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1.
Int. j. clin. health psychol. (Internet) ; 21(1): 203-203, ene.-abr. 2021. tab, graf
Artículo en Inglés | IBECS | ID: ibc-200215

RESUMEN

BACKGROUND/OBJECTIVE: Brief transdiagnostic psychotherapies are a possible treatment for emotional disorders. We aimed to determine their efficacy on mild/moderate emotional disorders compared with treatment as usual (TAU) based on pharmacological interventions. METHOD: This study was a single-blinded randomized controlled trial with parallel design of three groups. Patients (N = 102) were assigned to brief individual psychotherapy (n = 34), brief group psychotherapy (n = 34) or TAU (n = 34). Participants were assessed before and after the interventions with the following measures: PHQ-15, PHQ-9, PHQ-PD, GAD-7, STAI, BDI-II, BSI-18, and SCID. We conducted per protocol and intention-to-treat analyses. RESULTS: Brief psychotherapies were more effective than TAU for the reduction of emotional disorders symptoms and diagnoses with moderate/high effect sizes. TAU was only effective in reducing depressive symptoms. CONCLUSIONS: Brief transdiagnostic psychotherapies might be the treatment of choice for mild/moderate emotional disorders and they seem suitable to be implemented within health care systems


ANTECEDENTES/OBJETIVO: Las psicoterapias breves son un posible tratamiento para los trastornos emocionales. Nuestro propósito fue determinar su eficacia en los trastornos emocionales leves/moderados en comparación con el tratamiento habitual basado en intervenciones farmacológicas. MÉTODO: Este estudio fue un ensayo clínico aleatorizado simple ciego con diseño paralelo de tres grupos. Los pacientes (N = 102) fueron asignados a psicoterapia breve individual (n = 34), psicoterapia breve grupal (n = 34) o tratamiento habitual (n = 34). Los participantes fueron evaluados antes y después del tratamiento con los siguientes instrumentos: PHQ-15, PHQ-9, PHQ-PD, GAD-7, STAI, BDI-II, BSI-18 y SCID. Se realizaron análisis por protocolo y por intención de tratar. RESULTADOS: Las psicoterapias breves fueron más efectivas que el tratamiento habitual para la reducción de síntomas y diagnósticos de los trastornos emocionales. El tratamiento habitual solo fue efectivo en reducir los síntomas depresivos. CONCLUSIONES: Las psicoterapias breves pueden ser el tratamiento de elección para los trastornos emocionales leves/moderados y podrían implementarse en los sistemas de salud


Asunto(s)
Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Psicoterapia Breve/métodos , Síntomas Afectivos/terapia , Atención Primaria de Salud , Índice de Severidad de la Enfermedad , Método Simple Ciego , Escalas de Valoración Psiquiátrica , Resultado del Tratamiento , Análisis de Intención de Tratar
2.
N Engl J Med ; 384(9): 829-841, 2021 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-33657295

RESUMEN

BACKGROUND: The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known. METHODS: In this phase 3, randomized, open-label trial, we randomly assigned adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle). The primary end point was progression-free survival, as determined by blinded independent central review. Secondary end points included overall survival, objective response as determined by independent review, and safety. Health-related quality of life was an exploratory end point. RESULTS: Overall, 651 patients were assigned to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). At a median follow-up of 18.1 months for overall survival, the median progression-free survival was 16.6 months (95% confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.64; P<0.001). The probability of overall survival at 12 months was 85.7% (95% CI, 81.3 to 89.1) with nivolumab plus cabozantinib and 75.6% (95% CI, 70.5 to 80.0) with sunitinib (hazard ratio for death, 0.60; 98.89% CI, 0.40 to 0.89; P = 0.001). An objective response occurred in 55.7% of the patients receiving nivolumab plus cabozantinib and in 27.1% of those receiving sunitinib (P<0.001). Efficacy benefits with nivolumab plus cabozantinib were consistent across subgroups. Adverse events of any cause of grade 3 or higher occurred in 75.3% of the 320 patients receiving nivolumab plus cabozantinib and in 70.6% of the 320 patients receiving sunitinib. Overall, 19.7% of the patients in the combination group discontinued at least one of the trial drugs owing to adverse events, and 5.6% discontinued both. Patients reported better health-related quality of life with nivolumab plus cabozantinib than with sunitinib. CONCLUSIONS: Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.).


Asunto(s)
Anilidas/administración & dosificación , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Nivolumab/administración & dosificación , Piridinas/administración & dosificación , Sunitinib/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Anilidas/efectos adversos , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno B7-H1/antagonistas & inhibidores , Carcinoma de Células Renales/mortalidad , Femenino , Humanos , Análisis de Intención de Tratar , Neoplasias Renales/mortalidad , Masculino , Persona de Mediana Edad , Nivolumab/efectos adversos , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Piridinas/efectos adversos , Calidad de Vida , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Sunitinib/efectos adversos , Análisis de Supervivencia
3.
N Engl J Med ; 384(13): 1191-1203, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33789008

RESUMEN

BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer. METHODS: We conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival. RESULTS: The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001). Disease-free survival favored nivolumab across multiple prespecified subgroups. Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group. CONCLUSIONS: Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 577 ClinicalTrials.gov number, NCT02743494.).


Asunto(s)
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Unión Esofagogástrica , Nivolumab/uso terapéutico , Adenocarcinoma/inmunología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Método Doble Ciego , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Nivolumab/efectos adversos , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/terapia
4.
Lancet Gastroenterol Hepatol ; 6(5): 350-358, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33740415

RESUMEN

BACKGROUND: Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Prophylactic rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) is considered as standard of care to reduce the risk of post-ERCP pancreatitis. It has been suggested that aggressive hydration might further reduce this risk. Guidelines already recommend aggressive hydration in patients who are unable to receive rectal NSAIDs, although it is laborious and time consuming. We aimed to evaluate the added value of aggressive hydration in patients receiving prophylactic rectal NSAIDs. METHODS: FLUYT, a multicentre, open-label, randomised, controlled trial done across 22 Dutch hospitals, included patients aged between 18 and 85 years with moderate to high risk of post-ERCP pancreatitis. Patients were randomly assigned (1:1) by a web-based module with varying block sizes to a combination of aggressive hydration and rectal NSAIDs (100 mg diclofenac or indomethacin; aggressive hydration group) or rectal NSAIDs (100 mg diclofenac or indomethacin) alone (control group). Randomisation was stratified according to treatment centre. Aggressive hydration comprised 20 mL/kg intravenous Ringer's lactate solution within 60 min from the start of ERCP, followed by 3 mL/kg per h for 8 h. The control group received normal intravenous saline with a maximum of 1·5 mL/kg per h and 3 L per 24 h. The primary endpoint was post-ERCP pancreatitis and was analysed on a modified intention-to-treat basis (including all patients who underwent randomisation and an ERCP and for whom data regarding the primary outcome were available). The trial is registered with the ISRCTN registry, ISRCTN13659155. FINDINGS: Between June 5, 2015, and June 6, 2019, 826 patients were randomly assigned, of whom 388 in the aggressive hydration group and 425 in the control group were included in the modified intention-to-treat analysis. Post-ERCP pancreatitis occurred in 30 (8%) patients in the aggressive hydration group and in 39 (9%) patients in the control group (relative risk 0·84, 95% CI 0·53-1·33, p=0·53). There were no differences in serious adverse events, including hydration-related complications (relative risk 0·99, 95% CI 0·59-1·64; p=1·00), ERCP-related complications (0·90, 0·62-1·31; p=0·62), intensive care unit admission (0·37, 0·07-1·80; p=0·22), and 30-day mortality (0·95, 0·50-1·83; p=1·00). INTERPRETATION: Aggressive periprocedural hydration did not reduce the incidence of post-ERCP pancreatitis in patients with moderate to high risk of developing this complication who routinely received prophylactic rectal NSAIDs. Therefore, the burden of laborious and time-consuming aggressive periprocedural hydration to further reduce the risk of post-ERCP pancreatitis is not justified. FUNDING: Netherlands Organisation for Health Research and Development and Radboud University Medical Center.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Fluidoterapia/métodos , Pancreatitis/prevención & control , Administración Rectal , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Humanos , Incidencia , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Pancreatitis/epidemiología , Pancreatitis/etiología , Resultado del Tratamiento , Adulto Joven
5.
Int J Qual Health Care ; 33(1)2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33693639

RESUMEN

BACKGROUND: Reorientation programmes have been an important component of neurotrauma rehabilitation for adults who suffer from post-traumatic amnesia (PTA) after traumatic brain injury (TBI); however, research testing the efficacy of acute programmes is limited. OBJECTIVE: This study aimed to determine if it is feasible to provide a standardized environmental reorientation programme to adults suffering from PTA after TBI in an acute care hospital setting, and whether it is likely to be beneficial. METHODS: We conducted a randomized controlled trial with concealed allocation and intention-to-treat analysis. A total of 40 participants suffering from PTA after TBI were included. The control group received usual care; the experimental group received usual care plus a standardized orientation programme inclusive of environmental cues. The primary outcome measure was time to emergence from PTA measured by the Westmead PTA Scale, assessed daily from hospital admission or on regaining consciousness. RESULTS: Adherence to the orientation programme was high, and there were no study-related adverse responses to the environmental orientation programme. Although there were no statistically significant between-group differences in time to emergence, the median time to emergence was shorter for those who received the standardized reorientation programme (9.0 (6.4-11.6) versus 13.0 (4.5-21.5) days). Multivariate analysis showed that the Glasgow Coma Scale (GCS) at scene (P = 0.041) and GCS at arrival at hospital (P = 0.0001) were significant factors contributing to the longer length of PTA. CONCLUSION: Providing an orientation programme in acute care is feasible for adults suffering from PTA after TBI. A future efficacy trial would require 216 participants to detect a between-group difference of 5 days with an alpha of 0.05 and a power of 80%.


Asunto(s)
Amnesia/etiología , Amnesia/rehabilitación , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/rehabilitación , Orientación , Adulto , Estudios de Factibilidad , Femenino , Escala de Coma de Glasgow , Humanos , Análisis de Intención de Tratar , Masculino , Proyectos Piloto , Estudios Prospectivos , Victoria
6.
Lancet Haematol ; 8(4): e267-e277, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33667420

RESUMEN

BACKGROUND: R-MegaCHOEP was the first phase 3 study comparing high-dose chemotherapy plus rituximab followed by autologous haematopoietic stem-cell transplantation (HSCT) with conventional chemotherapy plus rituximab in first-line therapy for patients aged 60 years or younger with high-risk aggressive B-cell lymphoma. Little is known about the long-term outcomes of these patients. We aimed to evaluate the long-term efficacy and safety of conventional chemotherapy versus high-dose chemotherapy after 10 years of follow-up in the R-MegaCHOEP trial. METHODS: In this open-label, randomised, phase 3 trial done across 61 centres in Germany, patients aged 18-60 years with newly diagnosed, high-risk (age-adjusted International Prognostic Index [IPI] 2 or 3) aggressive B-cell lymphoma were randomly assigned (1:1, using Pocock minimisation) to eight cycles of conventional chemotherapy (cyclosphosphamide, doxorubicin, vincristine, etoposide, and prednisolone) plus rituximab (R-CHOEP-14) or four cycles of high-dose chemotherapy plus rituximab followed by autologous HSCT (R-MegaCHOEP). The trial was unmasked. Patients were stratified by age-adjusted IPI factors, presence of bulky disease (tumour mass ≥7·5 cm diameter), and treatment centre. The primary endpoint was event-free survival, analysed here 10 years after randomisation. 10-year overall survival, progression-free survival, conditional survival, relapse patterns, secondary malignancies, and molecular characteristics were also analysed. All analyses were done on the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT00129090. FINDINGS: Between March 3, 2003, and April 7, 2009, 275 patients were randomly assigned to R-CHOEP-14 (n=136) or R-MegaCHOEP (n=139). 130 patients in the R-CHOEP-14 group and 132 patients in the R-MegaCHOEP group were included in the intention-to-treat population. After a median follow-up of 9·3 years (IQR 5·1-11·1), 10-year event-free survival was 51% (95% CI 42-61) in the R-MegaCHOEP group and 57% (47-67) in the R-CHOEP-14 group (adjusted hazard ratio [HR] 1·3 [95% CI 0·9-1·8], p=0·23). 10-year progression-free survival was 59% (50-68) in the R-MegaCHOEP group and 60% (51-70) in the R-CHOEP-14 group (adjusted HR 1·1 [0·7-1·7], p=0·64). 10-year overall survival was 66% (57-76) in the R-MegaCHOEP group and 72% (63-81) in the R-CHOEP-14 group (adjusted HR 1·3 [0·8-2·1], p=0·26). Relapse occurred in 30 (16% [95% CI 11-22]) of 190 patients who had complete remission or unconfirmed complete remission; 17 (17%) of 100 patients in the R-CHOEP-14 group and 13 (14%) of 90 patients in the R-MegaCHOEP group. Seven (23%) of 30 patients had low-grade histology at relapse and had better outcomes compared with patients who relapsed with aggressive histologies. Lymphoma affected the CNS in 18 (28%) of 64 patients with treatment failure. 22 secondary malignancies were reported in the intention-to-treat population; in 12 (9%) of 127 patients in the R-CHOEP-14 group and ten (8%) of 126 patients in the R-MegaCHOEP group. INTERPRETATION: Event-free survival and overall survival were similar between groups after 10 years of follow-up; outcomes were not improved in the R-MegaCHOEP group by high-dose chemotherapy and autologous HSCT. Patients who relapsed with aggressive histology showed a high incidence of CNS involvement and poor prognosis. For these patients, novel therapies are greatly warranted. FUNDING: Deutsche Krebshilfe (German Cancer Aid).


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma de Células B/tratamiento farmacológico , Rituximab/uso terapéutico , Adulto , Enfermedades del Sistema Nervioso Central/epidemiología , Enfermedades del Sistema Nervioso Central/patología , Etopósido/uso terapéutico , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Análisis de Intención de Tratar/métodos , Masculino , Persona de Mediana Edad , Prednisolona/uso terapéutico , Supervivencia sin Progresión , Seguridad , Inhibidores de Topoisomerasa II/uso terapéutico , Trasplante Autólogo/métodos , Resultado del Tratamiento , Vincristina/uso terapéutico
7.
Lancet Haematol ; 8(4): e289-e298, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33770484

RESUMEN

BACKGROUND: Primary immune thrombocytopenia is an autoimmune bleeding disorder. Preclinical reports suggest that the sialidase inhibitor oseltamivir induces a platelet response in the treatment of immune thrombocytopenia. This study investigated the activity and safety of dexamethasone plus oseltamivir versus dexamethasone alone as initial treatment in adult patients with primary immune thrombocytopenia. METHODS: This multicentre, randomised, open-label, parallel group, phase 2 trial was done in five tertiary medical hospitals in China. Eligible patients were aged 18 years or older with newly diagnosed, treatment-naive primary immune thrombocytopenia. Participants were randomly assigned (1:1), using block randomisation, to receive either dexamethasone (orally at 40 mg per day for 4 days) plus oseltamivir (orally at 75 mg twice a day for 10 days) or dexamethasone monotherapy (orally at 40 mg a day for 4 days). Patients who did not respond to treatment (platelet counts remained <30 × 109 cells per L or showed bleeding symptoms by day 10) were given an additional cycle of dexamethasone for 4 days in each group. Patients in the dexamethasone plus oseltamivir group who relapsed (platelet counts reduced again to <30 × 109 cells per L) after an initial response were allowed a supplemental course of oseltamivir (75 mg twice a day for 10 days). The coprimary endpoints were 14-day initial overall response and 6-month overall response. Complete response was defined as a platelet count at or above 100 × 109 cells per L and an absence of bleeding. Partial response was defined as a platelet count at or above 30 × 109 cells per L but less than 100 × 109 cells per L and at least a doubling of the baseline platelet count and an absence of bleeding. A response lasting for at least 6 months without any additional primary immune thrombocytopenia-specific intervention was defined as sustained response. All patients who were randomly assigned and received the allocated intervention were included in the modified intention-to-treat population analysis. This study has been completed and is registered with ClinicalTrials.gov, number NCT01965626. FINDINGS: From Feb 1, 2016, to May 1, 2019, 120 patients were screened for eligibility, of whom 24 were ineligible and excluded, 96 were enrolled and randomly assigned to receive dexamethasone plus oseltamivir (n=47) or dexamethasone (n=49), and 90 were included in the modified intention-to-treat analysis. Six patients did not receive the allocated intervention. Patients in the dexamethasone plus oseltamivir group had a significantly higher initial response rate (37 [86%] of 43 patients) than did those in the dexamethasone group (31 [66%] of 47 patients; odds ratio [OR] 3·18; 95 CI% 1·13-9·23; p=0·030) at day 14. The 6-month sustained response rate in the dexamethasone plus oseltamivir group was also significantly higher than that in the dexamethasone group (23 [53%] vs 14 [30%]; OR 2·17; 95 CI% 1·16-6·13; p=0·032). During the median follow-up of 8 months (IQR 5-14), two of 90 patients discontinued treatment due to serious adverse events (grade 3); one (2%) patient with general oedema in the dexamethasone plus oseltamivir group and one (2%) patient with fever in the dexamethasone group. The most frequently observed adverse events of any grade were fatigue (five [12%] of 43 in the dexamethasone plus oseltamivir group vs eight [17%] of 47 in the dexamethasone group), gastrointestinal reactions (eight [19%] vs three [6%]), insomnia (seven [16%] vs four [9%]), and anxiety (five [12%] vs three [6%]). There were no grade 4 or 5 adverse events and no treatment-related deaths. INTERPRETATION: Dexamethasone plus oseltamivir offers a readily available combination therapy in the management of newly diagnosed primary immune thrombocytopenia. The preliminary activity of this combination warrants further investigation. Multiple cycles of oseltamivir, as a modification of current first-line treatment, might be more effective in maintaining the platelet response. FUNDING: National Natural Science Foundation of China.


Asunto(s)
Dexametasona/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Glucocorticoides/uso terapéutico , Oseltamivir/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Administración Oral , Adulto , China/epidemiología , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/efectos adversos , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Hemorragia/epidemiología , Humanos , Análisis de Intención de Tratar/métodos , Masculino , Persona de Mediana Edad , Oseltamivir/administración & dosificación , Oseltamivir/efectos adversos , Recuento de Plaquetas/estadística & datos numéricos , Recuento de Plaquetas/tendencias , Púrpura Trombocitopénica Idiopática/inmunología , Seguridad , Resultado del Tratamiento
8.
Cochrane Database Syst Rev ; 2: CD012968, 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33629404

RESUMEN

BACKGROUND: Breast cancer is one of the most common cancers among women. Surgical removal of the cancer is the mainstay of treatment; however, tumour handling during surgery can cause microscopic dissemination of tumour cells and disease recurrence. The body's hormonal response to surgery (stress response) and general anaesthesia may suppress immunity, promoting tumour dissemination. Paravertebral anaesthesia numbs the site of surgery, provides good analgesia, and blunts the stress response, minimising the need for general anaesthesia. OBJECTIVES: To assess the effects of paravertebral anaesthesia with or without sedation compared to general anaesthesia in women undergoing breast cancer surgery, with important outcomes of quality of recovery, postoperative pain at rest, and mortality. SEARCH METHODS: On 6 April 2020, we searched the Specialised Register of the Cochrane Breast Cancer Group (CBCG); CENTRAL (latest issue), in the Cochrane Library; MEDLINE (via OvidSP); Embase (via OvidSP); the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal; and ClinicalTrials.gov for all prospectively registered and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) conducted in adult women undergoing breast cancer surgery in which paravertebral anaesthesia with or without sedation was compared to general anaesthesia. We did not include studies in which paravertebral anaesthesia was given as an adjunct to general anaesthesia and then this was compared to use of general anaesthesia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted details of trial methods and outcome data from eligible trials. When data could be pooled, analyses were performed on an intention-to-treat basis, and the random-effects model was used if there was heterogeneity. When data could not be pooled, the synthesis without meta-analysis (SWiM) approach was applied. The GRADE approach was used to assess the certainty of evidence for each outcome. MAIN RESULTS: Nine studies (614 participants) were included in the review. All were RCTs of parallel design, wherein female patients aged > 18 years underwent breast cancer surgery under paravertebral anaesthesia or general anaesthesia. None of the studies assessed quality of recovery in the first three postoperative days using a validated questionnaire; most assessed factors affecting quality of recovery such as postoperative analgesic use, postoperative nausea and vomiting (PONV), hospital stay, ambulation, and patient satisfaction. Paravertebral anaesthesia may reduce the 24-hour postoperative analgesic requirement (odds ratio (OR) 0.07, 95% confidence interval (CI) 0.01 to 0.34; 5 studies, 305 participants; low-certainty evidence) compared to general anaesthesia. Heterogeneity (I² = 70%) was attributed to the fixed dose of opioids and non-steroidal analgesics administered postoperatively in one study (70 participants), masking a difference in analgesic requirements between groups. Paravertebral anaesthesia probably reduces the incidence of PONV (OR 0.16, 95% CI 0.08 to 0.30; 6 studies, 324 participants; moderate-certainty evidence), probably results in a shorter hospital stay (mean difference (MD) -79.39 minutes, 95% CI -107.38 to -51.40; 3 studies, 174 participants; moderate-certainty evidence), and probably reduces time to ambulation compared to general anaesthesia (SWiM analysis): percentages indicate vote counting based on direction of effect (100%, 95% CI 51.01% to 100%; P = 0.125; 4 studies, 375 participants; moderate-certainty evidence). Paravertebral anaesthesia probably results in higher patient satisfaction (MD 5.52 points, 95% CI 1.30 to 9.75; 3 studies, 129 participants; moderate-certainty evidence) on a 0 to 100 scale 24 hours postoperatively compared to general anaesthesia. Postoperative pain at rest and on movement was assessed at 2, 6, and 24 postoperative hours on a 0 to 10 visual analogue scale (VAS). Four studies (224 participants) found that paravertebral anaesthesia as compared to general anaesthesia probably reduced pain at 2 postoperative hours (MD -2.95, 95% CI -3.37 to -2.54; moderate-certainty evidence). Five studies (324 participants) found that paravertebral anaesthesia may reduce pain at rest at 6 hours postoperatively (MD -1.54, 95% CI -3.20 to 0.11; low-certainty evidence). Five studies (278 participants) found that paravertebral anaesthesia may reduce pain at rest at 24 hours postoperatively (MD -1.19, 95% CI -2.27 to -0.10; low-certainty evidence). Differences in the methods of two studies (119 participants) and addition of clonidine to the local anaesthetic in two studies (109 participants), respectively, contributed to the heterogeneity (I² = 96%) observed for these two outcomes. Two studies (130 participants) found that paravertebral anaesthesia may reduce pain on movement at 6 hours (MD-2.57, 95% CI -3.97 to -1.17) and at 24 hours (MD -2.12, 95% CI -4.80 to 0.55; low-certainty evidence). Heterogeneity (I² = 96%) was observed for both outcomes and could be due to methodological differences between studies. None of the studies reported mortality related to the anaesthetic technique. Eight studies (574 participants) evaluated adverse outcomes with paravertebral anaesthesia: epidural spread (0.7%), minor bleeding (1.4%), pleural puncture not associated with pneumothorax (0.3%), and Horner's syndrome (7.1%). These complications were self-limiting and resolved without treatment. No data are available on disease-free survival, chronic pain, and quality of life. Blinding of personnel or participants was not possible in any study, as a regional anaesthetic technique was compared to general anaesthesia. Risk of bias was judged to be serious, as seven studies had concerns of selection bias and three of detection bias. AUTHORS' CONCLUSIONS: Moderate-certainty evidence shows that paravertebral anaesthesia probably reduces PONV, hospital stay, postoperative pain (at 2 hours), and time to ambulation and results in greater patient satisfaction on the first postoperative day compared to general anaesthesia. Paravertebral anaesthesia may also reduce postoperative analgesic use and postoperative pain at 6 and 24 hours at rest and on movement based on low-certainty evidence. However, RCTs using validated questionnaires are needed to confirm these results. Adverse events observed with paravertebral anaesthesia are rare.


Asunto(s)
Analgesia/métodos , Anestesia General/métodos , Anestesia Raquidea/métodos , Neoplasias de la Mama/cirugía , Estrés Fisiológico/efectos de los fármacos , Adulto , Periodo de Recuperación de la Anestesia , Anestesia Raquidea/efectos adversos , Sesgo , Neoplasias de la Mama/inmunología , Ambulación Precoz , Femenino , Síndrome de Horner/epidemiología , Humanos , Incidencia , Análisis de Intención de Tratar , Tiempo de Internación , Bloqueo Nervioso/métodos , Dimensión del Dolor/métodos , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/prevención & control , Satisfacción del Paciente , Náusea y Vómito Posoperatorios/epidemiología , Náusea y Vómito Posoperatorios/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto
9.
N Engl J Med ; 384(12): 1125-1135, 2021 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-33577729

RESUMEN

BACKGROUND: Patients with advanced urothelial carcinoma have poor overall survival after platinum-containing chemotherapy and programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor treatment. METHODS: We conducted a global, open-label, phase 3 trial of enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-containing chemotherapy and had had disease progression during or after treatment with a PD-1 or PD-L1 inhibitor. Patients were randomly assigned in a 1:1 ratio to receive enfortumab vedotin (at a dose of 1.25 mg per kilogram of body weight on days 1, 8, and 15 of a 28-day cycle) or investigator-chosen chemotherapy (standard docetaxel, paclitaxel, or vinflunine), administered on day 1 of a 21-day cycle. The primary end point was overall survival. RESULTS: A total of 608 patients underwent randomization; 301 were assigned to receive enfortumab vedotin and 307 to receive chemotherapy. As of July 15, 2020, a total of 301 deaths had occurred (134 in the enfortumab vedotin group and 167 in the chemotherapy group). At the prespecified interim analysis, the median follow-up was 11.1 months. Overall survival was longer in the enfortumab vedotin group than in the chemotherapy group (median overall survival, 12.88 vs. 8.97 months; hazard ratio for death, 0.70; 95% confidence interval [CI], 0.56 to 0.89; P = 0.001). Progression-free survival was also longer in the enfortumab vedotin group than in the chemotherapy group (median progression-free survival, 5.55 vs. 3.71 months; hazard ratio for progression or death, 0.62; 95% CI, 0.51 to 0.75; P<0.001). The incidence of treatment-related adverse events was similar in the two groups (93.9% in the enfortumab vedotin group and 91.8% in the chemotherapy group); the incidence of events of grade 3 or higher was also similar in the two groups (51.4% and 49.8%, respectively). CONCLUSIONS: Enfortumab vedotin significantly prolonged survival as compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-based treatment and a PD-1 or PD-L1 inhibitor. (Funded by Astellas Pharma US and Seagen; EV-301 ClinicalTrials.gov number, NCT03474107.).


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Moléculas de Adhesión Celular/antagonistas & inhibidores , Neoplasias Urológicas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Resistencia a Antineoplásicos , Femenino , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Proteína 2 Ligando de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Supervivencia sin Progresión , Análisis de Supervivencia , Neoplasias Urológicas/mortalidad , Neoplasias Urológicas/patología , Urotelio/patología
11.
Bone Joint J ; 103-B(2): 256-263, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33390029

RESUMEN

AIMS: Surgical treatment of hip fracture is challenging; the bone is porotic and fixation failure can be catastrophic. Novel implants are available which may yield superior clinical outcomes. This study compared the clinical effectiveness of the novel X-Bolt Hip System (XHS) with the sliding hip screw (SHS) for the treatment of fragility hip fractures. METHODS: We conducted a multicentre, superiority, randomized controlled trial. Patients aged 60 years and older with a trochanteric hip fracture were recruited in ten acute UK NHS hospitals. Participants were randomly allocated to fixation of their fracture with XHS or SHS. A total of 1,128 participants were randomized with 564 participants allocated to each group. Participants and outcome assessors were blind to treatment allocation. The primary outcome was the EuroQol five-dimension five-level health status (EQ-5D-5L) utility at four months. The minimum clinically important difference in utility was pre-specified at 0.075. Secondary outcomes were EQ-5D-5L utility at 12 months, mortality, residential status, mobility, revision surgery, and radiological measures. RESULTS: Overall, 437 and 443 participants were analyzed in the primary intention-to-treat analysis in XHS and SHS treatment groups respectively. There was a mean difference of 0.029 in adjusted utility index in favour of XHS with no evidence of a difference between treatment groups (95% confidence interval -0.013 to 0.070; p = 0.175). There was no evidence of any differences between treatment groups in any of the secondary outcomes. The pattern and overall risk of adverse events associated with both treatments was similar. CONCLUSION: Any difference in four-month health-related quality of life between the XHS and SHS is small and not clinically important. There was no evidence of a difference in the safety profile of the two treatments; both were associated with lower risks of revision surgery than previously reported. Cite this article: Bone Joint J 2021;103-B(2):256-263.


Asunto(s)
Placas Óseas , Tornillos Óseos , Fijación Intramedular de Fracturas/instrumentación , Fracturas de Cadera/cirugía , Calidad de Vida , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Estudios de Seguimiento , Fijación Intramedular de Fracturas/métodos , Indicadores de Salud , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Estudios Prospectivos
12.
N Engl J Med ; 384(4): 335-344, 2021 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-33503342

RESUMEN

BACKGROUND: In the United States, more intrauterine device (IUD) users select levonorgestrel IUDs than copper IUDs for long-term contraception. Currently, clinicians offer only copper IUDs for emergency contraception because data are lacking on the efficacy of the levonorgestrel IUD for this purpose. METHODS: This randomized noninferiority trial, in which participants were unaware of the group assignments, was conducted at six clinics in Utah and included women who sought emergency contraception after at least one episode of unprotected intercourse within 5 days before presentation and agreed to placement of an IUD. We randomly assigned participants in a 1:1 ratio to receive a levonorgestrel 52-mg IUD or a copper T380A IUD. The primary outcome was a positive urine pregnancy test 1 month after IUD insertion. When a 1-month urine pregnancy test was unavailable, we used survey and health record data to determine pregnancy status. The prespecified noninferiority margin was 2.5 percentage points. RESULTS: Among the 355 participants randomly assigned to receive levonorgestrel IUDs and 356 assigned to receive copper IUDs, 317 and 321, respectively, received the interventions and provided 1-month outcome data. Of these, 290 in the levonorgestrel group and 300 in the copper IUD group had a 1-month urine pregnancy test. In the modified intention-to-treat and per-protocol analyses, pregnancy rates were 1 in 317 (0.3%; 95% confidence interval [CI], 0.01 to 1.7) in the levonorgestrel group and 0 in 321 (0%; 95% CI, 0 to 1.1) in the copper IUD group; the between-group absolute difference in both analyses was 0.3 percentage points (95% CI, -0.9 to 1.8), consistent with the noninferiority of the levonorgestrel IUD to the copper IUD. Adverse events resulting in participants seeking medical care in the first month after IUD placement occurred in 5.2% of participants in the levonorgestrel IUD group and 4.9% of those in the copper IUD group. CONCLUSIONS: The levonorgestrel IUD was noninferior to the copper IUD for emergency contraception. (Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT02175030.).


Asunto(s)
Anticoncepción Postcoital/métodos , Dispositivos Intrauterinos de Cobre , Dispositivos Intrauterinos Medicados , Levonorgestrel/administración & dosificación , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Humanos , Análisis de Intención de Tratar , Embarazo , Índice de Embarazo , Pruebas de Embarazo , Sexo Inseguro , Adulto Joven
13.
Cochrane Database Syst Rev ; 1: CD001415, 2021 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-33434292

RESUMEN

BACKGROUND: This is an updated version of the Cochrane Review previously published in 2018. Epilepsy is a common neurological disorder characterised by recurrent seizures. Most people with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop drug-resistant epilepsy, especially people with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCTs) of gabapentin, when used as an add-on treatment for drug-resistant focal epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 11 August 2020. CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy. We imposed no language restrictions. SELECTION CRITERIA: Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant focal epilepsy. We also included trials using an active drug control group or comparing different doses of gabapentin. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: seizure frequency, seizure freedom, treatment withdrawal (any reason) and adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best-case and worst-case analyses. We estimated summary risk ratios (RR) for each outcome and evaluated dose-response in regression models. MAIN RESULTS: We identified no new studies for this update, therefore, the results and conclusions are unchanged. In the previous update of this review, we combined data from six trials in meta-analyses of 1206 randomised participants. The overall risk ratio (RR) for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 studies, 1206 participants; moderate-certainty evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (95% CI 19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (95% CI 8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate-certainty evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low-certainty evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate-certainty evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low-certainty evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate-certainty evidence). There was no evidence of a difference for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate-certainty evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate-certainty evidence). Overall, the studies were at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall certainty of the evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide CIs. AUTHORS' CONCLUSIONS: Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy, and seems to be fairly well-tolerated. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a three-month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types. Further trials are needed to assess the long-term effects of gabapentin, and to compare gabapentin with other add-on drugs.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Epilepsia Refractaria/tratamiento farmacológico , Epilepsias Parciales/tratamiento farmacológico , Gabapentina/uso terapéutico , Ácido gamma-Aminobutírico/uso terapéutico , Adulto , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Niño , Quimioterapia Combinada/métodos , Gabapentina/administración & dosificación , Gabapentina/efectos adversos , Humanos , Análisis de Intención de Tratar , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto
14.
PLoS Med ; 18(1): e1003475, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33406130

RESUMEN

BACKGROUND: Effective implementation strategies are needed to increase engagement in HIV services in hyperendemic settings. We conducted a pragmatic cluster-randomized trial in a high-risk, highly mobile fishing community (HIV prevalence: approximately 38%) in Rakai, Uganda, to assess the impact of a community health worker-delivered, theory-based (situated Information, Motivation, and Behavior Skills), motivational interviewing-informed, and mobile phone application-supported counseling strategy called "Health Scouts" to promote engagement in HIV treatment and prevention services. METHODS AND FINDINGS: The study community was divided into 40 contiguous, randomly allocated clusters (20 intervention clusters, n = 1,054 participants at baseline; 20 control clusters, n = 1,094 participants at baseline). From September 2015 to December 2018, the Health Scouts were deployed in intervention clusters. Community-wide, cross-sectional surveys of consenting 15 to 49-year-old residents were conducted at approximately 15 months (mid-study) and at approximately 39 months (end-study) assessing the primary programmatic outcomes of self-reported linkage to HIV care, antiretroviral therapy (ART) use, and male circumcision, and the primary biologic outcome of HIV viral suppression (<400 copies/mL). Secondary outcomes included HIV testing coverage, HIV incidence, and consistent condom use. The primary intent-to-treat analysis used log-linear binomial regression with generalized estimating equation to estimate prevalence risk ratios (PRR) in the intervention versus control arm. A total of 2,533 (45% female, mean age: 31 years) and 1,903 (46% female; mean age 32 years) residents completed the mid-study and end-study surveys, respectively. At mid-study, there were no differences in outcomes between arms. At end-study, self-reported receipt of the Health Scouts intervention was 38% in the intervention arm and 23% in the control arm, suggesting moderate intervention uptake in the intervention arm and substantial contamination in the control arm. At end-study, intention-to-treat analysis found higher HIV care coverage (PRR: 1.06, 95% CI: 1.01 to 1.10, p = 0.011) and ART coverage (PRR: 1.05, 95% CI: 1.01 to 1.10, p = 0.028) among HIV-positive participants in the intervention compared with the control arm. Male circumcision coverage among all men (PRR: 1.05, 95% CI: 0.96 to 1.14, p = 0.31) and HIV viral suppression among HIV-positive participants (PRR: 1.04, 95% CI: 0.98 to 1.12, p = 0.20) were higher in the intervention arm, but differences were not statistically significant. No differences were seen in secondary outcomes. Study limitations include reliance on self-report for programmatic outcomes and substantial contamination which may have diluted estimates of effect. CONCLUSIONS: A novel community health worker intervention improved HIV care and ART coverage in an HIV hyperendemic setting but did not clearly improve male circumcision coverage or HIV viral suppression. This community-based, implementation strategy may be a useful component in some settings for HIV epidemic control. TRIAL REGISTRATION: ClinicalTrials.gov NCT02556957.


Asunto(s)
Agentes Comunitarios de Salud , Infecciones por VIH/prevención & control , Promoción de la Salud/métodos , Aplicaciones Móviles , Entrevista Motivacional , Adolescente , Adulto , Fármacos Anti-VIH/uso terapéutico , Circuncisión Masculina , Condones , Femenino , Infecciones por VIH/epidemiología , Humanos , Incidencia , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Prevalencia , Uganda/epidemiología
15.
Am Heart J ; 235: 54-64, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33516752

RESUMEN

OBJECTIVE: The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD). BACKGROUND: IPE is a highly purified and stable omega-3 fatty acid prescription medication that is approved for cardiovascular risk reduction in high-risk adults on statin therapy with elevated triglycerides. Preclinical data and clinical observations suggest that IPE may have pleiotropic effects including antiviral and anti-inflammatory properties that may prevent or reduce the downstream sequelae and cardiopulmonary consequences of viral URIs. METHODS: MITIGATE is a virtual, electronic health record-based, open-label, randomized, pragmatic clinical trial enrolling ∼16,500 participants within Kaiser Permanente Northern California - a fully integrated and learning health care delivery system with 21 hospitals and >255 ambulatory clinics serving ∼4.5 million members. Adults ≥50 years with established ASCVD and no prior history of coronavirus disease 2019 (COVID-19) will be prospectively identified and pre-randomized in a 1:10 allocation ratio (∼ 1,500 IPE: ∼15,000 usual care) stratified by age and previous respiratory health status to the intervention (IPE 2 grams by mouth twice daily with meals) vs the control group (usual care) for a minimum follow-up duration of 6 months. The co-primary endpoints are moderate-to-severe laboratory-confirmed viral URI and worst clinical status due to a viral URI at any point in time. CONCLUSION: The MITIGATE study will inform clinical practice by providing evidence on the real-world clinical effectiveness of pretreatment with IPE to prevent and/or reduce the sequelae of laboratory-confirmed viral URIs in a high-risk cohort of patients with established ASCVD.


Asunto(s)
Aterosclerosis/complicaciones , Enfermedades Cardiovasculares/prevención & control , Ácido Eicosapentaenoico/análogos & derivados , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anciano , Enfermedades Cardiovasculares/complicaciones , Ácido Eicosapentaenoico/uso terapéutico , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/virología
16.
J Affect Disord ; 282: 354-363, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33421863

RESUMEN

BACKGROUND: Patients with unipolar depressive disorder are frequently hospitalized, and the period following discharge is a high-risk-period. Smartphone-based treatments are receiving increasing attention among researchers, clinicians, and patients. We aimed to investigate whether a smartphone-based monitoring and treatment system reduces the rate and duration of readmissions, more than standard treatment, in patients with unipolar depressive disorder following hospitalization. METHODS: We conducted a pragmatic, investigator-blinded, randomized controlled trial. The intervention group received a smartphone-based monitoring and treatment system in addition to standard treatment. The system allowed patients to self-monitor symptoms and access psycho-educative information and cognitive modules. The patients were allocated a study-nurse who, based on the monitoring data, guided and supported them. The control group received standard treatment. The trial lasted six months, with outcome assessments at 0, 3, and 6 months. RESULTS: We included 120 patients with unipolar depressive disorder (ICD-10). Intention-to-treat analyses showed no statistically significant differences in time to readmission (Log-Rank p=0.9) or duration of readmissions (B=-16.41,95%CI:-47.32;25.5,p=0.3) (Primary outcomes). There were no differences in clinically rated depressive symptoms (p=0.6) or functioning (p=0.1) (secondary outcomes). The intervention group had higher levels of recovery (B=7,29, 95%CI:0.82;13,75,p=0.028) and a tendency towards higher quality of life (p=0.07), wellbeing (p=0,09) satisfaction with treatment (p=0.05) and behavioral activation (p=0.08) compared with the control group (tertiary outcomes). LIMITATIONS: Patients and study-nurses were unblinded to allocation. CONCLUSIONS: We found no effect of the intervention on primary or secondary outcomes. In tertiary outcomes, patients in the intervention group reported higher levels of recovery compared to the control group.


Asunto(s)
Trastorno Depresivo , Readmisión del Paciente , Humanos , Análisis de Intención de Tratar , Calidad de Vida , Teléfono Inteligente , Resultado del Tratamiento
17.
Pediatrics ; 147(1)2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33386338

RESUMEN

BACKGROUND AND OBJECTIVES: Evidence suggests that intramuscular vitamin A reduces the risk of bronchopulmonary dysplasia (BPD) in preterm infants. Our objective was to compare enteral water-soluble vitamin A with placebo supplementation to reduce the severity of BPD in extremely preterm infants. METHODS: We conducted a double-blind randomized controlled trial in infants <28 weeks' gestation who were to receive either enteral water-soluble vitamin A (5000 IU per day) or a placebo. Supplementation was started within 24 hours of introduction of feeds and continued until 34 weeks' postmenstrual age (PMA). The primary outcome was the severity of BPD, assessed by using the right shift of the pulse oximeter saturation versus the inspired oxygen pressure curve. RESULTS: A total of 188 infants were randomly assigned. The mean ± SD birth weight (852 ± 201 vs 852 ± 211 g) and gestation (25.8 ± 1.49 vs 26.0 ± 1.39 weeks) were comparable between the vitamin A and placebo groups. There was no difference in the right shift (median [25th-75th percentiles]) of the pulse oximeter saturation versus inspired oxygen pressure curve (in kilopascals) between the vitamin A (11.1 [9.5-13.7]) and placebo groups (10.7 [9.5-13.1]) (P = .73). Enteral vitamin A did not affect diagnosis of BPD or other clinical outcomes. Plasma retinol levels were significantly higher in the vitamin A group versus the placebo group on day 28 and at 34 weeks' PMA. CONCLUSIONS: Enteral water-soluble vitamin A supplementation improves plasma retinol levels in extremely preterm infants but does not reduce the severity of BPD.


Asunto(s)
Displasia Broncopulmonar/tratamiento farmacológico , Recien Nacido Extremadamente Prematuro , Vitamina A/administración & dosificación , Vitaminas/administración & dosificación , Administración Oral , Displasia Broncopulmonar/diagnóstico , Método Doble Ciego , Femenino , Humanos , Recién Nacido , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Vitamina A/uso terapéutico , Vitaminas/uso terapéutico
18.
N Engl J Med ; 384(7): 610-618, 2021 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-33406353

RESUMEN

BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. RESULTS: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. CONCLUSIONS: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).


Asunto(s)
/terapia , Inmunoglobulina G/sangre , Insuficiencia Respiratoria/prevención & control , /inmunología , Anciano , Anciano de 80 o más Años , Transfusión de Componentes Sanguíneos , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Inmunización Pasiva , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Insuficiencia Respiratoria/etiología , Índice de Severidad de la Enfermedad
19.
N Engl J Med ; 384(1): 20-30, 2021 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-33332779

RESUMEN

BACKGROUND: Coronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti-interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear. METHODS: We randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28. RESULTS: A total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P = 0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, -5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group. CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.).


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , /tratamiento farmacológico , Adulto , Anciano , /mortalidad , Progresión de la Enfermedad , Femenino , Hospitalización , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Neumonía Viral/tratamiento farmacológico , Respiración Artificial , Tasa de Supervivencia
20.
N Engl J Med ; 384(10): 905-914, 2021 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-33356051

RESUMEN

BACKGROUND: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19. METHODS: In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo. In addition, all the patients received high-quality supportive care as background therapy, including the antiviral drug remdesivir and, when indicated, supplemental oxygen and glucocorticoids. LY-CoV555 (at a dose of 7000 mg) or placebo was administered as a single intravenous infusion over a 1-hour period. The primary outcome was a sustained recovery during a 90-day period, as assessed in a time-to-event analysis. An interim futility assessment was performed on the basis of a seven-category ordinal scale for pulmonary function on day 5. RESULTS: On October 26, 2020, the data and safety monitoring board recommended stopping enrollment for futility after 314 patients (163 in the LY-CoV555 group and 151 in the placebo group) had undergone randomization and infusion. The median interval since the onset of symptoms was 7 days (interquartile range, 5 to 9). At day 5, a total of 81 patients (50%) in the LY-CoV555 group and 81 (54%) in the placebo group were in one of the two most favorable categories of the pulmonary outcome. Across the seven categories, the odds ratio of being in a more favorable category in the LY-CoV555 group than in the placebo group was 0.85 (95% confidence interval [CI], 0.56 to 1.29; P = 0.45). The percentage of patients with the primary safety outcome (a composite of death, serious adverse events, or clinical grade 3 or 4 adverse events through day 5) was similar in the LY-CoV555 group and the placebo group (19% and 14%, respectively; odds ratio, 1.56; 95% CI, 0.78 to 3.10; P = 0.20). The rate ratio for a sustained recovery was 1.06 (95% CI, 0.77 to 1.47). CONCLUSIONS: Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 without end-organ failure. (Funded by Operation Warp Speed and others; TICO ClinicalTrials.gov number, NCT04501978.).


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Neutralizantes/uso terapéutico , Antivirales/uso terapéutico , /tratamiento farmacológico , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adulto , Anciano , Alanina/análogos & derivados , Alanina/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Neutralizantes/efectos adversos , Antivirales/efectos adversos , Método Doble Ciego , Quimioterapia Combinada , Femenino , Glucocorticoides/uso terapéutico , Hospitalización , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Insuficiencia del Tratamiento
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