Observational Study Mortality in Treated Primary Aldosteronism: The German Conn's Registry

In comparison with essential hypertension, primary aldosteronism (PA) is associated with an increased risk of cardiovascular morbidity. To date, no data on mortality have been published. We assessed mortality of patients treated for PA within the German Conn's registry and identified risk factors for adverse outcome in a case-control study. Patients with confirmed PA treated in 3 university centers in Germany since 1994 were included in the analysis. All of the patients were contacted in 2009 and 2010 to verify life status. Subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg served as controls. Final analyses were based on 600 normotensive controls, 600 hypertensive controls, and 300 patients with PA. Kaplan-Meyer survival curves were calculated for both cohorts. Ten-year overall survival was 95% in normotensive controls, 90% in hypertensive controls, and 90% in patients with PA (P value not significant). In multivariate analysis, age (hazard ratio, 1.09 per year [95% CI, 1.03-1.14]), angina pectoris (hazard ratio, 3.6 [95% CI, 1.04-12.04]), and diabetes mellitus (hazard ratio, 2.55 [95% CI, 1.07-6.09]) were associated with an increase in all-cause mortality, whereas hypokalemia (hazard ratio, 0.41 per mmol/L [95% CI, 0.17-0.99]) was associated with reduced mortality. Cardiovascular mortality was the main cause of death in PA (50% versus 34% in hypertensive controls; P<0.05). These data indicate that cardiovascular mortality is increased in patients treated for PA, whereas all-cause mortality is not different from matched hypertensive controls.     

Thyroid effects of endocrine disrupting chemicals

In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties.     

Childhood maltreatment is associated with an automatic negative emotion processing bias in the amygdala

Major depression has been repeatedly associated with amygdala hyper‐responsiveness to negative (but not positive) facial expressions at early, automatic stages of emotion processing using subliminally presented stimuli. However, it is not clear whether this “limbic bias” is a correlate of depression or represents a vulnerability marker preceding the onset of the disease. Because childhood maltreatment is a potent risk factor for the development of major depression in later life, we explored whether childhood maltreatment is associated with amygdalar emotion processing bias in maltreated but healthy subjects. Amygdala responsiveness to subliminally presented sad and happy faces was measured by means of fMRI at 3 T in N = 150 healthy subjects carefully screened for psychiatric disorders. Childhood maltreatment was assessed by the 25‐item childhood trauma questionnaire (CTQ). A strong association of CTQ‐scores with amygdala responsiveness to sad, but not happy facial expressions emerged. This result was further qualified by an interaction of emotional valence and CTQ‐scores and was not confounded by trait anxiety, current depression level, age, gender, intelligence, education level, and more recent stressful life‐events. Childhood maltreatment is apparently associated with detectable changes in amygdala function during early stages of emotion processing which resemble findings described in major depression. Limbic hyper‐responsiveness to negative facial cues could be a consequence of the experience of maltreatment during childhood increasing the risk of depression in later life. Limitation: the present association of limbic bias and maltreatment was demonstrated in the absence of psychopathological abnormalities, thereby limiting strong conclusions. Hum Brain Mapp 34:2899–2909, 2013. © 2012 Wiley Periodicals, Inc.     

Paternal deprivation alters the development of catecholaminergic innervation in the prefrontal cortex and related limbic brain regions

The impact of paternal care on the development of catecholaminergic fiber innervations in the prefrontal cortex, nucleus accumbens, hippocampus and the amygdala was quantitatively investigated in the biparental Octodon degus. Two age (juvenile, adult) and rearing groups: (1) degus reared without father and (2) degus raised by both parents were compared. Juvenile father-deprived animals showed significantly elevated densities of TH-immunoreactive fibers in all analyzed regions, except in the orbitofrontal cortex, as compared to biparentally reared animals. This difference between the two rearing groups was still evident in adulthood in the prelimbic and infralimbic cortices and in the hippocampal formation. Interestingly, the elevated TH fiber density in both nucleus accumbens subregions was reversed in adulthood, i.e. adult father-deprived animals showed strongly reduced TH fiber densities as compared to biparentally reared animals. We show here that paternal care plays a critical role in the functional maturation of catecholaminergic innervation patterns in prefrontal and limbic brain circuits.     

Access to the next wave of biologic therapies (Abatacept and Tocilizumab) for the treatment of rheumatoid arthritis in England and Wales

Patients in England and Wales with rheumatoid arthritis (RA) receive treatment from the National Health Service (NHS) with therapies approved by the European Medicines Agency (EMA), under guidance from the National Institute for Health and Clinical Excellence (NICE). This document overviews the current NICE guidelines for the treatment of RA and identifies scenarios when such guidance may not represent the optimum management strategy for individual patients. Specifically, we consider the use of tocilizumab or abatacept as the most appropriate treatments for some patients. In such scenarios, it may be possible for the clinician to secure access to the required therapy through an application procedure known as an 'individual funding request', the process of which is described in detail here. At present, it is unclear the extent to which the proposed reform of the NHS will affect the role of NICE in providing guidance and setting standards of care. Until the full impact of the proposed changes are realized, individual funding requests will remain a valuable way of securing the optimal treatment for all patients suffering from RA.