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1.
Nat Commun ; 12(1): 915, 2021 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-33568665

RESUMEN

Dexamethasone can reduce mortality in hospitalised COVID-19 patients needing oxygen and ventilation by 18% and 36%, respectively. Here, we estimate the potential number of lives saved and life years gained if this treatment were to be rolled out in the UK and globally, as well as the cost-effectiveness of implementing this intervention. Assuming SARS-CoV-2 exposure levels of 5% to 15%, we estimate that, for the UK, approximately 12,000 (4,250 - 27,000) lives could be saved between July and December 2020. Assuming that dexamethasone has a similar effect size in settings where access to oxygen therapies is limited, this would translate into approximately 650,000 (240,000 - 1,400,000) lives saved globally over the same time period. If dexamethasone acts differently in these settings, the impact could be less than half of this value. To estimate the full potential of dexamethasone in the global fight against COVID-19, it is essential to perform clinical research in settings with limited access to oxygen and/or ventilators, for example in low- and middle-income countries.


Asunto(s)
/tratamiento farmacológico , Dexametasona/uso terapéutico , /economía , /terapia , Análisis Costo-Beneficio , Dexametasona/economía , Mortalidad Hospitalaria , Hospitalización , Humanos , Años de Vida Ajustados por Calidad de Vida , Respiración Artificial , Reino Unido/epidemiología , Ventiladores Mecánicos
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 131-136, 2021 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33554809

RESUMEN

OBJECTIVE: To investigate the efficacy, survival and adverse effects of non-transplanted multiple myeloma (MM) patients treated with bortezomib maintenance. METHODS: A total of 25 newly diagnosed/relapsed non-transplanted MM patients treated in West District of Beijing Chaoyang Hospital from June 2004 to November 2015 were analyzed retrospectively. All patients received PD regimen (bortezomib and dexamethasone), including bortezomib at a dose of 1.3 mg/m2 and dexamethasone 20 mg on days 1, 8, 15, 22 in a 3-month cycle. RESULTS: Till November 1, 2017, 5 patients achieved stringent complete response (sCR), 8 patients achieved complete response (CR), 7 patients achieved very good partial response (VGPR), 4 patients achieved partial reponse (PR), while 1 patient achieved stable disease (SD). After maintenance therapy, 21 patients maintained the efficacy above PR, of which 1 patient was improved from CR to sCR; 4 patients adjusted chemotherapy after disease progressed. Median maintenance therapy was 9 cycles (range from 6 to 31), and the median maintenance time was 27 months (range from 18 to 97). Median follow-up time was 73 months (range from 25 to 171). Median progress-free survival (PFS) time was 30 months (range from 9 to 105) and overall survival (OS) time was 57 months (range from 27 to 160). Till November 1, 2019, 3-year survival rate was 84% (21/25), and 5-year survival rate was 72% (13/18). The most common adverse events were transient leukopenia, thrombocytopenia and peripheral neuropathy, which the patients could tolerate after the prevention and treatment. CONCLUSION: Bortezomib-based maintenance therapy for non-transplanted MM patients can be an option in consideration of its safety and efficacy.


Asunto(s)
Mieloma Múltiple , Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Mieloma Múltiple/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 137-144, 2021 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33554810

RESUMEN

OBJECTIVE: To investigate the short-term efficacy and safety of generic bortezomib in the treatment of Chinese patients with multiple myeloma (MM). METHODS: Clinical data of 62 MM patients (median age of 62 years) who had accepted at least 2 cycles of chemotherapy based on generic bortezomib in our center from December 2017 to July 2019 were retrospectively analyzed, including 47 newly diagnosed patients and 15 with disease recurrence or progression. RESULTS: Anemia, renal dysfunction, hypoproteinemia and high level of ß 2-microglobulin were all improved rapidly after induction treatment. In 56 patients who had completed at least 4 cycles of chemotherapy, the overall response rate (ORR) was 85.7%, and 64.3% of the patients achieved very good partial response (VGPR) or better, and 28.6% achieved complete remission (CR) or better. In the 19 patients who had already completed all planned induction and consolidation treatment (9 cycles of chemotherapy or 4-6 cycles of chemotherapy plus autologous hematopoietic stem cell transplantation), 84.2% achieved VGPR or better, and 57.9% achieved CR or stringent complete remission (sCR). Median follow-up time was 300 days with data cut-off date of September 20, 2019, and the progression-free survival (PFS) rate and overall survival (OS) rate were 62.1% and 85.3%, respectively. The possible adverse reactions associated with bortezomib were grade 1-2, the most common hematologic adverse reaction was thrombocytopenia (27.4%), and the most common non-hematologic adverse reaction was peripheral neuropathy (43.5%), followed by asthenia (37.1%). CONCLUSION: The disease severity can be rapidly alleviated after generic bortezomib-based chemotherapy, and a favorable short-term efficacy and survival have been observed with a generally acceptable toxicity profile. However, the long-term outcomes will be examined through further follow-up.


Asunto(s)
Mieloma Múltiple , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento
4.
Rinsho Ketsueki ; 62(1): 14-19, 2021.
Artículo en Japonés | MEDLINE | ID: mdl-33551419

RESUMEN

Although classic Hodgkin's lymphoma (CHL) sometimes develops after treatment for multiple myeloma (MM), simultaneous diagnosis of both malignancies is extremely rare without previous treatment history. Here we describe a case of a 54-year-old female who complained of left cervical lymphadenopathy. Biopsy specimen from the left cervical lymph node revealed mixed-cellularity CHL. Bone marrow aspirate comprised 10.3% plasma cells. She was diagnosed with MM due to involved: uninvolved serum free light chain ratio of >100. She achieved complete response for CHL after 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy along with 30 Gy of involved-field radiotherapy. Three years later, bortezomib, lenalidomide, and dexamethasone (VRd-lite) therapy was initiated for MM. Severe neutropenia during her 1st cycle prompted a dosage reduction of lenalidomide and bortezomib. Partial response was achieved after 4 cycles of VRd-lite followed by high-dose melphalan/autologous stem cell transplantation. No severe adverse events were recorded. This was followed by 4 cycles of carfilzomib, lenalidomide, and dexamethasone therapy, which resulted in complete remission. As the number of elderly people increases, multiple myeloma patients with previous history of other malignancies would increase. Our case has shown that VRd-lite therapy may be suitable for those patients.


Asunto(s)
Enfermedad de Hodgkin , Mieloma Múltiple , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Femenino , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/terapia , Humanos , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/terapia , Trasplante Autólogo
5.
Medicine (Baltimore) ; 100(3): e24206, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33546038

RESUMEN

BACKGROUND: Traumatic brain injury (TBI) constitutes a leading cause of death and disability. Patients with TBI and cerebral contusions developing pericontusional edema are occasionally given dexamethasone on the belief that this edema is similar to that of tumors, in which the beneficial effect of dexamethasone has been demonstrated. METHODS: The DEXCON TBI trial is a multicenter, pragmatic, randomized, triple-blind, placebo controlled trial to quantify the effects of dexamethasone on the prognosis of TBI patients with brain contusions and pericontusional edema. Adult patients who fulfill the elegibility criteria will be randomized to dexamethasone/placebo in a short and descending course: 4 mg/6 h (2 days); 4 mg/8 hours (2 days); 2 mg/6 hours (2 days); 2 mg/8 hours (2 days); 1 mg/8 hours (2 days); 1 mg/12 hours (2 days). The primary outcome is the Glasgow Scale Outcome Extended (GOSE) performed 1 month and 6 months after TBI. Secondary outcomes are: number of episodes of neurological deterioration; symptoms associated with TBI; adverse events; volume of pericontusional edema before and after 12 days of treatment; results of the neuropsychological tests one month and 6 months after TBI. The main analysis will be on an "intention-to-treat" basis. Logistic regression will estimate the effect of dexamethasone/placebo on GOSE at one month and at 6 months, dichotomized in unfavorable outcome (GOSE 1-6) and favorable outcome (GOSE 7-8). Efficacy will also be analyzed using the 'sliding dichotomy'. An interim and safety analysis will be performed including patients recruited during the first year to calculate the conditional power. A study with 600 patients would have 80% power (2 sided alpha = 5%) to detect a 12% absolute increase (from 50% to 62%) in good recovery. DISCUSSION: This is a confirmative trial to elucidate the therapeutic efficacy of dexamethasone in a very specific group of TBI patients: patients with brain contusions and pericontusional edema. This trial could become an important milestone for TBI patients as nowadays there is no effective treatment in this type of patients. TRIAL REGISTRATION: eudraCT: 2019-004038-41; Clinical Trials.gov: NCT04303065.


Asunto(s)
Antiinflamatorios/uso terapéutico , Contusión Encefálica/tratamiento farmacológico , Edema Encefálico/tratamiento farmacológico , Dexametasona/uso terapéutico , Contusión Encefálica/complicaciones , Edema Encefálico/etiología , Método Doble Ciego , Humanos , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto
6.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33541971

RESUMEN

COVID-19 is a biphasic illness with an initial viraemia phase and later effective adaptive immune phase, except in a minority of people who develop severe disease. Immune regulation is the key target to treat COVID illness. In anticipation, an elderly man self-medicated himself with dexamethasone on the day of symptom onset of a flu-like illness, took other symptomatic measures and was tested positive for SARS-CoV-2. His condition deteriorated with each passing day resulting in hospitalisation. He demanded oxygen and declared as severe COVID. With supportive treatment, he recovered after the 20th day of illness. Immunosuppression and anti-inflammation are likely to benefit when the immune response is dysregulated and turning into a cytokine storm. A medication that has saved many could be the one predisposing to severity if taken as a preventive measure, too early in the disease course, especially the viraemia phase.


Asunto(s)
Antiinflamatorios/efectos adversos , Dexametasona/efectos adversos , Viremia/tratamiento farmacológico , Anciano , Antiinfecciosos/uso terapéutico , Antiinflamatorios/uso terapéutico , Dexametasona/uso terapéutico , Hospitalización , Humanos , Hidroxicloroquina/uso terapéutico , Masculino , Neumonía Viral/complicaciones , Neumonía Viral/tratamiento farmacológico , Automedicación/métodos , Esteroides/efectos adversos , Esteroides/uso terapéutico , Resultado del Tratamiento , Viremia/complicaciones
8.
BMJ Case Rep ; 14(1)2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33408106

RESUMEN

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder of excessive immune activation. It is mostly seen in the paediatric population and is rarely observed in adults. HLH can be inherited or acquired and is commonly triggered by activation of the immune system by an underlying viral infection or in immune system deficiency such as malignancy or underlying rheumatological disease. HLH is a difficult entity to diagnose due to the rarity of this disorder, variable clinical presentation and non-specific clinical and laboratory findings. HLH carries a high mortality if left untreated, and therefore prompt diagnosis and initiation of immunosuppressive, immunomodulatory and cytostatic medications are critical to improve survival in affected patients. Here, we present a case of lamotrigine-associated HLH. To our knowledge, only eight other cases of lamotrigine-associated HLH have been reported in adult patients.


Asunto(s)
Anticonvulsivantes/administración & dosificación , Lamotrigina/efectos adversos , Linfohistiocitosis Hemofagocítica/inducido químicamente , Convulsiones/tratamiento farmacológico , Adulto , Biopsia , Médula Ósea/patología , Dexametasona/uso terapéutico , Diagnóstico Diferencial , Etopósido/uso terapéutico , Humanos , Linfohistiocitosis Hemofagocítica/sangre , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Masculino
9.
BMJ Case Rep ; 14(1)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33509883
11.
Medicine (Baltimore) ; 100(2): e24122, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33466183

RESUMEN

OBJECTIVE: To assess the impact of intraoperative intravenous dexamethasone on the reduction of postoperative morbidity in children undergoing adenotonsillectomy. METHODS: A double blind randomized controlled trial conducted among children undergoing adenotonsillectomy at a tertiary hospital in Korea from November 2018 to June 2019. Children were randomly assigned to receive dexamethasone (0.5 mg/kg, maximum dose 24 mg) or placebo intravenously after induction of anesthesia. The primary endpoint was the reduction of postoperative pain and postoperative nausea and vomiting (PONV); secondary endpoints were adverse effects like postoperative hemorrhage. RESULTS: The study included 105 children, and 67 were male. Their mean age was 6.2 ±â€Š2.1 years. There was no significant difference between the groups in terms of demographic data or the operation time. The pain scores of the dexamethasone group were lower than those of the control group, but no significant difference was found (all P > .05). The average pain visual analog scale (VAS) during the study period (day 0-7) was 3.67 ±â€Š1.59 and 4.40 ±â€Š2.01 in the dexamethasone group and control group, respectively (P-value = .107). When we compared early pain VAS (day 0-2) and late pain VAS (day 5-7), the dexamethasone group showed significantly lower early mean VAS compared to the control group (4.55 ±â€Š1.78 vs 5.40 ±â€Š2.05, P-value = .046). The mean VAS for PONV was significantly lower in the dexamethasone group than in the control group (1.89 ±â€Š2.22 vs 3.00 ±â€Š2.37, P value = .044). CONCLUSION: In children undergoing adenotonsillectomy, dexamethasone decreased the early postoperative pain and PONV without increasing postoperative hemorrhage.


Asunto(s)
Adenoidectomía/efectos adversos , Dexametasona/farmacología , Dolor Postoperatorio/tratamiento farmacológico , Náusea y Vómito Posoperatorios/tratamiento farmacológico , Tonsilectomía/efectos adversos , Adenoidectomía/métodos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Niño , Preescolar , Dexametasona/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Masculino , Dolor Postoperatorio/etiología , Pediatría/métodos , Náusea y Vómito Posoperatorios/etiología , República de Corea , Tonsilectomía/métodos , Escala Visual Analógica
13.
Eur J Pharmacol ; 894: 173854, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33428898

RESUMEN

The current outbreak of novel COVID-19 challenges the development of an efficient treatment plan as soon as possible. Several promising treatment options stand out as potential therapy of COVID-19, including plasma-derived drugs, monoclonal antibodies, antivirals, antimalarial, cell therapy, and corticosteroids. Dexamethasone an approved corticosteroid medication, acting as an anti-inflammatory and immunosuppressant agent. In the current pandemic, dexamethasone is declared a "major development" in the fight against COVID-19. Steroidal dexamethasone was presented as the recent advancement that significantly reduces the mortality rate among severe COVID-19 cases. This review summarizes the preliminary opinion about the dexamethasone outbreak, therapeutic potential, risks, and strategies during the COVID-19 pandemic.


Asunto(s)
Antiinflamatorios/uso terapéutico , Dexametasona/uso terapéutico , Inmunosupresores/uso terapéutico , Pandemias , Antiinflamatorios/efectos adversos , /mortalidad , Dexametasona/efectos adversos , Humanos , Inmunosupresores/efectos adversos , /etiología
14.
AAPS PharmSciTech ; 22(1): 16, 2021 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-33389218

RESUMEN

Many anti-inflammatory therapies targeting neutrophils have been developed so far. A sialic acid (SA)-modified liposomal (SAL) formulation, based on the high expression of L-selectin in peripheral blood neutrophils (PBNs) and SA as its targeting ligand, has proved to be an effective neutrophil-mediated drug delivery system targeting rheumatoid arthritis (RA). The objective of this study was to investigate the influence of particle size of drug-carrying SALs transported and delivered by neutrophils on their anti-RA effect. Dexamethasone palmitate-loaded SALs (DP-SALs) of different particle sizes (300.2 ± 5.5 nm, 150.3 ± 4.3 nm, and 75.0 ± 3.9 nm) were prepared with DP as a model drug. Our study indicated that DP-SALs could efficiently target PBNs, with larger liposomes leading to higher drug accumulation in cells. However, a high intake of large DP-SALs by PBNs inhibited their migration ability and capacity to release the payload at the target site. In contrast, small DP-SALs (75.0 ± 3.9 nm) could maintain the drug delivery potential of PBNs, leading to their efficient accumulation at the inflammatory site, where PBNs would be excessively activated to form neutrophil extracellular traps along with efficient payload release (small DP-SALs) and finally to induce excellent anti-RA effect.


Asunto(s)
Antiinflamatorios/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Dexametasona/administración & dosificación , Liposomas/química , Neutrófilos/efectos de los fármacos , Ácidos Siálicos/química , Animales , Antiinflamatorios/uso terapéutico , Dexametasona/uso terapéutico , Sistemas de Liberación de Medicamentos , Humanos , Masculino , Ácido N-Acetilneuramínico/metabolismo , Ácido N-Acetilneuramínico/farmacología , Ácido N-Acetilneuramínico/uso terapéutico , Tamaño de la Partícula , Ratas , Ratas Wistar
15.
Vet Res ; 52(1): 1, 2021 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397469

RESUMEN

Psoroptic mange is a common disease of livestock, caused by Psoroptes ovis. Compared to Holstein-Friesian (HF) cattle, the Belgian Blue (BB) cattle breed is highly susceptible to the infestation. However, the mechanism for this difference is still unclear. To determine the factors responsible for this breed susceptibility, the immune response to P. ovis was studied in experimentally infested BB and HF cattle, using clinical signs, histology, immunohistochemical profiling and gene expression analysis of skin biopsies. The mite numbers and lesion area of BB cattle were greater than in HF during the whole study period. Significant influxes of eosinophils in the epidermis and dermis were detected in comparison with the pre-infestation samples in both breeds, with significantly higher eosinophils in BB at 6 weeks post infestation (wpi). Mast cell numbers were unaffected at all stages of infestation in HF, but were significantly elevated relative to pre-infestation in BB cattle at 2 and 6 wpi. The more pronounced cutaneous eosinophilia and higher IL-4 levels at 6 wpi in BB cattle suggest that a Th2-type immune response is underlying the higher susceptibility of the BB breed. In naturally infested BB cattle, development of the psoroptic mange lesions and eosinophils and CD3+ T cell areas were severely depressed after anti-inflammatory treatment with dexamethasone. Together, these results suggest that a stronger Th2-type immune response to P. ovis causes the skin lesions in psoroptic mange in BB cattle and that local anti-inflammatory treatment could potentially be an alternative to control the pathology caused by this parasite.


Asunto(s)
Antiinflamatorios/uso terapéutico , Enfermedades de los Bovinos/parasitología , Dexametasona/uso terapéutico , Infestaciones por Ácaros/veterinaria , Psoroptidae , Animales , Bovinos , Enfermedades de los Bovinos/tratamiento farmacológico , Enfermedades de los Bovinos/inmunología , Infestaciones por Ácaros/tratamiento farmacológico , Infestaciones por Ácaros/inmunología , Psoroptidae/inmunología , Piel/inmunología , Piel/parasitología , Especificidad de la Especie
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