Bmc Med
-
Sleep-wakefulness cycles are an essential diagnostic criterion for disorders of consciousness (DOC), differentiating prolonged DOC from coma. Specific sleep features, like the presence of sleep spindles, are an important marker for the prognosis of recovery from DOC. Based on increasing evidence for a link between sleep and neuronal plasticity, understanding sleep in DOC might facilitate the development of novel methods for rehabilitation. Yet, well-controlled studies of sleep in DOC are lacking. Here, we aimed to quantify, on a reliable evaluation basis, the distribution of behavioral and neurophysiological sleep patterns in DOC over a 24-h period while controlling for environmental factors (by recruiting a group of conscious tetraplegic patients who resided in the same hospital). ⋯ The distribution of sleep signs in DOC over 24 h differs significantly from the normal sleep-wakefulness pattern. These abnormalities of sleep in DOC are independent of external factors such as severe immobility and hospital environment.
-
Randomized Controlled Trial
Adding flexibility to clinical trial designs: an example-based guide to the practical use of adaptive designs.
Adaptive designs for clinical trials permit alterations to a study in response to accumulating data in order to make trials more flexible, ethical, and efficient. These benefits are achieved while preserving the integrity and validity of the trial, through the pre-specification and proper adjustment for the possible alterations during the course of the trial. ⋯ One major reason for this is that different adaptations to trial designs, as well as their advantages and limitations, remain unfamiliar to large parts of the clinical community. The aim of this paper is to clarify where adaptive designs can be used to address specific questions of scientific interest; we introduce the main features of adaptive designs and commonly used terminology, highlighting their utility and pitfalls, and illustrate their use through case studies of adaptive trials ranging from early-phase dose escalation to confirmatory phase III studies.
-
Cannabis use is increasing in women of reproductive age, but whether cannabis use disorders increase the long-term risk of cardiovascular disease in this population is not known. Cannabis may cause tachycardia, hypertension, cerebral vasoconstriction, and other adverse cardiovascular effects and has been associated with acute myocardial infarction and stroke. Data on the long-term effects of cannabis on the cardiovascular system are more limited. We assessed the relationship between cannabis use disorders early in life and the future risk of cardiovascular disease in women. ⋯ Cannabis use disorders may increase the long-term risk of cardiovascular disease in women, particularly hemorrhagic stroke. However, some of the excess risk may be due to concomitant use of other substances.
-
Metastatic breast cancer is a major cause of cancer-related deaths in woman. Brain metastasis is a common and devastating site of relapse for several breast cancer molecular subtypes, including oestrogen receptor-positive disease, with life expectancy of less than a year. While efforts have been devoted to developing therapeutics for extra-cranial metastasis, drug penetration of blood-brain barrier (BBB) remains a major clinical challenge. Defining molecular alterations in breast cancer brain metastasis enables the identification of novel actionable targets. ⋯ ADAM22 expression in advanced breast cancer supports development of breast cancer brain metastasis. Targeting ADAM22 with a peptide mimetic LGI1MIM represents a new therapeutic option to treat metastatic brain disease.
-
Duchenne muscular dystrophy (DMD) is a progressive, degenerative muscular disorder and cognitive dysfunction caused by mutations in the dystrophin gene. It is characterized by excess inflammatory responses in the muscle and repeated degeneration and regeneration cycles. Neutral sphingomyelinase 2/sphingomyelin phosphodiesterase 3 (nSMase2/Smpd3) hydrolyzes sphingomyelin in lipid rafts. This protein thus modulates inflammatory responses, cell survival or apoptosis pathways, and the secretion of extracellular vesicles in a Ca2+-dependent manner. However, its roles in dystrophic pathology have not yet been clarified. ⋯ nSMase2/Smpd3-modulated lipid raft integrity is a potential therapeutic target for DMD.