Research Spotlight

Flores, A. and S. K. Asrani (2016). “Editorial: Magnetic resonance elastography and non-alcoholic fatty liver disease: Time for an upgrade?” Am J Gastroenterol 111(7): 995-996.

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Elastography techniques, such as two-dimensional magnetic resonance elastography (2D-MRE) are increasingly used for the non-invasive assessment of liver fibrosis in patients with nonalchoholic fatty liver disease (NAFLD). Loomba et al. demonstrate that 3D-MRE (shear wave frequency 40 Hz) had even greater diagnostic accuracy than the commercially available 2D-MRE (shear wave frequency 60 Hz) in diagnosing advanced fibrosis (area under the receiver operator curve, AUROC 0.981 vs. 0.921, P<0. 05) using liver biopsy as reference standard. Despite limitations, MRE serves as an important tool in risk stratification for patients with NAFLD.

Zaman, A., R. Dubiel, S. Driver, M. Bennett, V. Diggs and L. Callender (2016). “Seizure prophylaxis guidelines following traumatic brain injury: An evaluation of compliance.” J Head Trauma Rehabil: 2016 June [Epub ahead of print].

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OBJECTIVE: To determine degree of adherence to guidelines for seizure prophylaxis following traumatic brain injury (TBI). SETTING: Tertiary care level 1 trauma center and affiliated inpatient rehabilitation facility. PARTICIPANTS: A total of 173 individuals with TBI who required inpatient rehabilitation from January 1, 2007, to December 31, 2013. DESIGN: Retrospective medical record review. MAIN MEASURES: Overutilization rate of prophylactic antiepileptic drugs (AEDs); failure to stop rate of AED utilization upon admission to and during inpatient rehabilitation; and duration of overutilization. RESULTS: Of the 173 participants included, 77 were started on seizure prophylaxis at hospital presentation and 96 were not. Of the 77 participants, 11 had a posttraumatic seizure. Of the 66 remaining, 18 participants (10.4%) were continued on AEDs for more than 7 days after injury. Of these 18 participants, 12 were continued on AEDs without indication upon admission to inpatient rehabilitation. Finally, 8 of the 12 were continued on AEDs at discharge from rehabilitation, resulting in a failure to stop rate of 66.67%. CONCLUSION: Despite existing guidelines for stopping seizure prophylaxis after TBI, some patients remain on AEDs and may be inappropriately exposed to possible medication side effects. These findings highlight the importance of communication at the time of rehabilitation transfer and the need for ongoing education about AED guidelines.

Wardly, D., L. M. Wolford and V. Veerappan (2016). “Idiopathic intracranial hypertension eliminated by counterclockwise maxillomandibular advancement: A case report.” Cranio: 1-9 [Epub ahead of print].

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INTRODUCTION: Obstructive sleep apnea (OSA) is a secondary cause of intracranial hypertension (IH). Decreased jugular venous drainage has been seen in patients with idiopathic IH. CLINICAL PRESENTATION: A complex case of a 48-year-old female whose idiopathic IH was put into remission after counterclockwise maxillomandibular advancement (CC-MMA), despite persistence of her OSA. CONCLUSION: This case highlights the relationship between OSA and IH and points to the significant morbidity that can result from mild OSA and from what are considered borderline intracranial pressures. This indicates the need for a high index of suspicion for actual underlying pathology that can be surgically corrected when patients manifest symptoms of a somatic syndrome. This is the first report in the medical literature of clinical elimination of IH by CC-MMA. The authors propose that this positive outcome was effected via mandibular advancement producing a decrease in jugular venous resistance, allowing improved absorption of cerebrospinal fluid.

Vardeny, O., B. Claggett, M. Packer, M. R. Zile, J. Rouleau, K. Swedberg, J. R. Teerlink, A. S. Desai, M. Lefkowitz, V. Shi, J. J. McMurray and S. D. Solomon (2016). “Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: The paradigm-hf trial.” Eur J Heart Fail: 2016 June [Epub ahead of print].

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AIMS: In this analysis, we utilized data from PARADIGM-HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril. METHODS AND RESULTS: In a post-hoc analysis from PARADIGM-HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2-2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70-0.93, P < 0.001) to that observed in patients who had not experienced any dose reduction (HR 0.79, 95% CI 0.71-0.88, P < 0.001). CONCLUSIONS: In PARADIGM-HF, study medication dose reduction identified patients at higher risk of a major cardiovascular event. The magnitude of benefit for patients on lower doses of sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs.

Tolia, V. N., S. Desai, H. Qin, P. D. Rayburn, G. Poon, K. Murthy, D. L. Ellsbury and A. Chiruvolu (2016). “Implementation of an automatic stop order and initial antibiotic exposure in very low birth weight infants.” Am J Perinatol: 2016 June [Epub ahead of print].

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Objective: To evaluate if an antibiotic automatic stop order (ASO) changed early antibiotic exposure (use in the first 7 days of life) or clinical outcomes in very low birth weight (VLBW) infants. Study Design We compared birth characteristics, early antibiotic exposure, morbidity, and mortality data in VLBW infants (with birth weight <= 1500 g) born 2 years before (pre-ASO group, n = 313) to infants born in the 2 years after (post-ASO, n = 361) implementation of an ASO guideline. Early antibiotic exposure was quantified by days of therapy (DOT) and antibiotic use > 48 hours. Secondary outcomes included mortality, early mortality, early onset sepsis (EOS), and necrotizing enterocolitis. Results Birth characteristics were similar between the two groups. We observed reduced median antibiotic exposure (pre-ASO: 6.5 DOT vs. Post-ASO: 4 DOT; p < 0.001), and a lower percentage of infants with antibiotic use > 48 hours (63.4 vs. 41.3%; p < 0.001). There were no differences in mortality (12.1 vs 10.2%; p = 0.44), early mortality, or other reported morbidities. EOS accounted for less than 10% of early antibiotic use. Conclusions Early antibiotic exposure was reduced after the implementation of an ASO without changes in observed outcomes.