Oral corticosteroids (OCS) are a key part of therapy regimens for a diverse variety of conditions. Despite their efficacy, they are associated with a wide variety of adverse events. The purpose of this review was to identify the range of adverse events that have been reported to be related to oral corticosteroids, examine the factors that influence their incidence and estimate the economic burden caused by these adverse events. In 61 identified studies, 21 different categories of OCS related adverse events were reported with increased fracture risk being the category most frequently described. Most studies that examined factors linked to the incidence of OCS related adverse events found that dose, age, gender, duration of use, treatment history, smoking habits or cholesterol level were influential in determining risk. Additionally, a cumulative economic analysis of selected adverse events found the annual cost of treating these events in the UK to be at least 165 pounds per patient taking OCS. The clinical and economic burden of OCS related adverse events highlights the need for OCS sparing therapies to be developed.

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BACKGROUND Health‐related quality of life (HRQoL) was an exploratory endpoint in the PALETTE trial, a global, double‐blind, randomized, phase 3 trial of pazopanib 800 mg versus placebo as second‐line or later treatment for patients with advanced soft tissue sarcoma (N = 369). In that trial, progression‐free survival was significantly improved in the pazopanib arm (median, 4.6 vs 1.6 months; hazard ratio, 0.31; P < .001), and toxicity of pazopanib consisted mainly of fatigue, diarrhea, nausea, weight loss, and hypertension. METHODS HRQoL was assessed using the 30‐item core European Organization for the Research and Treatment of Cancer (EORTC) Quality‐of‐Life Questionnaire (EORTC QLQ‐C30) at baseline and at weeks 4, 8, and 12 in patients who received treatment on protocol. The primary HRQoL endpoint was the EORTC QLQ‐C30 global health status scale. RESULTS Compliance with HRQoL assessments was good, ranging from 94% at baseline to 81% at week 12. Differences in scores on the EORTC QLQ‐C30 global health status subscale between the 2 treatment arms were not statistically significant and did not exceed the predetermined, minimal clinically important difference of 10 points (P = .291; maximum difference, 3.8 points). Among the other subscales, the pazopanib arm reported significantly worse symptom scores for diarrhea (P < .001) loss of appetite (P < .001), nausea/vomiting (P < .001), and fatigue (P = .012). In general, HRQoL scores tended to decline over time in both arms. CONCLUSIONS HRQoL did not improve with the receipt of pazopanib. However, the observed improvement in progression‐free survival without impairment of HRQoL was considered a meaningful result. The toxicity profile of pazopanib was reflected in the patients’ self‐reported symptoms but did not translate into significantly worse overall global health status during treatment. Cancer 2015;121:2933–2941. © 2015 American Cancer Society.

Motor control demands coordinated excitation and inhibition across distributed brain neuronal networks. Recent work has suggested that multiple sclerosis (MS) may be associated with impairments of neuronal inhibition as part of more general progressive impairments of connectivity. Here, we report results from a prospective, multi-centre fMRI study designed to characterise the changes in patients relative to healthy controls during a simple cued hand movement task. This study was conducted at eight European sites using 1.5 Tesla scanners. Brain deactivation during right hand movement was assessed in 56 right-handed patients with relapsing-remitting or secondary progressive MS without clinically evident hand impairment and in 60 age-matched, healthy subjects. The MS patients showed reduced task-associated deactivation relative to healthy controls in the pre- and postcentral gyri of the ipsilateral hemisphere in the region functionally specialised for hand movement control. We hypothesise that this impairment of deactivation is related to deficits of transcallosal connectivity and GABAergic neurotransmission occurring with the progression of pathology in the MS patients. This study has substantially extended previous observations with a well-powered, multicentre study. The clinical significance of these deactivation changes is still uncertain, but the functional anatomy of the affected region suggests that they could contribute to impairments of motor control.