Search

Objectives The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendations were not provided- a critical gap which the current update aims to address. Method Overview of research regarding mixed presentations in BD, with treatment recommendations developed using a modified CANMAT/ISBD rating methodology. Limitations are discussed, including the dearth of high-quality data and reliance on expert opinion. Results No agents met threshold for first line treatment of DSM-5 manic or depressive episodes with mixed features. For mania + mixed features second line treatment options include asenapine, cariprazine, divalproex, and aripiprazole. In depression + mixed features, cariprazine and lurasidone are recommended as second line options. For DSM-IV defined mixed episodes, with a longer history of research, asenapine and aripiprazole are first line, and olanzapine (monotherapy or combination), carbamazepine, and divalproex are second line. Research on maintenance treatments following a DSM-5 mixed presentation is extremely limited, with third-line recommendations based on expert opinion. For maintenance treatment following a DSM-IV mixed episode, quetiapine (monotherapy or combination) is first line, and lithium and olanzapine identified as second line options. Conclusion The CANMAT and ISBD groups hope these guidelines provide valuable support for clinicians providing care to patients experiencing mixed presentations, as well as further influence investment in research to improve diagnosis and treatment of this common and complex clinical state.

Purpose In this exploratory study, the effect of postprocedural flushing with crystalloids after oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) on platinum concentrations in peritoneal tissue, blood, and drain fluid was studied. Interpatient variability in oxaliplatin pharmacokinetics and the relation between platinum concentration in peritoneal fluid and platinum exposure in tissue and blood was explored. Methods Ten patients with peritoneal carcinomatosis of colorectal origin were treated with HIPEC including postprocedural flushing, followed by ten patients without flushing afterwards. Tissue, peritoneal fluid, blood, and drain fluid samples were collected for measurement of total and ultrafiltered platinum concentrations. Results Peritoneal tissue concentration and systemic ultrafiltered platinum exposure showed large inter individual variability, ranging from 65 to 1640 µg/g dry weight and 10.5 to 28.0 µg*h/ml, respectively. No effect of flushing was found on geometric mean platinum concentration in peritoneal tissue (348 vs. 356 µg/g dry weight), blood (14.8 vs. 18.1 µg*h/ml), or drain fluid (day 1: 7.6 vs. 7.7 µg/ml; day 2: 1.7 vs. 1.9 µg/ml). The platinum concentration in peritoneal fluid at the start of HIPEC differed twofold between patients and was positively correlated with systemic exposure (p = .04) and peak plasma concentration (p = .04). Conclusion In this exploratory study, no effect was found for postprocedural flushing on platinum concentrations in peritoneal tissue, blood, or drain fluid. BSA-based HIPEC procedure leads to large interpatient variability in platinum exposure in all compartments. The study was registered at ClinicalTrials.gov on 7 December 2017 under registration number NCT03364907.

A study regarding the role and uniqueness of psychiatric nursing was conducted with 94 participants from Manitoba, Canada. The primary theme of comprehensive knowledge of mental health, mental illness, and addictions was foundational for the application of the sub-themes of therapeutic relationship, holistic approach, recovery orientation, stigma reduction, and advocacy for change. Values, beliefs, and attitudes towards people with mental illness and addictions need to be instilled in psychiatric nursing students throughout their educational program to provide high quality, compassionate, and safe care. Implications for incorporation of the theme and sub-themes into psychiatric nursing curriculum are described in the paper.

Contains fulltext : 218875.pdf (Publisher’s version ) (Open Access) Myxofibrosarcoma(MFS) is the most common soft tissue sarcoma(STS) in elderly patients. Surgical resection remains the main treatment modality but tumor borders can be difficult to delineate with conventional clinical methods. Incomplete resections are a common problem and local recurrence remains a clinical issue. A technique that has shown great potential in improving surgical treatment of solid tumors is tumor targeted imaging and image-guided surgery with near-infrared fluorescence. To facilitate this technique, it is essential to identify a biomarker that is highly and homogenously expressed on tumor cells, while being absent on healthy non-malignant tissue. The purpose of this study was to identify suitable molecular targets for tumor-targeted imaging of myxofibrosarcoma. Ten potential molecular targets for tumor targeted imaging were investigated with immunohistochemical analysis in myxofibrosarcoma tissue (n = 34). Results were quantified according to the immunoreactive score(IRS). Moderate expression rates were found for uPAR, PDGFRa and EMA/MUC1. High expression rates of VEGF and TEM1 were seen. Strong expression was most common for TEM1 (88.2%). These results confirms that TEM1 is a suitable target for tumor-targeted imaging of myxofibrosarcoma. Keywords Image-guided surgery; Immunohistochemistry; Molecular imaging; Myxofibrosarcoma; Soft tissue sarcoma; Tumor endothelial marker 1(TEM1), Vascular endothelial growth factor (VEGF).

OBJECTIVES While clinical guidelines exist for the management of bipolar disorder (BD), there are significant challenges to their widespread dissemination and implementation in clinical practice. The Canadian Network of Mood and Anxiety Treatment Improving Patient Care and Outcomes in the Treatment of Bipolar Disorder (C-IMPACT BD) web-based application was developed for use at the point-of-care to improve adherence to guidelines for evidence-based pharmacological management of BD. METHODS C-IMPACT BD uses a point-of-care practice assessment which, via adaptive questioning of patient-specific information, text/video descriptions of the guidelines, and pop-up prompts delivers personalized, evidence-based treatment recommendations for patients with BD. In order to inform quality improvement of the newly developed tool, a sample of Canadian physicians were invited to use the application and record its influence on their prescribing behavior. RESULTS Of 375 patients with bipolar I (BD-I) or bipolar II (BD-II) disorder for whom a point-of-care practice assessment was completed, a change in therapy was considered for 225 (60.0%). Prior to completing the assessment, 59.6% of these patients were receiving first-line therapy recommended for their phase of illness. Following the assessment, the overall number of patients for whom a first-line recommended therapy was being considered increased significantly to 76.9% (p = 0.0001). CONCLUSIONS Outcomes suggest that the C-IMPACT BD web-based application has the potential to improve physician adherence to clinical treatment guidelines. Formal research investigations are warranted to explore the impact of this tool on physician prescribing behavior and patient outcomes.

Introduction: Neoadjuvant chemotherapy (CT) for locally advanced colon cancer (LACC) could potentially lead to tumor shrinkage, eradication of micrometastases, and prevention of tumor cell shedding during surgery. This retrospective study investigates the surgical and oncological outcomes of preoperative CT for LACC. Methods: Using the Netherlands Cancer Registry, data of patients with stage II or III colon cancer, diagnosed between 2008 and 2016 was collected. A propensity score matching (PSM; 1:2) was performed and compared patients with clinical tumor (cT) 4 colon cancer who were treated with neoadjuvant CT to patients with cT4 colon cancer treated with adjuvant CT (Fig. 1). Results: A total of 192 patients treated with neoadjuvant CT were compared to 1,954 patients that received adjuvant CT. After PSM, 149 patients in the neoadjuvant group were compared to 298 patients in the control group. No significant differences were found in baseline characteristics after PSM. After neoadjuvant CT, a significant response was observed in 13 (9%) patients with 5 (4%) patients showing a complete response. Complete resection margins (R0) were achieved in 77% in the neoadjuvant group versus 86% in the adjuvant treated group (p = 0.037). Significantly less tumor positive lymph nodes were found in the neoadjuvant group (median 0 vs. 2, p < 0.001). Major complication rates and 5-year overall survival did not differ between both groups (67–65%, p = 0.87). Conclusion: Neoadjuvant CT seems safe and feasible with similar long-term survival compared to patients who are treated with adjuvant CT.

Psychiatric nurses often experience associative stigma. Associative stigma may impact psychiatric nurses' views of their professional identity which ultimately impacts the health care of individuals experiencing mental health concerns. Very little research has been conducted on associative stigma in the western Prairie Provinces, including Manitoba. The authors conducted a secondary analysis on the results of an explanatory sequential mixed methods research study to determine if psychiatric nurses in Manitoba are influenced by associative stigma. Three themes were identified through this analysis, specifically: (1) the perception that RPNs are not "Real" Nurses; (2) lack of recognition of specialized training; and (3) working with a stigmatized population. Associative stigma was intertwined in all of the participants' narratives indicating a need to dismantle associative stigma. Strategies to enhance the public perception of psychiatric nursing and decrease associative stigma within the profession are described.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

OBJECTIVE There is a bidirectional relationship between obesity and mood disorders, with each increasing the risk of developing the other. This relationship suggests that they have overlapping pathophysiologic mechanisms. Adipose tissue-derived hormones, or adipokines, regulate appetite and metabolism and have activity in limbic brain regions, making them potential shared etiologic factors between elevated body mass index (BMI) and mood disorders. However, the precise relationships between BMI, mood, and adipokines are unknown. METHODS We measured the serum levels of adiponectin, lipocalin-2, resistin, adipsin, and leptin in 53 people with early-stage DSM-IV-defined bipolar disorder, diagnosed with the Mini-International Neuropsychiatric Interview, and 22 healthy comparison subjects. Participants were followed at the University of British Columbia Mood Disorders Centre between June 2004 and June 2012. We were primarily interested in determining, in patients, (1) whether BMI and recent mood episodes predicted adipokine levels and (2) whether adipokine levels in turn predicted subsequent mood relapses and change in BMI. RESULTS Using linear regression, we found that (1) past-6-month mood episodes predicted lower adiponectin (β = -0.385, P = .04) and adipsin (β = -0.376, P = .03) levels and higher lipocalin-2 levels (β = 0.411, P = .03), (2) BMI did not predict adipokine levels, and (3) treatment with second-generation antipsychotics was associated with higher resistin levels (β = 0.482, P < .01). Furthermore, lower adiponectin (β = -0.353, P = .01) and leptin (β = -0.332, P = .02) levels predicted depressive relapse over 12 months, while higher adipsin (β = 0.496, P < .01) and leptin (β = 0.421, P < .01) levels predicted BMI gain. CONCLUSIONS Our results suggest that mood episodes and medication treatment contribute to adipokine abnormalities in bipolar disorder and that adipokines influence psychiatric illness course and BMI change. Adipokines may represent a novel pathophysiologic mechanism linking elevated BMI and mood disorders and deserve further study as potential mood-regulating molecules.

Background The HOPE-BD was a naturalistic study established to follow individuals in Canada seeking treatment for bipolar disorder (BD). The study aimed to examine the course of BD and describe how clinical and sociodemographic factors are associated with outcomes. Methods Individuals with BD had their clinical data recorded at enrolment and were naturalistically treated. Participant were followed for up to four years, and visits occurred at least once every three months. We investigated the longitudinal outcomes with logistic, Cox, and quantile regressions. Results Among the 354 participants, 57.3% had BD type I. Depression as first episode, younger ages at onset and older ages of the first professional help predicted longer delays in correct diagnosis. Among the symptomatic patients at baseline, the median time to remission was 10.9 months. Comorbid alcohol use disorder and the severity of baseline depressive symptoms predicted longer times to remission. Among the euthymic participants, the median time to recurrence was 14.5 months. History of anxiety disorder and younger ages at onset predicted shorter times to recurrence. Baseline depression scores predicted recurrence in euthymic patients. Limitations We did not investigate the predictors of each polarity. Our findings may not apply to individuals followed in non-specialised outpatient services. Conclusion Our study reinforces the necessity of early diagnosis and interventions, as well as the importance of treating depressive symptoms and comorbidities.

Background Prescribers at a 400-bed metropolitan teaching hospital applied for approval to prescribe restricted antimicrobials using Guidance DS® (GDS), an electronic antimicrobial approval system (EAAS). The implementation of Cerner Millennium® (CM), a computerised physician order entry system (CPOE), necessitated a new but cumbersome workflow for prescribers. This prompted an evaluation of the value of a stand-alone EAAS, which has no interface with a CPOE, for antimicrobial stewardship. Aim This study compares the performance of an EAAS and CPOE, used alone and in combination, for surveillance of restricted antimicrobials and compliance with antimicrobial restriction policy. Method General medical and surgical patients prescribed restricted antimicrobials over three defined periods were retrospectively recruited; period one (P1) used GDS plus National Inpatient Medication Chart, period two (P2), GDS plus CM, and period three (P3), CM alone. For each period, 100 medical and 100 surgical restricted antimicrobial orders were collected. Data collection included prescribing date, indication, approvals obtained, and time to approval. Surveillance rate and compliance was compared. Results The introduction of CM improved surveillance from 10.5% (P1) to 65% (P2) and 100% (P3) via a CM reporting module (p < 0.0001). Compliance improved from 6% (P1), to 55% (P2) and 76% (P3) (p < 0.0001). Documentation of a clear/complete indication improved from 10% (P1) to 56.5% (P2) and 76.5% (P3) (p < 0.0001). Approvals obtained within 24 h of prescribing improved from 61.9% (P1), to 96.9% (P2), and 100% (P3). Conclusion Cerner Millennium®, with customisation, optimises surveillance and significantly improves compliance with policy, negating the need for a stand-alone EAAS.

Objective: Previous studies reported decreased N-acetyl aspartate and increased Glx (the sum of glutamate plus glutamine) in bipolar disorder. Since these studies included patients at different stages of illness, it is unknown whether these changes have a causal role or a consequence of multiple episodes and treatments. The studies in early-stage bipolar disorder patients have the potential to provide answers to these issues. Therefore, we evaluated N-acetyl aspartate and Glx levels in hippocampi of first-episode bipolar disorder patients and health subjects at baseline and at 12 months, and examined the impact of episode recurrence on these measures. Method: We used single-voxel proton magnetic resonance spectroscopy to compare the hippocampal neurometabolites ( N-acetyl aspartate and Glx) levels between 41 patients with bipolar disorder following recovery from their first-manic episode and 27 matched healthy subjects at recruitment and 12 months later. We also compared N-acetyl aspartate and Glx levels between patients who had a recurrence of a mood episode and those who did not. Results: There was no main effect of either group (diagnosis) or time for hippocampal N-acetyl aspartate and Glx levels in bipolar disorder patients and healthy subjects. We also did not find any group-by-time interaction for the levels of these metabolites. There were also no differences in N-acetyl aspartate and Glx between patients who experienced a recurrence of a mood episode and those who did not over 12-month follow-up. Conclusion: Our data suggest that N-acetyl aspartate and Glx levels are not altered in early stage bipolar disorder. Further, these data suggest that episode recurrence in early stages does not have a significant impact on the levels of these metabolites. These may suggest that there may be an early window for intervention to potentially arrest neuroprogression of the disease.

Bipolar I disorder (BD) is associated with increased inflammation, which is believed to be central to disease etiology and progression. However, BD patients also have high rates of obesity, itself an inflammatory condition, and the relative contributions of mood illness and obesity to inflammation are unknown. Moreover, the impact of inflammation on clinical illness course has not been well studied. The objectives of this analysis were therefore: (1) to determine if inflammation in BD is mood illness-related or secondary to elevated body mass index (BMI), and (2) to investigate the impact of inflammation on prospectively-ascertained relapse into depression and mania. We measured the serum levels of 7 inflammatory cytokines (TNF-α, γ-interferon, monocyte chemoattractant protein-1 [MCP-1], IL-1α, IL-2, IL-6, and IL-8) and 2 anti-inflammatory cytokines (IL-4 and IL-10) in 52 early-stage BD patients and 22 healthy subjects. In patients, a multivariate multiple regression model that controlled for psychotropic medications found that higher BMI, but not recent (past-6-month) mood episodes, predicted greater inflammatory cytokines (p=.05). Healthy subjects also had a BMI-related increase in inflammatory cytokines (p

TPS4119 Background: Successful treatment of patients with colorectal peritoneal carcinomatosis highly depends on complete surgical tumor resection of all tumor. Oncological outcomes can potentially be improved by intraoperative imaging using a tumor-targeting antibody conjugated to a fluorophore and a radiotracer. This enables preoperative radionuclide imaging, real-time intraoperative fluorescence imaging and gamma detection. In this study we investigate the feasibility, accuracy and safety of CEA-targeted preoperative SPECT/CT and intraoperative fluorescence imaging in patients with colorectal PC. Methods: In this phase I/II single arm protein dose escalation study patients with peritoneal metastases of colorectal origin who are scheduled for cytoreductive surgery and HIPEC will receive an intravenous injection of the CEA-targeting tracer 111In-DOTA-labetuzumab-IRDye800CW. The first 15 patients will receive a single dose of 2,10 or 50 mg 6 to 7 days prior to surgery. Four to five days after injection SPECT/CT imaging of the thorax and abdomen is performed to determine intra-abdominal tumor load and detect extra-abdominal metatases. At day 6/7 after injection, standard cytoreductive surgical resection extended with real-time near-infrared fluorescence imaging and radio guidance is performed. After surgery, the peritoneal cavity will be re-examined for residual disease with fluorescence imaging. Resected specimens are analyzed microscopically, immunohistochemically (CEA and H&E) and by gamma counting. Blood samples are drawn for farmacokinetics and safety analysis at 180 minutes, 4 days, 6 days and 3 weeks after tracer injection. In the phase II dose expansion cohort, 14 more patients will receive the optimal dose as determined in the phase I trial. The primary objectives of the trial are to assess the safety, feasibility and accuracy of preoperative SPECT/CT and intraoperative fluorescence imaging after administration of 111In- labetuzumab-IRDye800CW in patients with peritoneal carcinomatosis of colorectal origin who will undergo cytoreductive surgery and HIPEC. The secondary objectives are to assess whether additional malignant lesions can be visualized by fluorescence imaging after cytoreductive surgery, to assess the intensity of fluorescence in malignant and non-malignant tissue, to assess the correlation between localization of the dual-labeled antibody and CEA expression in tumor and healthy tissue and to determine blood concentrations of the dual labelled antibody at several time points in patients. Clinical trial information: NCT03699332 .

Verbal memory (VM) impairment is a trait feature of bipolar I disorder (BDI) that is present at illness onset and associated with functional outcome. However, little is known about the morphological abnormalities underlying this deficit early in the disease course. This study examined the neurobiological correlates of VM impairment in euthymic newly diagnosed patients, with attention to frontal and medial temporal (MT) structures known to contribute to VM.Euthymic patients with BDI recently recovered from their first episode of mania (n = 42) were compared with healthy subjects (n = 37) using measures of the California Verbal Learning Test (CVLT-II) associated with frontal and MT functioning. A subset of participants had 3T MRI scan (n = 31 patient group, n = 30 healthy subject group). Hippocampal and prefrontal volumes were analyzed using FreeSurfer 5.1 and correlated with their corresponding CVLT-II subscores.Patients showed decreased performance in total learning as well as short and long delay verbal recall. Consistent with MT dysfunction, they also showed deficits in recognition discriminability and learning slope. In the patient group only, left hippocampal volumes were negatively correlated with these measures.These results suggest that anomalous MT functioning is involved with VM impairment early in the course of BDI.

In bipolar disorder (BD), lithium and valproate are both reportedly associated with mild cognitive deficits with impaired psychomotor speed and verbal memory ascribed to both while impairments in learning and attention are mainly attributed to valproate. However, there are few direct comparisons of the impact of lithium and valproate on cognitive function in early BD. Using data from the STOP-EM study, we compared neurocognitive functioning in BD patients, who had recently recovered from a first episode of mania, and were on treatment with lithium (n = 34) or valproate (n = 38), to a comparable sample of healthy controls (HC; n = 40), on the domains of processing speed, attention, verbal memory, nonverbal memory, working memory and executive functions. The three groups were comparable on socio-demographic (all p0.12) and clinical variables (all p0.08). MANOVA revealed a significant difference between the three groups on overall cognitive functioning (Wilk's lambda = 0.644; F = 3.775; p0.001). On post-hoc Tukey test, the valproate group performed poorer on working memory compared to the lithium (p = 0.001) and HC groups (p0.001). There was no significant difference between the lithium and valproate groups on other cognitive domains (all p0.13). Treatment with valproate and not lithium may be associated with working memory deficits early in the course of BD.

Background Psychosis in bipolar I disorder (BDI) has been associated with increased cognitive dysfunction, which may relate to poorer functional outcomes. However, it is not known whether cognition differs between BDI patients with (BDP+) or without (BDP-) history of psychosis early in the disease course, or if it is impacted by the presence of mood congruent (MCP) versus incongruent (MIC) psychotic features. We compare cognition between these groups in BDI patients recently recovered from first episode of mania. Methods Attention, verbal learning/memory, processing speed and executive functioning were compared between: 1) all BDI patients (n = 73) and healthy controls (HC, n = 45), 2) BDP+ (n = 60) and BDP- (n = 13) patients and 3) MCP (n = 27) and MIC (n = 33) patients. Post-hoc analyses compared all patient groups with HC. Results While BDI patients performed worse than HC in all domains, there were no significant differences between BDP+ and BDP-, or MCP and MIC, patients. However, BDP+ and MIC groups demonstrated different patterns of impairment compared to HC then did BDP- or MCP. Executive functioning and cognitive flexibility in particular appeared to be a deficit area in BDP+ patients. Limitations This study may have been underpowered to detect differences in direct comparison between BDP+ and BDP- patients. Conclusion While replication in larger samples is required, these results suggest that subtle cognitive differences between BDP+ and BDP-, and between MIC and MCP, patients may be present shortly after disease onset. These patient subsets may therefore be of interest in examining early intensive strategies to preserve cognition.

Objective: Obesity is frequent in people with bipolar I disorder (BD I) and has a major impact on the course of the illness. Although obesity negatively influences cognitive function in patients with BD, its impact in the early phase of the disorder is unknown. We investigated the impact of overweight and obesity on cognitive functioning in clinically stable patients with BD recently recovered from their first manic episode. Method: Sixty-five patients with BD (25 overweight or obese and 40 normal weight) recently remitted from a first episode of mania and 37 age- and sex-matched healthy control subjects (9 overweight or obese and 28 normal weight) were included in this analysis from the Systematic Treatment Optimization Program for Early Mania (commonly referred to as STOP-EM). All subjects had their cognitive function assessed using a standard neurocognitive battery. We compared cognitive function between normal weight patients, overweight-obese patients, and normal weight healthy control subjects. Results: There was a negative affect of BD diagnosis on the domains of attention, verbal memory, nonverbal memory, working memory, and executive function, but we were unable to find an additional effect of weight on cognitive functioning in patients. There was a trend for a negative correlation between body mass index and nonverbal memory in the patient group. Conclusions: These data suggest that overweight-obesity does not negatively influence cognitive function early in the course of BD. Given that there is evidence for a negative impact of obesity later in the course of illness, there may be an opportunity to address obesity early in the course of BD.

Cognitive impairments are present immediately following recovery from a first episode of mania, although at a lesser severity than those seen in more chronic patients with bipolar I disorder. Little is known about how deficits evolve over the course of illness, however, and whether these changes are associated with disease progression.Patients with bipolar I disorder (DSM-IV-TR) receiving naturalistic clinical follow-up from the Systematic Treatment Optimization Program for Early Mania (STOP-EM) from July 2004 to May 2013 completed a comprehensive cognitive battery following recovery from their first manic episode and again 1 year later. Performance was compared between patients who experienced a recurrence of a mood episode (BDrecur) (n = 26) versus those that maintained remission (BDwell) (n = 27) over follow-up, as well as healthy comparison subjects (HS) (n = 31).While both BDrecur and BDwell had impairments in overall cognitive performance relative to HS at baseline (mean difference = -0.59, P.001; mean difference = -0.43, P.05, respectively), at follow-up BDrecur showed deficits compared to both HS (mean difference = -0.62, P = .001) and BDwell (mean difference = -0.41, P = .05), with BDwell cognition similar to that in HS (mean difference = -0.21, P.4). BDwell showed larger improvements over follow-up relative to both other groups (P.05). While changes in BDrecur did not differ from HS, in this group more days in a manic or hypomanic episode was associated with performance declines (r = -0.40, P.05).While cognitive function improves in patients who sustain remission in the year following a first manic episode, those who experience a recurrence remain impaired, with performance declines being most apparent in those who experienced longer manic or hypomanic episodes.

Studies investigating bipolar disorder (BD) showed that healthy patterns of sex differences in cognitive functioning are altered within this population, but is it unknown whether these alterations are present in BD patients early in their course of illness.Patients with bipolar I disorder (36 males, 38 female), who had recently experienced their first manic or mixed episode were tested along with healthy controls (39 males, 59 females) similar in age, sex and premorbid IQ. Cognitive function was assessed through a comprehensive neuropsychological test battery.Significant group effects were found in a majority of administered tests (p0.05) with patients performing worse than healthy controls. Significant sex effects (p0.05) were observed on tasks of spatial working memory and sustained attention, with males performing better than females. No significant group by sex interaction was found in any of the tasks administered.The cognitive battery employed in this study may not have been optimally sensitive in detecting sex differences.The results suggest that unlike patients with long standing multi-episode BD or schizophrenia, healthy cognitive sex differences are maintained in patients with early BD, following recovery from a first-episode of mania. These findings highlight the progressive nature of the illness and provide justification for an early intervention.

Adenomyoepithelioma (AME) is a biphasic neoplasm of epithelial and myoepithelial cells. It is most commonly found in the breast, although rare cases have been reported from the lung, salivary glands, and skin. There are 5 well-documented cases of cutaneous AME in the literature. We report a new case of cutaneous AME. Our case was commingled with apocrine hidrocystoma. This is the first report of cutaneous AME in a male patient and the first to describe SOX10 immunostaining in cutaneous AME. We review the literature on cutaneous AME and note the greater than chance colocalization with other adnexal tumors. We speculate that AME may represent localized overgrowth of myoepithelial cells within a pre-existent sweat gland tumor. Histopathologists should be aware of the potential of SOX10-positive myoepithelial neoplasms to mimic nodular melanocytic proliferations.

Background Our health service is introducing an electronic medication management system (eMMs). Obtaining baseline data on the work patterns of pharmacists will allow assessment of the impact of the eMMs on pharmacists' work patterns. Aim To quantify the time clinical pharmacists spend on various activities over their working day prior to the implementation of an eMMs. Method During this continuous observational time-and-motion study (23 November to 17 December 2009), clinical pharmacists assigned to general medical and surgical wards were shadowed by two independent observers over their entire working days. A customised Access application was used to log times and calculate average times spent on each activity. Other data collected included time from admission to interview and opportunities for medication chart review. Results 9 pharmacists were observed for 265.3 hours over 30 separate pharmacist observation days. Clinical activities (56% of total time) included professional communication (20%), medication chart review (9.6%), medication history interview (9.5%), clinical review (9.1%), providing information to patients/carers (5.5%), ascertaining discharge drugs required (1.6%), and obtaining drug information (0.5%). Non-clinical activities (44% of total time) included social activities/breaks (13%), meetings (6.9%), ordering/distribution (6.6%), discharge dispensing (6.3%), walking between wards/pharmacy (5.2%), looking for something (3.1%), and other activities (2.8%). On an average day, each pharmacist reviewed 21 of a possible 38 medication charts (55%), spent 20 minutes on clinical interventions and completed 4.5 medication history interviews. Average time from admission to interview was 67 hours. 18% of pharmacists' time was taken up with discharge/transfer of patients. Most patients 130/141 (93%) at discharge did not require further medication history clarification. Conclusion This study provides baseline data for comparison of the impact of the eMMs on pharmacist workflow.

Although associations between antipsychotic use and neuropsychological impairment in bipolar I disorder have been observed, there is a lack of studies comparing the effects of specific agents used in this population. We compared performance between patients receiving maintenance treatment with mood stabilizer monotherapy (n=15), adjunctive risperidone (n=15) or quetiapine (n=17), and a group of demographically matched healthy controls (n=28) on tests of executive function (working memory, set shifting, and inhibition) and verbal learning. Despite having a similar clinical profile, patients being treated with risperidone showed significantly impaired working memory, set-shifting, and verbal learning (P0.05) compared with those either on mood stabilizer monotherapy or adjunctive quetiapine. Although randomized controlled trials are required to confirm the cognitive side effects of medications prescribed for maintenance treatment of bipolar I disorder, preliminary results indicate that addition of risperidone to a mood stabilizer has a negative impact on executive function and verbal learning, an effect not shared with quetiapine.

Aim: To describe the implementation of pharmacist-initiated e-script transcription service (PETS) in a teaching hospital; to validate the service through process indicators; and to explore the views of stakeholders. Method: Following an initial trial, PETS was implemented in 7 medical and surgical units at Frankston Hospital. Data were collected on activities and discharge prescription errors. Stakeholders' satisfaction was measured using a Likert scale based survey and group interviews. Transcripts of group interviews were analysed by informal word-based techniques, noting words or synonyms used repeatedly to discover themes. Results: During the implementation phase (8 to 29 February 2008), a daily average of 15 prescriptions (112 items) were prepared by the PETS pharmacist, i.e 30 to 60% of weekday discharge prescriptions. The discharge prescription error/ amendment rate was 0.06 per patient. 163 respondents (92%) were satisfied or very satisfied with PETS. As a result of 3 group interviews of 10 doctors, 10 nurses and 10 pharmacists, several areas for enhancement were identified and implemented. Conclusion: PETS has transitioned from trial to mainstream service, facilitating the discharge process and improving continuity of care.

Aim: To evaluate a pharmacist-initiated e-script transcription service for discharged patients. Method: A sequential prospective study of 2 groups of 40 eligible medical patients recruited from the neurology and respiratory wards. Pre-implementation of the service, baseline data were collected from 40 consecutive medical patients. After the new service was implemented and allowing for a 2 week run-in period, data were collected from a further 40 consecutive medical patients. The outcome indicators were the time taken to discharge patients and the number of prescribing errors. Results: The pharmacist-initiated e-script transcription service was successfully implemented. The discharge process was faster with the time taken from decision to discharge to actual discharge decreased by 34% (p = 0.02). The time spent by dispensing pharmacists in clarifying and amending discharge prescriptions decreased from 9.5 to 1.5 minutes per patient. The time spent by doctors in preparing discharge prescriptions fell from 15 to 2 minutes per patient. There were also fewer prescribing errors – number of errors decreased from 0.83 to 0.1 per patient (p = 0.0005) and from 0.0962 to 0.0137 per item (p = 0.011). Conclusion: Combining a prescribing role with the medication safety elements of electronic prescribing and medication reconciliation has resulted in significant improvements in the quality, accuracy and timeliness of discharge prescriptions. The centralised discharge transcription service is transferable to a wide variety of health settings. The principles of workforce substitution and process change is important as the health system struggles to meet ever increasing demands. J Pharm Pract Res 2009; 39: 39-42.

Purpose: This paper describes a process for the identification of genes that can report on the aggressiveness of prostate tumors and thereby add to the information provided by current pathologic analysis. Materials and Methods: Expression profiling data from over 100 laser capture microdissection derived samples from nonneoplastic epithelium; Gleason patterns 3, 4, and 5 and node metastasis prostate cancer were used to identify genes at abnormally high levels in only some tumors. These variably overexpressed genes were stratified by their association with aggressive phenotypes and were subsequently filtered to exclude genes with redundant expression patterns. Selected genes were validated in a case-control study in which cases (systemic progression within 5 years) and controls (no systemic progression at 7 years of follow-up) were matched for all clinical and pathologic criteria from time of prostatectomy (n = 175). Both cases and controls, therefore, could have nodal invasion or seminal vesicle involvement at the time of initial treatment. Results: A number of candidate variably overexpressed genes selected for their association with aggressive prostate cancer phenotype were evaluated in the case control study. The most prominent candidates were SSTR1 and genes related to proliferation, including TOP2A. Conclusions: The process described here identified genes that add information not available from current clinical measures and can improve the prognosis of prostate cancer.

Objectives Bipolar I disorder (BD-I) is associated with gray matter volume (GMV) alterations in neural regions important for emotional regulation. Reductions found in patients with multiple episodes are not seen at illness onset, suggesting that changes occur with illness progression, although no prospective studies to date have examined this. In the present study, we assessed GMV at baseline and one year following a first manic episode, examining the impact of episode recurrence on the trajectory of change. Methods A total of 41 recently remitted first manic episode patients with BD-I and 25 healthy subjects (HS) underwent 3T magnetic resonance imaging at baseline and one year later. Using voxel-based morphometry, we compared GMV change between HS, patients who experienced a recurrence of a mood episode (BDrecurr), and patients in sustained remission (BDwell). Results The GMV change from baseline to one year did not differ significantly between HS and the full BD-I group or BDwell and HS. However, the BDrecurr group had greater GMV loss than HS in left frontal and bilateral temporal regions, and BDwell patients involving bilateral frontal, temporal and left parietal regions. Conclusions GMV change early in the course of BD-I is associated with clinical outcome, such that neuroprogression found in patients who experience a recurrence of a mood episode is not seen in those with sustained remission. These findings have important implications for the treatment of BD-I as they suggest that prevention of recurrence might minimize neuroprogression of the disease, possibly requiring a multipronged early intervention approach to achieve this goal.

The aim of this study was to demonstrate that telehomecare linking homebound patients with their home health-care nurses over the plain old telephone system (POTS) provides high-quality, clinically useful, and patient satisfactory interactions. Congestive heart failure, chronic obstructive pulmonary disease, and chronic wound-care patients receiving skilled home nursing care were randomized into control (standard home health care, HHC) and two intervention (standard care plus video conferencing/Internet access; the above plus physiological monitoring) groups. Virtual visits (VVs), consisting of two-way audio and video interactions between the central site HHC nurse and the subject at home, were compared for technical quality and clinical usefulness by the HHC nurses who performed the VVs. Subject perception of telehomecare and satisfaction with their HHC were assessed over the course of the project. There were a total of 567 virtual and 1,057 actual visits conducted for the 53 subjects completing the study. The technical quality of VVs were rated at 94.7%. They were considered to be as useful as actual visits in 90.7% of cases. Subject telehomecare perception increased after experiencing the process. All subjects were satisfied with their HHC; satisfaction increased with an increasing level of telehomecare intervention. Subjects receiving physiological monitoring and video conferencing/Internet access in addition to standard care were most satisfied with their care. VVs can be conducted over POTS. Patients can use telehomecare with moderate levels of training. These programs can provide timely and quality home health nursing care with VVs augmenting traditional home visits.

Several studies have reported cognitive functioning as a significant predictor of quality of life (QoL) in patients with established bipolar disorder (BD), in addition to mood symptoms. However, it is unclear whether cognitive functioning predicts QoL early in the course of illness. The purpose of this study was therefore to evaluate the relationship between mood and neuropsychological variables and self-reported QoL early in the course of BD.Patients with BD-I (n=54) completed a neuropsychological battery and clinical assessment within 3 months of resolution of their first manic episode. QoL was assessed 6 months later using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Cognitive predictors of QoL were assessed through Pearson correlations and hierarchical multiple regression.After accounting for mood rating scores at the time of cognitive testing (ΔR²=.27, p.001), measures of sustained attention (ΔR²=.08, p.05), verbal memory (ΔR²=.09, p.01), working memory (ΔR²=.06, p.05), and executive functioning (ΔR²=.08, p.05) each predicted QoL when entered independently in separate regression models. When entered simultaneously, the cognitive domains explained 15% (R(2)=.42, p.05) of the variance in QoL beyond mood.Some aspects of QoL that are particularly important in BD may be missing as a result of using the Q-LES-Q, because the measure was not specifically developed to assess QoL in BD.In addition to mood symptoms, poorer cognitive functioning is a significant predictor of reduced QoL early in the course of BD. Recently diagnosed patients with BD may benefit from early cognitive-enhancing interventions to maintain or restore their QoL.

BackgroundAlthough manic episodes reportedly contribute to cognitive deficits in bipolar I disorder, the contribution of depressive episodes is poorly researched.AimsWe investigated the impact of depressive episodes on cognitive function early in the course of bipolar I disorder.MethodA total of 68 patients and 38 controls from the Systematic Treatment Optimization Programme for Early Mania (STOP-EM) first-episode mania programme were examined. We conducted (a) a cross-sectional analysis of the impact of prior depressive episodes on baseline cognitive function and (b) a prospective analysis assessing the contribution of depression recurrence within 1 year following a first episode of mania on cognitive functioning.ResultsThe cross-sectional analysis showed no significant differences between patients with past depressive episodes compared with those without, on overall or individual domains of cognitive function (allP>0.09). The prospective analysis failed to reveal a significant group×time interaction for cognitive decline from baseline to 1 year (P= 0.99) in patients with a recurrence of depressive episodes compared with those with no recurrence. However, impaired verbal memory at baseline was associated with a depression recurrence within 1 year.ConclusionsAlthough deficits in all domains of cognitive function are seen in patients early in the course of bipolar disorder, depressive episodes do not confer additional burden on cognitive function. However, poorer verbal memory may serve as a marker for increased susceptibility to depression recurrence early in the course of illness.

Over 880 communities have put regulations in place to reduce or eliminate tobacco use in buildings used by the public. This study examines the experience of one such community—Well City, Ohio. The nonsmoker protection efforts in Well City help us identify and discuss eight important considerations affecting policy development and implementation: (1) anticipate community opposition, (2) identify and collaborate with a support network, (3) control the community hearing process, (4) anticipate outside interests, (5) recognize the potential for legal challenges, (6) address life with legal limbo, (7) start strong, and (8) watch the mix of politics and public health. Current clean indoor air efforts seem to focus on establishing coalitions and encouraging employers to voluntarily establish tobacco-free workplaces and restaurants. These efforts certainly need to continue but as a basic part of a comprehensive program which recognizes the importance and fosters the development of strong nonsmoker protection regulations developed at the local level by health boards, county boards of supervisors, and/or city councils.

Childhood trauma (CT) has been associated with abnormalities in the corpus callosum (CC). Decreased CC volumes have been reported in children and adolescents with trauma as well as adults with CT compared to healthy controls. CC morphology is potentially susceptible to the effects of Bipolar Disorder (BD) itself. Therefore, we evaluated the relationship between CT and CC morphology in BD. We using magnetic resonance imaging in 53 adults with BD recently recovered from their first manic episode, with (n = 23) and without (n = 30) CT, defined using the Childhood Trauma Questionnaire (CTQ) and 16 healthy controls without trauma. ANCOVA was performed with age, gender and intracranial volume as covariates in order to evaluate group differences in CC volume. The total CC volume was found to be smaller in BD patients with trauma compared to BD patients without trauma (p < .05). The differences were more pronounced in the anterior region of the CC. There was a significant negative correlation between CTQ scores and total CC volume in BD patients with trauma (p = .01). We did not find significant differences in the CC volume of patients with/without trauma compared to the healthy subjects. Our sample consists of patients recovered from a first episode of mania and are early in the course of illness and reductions in CC volume may occur late in the course of BD. It might mean there may be two sources of CC volume reduction in these patients: the reduction due to trauma, and the further reduction due to the illness.

Hypoxia has been associated with malignant progression, metastasis and resistance to therapy. Hence, we studied expression of hypoxia-regulated genes in 100 prostate cancer (CaP) bulk tissues and 71 adjacent benign tissues. We found 24 transcripts significantly overexpressed (p ≤ 0.02). Importantly, higher transcript levels of disc large (drosophila) homolog-associated protein 5 (DLGAP5)/discs large homolog 7 (DLG7)/hepatoma up-regulated protein (HURP), hyaluronan-mediated motility receptor (HMMR) and cyclin B1 (CCNB1) were associated with higher Gleason score and more advanced systemic progression. Since the products of HMMR and CCNB1 have been identified recently as molecular markers of CaP progression, we postulated that DLG7 has prognostic value too. To test this hypothesis, we measured transcript levels for DLG7 in a 150-pair case-control cohort. The cases (progression to systemic disease within six years of surgery) and controls (no progression within eight years) were matched for clinical and pathologic prognostic variables, including grade, stage, and preoperative serum levels of PSA. The overall prognostic ability of DLG7, as tested in receiver operating characteristic analysis was of 0.74 (95% CI, 0.68 to 0.8). Overall, our data indicate that expression of DLG7, a hypoxia-controlled gene, holds prognostic potential in high-risk CaP; this also demonstrates that variation of oxygen tension may constitute a tool for identification of novel biomarkers for CaP.

Objectives Although cognitive deficits are observed in the early stages of bipolar disorder, the longitudinal course of neuropsychological functioning during this period is unknown. Such knowledge could provide etiologic clues into the cognitive deficits associated with the illness, and could inform early treatment interventions. The purpose of the present study was to evaluate cognitive change in bipolar disorder in the first year after the initial manic episode. Methods From an initial pool of 65 newly diagnosed patients with bipolar disorder (within three months of the end of the first manic or mixed episode) and 36 demographically similar healthy participants, 42 patients [mean age 22.9 years, standard deviation (SD) = 4.0] and 23 healthy participants [mean age 22.9 years (SD = 4.9)] completed baseline, six-month, and one-year neuropsychological assessments of multiple domains including processing speed, attention, verbal and nonverbal memory, working memory, and executive function. Patients also received clinical assessments, including mood ratings. Results Although patients showed consistently poorer cognitive performance than healthy individuals in most cognitive domains, patients showed a linear improvement over time in processing speed (p = 0.008) and executive function (p = 0.004) relative to the comparison group. Among patients, those without a history of alcohol/substance abuse or who were taken off an antipsychotic treatment during the study showed better improvement. Conclusions The early course of cognitive functioning in bipolar disorder is likely influenced by multiple factors. Nevertheless, patients with bipolar disorder showed select cognitive improvements in the first year after resolution of their initial manic episode. Several clinical variables were associated with better recovery, including absence of substance abuse and discontinuation of antipsychotic treatment during the study. These and other factors require further investigation to better understand their contributions to longitudinal cognitive functioning in early bipolar disorder.

Immunosuppressive therapies that block the CD40/CD154 costimulatory pathway have proven to be uniquely effective in preclinical xenotransplant models. Given the challenges facing clinical translation of CD40/CD154 pathway blockade, we examined the efficacy and tolerability of CD40/CD154 pathway-sparing immunomodulatory strategies in a pig-to-nonhuman primate islet xenotransplant model. Rhesus macaques were rendered diabetic with streptozocin and given an intraportal infusion of ≈ 50 000 islet equivalents/kg wild-type neonatal porcine islets. Base immunosuppression for all recipients included maintenance therapy with belatacept and mycophenolate mofetil plus induction with basiliximab and LFA-1 blockade. Cohort 1 recipients (n = 3) were treated with the base regimen alone; cohort 2 recipients (n = 5) were additionally treated with tacrolimus induction and cohort 3 recipients (n = 5) were treated with alefacept in place of basiliximab, and more intense LFA-1 blockade. Three of five recipients in both cohorts 2 and 3 achieved sustained insulin-independent normoglycemia (median rejection-free survivals 60 and 111 days, respectively), compared to zero of three recipients in cohort 1. These data show that CD40/CD154 pathway-sparing regimens can promote xenoislet survival. Further optimization of these strategies is warranted to aid the clinical translation of islet xenotransplantation.

The objective of this study was to assess the relationship of the tumor protein levels of TOP2A and MIB-1 and ERG status with cancer-specific outcomes in men with high-risk prostate cancer treated by radical prostatectomy (RP). A 150-pair case-control study was designed from RP patients who developed systemic progression (SP) within 6 years of RP (cases) and men who were free of disease at least 8 years after RP (controls). The cases and controls were matched on conventional prognostic clinical parameters. TOP2A and MIB-1 levels were assessed by immunohistochemical methods, and ERG status was assessed by quantitative reverse transcription-PCR. The prognostic abilities of TOP2A and MIB-1 were significantly better in ERG(−) patients, and TOP2A was superior to MIB-1. In receiver operating characteristic analysis, the TOP2A and MIB-1 scores exhibited AUCs of 0.81 and 0.78 for ERG(−) patients, versus 0.67 and 0.68 for ERG(+) patients, respectively. Clinical parameters attained an AUC of 0.65 in ERG(−) patients and 0.54 in ERG(+) patients. When both markers were incorporated into a model for ERG(−) patients, the AUC increased to 0.83, with TOP2A showing a stronger association with SP than MIB-1. The time to SP was significantly associated with TOP2A; higher 5-year SP rates were observed in patients with higher TOP2A protein levels. In addition, although patient numbers are small, the response to adjuvant androgen deprivation therapy is associated with ERG status, showing more significant treatment effect in ERG(+) patients. Cancer Res; 70(22); 8994–9002. ©2010 AACR.

ETS variant 1 (ETV1), also known as ETS-related protein 81, is overexpressed in prostate tumors, but whether and how this transcription factor affects tumorigenesis has remained elusive. Here, we show that ETV1 is primarily overexpressed in the most aggressive human prostate tumors. Transgenic ETV1 mice developed prostatic intraepithelial neoplasia as well as hyperplasia/neoplasia in seminal vesicles. Moreover, ETV1 cooperated with the androgen receptor (AR) to bind to the prostate-specific antigen enhancer and stimulate gene transcription. Consistent with its ability to physically interact with AR, ETV1 rendered an ETV1 binding site–driven reporter androgen inducible, and, on the other hand, ETV1 superinduced transcription from an AR binding site on androgen stimulation. In conclusion, our study substantiates that ETV1 overexpression is an underlying cause in the development of prostate and possibly also seminal vesicle cancer. Its interaction with and activation of AR provides a molecular mechanism on how ETV1 exerts its deleterious function. Thus, inhibiting ETV1 or blocking its interaction with AR may represent novel strategies in prostate cancer therapy. [Cancer Res 2009;69(20):8102–10]

Thirty patients with chemotherapy-induced anemia were treated with recombinant human erythropoietin for 4 weeks. In this dose-escalation study, cohorts of five to eight patients were treated per dose level. The doses of erythropoietin were 25, 50, 100, 200, or 300 IU/kg/d given intravenously for 5 days each week. Of 30 patients, 15 (50%) had a greater than 10% increase of their hemoglobin (Hb) values and were considered responders. At the two highest dose levels, 11 of 13 patients (85%) responded. In the 15 responding patients, the mean Hb level increased by 1.7 g/dL from baseline compared with an average decrease of 1.5 g/dL in the previous cycles of chemotherapy without erythropoietin administration. Recombinant human erythropoietin is effective in ameliorating chemotherapy-induced anemia when administered in adequate doses.

Background. Pulsed dye laser treatment of port-wine stains is safe and effective. However, the pain associated with this treatment is often difficult to tolerate, especially for children. A laser-coupled delivery system known as dynamic epidermal cooling has recently been developed to improve local anesthesia. Objective. To report laser ignition of a commercially-available, hand-held cryogen spray used for local anesthesia, and describe possible mechanisms of the fire; to define the chemical characteristics of other skin coolants suitable and unsuitable for skin cooling with laser treatment. Methods. Case report and literature review. Conclusions. Clinicians must be aware of the thermodynamic properties, potential for skin damage, cost and environmental consequences of commercially available cryogens before considering their use for topical anesthesia with laser surgery.

Tumor-associated hypoxia has been associated with malignant progression, metastasis, resistance to therapy, and poor clinical outcome in prostate cancer (CaP). Prompted by the evidence that hypoxia affects CaP, we studied global gene expression in 100 CaP tissues and 71 samples of adjacent benign tissues. RNA was extracted from cancer cells isolated by laser-capture microdissection (LCM) or without isolation (“bulk tissue”). We found 24 hypoxia-associated genes significantly overexpressed in CaP (p≤0.02), both in bulk tissue and LCM. Among hypoxia-associated genes, the disc large (drosophila) homolog-associated protein 5 (DLG7), hyaluronan-mediated motility receptor (HMMR) and cyclin B1 (CCNB1) were associated with Gleason score and systemic progression. Since the products of HMMR and CCNB1 have been recently identified as molecular markers of CaP progression, we postulated that DLG7 has prognostic value also. To test this hypothesis we measured transcript levels for DLG7 in a 150-pair case-control cohort. The cases (progression to systemic disease within five years of surgery) and controls (no progression within seven years) were matched for clinical and pathologic prognostic variables, including grade, stage, and preoperative serum levels of PSA. The overall prognostic ability of DLG7, as tested in receiver operating characteristic analysis was of 0.74 (95% CL, 0.68 to 0.8), independent of the for ERG status. Overall, our data indicate that DLG7, a hypoxia-controlled gene have a prognostic value in high-risk CaP. To better define the value of DLG7 as a molecular predictor of CaP progression, we are currently assessing DLG7 protein levels by immunohistochemistry. Then we will analyze the association of DLG7 levels with clinical parameters. Introduction of oxygen tension as a variable may constitute a tool for the identification of novel biomarkers for CaP. Present address CRG: University of Mississippi Cancer Institute, Jackson, MS, USA. Support: DOD PC094680 (CRG), PCF Creativity Award (CRG), Mayo Clinic Prostate SPORE 5P50CA091956 (SV-P); Mrs. Adelyn L. Luther, Singer Island, Florida and Mayo Clinic Cancer Center (SV-P). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 116. doi:1538-7445.AM2012-116

Tumor-associated hypoxia has been associated with malignant progression, metastasis and resistance to therapy. We studied the role of oxygen tension (pO2) in modulating the properties of cultured human prostate cancer (CaP) cells. In air, where oxygen tension (pO2) is approximately 20 kPa, cultured CaP cells expressed lower levels of transcripts associated with cancer and urologic disease; reducing pO2 to 2 kPa made these levels comparable to those in surgical CaP specimens suggesting that hypoxically cultured cells, rather than normoxically cultured cells, express genes at levels akin to those in tumor cells in situ. In human primary CaP tissue, transcripts of hypoxia-associated genes DLG7, CCNB1 and HMMR were overexpressed and associated with Gleason score and disease prognosis; this implies the potential prognostic value of these transcripts. While hypoxia affected the CaP cell proteome mostly quantitatively, it did affect expression of tumor–associated antigens and suggested the potential therapeutic relevance of the hypoxic antigenic landscape. Overall, our results suggest that hypoxia modifies cellular properties of cultured CaP cells towards a phenotype more similar to tumor cells in situ. Introduction of pO2 as a variable can constitute a tool for the identification of more effective prognostic biomarkers and development of better therapy for CaP and, possibly, other tumors. Citation Format: Christian R. Gomez, Stanimir Vuk-Pavlovic, Farhad Kosari, Jan Marie Munz, Claire Schreiber, Gaylord Knutson, Cristine Charlesworth, R. Jeffrey Karnes, John Cheville, George Vasmatzis. Prognostic value of hypoxia-associated genes in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C43.

Background: Serious and life-threatening adverse drug events are often attributed to intravenous medication administration errors. Although smart infusion pumps are increasingly being adopted by hospitals to prevent such errors, data are lacking on their effectiveness in clinical practice. Aim: To measure and characterise intravenous medication administration errors and their clinical significance before and after the implementation of smart infusion pumps. Method: In the pre-intervention period, an independent observer over 41 working days recorded the prescribing and administration details of infusions administered via the IMED Gemini Volumetric Infusion Pumps. 20 months after the introduction of the smart pumps - Alaris GP Volumetric Pump with Guardrails software - a repeat audit was conducted over 27 working days. Only infusions containing drugs that were to be incorporated into Guardrails (the medication-error-prevention software of the Alaris GP pump) were evaluated. The clinical significance of the identified errors was evaluated by 2 independent assessors (pharmacist and doctor) and rated as 'low', 'moderate', 'high' or 'extreme'. Results: In the pre-intervention period, 76 infusions (n = 432, 18%) had one or more errors compared to 25 infusions (n = 266, 9.4%) following the introduction of the smart pumps. Of the 165 infusions administered using Guardrails, only 6 infusions with errors (3.6%) were identified. When drugs were infused with the Alaris GP pumps without Guardrails, the number of errors post-intervention when compared with errors in the pre-intervention period were not statistically significant (p = 0.8). When Alaris GP pumps with Guardrails were used there were no errors of 'extreme' clinical significance and only 1 error of 'high' clinical significance compared to the pre-intervention period where 1 'extreme' and 30 errors with 'high' clinical significance were identified. Conclusion: Alaris GP pumps with Guardrails resulted in significant reductions in the number and clinical significance of intravenous medication administration errors.