasopharyngitis, rhinitis, upper respiratory tract infection, influenza, cough, nausea, back pain or arthralgia was observed with benralizumab compared with placebo. CONCLUSIONS: Benralizumab reduced the risk of SAEs, asthma exacerbation, bronchitis and sinusitis, and aggravated the risk of headache and pyrexia. Other AEs were comparable between the benralizumab group and placebo group. Therefore, benralizumab is a relatively safe drug, but vigilance regarding AEs is imperative during long-term treatment.


Assuntos
Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Asma/tratamento farmacológico , Eosinofilia Pulmonar/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Método Duplo-Cego , Feminino , Febre/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
15.
N Engl J Med ; 381(7): 614-625, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31050279

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two thirds of cases are associated with aquaporin-4 antibodies (AQP4-IgG) and complement-mediated damage to the central nervous system. In a previous small, open-label study involving patients with AQP4-IgG-positive disease, eculizumab, a terminal complement inhibitor, was shown to reduce the frequency of relapse. METHODS: In this randomized, double-blind, time-to-event trial, 143 adults were randomly assigned in a 2:1 ratio to receive either intravenous eculizumab (at a dose of 900 mg weekly for the first four doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4) or matched placebo. The continued use of stable-dose immunosuppressive therapy was permitted. The primary end point was the first adjudicated relapse. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS), which ranges from 0 (no disability) to 10 (death). RESULTS: The trial was stopped after 23 of the 24 prespecified adjudicated relapses, given the uncertainty in estimating when the final event would occur. The mean (±SD) annualized relapse rate in the 24 months before enrollment was 1.99±0.94; 76% of the patients continued to receive their previous immunosuppressive therapy during the trial. Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group (hazard ratio, 0.06; 95% confidence interval [CI], 0.02 to 0.20; P<0.001). The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01 to 0.15; P<0.001). The mean change in the EDSS score was -0.18 in the eculizumab group and 0.12 in the placebo group (least-squares mean difference, -0.29; 95% CI, -0.59 to 0.01). Upper respiratory tract infections and headaches were more common in the eculizumab group. There was one death from pulmonary empyema in the eculizumab group. CONCLUSIONS: Among patients with AQP4-IgG-positive NMOSD, those who received eculizumab had a significantly lower risk of relapse than those who received placebo. There was no significant between-group difference in measures of disability progression. (Funded by Alexion Pharmaceuticals; PREVENT ClinicalTrials.gov number, NCT01892345; EudraCT number, 2013-001150-10.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Aquaporina 4/imunologia , Complemento C5/antagonistas & inibidores , Inativadores do Complemento/uso terapêutico , Imunossupressores/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Autoanticorpos/sangue , Inativadores do Complemento/efeitos adversos , Avaliação da Deficiência , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Cefaleia/induzido quimicamente , Humanos , Imunoglobulina G/sangue , Imunossupressores/efeitos adversos , Masculino , Neuromielite Óptica/imunologia , Qualidade de Vida , Infecções Respiratórias/etiologia , Prevenção Secundária
16.
Drugs Aging ; 36(7): 639-645, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31054113

RESUMO

INTRODUCTION: Overactive bladder (OAB) affects adults of all ages. The risk for medication-related adverse events (AEs) may differ between age groups, given age-related changes in pharmacokinetics and pharmacodynamics. No previous study has differentiated the risk of AEs between older and non-older adults with OAB. OBJECTIVE: Our objective was to assess the risk of AEs and treatment discontinuations between older and non-older adults with OAB initiated on an antimuscarinic. METHODS: We searched MEDLINE (PubMed interface), Embase, SCOPUS, and Cochrane Central Register for Controlled Trials in a previous analysis in February 2015 and repeated the search in August 2018, with no additional studies identified. Studies that delineated AEs or treatment discontinuations between the older and non-older (age <65 years) subjects were included. RESULTS: Six studies that made nine comparisons between older and non-older subjects met the inclusion criteria. The AEs of dry mouth (46.7%), constipation (10.3%), and headache (7.7%) were most frequently reported. Older subjects were more likely to experience dry mouth (relative risk [RR] 1.09; 95% confidence interval [CI] 1.00-1.19), constipation (RR 1.92; 95% CI 1.52-2.43), dizziness (RR 2.37; 95% CI 1.21-4.62), and urinary retention (RR 4.17; 95% CI 1.76-9.89) than were non-older subjects. Headache was less likely to occur in older subjects (RR 0.58; 95% CI 0.40-0.86). Treatment discontinuations due to AEs were more likely to occur in the older subjects (RR 1.59; 95% CI 1.20-2.11). CONCLUSION: Treatment of OAB with antimuscarinics in the older population resulted in significantly higher rates of AEs, barring headache, when compared with non-older subjects.


Assuntos
Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/efeitos adversos , Bexiga Urinária Hiperativa/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Constipação Intestinal/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Xerostomia/induzido quimicamente
17.
Drugs R D ; 19(2): 191-200, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31004286

RESUMO

BACKGROUND: Two studies of intranasal 0.5% carbomer 980 gel were conducted evaluating nasal tolerability in healthy volunteers and safety and efficacy in adults with common cold symptoms. METHODS: Study 1 randomly assigned healthy adults to 0.5% carbomer 980 gel (n = 20) or placebo (n = 10) administered intranasally four times daily for 7 days. Nasal examinations were conducted at baseline and daily throughout the study. The primary endpoint was local nasal tolerability. Study 2 randomly assigned adults with an investigator-confirmed diagnosis of symptomatic common cold to 0.5% carbomer 980 gel (n = 87) or placebo (n = 81), administered intranasally four times daily for 7 days (except for day 1, where subjects who received their first dose mid-day administered only three doses). The primary efficacy endpoint was the average nasal symptom score over days 1‒4 (ANSS1-4). Secondary efficacy endpoints included ANSS over days 1‒7 and average total symptom score (ATSS). Adverse events (AEs) were recorded throughout the study. RESULTS: In study 1, subjects assigned to 0.5% carbomer 980 gel had no mucosal grading higher than grade 1B (superficial nasal mucosal erosion) and low incidences of mucosal bleeding and crusting. In study 2, there were no statistically significant differences between treatments for any efficacy endpoints. Active treatment was well-tolerated; the most commonly reported AEs were headache, myalgia, and cough. CONCLUSION: While 0.5% carbomer 980 gel nasal spray demonstrated good local nasal tolerability in healthy volunteers, the spray did not significantly impact the course of infection or resolution of cold symptoms in subjects with common cold.


Assuntos
Resinas Acrílicas/efeitos adversos , Resfriado Comum/tratamento farmacológico , Resinas Acrílicas/administração & dosagem , Administração Intranasal/efeitos adversos , Adulto , Tosse/induzido quimicamente , Tosse/epidemiologia , Método Duplo-Cego , Feminino , Géis , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mialgia/induzido quimicamente , Mialgia/epidemiologia , Resultado do Tratamento
18.
Aerosp Med Hum Perform ; 90(5): 480-483, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31023409

RESUMO

INTRODUCTION: Modafinil is a wakefulness-promoting stimulant that has been approved by the Republic of Singapore Air Force (RSAF) as a fatigue countermeasure medication since 2011. Each RSAF aircrew member must undergo a ground test to exclude operationally relevant adverse drug effects prior to consuming the medication for operational reasons. This study describes the RSAF's modafinil ground testing outcomes over a 7-yr period.METHODS: This is a retrospective case series of 243 RSAF aircrew members who underwent modafinil 100-mg test dosing over the 7-yr period from September 2011 to September 2018.RESULTS: The median age was 31 yr (range, 21-53 yr) and mean age was 31.7 yr ± 6.19 yr. Of the aircrew members, 234 (96.3%) were men and all were of Asian ethnicity. Of the subjects, 237 (97.5%) were medically cleared for the operational use of modafinil. Among the six (2.47%) who failed modafinil ground testing, headache (cumulative incidence, 1.65%), anxiety (cumulative incidence, 0.41%), diarrhea (cumulative incidence, 0.41%), and insomnia (cumulative incidence, 0.41%) were reported as the side effects experienced. None of the aircrew members experienced major adverse drug events.DISCUSSION: Our findings suggest a low occurrence of adverse drug effects among military aircrew members who undergo modafinil test dosing prior to using the drug operationally. To our knowledge, this is the single largest published case series of modafinil ground testing outcomes among Asian military aviators.Ooi T, Wong SH, See B. Modafinil as a stimulant for military aviators. Aerosp Med Hum Perform. 2019; 90(5):480-483.


Assuntos
Medicina Aeroespacial/métodos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Militares , Modafinila/efeitos adversos , Pilotos , Acidentes Aeronáuticos/prevenção & controle , Adulto , Ansiedade/induzido quimicamente , Ansiedade/epidemiologia , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Relação Dose-Resposta a Droga , Fadiga/prevenção & controle , Feminino , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modafinila/administração & dosagem , Estudos Retrospectivos , Singapura , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Vigília/efeitos dos fármacos , Adulto Jovem
19.
Arthritis Rheumatol ; 71(10): 1727-1732, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31008548

RESUMO

OBJECTIVE: Oral ulcers, the hallmark lesion of Behçet's disease (BD), can be disabling and resistant to conventional treatment, and there is a need for safe and effective treatment. We undertook this study to investigate the long-term safety and efficacy of ustekinumab therapy for BD-related oral ulcers that are resistant to colchicine. METHODS: This multicenter, prospective, open-label study included 30 patients who fulfilled the criteria of the International Study Group for BD and who were diagnosed as having active oral ulcers resistant to colchicine. Patients were treated subcutaneously with ustekinumab 90 mg at inclusion, at week 4, and then once every 12 weeks. Each patient was assessed longitudinally for the presence and number of oral ulcers, and median numbers of oral ulcers (with interquartile range [IQR]) were calculated. The primary efficacy end point was the proportion of patients at week 12 who experienced complete response, defined as having no oral ulcers. RESULTS: The median number of oral ulcers per patient during ustekinumab therapy was significantly lower at week 12 compared to baseline (0 [IQR 0-1] versus 2 [IQR 2-3]; P < 0.0001). Complete response was achieved in 60.0% and 88.9% of patients at weeks 12 and 24, respectively. The median Behçet's Syndrome Activity Score (in which higher scores indicate more active disease) was significantly lower at weeks 12 and 24 (17.5 [IQR 10-42.5] and 10 [IQR 8-11], respectively) versus baseline (70 [IQR 50-70]; P < 0.0001). After a median follow-up of 12 months (IQR 6-16 months), 26 patients (86.7%) were still receiving ustekinumab treatment. Reasons for ustekinumab discontinuation included BD flare (n = 3) and side effects (n = 1). Seven patients (23.3%) experienced adverse events, including headaches (n = 4) and asthenia (n = 2), with no serious side effects. CONCLUSION: Ustekinumab seems to be effective in treating BD-related oral ulcers that are resistant to treatment with colchicine.


Assuntos
Síndrome de Behçet/tratamento farmacológico , Úlceras Orais/tratamento farmacológico , Ustekinumab/uso terapêutico , Adulto , Astenia/induzido quimicamente , Colchicina/uso terapêutico , Feminino , Cefaleia/induzido quimicamente , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Falha de Tratamento , Resultado do Tratamento , Moduladores de Tubulina/uso terapêutico
20.
Cochrane Database Syst Rev ; 3: CD011268, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30883669

RESUMO

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on second-generation antidepressants (SGAs). OBJECTIVES: To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. SELECTION CRITERIA: For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non-randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full-text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random-effects (Mantel-Haenszel) meta-analyses. We assessed statistical heterogeneity by calculating the Chi2 statistic and the Cochran Q. We used the I2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. MAIN RESULTS: We identified 3745 citations after de-duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full-text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates.Overall, moderate-quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate-quality evidence), insomnia and nausea (both low-quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively.We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. AUTHORS' CONCLUSIONS: Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high-risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non-pharmacological interventions.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/uso terapêutico , Transtorno Afetivo Sazonal/tratamento farmacológico , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Bupropiona/efeitos adversos , Diarreia/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Incidência , Náusea/induzido quimicamente , Números Necessários para Tratar , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Transtorno Afetivo Sazonal/epidemiologia , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA