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Oncogene amplification on extrachromosomal DNA (ecDNA) is strongly associated with treatment resistance and shorter survival for patients with cancer, including patients with glioblastoma. The non-chromosomal inheritance of ecDNA during cell division is a major contributor to intratumoral genetic heterogeneity. At present, the spatial dynamics of ecDNA, and the impact on tumor evolutionary trajectories, are not well understood. Here, we investigate the spatial-temporal evolution of ecDNA and its clinical impact by analyzing tumor samples from 94 treatment-naive human IDH -wildtype glioblastoma patients. We developed a spatial-temporal computational model of ecDNA positive tumors ('SPECIES') that integrates whole-genome sequencing, multi-region DNA FISH, and nascent RNAscope, to provide unique insight into the spatial dynamics of ecDNA evolution. Random segregation in combination with positive selection of ecDNAs induce large, predictable spatial patterns of cell-to-cell ecDNA copy number variation that are highly dependent on the oncogene encoded on the circular DNA. EGFR ecDNAs often reach high mean copy number (mean of 50 copies per tumor cell), are under strong positive selection (mean selection coefficient, s > 2) and do not co-amplify other oncogenes on the same ecDNA particles. In contrast, PDGFRA ecDNAs have lower mean copy number (mean of 15 copies per cell), are under weaker positive selection and frequently co-amplify other oncogenes on the same ecDNA. Evolutionary modeling suggests that EGFR ecDNAs often accumulate prior to clonal expansion. EGFR structural variants, including vIII and c-terminal deletions are under strong positive selection, are found exclusively on ecDNA, and are intermixed with wild-type EGFR ecDNAs. Simulations show EGFRvIII ecDNA likely arises after ecDNA formation in a cell with high wild-type EGFR copy number (> 10) before the onset of the most recent clonal expansion. This remains true even in cases of co-selection and co-amplification of multiple oncogenic ecDNA species in a subset of patients. Overall, our results suggest a potential time window in which early ecDNA detection may provide an opportunity for more effective intervention., Highlights: ecDNA is the most common mechanism of focal oncogene amplification in IDH wt glioblastoma. EGFR and its variants on ecDNA are particularly potent, likely arising early in tumor development, providing a strong oncogenic stimulus to drive tumorigenesis. Wild-type and variant EGFR ecDNA heteroplasmy (co-occurrence) is common with EGFR vIII or c-terminal deletions being derived from EGFR wild-type ecDNA prior to the most recent clonal expansion. Tumors with ecDNA amplified EGFR versus PDGFRA exhibit different evolutionary trajectories. SPECIES model can infer spatial evolutionary dynamics of ecDNA in cancer.A delay between ecDNA accumulation and subsequent oncogenic mutation may give a therapeutic window for early intervention.

Background: There is a need to understand the clinical decision-making and work practices within ostomy nursing care to support expanding nursing training., Objective: To develop and evaluate a new metric-based simulation for assessing ostomy nursing care using a human factors approach., Sample: This pilot study involved eleven stakeholders in the needs assessment, six nurse participants performing simulated ostomy care, and three independent observers assessing procedure reliability., Method: We conducted a needs assessment of ostomy nursing care and training, developed an enhanced metric-based simulation for ostomy appliance change procedures, and statistically evaluated its reliability for measuring the simulated tasks., Results: The enhanced metric-based simulation captured different tasks within four task categories: product selection; stoma and peristomal skin care; baseplate sizing and adhesion; and infection control strategies. The video review procedure was reliable for assessing continuous (average ICC≥0.96) and categorical (average κ>0.96) variables., Conclusion: The new metric-based simulation was suitable for characterizing a broad range of clinical decision-making and work practices in ostomy nursing care.

Introduction Health systems internationally have developed new models of primary care to address health-care challenges. One such model is the Health Care Home (HCH),which has been widely adopted across New Zealand. Aim To explore the facilitators and barriers to implementation of the HCH in the southern health district (Otago and Southland). Methods Interviews with staff (n  = 15) from seven general practices were undertaken. A rapid thematic analysis informed by the Consolidated Framework for Implementation Research (CFIR) was conducted using the framework method. Results A number of implementation facilitators and barriers across three CFIR domains were identified: intervention characteristics, inner setting and implementation process. The intervention - the HCH - has well-designed core components (eg clinician triage, patient portals), but the adaptable periphery also needs addressing to ensure the core components fit the local context. In the inner setting, a positive implementation climate and readiness for change (a strong need for the change, compatibility, strong leadership, availability of resources, and a clear understanding of the HCH and timely practical support) were key for successful implementation. Although the HCH practices had detailed planning and performance monitoring systems in place, a successful implementation process required having a change management plan and ensuring whole-of-practice engagement. Discussion This evaluation has identified facilitators and barriers to implementing the HCH in one health district using implementation science theory (CFIR). It is imperative to tailor the HCH model to local needs and individual general practices for successful implementation.

Members of the αv family of integrins regulate activation of transforming growth factor beta (TGFβ) and are directly involved in pro-tumorigenic phenotypes. Thus, αv integrins may be therapeutic targets for fibrosis and cancer, yet the isolation of selective inhibitors is currently a challenge. We generated synthetic antibodies selective for αv integrins by phage display selections on cell lines that displayed integrin heterodimers. We identified antibodies that targeted two distinct epitopes on cell-surface αv integrins and partially inhibited cell adhesion mediated by interactions between integrins and the latency-associated peptide, part of the pro-form of TGFβ. Using the isolated antibody paratope sequences we engineered a bispecific antibody capable of binding to both epitopes simultaneously; this antibody potently and completely inhibited cell adhesion mediated by integrins αvβ1, αvβ3 and αvβ5. In addition, the bispecific antibody inhibited proliferation and migration of lung carcinoma lines, where the highest and lowest potencies observed correlated with integrin-αv cell surface expression levels. Taken together, our results demonstrate that phage display selections with live cells can yield high quality anti-integrin antibodies, which we used as biparatopic building blocks to construct a bispecific antibody that strongly inhibited integrin function and may be a therapeutic candidate for cancer and fibrosis., Competing Interests: Conflict of Interest Statement The authors declare no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Inotuzumab ozogamicin (InO), an anti-CD22 monoclonal antibody conjugated to calicheamicin, is approved in Europe and the United States for treatment of adults with relapsed or refractory acute lymphoblastic leukemia (ALL). Population analyses were performed to evaluate the relationship between InO exposure and efficacy and safety end points in patients with ALL. The probability of achieving complete remission/complete remission with incomplete hematologic recovery (CR/CRi) and minimal residual disease (MRD)-negativity for InO relative to chemotherapy was also investigated. Data from study 1010 (NCT01363297) and INO-VATE (NCT01564784) were pooled for exposure-response (InO, n = 234) and treatment-response (InO, n = 234; chemotherapy, n = 143) analyses. The analyses demonstrated that InO exposure was significantly correlated with achieving CR/CRi and MRD-negativity, as well as with hepatic event adjudication board-reported veno-occlusive disease/sinusoidal obstruction. Patients with ALL treated with InO had significantly greater odds of achieving CR/CRi (7-times higher) and MRD-negativity (13-times higher) than those receiving chemotherapy., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Introduction: Dacomitinib is an epidermal growth factor receptor (EGFR) inhibitor approved for the treatment of metastatic non-small cell lung cancer (NSCLC) in the first line in patients with EGFR activating mutations. Dacomitinib is taken orally once daily at 45 mg with or without food, until disease progression or unacceptable toxicity occurs. Oncology patients often can develop gastroesophageal reflux disease (GERD), which may require management with an acid-reducing agent. Proton pump inhibitors (PPIs), such as rabeprazole, inhibit sodium-potassium adenosine triphosphatase (H + /K + -ATPase) pumps that stimulate acid secretion in the stomach and have a prolonged pharmacodynamic effect that extends beyond 24 h post-administration. The aim of this work was to characterize the absorption of dacomitinib via modeling with a particular interest in quantifying the impact of rabeprazole on the pharmacokinetics (PK) of dacomitinib., Materials and Methods: The pooled dataset consisted of five clinical pharmacology healthy volunteer studies, which collected serial pharmacokinetic concentration-time profiles of dacomitinib. Non-linear mixed effects modeling was carried out to characterize dacomitinib pharmacokinetics in the presence and absence of the concomitant use of a PPI, rabeprazole. Several absorption models, some more empirical, and some more physiologically based, were tested: transit compartment, first-order absorption with and without lag time, and variations of combined zero- and first-order absorption kinetics models., Results: The presence of a PPI was a significant covariate affecting the extent ( F ) and rate (ka) of dacomitinib absorption, as previously reported in the dedicated clinical study. A transit compartment model was able to best describe the absorption phase of dacomitinib.

The Wnt/β-catenin signaling pathway has been implicated in human proliferative diseases such as cancer and fibrosis. The functions of β-catenin and several other components of this pathway have been investigated in fibrosis. However, the potential role of R-spondin proteins (RSPOs), enhancers of the Wnt/β-catenin signaling, has not been described. A specific interventional strategy targeting this pathway for fibrosis remains to be defined. We developed monoclonal antibodies against members of the RSPO family (RSPO1, 2, and 3) and probed their potential function in fibrosis in vivo. We demonstrated that RSPO3 plays a critical role in the development of fibrosis in multiple organs. Specifically, an anti-RSPO3 antibody, OMP-131R10, when dosed therapeutically, attenuated fibrosis in carbon tetrachloride (CCl4)-induced liver fibrosis, bleomycin-induced pulmonary and skin fibrosis models. Mechanistically, we showed that RSPO3 induces multiple pro-fibrotic chemokines and cytokines in Kupffer cells and hepatocytes. We found that the anti-fibrotic activity of OMP-131R10 is associated with its inhibition of β-catenin activation in vivo. Finally, RSPO3 was found to be highly elevated in the active lesions of fibrotic tissues in mouse models of fibrosis and in patients with idiopathic pulmonary fibrosis (IPF) and nonalcoholic steatohepatitis (NASH). Together these data provide an anti-fibrotic strategy for targeting the Wnt/β-catenin pathway through RSPO3 blockade and support that OMP-131R10 could be an important therapeutic agent for fibrosis., Competing Interests: Mingjun Zhang, Michael Haughey, Nai-Yu Wang, Kate Blease, Suzana Couto, Igor Belka, Matthew Groza, James Hartke, Brydon Bennett, Brent Benish, Paola Castigilioni, Clifton Drew, Jean Lachowicz, Leon Carayannopoulos, Kandasamy Hariharan, Ho Cho, and Weilin Xie are employees of Celgene Corporation, whose company funded this study. Ann M. Kapoun, Timothy Hoey, Jennifer Cain, and Austin Gurney are employees of Oncomed Pharmaceuticals. OMP-131R10 is an Oncomed Pharmaceuticals product. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Introduction: Clinical assessment of medical students in emergency medicine (EM) clerkships is a highly variable process that presents unique challenges and opportunities. Currently, clerkship directors use institution-specific tools with unproven validity and reliability that may or may not address competencies valued most highly in the EM setting. Standardization of assessment practices and development of a common, valid, specialty-specific tool would benefit EM educators and students., Methods: A two-day national consensus conference was held in March 2016 in the Clerkship Directors in Emergency Medicine (CDEM) track at the Council of Residency Directors in Emergency Medicine (CORD) Academic Assembly in Nashville, TN. The goal of this conference was to standardize assessment practices and to create a national clinical assessment tool for use in EM clerkships across the country. Conference leaders synthesized the literature, articulated major themes and questions pertinent to clinical assessment of students in EM, clarified the issues, and outlined the consensus-building process prior to consensus-building activities., Results: The first day of the conference was dedicated to developing consensus on these key themes in clinical assessment. The second day of the conference was dedicated to discussing and voting on proposed domains to be included in the national clinical assessment tool. A modified Delphi process was initiated after the conference to reconcile questions and items that did not reach an a priori level of consensus., Conclusion: The final tool, the National Clinical Assessment Tool for Medical Students in Emergency Medicine (NCAT-EM) is presented here., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

Background: Animal and cellular studies support the importance of autophagy inhibition in lymphangioleiomyomatosis (LAM). In a cohort of subjects with LAM, we tested the hypothesis that treatment with sirolimus and hydroxychloroquine (an autophagy inhibitor) at two different dose levels is safe and well tolerated. Secondary end points included changes in lung function., Methods: This 48-week, two-center phase I trial evaluated the safety of escalating oral hydroxychloroquine doses (100-200 mg) given twice a day in combination with sirolimus to eligible patients ≥ 18 years old with LAM. Subjects received combination therapy for 24 weeks followed by an observation phase without taking study drugs for an additional 24 weeks., Results: Fourteen patients provided written informed consent. Thirteen were treated in cohorts of three patients each with escalating hydroxychloroquine doses (200 and 400 mg) and an extension phase at the 400-mg dose. The most common adverse events were mucositis, headache, and diarrhea. No drug-related serious adverse events were reported. Secondary end points showed improvement in lung function at 24 weeks, with a decrease in lung function at the 48-week time point. When the higher dose of hydroxychloroquine was analyzed separately, FEV 1 and FVC remained stable at 48 weeks, but the 6-min walk distance showed a decrease toward baseline., Conclusions: The combination of sirolimus and hydroxychloroquine is well tolerated, with no dose-limiting adverse events observed at 200 mg twice a day. Potential effects on lung function should be explored in larger trials., Trial Registry: ClinicalTrials.gov; No.: NCT01687179; URL: www.clinicaltrials.gov., (Copyright © 2017 American College of Chest Physicians. All rights reserved.)

Competing Interests: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. The authors disclosed none.

Background: Oral mechanistic target of rapamycin inhibitors have been shown to reduce visceral tumor volume in patients with tuberous sclerosis complex (TSC)., Objective: We sought to evaluate the cutaneous response to oral sirolimus in patients with TSC and an indication for systemic treatment, including long-term effects., Methods: A retrospective analysis of 14 adult patients with TSC prescribed sirolimus to treat lymphangioleiomyomatosis was performed. Serial photographs of angiofibromas, shagreen patches, and ungual fibromas taken before, during, and after the treatment period were blinded, then assessed using the Physician Global Assessment of Clinical Condition (PGA). Microscopic and molecular studies were performed on skin tumors harvested before and during treatment., Results: Sirolimus significantly improved angiofibromas (median treatment duration 12 months; median PGA score 4.5 [range 1.5-5]; Wilcoxon signed rank test, P = .018) and shagreen patches (median treatment duration 10 months; median PGA score 4.5 [range 3.5-5]; Wilcoxon signed rank test, P = .039), whereas ungual fibromas improved in some patients (median treatment duration 6.5 months; median PGA score 4.66 [range 2.75-5]; Wilcoxon signed rank test, P = .109). Clinical, immunohistochemical, or molecular evidence of resistance was not observed (range 5-64 months of treatment)., Limitations: This was a retrospective analysis limited to adult women with lymphangioleiomyomatosis., Conclusion: Oral sirolimus is an effective long-term therapy for TSC skin tumors, particularly angiofibromas, in patients for whom systemic treatment is indicated., (Published by Elsevier Inc.)

Pd(II)-catalysed ortho-arylation of benzylic heterocycles with arylboronic acid pinacol esters (Ar-BPin) via directed C-H bond activation to generate the desired biaryl products is reported. This methodology is efficient and applicable to a wide range of functionalised Ar-BPin and benzylic heterocycles, allowing the direct synthesis of important biaryl motifs in modest to good yield.

Background: Lymphangioleiomyomatosis (LAM), sporadic or in women with tuberous sclerosis complex (TSC), is characterized by cystic lung destruction, lymphatic involvement (eg, chylous pleural effusions, lymphangioleiomyomas), and renal angiomyolipomas (AMLs). The multisystem manifestations of LAM appear to result from metastatic dissemination of LAM cells bearing inactivating mutations or having loss of heterozygosity (LOH) of the tumor suppressor genes TSC1 or TSC2, which leads to hyperactivation of the mammalian target of rapamycin. Sirolimus slows the decline of lung function, reduces chylous effusions, and shrinks the size of AMLs. The purpose of this study was to determine the effect of sirolimus on circulating LAM cells., Methods: Cells from blood were isolated by a density-gradient fractionation system and from urine and chylous effusions by centrifugation. Blood cells were incubated with anti-CD45-fluorescein isothiocyanate (FITC) and anti-CD235a-R-phycoerythrin (PE) antibodies, and urine and chylous effusion cells were incubated with anti-CD44v6-FITC and anti-CD9-R-PE antibodies. Cells were sorted and analyzed for TSC2 LOH., Results: LAM cells with TSC2 LOH were identified in 100% of blood specimens and 75% of urine samples from patients before therapy. Over a mean duration of 2.2 ± 0.4 years of sirolimus therapy, detection rates of LAM cells were significantly decreased to 25% in blood (P < .001) and 8% in urine (P = .003). Following therapy, a greater loss of circulating LAM cells was seen in postmenopausal patients (P = .025)., Conclusions: Patients receiving sirolimus had a progressive loss of circulating LAM cells that depended on time of treatment and menopausal status.

Dysfunctional uterine bleeding (DUB) is a common presentation in the emergency department and has a wide differential. Most presentations of DUB are in hemodynamically stable patients and can be evaluated as an outpatient. Uterine arteriovenous malformation (AVM) is one presentation that can result in a life-threatening medical emergency with unexpected sudden and massive vaginal bleeding. We describe a case of a 24-year-old female with sudden heavy vaginal bleeding requiring a blood transfusion, ultrasound evidence of uterine AVM, and a treatment method of expectant management using an intrauterine device in an attempt to preserve fertility.

Objective: To test the hypothesis that there were no differences in the skeletal and dental effects of banded vs bonded expanders when evaluated using cone beam computed tomography (CBCT)., Materials and Methods: The experimental sample consisted of 23 patients: 13 (seven male, six female; mean age  =  12.6 ±1.8 years) and 10 (five male, five female; mean age  =  13.5 ± 2.1 years) treated with banded and bonded maxillary expanders, respectively. CBCT images were taken at T1 (pretreatment) and T2 (immediately after expansion) to evaluate the changes in the naso-maxillary complex. Relationships between and within groups were assessed using analysis of variance. If the results were significant, post hoc t-tests were used to determine where the significant differences occurred., Results: Regardless of the appliance, the maxilla was expanded equally at the level of the canines and first and second premolars. At the level of the first molars, more dental tipping and alveolar bending were evident in the banded expander group. Both appliances equally increased the skeletal and soft tissue dimensions of the nasal cavity and maxillary sinus volume. The posterior airway volume did not significantly change with either method of expansion., Conclusions: The hypothesis was rejected. Both appliances expanded the maxilla similarly. However, in the banded group, more dental tipping and alveolar bending occurred at the level of the first molars. Maxillary expansion affected the palatal suture and demonstrated anterior and posterior skeletal widening of the nasal cavity, with corresponding soft tissue changes and increased airway volume.

Unlabelled: Previous studies have identified subclinical lung disease in family members of probands with familial pulmonary fibrosis, but the natural history of preclinical pulmonary fibrosis is uncertain. The purpose of this study was to determine whether individuals with preclinical lung disease will develop pulmonary fibrosis. After a 27-year interval, two subjects with manifestations of preclinical familial pulmonary fibrosis, including asymptomatic alveolar inflammation and alveolar macrophage activation, were reevaluated for lung disease. CT scans of the chest, pulmonary function tests, and BAL were performed, and genomic DNA was analyzed for mutations in candidate genes associated with familial pulmonary fibrosis. One subject developed symptomatic familial pulmonary fibrosis and was treated with oxygen; her sister remained asymptomatic but had findings of pulmonary fibrosis on high-resolution CT scan of the chest. High concentrations of lymphocytes were found in BAL fluid from both subjects. Genetic sequencing and analyses identified a novel heterozygous mutation in telomerase reverse transcriptase (TERT, R1084P), resulting in telomerase dysfunction and short telomeres in both subjects. In familial pulmonary fibrosis, asymptomatic preclinical alveolar inflammation associated with mutation in TERT and telomerase insufficiency can progress to fibrotic lung disease over 2 to 3 decades., Trial Registry: ClinicalTrials.gov; No.: NCT00071045; URL: www.clinicaltrials.gov.

Rationale: Lymphangioleiomyomatosis (LAM), occurring sporadically (S-LAM) or in patients with tuberous sclerosis complex (TSC), results from abnormal proliferation of LAM cells exhibiting mutations or loss of heterozygosity (LOH) of the TSC genes, TSC1 or TSC2., Objectives: To identify molecular markers useful for isolating LAM cells from body fluids and determine the frequency of TSC1 or TSC2 LOH., Methods: Candidate cell surface markers were identified using gene microarray analysis of human TSC2⁻(/)⁻ cells. Cells from bronchoalveolar lavage fluid (BALF), urine, chylous effusions, and blood were sorted based on reactivity with antibodies against these proteins (e.g., CD9, CD44v6) and analyzed for LOH using TSC1- and TSC2-related microsatellite markers and single nucleotide polymorphisms in the TSC2 gene., Measurements and Main Results: CD44v6(+)CD9(+) cells from BALF, urine, and chyle showed TSC2 LOH in 80%, 69%, and 50% of patient samples, respectively. LAM cells with TSC2 LOH were detected in more than 90% of blood samples. LAM cells from different body fluids of the same patients showed, in most cases, identical LOH patterns, that is, loss of alleles at the same microsatellite loci. In a few patients with S-LAM, LAM cells from different body fluids differed in LOH patterns. No patients with S-LAM with TSC1 LOH were identified, suggesting that TSC2 abnormalities are responsible for the vast majority of S-LAM cases and that TSC1-disease may be subclinical., Conclusions: Our data support a common genetic origin of LAM cells in most patients with S-LAM, consistent with a metastatic model. In some cases, however, there was evidence for genetic heterogeneity between LAM cells in different sites or within a site.

Objective: Many of the individuals most at risk for HIV infection (i.e., minority populations, women, adolescents) are also the most marginalized by our health care system. Lacking primary care providers, they rely on the Emergency Department (ED) for their health care needs and education. In this prospective randomized controlled trial, we compared the educational effectiveness of a 15-minute posttest counseling video with the normal practice of a session with an HIV counselor. The study population was composed of ambulatory patients recruited for rapid HIV testing in the ED., Methods: The RAs (research assistants) recruited a convenience sample of stable patients presenting to the walk-in section of an inner-city adult ED for rapid HIV testing. Eligible patients for this study included patients who consented for the rapid HIV test and completed measures on condom intention and condom use self-efficacy. Before receiving their results, participants who consented to be in this study were randomized to either a 15-minute HIV posttest educational video available in English/Spanish or to a posttest educational session with an HIV counselor. Afterwards, both groups completed an assessment tool concerning HIV prevention and transmission., Results: Of the 128 participants, 61 and 67 patients were randomized to the video and counselor groups, respectively. The groups were similar with respect to gender, ethnicity and experience with prior HIV testing. Mean knowledge scores were higher in the video group (76.20% vs. 69.3%; 90% CI for the difference, 2.8, 11.2). As the lower bound of the CI for the difference was higher than the lower equivalence boundary (-5%), we infer that the video was at least as effective as the counselor educational session., Conclusions: The use of an educational counseling video is a valid alternative for providing posttest education and prevention information during the waiting period associated with the 20-minute HIV rapid test. Without disruption in clinical flow, both testing and education can be accomplished in a meaningful way in a busy ED.

Objective: To test a model designed to increase willingness of patients presenting to the emergency department off hours to be tested for human immunodeficiency virus (HIV) by using a pretest counseling video as a substitute for face-to-face counseling., Methods: We conducted a randomized controlled trial comparing the rate of testing in patients randomized to receive video counseling with immediate testing (video group) versus standard care, which was referral to counseling and testing the next day (standard referral group)., Results: Fifty percent of 805 eligible patients consented to participate in the study, indicating willingness to be tested. The HIV testing rate was higher in the video group 92.6% (187 of 202) than in the standard referral group 4.5% (9 of 202) (difference = 88.1%, 95% confidence interval: 83.5%-92.7%). Thirty percent of 187 patients in the video group who were tested returned for their results; 8 of 9 patients in standard care returned to be tested and to get their results., Conclusion: Half of the patients who were solicited for HIV testing agreed to be tested. When testing was immediate the patient was more likely to have the test completed.

Study Objective: Multiple barriers to traditional pretest HIV counseling make HIV testing difficult to accomplish in the emergency department setting in off hours. This study compares the educational effectiveness of a 10-minute pretest counseling video with the usual practice of a session with an HIV counselor., Methods: This was a prospective randomized controlled trial of adult patients presenting to the urgent care area of a busy inner-city hospital. Patients either viewed an HIV educational video or spoke with an HIV counselor for pretest counseling. The video was developed by 2 of the investigators (YC, MH) and covered essential educational elements for HIV testing, as required by the New York State Department of Health. All participants completed a measure of HIV knowledge after their intervention. An equivalence analysis was performed to assess whether the video was at least as good as counseling in terms of overall mean knowledge score., Results: Of 129 patients recruited for the study, 65 patients were randomized to the intervention and 64 patients to the control group. Five patients were unable to complete the study. The final analysis was based on 124 patients. Mean knowledge scores were higher in the intervention (85.3% versus 79.7%; 90% confidence interval for the difference 2.6% to 8.7%)., Conclusion: We conclude that the use of an educational video with an inner-city adult population was at least as effective as in-person pretest counseling in conveying information related to HIV testing.

Objective: Ten years have passed since Congress enacted the Patient Self-Determination Act to promote the use of advance directives (ADs). This study was performed to determine the frequency, type, demographic distribution, and utility of ADs that accompany residents of skilled nursing facilities (SNFs) transferred to emergency departments (EDs)., Methods: This was an observational, cross-sectional cohort of SNF residents, transferred to two urban, academic EDs. Chart review and physician interviews were conducted on consecutive patients arriving during 12-hour data collection shifts., Results: Among 715 patients entered, 315 [44%, 95% confidence interval (95% CI) = 40% to 48%] had an AD. Advance directives were significantly more prevalent among white (50%) than African American (34%) or Hispanic (39%) patients (p < 0.001), and varied from 0% to 94% among SNFs. Of the 315 patients with ADs, do-not-resuscitate (DNR) orders were the most prevalent (65%, 95% CI = 58% to 69%). Although 75% (95% CI = 69% to 81%) of the DNR orders addressed cardiopulmonary resuscitation (CPR), only 12% (95% CI = 8% to 16%) addressed intubation. Among 39 patients who required intubation or CPR, 44% had ADs, 82% (95% CI = 57% to 96%) of which were deemed useful., Conclusions: Despite a decade of legislation promoting their use, ADs are lacking in most SNF residents transferred to EDs for evaluation and in most settings in which a clinical indication exists for intubation or CPR. Variation in their prevalence appears to be associated with both ethnicity and SNF origin. Although about three-fourths of DNR ADs addressed CPR, only about one in ten offered guidance regarding intubation. When available, ADs are used in most instances to guide emergency care.

Health promotion is increasingly being recognized as making an important contribution to the well-being of Canada's seniors. Most research relating to this topic, however, has focused on middle-income senior men and women. An exploratory study using ethnographic methods was conducted to explore and describe the health promotion experience of senior women living on limited incomes. Interviews with a total of 11 urban senior women living on limited incomes were analyzed. A major finding of this study was that the women utilized a wide variety of "ways of living" that are presented in the model, Health Promotion as Self Nurturance. Health promotion was perceived to be influenced by living on a limited income by most participants; however, 3 of the participants believed that their health status and income level were unrelated. Findings are discussed and implications for community health nurses are offered.

The caregiver respite experience is seen as one way to moderate the negative consequences of caregiving. From an interpretivist research orientation, this study explored how 10 family caregivers of persons with dementia experienced respite. From a coping theoretical perspective, the caregiver respite experience is discussed as a process of "getting out" of the caregiver world, and is linked to avoidance strategies of emotion-focused coping. The following three phases within the coping dimension of the respite experience were found: caregivers recognizing their need to get out of the caregiver world, giving themselves permission to actually get out from it temporarily, and having the appropriate social support resources available to facilitate the getting out. The critical practice and research implications linked to caregivers' ability to acknowledge their need for respite are described.

The vasopressin-sensitive water channel (aquaporin 2; AQP-2) mediates water transport across the apical plasma membrane of the renal collecting ducts and is excreted in human urine. This study presents the hypothesis that measurements of the AQP-2 excretion rate might be used as a marker of collecting-duct responsiveness to vasopressin, and therefore could be useful in the clinical evaluation of various water-balance disorders. This study presents information about the development of an antibody to human AQP-2, and measures the urinary excretion of AQP-2 by quantitative Western analysis. A standard curve of band densities was generated by using known quantities of the modified immunizing peptide to derive the amount of AQP-2 contained in aliquots of urine. AQP-2 urinary excretion changed with short-term alterations in hydration status produced either by water loading (76% decrease, P < 0.01) or by 3% sodium chloride (760% increase, P < 0.01). Steady-state 24-h urinary excretion of AQP-2 was 43 +/- 10 nmol/24 h (or 28.5 +/- 6.9 pmol/mg creatinine), and 20 +/- 6 nmol/24 h (or 18.3 +/- 7.9 pmol/mg creatinine) in men and women, respectively. Therefore, urinary AQP-2 excretion can be quantified by using Western analysis, and may serve as a marker of collecting-duct responsiveness to vasopressin in different physiologic settings.