REDUCING INAPPROPRIATE SERUM T3 LABORATORY TEST ORDERING IN PATIENTS WITH TREATED HYPOTHYROIDISM.

Objective: Choosing Wisely is a campaign of the American Board of Internal Medicine that aims to promote evidence-based practices to reduce unnecessary ordering of tests or procedures. As part of this campaign, the Endocrine Society advises against ordering a serum total or free triiodothyronine (T3) level when assessing levothyroxine dosing in hypothyroid patients. This study was performed to assess and reduce inappropriate laboratory ordering practices among providers who manage patients with hypothyroidism within a large U.S. academic health system. Methods: A best practice alert (BPA) in the health record was developed and implemented following the collection of baseline data. This alert consisted of a popup window that was triggered when a serum T3 laboratory test was ordered for patients prescribed levothyroxine. The alert required user acknowledgement before the serum T3 laboratory test could be ordered. Results: During the 6-week period prior to launching the BPA, serum T3 tests were ordered a mean of 162.3 ± 15.4 (standard deviation) occurrences per 10,000 patients per week. Over a 15-week period following implementation of the BPA, the frequency of serum T3 orders steadily decreased and resulted in >44% fewer inappropriate tests being ordered. Conclusion: Although national societal guidelines recommend against ordering serum T3 concentrations while monitoring patients with hypothyroidism managed with levothyroxine, these laboratory tests are frequently ordered. Development of a triggered alert in the health record may reduce inappropriate monitoring practices, decrease costs, and improve utilization of limited health-care resources for this common clinical condition. Abbreviations: ATA = American Thyroid Association; BPA = best practice alert; T3 = triiodothyronine; TSH = thyroid-stimulating hormone.

Two uncommon cases of parathyroid hormone-related peptide mediated hypercalcemia in bladder carcinoma / Dos casos infrecuentes de hipercalcemia mediada por el péptido relacionado con la hormona paratiroidea en carcinoma de vejiga

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Tenofovir exposure alters associations of serum bicarbonate with chronic kidney disease risk in HIV-infected veterans.

OBJECTIVE: Among HIV-infected persons, tenofovir disoproxil fumarate (TDF) use is associated with higher risk of developing chronic kidney disease (CKD). Because lower serum bicarbonate concentrations may precede CKD onset, this study investigated the associations between TDF use and bicarbonate concentrations, and between bicarbonate with CKD risk among TDF users and nonusers. METHODS: Retrospective cohort study of 16,070 HIV-infected US veterans who initiated antiretroviral therapy between 1997-2011. The association between TDF use with longitudinal bicarbonate concentrations and associations between bicarbonate with incident CKD stratified by TDF use (never, initial, and later user) were evaluated. RESULTS: Compared with TDF users, never users had faster declines in bicarbonate concentrations: change in bicarbonate -0.11 mmol/l per year (95% confidence interval -0.16, -0.05), compared with -0.04 mmol/l per year (-0.06, 0.05) in initial users and -0.02 mmol/l per year (-0.05, 0.01) in later users. Low baseline bicarbonate (<22 mmol/l) was significantly associated with CKD risk among TDF never users (1.80; 1.21, 2.68), but not among TDF users (0.98; 0.69, 1.38). Similarly, declining bicarbonate concentrations were associated with higher CKD risk among never users (hazard ratio 1.67 per mmol/l; 1.34, 2.08), but not among TDF users (1.09; 0.98, 1.22). Interactions were highly significant for both analyses (P value = 0.001). CONCLUSION: Despite associations with nephrotoxicity, TDF use was associated with higher serum bicarbonate concentrations longitudinally. Additionally, TDF use obscured the strong associations of bicarbonate with CKD risk in HIV-infected persons. Therefore, the role of bicarbonate concentrations as a tool to monitor kidney health in HIV-infected persons may be limited in the setting of TDF use.

Modulation of remifentanil-induced postinfusion hyperalgesia by the ß-blocker propranolol in humans.

Acute and chronic exposure to opioids has been associated with hyperalgesia in both animals and humans. A genetic analysis of opioid-induced hyperalgesia in mice linked the ß(2)-adrenergic receptor to mechanical sensitization after opioid exposure. In humans, expansion of the area of mechanical hyperalgesia surrounding an experimentally induced lesion after the cessation of remifentanil infusion is a commonly used model of opioid hyperalgesia (remifentanil-induced postinfusion hyperalgesia, RPH). The purpose of our translational study was to test the hypothesis that the ß-adrenergic receptor antagonist propranolol modulates the expression of RPH in humans. This double-blinded, randomized, placebo-controlled, crossover study was performed in 10 healthy human volunteers. During test sessions, intracutaneous electrical stimulation was used to generate areas of secondary mechanical hyperalgesia. The area of this sensitization was measured before, during, and after remifentanil infusion. Heat pain sensitivity was also followed. During one test session, subjects received propranolol infusion. We observed an average increase in the areas of secondary mechanical hyperalgesia to 141% of the baseline in subjects infused with remifentanil and placebo (P=0.00040). However, when remifentanil infusion was combined with propranolol, the area of secondary hyperalgesia after terminating remifentanil was not significantly different than the area before beginning the opioid infusion (P=0.13). Thermal hyperalgesia was not observed after remifentanil infusion. Propranolol infusion at the selected dose had minor hemodynamic effects. Concomitant infusion of propranolol with remifentanil prevented the expression of RPH. ß-adrenergic receptor blockade may be a useful pharmacological strategy for preventing hyperalgesia in patients exposed to opioids.

GRLD-1 regulates cell-wide abundance of glutamate receptor through post-transcriptional regulation.

AMPA receptors mediate most of the fast postsynaptic response at glutamatergic synapses. The abundance of AMPA receptors in neurons and at postsynaptic membranes is tightly regulated. It has been suggested that changes in synaptic AMPA receptor levels are an important regulatory event in synaptic plasticity and learning and memory. Although the local, synapse-specific regulation of AMPA receptors has been intensely studied, global, cell-wide control is less well understood. Using a forward genetic approach, we identified glutamate receptor level decreased-1 (GRLD-1), a putative RNA-binding protein that was required for efficient production of GLR-1 in the AVE interneurons in the nematode Caenorhabditis elegans. In grld-1 mutants, GLR-1 levels were markedly reduced. Consistently, glutamate-induced currents in AVE were diminished and glr-1-dependent nose-touch avoidance behavior was defective in grld-1 mutants. We propose that this evolutionarily conserved family of proteins controls the abundance of GLR-1 by regulating glr-1 transcript splicing.