Articles: placebo.
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The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics. ⋯ Approaches using membrane transporters and receptor-mediated transcytosis are less invasive than are other techniques, but they can have off-target effects. Nanotherapeutics have shown promise, but these strategies are in early stages of development. Advancements in drug delivery across the blood-brain barrier will require appropriately designed and powered clinical studies, with a focus on the timing of treatment, demographic and genetic considerations, head-to-head comparison with other treatment strategies (rather than a placebo), and relevant primary and secondary outcome measures.
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Introduction: Light profoundly influences human physiology, behaviour and cognition by affecting various functions through light-sensitive cells in the retina. Light therapy has proven effective in treating seasonal depression and other disorders. However, designing appropriate control conditions for light-based interventions remains a challenge. ⋯ Special cases like dynamic lighting, simulated dawn and dusk, complex interventions and studies involving blind or visually impaired patients are also considered. Results: The practical guide outlines steps for selection, implementation, evaluation and reporting, emphasizing the importance of α-opic calculations and physiological validation. Conclusion: In conclusion, constructing effective control conditions is crucial for demonstrating the efficacy of light interventions in various research scenarios.
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Review Meta Analysis
The impact of contextual effects in exercise therapy for low back pain: a systematic review and meta-analysis.
Low back pain is the leading cause of global disability for which exercise therapy is a widely recommended treatment. Research indicates that contextual factors may also influence treatment outcomes in low back pain. Examples include the patient-therapist relationship and other treatment-related circumstances that affect patient expectations. By focusing on the specific treatment effect, clinical trials often ignore the effect of contextual factors, thereby contributing to the so-called efficacy paradox. This means that treatment effects observed in clinical practice are often greater than those reported in clinical trials. This systematic review aims to investigate the proportion of improvement in pain and disability that can be attributed to contextual effects in the outcome of exercise therapy for patients with low back pain. ⋯ A large extent of pain and disability improvement after exercise therapy in low back pain is attributable to contextual effects although this conclusion is based on low certainty evidence.
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Meta Analysis
Genicular Nerve Block for Knee Osteoarthritis: A Systematic Review and meta-analysis of Randomized Clinical Trials.
Genicular nerve block (GNB) has emerged as a novel nonsurgical therapy for symptomatic knee osteoarthritis (KOA). The objective was to evaluate GNB versus placebo and other intra-articular (IA) therapies. ⋯ Although, GNB achieved the MCID for KOA pain and statistically significant results for knee functions. We cannot recommend its routine use besides being a safe procedure so far, evidence is fair on GNB for primary KOA due to study heterogeneity and limited follow-up.
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Racemic ketamine is a 1:1 mixture of 2 enantiomers that turn light in opposite direction: Dextrorotatory esketamine is approximately 4 times more affine for the N-methyl-D-aspartate (NMDA) receptor than levorotatory arketamine, which may explain why esketamine is about twice as potent as an analgesic and anesthetic as the racemate. Esketamine has attracted renewed interest in view of the opioid crisis, racemic ketamine's abuse, and esketamine's approval for expanded use. We evaluated the anesthesia literature concerning mental, cardiovascular, cerebral, and antinociceptive effects of esketamine published in English between 1980 and 2022. ⋯ In comparison of esketamine with placebo, esketamine shows cardiocirculatory stabilizing and neuroprotective effects which can be seen in anesthesia induction, cardiac surgery, and analgesia and sedation in brain injury. Evidence of esketamine's antinociceptive efficacy is inconsistent, although a recent meta-analysis reports improved pain relief after surgery in a study with short observation time. To better define esketamine's place, direct head-to-head comparison with the racemate at equi-analgesic/anesthetic dose is warranted.