RESUMEN
INTRODUCTION: Nonspecific interstitial pneumonia (NSIP) are rare but severe diseases, with high mortality and morbidity, with no effective pharmacological treatment allowing for long-term remission, and therefore no clear therapeutic recommendations. Classic immunosuppressants are used as first-line treatment, with only one third of patients being responders and no clear recommendations exist for the choice of the second-line therapy. The EvER-ILD study is the first one to prospectively evaluate the efficacy and safety of rituximab and mycophenolate mofetil (MMF) versus placebo and MMF in a broad range of NSIP patients that did not respond to a first-line therapy. A pharmacokinetic-pharmacodynamic analysis based on rituximab serum concentrations will allow identification of potential factors associated with therapeutic response and/or adverse effects. METHODS: EvER-ILD study is a French multicenter, prospective, randomized, double blind, placebo-controlled, superiority trial. Patients with severe and progressive NSIP non-responding to a first line immunosuppressive treatment will be randomized in 2 groups of treatment: one course of rituximab plus 6 months MMF (RTX-MMF group) and one course of placebo plus 6 months MMF (Placebo-MMF group). The primary outcome is the change in Forced Vital Capacity (FVC, % of predicted) from baseline to 6 months. Several clinical, biological, and quality of life secondary outcomes will be measured at 3, 6 and 12 months. A sample size of 122 patients (61 patients per group) would allow to show a point difference between groups in the change of FVC at 6 months, based on a common standard deviation for FVC change of 8% with a power of 90%, alpha 5% two-sided, and anticipating an extreme 10% drop-out rate. ETHICS AND DISSEMINATION: The protocol was approved by the French Research Ethics Committee (CPP Tours Ouest 1 2016-R28) on November 10, 2016, and by the French competent authority (ANSM, reference 160771A-22) on December 1st, 2016. This article refers to protocol V2, dated November 18, 2016. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. Results will be disseminated via peer reviewed publication and presentation at international conferences. TRIAL REGISTRATION NUMBER: NCT02990286 (clinicaltrials.gov), EudraCT 2016-003026-16 (European Medicines agency).
Asunto(s)
Neumonías Intersticiales Idiopáticas/tratamiento farmacológico , Ácido Micofenólico/administración & dosificación , Rituximab/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Resistencia a Medicamentos/efectos de los fármacos , Quimioterapia Combinada , Femenino , Francia , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Rituximab/efectos adversos , Resultado del TratamientoRESUMEN
Beta-blockers (BB) are an heterogenous set of molecules actively blocking ß adrenergic receptors. Their pharmacological properties depend on their various effects on the adrenergic signalling. Although they are no longer a first-choice treatment in hypertensive patients, they remain a cornerstone of pharmacological strategy in several cardiovascular diseases such as stable angina, heart failure, arrythmia and aortic related connective diseases. Beyond their usual non cardiovascular indications such as migraine, hepatic cirrhosis, glaucoma, infantile hemangioma, and hyperthyroidism, new therapeutic fields are under scrutiny. Potential BB therapeutic repurposing is being investigated in COPD and cancer patients. This narrative review first encompasses the basic pharmacological knowledge that may be useful for the clinician. Then it will detail BB main indications before exploring new therapeutic fields.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/uso terapéutico , Medicina Interna/tendencias , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Reposicionamiento de Medicamentos/métodos , Reposicionamiento de Medicamentos/tendencias , Humanos , Medicina Interna/métodos , Neoplasias/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Transducción de Señal/efectos de los fármacosRESUMEN
AIM: Recent US recommendations indicate a target blood pressure (BP) of 130/80mmHg for patients with type 2 diabetes (T2D). Our aim was to characterize the association between risk of cardiovascular events and differences in BP decreases in randomized trials of a T2D population. METHODS: A systematic search was made for randomized clinical trials assessing the effects of antihypertensive treatments in T2D patients on mortality, and fatal and non-fatal cardiovascular events, using a meta-regression technique to explore the influence of BP decreases on treatment effects. RESULTS: A total of 88,503 patients from 44 randomized trials were included. There was no significant association between BP decreases and risk of all-cause or cardiovascular mortality, cardiovascular events or myocardial infarction. However, stroke risk was influenced by BP decreases: compared with no reduction, a 10-mmHg reduction in systolic BP was associated with a relative odds ratio (OR) decrease of 33% (OR: 0.67, 95% CI: 0.54-0.82), and a 5-mmHg diastolic BP reduction was associated with a relative OR decrease of 38% (OR: 0.62, 95% CI: 0.50-0.76). Restricting the analysis to double-blind studies did not change the results for diastolic BP. CONCLUSION: A reduction in BP lowers the risk of stroke, but does not appear to affect the risk of other cardiovascular events in a T2D population.
Asunto(s)
Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/mortalidad , Angiopatías Diabéticas/prevención & control , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Análisis de Regresión , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidadRESUMEN
BACKGROUND: With the rapid adoption of the robotic surgery, more and more learning curve (LC) papers are being published but there is no set definition of what should constitute a rigorous analysis and represent a true LC. A systematic review of the robotic surgical literature was undertaken to determine the range and heterogeneity of parameters reported in studies assessing the LC in robotic surgery. METHODS: The search was conducted in July 2017 in PubMed. All studies reporting a LC in robotic surgery were included. 268 (25%) of the identified studies met the inclusion criteria. RESULTS: 102 (38%) studies did not define nor explicitly state the LC with appropriate evidence; 166 studies were considered for quantitative analysis. 46 different parameters of 6 different outcome domains were reported with a median of two parameters (1-8) and 1 domain (1-5) per study. Overall, three domains were only technical and three domains were both technical and clinical/patient-centered outcomes. The two most commonly reported domains were operative time [146 studies (88%)] and intraoperative outcomes [31 studies (19%)]. Postoperative outcomes [16 studies (9%)] and surgical success [11 studies (7%)] were reported infrequently. Purely technical outcomes were the most frequently used to assess LC [131 studies (79%)]. CONCLUSIONS: The outcomes reported in studies assessing LC in robotic surgery are extremely heterogeneous and are most often technical indicators of surgical performance rather than clinical and patient-centered outcomes. There is no single outcome that best represents the surgical success. A standardized multi-outcome approach to assessing LC is recommended.
Asunto(s)
Competencia Clínica , Curva de Aprendizaje , Procedimientos Quirúrgicos Robotizados/educación , Humanos , Tempo Operativo , Evaluación de Resultado en la Atención de Salud , Procedimientos Quirúrgicos Robotizados/psicologíaAsunto(s)
Amitriptilina/efectos adversos , Analgésicos no Narcóticos/efectos adversos , Industria Farmacéutica/tendencias , Trastornos Migrañosos/prevención & control , Topiramato/efectos adversos , Adolescente , Adulto , Factores de Edad , Amitriptilina/administración & dosificación , Analgésicos no Narcóticos/administración & dosificación , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Niño , Úlcera Duodenal/tratamiento farmacológico , Femenino , Francia , Reflujo Gastroesofágico/tratamiento farmacológico , Humanos , Masculino , Farmacovigilancia , Fenitoína/administración & dosificación , Fenitoína/efectos adversos , Fenitoína/análogos & derivados , Sustitutos del Plasma/administración & dosificación , Sustitutos del Plasma/efectos adversos , Poligelina/administración & dosificación , Poligelina/efectos adversos , Inhibidores de la Bomba de Protones/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Factores Sexuales , Úlcera Gástrica/tratamiento farmacológico , Topiramato/administración & dosificaciónAsunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Fármacos Antiobesidad/efectos adversos , Anticonvulsivantes/efectos adversos , Aorta/efectos de los fármacos , Aneurisma de la Aorta/prevención & control , Atenolol/uso terapéutico , Fisura del Paladar/inducido químicamente , Fructosa/análogos & derivados , Hemangioma/congénito , Hemangioma/epidemiología , Losartán/uso terapéutico , Síndrome de Marfan/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal , Neoplasias Cutáneas/congénito , Neoplasias Cutáneas/epidemiología , Femenino , Humanos , Masculino , EmbarazoRESUMEN
Recent recommendations regarding type 2 diabetes (T2D) patients' treatments have focused on personalizing glycosylated haemoglobin (HbA1c) targets. Because the relationship between HbA1c and diabetes prognosis has been established from large prospective cohorts, it is valid to question the extrapolation from population-based risk reduction estimations to individual predictions. Our study aimed to investigate the relationship between HbA1c reductions and clinical outcomes in randomized controlled trials (RCTs), using a meta-regression approach. Included were RCTs comparing intensive vs. standard glucose-lowering regimens for cardiovascular events and microvascular complications in T2D patients. Eight studies (33,396 patients) providing data for HbA1c reductions were found. In our meta-regression, HbA1c decreases were not significantly associated with reductions in our main study outcomes: total and cardiovascular mortality. They were also not associated with any of the secondary endpoints, including myocardial infarction, stroke and severe hypoglycaemia. Sensitivity analysis showed a significant correlation only between HbA1c-lowering and severe hypoglycaemia (P = 0.014). Meta-regression analysis could find no significant association between HbA1c-lowering and a decrease in clinical outcomes, thereby questioning the use of HbA1c as a surrogate outcome for T2D-related complications. Thus, RCTs vs. placebo are urgently required to evaluate the risk-benefit ratios of therapeutic strategies beyond HbA1c control in T2D patients.
Asunto(s)
Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Hemoglobina Glucada/análisis , Anciano , Medicina Basada en la Evidencia , Humanos , Hipoglucemiantes , Persona de Mediana Edad , Análisis de RegresiónRESUMEN
Nifedipine and nicardipine are both calcium channel inhibitors, used off-label as tocolytics in preterm labour. Their use is related to their relaxing effects on uterin muscle by L-type voltage dependent calcium channels blockade. This article describes pharmacological effects, pharmacokinetics properties and tolerance of these drugs. It also discusses serious adverse effects, such as pulmonary edema, reported with both nifedipine and nicardipine in preterm labour.
Asunto(s)
Bloqueadores de los Canales de Calcio , Nicardipino , Nifedipino , Trabajo de Parto Prematuro/tratamiento farmacológico , Tocolíticos , Adulto , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/farmacocinética , Bloqueadores de los Canales de Calcio/farmacología , Femenino , Humanos , Nicardipino/administración & dosificación , Nicardipino/efectos adversos , Nicardipino/farmacocinética , Nicardipino/farmacología , Nifedipino/administración & dosificación , Nifedipino/efectos adversos , Nifedipino/farmacocinética , Nifedipino/farmacología , Embarazo , Tocolíticos/administración & dosificación , Tocolíticos/efectos adversos , Tocolíticos/farmacocinética , Tocolíticos/farmacologíaAsunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Uso Fuera de lo Indicado , Guías de Práctica Clínica como Asunto/normas , Tocólisis/normas , Tocolíticos/farmacología , Bloqueadores de los Canales de Calcio/efectos adversos , Femenino , Humanos , Embarazo , Tocolíticos/efectos adversosRESUMEN
The literature suggests that misoprostol can be offered to patients for off-label use as it has reasonable efficacy, risk/benefit ratio, tolerance and patient satisfaction, according to the criteria for evidence-based medicine. Both the vaginal and sublingual routes are more effective than the oral route for first-trimester cervical dilatation. Vaginal misoprostol 800µg, repeated if necessary after 24 or 48h, is a possible alternative for management after early pregnancy failure. However, misoprostol has not been demonstrated to be useful for the evacuation of an incomplete miscarriage, except for cervical dilatation before vacuum aspiration. Oral mifepristone 200mg, followed 24-48h later by vaginal, sublingual or buccal misoprostol 800µg (followed 3-4h later, if necessary, by misoprostol 400µg) is a less efficacious but less aggressive alternative to vacuum aspiration for elective or medically-indicated first-trimester terminations; this alternative becomes increasingly less effective as gestational age increases. In the second trimester, vaginal misoprostol 800-2400µg in 24h, 24-48h after at least 200mg of mifepristone, is an alternative to surgery, sulprostone and gemeprost. Data for the third trimester are sparse. For women with an unripe cervix and an unscarred uterus, vaginal misoprostol 25µg every 3-6h is an alternative to prostaglandin E2 for cervical ripening at term for a live fetus. When oxytocin is unavailable, misoprostol can be used after delivery for prevention (sublingual misoprostol 600µg) and treatment (sublingual misoprostol 800µg) of postpartum haemorrhage. The use of misoprostol to promote cervical dilatation before diagnostic hysteroscopy or surgical procedures is beneficial for premenopausal women but not for postmenopausal women. Nonetheless, in view of the side effects of misoprostol, its use as a first-line treatment is not indicated, and it should be reserved for difficult cases. Misoprostol is not useful for placing or removing the types of intra-uterine devices used in Europe, regardless of parity.
Asunto(s)
Abortivos no Esteroideos , Ginecología/métodos , Misoprostol/administración & dosificación , Obstetricia/métodos , Uso Fuera de lo Indicado , Aborto Inducido/métodos , Administración Intravaginal , Administración Sublingual , Maduración Cervical , Femenino , Muerte Fetal , Francia , Edad Gestacional , Humanos , Hemorragia Posparto/tratamiento farmacológico , EmbarazoRESUMEN
Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Presión Arterial/efectos de los fármacos , Diuréticos/uso terapéutico , Hipertensión/tratamiento farmacológico , Indapamida/uso terapéutico , Perindopril/uso terapéutico , Adulto , Factores de Edad , Anciano , Estudios Cruzados , Método Doble Ciego , Femenino , Francia , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Selección de Paciente , Factores Sexuales , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Antiinflamatorios/efectos adversos , Anticonvulsivantes/efectos adversos , Peso al Nacer/efectos de los fármacos , Sistema Inmunológico/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Susceptibilidad a Enfermedades , Femenino , Fructosa/efectos adversos , Fructosa/análogos & derivados , Humanos , Sistema Inmunológico/embriología , Recién Nacido , Infecciones/etiología , Infliximab , Embarazo , Efectos Tardíos de la Exposición Prenatal , TopiramatoRESUMEN
Misoprostol is a synthetic analogue of prostaglandin E1. It is used in gynaecology because of its properties of myometrium smooth muscle cells contraction and its effects on the cervix. Misoprostol oral bioavailability is low and several authors have assessed whether the administration by other routes increased its pharmacodynamic effects. This paper summarizes the pharmacokinetic studies after other routes of administration: vaginal, sublingual, buccal or rectal. It also provides an update on its adverse effects and teratogenic effects.