Forslag til endring av retningslinje ved konservativ behandling av NSTEMI

Sammendrag Bakgrunn Studier gjort internasjonalt har vist at fondaparinuks gir lavere morbiditet og mortalitet på lang sikt, sammenlignet med det lavmolekylære heparinet enoksaparin, ved konservativ antitrombotisk behandling av NSTEMI. Med bakgrunn i dette har vi sett på nåværende praksis for slik behandling av denne pasientgruppen på hjerteavdelingen på Ullevål Universitetssykehus (UUS). Da det ikke er samsvar mellom praksis på UUS og internasjonale guidelines, ønsket vi å utarbeide en strategi for implementering av en ny retningslinje for antitrombotisk behandling ved NSTEMI, med bytte fra enoksaparin til fondaparinuks. Metode Kunnskapsgrunnlaget ble bekreftet ved søk i medline/pubmed, og det ble gjort en spørreskjemaundersøkelse for å avdekke gjeldende praksis. Videre ble det gjort litteratursøk i Medline/Ovid for å finne dokumenterte implementeringstiltak. Resultater Ved UUS brukes det i hovedsak dalteparin ved konservativ behandling av NSTEMI, hvilket samsvarer med de nasjonale retningslinjer. Flere tiltak for endring av den lokale retningslinjen ble vurdert, og følgende tiltak foreslås: 1. Avdelingsledelsen nedsetter en ansvarlig prosjektgruppe med en prosjektkoordinator. 2. Felles undervisningsmøter med utdeling av spørreskjemaer for tilbakemelding. 3. Muntlig orientering samt informasjonsskriv om det nye tiltaket til personalet. 4. Regelmessige møter i prosjektgruppen med evaluering av resultater samt tilbakemeldinger fra personalet. 5. Kontinuerlig oppdatering om resultatene av prosjektet til personalet både muntlig og via e-post, samt oppfordring til å gi respons på hvordan det fungerer. 6. Evaluering av prosjektet etter ett år. Her benyttes indikatoren ”andelen pasienter med NSTEMI som blir behandlet konservativt i akuttfasen med fondaparinuks ved hjerteavdelingen på UUS.” Konklusjon Kunnskapsgrunnlaget viser at et bytte til fondaparinuks er fordelaktig med tanke på redusert morbiditet og mortalitet på lang sikt, lettere administrasjon og reduserte kostnader. De tiltakene vi har kommet frem til kan være praktisk gjennomførbare i den aktuelle avdelingen, og kan være hensiktsmessige i innføringen av en ny retningslinje

Plasma-Metanephrines in Patients with Autoimmune Addison’s Disease with and without Residual Adrenocortical Function

Purpose: Residual adrenocortical function, RAF, has recently been demonstrated in one-third of patients with autoimmune Addison’s disease (AAD). Here, we set out to explore any influence of RAF on the levels of plasma metanephrines and any changes following stimulation with cosyntropin. Methods: We included 50 patients with verified RAF and 20 patients without RAF who served as controls upon cosyntropin stimulation testing. The patients had abstained from glucocorticoid and fludrocortisone replacement > 18 and 24 h, respectively, prior to morning blood sampling. The samples were obtained before and 30 and 60 min after cosyntropin stimulation and analyzed for serum cortisol, plasma metanephrine (MN), and normetanephrine (NMN) by liquid-chromatography tandem-mass pectrometry (LC-MS/MS). Results: Among the 70 patients with AAD, MN was detectable in 33%, 25%, and 26% at baseline, 30 min, and 60 min after cosyntropin stimulation, respectively. Patients with RAF were more likely to have detectable MN at baseline (p = 0.035) and at the time of 60 min (p = 0.048) compared to patients without RAF. There was a positive correlation between detectable MN and the level of cortisol at all time points (p = 0.02, p = 0.04, p < 0.001). No difference was noted for NMN levels, which remained within the normal reference ranges. Conclusion: Even very small amounts of endogenous cortisol production affect MN levels in patients with AAD

Residual Corticosteroid Production in Autoimmune Addison Disease

Context - Contrary to current dogma, growing evidence suggests that some patients with autoimmune Addison disease (AAD) produce corticosteroids even years after diagnosis. Objective - To determine frequencies and clinical features of residual corticosteroid production in patients with AAD. Design - Two-staged, cross-sectional clinical study in 17 centers (Norway, Sweden, and Germany). Residual glucocorticoid (GC) production was defined as quantifiable serum cortisol and 11-deoxycortisol and residual mineralocorticoid (MC) production as quantifiable serum aldosterone and corticosterone after > 18 hours of medication fasting. Corticosteroids were analyzed by liquid chromatography–tandem mass spectrometry. Clinical variables included frequency of adrenal crises and quality of life. Peak cortisol response was evaluated by a standard 250 µg cosyntropin test. Results - Fifty-eight (30.2%) of 192 patients had residual GC production, more common in men (n = 33; P P P P P P P  Conclusion - In established AAD, one-third of the patients still produce GCs even decades after diagnosis. Residual production is more common in men and in patients with shorter disease duration but is not associated with adrenal crises or quality of life

Altered biomarkers for cardiovascular disease and inflammation in autoimmune Addison's disease - a cross-sectional study

Objective - Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood. Methods - We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex. Biomarker levels were correlated with the frequency of adrenal crises and quality of life (QoL) by AddiQoL-30. Finally, we investigated changes in biomarker levels following 250 µg tetracosactide injection in patients without residual adrenocortical function (RAF) to explore glucocorticoid-independent effects of high ACTH. Results - Nineteen biomarkers significantly differed between patients with AAD and controls; all but 1 (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, and PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r = 0.415, P = .006) and AddiQoL-30 scores (r = −0.347, P = .028) but not after correction for multiple testing. PDL2 and leptin significantly declined 60 min after injection of ACTH in AAD without RAF (−0.15 normalized protein expression [NPX], P = .0001, and −0.25 NPX, P = .0003, respectively). Conclusions - We show that cardiovascular and inflammatory biomarkers are altered in AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with more adrenal crises and reduced QoL. High ACTH reduced PDL2 and leptin levels in a glucocorticoid-independent manner but the overall effect on biomarker profiles was small

Musikkens innvirkning på hjernen og hjernefunksjoner

In this review I present studies concerning the processing of music in the brain. The aim of the review was to identify neurobiological mechanisms underlying music therapy effects, with special focus on music used for pain relief. One of the main challenges in the field of music therapy seems to be the lack of a common theoretical framework for the diverse music therapy working areas and practitioners. Hillecke et al thus proposed a working factor model based on five ingredients or working factors that seem to be central aspects of music therapeutic work. The five factors are the attentiveness factor, the emotional factor, the cognitive factor, the motor behavioural factor, and the interpersonal factor. The authors suggest these five factors as a common theoretical basis for music therapy work. In addition, the literature mentions a sixth factor which might be of significant importance for future music therapy research and clinical use: the physiological factor. There is some evidence that music may induce physiological responses through the hypothalamic-pituitary axis. Another challenge in the field of music therapy is the specificity problem. It is difficult to tell whether an observed change is due to the music itself or to other contributory factors like the therapist-patient relationship. Many authors suggest that music can influence the neuronal plasticity of our brains in several favourable ways. With regard to music as treatment for pain, a meta-analysis revealed that the clinical significance of music is unsure. However, the possible physiological effects of music, an other possible indirect effects of music on pain processing should be investigated

Primary adrenal lymphoma as a cause of adrenal insufficiency, a report of two cases

Primary adrenal lymphoma (PAL) is a rare cause of adrenal insufficiency. More than 90% is of B-cell origin. The condition is bilateral in up to 75% of cases, with adrenal insufficiency in two of three patients. We report two cases of adrenal insufficiency presenting at the age of 70 and 79 years, respectively. Both patients had negative 21-hydroxylase antibodies with bilateral adrenal lesions on CT. Biopsy showed B-cell lymphoma. One of the patients experienced intermittent disease regression on replacement dosage of glucocorticoids

Clues for early detection of autoimmune Addison's disease - myths and realities

BACKGROUND: Early detection of autoimmune Addison's disease (AAD) is important as delay in diagnosis may result in a life-threatening adrenal crisis and death. The classical clinical picture of untreated AAD is well-described, but methodical investigations are scarce. OBJECTIVE: Perform a retrospective audit of patient records with the aim of identifying biochemical markers for early diagnosis of AAD. MATERIAL AND METHODS: A multicentre retrospective study including 272 patients diagnosed with AAD at hospitals in Norway and Sweden during 1978-2016. Scrutiny of medical records provided patient data and laboratory values. RESULTS: Low sodium occurred in 207 of 247 (84%), but only one-third had elevated potassium. Other common nonendocrine tests were largely normal. TSH was elevated in 79 of 153 patients, and hypoglycaemia was found in 10%. Thirty-three per cent were diagnosed subsequent to adrenal crisis, in whom electrolyte disturbances were significantly more pronounced (P < 0.001). Serum cortisol was consistently decreased (median 62 nmol L(-1) [1-668]) and significantly lower in individuals with adrenal crisis (38 nmol L(-1) [2-442]) than in those without (81 nmol L(-1) [1-668], P < 0.001). CONCLUSION: The most consistent biochemical finding of untreated AAD was low sodium independent of the degree of glucocorticoid deficiency. Half of the patients had elevated TSH levels. Only a minority presented with marked hyperkalaemia or other nonhormonal abnormalities. Thus, unexplained low sodium and/or elevated TSH should prompt consideration of an undiagnosed AAD, and on clinical suspicion bring about assay of cortisol and ACTH. Presence of 21-hydroxylase autoantibodies confirms autoimmune aetiology. Anticipating additional abnormalities in routine blood tests may delay diagnosis

Autoimmune Thyroid Disorders in Autoimmune Addison Disease

Context: Autoimmune thyroid disease is the most common endocrine co-morbidity in autoimmune Addison's disease (AAD), but detailed investigations of prevalence and clinical course is lacking. Objective: Provide comprehensive epidemiological and clinical data on autoimmune thyroid disorders in AAD. Design and patients: A nationwide registry-based study including 442 patients with AAD and autoimmune thyroid disease, identified through the Norwegian National Registry of Autoimmune Diseases. Results: Of 912 registered AAD patients, 442 (48%) were diagnosed with autoimmune thyroid disease. Three hundred and eighty (42%) had autoimmune hypothyroidism. Of the 302 with available thyroid function tests at time for diagnosis, 20% had overt hypothyroidism, 73% had subclinical hypothyroidism and 7% had thyroid levels in the normal range. Negative thyroid peroxidase antibodies was found in 32%. Ninety-eight percent were treated with levothyroxine, 5% with combination therapy with liothyronine or thyroid extracts, and 1% were observed without treatment. Seventy-eight patients (9%) were diagnosed with Graves' disease (GD), of whom 16 (21%) were diagnosed with autoimmune hypothyroidism either before onset or after remission of GD. At the end of follow-up 33% had normal thyroid hormone levels without antithyroid-drugs or levothyroxine treatment. The remaining had either active disease (5%), had undergone ablative treatment (41%), or had developed autoimmune hypothyroidism (21%). Conclusion: The true prevalence of hypothyroidism in AAD is lower than reported in current literature. Careful consideration of the indication to start thyroxin therapy is warranted. Long-term remission rates in GD patients with AAD are comparable to recent reports on long-term follow-up of patients without AAD

Autoimmune Thyroid Disorders in Autoimmune Addison Disease

Context: Autoimmune thyroid disease is the most common endocrine co-morbidity in autoimmune Addison's disease (AAD), but detailed investigations of prevalence and clinical course is lacking. Objective: Provide comprehensive epidemiological and clinical data on autoimmune thyroid disorders in AAD. Design and patients: A nationwide registry-based study including 442 patients with AAD and autoimmune thyroid disease, identified through the Norwegian National Registry of Autoimmune Diseases. Results: Of 912 registered AAD patients, 442 (48%) were diagnosed with autoimmune thyroid disease. Three hundred and eighty (42%) had autoimmune hypothyroidism. Of the 302 with available thyroid function tests at time for diagnosis, 20% had overt hypothyroidism, 73% had subclinical hypothyroidism and 7% had thyroid levels in the normal range. Negative thyroid peroxidase antibodies was found in 32%. Ninety-eight percent were treated with levothyroxine, 5% with combination therapy with liothyronine or thyroid extracts, and 1% were observed without treatment. Seventy-eight patients (9%) were diagnosed with Graves' disease (GD), of whom 16 (21%) were diagnosed with autoimmune hypothyroidism either before onset or after remission of GD. At the end of follow-up 33% had normal thyroid hormone levels without antithyroid-drugs or levothyroxine treatment. The remaining had either active disease (5%), had undergone ablative treatment (41%), or had developed autoimmune hypothyroidism (21%). Conclusion: The true prevalence of hypothyroidism in AAD is lower than reported in current literature. Careful consideration of the indication to start thyroxin therapy is warranted. Long-term remission rates in GD patients with AAD are comparable to recent reports on long-term follow-up of patients without AAD.publishedVersio