Therapeutic Inertia and Treatment Intensification.

PURPOSE OF REVIEW: This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. RECENT FINDINGS: Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.

Ultrasound evaluation of sinus fluid levels in swine during microgravity conditions.

BACKGROUND: Acute rhinosinusitis is a common problem that could occur in space secondary to absence of gravity-dependent drainage or odontogenic or external sources of infection. The purpose of this study was to determine the efficacy of ultrasound to determine sinus fluid distribution levels in swine and to assess the accuracy of ultrasound in the animal during normal and microgravity conditions. METHODS: Anesthetized swine had a catheter placed through a frontal bone window to allow aliquots of a viscous solution to be injected at 1 G (N = 4) or during brief microgravity parabolic flights (N = 4). Ultrasound examinations were performed with a high frequency probe during baseline and fluid-induced conditions. RESULTS: There was a consistent air-fluid level interface seen on ultrasound examination with the injection of 1 ml of fluid during 1-G conditions. Microgravity conditions caused the rapid (< 10 s) dissolution of the air-fluid level associated with dispersion of the fluid to the walIs of the sinus cavity in a uniform fashion. The air-fluid interface was recreated with return to 1 G. CONCLUSIONS: Ultrasound is a reliable diagnostic test for assessing fluid levels; these experiments demonstrate the technique can be used during microgravity conditions with attention to altered fluid behavior in the absence of gravity.

IGF1 receptor and thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is a vexing and poorly understood autoimmune process involving the upper face and tissues surrounding the eyes. In TAO, the orbit can become inflamed and undergo substantial remodeling that is disfiguring and can lead to loss of vision. There are currently no approved medical therapies for TAO, the consequence of its uncertain pathogenic nature. It usually presents as a component of the syndrome known as Graves' disease where loss of immune tolerance to the thyrotropin receptor (TSHR) results in the generation of activating antibodies against that protein and hyperthyroidism. The role for TSHR and these antibodies in the development of TAO is considerably less well established. We have reported over the past 2 decades evidence that the insulin-like growth factorI receptor (IGF1R) may also participate in the pathogenesis of TAO. Activating antibodies against IGF1R have been detected in patients with GD. The actions of these antibodies initiate signaling in orbital fibroblasts from patients with the disease. Further, we have identified a functional and physical interaction between TSHR and IGF1R. Importantly, it appears that signaling initiated from either receptor can be attenuated by inhibiting the activity of IGF1R. These findings underpin the rationale for therapeutically targeting IGF1R in active TAO. A recently completed therapeutic trial of teprotumumab, a human IGF1R inhibiting antibody, in patients with moderate to severe, active TAO, indicates the potential effectiveness and safety of the drug. It is possible that other autoimmune diseases might also benefit from this treatment strategy.