AudioAbstracts

A phase 3, multi-center, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of levofloxacin inhalation solution (APT-1026) in stable cystic fibrosis patients. Flume PA, VanDevanter DR, Morgan EE, Dudley MN, Loutit JS, Bell SC, Kerem E, Fischer R, Smyth AR, Aaron SD, Conrad D, Geller DE,Elborn JS.

J Cyst Fibros. 2016 Jul;15(4):495-502. doi: 10.1016/j.jcf.2015.12.004. Epub 2016 Feb 4.

Abstract

RATIONALE:

For patients with cystic fibrosis (CF), the use of inhaled antibiotics has become standard of care to suppress chronic Pseudomonas airways infection. There are limited antibiotic options formulated and approved for inhaled use and antibiotic efficacies attenuate over time, making additional inhaled antibiotic classes desirable. APT-1026 (levofloxacin inhalation solution, LIS) is a fluoroquinolone in development for management of chronic P. aeruginosa airways infection in patients with CF.

OBJECTIVES:

To compare the safety and efficacy of a 28-day course of treatment with LIS 240mg or placebo BID in persons ≥12years old with CF and chronic P. aeruginosa infection.

METHODS:

A multinational, randomized (2:1), double-blinded study of LIS and placebo over 28days in CF patients ≥12years with chronic P. aeruginosa infection. Time to exacerbation was the primary endpoint. FEV1 (% predicted) and patient-reported …

Microbial colonization and lung function in adolescents with cystic fibrosis. Hector A, Kirn T, Ralhan A, Graepler-Mainka U, Berenbrinker S, Riethmueller J, Hogardt M, Wagner M, Pfleger A, Autenrieth I, Kappler M, Griese M, Eber E, Martus P, Hartl D.

J Cyst Fibros. 2016 May;15(3):340-9. doi: 10.1016/j.jcf.2016.01.004. Epub 2016 Feb 5.

Abstract

With intensified antibiotic therapy and longer survival, patients with cystic fibrosis (CF) are colonized with a more complex pattern ofbacteria and fungi. However, the clinical relevance of these emerging pathogens for lung function remains poorly defined. The aim ofthis study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with CF. Microbial colonization patterns and lung function parameters were assessed in 770 adolescent European (German/Austrian) CF patients in a retrospective study (median follow-up time: 10years). Colonization with Pseudomonas aeruginosa and MRSA were most strongly associated with loss of lung function, while mainly colonization with Haemophilus influenzae was associated with preservedlung function. Aspergillus fumigatus was the only species that was associated with an increased risk for infection with P. aeruginosa.Microbial interaction analysis revealed three distinct microbial clusters within the longitudinal course of CF lung disease. …

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

Tosco A, De Gregorio F, Esposito S, De Stefano D, Sana I, Ferrari E, Sepe A, Salvadori L, Buonpensiero P, Di Pasqua A, Grassia R, Leone CA,Guido S, De Rosa G, Lusa S, Bona G, Stoll G, Maiuri MC, Mehta A, Kroemer G, Maiuri L, Raia V.

Cell Death Differ. 2016 Aug;23(8):1380-93. doi: 10.1038/cdd.2016.22. Epub 2016 Apr 1.

Abstract
We previously reported that the combination of two safe proteostasis regulators, cysteamine andepigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosistransmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR …

Individual detection of 14 high risk human papilloma virus genotypes by the PapType test for the prediction of high grade cervical lesions. Cuzick J, Ho L, Terry G, Kleeman M, Giddings M, Austin J, Cadman L, Ashdown-Barr L, Costa MJ, Szarewski A.

J Clin Virol. 2014 May;60(1):44-9. doi: 10.1016/j.jcv.2014.02.002. Epub 2014 Feb 14.

Abstract

BACKGROUND:

HR HPV genotypes when assayed collectively, achieve high sensitivity but low specificity for the prediction of CIN2+. Knowledge of the specific genotypes in an infection may facilitate the use of HR HPV detection in routine clinical practice.

OBJECTIVES:

To compare the rate of HR HPV detection and the accuracy of CIN2+ prediction between PapType test (Genera Biosystems) and other commercially available HR HPV assays, and to examine the value of full HPV genotyping.

STUDY DESIGN:

PreservCyt samples from 1099 women referred for abnormal cervical cytology were used. CIN2+ was chosen as the primary end-point but CIN3+ was also evaluated. A hierarchy of HR HPV genotypes was created using PPV and this was used to create 3 groups of genotypes with potentially different …

Host: Thomas C. Wright, Jr., MD

A study of HPV typing for the management of HPV-positive ASC-US cervical cytologic results. Schiffman M, Vaughan LM, Raine-Bennett TR, Castle PE, Katki HA, Gage JC, Fetterman B, Befano B, Wentzensen N.

Gynecol Oncol. 2015 Sep;138(3):573-8. doi: 10.1016/j.ygyno.2015.06.040. Epub 2015 Jul 4.

Abstract

BACKGROUND:

In US cervical screening, immediate colposcopy is recommended for women with HPV-positive ASC-US(equivocal) cytology. We evaluated whether partial typing by Onclarity™ (BD) might identify HPV-positive women with low enough CIN3+ risk to permit 1-year follow-up instead.

METHODS:

The NCI-Kaiser Permanente Northern California Persistence and Progression cohort includes a subset of 13,890 women aged 21+ with HC2 (Qiagen)-positive ASC-US at enrollment; current median …

Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies Diana W. Bianchi, MD; Darya Chudova, PhD; Amy J. Sehnert, MD; Sucheta Bhatt, MD; Kathryn Murray, MS; Tracy L. Prosen, MD; Judy E. Garber, MD; Louise Wilkins-Haug, MD, PhD; Neeta L. Vora, MD; Stephen Warsof, MD; James Goldberg, MD; Tina Ziainia, MD; Meredith Halks-Miller, MD JAMA. 2015;314(2):162-169. doi:10.1001/jama.2015.7120

Importance: Understanding the relationship between aneuploidy detection on noninvasive prenatal testing (NIPT) and occult maternal malignancies may explain results that are discordant with the fetal karyotype and improve maternal clinical care.

Objective: To evaluate massively parallel sequencing data for patterns of copy-number variations that might prospectively identify occult maternal malignancies.

Design, Setting, and Participants: Case series identified from 125 426 samples submitted between February 15, 2012, and September 30, 2014, from asymptomatic pregnant women who underwent plasma cell-free DNA sequencing for clinical prenatal aneuploidy screening. Analyses were conducted in a clinical laboratory that performs DNA sequencing. Among the clinical samples, abnormal results were detected in 3757 (3%); these were reported to the ordering physician with recommendations for further evaluation.

Exposures: NIPT for …

Outcomes of Daytime Procedures Performed by Attending Surgeons after Night Work

Anand Govindarajan, M.D., David R. Urbach, M.D., Matthew Kumar, M.Sc., Qi Li, M.Sc., Brian J. Murray, M.D., David Juurlink, M.D., Ph.D., Erin Kennedy, M.D., Ph.D., Anna Gagliardi, Ph.D., Rinku Sutradhar, Ph.D., and Nancy N. Baxter, M.D., Ph.D.

N Engl J Med 2015; 373:845-853 DOI: 10.1056/NEJMsa1415994

August 27, 2015

Background: Sleep loss in attending physicians has an unclear effect on patient outcomes. In this study, researchers examined the effect of medical care provided by physicians after midnight on the outcomes of their scheduled elective procedures performed during the day.

Methods: The study authors conducted a population-based, retrospective, matched-cohort study in Ontario, Canada. Patients undergoing 1 of 12 elective daytime procedures performed by a physician who had treated patients from midnight to 7 a.m. were matched in a 1:1 ratio to patients undergoing the same procedure by the same physician on a day when the physician had not treated patients after midnight. Outcomes included death, readmission, complications, length of stay, and procedure duration. Generalized estimating equations were used to compare outcomes between patient groups.

Results: The authors included 38,978 patients, treated by 1448 …

Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial

Andrew Appelboam, FRCEM, Adam Reuben, FRCEM, Clifford Mann, FRCEM, James Gagg, FRCEM, Prof Paul Ewings, PhD, Andrew Barton, MSc, Trudie Lobban, MRCP, Mark Dayer, FRCP, Jane Vickery, MSc, Prof Jonathan Benger, MD on behalf of the REVERT trial collaborators

The Lancet. 2015; DOI:10.1016/S0140-6736(15)61485-4

Published Online: 24 August 2015

Background: The Valsalva manoeuvre is an internationally recommended treatment for supraventricular tachycardia, but cardioversion is rare in practice (5–20%), necessitating the use of other treatments including adenosine, which patients often find unpleasant. Researchers assessed whether a postural modification to the Valsalva manoeuvre could improve its effectiveness.

Methods: The study authors did a randomised controlled, parallel-group trial at emergency departments in England. They randomly allocated adults presenting with supraventricular tachycardia (excluding atrial fi brillation and flutter) in a 1:1 ratio to undergo a modified Valsalva manoeuvre (done semi-recumbent with supine repositioning and passive leg raise immediately after the Valsalva strain), or a standard semi-recumbent Valsalva manoeuvre. A 40 mm Hg pressure, 15 s standardised strain was used in both groups. Randomisation, stratified by centre, was done centrally and independently, with allocation with serially numbered, …