Correction to: The contribution of physician associates or assistants to the emergency department: A systematic scoping review.

[This corrects the article DOI: 10.1002/emp2.12989.].

The contribution of physician associates or assistants to the emergency department: A systematic scoping review.

Background: New health care professionals, such as the physician associate or assistant (PA), have expanded the ability of health systems to meet the needs of the population in both primary and secondary health care settings. Although PAs are widely deployed in the emergency department (ED), their role in the ED has not previously been formally described. This systematic scoping review synthesizes and critically analyzes existing literature on the impact and perception of the role of PAs working in the ED. Methods: We performed a systematic scoping review. We searched Medline, PubMed, Scopus, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (EMBASE) and EMCare for English language peer-reviewed studies describing PA roles in the ED. Both qualitative and quantitative studies were included. We assessed the quality of the articles using QualSyst and the mixed methods appraisal tool. Themes regarding PA roles in the ED were identified. Results: We included a total of 31 studies. Themes identified in the review included perceptions of the PA, wait times, acuity of patients seen, length of stay, those leaving without being seen (LWBS), clinical outcomes, pre-admission rates, well-being and scope of practice. Both the doctors' and patients' perception of PAs in the ED were generally high. The hindrance of them not being able to prescribe was evident. Studies showed a reduction in waiting times, length of stay, readmission rates, and those leaving without being seen when PAs work in the ED seeing moderate- to low-acuity patients. Evidence shows that PAs have a positive impact and the perceptions of the PAs are high in international EDs. There is significant evidence of PAs being key members of the health care team. Their work is particularly helpful for low- to moderate-acuity patients. With the increase in health care demand and a suffering UK National Health Service (NHS), the evidence synthesized in this review supports the potential positive impact PAs can have on the NHS and more specifically, the improvements of ED throughput metrics. Conclusions: This review identified the roles and positive influence of PAs in the ED. These findings highlight current and future challenges for PAs in the ED.

Epigenetics: new insights into postoperative adhesion development.

BACKGROUND: The link between post-operative adhesion development and epigenetic modifications is important in understanding the mechanism behind their formation. The purpose of this study was to determine whether epigenetic differences exist between primary fibroblasts of normal peritoneum and adhesion tissues isolated from the same patient(s). METHODS: DNA from fibroblasts isolated from normal peritoneum and adhesion tissues was isolated using Qiagen's EZ1 Advanced Kit. Methylation patterns of genes were quantified and compared in both cell lines using the Infinium Human Methylation 27 Beadchip system. RESULTS: A total of 7364 genes had been found to manifest significantly different DNA methylation levels in adhesion fibroblasts as compared to normal peritoneal fibroblasts (p<0.01). A total of 1685 genes were found to have increased DNA methylation by 50% in adhesion compared to peritoneal fibroblasts, and were enriched in Gene Ontology categories, Glycoprotein, and Defense Response. Furthermore, 1287 genes were found to have decreased DNA methylation patterns with enriched Gene Ontology categories, "Homeobox", and Transcription Factor Activity in adhesion fibroblasts. CONCLUSIONS: Epigenetic differences in fibroblasts isolated from normal peritoneum and adhesion tissues were observed. Future studies focusing on the precise role of these genes in the development of post operative adhesions will allow us to more fully appreciate regulatory mechanisms leading to adhesion development, thereby establishing targets for therapeutic interventions to prevent or limit adhesion development.

Extravasation of fluid in arthroscopic shoulder surgery requiring prolonged intubation: a case report.

BACKGROUND: Shoulder arthroscopy is a safe and effective procedure with a low complication rate. Although rare, there are potentially life-threatening risks such as fluid extravasation causing airway compromise. CASE PRESENTATION: We report the case of a 65-year-old female treated with an arthroscopic rotator cuff repair who had significant extravasation of arthroscopic fluid causing severe facial and neck swelling. Overnight intubation was required for respiratory monitoring until the edema had resolved enough to allow safe extubation. CONCLUSION: This case highlights the risk factors and clinical course of a patient with airway compromise caused by extravasation of fluid during shoulder arthroscopy. Although shoulder arthroscopy is a safe procedure, surgeon familiarity with the risk factors for this complication and close monitoring can aid in its identification and allow for appropriate treatment.

Retrospective analysis of quality improvement when using liposome bupivacaine for postoperative pain control.

BACKGROUND/OBJECTIVE: Liposome bupivacaine, a prolonged-release bupivacaine formulation, recently became available at the Naval Medical Center San Diego (NMCSD); before availability, postsurgical pain for large thoracic/abdominal procedures was primarily managed with opioids with/without continuous thoracic epidural (CTE) anesthesia. This retrospective chart review was part of a clinical quality initiative to determine whether postsurgical outcomes improved after liposome bupivacaine became available. METHODS: Data from patients who underwent laparotomy, sternotomy, or thoracotomy at NMCSD from May 2013 to May 2014 (after liposome bupivacaine treatment became available) were compared with data from patients who underwent these same procedures from December 2011 to May 2012 (before liposome bupivacaine treatment became available). Collected data included demographics, postoperative pain control methods, opioid consumption, perioperative pain scores, and lengths of intensive care unit and overall hospital stays. RESULTS: Data from 182 patients were collected: 88 pre-liposome bupivacaine (laparotomy, n=52; sternotomy, n=26; and thoracotomy, n=10) and 94 post-liposome bupivacaine (laparotomy, n=49; sternotomy, n=31; and thoracotomy, n=14) records. Mean hospital stay was 7.0 vs 5.8 days (P=0.009) in the pre- and post-liposome bupivacaine groups, respectively, and mean highest reported postoperative pain score was 7.1 vs 6.2 (P=0.007), respectively. No other significant between-group differences were observed for the overall population. In the laparotomy subgroup, there was a reduction in the proportion of patients who received CTE anesthesia post-liposome bupivacaine (22% [11/49] vs 35% [18/52] pre-liposome bupivacaine). CONCLUSION: Surgeons and anesthesiologists have changed the way they manage postoperative pain since the time point that liposome bupivacaine was introduced at NMCSD. Our findings suggest that utilization of liposome bupivacaine may be a useful alternative to epidural anesthesia.

Trends in 'poor responder' research: lessons learned from RCTs in assisted conception.

BACKGROUND: A substantial minority of women undergoing IVF will under-respond to controlled ovarian hyperstimulation. These women-so-called 'poor responders'-suffer persistently reduced success rates after IVF. Currently, no single intervention is unanimously accepted as beneficial in overcoming poor ovarian response (POR). This has been supported by the available research on POR, which consists mainly of randomized controlled trials (RCTs ) with an inherent high-risk of bias. The aim of this review was to critically appraise the available experimental trials on POR and provide guidance towards more useful-less wasteful-future research. METHODS: A comprehensive review was undertaken of RCTs on 'poor responders' published in the last 15 years. Data on various methodological traits as well as important clinical characteristics were extracted from the included studies and summarized, with a view to identifying deficiencies from which lessons can be learned. Based on this analysis, recommendations were provided for further research in this field of assisted conception. RESULTS: We selected and analysed 75 RCTs. A valid, 'low-risk' randomization method was reported in three out of four RCTs. An improving trend in reporting concealment of patient allocation was also evident over the 15-year period. In contrast, <1 in 10 RCTs 'blinded' patients and <1 in 5 RCTs 'blinded' staff to the proposed intervention. Only 1 in 10 RCTs 'blinded' ultrasound practitioners to patient allocation, when assessing the outcome of early pregnancy. The majority of trials reported an intention-to-treat analysis for at least one of their outcomes, with an improving trend in the recent years. Substantial variation was noted in the definitions used for 'poor responders', the most popular being 'low ovarian response at previous stimulation'. The preferred cut-off value for defining previous low response has been 'less or equal to three retrieved oocytes'. The most popular tests used for diagnosing diminished ovarian reserve have been antral follicle count and FSH. Although the Bologna criteria for POR were only recently introduced, they are expected to become a popular definition in future 'poor responder' trials. Numerous interventions have been studied on 'poor responders'. Most of these have been applied before/during controlled ovarian hyperstimulation. The antagonist protocol, the microdose flare protocol and the long down-regulation protocol have been among the most popular interventions. The analysis of outcomes revealed a clear improving trend in reporting live birth. In contrast, only 10% of RCTs reported significant improvement in reproductive outcomes among tested interventions. Twelve 'significant' interventions were reported, each supported by a single 'positive' RCT. Finally, trials of higher methodological quality were more likely to have been published in a high-impact journal. CONCLUSIONS: Overall, the majority of published trials on POR suffer from methodological flaws and are, thus, regarded as being high-risk for bias. The same trials have used a variety of definitions for their poor responders and a variety of interventions for their head-to-head comparisons. Not surprisingly, discrepancies are also evident in the findings of trials comparing similar interventions. Based on the identified deficiencies, this novel type of 'methodology and clinical' review has introduced custom recommendations on how to improve future experimental research in the 'poor responder' population.

The metabolic profile of intrahepatic cholestasis of pregnancy is associated with impaired glucose tolerance, dyslipidemia, and increased fetal growth.

OBJECTIVE: Quantification of changes in glucose and lipid concentrations in women with intrahepatic cholestasis of pregnancy (ICP) and uncomplicated pregnancy and study of their influence on fetal growth. RESEARCH DESIGN AND METHODS: A prospective study comparing metabolic outcomes in cholestastic and uncomplicated singleton pregnancies was undertaken at two university hospitals in the U.K. and U.S. from 2011-2014. A total of 26 women with ICP and 27 control pregnancies with no prior history of gestational diabetes mellitus were recruited from outpatient antenatal services and followed until delivery. Alterations in glucose, incretins, cholesterol, and triglycerides were studied using a continuous glucose monitoring (CGM) system and/or a standard glucose tolerance test (GTT) in conjunction with GLP-1 and a fasting lipid profile. Fetal growth was quantified using adjusted birth centiles. RESULTS: Maternal blood glucose concentrations were significantly increased in ICP during ambulatory CGM (P < 0.005) and following a GTT (P < 0.005). ICP is characterized by increased fasting triglycerides (P < 0.005) and reduced HDL cholesterol (P < 0.005), similar to changes observed in metabolic syndrome. The offspring of mothers with ICP had significantly larger customized birth weight centiles, adjusted for ethnicity, sex, and gestational age (P < 0.005). CONCLUSIONS: ICP is associated with impaired glucose tolerance, dyslipidemia, and increased fetal growth. These findings may have implications regarding the future health of affected offspring.

Anxiety, depression and saliva cortisol in women with a medical disorder during pregnancy.

Anxiety and depression during pregnancy increase the risk for an adverse pregnancy outcome and neurodevelopmental problems in the child. The aim of this study was to investigate anxiety and depression in women with a medical disorder of pregnancy compared with control antenatal women, and any association with saliva cortisol. One hundred and twenty pregnant women (60 with a known medical disorder and 60 without, mean gestation 32 weeks) completed five self-rating questionnaires (Spielberger State and Trait Anxiety, Edinburgh Postnatal Depression Scale (EPDS), the Adult Wellbeing Scale and a Life Events Questionnaire). Diurnal saliva samples were obtained from 39 women with a medical disorder and 50 controls for cortisol analysis. The medical disorders group were significantly more anxious and depressed than the controls (mean (SD)) state anxiety 40.0 (11.5) vs. 31.6 (8.8), p = 0.00; trait anxiety 39.4 (9.5) vs. 35.2 (9.2), p = 0.02; adult wellbeing 15.9 (7.5) vs. 12.3 (7.5) p = 0.01; and EPDS 9.6 (5.4) vs. 5.9 (4.8), p = 0.00). There was no difference in the life events scores between the groups. The subgroup of women suffering from hyperemesis gravidarum had particularly high EPDS scores, (16.2 (3), n = 5, p = 0.00) compared with controls. There were no significant differences in the cortisol levels between the groups. Some women with a medical disorder during pregnancy showed considerably elevated levels of anxiety and depression. Health professionals need to be aware that these women need extra psychological support.

Overproduction of DNA polymerase eta does not raise the spontaneous mutation rate in diploid human fibroblasts.

Telomerase-immortalized lines of diploid xeroderma pigmentosum variant (XP-V) fibroblasts (XP115LO and XP4BE) were complemented for constitutive or regulated expression of wild-type human DNA polymerase eta (hpol eta). The ectopic gene was expressed from a retroviral LTR at a population average of 34- to 59-fold above the endogenous (mutated) mRNA and high levels of hpol eta were detected by immunoblotting. The POLH cDNA was also cloned downstream from an ecdysone-regulated promoter and transduced into the same recipient cells. Abundance of the wild-type mRNA increased approximately 10-fold by addition of ponasterone to the culture medium. Complemented cell lines acquired normal resistance to the cytotoxic effects of UVC, even in the presence of 1mM caffeine. They also tolerated higher levels of UVC-induced template lesions during nascent DNA elongation when compared to normal fibroblasts (NHF). UVC-induced mutation frequencies at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus were measured in the XP115LO+XPV cell line overproducing hpol eta constitutively (E. Bassett, N.M. King, M.F. Bryant, S. Hector, L. Pendyala, S.G. Chaney, M. Cordeiro-Stone, The role of DNA polymerase eta in translesion synthesis past platinum-DNA adducts in human fibroblasts, Cancer Res. 64 (2004) 6469-6475). Induced mutation frequencies were significantly reduced, even below those observed in NHF; however, the average mutation frequency in untreated cultures was about three-fold higher than in the isogenic vector-control cell line. In this study, spontaneous HPRT mutation frequencies were measured at regular intervals, as isogenic fibroblasts either lacking or overproducing hpol eta were expanded for 100 population doublings. The mutation rates estimated from these results were not significantly increased in XP115LO cells expressing abnormal levels of hpol eta, relative to the cells lacking this specialized polymerase. These findings suggest that diploid human fibroblasts with normal DNA repair capacities and intact checkpoints are well protected against the potential mutagenic outcome of overproducing hpol eta, while still benefiting from accurate translesion synthesis of UV-induced pyrimidine dimers.

The role of DNA polymerase eta in translesion synthesis past platinum-DNA adducts in human fibroblasts.

Cisplatin, a widely used chemotherapeutic agent, has been implicated in the induction of secondary tumors in cancer patients. This drug is presumed to be mutagenic because of error-prone translesion synthesis of cisplatin adducts in DNA. Oxaliplatin is effective in cisplatin-resistant tumors, but its mutagenicity in humans has not been reported. The polymerases involved in bypass of cisplatin and oxaliplatin adducts in vivo are not known. DNA polymerase eta is the most efficient polymerase for bypassing platinum adducts in vitro. We evaluated the role of polymerase eta in translesion synthesis past platinum adducts by determining cytotoxicity and induced mutation frequencies at the hypoxanthine guanine phosphoribosyltransferase (HPRT) locus in diploid human fibroblasts. Normal human fibroblasts (NHF1) were compared with xeroderma pigmentosum variant (XPV) cells (polymerase eta-null) after treatment with cisplatin. In addition, XPV cells complemented for polymerase eta expression were compared with the isogenic cells carrying the empty expression vector. Cytotoxicity and induced mutagenicity experiments were measured in parallel in UVC-irradiated fibroblasts. We found that equitoxic doses of cisplatin induced mutations in fibroblasts lacking polymerase eta at frequencies 2- to 2.5-fold higher than in fibroblasts with either normal or high levels of polymerase eta. These results indicate that polymerase eta is involved in error-free translesion synthesis past some cisplatin adducts. We also found that per lethal event, cisplatin was less mutagenic than UVC. Treatment with a wide range of cytotoxic doses of oxaliplatin did not induce mutations above background levels in cells either expressing or lacking polymerase eta, suggesting that oxaliplatin is nonmutagenic in human fibroblasts.