Assessing Risk of Future Suicidality in Emergency Department Patients

Background. Emergency Departments (ED) are the first line of evaluation for patients at risk and in crisis, with or without overt suicidality (ideation, attempts). Currently employed triage and assessments methods miss some of the individuals who subsequently become suicidal. The Convergent Functional Information for Suicidality (CFI-S) 22 item checklist of risk factors, that does not ask directly about suicidal ideation, has demonstrated good predictive ability for suicidality in previous studies in psychiatric outpatients, but has not been tested in the real world-setting of emergency departments (EDs). Methods. We administered CFI-S prospectively to a convenience sample of consecutive ED patients. Median administration time was 3 minutes. Patients were also asked at triage about suicidal thoughts or intentions per standard ED suicide clinical screening (SCS), and the treating ED physician was asked to fill a physician gestalt visual analog scale (VAS) for likelihood of future suicidality spectrum events (SSE) (ideation, preparatory acts, attempts, completed suicide). We performed structured chart review and telephone follow-up at 6 months post index visit. Results. The median time to complete the CFI-S was three minutes (1st to 3rd quartile 3–6 minutes). Of the 338 patients enrolled, 45 (13.3%) were positive on the initial SCS, and 32 (9.5%) experienced a SSE in the 6 months follow-up. Overall, across genders, SCS had a modest diagnostic discrimination for future SSE (ROC AUC 0.63,). The physician VAS was better (AUC 0.76 CI 0.66–0.85), and the CFI-S was slightly higher (AUC 0.81, CI 0.76–0.87). The top CFI-S differentiating items were psychiatric illness, perceived uselessness, and social isolation. The top CFI-S items were family history of suicide, age, and past history of suicidal acts. Conclusions. Using CFI-S, or some of its items, in busy EDs may help improve the detection of patients at high risk for future suicidality

Metastasis of a cecal adenocarcinoma to the prostate five years after a right hemicolectomy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Prostatic metastasis from a primary bowel adenocarcinoma has been only rarely reported in the medical literature. The case reported here is rare in the fact that the primary tumor was from a right-sided bowel adenocarcinoma. It is unusual because initial immunostaining was not fully conclusive, and so a relatively new method of immunostaining, CDX2, was used to ascertain its histopathology.</p> <p>Case presentation</p> <p>We describe the case of a 54-year-old Caucasian man who had a right hemicolectomy for a primary cecal adenocarcinoma, which was completely excised. Following the procedure, he received adjuvant chemotherapy. Computed tomography scans showed no evidence of local recurrence or metastatic disease. Then, five years later, he presented to his general practitioner with urinary symptoms. An abnormal prostate was palpated on digital rectal examination. Trans-rectal prostatic biopsies were performed, which showed colorectal metastases within the prostate gland. This was confirmed with CDX2 immunohistochemistry. There was no further evidence of distant metastases on positron emission tomography-computed tomography scans.</p> <p>Conclusions</p> <p>This case demonstrates a rare isolated hematogenous spread to the prostate from a primary cecal adenocarcinoma, several years after definitive treatment and excision. This highlights the importance of accurate immunohistochemistry and imaging in planning further management and treatment.</p

Social functioning and behaviour in Mucopolysaccharidosis IH [Hurlers Syndrome]

Background: Mucopolysaccharidosis type IH (MPS-IH) [Hurlers Syndrome] is a developmental genetic disorder characterised by severe physical symptoms and cognitive decline. This study aimed to investigate the behavioural phenotype of MPS-IH treated by haematopoietic cell transplantation, focusing on social functioning and sleep. Parental stress was also measured. Methods: Participants were 22 children with MPS-IH (mean age 9 years 1 month), of whom 10 were male (45%). Parents completed the Social Responsiveness Scale (SRS), Child Behaviour Checklist (CBCL), Children’s Sleep Habit Questionnaire and Parent Stress Index, Short Form (PSI-SF). Results: Twenty-three per cent of children with MPS-IH scored in the severe range of the SRS, suggesting significant difficulties in social functioning. Children with MPS-IH were more than 30 times more likely to receive scores in the severe range than typically developing children. Thirty-six per cent scored in the mild-to-moderate range, suggesting milder, but marked, difficulties in social interaction. Although children with MPS-IH did not show significantly higher rates of internalising, externalising or total behaviour problems than the normative sample, they received scores that were significantly higher on social, thought and attention problems and rule-breaking behaviour, and all the competence areas of the CBCL. Parents of children with MPS-IH did not score significantly higher on parental stress than parents in a normative sample. Conclusions: Parents of children with MPS-IH rate their children as having problems with social functioning and various areas of competence more frequently than previously thought, with implications for clinical support

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell

Cerebrospinal Fluid B Cells Correlate with Early Brain Inflammation in Multiple Sclerosis

Background: There is accumulating evidence from immunological, pathological and therapeutic studies that B cells are key components in the pathophysiology of multiple sclerosis (MS). Methodology/Principal Findings: In this prospective study we have for the first time investigated the differences in the inflammatory response between relapsing and progressive MS by comparing cerebrospinal fluid (CSF) cell profiles from patients at the onset of the disease (clinically isolated syndrome, CIS), relapsing-remitting (RR) and chronic progressive (CP) MS by flow cytometry. As controls we have used patients with other neurological diseases. We have found a statistically significant accumulation of CSF mature B cells (CD19+CD1382) and plasma blasts (CD19+CD138+) in CIS and RRMS. Both B cell populations were, however, not significantly increased in CPMS. Further, this accumulation of B cells correlated with acute brain inflammation measured by magnetic resonance imaging and with inflammatory CSF parameters such as the number of CSF leukocytes, intrathecal immunoglobulin M and G synthesis and intrathecal production of matri

The Actin Associated Protein Palladin Is Important for the Early Smooth Muscle Cell Differentiation

Palladin, an actin associated protein, plays a significant role in regulating cell adhesion and cell motility. Palladin is important for development, as knockdown in mice is embryonic lethal, yet its role in the development of the vasculature is unknown. We have shown that palladin is essential for the expression of smooth muscle cells (SMC) marker genes and force development in response to agonist stimulation in palladin deficient SMCs. The goal of the study was to determine the molecular mechanisms underlying palladin's ability to regulate the expression of SMC marker genes. Results showed that palladin expression was rapidly induced in an A404 cell line upon retinoic acid (RA) induced differentiation. Suppression of palladin expression with siRNAs inhibited the expression of RA induced SMC differentiation genes, SM α-actin (SMA) and SM22, whereas over-expression of palladin induced SMC gene expression. Chromatin immunoprecipitation assays provided evidence that palladin bound to SMC genes, whereas co-immunoprecipitation assays also showed binding of palladin to myocardin related transcription factors (MRTFs). Endogenous palladin was imaged in the nucleus, increased with leptomycin treatment and the carboxyl-termini of palladin co-localized with MRTFs in the nucleus. Results support a model wherein palladin contributes to SMC differentiation through regulation of CArG-SRF-MRTF dependent transcription of SMC marker genes and as previously published, also through actin dynamics. Finally, in E11.5 palladin null mouse embryos, the expression of SMA and SM22 mRNA and protein is decreased in the vessel wall. Taken together, our findings suggest that palladin plays a key role in the differentiation of SMCs in the developing vasculature

Improving the use of research evidence in guideline development: 10. Integrating values and consumer involvement

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 10(th )of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on integrating values and consumers in guideline development. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We reviewed the titles of all citations and retrieved abstracts and full text articles if the citations appeared relevant to the topic. We checked the reference lists of articles relevant to the questions and used snowballing as a technique to obtain additional information. We did not conduct a full systematic review ourselves. Our conclusions based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: We did not find a systematic review of methods for integrating values in guidelines, but we found several systematic reviews that dealt with related topics. Whose values should WHO use when making recommendations? • Values, the relative importance or worth of a state or consequences of a decision (outcomes relating to benefits, harms, burden and costs), play a role in every recommendation. Ethical considerations, concepts that determine what is right, also play a role. • The values used in making recommendations should reflect those of the people affected. Judgements should be explicit and should be informed by input from those affected (including citizens, patients, clinicians and policy makers). • When differences in values may lead to different decisions or there is uncertainty about values, this should also be explicit. If differences in values are likely to affect a decision, such that people in different setting would likely make different choices about interventions or actions based on differences in their values, global recommendations should be explicit in terms of which values were applied and allow for adaptation after incorporating local values. How should WHO ensure that appropriate values are integrated in recommendations? • All WHO guideline groups should uniformly apply explicit, transparent and clearly described methods for integrating values. • WHO should consider involving relevant stakeholders if this is feasible and efficient. • WHO should develop a checklist for guidelines panels to help them to ensure that ethical considerations relevant to recommendations are addressed explicitly and transparently. How should users and consumers be involved in generating recommendations? • Including consumers in groups that are making global recommendations presents major challenges with respect to the impossibility of including a representative spectrum of consumers from a variety of cultures and settings. Nonetheless, consideration should be given to including consumers in groups who are able to challenge assumptions that are made about the values used for making recommendations, rather than represent the values of consumers around the world. • WHO should establish a network to facilitate involvement of users. • Draft recommendations should be reviewed by consumers, who should be asked explicitly to consider the values that were used. How should values be presented in recommendations? • Recommendations should include a description of how decisions were made about the relative importance of the consequences (benefits, harms and costs) of a decision. • Values that influence recommendations should be reported along with the research evidence underlying recommendations. • When differences in values would lead to different decisions or there is important uncertainty about values that are critical to a decision, this should be flagged and reflected in the strength of the recommendation. • Adaptable guideline templates that allow for integration of different values should be developed and used when differences in values are likely to be critical to a decision

Patterns of comorbidity in community-dwelling older people hospitalised for fall-related injury: A cluster analysis

<p>Abstract</p> <p>Background</p> <p>Community-dwelling older people aged 65+ years sustain falls frequently; these can result in physical injuries necessitating medical attention including emergency department care and hospitalisation. Certain health conditions and impairments have been shown to contribute independently to the risk of falling or experiencing a fall injury, suggesting that individuals with these conditions or impairments should be the focus of falls prevention. Since older people commonly have multiple conditions/impairments, knowledge about which conditions/impairments coexist in at-risk individuals would be valuable in the implementation of a targeted prevention approach. The objective of this study was therefore to examine the prevalence and patterns of comorbidity in this population group.</p> <p>Methods</p> <p>We analysed hospitalisation data from Victoria, Australia's second most populous state, to estimate the prevalence of comorbidity in patients hospitalised at least once between 2005-6 and 2007-8 for treatment of acute fall-related injuries. In patients with two or more comorbid conditions (multicomorbidity) we used an agglomerative hierarchical clustering method to cluster comorbidity variables and identify constellations of conditions.</p> <p>Results</p> <p>More than one in four patients had at least one comorbid condition and among patients with comorbidity one in three had multicomorbidity (range 2-7). The prevalence of comorbidity varied by gender, age group, ethnicity and injury type; it was also associated with a significant increase in the average cumulative length of stay per patient. The cluster analysis identified five distinct, biologically plausible clusters of comorbidity: cardiopulmonary/metabolic, neurological, sensory, stroke and cancer. The cardiopulmonary/metabolic cluster was the largest cluster among the clusters identified.</p> <p>Conclusions</p> <p>The consequences of comorbidity clustering in terms of falls and/or injury outcomes of hospitalised patients should be investigated by future studies. Our findings have particular relevance for falls prevention strategies, clinical practice and planning of follow-up services for these patients.</p