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In this review we will discuss how regulatory T cells (Tregs), innate lymphoid cells (ILCs), natural killer T cells (NKT cells), TCR-a CD4 CD8 double-negative T cells (DN T cells) and B cells can contribute to the development of post-traumatic and septic immunosuppression. Altogether, we seek to fill a gap in the understanding of the contribution of lymphocyte immunosuppression and dysfunction to the development of chronic immune disbalance. Further, we will provide an overview of promising diagnostic and therapeutic interventions, whose potential to overcome the detrimental immunosuppression after trauma and sepsis is currently being tested.

Little is known about risk factors for emergency department (ED) attendance for chronic pain (CP) management and the relative service burden. We examined ED utilisation in patients with CP, identified risk factors associated with attendance for chronic musculoskeletal pain (CMP), and estimated the comparative cost of treatment. The study cohort comprised a random sample of 3700 adults from the general population in Tayside, Scotland. Linked regional extracts, spanning a 12-month period, were obtained from national registers, providing information on ED attendances, community-dispensed prescribing, and outpatient clinic attendances. The National Health Service Scotland Cost Book was used to ascertain the current average cost of an ED attendance (£130; ∼$167). All-cause ED attendance was higher in those with CP (68.5%; n = 252) than without (29.3%; n = 967). In the entire cohort, more patients attended the ED for the treatment of CMP than for any other medical condition (n = 119; 32.3% of those with CP). RiskOR = 0.21); transitioning from nonopioid to opioid analgesics (OR = 0.25); recent analgesic dose increases (OR = 0.24); and being prescribed tricyclic antidepressants (OR = 0.10), benzodiazepines (OR = 0.46), or hypnotics (OR = 0.45). Chronic musculoskeletal pain was one of the most expensive conditions to treat (£17,680 [∼$22,668] per annum), conferring a substantial burden on ED services. Improved understanding of the risk/protective factors could inform healthcare redesign to reduce avoidable ED attendances for CMP management.

This nationwide study aimed to compare use of oxycodone and doctor shopping for oxycodone in 2010 and 2016, and to quantify doctor shopping for oxycodone by sex, age, formulation, and dosage in 2010 and 2016. This study is a cross-sectional comparative analysis of doctor shopping based on all dispensings of oxycodone in France, in 2010 and 2016. Dispensings of oxycodone were extracted from the Système national des données de santé, which covers the 67 million inhabitants in France. Quantification of doctor shopping relies on an algorithm accounting for overlapping prescriptions, which is a proxy for potential misuse or abuse. The number of subjects who received oxycodone increased by 214% from 67,838 subjects in 2010 to 212,753 subjects in 2016, and the number of subjects with doctor-shopping behavior increased by 197%, from 1066 subjects in 2010 to 3163 subjects in 2016. For 30- to 44-year-old men, the total quantity of oxycodone obtained by doctor shopping increased by 391%, from 4582 defined daily doses xycodone to prevent misuse, potential abuse, and potential oxycodone-related deaths, but it requires caution to prevent compromising effective treatment of pain.

Although overall outpatient dispensing of opioid analgesic prescriptions has declined, there may still be overprescribing. Understanding how many opioid analgesic units, primarily tablets, are dispensed with the intention of shorter-vs longer-term use can inform public health interventions. We used pharmacy prescription data to estimate the number of opioid analgesic tablets dispensed annually in the U.S. We studied patterns of new use of opioid analgesics by evaluating how many opioid analgesic prescriptions and tablets were dispensed to patients with no opioid analgesic prescriptions in the previous year. Estimated opioid analgesic tablets dispensed declined from a peak of 17.8 billion in 2012 to 11.1 billion in 2018. Patients newly starting opioid analgesics declined from 47.4 million patients in 2011 to 37.1 million patients in 2017. Approximately 40% fewer tablets were dispensed within a year to patients starting in 2017 (2.4 billion) compared with 2011 (4.0 billion). In 2011, patients with ≥5 opioid a newly starting therapy. However, these patients received almost half of all tablets dispensed within a year to patients in our study, despite a larger decline than tablets dispensed to patients with less then 5 prescriptions within a year.

Mechanisms of visceral pain sensitization and referred somatic hypersensitivity remain unclear. AS1842856 solubility dmso We conducted calcium imaging in Pirt-GCaMP6s mice to gauge responses of dorsal root ganglion (DRG) neurons to visceral and somatic stimulation in vivo. Intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced colonic inflammation and increased the percentage of L6 DRG neurons that responded to colorectal distension above that of controls at day 7. Colorectal distension did not activate L4 DRG neurons. TNBS-treated mice exhibited more Evans blue extravasation than did control mice and developed mechanical hypersensitivity in low-back skin and hind paws, which are innervated by L6 and L4 DRG neurons, respectively, suggesting that colonic inflammation induced mechanical hypersensitivity in both homosegmental and heterosegmental somatic regions. Importantly, the percentage of L4 DRG neurons activated by hind paw pinch and brush stimulation and calcium responses of L6 DRG neurons to low-back bruw pinch and the response of L6 DRG neurons to low-back brush stimulation. These findings suggest that TNBS-induced colitis and capsaicin-induced visceral irritation may sensitize L6 DRG neurons to colorectal and somatic inputs and also increase the excitability of L4 DRG neurons that do not receive colorectal inputs. These changes may represent a potential peripheral neuronal mechanism for visceral pain sensitization and referred somatic hypersensitivity.