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1.
N Engl J Med ; 381(13): 1201-1214, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31553833

RESUMO

BACKGROUND: The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown. METHODS: We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range-based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). RESULTS: The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P<0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P = 0.002 and P<0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo. CONCLUSIONS: Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis. (Funded by Janssen Research and Development; UNIFI ClinicalTrials.gov number, NCT02407236.).


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Ustekinumab/uso terapêutico , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Quimioterapia de Indução , Infusões Intravenosas , Injeções Subcutâneas , Quimioterapia de Manutenção , Masculino , Gravidade do Paciente , Indução de Remissão/métodos , Ustekinumab/administração & dosagem , Ustekinumab/efeitos adversos
2.
N Engl J Med ; 381(13): 1215-1226, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31553834

RESUMO

BACKGROUND: Biologic therapies are widely used in patients with ulcerative colitis. Head-to-head trials of these therapies in patients with inflammatory bowel disease are lacking. METHODS: In a phase 3b, double-blind, double-dummy, randomized trial conducted at 245 centers in 34 countries, we compared vedolizumab with adalimumab in adults with moderately to severely active ulcerative colitis to determine whether vedolizumab was superior. Previous exposure to a tumor necrosis factor inhibitor other than adalimumab was allowed in up to 25% of patients. The patients were assigned to receive infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). Dose escalation was not permitted in either group. The primary outcome was clinical remission at week 52 (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). To control for type I error, efficacy outcomes were analyzed with a hierarchical testing procedure, with the variables in the following order: clinical remission, endoscopic improvement (subscore of 0 to 1 on the Mayo endoscopic component), and corticosteroid-free remission at week 52. RESULTS: A total of 769 patients underwent randomization and received at least one dose of vedolizumab (383 patients) or adalimumab (386 patients). At week 52, clinical remission was observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group (31.3% vs. 22.5%; difference, 8.8 percentage points; 95% confidence interval [CI], 2.5 to 15.0; P = 0.006), as was endoscopic improvement (39.7% vs. 27.7%; difference, 11.9 percentage points; 95% CI, 5.3 to 18.5; P<0.001). Corticosteroid-free clinical remission occurred in 12.6% of the patients in the vedolizumab group and in 21.8% in the adalimumab group (difference, -9.3 percentage points; 95% CI, -18.9 to 0.4). Exposure-adjusted incidence rates of infection were 23.4 and 34.6 events per 100 patient-years with vedolizumab and adalimumab, respectively, and the corresponding rates for serious infection were 1.6 and 2.2 events per 100 patient-years. CONCLUSIONS: In this trial involving patients with moderately to severely active ulcerative colitis, vedolizumab was superior to adalimumab with respect to achievement of clinical remission and endoscopic improvement, but not corticosteroid-free clinical remission. (Funded by Takeda; VARSITY ClinicalTrials.gov number, NCT02497469; EudraCT number, 2015-000939-33.).


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Adalimumab/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Indução de Remissão/métodos
4.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(8): 774-780, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31422617

RESUMO

Objective: To investigate the clinical value of laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis. Methods: From January 2019 to June 2019, the clinical data of 6 patients diagnosed as gastric cancer with peritoneal metastasis were retrospectively analyzed in the Gastrointestinal Surgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Five were male and 1 was female. The median age was 69.5 (28-77) years. The median body mass index (BMI) was 22.8 (19.6-23.5). All procedures were performed under general anesthesia with endotracheal intubation. The patient's body position and facility layout in the operating room were consistent with those of laparoscopic gastrectomy. The operator's position: the main surgeon was located on the right side of the patient, the first assistant stood on the left side of the patient, and the scopist stood between the patient's legs. Surgical procedure: (1) trocar location: three abdominal trocars was adopted, with one 12 mm umbilical port for the 30° laparoscope (point A). Location of the other two trocars was dependent on the procedure of exploration or biopsy as well as the two polyester cuff position of the peritoneal dialysis catheter: Usually one 5 mm port in the anterior midline 5 cm inferior to the umbilicus point was selected as point B to ensure that the distal end of the catheter could reach the Douglas pouch. The other 5 mm port was located in the right lower quadrant lateral to the umbilicus to establish the subcutaneous tunnel tract, and the proximal cuff was situated 2 cm away from the desired exit site (point C).(2) exploration of the abdominal cavity: a 30° laparoscope was inserted from 12 mm trocar below the umbilicus to explore the entire peritoneal cavity. The uterus and adnexa should be explored additionally for women. Once peritoneal metastasis was investigated and identified, primary laparoscopic peritoneal dialysis catheter implantation was performed so as to facilitate subsequent peritoneal chemotherapy. Ascites were collected for cytology in patients with ascites. (3) peritoneal dialysis catheter placement: the peritoneal dialysis catheter was introduced into the abdominal cavity from point A. Under the direct vision of laparoscopy, 2-0 absorbable ligature was reserved at the expected fixation point of the proximal cuff (point B) for the final knot closure. Non-traumatic graspers were used to pull the distal cuff of peritoneal dialysis catheter out of the abdominal cavity through point B. The 5-mm trocar was removed simultaneously, and the distal cuff was fixed between bilateral rectus sheaths at the anterior midline port site preperitoneally. To prevent subsequent ascites and chemotherapy fluid extravasation, the reserved crocheted wire was knotted. From point C the subcutaneous tunnel tract was created before the peritoneal steath towards the port site lateral to the umbilicus. Satisfactory catheter irrigation and outflow were then confirmed. Chemotherapy regimen after peritoneal dialysis catheterization: all patients began intraperitoneal chemotherapy on the second day after surgery. On the 1st and 8th day of each 3-weeks cycle, paclitaxel (20 mg/m(2)) was administered through peritoneal dialysis catheter, and paclitaxel (50 mg/m(2)) was injected intravenously. Meanwhile, S-1 was orally administered twice daily at a dose of 80 mg·m(-2)·d(-1) for 14 consecutive days followed by 7-days rest. To observe the patients' intraoperative and postoperative conditions. Results: All the procedures were performed successfully without intraoperative complications or conversion to laparotomy. No 30 day postoperative complications were observed. The median operative time was 33.5 (23-38) min. The median time to first flatus was 1(1-2) days, and the median postoperative hospital stay was 3 (3-4) days, without short-term complications within 30 days postoperatively. The last follow-up was up to July 10, 2019, and the patients were followed for 4(1-6) months. No ascites extravasation was observed and no death occurred in the 6 patients. There was no catheter obstruction or peritoneal fluid extravasation during and after chemotherapy. Conclusion: Laparoscopic peritoneal dialysis catheter implantation was safe and feasible for patients with peritoneal metastasis of gastric cancer. The abdominal exploration, tumor staging and the abdominal chemotherapy device implantation can be completed simultaneously, which could simplify the surgical approach, improve the quality of life for patients and further propose a new direction for the development of abdominal chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Paclitaxel/administração & dosagem , Diálise Peritoneal/instrumentação , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Cateterismo/métodos , Cateteres de Demora , China , Feminino , Humanos , Infusões Intravenosas , Infusões Parenterais , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/métodos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto Jovem
6.
N Engl J Med ; 381(8): 716-726, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31433919

RESUMO

BACKGROUND: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 µg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P = 0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P = 0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).


Assuntos
Doenças Cardiovasculares/mortalidade , Insuficiência Cardíaca/tratamento farmacológico , Relaxina/uso terapêutico , Vasodilatadores/uso terapêutico , Doença Aguda , Idoso , Pressão Sanguínea/efeitos dos fármacos , Progressão da Doença , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Incidência , Infusões Intravenosas , Masculino , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Relaxina/efeitos adversos , Relaxina/farmacologia , Falha de Tratamento , Vasodilatadores/efeitos adversos
7.
Medicine (Baltimore) ; 98(32): e16592, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393358

RESUMO

RATIONALE: Refractory nasopharyngeal carcinoma is challenging to treat and at present there is no standard treatment or any good choice. PATIENT CONCERNS: Although the three patients in our case reports had already underwent multiple treatments before, they still suffered from disease recurrence of nasopharyngeal carcinoma. DIAGNOSIS: They were diagnosed as refractory nasopharyngeal carcinoma. INTERVENTIONS: A continuous infusion of Endostar, an antiangiogenic agent, combined with chemotherapy and radiation therapy was given to treat the patients. OUTCOMES: Patients showed complete or partial response to the combined therapy as evidenced by regression of tumors and decrease in plasma Epstein-Barr virus (EBV) DNA load. LESSONS: Continuous infusions of Endostar in combination with chemotherapy and/or radiation therapy showed promising efficacy and safety. The combination therapy indicates a new approach to treat refractory nasopharyngeal carcinoma.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Endostatinas/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Adulto , Quimiorradioterapia/métodos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia
8.
Medicine (Baltimore) ; 98(32): e16779, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393402

RESUMO

BACKGROUND: Magnesium sulfate is the ideal drug for the prevention and treatment of eclampsia. Nevertheless, the best regimen for protection against eclampsia with minimal side effects remains to be established. This study aimed to compare serum magnesium levels during intravenous infusion of magnesium sulfate at 1 gram/hour versus 2 grams/hour as a maintenance dose to prevent eclampsia in pregnant and postpartum women with severe preeclampsia. METHODS: A randomized, triple-blind clinical trial was conducted, comparing serum magnesium levels during the intravenous infusion of magnesium sulfate at 1 gram/hour versus 2 grams/hour as a maintenance dose for the prevention of eclampsia in 62 pregnant and postpartum women with severe preeclampsia, 31 in each group. An intravenous loading dose of 6 grams of magnesium sulfate was administered over 30 minutes in both groups. The patients were then randomized to receive a maintenance dose of either 1 or 2 grams/hour for 24 hours. Primary outcomes consisted of serum magnesium levels at the following time points: baseline, 30 minutes, every 2 hours until the end of the first 6 hours, and every 6 hours thereafter until the termination of magnesium sulfate infusion. Side effects, maternal complications, and neonatal outcomes were the secondary outcomes. RESULTS: Serum magnesium levels were higher in the 2-gram/hour group, with a statistically significant difference from 2 hours after the beginning of the magnesium sulfate infusion (P <.05). Oliguria was the most common complication recorded in both groups, with no significant difference between the 2 regimens (RR 0.88; 95% CI: 0.49-1.56; P = .65). No cases of eclampsia occurred. Side effects were more common in the 2-gram/hour group (RR 1.89; 95% CI: 1.04-3.41; P = .02); however, all were mild. There were no differences between the 2 groups regarding neonatal outcomes, except for admission to neonatal intensive care, which was more frequent in the 1-gram/hour group (25% vs 6.3%; P = .04). CONCLUSION: Magnesium sulfate therapy at the maintenance dose of 1 gram/hour was just as effective as the 2-gram maintenance dose, with fewer side effects.


Assuntos
Eclampsia/prevenção & controle , Sulfato de Magnésio/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Adulto , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Sulfato de Magnésio/administração & dosagem , Sulfato de Magnésio/efeitos adversos , Sulfato de Magnésio/sangue , Período Pós-Parto , Gravidez , Resultado da Gravidez , Adulto Jovem
9.
Medicine (Baltimore) ; 98(34): e16810, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441852

RESUMO

BACKGROUD: The aim of this study was to compare the analgesic and adverse effects of oxycodone with 3 different infusion modes on postoperative pain after laparoscopic radical surgery of cervical cancer. METHODS: Ninety patients undergoing laparoscopic radical surgery of cervical cancer were randomly divided into 3 groups: Group A (continuous infusion with 0.01 mg/kg/h and a bolus dose with 0.03 mg/kg), Group B (a bolus dose with 0.03 mg/kg) and Group C (PCA was administered as a time-scheduled decremental continuous infusion based on lean body mass). A blinded observer recorded Visual Analogue Scale (VAS), Ramsay sedation score (RSS), infused cumulative dose of oxycodone and side effects at 1, 6, 12, 24, and 48 hours postoperatively, and satisfaction during the postoperative 48 hours. RESULTS: There were significant differences in the VAS pain score when resting or coughing among 3 groups at 1, 6 and 48 hours postoperatively (P <.05). VAS was significantly higher in Group B than in Group A and C until postoperative 1, 6, and 48 hours (P <.05). There were significant differences in cumulative PCA dose among the 3 groups at 1 and 48 hours postoperatively (P <.05). Group C showed significantly less amount of cumulative PCA dose compared to other 2 groups at 1 hour, whereas cumulative PCA dose of Group A at 48 hours was significantly more than other 2 groups (P <.05). There were no significant differences in postoperative nausea and vomiting, FAS, muscle chilling score and RSS among 3 groups at 1, 6, 12, 24 and 48 hours postoperatively. In addition, there was no difference in overall satisfaction during 48 hours postoperatively among 3 groups. CONCLUSIONS: Oxycodone provides significant analgesic effect in 3 different infusion modes over 48 hours after laparoscopic radical surgery of cervical cancer, and a time-scheduled decremental continuous infusion of oxycodone can become a better choice for patients after surgery of cervical cancer.


Assuntos
Analgesia Controlada pelo Paciente/métodos , Analgésicos Opioides/uso terapêutico , Oxicodona/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Adulto , Analgésicos não Entorpecentes/administração & dosagem , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Laparoscopia , Masculino , Pessoa de Meia-Idade , Oxicodona/administração & dosagem , Oxicodona/efeitos adversos , Medição da Dor , Estudos Prospectivos
11.
J Infus Nurs ; 42(4): 183-192, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31283660

RESUMO

Infusion-associated medication errors have the potential to cause the greatest patient harm. A 21-year review of errors and near-miss reports from a national medication error-reporting program found that infusion-associated medication errors resulted in the identification of numerous best practices that support patient safety. A content analysis revealed that most errors involved improper dosage, mistaken drug choice, knowledge-based mistakes, skill-based slips, and memory lapses. The multifaceted nature of administering medications via infusions was highlighted. Opportunities for improvements include best practices such as developing learning cultures and reinforcing the independent double-check process on medications. Staff will likely benefit from education on specific medications, prescription details, and smart pump technology.


Assuntos
Infusões Intravenosas/estatística & dados numéricos , Erros de Medicação/estatística & dados numéricos , Segurança do Paciente , Guias de Prática Clínica como Assunto/normas , Humanos , Near Miss , Recursos Humanos de Enfermagem no Hospital/educação
12.
J Infus Nurs ; 42(4): 203-208, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31283663

RESUMO

A cluster of 11 midline catheter failures occurred during a 2-week period in a Hospital in the Home program in an urban tertiary hospital in Australia. These failures prompted a 4-month retrospective audit of patients receiving outpatient antimicrobial therapy between December 1, 2016 and March 1, 2017. Primary outcomes were dwell time and catheter failure. Peripherally inserted central catheters had significantly fewer failures and significantly longer dwell times compared with midline catheters. Women experienced higher rates of midline catheter failure than men. The proportion of patients with midline catheters receiving continuous infusions who experienced a failure was markedly higher than those receiving bolus doses. Suggestions for further related research are discussed.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Hospitais/estatística & dados numéricos , Infusões Intravenosas , Antibacterianos/administração & dosagem , Austrália , Cateterismo Periférico/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
13.
N Engl J Med ; 381(1): 36-46, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31269364

RESUMO

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).


Assuntos
Ciclosporina/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclosporina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/efeitos adversos , Infusões Intravenosas , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteinúria/tratamento farmacológico , Indução de Remissão , Rituximab/efeitos adversos , Falha de Tratamento , Adulto Jovem
14.
Brain Nerve ; 71(8): 895-900, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31346146

RESUMO

Muse cells are non-tumorigenic reparative endogenous stem cells identified by SSEA-3+. They are pluripotent and are stably mobilized from the bone marrow to the peripheral blood and distribute to organ connective tissue, where they contribute to daily minute repair of damaged/lost cells by spontaneous differentiation into tissue-constituent cells. Muse cells specifically home to damaged site to repair the tissue by simultaneous differentiation into multiple tissue-constituent cells. When the number of endogenous Muse cells is not sufficient, administration of exogenous Muse cells delivers robust functional recovery. Muse cells do not need to be "induced" or genetically manipulated. Intravenous drip is the main method of administration, making surgical operation unnecessary. Because Muse cells have an immunomodulatory system similar to the placenta, donor-derived Muse cells can be directly administered to patients without HLA-matching or immunosuppression therapy. Allogeneic Muse cells remain in the host tissue as differentiated cells for more than half a year. Clinical trials for the treatment of myocardial infarction, stroke and epidermolysis bullosa with intravenous injection of donor-derived Muse cells are currently conducted by the Life Science Institute Inc. Muse cells may safely provide clinically relevant effects compatible with the 'body's natural repair systems' by a simple cost-effective strategy.


Assuntos
Infusões Intravenosas , Células-Tronco Pluripotentes/citologia , Medicina Regenerativa , Transplante de Células-Tronco , Diferenciação Celular , Humanos
15.
JAMA ; 322(4): 326-335, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31334795

RESUMO

Importance: Hyperglycemia during acute ischemic stroke is common and is associated with worse outcomes. The efficacy of intensive treatment of hyperglycemia in this setting remains unknown. Objectives: To determine the efficacy of intensive treatment of hyperglycemia during acute ischemic stroke. Design, Setting, and Participants: The Stroke Hyperglycemia Insulin Network Effort (SHINE) randomized clinical trial included adult patients with hyperglycemia (glucose concentration of >110 mg/dL if had diabetes or ≥150 mg/dL if did not have diabetes) and acute ischemic stroke who were enrolled within 12 hours from stroke onset at 63 US sites between April 2012 and August 2018; follow-up ended in November 2018. The trial included 1151 patients who met eligibility criteria. Interventions: Patients were randomized to receive continuous intravenous insulin using a computerized decision support tool (target blood glucose concentration of 80-130 mg/dL [4.4-7.2 mmol/L]; intensive treatment group: n = 581) or insulin on a sliding scale that was administered subcutaneously (target blood glucose concentration of 80-179 mg/dL [4.4-9.9 mmol/L]; standard treatment group: n = 570) for up to 72 hours. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on the 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) that was adjusted for baseline stroke severity. Results: Among 1151 patients who were randomized (mean age, 66 years [SD, 13.1 years]; 529 [46%] women, 920 [80%] with diabetes), 1118 (97%) completed the trial. Enrollment was stopped for futility based on prespecified interim analysis criteria. During treatment, the mean blood glucose level was 118 mg/dL (6.6 mmol/L) in the intensive treatment group and 179 mg/dL (9.9 mmol/L) in the standard treatment group. A favorable outcome occurred in 119 of 581 patients (20.5%) in the intensive treatment group and in 123 of 570 patients (21.6%) in the standard treatment group (adjusted relative risk, 0.97 [95% CI, 0.87 to 1.08], P = .55; unadjusted risk difference, -0.83% [95% CI, -5.72% to 4.06%]). Treatment was stopped early for hypoglycemia or other adverse events in 65 of 581 patients (11.2%) in the intensive treatment group and in 18 of 570 patients (3.2%) in the standard treatment group. Severe hypoglycemia occurred only among patients in the intensive treatment group (15/581 [2.6%]; risk difference, 2.58% [95% CI, 1.29% to 3.87%]). Conclusions and Relevance: Among patients with acute ischemic stroke and hyperglycemia, treatment with intensive vs standard glucose control for up to 72 hours did not result in a significant difference in favorable functional outcome at 90 days. These findings do not support using intensive glucose control in this setting. Trial Registration: ClinicalTrials.gov Identifier: NCT01369069.


Assuntos
Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Acidente Vascular Cerebral/complicações , Idoso , Isquemia Encefálica/complicações , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Hiperglicemia/complicações , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Infusões Intravenosas , Injeções Subcutâneas , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
16.
J Stroke Cerebrovasc Dis ; 28(9): 2488-2495, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31277995

RESUMO

BACKGROUND AND OBJECTIVE: Current standard practice guidelines recommend ICU admission for ischemic stroke patients treated with intravenous tissue plasminogen activator (IV-tPA). More recently, the trend in stroke care is to broaden eligibility for IV thrombolysis. Two examples are a more liberal inclusion criteria known as SMART criteria (sIV-tPA), and the transfer of patients to comprehensive stroke centers (CSC). The present study characterizes ICU interventions in these patients. Understanding which stroke patients that require ICU-level care may allow for placement of patients in the appropriate level of care at hospital admission. METHODS: We performed a retrospective review of consecutive transfer and nontransfer sIV-tPA-treated patients admitted to the ICU at a CSC. We evaluated the frequency, timing, and nature of ICU interventions. RESULTS: Three hundred and thirty one patients were treated with sIV-tPA and 42% required ICU interventions during ICU admission. Of patients requiring ICU interventions, 98% had an ICU intervention performed in triage, prior to admission. National Institute of Health Stroke Scale score only had a moderate association to requirement of ICU interventions. Neither transferring patients to a CSC nor the number of standard IV-tPA contraindications increased ICU interventions. CONCLUSIONS: Liberalized IV-tPA administration did not increase ICU interventions. Nearly all patients that required ICU interventions declared this need in triage, prior to ICU admission. This timing of ICU intervention use during triage is highly sensitive for whether a patient will require ongoing ICU-level care during hospital admission. Identifying ICU intervention use in triage may allow for more effective placement of post-IV-tPA patients in the appropriate inpatient care setting, leading to better utilization of scarce ICU resources.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Unidades de Terapia Intensiva , Admissão do Paciente , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Triagem , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Tomada de Decisão Clínica , Bases de Dados Factuais , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Infusões Intravenosas , Unidades de Terapia Intensiva/normas , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/normas , Seleção de Pacientes , Transferência de Pacientes , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/normas , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento , Triagem/normas
17.
J Stroke Cerebrovasc Dis ; 28(9): 2481-2487, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31277996

RESUMO

The Goal: The aim of the study was to investigate whether stroke volume or the presence of ischemic stroke lesion on follow-up computed tomography 1 day after admission had association with sleep apnea among ischemic stroke patients undergoing thrombolysis. MATERIALS AND METHODS: We prospectively recruited 110 consecutive ischemic stroke patients and performed computed tomography on admission and after 24 hours after intravenous thrombolysis. Stroke volume was measured from post-thrombolysis computed tomography scans. Unattended cardiorespiratory polygraphy with a 3-channel device was performed during 48 hours after admission. FINDINGS: Of 110 ischemic stroke patients treated with thrombolysis 65.5% were men. Mean age was 65.8 years and body mass index 27.5 kg/m2. The mean Epworth sleepiness scale score was 4.7. Eight patients (12.7%) with visible acute stroke after thrombolysis and none in the other group had hemorrhage as complication (P ˂ .001). Sleep apnea, determined as a respiratory event index greater than or equal to 5/hour, was diagnosed in 96.4% patients. Respiratory event index greater than 15/h was found in 72.8% of patients. Both mean baseline oxygen desaturation index (23.9 versus 16.5, P = .028) and obstructive apneas/hour (6.2 versus 2.7, P = .007) were higher in visible stroke group. Stroke volume (mean 15.9 mL) correlated with proportion of time spent below saturation less than 90%, P = .025. CONCLUSIONS: Acute ischemic stroke patients treated with thrombolysis with visible stroke were more likely to have nocturnal hypoxemia than patients with not visible strokes. Stroke volume correlated with time spent below saturation of 90%.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/efeitos adversos , Hipóxia/etiologia , Síndromes da Apneia do Sono/etiologia , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Hipóxia/diagnóstico , Hipóxia/fisiopatologia , Infusões Intravenosas , Pulmão/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração , Fatores de Risco , Sono , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/fisiopatologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Drugs ; 79(11): 1255-1262, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31270752

RESUMO

Onasemnogene abeparvovec (onasemnogene abeparvovec-xioi; formerly AVXS-101; ZOLGENSMA®) is an adeno-associated viral vector-based gene therapy designed to deliver a functional copy of the human survival motor neuron (SMN) gene to the motor neuron cells of patients with spinal muscular atrophy (SMA). It has been developed by AveXis, a Novartis company, and was approved in May 2019 in the USA for the treatment of paediatric patients aged < 2 years with SMA and bi-allelic mutations in the SMN1 gene (the primary gene encoding survival motor neuron protein). Onasemnogene abeparvovec is the first gene therapy to be approved for SMA in the USA. The recommended dose is 1.1 × 1014 vector genomes per kg of bodyweight, administered as a single intravenous infusion over 60 min. Regulatory assessments for this formulation of onasemnogene abeparvovec are underway in the EU and Japan; an intrathecal formulation is currently undergoing clinical development in the USA. This article summarizes the milestones in the development of onasemnogene abeparvovec leading to this first approval for the treatment of paediatric patients aged < 2 years with SMA and bi-allelic mutations in SMN1.


Assuntos
Atrofia Muscular Espinal/terapia , Proteínas do Complexo SMN/metabolismo , Dependovirus/genética , Aprovação de Drogas , Terapia Genética , Vetores Genéticos , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Neurônios Motores/metabolismo , Atrofia Muscular Espinal/genética , Mutação , Proteínas do Complexo SMN/genética , Estados Unidos , United States Food and Drug Administration
20.
Br J Anaesth ; 123(4): 430-438, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31255290

RESUMO

BACKGROUND: Vasopressor agents are used to prevent intraoperative hypotension and ensure adequate perfusion. Vasopressors are usually administered as intermittent boluses or manually adjusted infusions, but this practice requires considerable time and attention. We have developed a closed-loop vasopressor (CLV) controller to correct hypotension more efficiently. Here, we conducted a proof-of-concept study to assess the feasibility and performance of CLV control in surgical patients. METHODS: Twenty patients scheduled for elective surgical procedures were included in this study. The goal of the CLV system was to maintain MAP within 5 mm Hg of the target MAP by automatically adjusting the rate of a norepinephrine infusion using MAP values recorded continuously from an arterial catheter. The primary outcome was the percentage of time that patients were hypotensive, as defined by a MAP of 5 mm Hg below the chosen target. Secondary outcomes included the total dose of norepinephrine, percentage of time with hypertension (MAP>5 mm Hg of the chosen target), raw percentage "time in target" and Varvel performance criteria. RESULTS: The 20 subjects (median age: 64 years [52-71]; male (35%)) underwent elective surgery lasting 154 min [124-233]. CLV control maintained MAP within ±5 mm Hg of the target for 91.6% (85.6-93.3) of the intraoperative period. Subjects were hypotensive for 2.6% of the intraoperative period (range, 0-8.4%). Additional performance criteria for the controller included mean absolute performance error of 2.9 (0.8) and mean predictive error of 0.5 (1.0). No subjects experienced major complications. CONCLUSIONS: In this proof of concept study, CLV control minimised perioperative hypotension in subjects undergoing moderate- or high-risk surgery. Further studies to demonstrate efficacy are warranted. TRIAL REGISTRY NUMBER: NCT03515161 (ClinicalTrials.gov).


Assuntos
Infusões Intravenosas/instrumentação , Norepinefrina/administração & dosagem , Procedimentos Cirúrgicos Operatórios/métodos , Vasoconstritores/efeitos adversos , Idoso , Anestesia , Pressão Sanguínea/efeitos dos fármacos , Procedimentos Cirúrgicos Eletivos , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Hipertensão/induzido quimicamente , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Norepinefrina/uso terapêutico , Resultado do Tratamento , Vasoconstritores/uso terapêutico
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