Non-allelic homologous recombination (NAHR), non-homologous end joining (NHEJ), and microhomology-mediated replication-dependent recombination (MMRDR) have all been put forward as mechanisms to explain DNA rearrangements associated with genomic disorders. However, many nonrecurrent rearrangements in humans remain unexplained. To further investigate the mutation mechanisms of these copy number variations (CNVs), we performed breakpoint mapping analysis for 62 clinical cases with intragenic deletions in the human DMD gene (50 cases) and other known diseasecausing genes (one PCCB, one IVD, one DBT, three PAH, one STK11, one HEXB, three DBT, one HRPT1, and one EMD cases). While repetitive elements were found in only four individual cases, three involving DMD and one HEXB gene, microhomologies (2-10 bp) were observed at breakpoint junctions in 56% and insertions ranging from 1 to 48 bp were seen in 16 of the total 62 cases. Among these insertions, we observed evidence for tandem repetitions of short segments (5-20 bp) of reference sequence proximal to the breakpoints in six individual DMD cases (six repeats in one, four repeats in three, two repeats in one, and one repeat in one case), strongly indicating attempts by the replication machinery to surpass the stalled replication fork. We provide evidence of a novel template slippage event during replication rescue. With a deeper insight into the complex process of replication and its rescue during origin failure, brought forward by recent studies, we propose a hypothesis based on aberrant firing of replication origins to explain intragenic nonrecurrent rearrangements within genes, including the DMD gene.
In this ED-based study, patient preferences for diagnostic testing differed significantly across levels of risk, benefit, and cost of diagnostic testing. Cost was the strongest and most consistent factor associated with decreased desire for testing.
The desire for testing was strongly sensitive to the benefits, risks, and costs. Many participants wanted a test when there was no added cost, regardless of benefit or risk levels, but far fewer elected to receive the test as cost increased incrementally. This suggests that out-of-pocket costs may deter patients from undergoing diagnostic testing with low potential benefit.
A colectomy perioperative care bundle in Michigan is associated with improved value of surgical care. We will expand efforts to implement perioperative care bundles in Michigan to improve outcomes and reduce costs.
After reading the article, participants should be able to discuss the influence of financial incentives, accompanied with information regarding risk and benefit, on patient preferences for diagnostic testing. Activity Disclosures This activity received no commercial support. CME Editor Corey Heitz discloses no relevant financial relationships. This activity underwent peer review in line with standards of editorial integrity and publication ethics. Conflicts of interest have been identified and resolved in accordance with John Wiley and Sons, Inc.'s Policy on Activity Disclosure and Conflict of Interest. Accreditation John Wiley and Sons, Inc. is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. John Wiley and Sons, Inc. designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit TM. Physicians should only claim credit commensurate with the extent of their participation in the activity. For information on applicability and acceptance of continuing medical education credit for this activity, please consult your professional licensing board. This activity is designed to be completed within 1 hour. To successfully earn credit, participants must complete the activity during the valid credit period, which is up to two years from initial publication. Additionally, up to 3 attempts and a score of 70% or better is needed to pass the post test.
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Background
Perioperative controlled substance diversion and tracking have received increased regulatory focus throughout the United States. The authors’ institution developed and implemented an automated web-based software application for perioperative controlled substance management. The authors hypothesized that implementation of such a system reduces errors as measured by missing controlled substance medications, missing controlled substance kits (a package of multiple controlled substance medications), and missing witness signatures during kit return.
Methods
From December 1, 2014 to March 31, 2017, the authors obtained missing controlled substance medication, controlled substance kit, and witness return signature data during the preimplementation, implementation, and study period of the controlled substance management application at a single university hospital. This before and after study was based on a QI project at the authors’ institution. The authors included all cases requiring anesthesia services. The primary outcome of this study was the rate of missing controlled substance medications. Secondary outcomes included rates for kits not returned to pharmacy and missing kit return witness signatures.
Results
There were 54,302 cases during the preimplementation period, 57,670 cases during the implementation period, and 65,911 cases during the study period. The number of missing controlled substance medication (difference 0.7 per 1,000 cases; 95% CI, 0.38–1.02; P < 0.001) and kit return errors (difference 0.45 per 1,000 cases; 95% CI, 0.24–0.66, P < 0.001) declined after implementation of the application. There was no difference in the number of missing witness return signatures (difference 0.09 per 1,000 cases; 95% CI, −0.08 to 0.26, P = 0.350). A user survey with 206 of 485 (42%) response rate demonstrated that providers believed the new application managed controlled substances better than the previous system.
Conclusions
A software application that tracks perioperative controlled substance kits with deep integration into the electronic health record and pharmacy systems is associated with a decrease in management errors.
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