Articles: chronic.
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Responses to pharmacotherapy for acute and chronic pain are highly variable, and efficacy is often compromised by some form of toxicity. To increase our understanding of complexities of pharmacotherapy, the authors discuss an approach to identify analgesic responder subgroups and predictors of response. Additionally, analgesic efficacy and toxicity were combined in a single risk-benefit index (utility function) to quantify the probability of side effects in high- vs low-analgesic responders. ⋯ An important observation was that, irrespective of dose, low-analgesic responders to fentanyl had a greater probability of respiratory depression than analgesia while the reverse was true for high-analgesic responders. These data show dissociation between 2 μ-opioid end-points and explain the danger of treating poor analgesic responders with increasingly higher opioid doses. Apart from being valuable in drug development programs, the outlined approach can be used to determine the choice of drug and dose in the treatment of pain in patients with potent and toxic analgesics.
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Review Comparative Study
An official American Thoracic Society/European Respiratory Society statement: research questions in COPD.
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) research statement is to describe evidence related to diagnosis, assessment and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. ⋯ Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centred outcomes.
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An important property of the nociceptive system is its plasticity, ie, the ability to change in an experience-dependent manner, which is implicated in the transition from acute pain to chronic pathological pain. Disease-induced plasticity can occur at both structural and functional levels and manifests as changes in individual molecules, synapses, cellular function, and network activity. In this short review, the author discusses how synaptic plasticity may mediate pathophysiological alterations linked to chronic pain by virtue of shifting the balance between excitation and inhibition, with a particular emphasis on the spinal dorsal horn. ⋯ Structural remodeling and reorganization represent another exciting area of advance in our understanding of pain. Here, new insights into maladaptive structural plasticity of spinal synapses and molecular determinants thereof will be discussed. Finally, the role of synapse-to-nucleus communication in mediating long-term changes in nociceptive sensitivity is discussed from the view point of pain chronicity.
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Diagnosis of acute mesenteric ischemia in the early stages is now possible with modern computed tomography (CT), using intravenous contrast enhancement and imaging in the arterial and/or portal venous phase. The availability of CT around the clock means that more patients with acute mesenteric ischemia may be treated with urgent intestinal revascularization. ⋯ Intestinal revascularization in patients with arterial occlusive mesenteric ischemia reduces bowel morbidity and mortality. Observational studies report that both endovascular and open vascular therapy options are effective, but endovascular technique may be preferred in these often elderly and fragile patients.
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Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder of cilia structure, function, and biogenesis leading to chronic infections of the respiratory tract, fertility problems, and disorders of organ laterality. The diagnosis can be challenging, using traditional tools such as characteristic clinical features, ciliary function, and ultrastructural defects and newer screening tools such as nasal nitric oxide levels and genetic testing add to the diagnostic algorithm. There are 32 known PCD-causing genes, and in the future, comprehensive genetic testing may screen young infants before developing symptoms, thus improving survival. ⋯ As with cystic fibrosis (CF), standardized care at specialized centers using a multidisciplinary approach likely improves outcomes. In conjunction with the CF foundation, the PCD foundation, with experienced investigators and clinicians, is developing a network of PCD clinical centers to coordinate the effort in North America and Europe. As the network grows, clinical care and knowledge will improve.