Articles: function.
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Mayo Clinic proceedings · Aug 2023
ReviewQuestioning the Right to Pain Relief and Its Role in the Opioid Epidemic.
The new discipline of palliative care helped to establish the right to pain relief at the end of life and the necessity of using opioids to achieve that goal. Professional pain organizations followed the United Nations' model for universal human rights in their declaration of a universal right to pain management. Both palliative care and pain medicine specialties worked to establish pain as a legitimate focus of medical treatment separate from its association with disease. ⋯ This understanding of opioids as having distinct and separable analgesic and addictive potential was challenged by the 1970s discovery of an endogenous opioid system, which integrates pain and reward functions to support survival. Our modern pain neurophysiology places the patient with pain in a passive position from which it makes sense to assert a right to pain relief. To prevent future opioid epidemics we need to abandon clinical outpatient use of pain intensity scores and redefine the medical necessity of pain treatment as less about the reduction of pain intensity and more about the capacity to pursue personally valued activities.
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Comment Meta Analysis
In ischemic stroke, EVT improved 90-d function more than usual care across admission SBP levels.
Samuels N, van de Graaf RA, Mulder MJHL, et al; HERMES Collaborators. Admission systolic blood pressure and effect of endovascular treatment in patients with ischaemic stroke: an individual patient data meta-analysis. Lancet Neurol. 2023;22:312-319. 36931806.
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This study aimed to identify the clinical usefulness of assessing nutritional status using validated tools for the indication of enteral nutrition for patients with incurable cancer in palliative care. ⋯ Using the modified Glasgow Prognostic Score to identify the existence and severity of CC, which is associated with function, has the potential to help clinical decision making concerning the indication of enteral nutrition in patients with incurable cancer receiving palliative care.
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Anesthesia and analgesia · Aug 2023
Impact of Genetic Variants on Postoperative Pain and Fentanyl Dose Requirement in Patients Undergoing Major Breast Surgery: A Candidate Gene Association Study.
Postoperative analgesia is crucial for the early and effective recovery of patients undergoing surgery. Although postoperative multimodal analgesia is widely practiced, opioids such as fentanyl are still one of the best analgesics. The analgesic response of fentanyl varies widely among individuals, probably due to genetic and nongenetic factors. Among genetic factors, single nucleotide polymorphisms (SNPs) may influence its analgesic response by altering the structure or function of genes involved in nociceptive, fentanyl pharmacodynamic, and pharmacokinetic pathways. Thus, it is necessary to comprehensively ascertain if the SNPs present in the aforementioned pathways are associated with interindividual differences in fentanyl requirement. In this study, we evaluated the association between 10 candidate SNPs in 9 genes and 24-hour postoperative fentanyl dose (primary outcome) and also with postoperative pain scores and time for first analgesia (secondary outcomes). ⋯ The SNP opioid receptor mu-1 ( OPRM1 ) (rs1799971) was associated with higher postoperative fentanyl requirement in South Indian patients undergoing major breast surgery. Twenty-four hour postoperative pain scores were higher in catechol-O-methyl transferase ( COMT ) (rs4680) carriers and lower in ATP binding cassette subfamily B member 1 ( ABCB1 ) (rs1045642) carriers, whereas time for first analgesic was lower in potassium channel subunit 1 ( KCNS1 ) (rs734784) carriers. However, these exploratory findings must be confirmed in a larger study.
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Induced pluripotent stem cells (iPSCs) have enabled the generation of various difficult-to-access cell types such as human nociceptors. A key challenge associated with human iPSC-derived nociceptors (hiPSCdNs) is their prolonged functional maturation. While numerous studies have addressed the expression of classic neuronal markers and ion channels in hiPSCdNs, the temporal development of key signaling cascades regulating nociceptor activity has remained largely unexplored. ⋯ However, effective inhibition of forskolin-induced PKA-II activation by opioid receptor agonists required 70 days of in vitro differentiation. Our results identify a pronounced time difference between early expression of functionally important ion channels and emergence of regulatory metabotropic sensitizing and desensitizing signaling only at advanced stages of in vitro cultivation, suggesting an independent regulation of ionotropic and metabotropic signaling. These data are relevant for devising future studies into the development and regulation of human nociceptor function and for defining time windows suitable for hiPSCdN-based drug discovery.