Corticosteroid induced osteoporosis : guidelines for treatment

BACKGROUND: Last year, Australian Family Physician published Guidelines for Management of Postmenopausal Osteoporosis'. which were developed by Osteoporosis Australia. Recently, significant advances in our understanding of the treatment of corticosteroid osteoporosis have occurred.

OBJECTIVE: The following guidelines also developed by Osteoporosis Australia, and supported by the National Asthma Campaign, are to help general practitioners identify those patients at risk of this problem and to provide information about current treatment strategies.

DISCUSSION: Corticosteroids are widely used and effective agents for the control of many inflammatory diseases. Corticosteroid osteoporosis is a common problem associated with the long term high dose use of these medications.

Parent-initiated oral corticosteroid therapy for acute asthma: a survey of current practice

Aim: To determine (i) the proportion of doctors who recommend parent-initiated oral corticosteroids (PIOCS) for acute asthma; and (ii) the proportion of parents who have received this advice.

Methods: (i) An internet-based survey of doctors involved in the care of children with asthma; and (ii) a questionnaire-based survey of parents of children aged 4–13 years who were identified from a random sample of primary schools within the Barwon region of Victoria.

Results: Eight-five per cent (95% confidence interval 80.0–89.1%) of responding doctors reported recommending PIOCS to parents of children with asthma. However, only 16.5% (95% confidence interval 14.2–18.7%) of parents of children with recent asthma symptoms report that they have received such advice.

Conclusion: The majority of responding doctors involved in the care of children with asthma report recommending PIOCS to parents. By contrast, a minority of parents of children with asthma report that they have received such advice.

Differential corticosteroid receptor regulation of mesoaccumbens dopamine efflux during the peak and nadir of the circadian rhythm : a molecular equilibrium in the midbrain?

Corticosteroid receptor modulation of mesoaccumbens dopamine neurotransmission is believed to be a key neurobiological mechanism mediating the effects of stress in addiction. Importantly, nucleus accumbens (NAc) subregions (core and shell) are reported to respond differentially to fluctuating basal levels of glucocorticoids, with dopaminergic responses in the core of the NAc being somewhat impervious to fluctuating levels of glucocorticoids relative to the shell. To investigate the corticosteroid receptor mechanisms mediating basal dopamine efflux in the core of the NAc, we have used chronoamperometry in combination with stearate-modified graphite paste electrodes in urethane anesthetized male Long–Evans rats during the peak and nadir of the circadian cycle. Blockade of ventral tegmental area low-affinity glucocorticoid (GR) or high-affinity mineralocorticoid (MR) receptors with mifepristone (1 μg/μl) or spironolactone (0.2 μg/μl), respectively, indicated that endogenous phase-dependent corticosteroid receptor activation (GRs during peak; MRs during nadir) facilitated extracellular NAc dopamine efflux. Conversely, the alternate receptor's actions appeared inhibitory at these time points (MRs during peak; GRs during nadir). Pharmacological activation of either the GR or MR with corticosterone (2 μg/μl) or aldosterone (0.2 μg/μl), respectively, potentiated NAc dopamine efflux, irrespective of circadian phase. Together, these data suggest that dominant corticosteroid receptor activation stimulates tonic mesoaccumbens dopamine transmission, enabling MRs and GRs to differentially maintain basal NAc dopamine release over the course of the circadian cycle. This points to an important molecular mechanism through which relatively stable NAc core dopamine extracellular levels could be maintained in the face of fluctuating corticosterone circadian rhythms.

Corticosteroid-induced psychiatric disturbances: it is time for pharmacists to take notice.

Corticosteroids are widely used to relieve signs and symptoms arising from many diseases, including common inflammatory and autoimmune disorders affecting a number of organ systems. However, corticosteroids also induce significant adverse effects; in particular, a range of severe psychiatric adverse effects may occur including delirium, depression, mania, psychosis and cognitive/memory impairment. These adverse effects occur in up to 60% of patients taking corticosteroids and recent studies show an increased rate of psychopathologies in this population. Long-term adverse effects on mood and behavior are severely debilitating, thereby influencing the quality of life, employment and health status of individuals taking corticosteroids. Strategies used to manage corticosteroid-induced psychiatric disturbances through psychotropic drugs vary significantly. This commentary summarizes existing literature on mechanisms underlying corticosteroid-induced psychiatric adverse effects and evidence associated with using psychotropic drugs to manage these effects. Despite its importance, there is an absolute dearth in the literature examining pharmacists' understanding and perceptions of psychiatric adverse effects of corticosteroids. Educational programs need to be implemented so that pharmacists can counsel patients about how to recognize corticosteroid-induced psychiatric disturbances. Physicians do not consistently alert patients to watch for behavioral changes, and patients may feel that mood changes they experience fall within the category of 'normal behavior,' and thus are less likely to report them. Given that patients taking corticosteroids usually have complex medical histories, discussions of adverse effects with pharmacists are vital to improve health outcomes in this population.

A perspective on the role of natriuretic peptides in amphibian osmoregulation

The natriuretic peptide (NP) system is a complex family of peptides and receptors that is primarily linked to the maintenance of osmotic and cardiovascular homeostasis. In amphibians, the potential role(s) of NPs is complicated by the range of osmoregulatory strategies found in amphibians, and the different tissues that participate in osmoregulation. Atrial NP, brain NP, and C-type NP have been isolated or cloned from a number of species, which has enabled physiological studies to be performed with homologous peptides. In addition, three types of NP receptors have been cloned and partially characterised. Natriuretic peptides are always potent vasodilators in amphibian blood vessels, and ANP has been shown to increase the permeability of the microcirculation. In the perfused kidney, ANP causes vasodilation, diuresis and natriuresis that are caused by an increased GFR rather than effects in the renal tubules. These data are supported by the presence of ANP receptors only on the glomeruli and renal blood vessels. In the bladder and skin, the function of NPs is enigmatic because physiological analysis of the effects of ANP on bladder and skin function has yielded conflicting data with no clear role for NPs being revealed. Overall, NPs often have no direct effect, but in some studies they have been shown to inhibit the function of AVT. In addition, there is evidence that ANP can inhibit salt retention in amphibians since it can inhibit the ability of adrenocorticotrophic hormone or angiotensin II to stimulate corticosteroid secretion. It is proposed that an important role for cardiac NPs could be in the control of hypervolaemia during periods of rapid rehydration, which occurs in terrestrial amphibians.

A treatment algorithm for managing Achilles tendinopathy : new treatment options

Achilles tendinopathy affects athletes, recreational exercisers and even inactive people. The pathology is not inflammatory; it is a failed healing response. The source of pain in tendinopathy could be related to the neurovascular ingrowth seen in the tendon's response to injury. The treatment of Achilles tendinopathy is primarily conservative with an array of effective treatment options now available to the primary care practitioner. If conservative treatment is not successful, then surgery relieves pain in the majority of cases. Directing a patient through the algorithm presented here will maximise positive treatment outcomes.

Immune reconstitution sarcoidosis presenting with hypercalcaemia and renal failure in HIV infection

An HIV-positive white man developed hypercalcaemia and renal failure 15 months after starting highly active antiretroviral therapy. Investigations showed systemic sarcoidosis affecting parotids, skin and kidneys. This presentation was thought to be a manifestation of immune reconstitution inflammatory syndrome, and the patient was successfully treated with corticosteroid therapy.

Parent initiated prednisolone for acute asthma in children of school age : randomised controlled crossover trial

Objective To evaluate the efficacy of a short course of parent initiated oral prednisolone for acute asthma in children of school age.

Design Double blind, randomised, placebo controlled, crossover trial in which episodes of asthma, rather than participants, were randomised to treatment.

Setting The Barwon region of Victoria, Australia.

Participants Children aged 5-12 years with a history of recurrent episodes of acute asthma.

Intervention A short course of parent initiated treatment with prednisolone (1 mg/kg a day) or placebo.

Main outcome measures The primary outcome measure was the mean daytime symptom score over seven days. Secondary outcome measures were mean night time symptom score over seven days, use of health resources, and school absenteeism.

Results 230 children were enrolled in the study. Over a three year period, 131 (57%) of the participants contributed a total of 308 episodes of asthma that required parent initiated treatment: 155 episodes were treated with parent initiated prednisolone and 153 with placebo. The mean daytime symptom score was 15% lower in episodes treated with prednisolone than in those treated with placebo (geometric mean ratio 0.85, 95% CI 0.74 to 0.98; P=0.023). Treatment with prednisolone was also associated with a 16% reduction in the night time symptom score (geometric mean ratio 0.84, 95% CI 0.70 to 1.00; P=0.050), a reduced risk of health resource use (odds ratio 0.54, 95% CI 0.34 to 0.86; P=0.010), and reduced school absenteeism (mean difference −0.4 days, 95% CI −0.8 to 0.0 days; P=0.045).

Conclusion A short course of oral prednisolone initiated by parents when their child experiences an episode of acute asthma may reduce asthma symptoms, health resource use, and school absenteeism. However, the modest benefits of this strategy must be balanced against potential side effects of repeated short courses of an oral corticosteroid.

Which infants with eczema are at risk of food allergy? Results from a population-based cohort

BACKGROUND: The relationship between early onset eczema and food allergy among infants has never been examined in a population-based sample using the gold standard for diagnosis, oral food challenge. OBJECTIVE: We characterised the risk of challenge-proven food allergy among infants with eczema in the general population. METHODS: One-year-old infants (n = 4453 meeting criteria for this analysis) were assessed for history of eczema, received a nurse-administered eczema examination and underwent skin prick testing to peanut, egg and sesame. Those with a detectable wheal to one of the test foods underwent an oral food challenge irrespective of wheal size. The risk of food allergy, stratified by eczema severity and age of onset, was estimated using multivariate logistic regression with population sampling weights. RESULTS: One in five infants with eczema were allergic to peanut, egg white or sesame, compared to one in twenty-five infants without eczema (OR 6.2, 95% CI 4.9, 7.9, P < 0.001). The prevalence of peanut allergy was low in the absence of eczema (0.7% 95% CI 0.4, 1.1). Infants with eczema were 11.0 times more likely to develop peanut allergy (95% CI 6.6, 18.6) and 5.8 times more likely to develop egg allergy (95% CI 4.6, 7.4) by 12 months than infants without eczema. 50.8% of infants (95% CI 42.8, 58.9) with early eczema onset (<3 months) who required doctor-prescribed topical corticosteroid treatment developed challenge-proven food allergy. CONCLUSION AND CLINICAL RELEVANCE: Eczema, across the clinical severity spectrum in infancy, is a strong risk factor for IgE-mediated food allergy. Infants with eczema were six times more likely to have egg allergy and 11 times more likely to have peanut allergy by 12 months than infants without eczema. Our data suggest that a heightened awareness of food allergy risk among healthcare practitioners treating infants with eczema, especially if early onset and severe, is warranted.

Repeated acute activation of the hypothalamo-pituitary adrenal axis prior to and during estrus did not affect reproductive performance in gilts

We investigated the effects of repeated acute activation of the hypothalamo-pituitary adrenal axis, prior to and during estrus, on reproduction in gilts. Individual gilts (n = 24 per treatment) either served as controls or were subjected to daily acute stress ("negative handling," brief electric shock with a battery-operated prodder during confinement with the experimenter) commencing, on average, 8 days prior to estrus. Gilts subjected to negative handling had a significant elevation in plasma concentrations of cortisol that lasted at least 3-4 h, and these gilts were slower than control gilts to approach and interact with the experimenter in a standard test. Nevertheless, reproductive performance--as measured by sexual receptivity and proceptivity, ovulation, the percentage of gilts that became pregnant, the number of embryos 20-21 days after insemination, and the weight of embryos--was not affected by repeated acute activation of the hypothalamo-pituitary adrenal axis. Our results suggest that repeated acute activation of the hypothalamo-pituitary adrenal axis prior to and during estrus does not affect the factors that control estrus and ovulation in gilts.

Susceptibility of reproduction in female pigs to impairment by stress and the role of the hypothalamo-pituitary-adrenal axis

Although it is generally considered that stress can impair reproduction, we suggest that the impact of acute or repeated acute stress or acute or repeated acute elevations of cortisol are of little consequence in female pigs, even if these occur during the series of endocrine events that induce oestrus and ovulation. It is important to understand the impact of acute stress on reproduction because, in the intensive production of livestock, animals are often subjected to short-term challenges. There seems little doubt that reproduction in a proportion of female pigs is susceptible to impairment by severe and prolonged stress or the sustained elevation of cortisol but only when this continues for a substantial period. In female pigs, where reproduction is susceptible to impairment by severe prolonged stress, it is possible that the mediators of this suppression are cortisol, corticotrophin-releasing factor and vasopressin but, in pigs, there is evidence to suggest that adrenocorticotrophic hormone is not involved. Other substances secreted during stress may be involved but these are not considered in this review. It is possible that the mediators of stress act at any level of the hypothalamo-pituitary-ovarian axis. Although a variety of experimental manipulations have provided potential mediators and mechanisms for the stress-induced suppression of reproduction, these experimental manipulations rarely represented physiological circumstances so it is not clear if such mechanisms would be important in a physiological context. The precise mediators and mechanisms by which hormones released during stress may inhibit reproductive processes during severe prolonged stress are yet to be determined.