Managing pain medications in long-term care: nurses' views

The purpose of this study was to explore nurses' perceptions of their current practices related to administering pain medications to long-term care (LTC) residents. A cross-sectional survey design was used, including both quantitative and open-ended questions. Data were collected from 165 nurses (59% response rate) at nine LTC homes in southern Ontario, Canada. The majority (85%) felt that the medication administration system was adequate to help them manage residents' pain and 98% felt comfortable administering narcotics. In deciding to administer a narcotic, nurses were influenced by pain assessments, physician orders, diagnosis, past history, effectiveness of non-narcotics and fear of making dosage miscalculations or developing addictions. Finally, most nurses stated that they trusted the physicians and pharmacists to ensure orders were safe. These findings highlight nurses' perceptions of managing pain medications in LTC and related areas where continuing education initiatives for nurses are needed.

CD44-Mediated Activaton of α5β1-Intergrin, Cortactin and Paxillin Signaling Underpins Ashesion of basal-like breat cancer cells to Endotherlium and Fibronectin- enriched Matrices

CD44 expression is elevated in basal-like breast cancer (BLBC) tissue, and correlates with increased efficiency of distant metastasis in patients and experimental models. We sought to characterize mechanisms underpinning CD44-promoted adhesion of BLBC cells to vascular endothelial monolayers and extracellular matrix (ECM) substrates. Stimulation with hyaluronan (HA), the native ligand for CD44, increased expression and activation of β1-integrin receptors, and increased α5-integrin subunit expression. Adhesion assays confirmed that CD44-signalling potentiated BLBC cell adhesion to endothelium and Fibronectin in an α5B1-integrin-dependent mechanism. Co-immunoprecipitation experiments confirmed HA-promoted association of CD44 with talin and the β1-integrin chain in BLBC cells. Knockdown of talin inhibited CD44 complexing with β1-integrin and repressed HA-induced, CD44-mediated activation of β1-integrin receptors. Immunoblotting confirmed that HA induced rapid phosphorylation of cortactin and paxillin, through a CD44-dependent and β1-integrin-dependent mechanisms. Knockdown of CD44, cortactin or paxillin independently attenuated the adhesion of BL-BCa cells to endothelial monolayers and Fibronectin. Accordingly, we conclude that CD44 induced, integrin-mediated signaling not only underpins efficient adhesion of BLBC cells to BMECs to facilitate extravasation but initiates their adhesion to Fibronectin, enabling penetrant cancer cells to adhere more efficiently to underlying Fibronectin-enriched matrix present within the metastatic niche.

Safety of Spectacles for Children's Vision: A Cluster-Randomized Controlled Trial.

Purpose: To study safety of children’s glasses in rural China, where fear that glasses harm vision is an important barrier for families and policy-makers. Design: Exploratory analysis from a cluster-randomized, investigator-masked, controlled trial.Methods: Among primary schools (n=252) in western China, children were randomized by school to one of three interventions: free glasses provided in class, vouchers for free glasses at a local facility or glasses prescriptions only (Control group). The main outcome of this analysis is uncorrected visual acuity after 8 months, adjusted for baseline acuity.Results: Among 19,934 children randomly selected for screening, 5852 myopic (spherical equivalent refractive error <= -0.5 D) eyes of 3001 children (14.7%, mean age 10.5 years) had VA <= 6/12 without glasses correctable to > 6/12 with glasses, and were eligible. Among these, 1903 (32.5%), 1798 (30.7%), and 2151 (36.8%) were randomized to Control, Voucher and Free Glasses respectively. Intention-to-treat analyses were performed on all 1831 (96.2%), 1699 (94.5%), and 2007 (93.3%) eyes of children with follow-up in Control, Voucher and Free Glasses groups. Final visual acuity for eyes of children in the treatment groups (Free Glasses and Voucher) was significantly better than for Control children, adjusting only for baseline visual acuity (difference of 0.023 logMAR units [0.23 vision chart lines, 95% CI: 0.03, 0.43]) or for other baseline factors as well (0.025 logMAR units [0.25 lines, 95% CI 0.04, 0.45]). Conclusion: We found no evidence that spectacles promote decline in uncorrected vision with aging among children.

Endosomal signaling and oncogenesis

The endosomal system provides a route whereby nutrients, viruses, and receptors are internalized. During the course of endocytosis, activated receptors can accumulate within endosomal structures and certain signal-transducing molecules can be recruited to endosomal membranes. In the context of signaling and cancer, they provide platforms within the cell from which signals can be potentiated or attenuated. Regulation of the duration of receptor signaling is a pivotal means of refining growth responses in cells. In cancers, this is often considered in terms of mutations that affect receptor tyrosine kinases and maintain them in hyperactivated states of dimerization and/or phosphorylation. However, disruption to the regulatory control exerted by the assembly of protein complexes within the endosomal network can also contribute to disease among which oncogenesis is characterized in part by dysregulated growth, enhanced cell survival, and changes in the expression of markers of differentiation. In this chapter, we will discuss the role of proteins that regulate in endocytosis as tumor suppressors or oncogenes and how changing the fate of internalized receptors and concomitant endosomal signaling can contribute to cancer.

Adjusting HIV Prevalence Estimates for Non-participation: an Application to Demographic Surveillance

Introduction: HIV testing is a cornerstone of efforts to combat the HIV epidemic, and testing conducted as part of surveillance provides invaluable data on the spread of infection and the effectiveness of campaigns to reduce the transmission of HIV. However, participation in HIV testing can be low, and if respondents systematically select not to be tested because they know or suspect they are HIV positive (and fear disclosure), standard approaches to deal with missing data will fail to remove selection bias. We implemented Heckman-type selection models, which can be used to adjust for missing data that are not missing at random, and established the extent of selection bias in a population-based HIV survey in an HIV hyperendemic community in rural South Africa.

Methods: We used data from a population-based HIV survey carried out in 2009 in rural KwaZulu-Natal, South Africa. In this survey, 5565 women (35%) and 2567 men (27%) provided blood for an HIV test. We accounted for missing data using interviewer identity as a selection variable which predicted consent to HIV testing but was unlikely to be independently associated with HIV status. Our approach involved using this selection variable to examine the HIV status of residents who would ordinarily refuse to test, except that they were allocated a persuasive interviewer. Our copula model allows for flexibility when modelling the dependence structure between HIV survey participation and HIV status.

Results: For women, our selection model generated an HIV prevalence estimate of 33% (95% CI 27–40) for all people eligible to consent to HIV testing in the survey. This estimate is higher than the estimate of 24% generated when only information from respondents who participated in testing is used in the analysis, and the estimate of 27% when imputation analysis is used to predict missing data on HIV status. For men, we found an HIV prevalence of 25% (95% CI 15–35) using the selection model, compared to 16% among those who participated in testing, and 18% estimated with imputation. We provide new confidence intervals that correct for the fact that the relationship between testing and HIV status is unknown and requires estimation.

Conclusions: We confirm the feasibility and value of adopting selection models to account for missing data in population-based HIV surveys and surveillance systems. Elements of survey design, such as interviewer identity, present the opportunity to adopt this approach in routine applications. Where non-participation is high, true confidence intervals are much wider than those generated by standard approaches to dealing with missing data suggest.

Reasons for non-participation in the Northern Ireland Bowel Cancer Screening Programme: a qualitative study

OBJECTIVES: To identify the reasons why some people do not participate in bowel cancer screening so that steps can be taken to improve informed decision-making.

DESIGN: Qualitative study, using focus groups with thematic analysis of data to identify, analyse and report patterns. Transcripts were repeatedly read and inductively coded using a phenomenological perspective, and organised into key themes.

SETTING: Belfast and Armagh, two areas of Northern Ireland with relatively low uptake of bowel cancer screening.

PARTICIPANTS: Ten women and 18 men in three single-gender focus groups (two male and one female), each with 9-10 participants. Study participants were recruited by convenience sampling from the general public and were eligible for, but had not taken part in, the Northern Ireland Bowel Cancer Screening Programme.

RESULTS: Key themes identified were fear of cancer; the test procedure; social norms; past experience of cancer and screening; lack of knowledge or understanding about bowel cancer screening; and resulting behaviour towards the test. Fear about receiving bad news and reluctance to conduct the test themselves were reactions that participants seemed willing to overcome after taking part in open discussion about the test.

CONCLUSIONS: We identified barriers to participation in bowel cancer screening and used these insights to develop new materials to support delivery of the programme. Some of the issues raised have been identified in other UK settings, suggesting that knowledge about barriers, and strategies to improve uptake, may be generalisable.

The Dublin Lock Hospital: Medicine, Morality, Disease and Sin

Anecdotal evidence has it that when Dublin’s venereal disease hospital closed its doors for the last time in the 1950s, its administrative staff began to burn its records, starting with the most recent. This attempt to conceal the results of sexual profligacy is perhaps understandable in the rarefied climate of mid-century Catholic Ireland. However, the sense of shame attached to this institution has been pervasive. For example, of all Dublin’s major hospitals, the lock hospital remains the only one without a dedicated history. And, throughout its two centuries of existence, the ‘lock’ had often been a site of controversy and approbation.

The institution began in the eighteenth century as the most peripatetic, poor relation of the city’s voluntary hospitals, wandering indiscriminately through a series of temporary premises before finally achieving a permanent home and official recognition as a military-sponsored medical hospital in 1792. It also gained architectural extensions by both Richard and Francis Johnston and in the following decades. This new-found status and a growing re-conceptualisation of venereal disease as a legitimate medical problem rather than a matter of morality was, however, somewhat compromised by the choice of site at Townsend Street. The institution occupied a hidden part of city, appropriating the vacated home of the Hospital for Incurables, another marginalised group whose presence in the city had been viewed through the lens of superstition and fear. For the rest of its existence, the lock hospital would share this experience occupying a nebulous position between medicine and morality; disease and sin.

Using what’s left of the hospital’s records and a series of original architectural drawings, this paper discusses the presence and role of the lock hospital in the city in the eighteenth and early nineteenth century, tracking how changes in its administration and architectural form reflected wider attitudes towards disease, sexuality and gender in Georgian Dublin.

Behavioural reactivity of ewes and lambs during partial and total social isolation

This work investigated the differences in the reactivity of Sarda (primiparous n= 18, multiparous n= 17) and Dorset (multiparous n= 8) breeds of sheep and their singleton lambs to two challenging test situations involving a mother-lamb partial separation test and an isolation test. Non-parametric analysis used single behavioural variables and fear scores to evaluate the effect of parity, sex of lambs, and the association between mother-lamb behaviour. Amongst ewes, Dorset were characterised by a more calm temperament while Sarda (especially primiparous ewes) were more active in their response to challenge (i.e. more attempts to escape). As with their dams, lambs reflected to a certain extent this divergence and overall during isolation lamb fear score was on average significantly higher than dams. Correlations between measures of behavioural reactivity across tests were carried out to search for predictive measures of fear. A very strong correlation emerged linking vocalisation to locomotor activity. Vocalisation could be a good candidate as predictor factor of an active reaction of sheep to a fearful situation.

Validity of model devices used to assess canine temperament in behavioral tests

Temperament tests are widely accepted as instruments for profiling behavioral variability in dogs, and they are applied in numerous areas of investigation (e.g. suitability for adoption or for breeding). During testing, to elicit a dog's reaction toward novel stimuli and predict its behavior in everyday life, model devices such as a child-like doll, or a fake dog, are often employed. However, the reliability of these devices to accurately stimulate dogs' reactions to children or dogs, is unknown and perhaps overestimated. This may be a particular concern in the case of aggressive behavior toward humans, a significant public health issue. The aim of this study was to: (1) evaluate the correlation between dogs' reactions to these devices, and owners' reports of their dog's aggression history (using the C-BARQ ??); (2) compare reactions toward the devices of dogs with and without histories of aggression. Subjects were selected among those visiting for behavioral consultation at the Veterinary Hospital of the University of Pennsylvania, and previously categorized as aggressive toward unfamiliar children, conspecifics, or as non-aggressive dogs (control). The test consisted of different components: an unfamiliar female tester approaching the dog; the presentation of a child-like doll, an ambiguous object, and a fake plastic dog. All tests were videotaped and durations of behaviors were later analyzed on the basis of a specified ethogram. Dogs' reactions were compared to C-BARQ scores, and interesting correlations emerged for 'dog-directed aggression/fear' (R = 0.48, P = 0.004), and 'stranger-directed aggression' (R = 0.58, P <0.001) factors. Dogs differed in their reactions toward the devices: the child-like doll and the fake dog elicited more social behaviors than the ambiguous object used as a control stimulus. Issues concerning the reliability of these tools to assess canine temperament are discussed. ?? 2012 Elsevier B.V. All rights reserved.

TNF-α Sensitizes Mechanoreceptors in Human Odontoblasts

Background: Mechanotransduction in the dental pulp is mediated by mechano-sensitive trigeminal afferents but accumulating evidence suggests odontoblasts also contribute to mechano-sensory functions of the pulp as evidenced by expression of TRP channels, calcium-activated potassium channels and TREK-1 potassium channels. Activation of these mechano-sensitive channels is considered critical for the mechanotransduction of fluid movement within dentinal tubules into electrical signals transmitted by the pulpal afferents to elicit tooth sensitivity and pain. Since tooth pain and sensitivity are potentiated by inflammation we hypothesise that the inflammatory cytokine TNF-α sensitizes odontoblast responses to mechanical stimuli. Objective: To investigate the effect of TNF-α on the response of odontblast-like cells to mechanical stimuli. Method: Odontoblast-like cells were derived from dental pulp cells of immature third molars as previously described (El-karim et al 20112011 Pain, 152, 2211-2223). Odontoblast response to mechanical stimuli (application of hypotonic solution) was determined using ratiometric calcium imaging. Cells were treated with TNF-α for either 24hrs or short application for 10 mins prior to calcium imaging. Result: Odontoblast-like cells responded to hypotonic solution (230 mOSM) by increase in cytoplasmic Ca2+ concentration [Ca+2]i that was reduced to near base line in the presence of the TRPV4 antagonist RN-1734. Incubation of odontoblast -like cells with TNFα for 24 hrs resulted in a significant increase in cytoplasmic Ca2+ concentration in response to hypotonic stimuli compared to untreated cells. Similar results were obtained when cells were treated with TNF-α for 10 mins prior to imaging. Conclusion: Both short and long term treatment of odontoblasts-like cells with TNF-α resulted in enhanced responses to mechanical stimuli mediated via TRPV4 channel suggesting a role for this channel in inflammatory dental pain.

Spectacle acceptance among secondary school students in rural China: the Xichang Pediatric Refractive Error Study (X-PRES)--report 5.

PURPOSE: To assess determinants of spectacle acceptance and use among rural Chinese children. METHODS: Children with uncorrected acuity < or = 6/12 in either eye and whose presenting vision could be improved > or = 2 lines with refraction were identified from a school-based sample of 1892 students. Information on obtaining glasses and the benefits of spectacles was provided to children, families, and teachers. Purchase of new spectacles and reasons for nonpurchase were assessed by direct inspection and interview 3 months later. RESULTS: Among 674 (35.6%) children requiring spectacles (mean age, 14.7 +/- 0.8 years), 597 (88.6%) were followed up. Among 339 children with no glasses at baseline, 30.7% purchased spectacles, whereas 43.2% of 258 children with inaccurate glasses replaced them. Most (70%) subjects paid US$13 to $26. Among children with bilateral vision < or = 6/18, 45.6% bought glasses. In multivariate models, presenting vision < 6/12 (P < 0.009), refractive error < -2.0 D (P < 0.001), and amount willing to pay for glasses (P = 0.01) were predictors of purchase. Reasons for nonpurchase included satisfaction with current vision (78% of those with glasses at baseline, 49% of those without), concerns over price or parental refusal (18%), and fear glasses would weaken the eyes (13%). Only 26% of children stated that they usually wore their new glasses. CONCLUSIONS: Many families in rural China will pay for glasses, though spectacle acceptance was < 50%, even among children with poor vision. Acceptance could be improved by price reduction, education showing that glasses will not harm the eyes, and parent-focused interventions.

INVESTIGATING THE ROLE OF NOX NADPH OXIDASE SIGNALLING IN CELL MIGRATION AND ANGIOGENESIS OF ENDOTHELIAL COLONY-FORMING CELLS

Introduction. Endothelial colony-forming cells (ECFCs) hold great cytotherapeutic potential for ischaemic disease. Emerging evidence supports a key role for NADPH oxidases in underlying angiogenic processes of these and other endothelial cells. Aims. To study the influence of Nox NADPH oxidases on the pro-angiogenic function of ECFCs. Methods. Human ECFCs isolated from umbilical cord blood were treated with pro-oxidant PMA and assessed in vitro, both under basal conditions and after siRNA knockdown of Nox4, a key endothelial NADPH oxidase isoform, alongside primary mature human aortic endothelial cells (HAoECs) for comparison, using an established scratch-wound assay as the functional end-point. Results. PMA (500nM for 8h) increased cell migration (control 18.6±2.8, PMA 32.7±6.6% wound closure; n=6, P<0.05) in a superoxide-dependent manner, as indicated by attenuation of this effect in the presence of PEG-SOD. Although HAoEC migration in response to PMA also tended to increase, this did not reach statistical significance. Notably, cell migration at 16h was reduced by Nox4 knockdown in ECFCs (control siRNA 53.4±3.5, Nox4 siRNA 35.1±4.9% closure; n=3, P<0.05), but not in HAoECs, whilst the pro-migratory effect of PMA in ECFCs was potentiated after Nox4 knockdown (control siRNA 53.4±3.5, +PMA 61.5±3.2% closure; n=3, P=NS; Nox4 siRNA 35.1±4.9, +PMA 53.0±4.9% closure; n=3, P<0.05). Conclusion. ECFC migration is enhanced by low concentrations of superoxide, to a greater extent compared to mature endothelial cells, and appears to be at least partly dependent upon NADPH oxidase, including a specific role for Nox4. Although, the precise contribution of endothelial Nox NADPH oxidases isoforms remains to be determined, it is clear that these findings may have significant implications for potential ECFC-based therapies for ischaemic disease, which is associated with an oxidative microenvironment.

EFFECTS OF ENVIRONMENTAL ANTIOXIDANTS ON PRO-ANGIOGENIC ROS SIGNALLING IN ENDOTHELIAL COLONY FORMING CELLS IN VITRO

Introduction. Endothelial colony-forming cells (ECFCs) hold great cytotherapeutic potential for ischaemic disease. Whilst increasing evidence supports a key role for reactive oxygen species (ROS), specifically those derived from Nox NADPH oxidases, in the underlying angiogenic processes of these and other endothelial cells, such studies investigating the role of redox signalling may be hampered by the standard inclusion of antioxidant agents in endothelial cell media, such as phenol red. Aims. To study the effects of antioxidants present in culture media on pro-angiogenic function of ECFCs in vitro. Methods. Human ECFCs isolated from umbilical cord blood were maintained in media with and without antioxidant components (EGM2 and phenol red-free DMEM, respectively) prior to treatment with pro-oxidant PMA and assessment of their in vitro migratory capacity using a scratch-wound assay to measure pro-angiogenic activity. Results. Our previous work in our group indicated that PMA (500nM) increased ECFC migration in a both a superoxide and NADPH oxidase-dependent manner (control 18.6±2.8, PMA 32.7±6.6% wound closure; n=6, P<0.05), as indicated by attenuation with PEG-SOD and VAS2870. However, inconsistencies in the data generated under varying experimental conditions led us to hypothesise that antioxidant agents in the standard ECFC media may be influencing these effects. Indeed, a direct comparison of cell migration between ECFCs incubated in EGM2 DMEM demonstrated a clear trend towards higher migration in the latter (EGM2 9.0±4.5, DMEM 22.7±6.4%; n=3, P=NS). Similar to our previous EGM2 studies, cell migration was potentiated by PMA (control 11.6±1.6, PMA 25.1±2.8%; n=3, P<0.05), but at a lower dose (100nM), which is consistent with a reduction in media antioxidants. Notably, this response was attenuated by VAS2870 (PMA 37.6±7.3, PMA+VAS2870 10.3±2.9%; n=6, P<0.05), underlining a likely role for Nox NADPH oxidases. Conclusion. Taken together, these data indicate that ECFC migration is sensitive to different endothelial cell growth media, which appears to be dependent upon their antioxidant content. Although further experiments, such as quantification of cellular superoxide generation by dihydroethidium fluorescence may be required to confirm a specific role for antioxidants, such blunting of ROS signalling in vitro is clearly an important consideration which may significantly impact upon data interpretation.

Change in psychological distress in longer-term oesophageal cancer carers: are clusters of illness perception change a useful determinant?

Objective: This study provides a longitudinal assessment of distress in longer-term oesophageal cancer carers, while examining illness perception schema as a possible determinant of change in distress over time.
Methods: Oesophageal cancer carers (n=171), 48-months post-diagnosis, were assessed at baseline and 12-months later with the Illness Perception Questionnaire-Revised, Cancer Coping Questionnaire, Hospital Anxiety and Depression Scale and Concerns About Recurrence Scale.
Results: Findings report deterioration from normal to probable anxiety in 35.7% of carers and probable depression in 28.7% carers over time. Fear of recurrence remained stable. Changes in control, consequence and cause beliefs were identified as key determinants of a change in psychological morbidity.
Conclusions: Illness beliefs appear to be valuable targets for psychological intervention to improve wellbeing among carers of people with oesophageal cancer.

The neoliberalisation of the Cathedral Quarter and its contestations

Over time Belfast has been well researched as a site of ethnosectarian conflict, segregation and fear see (Boal et al 1976) and (Gaffiken and Morrisey 2011). The study of socio-spatial patterns of ‘ethnocracy’ is useful, but this article will argue how it is equally important to understand local forms of urban restructuring in terms of global processes that are linked to neoliberalism. To better understand the neoliberal urbanisation of Belfast this article is organised into two parts. The first part will demonstrate how the Northern Ireland State has sought legitimacy in the free market as ‘therapy’ for the production of neutral socio-spatial formations such as the Cathedral Quarter. Secondly it will examine this performance of neoliberal urbanism, as it ‘actually exists’ and demonstrate how market-led renewal has been extended through the clustering and non-sectarian interests, ‘soft’ arrangements of urban governance, cultural re-branding strategies, economic development incentives, and the development of various flagship projects. Critically this place-based grounding of neoliberalism is useful, as it also allows for the contestations of neoliberal urbanism to become real rather than just theoretical. The second part of the article will draw attention to the responses of local, and sometimes marginal, interests that have looked to challenge, adapt and, at times, divert the extension of market-led renewal. To be clear, this article does not want to overstate the performance of such interests. Nor does it want to claim that they significantly impact or obstruct the wider neoliberal urbanisation of Belfast. Instead it is interested in their behaviours and their different methods of working to explore what may be constituted as ‘alternative’, at least in the locality of the Cathedral Quarter. By studying how and why these interests have responded to the extension of neoliberal urbanism over time, it may just be possible to provide a better platform to articulate what more progressive forms of urban resistance might look like.