PCA-induced respiratory depression simulating stroke following endoluminal repair of abdominal aortic aneurysm: a case report

<p>Abstract</p> <p>Aim</p> <p>To report a case of severe respiratory depression with PCA fentanyl use simulating stroke in a patient who underwent routine elective endoluminal graft repair for abdominal aortic aneurysm (AAA)</p> <p>Case presentation</p> <p>A 78-year-old obese lady underwent routine endoluminal graft repair for AAA that was progressively increasing in size. Following an uneventful operation postoperative analgesia was managed with a patient-controlled analgesia (PCA) device with fentanyl. On the morning following operation the patient was found to be unusually drowsy and unresponsive to stimuli. Her GCS level was 11 with plantars upgoing bilaterally. A provisional diagnosis of stroke was made. Urgent transfer to a high-dependency unit (HDU) was arranged and she was given ventilatory support with a BiPap device. CT was performed and found to be normal. Arterial blood gas (ABG) analysis showed respiratory acidosis with PaCO₂81 mmHg, PaO₂140 mmHg, pH 7.17 and base excess -2 mmol/l. A total dose of 600 mcg of fentanyl was self-administered in the 16 hours following emergence from general anaesthesia. Naloxone was given with good effect. There was an increase in the creatinine level from 90 μmol/L preoperatively to 167 μmol/L on the first postoperative day. The patient remained on BiPap for two days that resulted in marked improvement in gas exchange. Recovery was complete.</p

Identifying strategies to improve access to credible and relevant information for public health professionals: a qualitative study

BACKGROUND: Movement towards evidence-based practices in many fields suggests that public health (PH) challenges may be better addressed if credible information about health risks and effective PH practices is readily available. However, research has shown that many PH information needs are unmet. In addition to reviewing relevant literature, this study performed a comprehensive review of existing information resources and collected data from two representative PH groups, focusing on identifying current practices, expressed information needs, and ideal systems for information access. METHODS: Nineteen individual interviews were conducted among employees of two domains in a state health department – communicable disease control and community health promotion. Subsequent focus groups gathered additional data on preferences for methods of information access and delivery as well as information format and content. Qualitative methods were used to identify themes in the interview and focus group transcripts. RESULTS: Informants expressed similar needs for improved information access including single portal access with a good search engine; automatic notification regarding newly available information; access to best practice information in many areas of interest that extend beyond biomedical subject matter; improved access to grey literature as well as to more systematic reviews, summaries, and full-text articles; better methods for indexing, filtering, and searching for information; and effective ways to archive information accessed. Informants expressed a preference for improving systems with which they were already familiar such as PubMed and listservs rather than introducing new systems of information organization and delivery. A hypothetical ideal model for information organization and delivery was developed based on informants' stated information needs and preferred means of delivery. Features of the model were endorsed by the subjects who reviewed it. CONCLUSION: Many critical information needs of PH practitioners are not being met efficiently or at all. We propose a dual strategy of: 1) promoting incremental improvements in existing information delivery systems based on the expressed preferences of the PH users of the systems and 2) the concurrent development and rigorous evaluation of new models of information organization and delivery that draw on successful resources already operating to deliver information to clinical medical practitioners

Identification and validation of DOCK4 as a potential biomarker for risk of bone metastasis development in patients with early breast cancer.

Skeletal metastasis occurs in around 75% of advanced breast cancers, with the disease incurable once cancer cells disseminate to bone, but there remains an unmet need for biomarkers to identify patients at high risk of bone recurrence. This study aimed to identify such a biomarker and to assess its utility in predicting response to adjuvant zoledronic acid. We used quantitative proteomics (SILAC-MS), to compare protein expression in a bone-homed variant (BM1) of the human breast cancer cell line MDA-MB-231 with parental non-bone-homing cells to identify novel biomarkers for risk of subsequent bone metastasis in early breast cancer. SILAC-MS showed that Dedicator of cytokinesis protein 4 (DOCK4) was upregulated in bone-homing BM1 cells, confirmed by Western blotting. BM1 cells also had enhanced invasive ability compared with parental cells which could be reduced by DOCK4-shRNA. In a training Tissue Microarray (TMA) comprising 345 patients with early breast cancer, immunohistochemistry followed by Cox regression revealed that high DOCK4 expression correlated with histological grade (p=0.004) but not oestrogen receptor status (p=0.19) or lymph node involvement (p=0.15). A clinical validation TMA used tissue samples and the clinical database from the large AZURE adjuvant study (n=689). Adjusted Cox regression analyses showed that high DOCK4 expression in the control arm (no zoledronic acid) was significantly prognostic for first recurrence in bone (HR 2.13, 95%CI 1.06-4.30, p=0.034). No corresponding association was found in patients who received zoledronic acid (HR 0.812, 95%CI 0.176-3.76, p=0.790), suggesting that treatment with zoledronic acid may counteract the higher risk for bone relapse from high DOCK4-expressing tumours. High DOCK4 expression was not associated with metastasis to non-skeletal sites when these were assessed collectively. In conclusion, high DOCK4 in early breast cancer is significantly associated with aggressive disease and with future bone metastasis and is a potentially useful biomarker for subsequent bone metastasis risk

Alignment of Biological Sequences with Jalview

In this chapter, we introduce core functionality of the Jalview interactive platform for the creation, analysis, and publication of multiple sequence alignments. A workflow is described based on Jalview's core functions: from data import to figure generation, including import of alignment reliability scores from T-Coffee and use of Jalview from the command line. The accompanying notes provide background information on the underlying methods and discuss additional options for working with Jalview to perform multiple sequence alignment, functional site analysis, and publication of alignments on the web

Effects of Two Commercial Electronic Prescribing Systems on Prescribing Error Rates in Hospital In-Patients: A Before and After Study

In a before-and-after study, Johanna Westbrook and colleagues evaluate the change in prescribing error rates after the introduction of two commercial electronic prescribing systems in two Australian hospitals

Composite structural motifs of binding sites for delineating biological functions of proteins

Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs which represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures.Comment: 34 pages, 7 figure

CAPG and GIPC1: Breast Cancer Biomarkers for Bone Metastasis Development and Treatment.

Bone is the predominant site of metastasis from breast cancer, and recent trials have demonstrated that adjuvant bisphosphonate therapy can reduce bone metastasis development and improve survival. There is an unmet need for prognostic and predictive biomarkers so that therapy can be appropriately targeted.Potential biomarkers for bone metastasis were identified using proteomic comparison of bone-metastatic, lung-metastatic, and nonmetastatic variants of human breast cancer MDA-MB-231 cells. Clinical validation was performed using immunohistochemical staining of tumor tissue microarrays from patients in a large randomized trial of adjuvant zoledronic acid (zoledronate) (AZURE-ISRCTN79831382). We used Cox proportional hazards regression, the Kaplan-Meier estimate of the survival function, and the log-rank test to investigate associations between protein expression, clinical variables, and time to distant recurrence events. All statistical tests were two-sided.Two novel biomarker candidates, macrophage-capping protein (CAPG) and PDZ domain-containing protein GIPC1 (GIPC1), were identified for clinical validation. Cox regression analysis of AZURE training and validation sets showed that control patients (no zoledronate) were more likely to develop first distant recurrence in bone (hazard ratio [HR] = 4.5, 95% confidence interval [CI] = 2.1 to 9.8, P < .001) and die (HR for overall survival = 1.8, 95% CI = 1.01 to 3.24, P = .045) if both proteins were highly expressed in the primary tumor. In patients with high expression of both proteins, zoledronate had a substantial effect, leading to 10-fold hazard ratio reduction (compared with control) for first distant recurrence in bone (P = .008).The composite biomarker, CAPG and GIPC1 in primary breast tumors, predicted disease outcomes and benefit from zoledronate and may facilitate patient selection for adjuvant bisphosphonate treatment

CareSearch: finding and evaluating Australia's missing palliative care literature

BACKGROUND: Palliative care is an evolving specialty with a growing evidence base. However, evidence is less accessible than it could be with a lower than average conversion of conference abstracts to articles in peer-reviewed journals and the need for more accessible tools to support evidence-based practice (EBP) in palliative care. The CareSearch project involved identifying, collecting and evaluating Australia's "grey" palliative care literature and identifying international published literature missing from the electronic indexing systems. The literature was then catalogued and made publicly available through the CareSearch website. RESULTS: To date over 2,500 items have been included in the CareSearch database and can be accessed and searched through a publicly available website. Nearly 2,000 items are conference abstracts and 178 are theses or government, organisational and planning documents. A further 410 items relate to articles from palliative journals that are not indexed on a major bibliographic database. The website also provides tools and facilities to support palliative care practice and research. CONCLUSION: CareSearch is a new evidence resource for palliative practitioners, educators and researchers. The palliative community now has access to a more comprehensive literature base as well as a resource that supports the integration of knowledge into practice. This specialised data repository enables users to access information on the body of work that has shaped palliative care development and prevents the potential loss or duplication of research work. It also provides a template for other emerging disciplines to use in capturing their literature and evidence

Brand Suicide? Memory and Liking of Negative Brand Names

Negative brand names are surprisingly common in the marketplace (e.g., Poison perfume; Hell pizza, and Monster energy drink), yet their effects on consumer behavior are currently unknown. Three studies investigated the effects of negative brand name valence on brand name memory and liking of a branded product. Study 1 demonstrates that relative to nonnegative brand names, negative brand names and their associated logos are better recognised. Studies 2 and 3 demonstrate that negative valence of a brand name tends to have a detrimental influence on product evaluation with evaluations worsening as negative valence increases. However, evaluation is also dependent on brand name arousal, with high arousal brand names resulting in more positive evaluations, such that moderately negative brand names are equally as attractive as some non-negative brand names. Study 3 shows evidence for affective habituation, whereby the effects of negative valence reduce with repeated exposures to some classes of negative brand name

Comparison between REBT and Visual/Kinaesthetic Dissociation in the Treatment of Panic Disorder: An Empirical Study

The aim of this study was to test the efficacy of two brief treatment methods for panic disorder: Rational Emotive Behaviour Therapy (REBT) and Visual/Kinaesthetic Dissociation (VKD), neither of which have been the object of scientific enquiry. The study is a two-way between-groups pre-test/post-test experimental design with baseline and follow-up measures. An innovative four-session treatment protocol was developed for each treatment method. Eighteen participants in North-East Surrey, England, who responded to media advertisements for cognitive-behavioural treatment for panic disorder and who met Diagnostic and Statistical Manual of Mental Disorders criteria for panic disorder with or without agoraphobia were randomly assigned to either REBT or VKD. Pre-test/post-test changes in panic were measured using the ACQ, PASQ, and HADS scales and a global panic rating measure. At post-test there was a statistically significant improvement on all measures for both groups, which was maintained at one-month follow-up. Taking into consideration limitations such as the small sample size and a short follow-up period, implications of this study and recommendations for future research are discussed