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1.
Bone Joint J ; 102-B(11): 1497-1504, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33135436

RESUMEN

AIMS: Intravenous dexamethasone has been shown to reduce immediate postoperative pain after total hip arthroplasty (THA), though the effects are short-lived. We aimed to assess whether two equivalent perioperative split doses were more effective than a single preoperative dose. METHODS: A total of 165 patients were randomly assigned into three groups: two perioperative saline injections (Group A, placebo), a single preoperative dose of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative doses of 10 mg dexamethasone (Group C). Patients, surgeons, and staff collecting outcome data were blinded to allocation. The primary outcome was postoperative pain level reported on a ten-point Numerical Rating Scale (NRS) at rest and during activity. The use of analgesic and antiemetic rescue, incidence of postoperative nausea and vomiting (PONV), CRP and interleukin-6 (IL-6) levels, range of motion (ROM), length of stay (LOS), patient satisfaction, and the incidence of surgical site infection (SSI) and gastrointestinal bleeding (GIB) in the three months postoperatively, were also compared. RESULTS: The pain scores at rest were significantly lower in Groups B and C than in Group A on postoperative days 1 and 2. The dynamic pain scores and CRP and IL-6 levels were significantly lower for Groups B and C compared to Group A on postoperative days 1, 2, and 3. Patients in Groups B and C had a lower incidence of PONV, reduced use of analgesic and antiemetic rescue, improved ROM, shorter LOS, and reported higher satisfaction than in Group A. Patients in Group C had significantly lower dynamic pain scores and IL-6 and CRP levels on postoperative days 2 and 3, and higher ROM and satisfaction on postoperative day 3 than in Group B. No SSI or GIB occurred in any group. CONCLUSION: Perioperative dexamethasone provides short-term advantages in reducing pain, PONV, and inflammation, and increasing range of motion in the early postoperative period after THA. A split-dose regimen was superior to a single high dose in reducing pain and inflammation, and increasing ROM, with better patient satisfaction. Level of evidence: I Cite this article: Bone Joint J 2020;102-B(11):1497-1504.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Dexametasona/administración & dosificación , Glucocorticoides/administración & dosificación , Osteoartritis de la Cadera/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Administración Intravenosa , Anciano , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
2.
J Int Med Res ; 48(10): 300060520964009, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33100064

RESUMEN

BACKGROUND: The causative virus of coronavirus disease 2019 (COVID-19) may cause severe fatal pneumonia. The clinical presentation includes asymptomatic infection, severe pneumonia, and acute respiratory failure. Data pertaining to acute renal injury due to COVID-19 in patients who have undergone renal transplantation are scarce. We herein report two cases of COVID-19 along with acute kidney injury following kidney transplantation.Case presentation: Two patients with COVID-19 underwent renal transplantation and were subsequently diagnosed with acute kidney injury. The first patient presented with progressive respiratory symptoms and acute renal injury. He was treated with diuretics and suspension of immunosuppressive therapy; however, the patient died. The second patient presented with respiratory tract symptoms, hypoxemia, and progressive deterioration of renal function followed by improvement. Her mycophenolate mofetil was stopped after admission, and tacrolimus was discontinued 10 days later. Moxifloxacin and methylprednisolone were continued in combination with albumin and gamma globulin infusion. A diuretic was administered, and prednisone was gradually reduced along with tacrolimus. The patient exhibited a satisfactory clinical recovery. CONCLUSION: Patients who develop COVID-19 after kidney transplantation are at risk of acute kidney injury, and their prednisone, immunosuppressant, and gamma globulin treatment must be adjusted according to their condition.


Asunto(s)
Lesión Renal Aguda/patología , Infecciones por Coronavirus/patología , Trasplante de Riñón/efectos adversos , Riñón/patología , Neumonía Viral/patología , Lesión Renal Aguda/virología , Adulto , Betacoronavirus , Esquema de Medicación , Femenino , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Riñón/virología , Masculino , Persona de Mediana Edad , Pandemias , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Receptores de Trasplantes , gammaglobulinas/administración & dosificación , gammaglobulinas/uso terapéutico
3.
Lancet Haematol ; 7(11): e808-e815, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33010817

RESUMEN

BACKGROUND: Hodgkin lymphoma is potentially curable. However, 15-35% of older patients (ie, >60 years) have a lower response rate, worse survival outcomes, and greater toxicity than younger patients. Brentuximab vedotin and nivolumab exhibit activity in patients with relapsed or refractory Hodgkin lymphoma. We therefore aimed to evaluate the safety and efficacy of brentuximab vedotin and nivolumab in untreated older patients with Hodgkin lymphoma or in younger patients considered unsuitable for standard ABVD (ie, doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy. METHODS: We did a multicentre, single-arm, phase 2 trial at eight cancer centres in the USA. Previously untreated patients with classic Hodgkin lymphoma were eligible for study enrolment if they were 60 years or older, or younger than 60 years but considered unsuitable for standard chemotherapy because of a cardiac ejection fraction of less than 50%, pulmonary diffusion capacity of less than 80%, or a creatinine clearance of 30 mL/min or more but less than 60 mL/min, or those who refused chemotherapy. Patients were also required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients received brentuximab vedotin at 1·8 mg/kg (dose cap at 180 mg) and nivolumab at 3 mg/kg both intravenously every 21 days for 8 cycles. The primary endpoint was the overall response, defined as a partial metabolic response or complete metabolic response at the end of 8 cycles of treatment. A per protocol analysis was done including all patients who received treatment in the activity and safety analyses. This study is registered with ClinicalTrials.gov, number NCT02758717. FINDINGS: Between May 13, 2016, and Jan 30, 2019, the study accrued 46 patients. The median age was 71·5 years (IQR 64-77), with two (4%) of 46 patients younger than 60 years. Median follow-up was 21·2 months (IQR 15·6-29·9), and 35 (76%) of 46 patients completed all 8 cycles of therapy. At the interim analysis on Oct 11, 2019, the first 25 evaluable patients had an overall response rate of 64% ([95% CI 43-82] 16 of 25 patients; 13 [52%] had a complete metabolic response and three [12%] had a partial metabolic response). The trial was closed to accrual on Oct 14, 2019, after the interim analysis failed to meet the predefined criteria. In all 46 evaluable patients, 22 (48%) patients achieved a complete metabolic response and six (13%) achieved a partial metabolic response (overall response rate 61% [95% CI 45-75]). 14 (30%) of 46 patients had 16 dose adjustments, primarily due to neurotoxicity. 22 (48%) of 46 patients had peripheral neuropathy (five [11%] patients had grade 3 peripheral neuropathy). Grade 4 adverse events included increased aminotranferases (one [2%] of 46), increased lipase or amylase (two [4%]), and pancreatitis (one [2%]). One (2%) patient died from cardiac arrest, possibly treatment related. INTERPRETATION: Although the trial did not meet the prespecified activity criteria, brentuximab vedotin plus nivolumab is active in older patients with previously untreated Hodgkin lymphoma with comorbidities. The regimen was also well tolerated in the majority of patients in this older population. Future trials should be based on optimising the dose and schedule, perhaps combined with other targeted agents that might permit chemotherapy-free strategies in older patients with Hodgkin lymphoma. FUNDING: Seattle Genetics and Bristol Myers Squibb.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Brentuximab Vedotina/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Nivolumab/uso terapéutico , Anciano , Antineoplásicos Inmunológicos/efectos adversos , Brentuximab Vedotina/efectos adversos , Esquema de Medicación , Quimioterapia Combinada , Femenino , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/etiología , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Nivolumab/efectos adversos , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/etiología , Supervivencia sin Progresión , Inducción de Remisión , Resultado del Tratamiento
4.
Clin Microbiol Rev ; 34(1)2020 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-33055231

RESUMEN

Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. In vivo, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/farmacología , Infecciones por Coronavirus/tratamiento farmacológico , Fiebre Hemorrágica Ebola/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Adenosina Monofosfato/farmacocinética , Adenosina Monofosfato/farmacología , Alanina/farmacocinética , Alanina/farmacología , Antivirales/farmacocinética , Betacoronavirus/efectos de los fármacos , Betacoronavirus/crecimiento & desarrollo , Betacoronavirus/patogenicidad , Ensayos Clínicos como Asunto , Ensayos de Uso Compasivo/métodos , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Esquema de Medicación , Ebolavirus/efectos de los fármacos , Ebolavirus/crecimiento & desarrollo , Ebolavirus/patogenicidad , Fiebre Hemorrágica Ebola/mortalidad , Fiebre Hemorrágica Ebola/patología , Fiebre Hemorrágica Ebola/virología , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Coronavirus del Síndrome Respiratorio de Oriente Medio/crecimiento & desarrollo , Coronavirus del Síndrome Respiratorio de Oriente Medio/patogenicidad , Pandemias , Seguridad del Paciente , Neumonía Viral/mortalidad , Neumonía Viral/patología , Neumonía Viral/virología , Virus del SRAS/efectos de los fármacos , Virus del SRAS/crecimiento & desarrollo , Virus del SRAS/patogenicidad , Síndrome Respiratorio Agudo Grave/mortalidad , Síndrome Respiratorio Agudo Grave/patología , Síndrome Respiratorio Agudo Grave/virología , Análisis de Supervivencia , Resultado del Tratamiento
5.
Medicine (Baltimore) ; 99(44): e22258, 2020 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-33126298

RESUMEN

We aimed to investigate the effect of interval between food intake and drug administration at fasting condition on the plasma concentrations of first-line anti- tuberculosis (TB) drugs in Chinese population. Newly diagnosed TB patients administered the anti-TB drugs under fasting conditions orally, and then had prepared breakfast at 30 minutes and 120 min after dosing, respectively. Blood sampling was also performed 120  minutes after dosing for the detection of Cmax purpose. Overall, twenty-five participants were included in our analysis. The Cmaxs of 30  minutes interval and 120  minutes interval were 21.8 ±â€Š2.0 and 19.2 ±â€Š2.0 µg/mL for rifampin, 1.6 ±â€Š0.2 and 2.1 ±â€Š0.2 µg/mL for isoniazid (INH), 1.5 ±â€Š0.1and 1.5 ±â€Š0.2 µg/mL for ethambutol (EMB), and 49.2 ±â€Š3.7 and 41.5 ±â€Š3.9 µg/mL for pyrazinamide, respectively. Statistical analysis revealed that there was no statistical difference between 2 groups. Additionally, 88.0% and 72.0% of the 25 participants at 2-hour interval group had peak concentrations less than the lower limit of the reference range for INH and EMB, respectively. The Cmaxs of INH were 0.9 ±â€Š0.4 µg/ml for rapid acetylator, which was significantly lower than those of intermediate (1.4 ±â€Š1.0 µg/mL), and slow acetylator (2.5 ±â€Š1.0 µg/mL), respectively (P < .01). In conclusion, our data demonstrate that early food intake at 30 minutes after drug administration had no significant influence on the plasma concentrations. In addition, a high proportion of patients receiving first-line anti-TB regimen fail to achieve the expected plasma drug ranges of INH and EMB (P > .05).


Asunto(s)
Antituberculosos/sangre , Ingestión de Alimentos , Ayuno/sangre , Factores de Tiempo , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/tratamiento farmacológico , Administración Oral , Adulto , Antituberculosos/administración & dosificación , China , Esquema de Medicación , Etambutol/administración & dosificación , Etambutol/sangre , Femenino , Humanos , Isoniazida/administración & dosificación , Isoniazida/sangre , Masculino , Pirazinamida/administración & dosificación , Pirazinamida/sangre , Rifampin/administración & dosificación , Rifampin/sangre , Resultado del Tratamiento
6.
Cardiovasc Ther ; 2020: 1494506, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33072188

RESUMEN

Background: Cardiac adverse events are common among patients presenting with acute stroke and contribute to overall morbidity and mortality. Prophylactic measures for the reduction of cardiac adverse events in hospitalized stroke patients have not been well understood. We sought to investigate the effect of early initiation of high-dose intravenous magnesium sulfate on cardiac adverse events in stroke patients. Methods: This is a secondary analysis of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized phase-3 clinical trial, conducted from 2005-2013. Consecutive patients with suspected acute stroke and a serum magnesium level within 72 hours of enrollment were selected. Twenty grams of magnesium sulfate or placebo was administered in the ambulance starting with a 15-minute loading dose intravenous infusion followed by a 24-hour maintenance infusion in the hospital. Results: Among 1126 patients included in the analysis of this study, 809 (71.8%) patients had ischemic stroke, 277 (24.6%) had hemorrhagic stroke, and 39 (3.5%) with stroke mimics. The mean age was 69.5 (SD13.4) and 42% were female. 565 (50.2%) received magnesium treatment, and 561 (49.8%) received placebo. 254 (22.6%) patients achieved the target, and 872 (77.4%) did not achieve the target, regardless of their treatment group. Among 1126 patients, 159 (14.1%) had at least one CAE. Treatment with magnesium was not associated with fewer cardiac adverse events. A multivariate binary logistic regression for predictors of CAEs showed a positive association of older age and frequency of CAEs (R = 1.04, 95% CI 1.03-1.06, p < 0.0001). Measures of early and 90-day outcomes did not differ significantly between the magnesium and placebo groups among patients who had CAEs. Conclusion: Treatment of acute stroke patients with magnesium did not result in a reduction in the number or severity of cardiac serious adverse events.


Asunto(s)
Cardiopatías/prevención & control , Hospitalización , Sulfato de Magnesio/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Administración Intravenosa , Anciano , Anciano de 80 o más Años , Comorbilidad , Esquema de Medicación , Femenino , Cardiopatías/diagnóstico , Cardiopatías/epidemiología , Humanos , Incidencia , Los Angeles/epidemiología , Sulfato de Magnesio/efectos adversos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Factores de Tiempo , Resultado del Tratamiento
7.
J Crohns Colitis ; 14(Supplement_3): S769-S773, 2020 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-33085972

RESUMEN

Patients with inflammatory bowel diseases [IBD] are frequently treated with immunosuppressant medications. During the coronavirus disease 2019 [COVID-19] pandemic, recommendations for IBD management have included that patients should stay on their immunosuppressant medications if they are not infected with the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], but to temporarily hold these medications if symptomatic with COVID-19 or asymptomatic but have tested positive for SARS-CoV-2. As more IBD patients are infected globally, it is important to also understand how to manage IBD medications during convalescence while an individual with IBD is recovering from COVID-19. In this review, we address the differences between a test-based versus a symptoms-based strategy as related to COVID-19, and offer recommendations on when it is appropriate to consider restarting IBD therapy in patients testing positive for SARS-CoV-2 or with clinical symptoms consistent with COVID-19. In general, we recommend a symptoms-based approach, due to the current lack of confidence in the accuracy of available testing and the clinical significance of prolonged detection of virus via molecular testing.


Asunto(s)
Betacoronavirus , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Huésped Inmunocomprometido , Inmunosupresores/administración & dosificación , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Pandemias/prevención & control , Neumonía Viral/inmunología , Neumonía Viral/prevención & control , Infecciones Asintomáticas , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/diagnóstico , Esquema de Medicación , Humanos , Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/inmunología , Neumonía Viral/diagnóstico , Medición de Riesgo
8.
Cochrane Database Syst Rev ; 10: CD006359, 2020 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-33112418

RESUMEN

BACKGROUND: A frozen embryo transfer (FET) cycle is when one or more embryos (frozen during a previous treatment cycle) are thawed and transferred to the uterus. Some women undergo fresh embryo transfer (ET) cycles with embryos derived from donated oocytes. In both situations, the endometrium is primed with oestrogen and progestogen in different doses and routes of administration. OBJECTIVES: To evaluate the most effective endometrial preparation for women undergoing transfer with frozen embryos or embryos from donor oocytes with regard to the subsequent live birth rate (LBR). SEARCH METHODS: The Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, LILACS, trials registers and abstracts of reproductive societies' meetings were searched in June 2020 together with reference checking and contact with study authors and experts in the field to identify additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. We analysed all available interventions versus placebo, no treatment, or between each other. The primary review outcome was live birth rate. Secondary outcomes were clinical and multiple pregnancy, miscarriage, cycle cancellation, endometrial thickness and adverse effects. MAIN RESULTS: Thirty-one RCTs (5426 women) were included. Evidence was moderate to very low-quality: the main limitations were serious risk of bias due to poor reporting of methods, and serious imprecision. Stimulated versus programmed cycle We are uncertain whether a letrozole-stimulated cycle compared to a programmed cycle, for endometrial preparation, improves LBR (odds ratio (OR) 1.26, 95% confidence interval (CI) 0.49 to 3.26; 100 participants; one study; very low-quality evidence). Stimulating with follicle stimulating hormone (FSH), letrozole or clomiphene citrate may improve clinical pregnancy rate (CPR) (OR 1.63, 95% CI 1.12 to 2.38; 656 participants; five studies; I2 = 11%; low-quality evidence). We are uncertain if they reduce miscarriage rate (MR) (OR 0.79, 95% CI 0.36 to 1.71; 355 participants; three studies; I2 = 0%; very low-quality evidence). Endometrial thickness (ET) may be reduced with clomiphene citrate (mean difference(MD) -1.04, 95% CI -1.59 to -0.49; 92 participants; one study; low-quality evidence). Other outcomes were not reported. Natural versus programmed cycle We are uncertain of the effect from a natural versus programmed cycle for LBR (OR 0.97, 95% CI 0.74 to 1.28; 1285 participants; four studies; I2 = 0%; very low-quality evidence) and CPR (OR 0.79, 95% CI 0.62 to 1.01; 1249 participants; five studies; I2 = 60%; very low-quality evidence), while a natural cycle probably reduces the cycle cancellation rate (CCR) (OR 0.60, 95% CI 0.44 to 0.82; 734 participants; one study; moderate-quality evidence). We are uncertain of the effect on MR and ET. No study reported other outcomes. Transdermal versus oral oestrogens From low-quality evidence we are uncertain of the effect transdermal compared to oral oestrogens has on CPR (OR 0.86, 95% CI 0.59 to 1.25; 504 participants; three studies; I2 = 58%) or MR (OR 0.55, 95% CI 0.27 to 1.09; 414 participants; two studies; I2 = 0%). Other outcomes were not reported. Day of starting administration of progestogen When doing a fresh ET using donated oocytes in a synchronised cycle starting progestogen on the day of oocyte pick-up (OPU) or the day after OPU, in comparison with recipients that start progestogen the day prior to OPU, probably increases the CPR (OR 1.87, 95% CI 1.13 to 3.08; 282 participants; one study, moderate-quality evidence). We are uncertain of the effect on multiple pregnancy rate (MPR) or MR. It probably reduces the CCR (OR 0.28, 95% CI 0.11 to 0.74; 282 participants; one study; moderate-quality evidence). No study reported other outcomes. Gonadotropin-releasing hormone (GnRH) agonist versus control A cycle with GnRH agonist compared to without may improve LBR (OR 2.62, 95% CI 1.19 to 5.78; 234 participants; one study; low-quality evidence). From low-quality evidence we are uncertain of the effect on CPR (OR 1.08, 95% CI 0.82 to 1.43; 1289 participants; eight studies; I2 = 20%), MR (OR 0.85, 95% CI 0.36 to 2.00; 828 participants; four studies; I2 = 0%), CCR (OR 0.49, 95% CI 0.21 to 1.17; 530 participants; two studies; I2 = 0%) and ET (MD -0.08, 95% CI -0.33 to 0.16; 697 participants; four studies; I2 = 4%). No study reported other outcomes. Among different GnRH agonists From very low-quality evidence we are uncertain if cycles among different GnRH agonists improves CPR or MR. No study reported other outcomes. GnRH agonists versus GnRH antagonists GnRH antagonists compared to agonists probably improves CPR (OR 0.62, 95% CI 0.42 to 0.90; 473 participants; one study; moderate-quality evidence). We are uncertain of the effect on MR and MPR. No study reported other outcomes. Aspirin versus control From very low-quality evidence we are uncertain whether a cycle with aspirin versus without improves LBR, CPR, or ET. Steroids versus control From very low-quality evidence we are uncertain whether a cycle with steroids compared to without improves LBR, CPR or MR. No study reported other outcomes. AUTHORS' CONCLUSIONS: There is insufficient evidence on the use of any particular intervention for endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers. In frozen embryo transfers, low-quality evidence showed that clinical pregnancy rates may be improved in a stimulated cycle compared to a programmed one, and we are uncertain of the effect when comparing a programmed cycle to a natural cycle. Cycle cancellation rates are probably reduced in a natural cycle. Although administering a GnRH agonist, compared to without, may improve live birth rates, clinical pregnancy rates will probably be improved in a GnRH antagonist cycle over an agonist cycle. In fresh synchronised oocyte donor cycles, the clinical pregnancy rate is probably improved and cycle cancellation rates are probably reduced when starting progestogen the day of or day after donor oocyte retrieval. Adequately powered studies are needed to evaluate each treatment more accurately.


Asunto(s)
Criopreservación , Transferencia de Embrión/métodos , Embrión de Mamíferos , Endometrio/efectos de los fármacos , Hormona Liberadora de Gonadotropina/agonistas , Donación de Oocito , Aborto Espontáneo/epidemiología , Sesgo , Clomifeno/administración & dosificación , Esquema de Medicación , Implantación del Embrión/fisiología , Endometrio/fisiología , Femenino , Hormona Folículo Estimulante/administración & dosificación , Humanos , Letrozol/administración & dosificación , Nacimiento Vivo/epidemiología , Embarazo , Índice de Embarazo , Progesterona/administración & dosificación , Progestinas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto
10.
Eur J Endocrinol ; 183(6): 561-569, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33055297

RESUMEN

Objective: The impact of different combinations of long-term gender-affirming hormone therapy (GAHT) in transwomen (TW) is largely unknown. To assess the effects of 5-year administration of cyproterone acetate (CPA) or leuprolide acetate (Leu) plus transdermal or oral estradiol (E). Design: Cohort study based on prospectively collected data. Fifty TW received 50 mg CPA daily orally (n = 25; CPA+E group) or 3.75 mg Leu i.m. monthly (n = 25; Leu+E group) with 1 or 2 mg E daily for 5 years. Reproductive hormones, biochemical and anthropometric parameters, body composition and bone mineral density (BMD) were assessed. Results: LH, FSH and total testosterone levels were similarly and significantly suppressed in both groups. Prolactin increased only in the CPA+E group (P = 0.002). Fasting insulin resistance and glucose progressively increased in the CPA+E group only (treatment × time effect P = 0.002 and P = 0.043, respectively). Total cholesterol increased more in the Leu+E group than in the CPA+E group and HDL-cholesterol decreased in the CPA+E group (time × treatment interaction effect, P = 0.007). Lumbar and total body BMD increased in both groups after 3 years. No serious adverse events were recorded. Conclusions: Both regimens were effective in suppression of T production. CPA+E worsened the metabolic profile with a slight increase in PRL levels. All subjects presented an increase in BMD regardless of treatment. These preliminary data could have clinical implications in the choice of GAHT, in particular for those TW not requiring gender-affirming surgery.


Asunto(s)
Acetato de Ciproterona/administración & dosificación , Estradiol/administración & dosificación , Leuprolida/administración & dosificación , Testosterona/sangre , Transexualidad/sangre , Transexualidad/tratamiento farmacológico , Adulto , Antagonistas de Andrógenos/administración & dosificación , Estudios de Cohortes , Esquema de Medicación , Quimioterapia Combinada , Estrógenos/administración & dosificación , Femenino , Fármacos para la Fertilidad Femenina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Testosterona/antagonistas & inhibidores , Personas Transgénero
11.
JAMA ; 324(16): 1651-1669, 2020 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-33052386

RESUMEN

Importance: Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices. Objective: To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV. Evidence Review: New evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations. Findings: From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic. Conclusion and Relevance: Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Factores de Edad , Antirretrovirales/economía , Betacoronavirus , Comorbilidad , Infecciones por Coronavirus/epidemiología , Esquema de Medicación , Costos de los Medicamentos , Farmacorresistencia Viral/genética , Sustitución de Medicamentos/normas , Quimioterapia Combinada/métodos , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/diagnóstico , Humanos , Agencias Internacionales , Masculino , Pandemias , Neumonía Viral/epidemiología , Polifarmacia , Profilaxis Pre-Exposición/métodos , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , ARN Viral/sangre , Sociedades Médicas , Estados Unidos , Carga Viral/genética
13.
Comput Math Methods Med ; 2020: 1391583, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33029193

RESUMEN

Purpose: We aimed to analyze and evaluate the safety signals of ribavirin-interferon combination through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS), so as to provide reference for the rationale use of these agents in the management of relevant toxicities emerging in patients with novel coronavirus pneumonia (COVID-19). Methods: Reports to the FAERS from 1 January 2004 to 8 March 2020 were analyzed. The proportion of report ratio (PRR), reporting odds ratio (ROR), and Bayesian confidence interval progressive neural network (BCPNN) method were used to detect the safety signals. Results: A total of 55 safety signals were detected from the top 250 adverse event reactions in 2200 reports, but 19 signals were not included in the drug labels. All the detected adverse event reactions were associated with 13 System Organ Classes (SOC), such as gastrointestinal, blood and lymph, hepatobiliary, endocrine, and various nervous systems. The most frequent adverse events were analyzed, and the results showed that females were more likely to suffer from anemia, vomiting, neutropenia, diarrhea, and insomnia. Conclusion: The ADE (adverse drug event) signal detection based on FAERS is helpful to clarify the potential adverse events related to ribavirin-interferon combination for novel coronavirus therapy; clinicians should pay attention to the adverse reactions of gastrointestinal and blood systems, closely monitor the fluctuations of the platelet count, and carry out necessary mental health interventions to avoid serious adverse events.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Interferones/efectos adversos , Neumonía Viral/tratamiento farmacológico , Ribavirina/efectos adversos , Adolescente , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Anciano , Algoritmos , Teorema de Bayes , Minería de Datos , Esquema de Medicación , Quimioterapia Combinada/efectos adversos , Femenino , Humanos , Interferones/administración & dosificación , Masculino , Persona de Mediana Edad , Redes Neurales de la Computación , Oportunidad Relativa , Pandemias , Seguridad del Paciente , Ribavirina/administración & dosificación , Adulto Joven
14.
Virology ; 550: 61-69, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32882638

RESUMEN

The world is in the midst of a pandemic caused by a novel coronavirus and is desperately searching for possible treatments. The antiviral remdesivir has shown some effectiveness against SARS-CoV-2 in vitro and in a recent animal study. We use data from a study of remdesivir in rhesus macaques to fit a viral kinetics model in an effort to determine the most appropriate mathematical descripton of the effect of remdesivir. We find statistically significant differences in the viral decay rate and use this to inform a possible mathematical formulation of the effect of remdesivir. Unfortunately, this model formulation suggests that the application of remdesivir will lengthen SARS-CoV-2 infections, putting into question its potential clinical benefit.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/farmacocinética , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Modelos Estadísticos , Neumonía Viral/tratamiento farmacológico , Adenosina Monofosfato/sangre , Adenosina Monofosfato/farmacocinética , Alanina/sangre , Alanina/farmacocinética , Animales , Antivirales/sangre , Betacoronavirus/crecimiento & desarrollo , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/virología , Modelos Animales de Enfermedad , Esquema de Medicación , Humanos , Inflamación , Macaca mulatta , Pandemias , Neumonía Viral/sangre , Neumonía Viral/virología , Carga Viral , Replicación Viral
15.
PLoS One ; 15(9): e0239452, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32956419

RESUMEN

BACKGROUND: Highly active antiretroviral therapy (HAART) has reduced HIV-related morbidity and mortality at all stages of infection and reduced transmission of HIV. Currently, the immediate start of HAART is recommended for all HIV patients, regardless of the CD4 count. There are several concerns, however, about starting treatment in critically ill patients. Unpredictable absorption of medication by the gastrointestinal tract, drug toxicity, drug interactions, limited reserve to tolerate the dysfunction of other organs resulting from hypersensitivity to drugs or immune reconstitution syndrome, and the possibility that subtherapeutic levels of drug may lead to viral resistance are the main concerns. The objective of our study was to compare the early onset (up to 5 days) with late onset (after discharge from the ICU) of HAART in HIV-infected patients admitted to the ICU. METHODS: This was a randomized, open-label clinical trial enrolling HIV-infected patients admitted to the ICU of a public hospital in southern Brazil. Patients randomized to the intervention group had to start treatment with HAART within 5 days of ICU admission. For patients in the control group, treatment should begin after discharge from the ICU. The patients were followed up to determine mortality in the ICU, in the hospital and at 6 months. The primary outcome was hospital mortality. The secondary outcome was mortality at 6 months. RESULTS: The calculated sample size was 344 patients. Unfortunately, we decided to discontinue the study due to a progressively slower recruitment rate. A total of 115 patients were randomized. The majority of admissions were for AIDS-defining illnesses and low CD4. The main cause of admission was respiratory failure. Regarding the early and late study groups, there was no difference in hospital (66.7% and 63.8%, p = 0.75) or 6-month (68.4% and 79.2%, p = 0.20) mortality. After multivariate analysis, the only independent predictors of in-hospital mortality were shock and dialysis during the ICU stay. For the mortality outcome at 6 months, the independent variables were shock and dialysis during the ICU stay and tuberculosis at ICU admission. CONCLUSIONS: Although the early termination of the study precludes definitive conclusions being made, early HAART administration for HIV-infected patients admitted to the ICU compared to late administration did not show benefit in hospital mortality or 6-month mortality. ClinicalTrials.gov, NCT01455688. Registered 20 October 2011, https://clinicaltrials.gov/show/NCT01455688.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Cuidados Críticos/métodos , Infecciones por VIH/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/etiología , Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/farmacocinética , Terapia Antirretroviral Altamente Activa/efectos adversos , Brasil , Recuento de Linfocito CD4 , Enfermedad Crítica , Esquema de Medicación , Femenino , Mortalidad Hospitalaria , Hospitales Públicos , Humanos , Síndrome Inflamatorio de Reconstitución Inmune/etiología , Síndrome Inflamatorio de Reconstitución Inmune/prevención & control , Unidades de Cuidados Intensivos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Respiración Artificial , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia
16.
J Stroke Cerebrovasc Dis ; 29(10): 105048, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32912514

RESUMEN

OBJECTIVE: Standards for reporting and analyzing adherence to medical therapy have recently improved due to international consensus efforts. If applied to clinical trial research in patients with stroke, these improvements have the potential to identify when in the sequence of trial operations participants are at risk for non-adherence and opportunities to safeguard adherence. METHODS: We analyzed three phases of adherence according to the European Society for Patient Adherence, COMpliance, and Persistence (ESPACOMP) Medication Adherence Reporting Guideline (EMERGE) taxonomy in the Insulin Resistance Intervention after Stroke (IRIS) trial: initiation (did patient start drug), implementation (did patient take a drug holiday, defined as temporary cessation lasting ≥14 days), and persistence (did patient prematurely and permanently discontinue drug). IRIS was a randomized, placebo controlled, double-blind trial testing pioglitazone to prevent stroke or myocardial infarction in patients with a recent ischemic stroke or transient ischemic attack. Adherence was classified by self-report. Researchers used coaching algorithms to seek adherence recovery if participants went off drug. RESULTS: During 2005-2013, 3876 participants were enrolled from 179 sites in seven countries and followed for a mean of 4.8 years. Less than 1% of participants in each group did not initiate study drug. 20% of patients assigned to pioglitazone and 17% assigned to placebo took at least one drug holiday. 36% and 30%, respectively, discontinued the study drug prematurely with or without a prior holiday. The risk for stopping the study drug (temporarily or permanently) in the first year after randomization was twice the risk in each of the subsequent four years. This was true both for patients assigned to active therapy and placebo. More participants assigned to pioglitazone, compared to placebo, took a drug holiday or permanently stopped study drug, but the difference in rates of discontinuation was only evident in year one. In years two through five, rates of discontinuation were similar in the two treatment groups. The difference in rates during year one was the result of adverse effects related to the active study drug, pioglitazone. During the remainder of the trial, the attribution of discontinuations to adverse effects potentially related to pioglitazone was reduced but still higher in those assigned to active drug. Other reasons for discontinuation were similar between treatment groups and were largely unrelated to pharmacodynamic effects of the study drug. Rates of discontinuation varied widely among research sites. CONCLUSION: Patients in a drug trial for stroke prevention are at greatest risk for premature drug discontinuation early after randomization. Reasons for discontinuation change over time. Variable discontinuation rates among sites suggests that adherence can be improved by using best practices from high-performing sites.


Asunto(s)
Hipoglucemiantes/administración & dosificación , Resistencia a la Insulina , Ataque Isquémico Transitorio/prevención & control , Cumplimiento de la Medicación , Infarto del Miocardio/prevención & control , Pioglitazona/administración & dosificación , Prevención Secundaria , Accidente Cerebrovascular/prevención & control , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Hipoglucemiantes/efectos adversos , Ataque Isquémico Transitorio/etiología , Ataque Isquémico Transitorio/fisiopatología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Infarto del Miocardio/fisiopatología , Pioglitazona/efectos adversos , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/fisiopatología , Factores de Tiempo , Resultado del Tratamiento
17.
J Stroke Cerebrovasc Dis ; 29(10): 105171, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32912546

RESUMEN

BACKGROUND: Prophylactic antiepileptic drugs (pAEDs) are often prescribed for seizure prophylaxis in patients undergoing surgical treatment of unruptured intracranial aneurysms (UIAs). We aimed to evaluate the benefit of pAEDs in patients undergoing surgical repair of UIAs. METHODS: We randomly assigned eligible patients undergoing surgical repair of UIAs to receive levetiracetam for seven days post-operatively or standard care alone. The primary outcome was the evaluation of seizures in the perioperative period (within 4 weeks). We also evaluated seizure occurrence throughout follow-up and assessed functional outcomes using the modified Rankin scale score (mRS). RESULTS: 35 patients were randomized to the "no-levetiracetam" group and 41 patients were randomized to receive levetiracetam. The two study groups had similar overall baseline characteristics and the surgical complication rate was similar for both groups (p = 0.8). One patient in the "no-levetiracetam" group had a seizure in the perioperative period versus 2 patients in the group randomized to receive levetiracetam (2.9% vs 4.9%, respectively, p = 1.00). No patients in the "no-levetiracetam" group had any additional late seizures (mean follow-up of 20.4 months), but three patients in the levetiracetam group had late seizures during follow-up (mean follow-up of 19.1 months) (0% vs 7.3%, p = 0.2). mRS score of 0-2 at 90 days and at the latest follow-up were similar between the two groups (p = 1.00). CONCLUSIONS: Perioperative seizure prophylaxis with levetiracetam does not reduce the rate of seizures as compared to controls in patients undergoing surgical repair of UIAs.


Asunto(s)
Anticonvulsivantes/administración & dosificación , Craneotomía/efectos adversos , Aneurisma Intracraneal/cirugía , Levetiracetam/administración & dosificación , Microcirugia/efectos adversos , Convulsiones/prevención & control , Adulto , Anciano , Anticonvulsivantes/efectos adversos , Esquema de Medicación , Femenino , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Levetiracetam/efectos adversos , Masculino , Michigan , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Convulsiones/etiología , Factores de Tiempo , Resultado del Tratamiento
18.
Int J Hematol ; 112(4): 466-476, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32869125

RESUMEN

Ravulizumab demonstrated noninferior efficacy and comparable safety to eculizumab in two open-label, phase 3 studies in patients with paroxysmal nocturnal hemoglobinuria (PNH) who complement inhibitor-naive (Study 301) or were previously treated with eculizumab (Study 302). This subgroup analysis assessed ravulizumab's efficacy and safety in Japanese patients in Studies 301 and 302, who are known to have different clinicopathologic features from white patients. Patients were randomly assigned (1:1) to eculizumab every-two-weeks or weight-based dosing of ravulizumab every-eight-weeks for 26 weeks. Co-primary endpoints were transfusion avoidance and lactate dehydrogenase (LDH) normalization in Study 301 and percentage change in LDH levels from baseline to day 183 in Study 302. Thirty-three Japanese patients (n = 18 ravulizumab; n = 15 eculizumab) enrolled in Study 301; 12 enrolled in Study 302 (n = 5 ravulizumab; n = 7 eculizumab). In the Study 301 ravulizumab group, 83.3% (15/18) of patients avoided transfusion; the adjusted prevalence of LDH normalization was 52.1%. In the Study 302 ravulizumab group, the least-squares-mean percentage change from baseline in LDH was 8.34%. No deaths or meningococcal infections occurred during the 6-month primary evaluation period in either study. In conclusion, ravulizumab's efficacy and safety were consistent in the Japanese and global patient populations with PNH in the phase 3 studies. Clinical Trial Identifier: NCT02946463; NCT03056040.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Hemoglobinuria Paroxística/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Grupo de Ascendencia Continental Asiática , Biomarcadores/sangre , Transfusión Sanguínea/estadística & datos numéricos , Peso Corporal , Esquema de Medicación , Femenino , Hemoglobinuria Paroxística/diagnóstico , Humanos , Japón , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Seguridad , Resultado del Tratamiento
19.
Circ Arrhythm Electrophysiol ; 13(10): e008686, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32907357

RESUMEN

BACKGROUND: Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine is being considered as prophylaxis and treatment of coronavirus disease-19 (COVID-19). Although hydroxychloroquine is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematosus and other rheumatic conditions, there may still be reluctance to institute this antimalarial during pregnancy for the sole purpose of antiviral therapy. METHODS: To provide data regarding any potential fetal/neonatal cardiotoxicity, we leveraged a unique opportunity in which neonatal ECGs and hydroxychloroquine blood levels were available in a recently completed study evaluating the efficacy of hydroxychloroquine 400 mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro (anti-Sjögren's Syndrome A/Ro) antibodies. RESULTS: Forty-five ECGs were available for corrected QT interval (QTc) measurement, and levels of hydroxychloroquine were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of hydroxychloroquine and the neonatal QTc (R=0.02, P=0.86) or the mean of hydroxychloroquine values obtained throughout each individual pregnancy and the QTc (R=0.04, P=0.80). In total 5 (11% [95% CI, 4%-24%]) neonates had prolongation of the QTc >2 SD above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal. CONCLUSIONS: In aggregate, these data provide reassurances that the maternal use of hydroxychloroquine is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01379573.


Asunto(s)
Antivirales/administración & dosificación , Electrocardiografía , Corazón Fetal/efectos de los fármacos , Bloqueo Cardíaco/congénito , Frecuencia Cardíaca/efectos de los fármacos , Hidroxicloroquina/administración & dosificación , Antivirales/efectos adversos , Antivirales/sangre , Cardiotoxicidad , Esquema de Medicación , Monitoreo de Drogas , Femenino , Sangre Fetal/metabolismo , Corazón Fetal/fisiopatología , Edad Gestacional , Bloqueo Cardíaco/diagnóstico , Bloqueo Cardíaco/fisiopatología , Bloqueo Cardíaco/prevención & control , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/sangre , Lactante , Recién Nacido , Masculino , Valor Predictivo de las Pruebas , Embarazo , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
20.
Am Heart J ; 228: 81-90, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32866928

RESUMEN

Recurrent pericarditis (RP) occurs in 15% to 30% of patients following a first episode, despite standard treatment with nonsteroidal anti-inflammatory drugs, colchicine, and corticosteroids; many patients become dependent on corticosteroids. Rilonacept (KPL-914), an interleukin-1α and ß inhibitor, is in development for the treatment of RP. RHAPSODY, a double-blind, placebo-controlled, randomized-withdrawal (RW) pivotal Phase 3 trial (NCT03737110), enrolls patients 12 years or older presenting with at least a third pericarditis episode, pericarditis pain score ≥4 (11-point numeric rating scale [NRS]), and C-reactive protein ≥1 mg/dL at screening. After a subcutaneous loading dose (adults, 320 mg; children, 4.4 mg/kg), all patients receive blinded weekly subcutaneous rilonacept (adults, 160 mg; children, 2.2 mg/kg) during the run-in period. Patients must taper and discontinue concomitant pericarditis medications during the blinded run-in period and achieve clinical response (C-reactive protein ≤0.5 mg/dL and weekly average NRS ≤2.0 during the 7 days prior to and including the day of randomization) by end of the run-in (while on rilonacept monotherapy) to be randomized to either continued rilonacept or placebo in the RW period. Primary efficacy end point was time to adjudicated pericarditis recurrence during the RW period; secondary efficacy end points were proportion of patients maintaining clinical response, percentage of days with NRS ≤2, and percentage of patients with no-to-minimal pericarditis symptoms at week 16 of the RW period. Safety evaluations include adverse event monitoring, physical examinations, and laboratory tests. The RHAPSODY trial will evaluate the efficacy and safety of rilonacept in the treatment of RP to improve outcomes and patient health-related quality of life.


Asunto(s)
Monitoreo de Drogas/métodos , Pericarditis , Calidad de Vida , Proteínas Recombinantes de Fusión , Prevención Secundaria/métodos , Adolescente , Adulto , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Ensayos Clínicos Fase III como Asunto , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Inyecciones Subcutáneas , Interleucina-1alfa/antagonistas & inhibidores , Interleucina-1beta/antagonistas & inhibidores , Masculino , Pericarditis/diagnóstico , Pericarditis/tratamiento farmacológico , Pericarditis/fisiopatología , Pericarditis/psicología , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos
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