Effect of traditional yoga, mindfulness-based cognitive therapy, and cognitive behavioral therapy, on health related quality of life: a randomized controlled trial on patients on sick leave because of burnout.

BACKGROUND: To explore if health related quality of life(HRQoL) increased after traditional yoga(TY), mindfulness based cognitive therapy(MBCT), or cognitive behavioral therapy(CBT), in patients on sick leave because of burnout. METHODS: Randomized controlled trial, blinded, in ninety-four primary health care patients, block randomized to TY, MBCT or CBT (active control) between September 2007 and November 2009. Patients were living in the Stockholm metropolitan area, Sweden, were aged 18-65 years and were on 50%-100% sick leave. A group treatment for 20 weeks, three hours per week, with homework four hours per week. HRQoL was measured by the SWED-QUAL questionnaire, comprising 67 items grouped into 13 subscales, each with a separate index, and scores from 0 (worse) to 100 (best). SWED-QUAL covers aspects of physical and emotional well-being, cognitive function, sleep, general health and social and sexual functioning. Statistics: Wilcoxon's rank sum and Wilcoxon's sign rank tests, Bonett-Price for medians and confidence intervals, and Cohen's D. RESULTS: Twenty-six patients in the TY (21 women), and 27 patients in both the MBCT (24 women) and in the CBT (25 women), were analyzed. Ten subscales in TY and seven subscales in MBCT and CBT showed improvements, p < 0.05, in several of the main domains affected in burnout, e.g. emotional well-being, physical well-being, cognitive function and sleep. The median improvement ranged from 0 to 27 points in TY, from 4 to 25 points in CBT and from 0 to 25 points in MBCT. The effect size was mainly medium or large. Comparison of treatments showed no statistical differences, but better effect (small) of both TY and MBCT compared to CBT. When comparing the effect of TY and MBCT, both showed a better effect (small) in two subscales each. CONCLUSIONS: A 20 week group treatment with TY, CBT or MBCT had equal effects on HRQoL, and particularly on main domains affected in burnout. This indicates that TY, MBCT and CBT can be used as both treatment and prevention, to improve HRQoL in patients on sick leave because of burnout, reducing the risk of future morbidity. TRIAL REGISTRATION: July 22, 2012, retrospectively registered. ClinicalTrails.gov NCT01168661 . FUNDING: Stockholm County Council, grant 2003-5.

Health-related quality of life in patients with Burnout on sick leave: descriptive and comparative results from a clinical study.

PURPOSE: To explore the health-related quality of life (HRQoL), the cause of being ill, and the pharmacological treatment in patients on sick leave because of Burnout. The HRQoL among these patients was also compared with that of individuals who were working full time. METHODS: HRQoL was measured using the SWED-QUAL questionnaire, comprising 67 items grouped into 13 subscales, scored from 0 (worst) to 100 (best) points, and covering aspects of physical and emotional well-being, cognitive function, sleep, general health, social, and sexual functioning. The Burnout group (n = 94), mean age 43 years, were on 50% sick leave or more. The comparison group consisted of healthy persons (n = 88) of similar age and educational level who were working full time. RESULTS: The Burnout group had markedly low scores in general. The cause of illness was mainly work-related. Psychotropic medication was prescribed for 55%. Significantly lower scores were found in the Burnout group than in the comparison group in all subscales, p < 0.001. The median differences in scores ranged from 10 to 56 points. Differences rated by effect size were large, 0.85-2.01. CONCLUSIONS: Patients on sick leave because of Burnout rated their HRQoL as very low in general, their cause of being ill was mainly work-related, and psychotropic medication was prescribed for a majority. Their scores were markedly lower in all subscales in comparison with healthy individuals working full time. The study adds to our understanding of the situation of patients with Burnout. The results can be useful in clinical work and future research.

Further characterization of human glucocorticoid receptor mutants, R477H and G679S, associated with primary generalized glucocorticoid resistance.

OBJECTIVE: Primary generalized glucocorticoid resistance is a rare condition characterized by a generalized insensitivity to glucocorticoids, to some extent due to an impaired function of the glucocorticoid receptor. Our earlier genetic analysis of the human glucocorticoid receptor (hGR) in 12 unrelated patients with primary generalized glucocorticoid resistance revealed two new mutations, R477H in exon 4 and G679S in exon 8 in two patients. In order to further study the molecular mechanisms underlying the phenotype of these mutations we have investigated their effect on glucocorticoid signal transduction. METHODS: We have studied the DNA-binding ability of the R477H mutant with an electrophoretic mobility shift assay (EMSA). The ability of the R477H and the G679S mutants to affect TNFα induced NF-κB activity and wild-type GR signalling was studied in transient transfection assays. RESULTS: In EMSA the R477H mutation showed a reduced ability to bind to a glucocorticoid-response element compared to the wild-type GR. In transient transfection assays both the R477H mutant and the G679S mutant showed a dominant negative effect on co-transfected wild-type GR in Cos 7 cells. However, both mutants showed full capacity to repress TNFα-induced NF-κB activity. CONCLUSION: The impaired DNA-binding of the hGR, R477H mutant may explain the severe phenotype of cortisol resistance seen with this mutation. The dominant negative effects of both mutants on wild-type GR signalling probably contribute to the patients' cortisol resistance.

L-thyroxine treatment in primary hypothyroidism does not increase the content of free triiodothyronine in cerebrospinal fluid: a pilot study.

The association between cerebrospinal fluid (CSF) and serum concentration of thyroid hormones and pituitary thyrotropin stimulating hormone (TSH) was studied in nine hypothyroid patients (HT) before and in seven after L-thyroxine treatment. With L-thyroxine, median free T4 increased 4-fold in serum (3.5 pmol/L vs 17.5 pmol/L) and 3-fold in CSF, (3.9 pmol/L vs 11.5 pmol/L). Correspondingly, total T3 in serum increased two-fold (0.9 nmol/L vs 2.2 nmol/L). Unexpectedly, free T3 concentration in CSF was similar (1.5 pmol/L vs.1.5 pmol/L) before and during treatment. In HT, TSH in serum correlated with TSH in CSF as did free T4 in serum and in CSF. During L-thyroxine, the correlation with TSH in serum and CSF remained. Likewise, the free T4 concentration in serum correlated with that in CSF. However, no correlation was found between T3 in serum and free T3 in CSF. It seems evident that free T4 in serum equilibrates with that in the CSF both in the HT and during L-thyroxine. Despite a two-fold increase in total serum T3, free T3 in CSF remained unchanged, which agrees with previous results in rats showing that T3 is less exchangeable between serum and CSF. Alternatively, an accelerated conversion of T4 to T3 might have maintained the concentration of T3, due to strongly increased levels of TSH found in the hypothyroid state. The notion that free T4 in serum reflects the CSF concentration of free T4 is consistent with previous reports from studies in animals.

Cytokine inhibition after glucocorticoid exposure in healthy men with low versus high basal cortisol levels.

OBJECTIVE: The balance between glucocorticoid (GC) release and GC sensitivity in target cells is believed to be important to maintain homeostasis in the neuroendocrine control of inflammation. We investigated the impact of in vivo exposure to adrenocorticotropic hormone (ACTH) and dexamethasone (DEX) on GC sensitivity measured in vitro in healthy individuals with high versus low baseline cortisol levels. METHODS: 136 healthy male volunteers were screened twice and sorted according to their 24-hour urinary free cortisol (UFC) excretion. The 10 individuals with the highest UFC (290 +/- 87 nmol/24 h) and the 10 with the lowest UFC (168 +/- 34 nmol/24 h) were further tested. Measurements were performed at baseline, after a low dose (0.5 microg/1.73 m(2)) of ACTH challenge and after 2 weeks' exposure to DEX (0.1 mg twice daily). GC sensitivity was assessed in vitro as the ability of DEX to inhibit lipopolysaccharide-stimulated production of the cytokines interleukin 1-beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in a whole-blood assay. RESULTS: After exposure to DEX in vivo, inhibition of IL-6 and TNF-alpha decreased. Also, after DEX in vivo, low-cortisol men showed lower inhibition of IL-1beta and IL-6, both compared to the high-cortisol group and their own baseline levels. CONCLUSION: A downregulation of GC sensitivity in leukocytes after exposure to an exogenous GC seems to occur most strongly in men with low cortisol levels.

Rapid down-regulation of thyroid hormones in acute myocardial infarction: is it cardioprotective in patients with angina?

BACKGROUND: In severe illness of any cause, down-regulation of the thyroid hormone system may occur. How this affects patients with acute myocardial infarction (AMI) is largely unknown. OBJECTIVE: To investigate changes in serum levels of the thyroid hormones during AMI and their association with cardiac function and outcome. METHODS: Forty-seven consecutive euthyroid patients with AMI were studied prospectively during the first 5 days and again 6 and 12 weeks later. Time from pain onset was used in all analyses. RESULTS: The thyroid hormone system was rapidly down-regulated with maximal changes 24 to 36 hours after onset of symptoms. The mean level of the hormone total triiodothyronine (T3) decreased 19% (P =.02), the inactive metabolite reverse T3 (rT3) levels increased 22% (P =.01), and thyrotropin levels declined 51% (P<.001) between the first 6-hour and the 24- to 36-hour period. The prohormone free thyroxine was largely unchanged. Patients with poor heart function or more intense inflammatory reaction showed more pronounced down-regulation of the thyroid system. No correlation was found with cardiac enzymes. Patients with prior angina pectoris had lower T(3) levels in early samples, smaller infarctions, and higher levels of C-reactive protein and the proinflammatory cytokine interleukin 6 on admittance. Peak levels of interleukin 6 correlated negatively with T3 (P =.005) and positively with rT3 (P<.05), suggesting that down-regulation before AMI may be cardioprotective. However, mortality was high among patients with the most pronounced thyroid level depression, indicating that down-regulation after AMI may be maladaptive. CONCLUSIONS: The thyroid hormone system is rapidly down-regulated in AMI. This may be beneficial during acute ischemia. Patients with angina had higher levels of interleukin 6 and C-reactive protein and more depressed thyroid hormone system in early samples. Thyroid level depression in patients with angina may possibly have been present before the infarction process started. This novel finding needs further evaluation in large studies to sort out cause-and-effect relationships.

[Cooperation reduces the risks of thyroid disease in pregnancy. Also mild maternal hypothyroidism can threaten the neurological development of the fetus]. / Samarbete minskar riskerna vid sköldkörtelsjukdom och graviditet. Aven mild hypotyreos hos modern kan hota fostrets neurologiska utveckling.

A history of thyroidal disease in a pregnant mother requires special attention. Untreated, or not adequately treated, hypothyreosis in a pregnant mother is likely to affect the neurological development of the fetus negatively. The authors refer the discussion on the need for screening for hypothyroidism in early pregnancy, but stress the need for everybody dealing with these patients (general practitioners, midwives, gynecologists, pediatricians and endocrinologists), to recognize women at risk and inform their patients on the need of careful monitoring of thyroid supplementation in case of pregnancy. On the other hand, women with Graves' disease should be carefully assessed for the presence of TRAK-antibodies, and be subject to specialist maternal care. Their babies risk neonatal thyreotoxicosis and need careful attention.

Increased DHEAS levels in patients with rheumatoid arthritis after treatment with tumor necrosis factor antagonists: evidence for improved adrenal function.

OBJECTIVE: To determine if major reduction of inflammation with longterm tumor necrosis factor (TNF) antagonist treatment has any influence on the adrenal and gonadal axes in patients with rheumatoid arthritis (RA). METHODS: Forty-eight patients with RA were treated with infliximab or etanercept for 2 years. Disease activity, clinical response, and physical function were evaluated and serum levels of high sensitivity C-reactive protein and interleukin 6 were analyzed before start of treatment and after 1 and 2 years. At the same timepoints adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone sulfate (DHEAS) were analyzed; luteinizing hormone (LH), estradiol, and testosterone were analyzed as well in 18 male patients. RESULTS: DHEAS increased (p