Citations

Summary This randomised, double‐blind, placebo‐controlled study compared the effect of perineural with intravenous dexamethasone, both administered concomitantly with interscalene brachial plexus block for shoulder surgery. Patients received 8 mg dexamethasone mixed with ropivacaine in the block injection (n = 42), 8 mg dexamethasone intravenously at the time of the block (n = 37), or intravenous saline (n = 41) at the time of the block. Perineural and intravenous dexamethasone resulted in prolonged mean ( SD ) duration of block to 16.9 (5.2) h and 18.2 (6.4) h, respectively, compared with 13.8 (3.8) h for saline (p = 0.001). Mean (SD) opioid consumption (morphine equivalents) during the first 24 h after postanaesthesia recovery arrival was 12.2 (9.3) mg in the perineural dexamethasone, 17.1 (15.9) mg in the intravenous dexamethasone and 24.1 (14.3) mg in the saline groups (p = 0.001). Dexamethasone via either route reduced anti‐emetic use (p = 0.046). There was no effect on patient satisfaction. These results suggest that both perineural and intravenous dexamethasone are useful adjuncts to ropivacaine interscalene block, with the intravenous route preferred as this avoids the possibility of neural toxicity of dexamethasone.

Objective To describe findings and outcomes of 331 bilateral inferior petrosal sinus sampling (BIPSS) procedures performed in 327 patients evaluated for Cushing disease (CD). Materials and methods The radiology department's electronic database was searched to identify all BIPSS procedures (1990–2013). Electronic medical records were used to identify demographics, laboratory, procedural, surgical and pathologic findings. Results A total of 331 BIPSS procedures were performed in 327 patients (254 F, 73 M), mean age 41 (range 7–81) years. The overall technical success rate was 88% for bilateral cannulation, though nearly two-thirds of the technical failures had unilateral sampling that diagnosed CD. Of the 331 BIPSS procedures, 40 were performed without, and 291 with stimulation by Acthrel or desmopressin. Sensitivity was 89–94% for unstimulated BIPSS, 96% for stimulated BIPSS, and 77% for MRI. BIPSS lateralization was accurate in about half of patients, compared with 75% accuracy for MRI. Mean inferior petrosal sinus (IPS):peripheral adrenocorticotropic hormone ratio was 17.3 (SE 1.8) at baseline, and 99.2 (SE 14.8) at 3 min, with decreasing values over time. All patients with follow-up after surgical resection for centralizing BIPSS were reported to be cured, with cortisol levels significantly decreased from 19 to 4 μg/dL (p<0.0001). Complications from BIPSS were rare, including groin hematoma (2.5%), but no thromboembolic complications were seen. Conclusions BIPSS remains the ‘gold standard’ for diagnosing CD. Stimulation with Acthrel or desmopressin is key to increasing specificity. When only one IPS can be successfully cannulated, results may still be diagnostic. BIPSS findings cannot be used to accurately lateralize lesions within the pituitary.

The legacy of human-Neandertal interbreeding Non-African humans are estimated to have inherited on average 1.5 to 4% of their genomes from Neandertals. However, how this genetic legacy affects human traits is unknown. Simonti et al. combined genotyping data with electronic health records. Individual Neandertal alleles were correlated with clinically relevant phenotypes in individuals of European descent. These archaic genetic variants were associated with medical conditions affecting the skin, the blood, and the risk of depression. Science , this issue p. 737

Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE‐PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of “precision medicine.” The February 2015 eMERGE‐PGx data release includes sequence‐derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation‐Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.

Abstract The American Medical Informatics Association convened the 2014 Health Policy Invitational Meeting to develop recommendations for updates to current policies and to establish an informatics research agenda for personalizing medicine. In particular, the meeting focused on discussing informatics challenges related to personalizing care through the integration of genomic or other high-volume biomolecular data with data from clinical systems to make health care more efficient and effective. This report summarizes the findings ( n = 6) and recommendations ( n = 15) from the policy meeting, which were clustered into 3 broad areas: (1) policies governing data access for research and personalization of care; (2) policy and research needs for evolving data interpretation and knowledge representation; and (3) policy and research needs to ensure data integrity and preservation. The meeting outcome underscored the need to address a number of important policy and technical considerations in order to realize the potential of personalized or precision medicine in actual clinical contexts.

Objective: Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be an effective and tolerable intervention for adolescents with treatment-resistant depression. There is limited rationale to inform coil placement for rTMS dosing in this population. We sought to examine and compare three localization techniques for coil placement in the context of an open-label trial of high-frequency rTMS for adolescents with treatment-resistant depression. Methods: Ten adolescents with treatment-resistant depression were enrolled in an open-label trial of high-frequency rTMS. Participants were offered 30 rTMS sessions (10 Hz, 120% motor threshold, left 3000 pulses applied to the dorsolateral prefrontal cortex) over 6–8 weeks. Coil placement for treatment was MRI guided. The scalp location for treatment was compared with the locations identified with standard 5 cm rule and Beam F3 methods. Results: Seven adolescents completed 30 rTMS sessions. No safety or tolerability concerns were identified. Depression severity as assessed with the Children's Depression Rating Scale Revised improved from baseline to treatment 10, treatment 20, and treatment 30. Gains in depressive symptom improvement were maintained at 6 month follow-up visits. An MRI-guided approach for coil localization was feasible and efficient. Our results suggest that the 5 cm rule, Beam F3, and the MRI-guided localization approaches provided variable scalp targets for rTMS treatment. Conclusions: Open-label, high-frequency rTMS was feasible, tolerable, and effective for adolescents with treatment-resistant depression. Larger, blinded, sham-controlled trials are needed for definitive safety and efficacy data. Further efforts to understand optimal delivery, dosing, and biomarker development for rTMS treatments of adolescent depression are warranted.

Abstract Aims We have previously reported that asymptomatic systolic heart failure (HF) is characterized by an impaired renal response to volume expansion due to lack of activation of urinary cGMP which is corrected by subcutaneous (SQ) BNP. In the current study, we sought to define the cardiorenal response to intravascular volume expansion after 12 weeks of SQ BNP therapy. Methods and results We utilized a double-blinded, placebo-controlled study to compare 12 weeks of twice-daily SQ BNP 10 µg/kg (n = 22) or placebo (n = 12) in asymptomatic systolic HF. Subjects underwent two study visits: baseline and after 12 weeks of therapy. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular volume expansion. The primary endpoint was change in urinary sodium excretion in response to volume expansion at 12 weeks, and we observed a greater increase in urinary sodium excretion [166 (77, 290) vs. 15 (−39, 72) mEq/min; P = 0.02] with SQ BNP treatment vs. placebo. Secondary endpoints included change in urine flow and glomerular filtration rate (GFR) in response to volume expansion at 12 weeks. We observed a significant increase in urine flow (P &lt; 0.01) and trend for differential response in GFR (P = 0.08) with SQ BNP treatment vs. placebo. Conclusion Among patients with asymptomatic systolic HF, twice-daily SQ BNP therapy improved the cardiorenal response to volume expansion at 12-week follow-up. Further studies are warranted to determine if these beneficial physiological observations with chronic natriuretic peptide administration translate into a delay in the progression to symptomatic HF.

Purpose Noninvasive stiffness imaging techniques (elastography) can image myocardial tissue biomechanics in vivo. For cardiac MR elastography (MRE) techniques, the optimal vibration frequency for in vivo experiments is unknown. Furthermore, the accuracy of cardiac MRE has never been evaluated in a geometrically accurate phantom. Therefore, the purpose of this study was to determine the necessary driving frequency to obtain accurate three‐dimensional (3D) cardiac MRE stiffness estimates in a geometrically accurate diastolic cardiac phantom and to determine the optimal vibration frequency that can be introduced in healthy volunteers. Methods The 3D cardiac MRE was performed on eight healthy volunteers using 80 Hz, 100 Hz, 140 Hz, 180 Hz, and 220 Hz vibration frequencies. These frequencies were tested in a geometrically accurate diastolic heart phantom and compared with dynamic mechanical analysis (DMA). Results The 3D Cardiac MRE was shown to be feasible in volunteers at frequencies as high as 180 Hz. MRE and DMA agreed within 5% at frequencies greater than 180 Hz in the cardiac phantom. However, octahedral shear strain signal to noise ratios and myocardial coverage was shown to be highest at a frequency of 140 Hz across all subjects. Conclusion This study motivates future evaluation of high‐frequency 3D MRE in patient populations. Magn Reson Med 77:351–360, 2017. © 2016 Wiley Periodicals, Inc.