RESUMEN
BACKGROUND: Buprenorphine is an effective and safe treatment for opioid use disorder, but the requirement for moderate opioid withdrawal symptoms to emerge prior to initiation is a significant treatment barrier. CASE PRESENTATION: We report on two cases of hospitalized patients with severe, active opioid use disorder, in which we initiated treatment with transdermal buprenorphine over 48 h, followed by the administration of a single dose of sublingual buprenorphine/naloxone and then extended-release subcutaneous buprenorphine. The patients did not experience precipitated withdrawal and only had mild withdrawal symptoms. CONCLUSIONS: This provides preliminary evidence for a rapid induction strategy that may improve tolerability, caregiver burden, and treatment retention as compared to previous induction strategies.
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Administración Cutánea , Buprenorfina , Preparaciones de Acción Retardada , Trastornos Relacionados con Opioides , Síndrome de Abstinencia a Sustancias , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Buprenorfina/administración & dosificación , Buprenorfina/uso terapéutico , Masculino , Adulto , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéutico , Femenino , Tratamiento de Sustitución de Opiáceos/métodos , Inyecciones Subcutáneas , Persona de Mediana Edad , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Combinación Buprenorfina y Naloxona/administración & dosificación , Combinación Buprenorfina y Naloxona/uso terapéuticoRESUMEN
Patients with chronic kidney disease (CKD) have a markedly increased risk for developing cardiovascular disease. Nontraditional risk factors, such as increased phosphate retention, increased serum fibroblast growth factor 23 (FGF-23), and deficiencies in vitamins D and K metabolism, likely play key roles in the development of vascular calcification during CKD progression. Calcitriol [1,25-(OH)2-D3] is a key transcriptional regulator of matrix Gla protein, a vitamin K-dependent protein that inhibits vascular calcification. We hypothesized that calcitriol treatment would inhibit the development of vascular calcification and this inhibition would be dependent on vitamin K status in a rat model of CKD. Rats were treated with dietary adenine (0.25%) to induce CKD, with either 0, 20, or 80 ng/kg of calcitriol with low or high dietary vitamin K1 (0.2 or 100 mg/kg) for 7 weeks. Calcitriol at both lower (20 ng/kg) and moderate (80 ng/kg) doses increased the severity of vascular calcification, and contrary to our hypothesis this was not significantly improved by high dietary vitamin K1. Calcitriol had a dose-dependent effect on: 1) lowering serum parathyroid hormone, 2) increasing serum calcium, and 3) increasing serum FGF-23. Calcitriol treatment significantly increased aortic expression of the calcification genes Runx2 and Pit-1 These data also implicate impaired vitamin D catabolism in CKD, which may contribute to the development of calcitriol toxicity and increased vascular calcification. The present findings demonstrate that in an adenine-induced rat model of CKD calcitriol treatment at doses as low as 20 ng/kg can increase the severity of vascular calcification regardless of vitamin K status.
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Calcitriol/farmacología , Hiperparatiroidismo Secundario/complicaciones , Hiperfosfatemia/complicaciones , Insuficiencia Renal Crónica/complicaciones , Calcificación Vascular/complicaciones , Calcificación Vascular/metabolismo , Vitamina K/metabolismo , Animales , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Hemodinámica/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Calcificación Vascular/fisiopatología , Vitamina K/sangreRESUMEN
BACKGROUND: The adoption of the flipped classroom in undergraduate medical education calls on students to learn from various self-paced tools-including online lectures-before attending in-class sessions. Hence, the design of online lectures merits special attention, given that applying multimedia design principles has been shown to enhance learning outcomes. OBJECTIVE: The aim of this study was to understand how online lectures have been integrated into medical school curricula, and whether published literature employs well-accepted principles of multimedia design. METHODS: This scoping review followed the methodology outlined by Arksey and O'Malley (2005). Databases, including MEDLINE, PsycINFO, Education Source, FRANCIS, ERIC, and ProQuest, were searched to find articles from 2006 to 2016 related to online lecture use in undergraduate medical education. RESULTS: In total, 45 articles met our inclusion criteria. Online lectures were used in preclinical and clinical years, covering basic sciences, clinical medicine, and clinical skills. The use of multimedia design principles was seldom reported. Almost all studies described high student satisfaction and improvement on knowledge tests following online lecture use. CONCLUSIONS: Integration of online lectures into undergraduate medical education is well-received by students and appears to improve learning outcomes. Future studies should apply established multimedia design principles to the development of online lectures to maximize their educational potential.
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Psychotic disorders are heterogeneous and complex, involving many putative causal factors interacting along the course of disease development. Many of the factors implicated in the pathogenesis of psychosis also appear to be involved in disease onset and subsequent neuroprogression. Herein, we highlight the pertinent literature implicating inflammation and oxidative stress in the pathogenesis of psychosis, and the potential contribution of N-methyl-D-aspartate receptors (NMDARs). We also emphasize the role of peripubertal social stress in psychosis, and the ways in which hippocampal dysfunction can mediate dysregulation of the hypothalamic-pituitary-adrenal axis and cortisol release. Finally, we propose a model wherein inflammation and oxidative stress act as a first hit, producing altered parvalbumin interneuron development, NMDAR hypofunction, microglial priming, and sensitivity to a second hit of peripubertal social stress. With a greater understanding of how these factors interact, it may be possible to detect, prevent, and treat psychosis more effectively.
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Hipocampo , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Trastornos Psicóticos , Estrés Psicológico , Hipocampo/fisiopatología , Humanos , Hidrocortisona , Inflamación , Interneuronas , Microglía , Estrés Oxidativo , Parvalbúminas/metabolismo , Trastornos Psicóticos/fisiopatología , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
Although our understanding of psychotic disorders has advanced substantially in the past few decades, very little has changed in the standard of care for these illnesses since the development of atypical anti-psychotics in the 1990s. Here, we integrate new insights into the pathophysiology with the increasing interest in early detection and prevention. First, we explore the role of N-methyl-d-aspartate receptors in a subpopulation of cortical parvalbumin-containing interneurons (PVIs). Postmortem and preclinical data has implicated these neurons in the positive and negative symptoms, as well as the cognitive dysfunction present in schizophrenia. These neurons also appear to be sensitive to inflammation and oxidative stress during the perinatal and peripubertal periods, which may be mediated in large part by aberrant synaptic pruning. After exploring some of the molecular mechanisms through which neuroinflammation and oxidative stress are thought to exert their effects, we highlight the progress that has been made in identifying psychosis prior to onset through the identification of individuals at clinical high risk for psychosis (CHR). By combining our understanding of psychosis pathogenesis with the increasing characterization of endophenotypes that precede frank psychosis, it may be possible to identify patients before they present with psychosis and intervene to reduce the burden of the disease to both patients and families.
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Estrés Oxidativo , Trastornos Psicóticos/metabolismo , Esquizofrenia/metabolismo , Animales , Humanos , Inflamación , Neuronas/metabolismo , Trastornos Psicóticos/patología , Receptores de N-Metil-D-Aspartato/metabolismo , Esquizofrenia/patologíaRESUMEN
Chronic kidney disease (CKD) patients are commonly treated with vitamin D analogs, such as calcitriol. Recent epidemiologic evidence revealed a significant interaction between vitamin D and magnesium, since an inverse relationship between vitamin D levels and mortality mainly occurs in patients with a high magnesium intake. The aim of the study was to assess the mechanisms involved by determining whether magnesium alone or combined with calcitriol treatments differentially impacts vascular calcification (VC) in male Sprague-Dawley rats with adenine-induced CKD. Treatment with moderate doses of calcitriol (80 µg/kg) suppressed parathyroid hormone to near or slightly below control levels. Given alone, this dose of calcitriol increased the prevalence of VC; however, when magnesium was given in combination, the severity of calcification was attenuated in the abdominal aorta (51% reduction), iliac (44%), and carotid arteries (46%) compared with CKD controls. The decreases in vascular calcium content were associated with a 20-50% increase in vascular magnesium. Calcitriol treatment alone significantly decreased TRPM7 protein (↓ to â¼11%), whereas the combination treatment increased both mRNA (1.7×) and protein (6.8×) expression compared with calcitriol alone. In summary, calcitriol increased VC in certain conditions, but magnesium prevented the reduction in TRPM7 and reduced the severity of VC, thereby increasing the bioavailable magnesium in the vascular microenvironment. These findings suggest that modifying the adverse effect profile of calcitriol with magnesium may be a plausible approach to benefiting the increasing number of CKD patients being prescribed calcitriol.