Research Spotlight

Posted July 15th 2016

Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.

Milton Packer M.D.

Milton Packer M.D.

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.


Posted July 15th 2016

Implementation of an Automatic Stop Order and Initial Antibiotic Exposure in Very Low Birth Weight Infants.

Arpitha Chiruvolu M.D.

Arpitha Chiruvolu M.D.

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.


Posted July 15th 2016

Editorial for neuroendocrine tumor for liver transplant.

James F. Trotter M.D.

James F. Trotter M.D.

Trotter, J. F. (2016). “Editorial for neuroendocrine tumor for liver transplant.” Am J Transplant: 2016 June [Epub ahead of print].

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Neuroendocrine tumor (NET) of the gastrointestinal tract and pancreas is a very rare indication for liver transplantation. The most definitive treatment of gastrointestinal NET is resection of the primary tumor and isolated hepatic metastasis, if possible. Other therapeutic options include local ablation and medical therapies (mTOR inhibitors and somatostatin analogues which significantly improve progression-free survival, but provide no survival benefit).


Posted July 15th 2016

Reduced serologic sensitivity to influenza A virus illness among inactivated influenza vaccinees.

Manjusha Gaglani M.D.

Manjusha Gaglani M.D.

Thompson, M. G., M. J. Gaglani, A. L. Naleway, S. H. Dowell, S. Spencer, S. Ball, M. Levine and A. Fry (2016). “Reduced serologic sensitivity to influenza a virus illness among inactivated influenza vaccinees.” Vaccine 34(30): 3443-3446.

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We compared >/=4-fold increases in antibody titers by hemagglutination inhibition assay to RT-PCR results among 42 adults with PCR-confirmed influenza A virus illnesses. Serologic sensitivity was higher among unvaccinated (69%, 95% confidence interval [CI]=48-90%) than vaccinated healthcare personnel (38%, 95% CI=29-46%) in a 2010-11 prospective cohort.


Posted July 15th 2016

Evaluation of Hallux Valgus Correction With Versus Without Akin Proximal Phalanx Osteotomy.

Naohiro Shibuya D.P.M.

Naohiro Shibuya D.P.M.

Shibuya, N., J. C. Thorud, L. R. Martin, B. S. Plemmons and D. C. Jupiter (2016). “Evaluation of hallux valgus correction with versus without akin proximal phalanx osteotomy.” J Foot Ankle Surg: 2016 June [Epub ahead of print].

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Although the efficacy of Akin proximal phalanx closing wedge osteotomy as a sole procedure for correction of hallux valgus deformity is questionable, when used in combination with other osseous corrective procedures, the procedure has been believed to be efficacious. However, a limited number of comparative studies have confirmed the value of this additional procedure. We identified patients who had undergone osseous hallux valgus correction with first metatarsal osteotomy or first tarsometatarsal joint arthrodesis with (n = 73) and without (n = 81) Akin osteotomy and evaluated their radiographic measurements at 3 points (preoperatively, within 3 months after surgery, and >/=6 months after surgery). We found that those people who had undergone the Akin procedure tended to have a larger hallux abduction angle and a more laterally deviated tibial sesamoid position preoperatively. Although the radiographic correction of the deformity was promising immediately after corrective surgery with the Akin osteotomy, maintenance of the correction was questionable in our cohort. The value of additional Akin osteotomy for correction of hallux valgus deformity is uncertain.