The use of oral glucocorticoids and the risk of major osteoporotic fracture in patients with myasthenia gravis.

Oral glucocorticoids may increase major osteoporotic fracture risk (MOF) in myasthenia gravis patients. To assess this risk, we performed a case-control study including all Danish patients with a MOF between 1995 and 2011. We also pooled our data with data from another study. We found no increased risk. Osteoporosis prevention remains advisable. PURPOSE/INTRODUCTION: The prolonged use of high doses of oral glucocorticoids (GCs), a common treatment in patients with myasthenia gravis (MG), may increase major osteoporotic fracture (MOF) risk. Previous epidemiological studies did not exclusively focus on patients with MG or had relatively few GC-exposed MG patients. Aims were to evaluate the risk of MOF in MG patients using oral GCs in a large study population and to perform a pooled analysis with data from previous work. METHODS: A population-based case-control study (1995-2011) was conducted using the Danish National Health Service. Cases had sustained a MOF, and controls had not. All were aged ≥ 18 years. Multivariate conditional logistic regression estimated odds ratios (ORs) among MG patients using oral GCs versus non-users. Adjustments were made for comorbidities and comedications. In the pooled analysis, results were pooled by the use of generic inverse variance methods, assuming a random-effects model. RESULTS: We identified 376,858 cases and 376,858 controls. MOF risk was not elevated in MG patients currently using oral GCs compared to MG patients not on oral GCs (ORadj.: 1.26 (95% CI 0.68-2.33)). The use of the highest cumulative dose of oral GCs (≥ 7 g) did not show an increased risk of MOF among MG patients (ORadj.: 2.00 (95% CI 0.90-4.44)). Our pooled analysis also showed no association between oral GC use and MOF risk. CONCLUSION: This study showed that oral GC use in patients with MG was not associated with increased risk of MOF in our case-control study and pooled analysis. Osteoporosis prevention in MG patients based on clinical guidelines remains advisable.

Study protocol for the randomized controlled EVA (early vascular adjustments) trial: tailored treatment of mild hypertension in pregnancy to prevent severe hypertension and preeclampsia.

BACKGROUND: In contrast to severe gestational hypertension, it is questioned whether antihypertensive medication for mild to moderate gestational hypertension prevents adverse maternal and offspring outcomes. Hypertensive drugs halve the risk of severe hypertension, but do not seem to prevent progression to preeclampsia or reduce the risk of complications in offspring. In fact, beta-blockers, a first line therapy option, are suspected to impair foetal growth. Disappointing effects of antihypertensive medication can be anticipated when the pharmacological mode of action does not match the underlying haemodynamic imbalance. Hypertension may result from 1) high cardiac output, low vascular resistance state, in which beta blockade is expected to be most effective, or 2) low cardiac output, high vascular resistance state where dihydropyridine calcium channel blockers or central-acting alpha agonists might be the best corrective medication. In the latter, beta-blockade might be maternally ineffective and even contribute to impaired foetal growth by keeping cardiac output low. We propose a randomized controlled trial to determine whether correcting the haemodynamic imbalance in women with mild to moderate hypertension reduces the development of severe hypertension and/or preeclampsia more than non-pharmacological treatment does, without alleged negative effects on foetal growth. METHODS: Women diagnosed with mild to moderate hypertension without proteinuria or signs of other organ damage before 37 weeks of pregnancy are invited to participate in this randomized controlled trial. Women randomized to the intervention group will be prescribed tailored antihypertensive medication, using a simple diagnostic and treatment algorithm based on the mean arterial pressure/heart rate ratio, which serves as an easy-to-determine proxy for maternal circulatory state. Women randomized to the control group will receive non-pharmacological standard care according to national and international guidelines. In total, 208 women will be randomized in a 1:1 ratio. The primary outcome is progression to severe hypertension and preeclampsia and the secondary outcomes are adverse maternal and neonatal outcomes. DISCUSSION: This trial will provide evidence of whether tailoring treatment of mild to moderate gestational hypertension to the individual haemodynamic profile prevents maternal disease progression. TRIAL REGISTRATION: NCT02531490 , registered on 24 August 2015.

Amoxicillin concentrations in relation to beta-lactamase activity in sputum during exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are often treated with antibiotics. Theoretically, to be maximally effective, the antibiotic concentration at sites of infection should exceed the minimum inhibitory concentration at which 90% of the growth of potential pathogens is inhibited (MIC90). A previous study showed that most hospitalized COPD patients had sputum amoxicillin concentrations