Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies

<p>Abstract</p> <p>Background</p> <p>Osteoporosis-related fractures are a significant public health concern. Interventions that increase detection and treatment of osteoporosis, as well as prevention of fractures and falls, are substantially underutilized. This paper outlines the protocol for a pragmatic randomised trial of a multifaceted community-based care program aimed at optimizing the evidence-based management of falls and fractures in patients at risk.</p> <p>Design</p> <p>6-month randomised controlled study.</p> <p>Methods</p> <p>This population-based study was completed in the Algoma District of Ontario, Canada a geographically vast area with Sault Ste Marie (population 78 000) as its main city. Eligible patients were allocated to an immediate intervention protocol (IP) group, or a delayed intervention protocol (DP) group. The DP group received usual care for 6 months and then was crossed over to receive the interventions. Components of the intervention were directed at the physicians and their patients and included patient-specific recommendations for osteoporosis therapy as outlined by the clinical practice guidelines developed by Osteoporosis Canada, and falls risk assessment and treatment. Two primary outcomes were measured including implementation of appropriate osteoporosis and falls risk management. Secondary outcomes included quality of life and the number of falls, fractures, and hospital admissions over a twelve-month period. The patient is the unit of allocation and analysis. Analyses will be performed on an intention to treat basis.</p> <p>Discussion</p> <p>This paper outlines the protocol for a pragmatic randomised trial of a multi-faceted, community-based intervention to optimize the implementation of evidence based management for patients at risk for falls and osteoporosis.</p> <p>Trial Registration</p> <p>This trial has been registered with clinicaltrials.gov (ID: NCT00465387)</p

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally

Local CD4 and CD8 T-Cell Reactivity to HSV-1 Antigens Documents Broad Viral Protein Expression and Immune Competence in Latently Infected Human Trigeminal Ganglia

Herpes simplex virus type 1 (HSV-1) infection results in lifelong chronic infection of trigeminal ganglion (TG) neurons, also referred to as neuronal HSV-1 latency, with periodic reactivation leading to recrudescent herpetic disease in some persons. HSV-1 proteins are expressed in a temporally coordinated fashion during lytic infection, but their expression pattern during latent infection is largely unknown. Selective retention of HSV-1 reactive T-cells in human TG suggests their role in controlling reactivation by recognizing locally expressed HSV-1 proteins. We characterized the HSV-1 proteins recognized by virus-specific CD4 and CD8 T-cells recovered from human HSV-1-infected TG. T-cell clusters, consisting of both CD4 and CD8 T-cells, surrounded neurons and expressed mRNAs and proteins consistent with in situ antigen recognition and antiviral function. HSV-1 proteome-wide scans revealed that intra-TG T-cell responses included both CD4 and CD8 T-cells directed to one to three HSV-1 proteins per person. HSV-1 protein ICP6 was targeted by CD8 T-cells in 4 of 8 HLA-discordant donors. In situ tetramer staining demonstrated HSV-1-specific CD8 T-cells juxtaposed to TG neurons. Intra-TG retention of virus-specific CD4 T-cells, validated to the HSV-1 peptide level, implies trafficking of viral proteins from neurons to HLA class II-expressing non-neuronal cells for antigen presentation. The diversity of viral proteins targeted by TG T-cells across all kinetic and functional classes of viral proteins suggests broad HSV-1 protein expression, and viral antigen processing and presentation, in latently infected human TG. Collectively, the human TG represents an immunocompetent environment for both CD4 and CD8 T-cell recognition of HSV-1 proteins expressed during latent infection. HSV-1 proteins recognized by TG-resident T-cells, particularly ICP6 and VP16, are potential HSV-1 vaccine candidates

Reliability of a tool for measuring theory of planned behaviour constructs for use in evaluating research use in policymaking

<p>Abstract</p> <p>Background</p> <p>Although measures of knowledge translation and exchange (KTE) effectiveness based on the theory of planned behavior (TPB) have been used among patients and providers, no measure has been developed for use among health system policymakers and stakeholders. A tool that measures the intention to use research evidence in policymaking could assist researchers in evaluating the effectiveness of KTE strategies that aim to support evidence-informed health system decision-making. Therefore, we developed a 15-item tool to measure four TPB constructs (intention, attitude, subjective norm and perceived control) and assessed its face validity through key informant interviews.</p> <p>Methods</p> <p>We carried out a reliability study to assess the tool's internal consistency and test-retest reliability. Our study sample consisted of 62 policymakers and stakeholders that participated in deliberative dialogues. We assessed internal consistency using Cronbach's alpha and generalizability (G) coefficients, and we assessed test-retest reliability by calculating Pearson correlation coefficients (<it>r</it>) and G coefficients for each construct and the tool overall.</p> <p>Results</p> <p>The internal consistency of items within each construct was good with alpha ranging from 0.68 to alpha = 0.89. G-coefficients were lower for a single administration (G = 0.34 to G = 0.73) than for the average of two administrations (G = 0.79 to G = 0.89). Test-retest reliability coefficients for the constructs ranged from <it>r </it>= 0.26 to <it>r </it>= 0.77 and from G = 0.31 to G = 0.62 for a single administration, and from G = 0.47 to G = 0.86 for the average of two administrations. Test-retest reliability of the tool using G theory was moderate (G = 0.5) when we generalized across a single observation, but became strong (G = 0.9) when we averaged across both administrations.</p> <p>Conclusion</p> <p>This study provides preliminary evidence for the reliability of a tool that can be used to measure TPB constructs in relation to research use in policymaking. Our findings suggest that the tool should be administered on more than one occasion when the intervention promotes an initial 'spike' in enthusiasm for using research evidence (as it seemed to do in this case with deliberative dialogues). The findings from this study will be used to modify the tool and inform further psychometric testing following different KTE interventions.</p

General hospital staff worries, perceived sufficiency of information and associated psychological distress during the A/H1N1 influenza pandemic

<p>Abstract</p> <p>Background</p> <p>Health care workers (HCWs) presented frequent concerns regarding their health and their families' health and high levels of psychological distress during previous disease outbreaks, such as the SARS outbreak, which was associated with social isolation and intentional absenteeism. We aimed to assess HCWs concerns and anxiety, perceived sufficiency of information, and intended behavior during the recent A/H1N1 influenza pandemic and their associations with psychological distress.</p> <p>Method</p> <p>Between September 1^stand 30^th, 2009, 469 health-care workers (HCWs) of a tertiary teaching hospital completed a 20-item questionnaire regarding concerns and worries about the new A/H1N1 influenza pandemic, along with Cassileth's Information Styles Questionnaire (part-I) and the GHQ-28.</p> <p>Results</p> <p>More than half of the present study's HCWs (56.7%) reported they were worried about the A/H1N1 influenza pandemic, their degree of anxiety being moderately high (median 6/9). The most frequent concern was infection of family and friends and the health consequences of the disease (54.9%). The perceived risk of being infected was considered moderately high (median 6/9). Few HCWs (6.6%) had restricted their social contacts and fewer (3.8%) felt isolated by their family members and friends because of their hospital work, while a low percentage (4.3%) indented to take a leave to avoid infection. However, worry and degree of worry were significantly associated with intended absenteeism (p < 0.0005), restriction of social contacts (p < 0.0005), and psychological distress (p = 0.036). Perceived sufficiency of information about several aspects of the A/H1N1 influenza was moderately high, and the overall information about the A/H1N1 influenza was considered clear (median 7.4/9). Also, perceived sufficiency of information for the prognosis of the infection was significantly independently associated with the degree of worry about the pandemic (p = 0.008).</p> <p>Conclusions</p> <p>A significant proportion of HCWs experienced moderately high anxiety about the pandemic, and their degree of worry was an independent correlate of psychological distress. Since perceived sufficiency of information about the A/H1N1 influenza prognosis was associated with reduced degree of worry, hospital managers and consultation-liaison psychiatry services should try to provide for HCWs' need for information, in order to offer favourable working conditions in times of extreme distress, such as the current and future pandemics.</p

The Influence of Victim Vulnerability and Gender on Police Officers’ Assessment of Intimate Partner Violence Risk

This study investigated the influence of victim vulnerability factors and gender on risk assessment for intimate partner violence (IPV). 867 cases of male and female perpetrated IPV investigated by Swedish police officers using the Brief Spousal Assault Form for the Evaluation of Risk (BSAFER) were examined. For male-to-female IPV, victim vulnerability factors were associated with summary risk judgments and risk management recommendations. For femaleto-male IPV, vulnerability factors were more often omitted, and consistent associations were not found between vulnerability factors, summary risk judgments, and risk management. Results indicate that B-SAFER victim vulnerability factors can assist in assessing male-to-female IPV risk. Further research is necessary to examine the use of B-SAFER victim vulnerability factors for female-to-male IPV, as results showed victim vulnerability factors to be less relevant to officers’ decision making, particularly their management recommendations. However, several variables external to the B-SAFER, such as the availability of management strategies may account for these findings

The added value of C-reactive protein to clinical signs and symptoms in patients with obstructive airway disease: results of a diagnostic study in primary care

BACKGROUND: To evaluate the diagnostic accuracy of clinical signs and symptoms, C-reactive protein (CRP) and spirometric parameters and determine their interrelation in patients suspected to have an obstructive airway disease (OAD) in primary care. METHODS: In a cross sectional diagnostic study, 60 adult patients coming to the general practitioner (GP) for the first-time with complaints suspicious for obstructive airway disease (OAD) underwent spirometry. Peak expiratory flow (PEF)-variability within two weeks was determined in patients with inconspicuous spirometry. Structured medical histories were documented and CRP was measured. The reference standard was the Tiffeneau ratio (FEV(1)/VC) in spirometry and the PEF-variability. OAD was diagnosed when FEV(1)/VC ≤ 70% or PEF-variability > 20%. RESULTS: 37 (62%) patients had OAD. The best cut-off value for CRP was found at 2 mg/l with a diagnostic odds ratio (OR) of 4.4 (95% CI 1.4–13.8). Self-reported wheezing was significantly related with OAD (OR 3.4; CI 1.1–10.3), whereas coughing was inversely related (OR 0.2; CI 0.1–0.7). The diagnostic OR of CRP increased when combined with dyspnea (OR 8.5; 95% CI 1.7–42.3) or smoking history (OR 8.4; 95% CI 1.5–48.9). CRP (p = 0.004), FEV(1 )(p = 0.001) and FIV(1 )(p = 0.023) were related with the severity of dyspnea. CRP increased with the number of cigarettes, expressed in pack years (p = 0.001). CONCLUSION: The diagnostic accuracy of clinical signs and symptoms was low. The diagnostic accuracy of CRP improved in combination with dyspnea and smoking history. Due to their coherence with the severity of dyspnea and number of cigarettes respectively, CRP and spirometry might allow risk stratification of patients with OAD in primary care. Further studies need to be done to confirm these findings

Spectrum of centrosome autoantibodies in childhood varicella and post-varicella acute cerebellar ataxia

BACKGROUND: Sera from children with post-varicella infections have autoantibodies that react with centrosomes in brain and tissue culture cells. We investigated the sera of children with infections and post-varicella ataxia and related conditions for reactivity to five recombinant centrosome proteins: γγ-enolase, pericentrin, ninein, PCM-1, and Mob1. METHODS: Sera from 12 patients with acute post-varicella ataxia, 1 with post-Epstein Barr virus (EBV) ataxia, 5 with uncomplicated varicella infections, and other conditions were tested for reactivity to cryopreserved cerebellum tissue and recombinant centrosome proteins. The distribution of pericentrin in the cerebellum was studied by indirect immunofluorescence (IIF) using rabbit antibodies to the recombinant protein. Antibodies to phospholipids (APL) were detected by ELISA. RESULTS: Eleven of 12 children with post-varicella ataxia, 4/5 children with uncomplicated varicella infections, 1/1 with post-EBV ataxia, 2/2 with ADEM, 1/2 with neuroblastoma and ataxia, and 2/2 with cerebellitis had antibodies directed against 1 or more recombinant centrosome antigens. Antibodies to pericentrin were seen in 5/12 children with post-varicella ataxia but not in any of the other sera tested. IIF demonstrated that pericentrin is located in axons and centrosomes of cerebellar cells. APL were detected in 75% of the sera from children with post-varicella ataxia and 50% of children with varicella without ataxia and in none of the controls. CONCLUSION: This is the first study to show the antigen specificity of anti-centrosome antibodies in children with varicella. Our data suggest that children with post-varicella ataxia have unique autoantibody reactivity to pericentrin

Community-based knowledge transfer and exchange: Helping community-based organizations link research to action

<p>Abstract</p> <p>Background</p> <p>Community-based organizations (CBOs) are important stakeholders in health systems and are increasingly called upon to use research evidence to inform their advocacy, program planning, and service delivery efforts. CBOs increasingly turn to community-based research (CBR) given its participatory focus and emphasis on linking research to action. In order to further facilitate the use of research evidence by CBOs, we have developed a strategy for community-based knowledge transfer and exchange (KTE) that helps CBOs more effectively link research evidence to action. We developed the strategy by: outlining the primary characteristics of CBOs and why they are important stakeholders in health systems; describing the concepts and methods for CBR and for KTE; comparing the efforts of CBR to link research evidence to action to those discussed in the KTE literature; and using the comparison to develop a framework for community-based KTE that builds on both the strengths of CBR and existing KTE frameworks.</p> <p>Discussion</p> <p>We find that CBR is particularly effective at fostering a climate for using research evidence and producing research evidence relevant to CBOs through community participation. However, CBOs are not always as engaged in activities to link research evidence to action on a larger scale or to evaluate these efforts. Therefore, our strategy for community-based KTE focuses on: an expanded model of 'linkage and exchange' (<it>i.e</it>., producers and users of researchers engaging in a process of asking and answering questions together); a greater emphasis on both producing and disseminating systematic reviews that address topics of interest to CBOs; developing a large-scale evidence service consisting of both 'push' efforts and efforts to facilitate 'pull' that highlight actionable messages from community relevant systematic reviews in a user-friendly way; and rigorous evaluations of efforts for linking research evidence to action.</p> <p>Summary</p> <p>Through this type of strategy, use of research evidence for CBO advocacy, program planning, and service delivery efforts can be better facilitated and continually refined through ongoing evaluations of its impact.</p

PPAR-γ Ligands Repress TGFβ-Induced Myofibroblast Differentiation by Targeting the PI3K/Akt Pathway: Implications for Therapy of Fibrosis

Transforming growth factor beta (TGFβ) induced differentiation of human lung fibroblasts to myofibroblasts is a key event in the pathogenesis of pulmonary fibrosis. Although the typical TGFβ signaling pathway involves the Smad family of transcription factors, we have previously reported that peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands inhibit TGFβ-mediated differentiation of human lung fibroblasts to myofibroblasts via a Smad-independent pathway. TGFβ also activates the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway leading to phosphorylation of AktS473. Here, we report that PPAR-γ ligands, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and 15-deoxy-(12,14)-15d-prostaglandin J2 (15d-PGJ2), inhibit human myofibroblast differentiation of normal and idiopathic pulmonary fibrotic (IPF) fibroblasts, by blocking Akt phosphorylation at Ser473 by a PPAR-γ-independent mechanism. The PI3K inhibitor LY294002 and a dominant-negative inactive kinase-domain mutant of Akt both inhibited TGFβ-stimulated myofibroblast differentiation, as determined by Western blotting for α-smooth muscle actin and calponin. Prostaglandin A1 (PGA1), a structural analogue of 15d-PGJ2 with an electrophilic center, also reduced TGFβ-driven phosphorylation of Akt, while CAY10410, another analogue that lacks an electrophilic center, did not; implying that the activity of 15d-PGJ2 and CDDO is dependent on their electrophilic properties. PPAR-γ ligands inhibited TGFβ-induced Akt phosphorylation via both post-translational and post-transcriptional mechanisms. This inhibition is independent of MAPK-p38 and PTEN but is dependent on TGFβ-induced phosphorylation of FAK, a kinase that acts upstream of Akt. Thus, PPAR-γ ligands inhibit TGFβ signaling by affecting two pro-survival pathways that culminate in myofibroblast differentiation. Further studies of PPAR-γ ligands and small electrophilic molecules may lead to a new generation of anti-fibrotic therapeutics