Gayle G. Page

The relationship between competence and performance: implications for assessing practice performance

Objective  This paper aims to describe current views of the relationship between competence and performance and to delineate some of the implications of the distinctions between the two areas for the purpose of assessing doctors in practice.

Evidence that postoperative pain is a mediator of the tumor-promoting effects of surgery in rats.

&NA; We have previously shown in rats that the provision of analgesic doses of morphine significantly reduces the tumor‐promoting effects of undergoing and recovering from surgery. Because morphine had no effect in non‐operated animals, and because a single preoperative dose given hours before tumor inoculation was effective, we have suggested that it is the pain‐relieving effects of the drug that underlies its beneficial impact. To support and strengthen this suggestion, two different regimens of analgesia were employed, the systemic administration of the more selective &mgr;‐agonist, fentanyl, and the intrathecal (i.t.) administration of bupivacaine plus morphine. To assess host resistance against metastasis, we used a lung clearance assay of the MADB106 mammary adenocarcinoma, a natural killer (NK)‐sensitive syngeneic cell line that metastasizes only to the lungs. Female and male Fischer 344 rats were randomly assigned to one of four groups using a 2×2 experimental design: experimental laparotomy under halothane anesthesia versus anesthesia alone, by drug treatment versus vehicle. In the first in vivo experiment, fentanyl was administered 20 min before surgery (40 &mgr;g/kg subcutaneously (s.c.)), and at the end of surgery in a slow‐release suspension (20 &mgr;g/kg s.c.). In the second in vivo experiment, bupivacaine (10 &mgr;g) plus morphine (20 &mgr;g) in 50 &mgr;l was administered i.t. before surgery. Surgery resulted in a 3‐ to 4‐fold increase in the lung retention of MADB106 cells in both males and females, and the observed surgery‐induced increase in lung tumor retention was reduced by more than 65% in the fentanyl‐treated animals and more than 45% in the animals receiving i.t. bupivacaine plus morphine. Neither drug regimen exerted effects in the anesthesia only animals. Surgery also resulted in a significant suppression of whole blood NK activity assessed at 5 h postoperatively, the same time point at which MADB106 tumor cells were inoculated in the in vivo studies. Unlike the in vivo study, fentanyl suppressed NK activity at this time point in non‐operated rats, but had no effect in operated rats. Taken together, these findings strengthen the suggestion that the management of perioperative pain is a critical factor in preventing surgery‐induced decreases in host resistance against metastasis. If similar relationships between pain and metastasis occur in humans, then pain control must become a priority in the postoperative care of individuals with cancer.

PTSD is Associated With an Excess of Inflammatory Immune Activities

PURPOSE. Post-traumatic stress disorder (PTSD) is associated with inflammatory-related medical conditions. This review examines studies of immune function in individuals with PTSD to determine if excessive inflammation is associated with PTSD. CONCLUSIONS. Current studies suggest an excess of inflammatory actions of the immune system in individuals with chronic PTSD. High levels of inflammatory cytokines have also been linked to PTSD vulnerability in traumatized individuals. There is also evidence that excessive inflammation is in part due to insufficient regulation by cortisol. PRACTICE IMPLICATIONS. An excess of inflammatory immune activity may contribute to health declines in individuals with PTSD, and treating PTSD symptoms may reduce these risks.

Low cortisol, high DHEA, and high levels of stimulated TNF‐α, and IL‐6 in women with PTSD

Posttraumatic stress disorder (PTSD) has been associated with hypothalamic-pituitary-adrenal (HPA) axis and immune function alterations; however, few studies have simultaneously investigated these systems in participants with PTSD. In this study, HPA axis and immune function in 26 women with PTSD with and without major depressive disorder was compared to 24 traumatized controls and to 21 nontraumatized controls. Posttraumatic stress disorder was associated with low cortisol and higher levels of DHEA and greater production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) compared to traumatized and healthy controls. Women with PTSD and depression exhibited greater production of IL-6 and higher levels of dehydroepiandrosterone (DHEA) than those with PTSD, but without depression. These findings suggest dysregulated HPA axis and immune function in women with PTSD, and that comorbid depression may contribute to these abnormalities.

Suppression of NK cell activity and of resistance to metastasis by stress: A role for adrenal catecholamines and β-adrenoceptors

Although acute stress has been reported to suppress natural killer cell activity (NKA) and host resistance to metastasis, it is unclear whether the sympathetic nervous system (SNS) has a role in these effects. The current study in Fischer 344 rats assessed the involvement of adrenal catecholamines and β1- and β2-adrenoceptors in mediating these deleterious effects of swim stress. In addition to assessing the number and activity of NK cells following swim stress, we used a tumor model based on the MADB106 mammary adenocarcinoma line: this syngeneic tumor metastasizes only to the lungs, and its lung tumor retention (LTR) and metastatic colonization are highly sensitive to NKA. The findings indicate that stress increased both LTR, assessed 24 h after inoculation, and the number of lung metastases, counted 3 weeks later. These effects were attenuated or completely abolished by the ganglionic blocker chlorisondamine (3 mg/kg i.p.), by adrenal demedullation, by a selective β-adrenergic antagonist (nadolol, 0.4 mg/kg), and additively by a selective β1- (atenolol, 1–6 mg/kg) and a selective β2-antagonist (either butoxamine 4–32 mg/kg or ICI-118,551 0.3–8 mg/kg). Stress also suppressed NKA, and adrenal demedullation prevented this suppression. Administration of adrenaline (0.1–1 mg/kg) or of a β-adrenergic agonist (metaproterenol, 0.8 mg/kg), in physiologically relevant doses, suppressed NKA in a dose-dependent manner, and increased LTR to levels characteristic of swim stress. Taken together, these findings suggest that acute stress, by releasing catecholamines from the adrenal glands and activating β1- and β2-adrenoceptors, suppresses NKA and consequently compromises resistance to NK-sensitive metastasis.

Association of catastrophizing with interleukin-6 responses to acute pain

Abstract Catastrophizing exerts its deleterious effects on pain via multiple pathways, and some researchers have reported that high levels of catastrophizing are associated with enhanced physiological reactivity to painful stimulation. In this project, 42 generally healthy adults underwent a series of psychophysical pain testing procedures assessing responses to noxious mechanical, heat, and cold stimuli. Pain catastrophizing cognitions were assessed prior to and then immediately after the various pain induction procedures. Blood samples were taken at baseline and then at several time points from the end of the procedures to 1 h post‐testing. Samples were assayed for serum levels of cortisol and interleukin‐6 (IL‐6). Both cortisol and IL‐6 increased from baseline during the post‐testing period (p’s < .05), with cortisol returning to baseline by 1 h post‐testing and IL‐6 remaining elevated. Pain catastrophizing, measured immediately after the pain procedures, was unrelated to cortisol reactivity, but was strongly related to IL‐6 reactivity (p < .01), with higher levels of catastrophizing predicting greater IL‐6 reactivity. In multivariate analyses, the relationship between catastrophizing and IL‐6 reactivity was independent of pain ratings. Collectively, these findings suggest that cognitive and emotional responses during the experience of pain can shape pro‐inflammatory immune system responses to noxious stimulation. This pathway may represent one important mechanism by which catastrophizing and other psychosocial factors shape the experience of both acute and chronic pain in a variety of settings.

Prostaglandin E2 Suppresses NK Activity In Vivo and Promotes Postoperative Tumor Metastasis in Rats

AbstractBackground: Prostaglandins (PGs) were shown in vitro to suppress several functions of cellular immunity. It is unclear, however, whether physiological levels of PGs can suppress cellular immunity in vivo and whether such suppression would compromise postoperative host resistance to metastasis. Methods: Fischer 344 rats were administered PGE2 in doses (18 to 300 μg/kg subcutaneously) that increased the serum levels approximately 2- to 4-fold. We then assessed the number and activity of circulating natural killer (NK) cells, as well as rats’ resistance to experimental metastasis of a syngeneic NK-sensitive tumor (MADB106). To study whether endogenously released PGs after surgery compromise these indices, we tested whether laparotomy adversely affects them and whether a cyclooxygenase-synthesis inhibitor, indomethacin (4 mg/kg), attenuates these effects. Results: PGE2 dose-dependently suppressed NK activity per NK cell and dose-dependently increased 4- and 24-hour MADB106 lung tumor retention (LTR); 240 μg/kg of PGE2 quadrupled the number of lung metastases counted 3 weeks later. Selective depletion of NK cells abrogated the promotion of LTR by PGE2. Surgery significantly suppressed NK activity and increased MADB106 LTR, and indomethacin halved these effects without affecting nonoperated rats. Conclusions:PGE2 is a potent in vivo suppressor of NK activity, and its postoperative release may promote tumor recurrence.

Pain sensitivity and pain reactivity in osteoarthritis.

To assess experimental pain sensitivity and compare the inflammatory response to pain in 26 osteoarthritis (OA) patients and 33 age‐ and sex‐matched controls from the general population in order to examine the nature of the association between pain and inflammation in OA.

When enough is enough: a conceptual basis for fair and defensible practice performance assessment

Introduction An essential element of practice performance assessment involves combining the results of various procedures in order to see the whole picture. This must be derived from both objective and subjective assessment, as well as a combination of quantitative and qualitative assessment procedures. Because of the severe consequences an assessment of practice performance may have, it is essential that the procedure is both defensible to the stakeholders and fair in that it distinguishes well between good performers and underperformers.

Enhanced reactivity to pain in patients with rheumatoid arthritis

IntroductionMaladaptive physiological responses to stress appear to play a role in chronic inflammatory diseases such as rheumatoid arthritis (RA). However, relatively little stress research in RA patients has involved the study of pain, the most commonly reported and most impairing stressor in RA. In the present study, we compared psychophysical and physiological responses to standardized noxious stimulation in 19 RA patients and 21 healthy controls.MethodsParticipants underwent a single psychophysical testing session in which responses to a variety of painful stimuli were recorded, and blood samples were taken at multiple time points to evaluate the reactivity of cortisol, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) to the experience of acute pain.ResultsThe findings suggest that RA patients display a fairly general hyperalgesia to mechanical and thermal stimuli across several body sites. In addition, while serum cortisol levels did not differ at baseline or following pain testing in patients relative to controls, the RA patients tended to show elevations in serum IL-6 and demonstrated enhanced pain-reactivity of serum levels of TNF-α compared with the healthy controls (P < 0.05).ConclusionsThese findings highlight the importance of pain as a stressor in RA patients and add to a small body of literature documenting amplified responses to pain in RA. Future studies of the pathophysiology of RA would benefit from the consideration of acute pain levels when comparing RA patients with other groups, and future trials of analgesic interventions in RA patients may benefit from evaluating the effects of such interventions on inflammatory activity.