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2,6-Dichlorohydroquinone 1,2-dioxygenase (PcpA) from Sphingobium chlorophenolicum ATCC 39723 is a member of a class of Fe(II)-containing hydroquinone dioxygenases that is involved in the mineralization of the pollutant pentachlorophenol. This enzyme has not been extensively characterized, despite its interesting ring-cleaving activity and use of Fe(II), which are reminiscent of the well-known extradiol catechol dioxygenases. On the basis of limited sequence homology to the extradiol catechol dioxygenases, the residues ligating the Fe(II) center were originally proposed to be H159, H227, and E276 (Xu et al. in Biochemistry 38:7659-7669, 1999). However, PcpA has higher sequence homology to a newly reported, crystallographically characterized zinc metalloenzyme that has a similar predicted fold. We generated a homology model of the structure of PcpA based upon the structure of this zinc metalloenzyme. The homology model predicts that the tertiary structure of PcpA differs significantly from that of the extradiol dioxygenases, and that the residues ligating the Fe(II) are H11, H227, and E276. This structural model was tested by mutating each of H11, H159, H227, and E276 to alanine. An additional residue that is predicted to lie near the active site and is conserved among PcpA, its closest homologues, and the extradiol dioxygenases, Y266, was mutated to phenylalanine. Of these mutants, only H159A retained significant activity, thus confirming the active-site location predicted by the homology-based structural model. The model provides an important basis for understanding the origin of the unique function of PcpA.

Background A nonroutine event is any aspect of clinical care perceived by clinicians or trained observers as a deviation from optimal care based on the context of the clinical situation. The authors sought to delineate the incidence and nature of intraoperative nonroutine events during anesthesia care. Methods The authors prospectively collected audio, video, and relevant clinical information on 556 cases at three academic hospitals from 1998 to 2004. In addition to direct observation, anesthesia providers were surveyed for nonroutine event occurrence and details at the end of each study case. For the 511 cases with reviewable video, 400 cases had no reported nonroutine events and 111 cases had at least one nonroutine event reported. Each nonroutine event was analyzed by trained anesthesiologists. Rater reliability assessment, comparisons (nonroutine event vs. no event) of patient and case variables were performed. Results Of 511 cases, 111 (21.7%) contained 173 nonroutine events; 35.1% of event-containing cases had more than one nonroutine event. Of the 173 events, 69.4% were rated as having patient impact and 12.7% involved patient injury. Longer case duration (25th vs. 75th percentile; odds ratio, 1.83; 95% CI, 1.15 to 2.93; P = 0.032) and presence of a comorbid diagnosis (odds ratio, 2.14; 95% CI, 1.35 to 3.40; P = 0.001) were associated with nonroutine events. Common contributory factors were related to the patient (63.6% [110 of 173]) and anesthesia provider (59.0% [102 of 173]) categories. The most common patient impact events involved the cardiovascular system (37.4% [64 of 171]), airway (33.3% [57 of 171]), and human factors, drugs, or equipment (31.0% [53 of 171]). Conclusions This study describes characteristics of intraoperative nonroutine events in a cohort of cases at three academic hospitals. Nonroutine event–containing cases were commonly associated with patient impact and injury. Thus, nonroutine event monitoring in conjunction with traditional error reporting may enhance our understanding of potential intraoperative failure modes to guide prospective safety interventions. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Many patients use opioids for nonmalignant pain, and opioid use in the general population has been associated with poor long‐term outcomes. The use of high‐risk medications, including opioid analgesics, may increase the risk of unplanned healthcare utilization. Methods and Results We performed a nested evaluation in the VICS (Vanderbilt Inpatient Cohort Study) (N=3000) on patients with an admitting diagnosis of acute coronary syndrome and/or acute decompensated heart failure. Patient enrollment occurred from October 2011 until December 2015 and involved a single investigational site, Vanderbilt University Medical Center (Nashville, TN). Of the 2495 eligible patients, 501 (20%) were discharged with an opioid prescription and were predominantly white and men, with a median age of 59 (interquartile range, 53–67) years. Our primary outcome was unplanned healthcare utilization, which included emergency department presentation or readmission. Secondary outcomes included mortality and a composite of planned utilization behaviors: cardiac rehabilitation and provider follow‐up within 30 days. Cox proportional hazards models did not show a statistically significant association with increased unplanned utilization (adjusted hazard ratio, 1.06; 95% CI, 0.87–1.28) or mortality (adjusted hazard ratio, 1.08; 95% CI , 0.84–1.39), compared with those without opioids at discharge. Patients discharged with opioids were less likely to complete planned healthcare utilization (adjusted odds ratio, 0.69; 95% CI , 0.52–0.91). Conclusions There are decreased odds of planned healthcare utilization among patients with acute coronary syndrome and acute decompensated heart failure discharged with opioid medication. It is imperative to understand how opioid use can affect a patient's relationship with the healthcare system.

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