Endothelial Protein C Receptor and Its Impact on Rheumatic Disease.

Endothelial Protein C Receptor (EPCR) is a key regulator of the activated protein C anti-coagulation pathway due to its role in the binding and activation of this protein. EPCR also binds to other ligands such as Factor VII and X, γδ T-cells, plasmodium falciparum erythrocyte membrane protein 1, and Secretory group V Phospholipases A2, facilitating ligand-specific functions. The functions of EPCR can also be regulated by soluble (s)EPCR that competes for the binding sites of membrane-bound (m)EPCR. sEPCR is created when mEPCR is shed from the cell surface. The propensity of shedding alters depending on the genetic haplotype of the EPCR gene that an individual may possess. EPCR plays an active role in normal homeostasis, anti-coagulation pathways, inflammation, and cell stemness. Due to these properties, EPCR is considered a potential effector/mediator of inflammatory diseases. Rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus are autoimmune/inflammatory conditions that are associated with elevated EPCR levels and disease activity, potentially driven by EPCR. This review highlights the functions of EPCR and its contribution to rheumatic diseases.

EPCR deficiency ameliorates inflammatory arthritis in mice by suppressing the activation and migration of T cells and dendritic cells.

OBJECTIVES: Endothelial protein C receptor (EPCR) is highly expressed in synovial tissues of patients with RA, but the function of this receptor remains unknown in RA. This study investigated the effect of EPCR on the onset and development of inflammatory arthritis and its underlying mechanisms. METHODS: CIA was induced in EPCR gene knockout (KO) and matched wild-type (WT) mice. The onset and development of arthritis was monitored clinically and histologically. T cells, dendritic cells (DCs), EPCR and cytokines from EPCR KO and WT mice, RA patients and healthy controls (HCs) were detected by flow cytometry and ELISA. RESULTS: EPCR KO mice displayed >40% lower arthritis incidence and 50% less disease severity than WT mice. EPCR KO mice also had significantly fewer Th1/Th17 cells in synovial tissues with more DCs in circulation. Lymph nodes and synovial CD4 T cells from EPCR KO mice expressed fewer chemokine receptors CXCR3, CXCR5 and CCR6 than WT mice. In vitro, EPCR KO spleen cells contained fewer Th1 and more Th2 and Th17 cells than WT and, in concordance, blocking EPCR in WT cells stimulated Th2 and Th17 cells. DCs generated from EPCR KO bone marrow were less mature and produced less MMP-9. Circulating T cells from RA patients expressed higher levels of EPCR than HC cells; blocking EPCR stimulated Th2 and Treg cells in vitro. CONCLUSION: Deficiency of EPCR ameliorates arthritis in CIA via inhibition of the activation and migration of pathogenic Th cells and DCs. Targeting EPCR may constitute a novel strategy for future RA treatment.

Development and validation of a theory-based questionnaire examining barriers and facilitators to discontinuing long-term benzodiazepine receptor agonist use.

BACKGROUND: Long-term use of benzodiazepine receptor agonists (BZRAs) is a persistent healthcare challenge and poses patient safety risks. Interventions underpinned by behaviour change theory are needed to support discontinuation of long-term BZRA use. The aim of this study was to develop and validate a questionnaire based on the Theoretical Domains Framework (TDF) to examine mediators of behaviour change relating to the discontinuation of long-term BZRA use. METHODS: An initial 52 item questionnaire was developed using the 14 domains of TDF version 2 and iteratively refined over two rounds. The questionnaire was disseminated online via online support groups that focused on BZRAs to community-based adults with either current or previous experience of taking BZRAs on a long-term basis (≥3 months). Confirmatory factor analysis was undertaken to assess the questionnaire's reliability, discriminant validity and goodness of fit. The Standardized Root Mean Square Residual (SRMR), Root Mean Square Error of Approximation (RMSEA) and Comparative Fit Index (CFI) were calculated. RESULTS: Following an iterative process of adjustment, the results obtained from confirmatory factor analysis resulted in the final questionnaire consisting of 29 items across nine theoretical domains. The internal consistency reliability values across these domains ranged from 0.62 to 0.85. For the final model, the SRMR was 0.23, the RMSEA was 0.11 and the CFI was 0.6. CONCLUSIONS: The questionnaire offers a potential tool that could be used to identify domains that need to be targeted as part of a behaviour change intervention at an individual patient level. Further research is needed to assess the questionnaire's acceptability and usability, and to develop a scoring system so that domains can be prioritised and subsequently targeted as part of an intervention.

Economic Evaluation of Anesthesiology-Led Cardiac Implantable Electronic Device Service.

BACKGROUND: Implementation of an anesthesiology-led cardiac implantable electronic device (CIED) service can be viewed to have economic and efficiency challenges. This study evaluates the cost savings of an anesthesiology-led CIED service. METHODS: A total of 830 patients presented in the pre-implementation period from 1 March 2016 to 31 December 2017, and 1981 patients presented in the post-implementation period from 1 January 2018 to 31 October 2021. Interrupted time-series analysis for single-group comparisons was used to evaluate the cost savings resulting from reduction in operating room (OR) start delays for patients with CIEDs. RESULTS: OR start-time delay was reduced by 10.6 min (95%CI: -20.5 to -0.83), comparing pre- to post-implementation. For an OR cost of USD 45/min, we estimated the direct cost to the department to be USD 1.68/min. The intervention translated into a total cost reduction during the intervention period of USD 250,000 (USD 18,000 to USD 470,000) per year for the institution and USD 9800 (USD 730 to USD 17,000) per year for the department. The yearly cost of employing a full-time team of CIED specialists would have been USD 135,456. The service triggered electrophysiology consultation on 13 device malfunctions. CONCLUSIONS: An anesthesiology-led CIED service resulted in substantial cost savings, increased OR efficiency and patient safety.

Osteomyelitis in Sickle Cell Anemia: Does Age Predict Risk of Salmonella Infection?

BACKGROUND: Osteomyelitis is a condition that disproportionately affects those with sickle cell anemia (SCA). Despite the frequency of osteomyelitis in this population, there are reports of increasing life expectancy and rates of Staphylococcus aureus infections, which contrasts the belief that Salmonella is the most common organism identified. The purpose of this systematic review is to determine the most commonly identified organism and identify whether age is associated with the development of Salmonella osteomyelitis in homozygous sickle cell patients. METHODS: A search of PubMed, EMBASE Cochrane and databases was performed for studies of all levels of evidence pertaining to osteomyelitis in SCA. Reasons for exclusion included non-English language, case reports, literature reviews, isolated septic arthritis without bony involvement and isolated oral-facial bony involvement. RESULTS: The most common pathogen cultured was nontyphoid Salmonella , which occurred in 117 of 192 (60.9%) of cases identified. This was followed by S. aureus 41 of 192 (21.8%) and other enteric bacteria 14 of 192 (7.2%). Subgroup analysis demonstrated differences at the age of initial presentation with Salmonella cohort at 6.8 years and S. aureus cohort at 22.1 years ( P = 0.0001). On geographic analysis, African countries had an older average age of diagnosis at 13.1 years with decreased rates of Salmonella infections and increased rates of infections from other organisms compared with the US, Middle East and Europe. CONCLUSIONS: This systematic review suggests that Salmonella is most commonly identified in patients with SCA (HbSS phenotype) especially those <12 years old presenting with acute osteomyelitis. Sub-Saharan African countries had later ages of diagnosis compared with the US, Middle East and Europe with bacterial profiles that favors a diagnosis of chronic osteomyelitis and missed acute initial presentation. Therefore, age of presentation is likely a surrogate for geographic and socioeconomic factors such as availability of medical screening and treatment.

Supporting safe and gradual reduction of long-term benzodiazepine receptor agonist use: Development of the SAFEGUARDING-BZRAs toolkit using a codesign approach.

INTRODUCTION: Long-term benzodiazepine receptor agonist (BZRA) use persists in healthcare settings worldwide and poses risks of patient harm. OBJECTIVE: This study aimed to develop an intervention to support discontinuation of long-term BZRA use among willing individuals. METHODS: The intervention development process aligned with the UK Medical Research Council's complex intervention framework. This involved a previous systematic review of brief interventions targeting long-term BZRA use in primary care and qualitative interviews based on the Theoretical Domains Framework that explored barriers and facilitators to discontinuing long-term BZRA use. A codesign approach was used involving an active partnership between experts by experience, researchers and clinicians. Intervention content was specified in terms of behaviour change techniques (BCTs). RESULTS: The SAFEGUARDING-BZRAs (Supporting sAFE and GradUAl ReDuctIon of loNG-term BenZodiazepine Receptor Agonist uSe) toolkit comprises 24 BCTs and includes recommendations targeted at primary care-based clinicians for operationalizing each BCT to support individuals with BZRA discontinuation. CONCLUSION: The SAFEGUARDING-BZRAs toolkit has been developed using a systematic and theory-based approach that addresses identified limitations of previous research. Further research is needed to assess its usability and acceptability by service users and clinicians, as well as its potential to effectively support safe and gradual reduction of long-term BZRA use. PATIENT OR PUBLIC CONTRIBUTION: The qualitative interview phase included patients as participants. The codesign process included 'experts by experience' with either current or previous experience of long-term BZRA use as collaborators.

'I just thought that it was such an impossible thing': A qualitative study of barriers and facilitators to discontinuing long-term use of benzodiazepine receptor agonists using the Theoretical Domains Framework.

INTRODUCTION: Existing interventions to reduce long-term benzodiazepine receptor agonist (BZRA) use lack theoretical underpinning and detailed descriptions. This creates difficulties in understanding how interventions work and how to replicate them in practice. The Theoretical Domains Framework (TDF) can be used to identify behaviour change determinants to target during intervention development. OBJECTIVE: To explore barriers and facilitators to discontinuing BZRA use from the perspective of both current and previous long-term BZRA users. DESIGN/SETTING AND PARTICIPANTS: Semistructured TDF-based interviews were conducted with community-based individuals with current or previous experience of long-term BZRA use. Data were recorded, transcribed and analysed using the framework method. RESULTS: Twenty-eight individuals were interviewed. Despite commonalities in perceived barriers/facilitators to discontinuing BZRA use within individual TDF domains, individual participants had different experiences of identified determinants of BZRA discontinuation. For example, both similarities and differences existed within and between each participant group in terms of knowledge of the appropriate duration of BZRA use ('Knowledge' domain) and experience of withdrawal symptoms ('Reinforcement' domain). Compared to previous users, current users typically anticipated more barriers to discontinuing BZRA use and fewer positive consequences of discontinuation. CONCLUSION: This study reports on barriers and facilitators to discontinuing BZRA use from the perspectives of current and previous long-term users. The findings highlight the challenging nature of BZRA discontinuation and a multitude of barriers that impact participants' behaviour regarding BZRA use. Future work will involve developing a theory-based intervention to support BZRA discontinuation in primary care. PATIENT CONTRIBUTION: The study included patients as participants.

A Versatile, Secure, and Sustainable All-in-One Biobank-Registry Data Solution: The A3BC REDCap Model.

Introduction: A key element in the big data revolution is large-scale biobanking and the associated development of high-quality data collections and supporting informatics solutions. As such, in establishing the Australian Arthritis and Autoimmune Biobank Collaborative (A3BC), we sought to establish a low-cost, nation-scale data management system capable of managing a multisite biobank registry with complex longitudinal sample and data requirements. Materials and Methods: We assessed several international commercial and nonprofit software platforms using standardized system requirement criteria and follow-up interviews. Vendor compliance scoring was prioritized to meet our project-critical requirements. Consumer/end-user codesign was integral to refining our system requirements for optimized adoption. Customization of the selected software solution was performed to optimize field auto-population between participant timepoints and forms, using modules that are transferable and that do not impact core code. Institutional and independent testing was used to ensure data security. Results: We selected the widely used research web application Research Electronic Data Capture (REDCap), which is "free" (under nonprofit license agreement terms), highly configurable, and customizable to a variety of biobank and registry needs and can be developed/maintained by biobank users with modest IT skill, time, and cost. We created a secure, comprehensive participant-centric biobank-registry database that includes: (1) best practice data security measures (incl. multisite access login using institutional user credentials), (2) permission-to-contact and dynamic itemized electronic consent, (3) a complete chain of custody from consent to longitudinal biospecimen data collection to publication, (4) complex longitudinal patient-reported surveys, (5) integration of record-level extracted/linked participant data, (6) significant form auto-population for streamlined data capture, and (7) native dashboards for operational visualizations. Conclusion: We recommend the versatile, reusable, and sustainable informatics model we have developed in REDCap for prospective chronic disease biobanks or registry biobanks (of local to national complexity) supporting holistic research into disease prediction, precision medicine, and prevention strategies.

Skin Barrier Dysregulation in Psoriasis.

The skin barrier is broadly composed of two elements-a physical barrier mostly localised in the epidermis, and an immune barrier localised in both the dermis and epidermis. These two systems interact cooperatively to maintain skin homeostasis and overall human health. However, if dysregulated, several skin diseases may arise. Psoriasis is one of the most prevalent skin diseases associated with disrupted barrier function. It is characterised by the formation of psoriatic lesions, the aberrant differentiation and proliferation of keratinocytes, and excessive inflammation. In this review, we summarize recent discoveries in disease pathogenesis, including the contribution of keratinocytes, immune cells, genetic and environmental factors, and how they advance current and future treatments.

PET/CT features of lung SABR chest wall toxicity.

Stereotactic ablative radiotherapy offers a radical treatment approach for early stage lung cancers and an aggressive local therapy for pulmonary oligometastases from other tumour sites. Chest wall toxicity is one of the key dose-limiting toxicities for intrathoracic stereotactic treatments. The description of stereotactic radiotherapy chest wall toxicity using functional imaging has not been reported previously. A 56-year-old male received 60 Gy in 8 fractions delivered by volumetric modulated arc therapy for a T1bN0M0 clinical left upper lobe lung cancer. The past medical history included poorly controlled type 1 diabetes mellitus, severe peripheral vascular disease and obesity. The patient attended 9 months later with left-sided, slowly progressive chest pain. An 18 FDG PET/CT performed in order to investigate contralateral pulmonary lesions revealed FDG-avid focal thickening at the left superio-lateral thoracic wall with overlying inflammatory stranding in keeping with an indolent inflammatory process. Chest wall toxicity may present as pain, swelling, fracture and skin changes, and has the 18 FDG PET/CT chjmirocteristics of an inflammatory process. Patients with risk factors for chest wall toxicity, such as obesity, diabetes and smoking should be informed of their higher propensity for this clinically significant treatment side effect. For patients developing chest wall toxicity as demonstrated in this case with associated functional imaging findings, anti-inflammatory treatment should be promptly commenced.

Spontaneous regression of ALK fusion protein-positive non-small cell lung carcinoma: a case report and review of the literature.

BACKGROUND: ALK-rearrangement is observed in < 5% non-small cell lung cancer (NSCLC) cases and prior to the advent of oral tyrosine kinase inhibitors, the natural history of oncogenic NSCLC was typically poor. Literature relating to regression of treatment-naïve NSCLC is limited, and regression without treatment has not been noted in the ALK-rearranged sub-population. CASE PRESENTATION: A 76 year old 'never smoker' female with an ALK-rearranged left upper lobe T2 N0 NSCLC experienced a stroke following elective DC cardioversion for new atrial fibrillation. Following a good recovery, updated imaging demonstrated complete regression of the left upper lobe lesion and a reduction of the previously documented mediastinal lymph node. Remaining atelectasis was non-avid on repeat PET-CT imaging, 8 months from the baseline PET-CT. When the patient developed new symptoms 6 months later a further PET-CT demonstrated FDG-avid local recurrence. She completed 55 Gy in 20 fractions but at 18 months post-radiotherapy there was radiological progression in the lungs with new pulmonary metastases and effusion and new bone metastases. Owing to poor performance status, she was not considered fit for targeted therapy and died 5 months later. CONCLUSION: All reported cases of spontaneous regression in lung cancer have been collated within. Documented precipitants of spontaneous regression across tumour types include biopsy and immune reconstitution; stroke has not been reported previously. The favourable response achieved with radical radiotherapy alone in this unusual case of indolent oncogenic NSCLC reinforces the applicability of radiotherapy in locally advanced ALK-rearranged tumours, in cases not behaving aggressively. As a common embolic event affecting the neurological and pulmonary vasculature is less likely, an immune-mediated mechanism may underpin the phenomenon described in this patient, implying that hitherto unharnessed principles of immuno-oncology may have relevance in oncogenic NSCLC. Alternatively, high electrical voltage applied percutaneously adjacent to the tumour during cardioversion in this patient may have induced local tumour cell lethality.

Psychological therapy for mood instability within bipolar spectrum disorder: a single-arm feasibility study of a dialectical behaviour therapy-informed approach.

BACKGROUND: We sought to evaluate the acceptability of a psychological therapy programme (Therapy for Inter-episode Mood Variability in Bipolar Disorder (ThrIVe-B)) for individuals with ongoing bipolar mood instability and the feasibility and acceptability of potential trial procedures. We also evaluated the performance of clinical and process outcome measures and the extent to which the programme potentially represents a safe and effective intervention. METHOD: We conducted an open (uncontrolled) trial in which 12 individuals with a bipolar spectrum diagnosis commenced the ThrIVe-B programme after completing baseline assessments. The programme comprised 16 group skills training sessions plus individual sessions and a supporting smartphone application. Follow-up assessments were at therapy end-point and 6 months post-treatment. RESULTS: Nine participants completed treatment. Ten provided end-of-treatment data; of these, nine were satisfied with treatment. Interviews with participants and clinicians indicated that the treatment was broadly feasible and acceptable, with suggestions for improvements to content, delivery and study procedures. Exploration of change in symptoms was consistent with the potential for the intervention to represent a safe and effective intervention. CONCLUSIONS: Conducting further evaluation of this approach in similar settings is likely to be feasible, whilst patient reports and the pattern of clinical change observed suggest this approach holds promise for this patient group. Future research should include more than one study site and a comparison arm to address additional uncertainties prior to a definitive trial. TRIAL REGISTRATION: Trial Registration: ClinicalTrials.gov NCT02637401; registered 22.12.15 (retrospectively registered).

Brief interventions targeting long-term benzodiazepine and Z-drug use in primary care: a systematic review and meta-analysis.

AIMS: To assess the effectiveness of brief interventions in primary care aimed at reducing or discontinuing long-term benzodiazepine/Z-drug (BZRA) use. METHOD: Systematic review of randomized controlled trials of brief interventions in primary care settings aimed at reducing or discontinuing long-term BZRA use in adults taking BZRAs for ≥ 3 months. Four electronic databases were searched: PubMed, EMBASE, PsycINFO and CENTRAL. The primary outcome was BZRA use, classified as discontinuation or reduction by ≥ 25%. The Theoretical Domains Framework (TDF) was used to retrospectively code behavioural determinants targeted by the interventions. The Behaviour Change Technique (BCT) Taxonomy was used to identify the interventions' active components. Study-specific estimates were pooled, where appropriate, to yield summary risk ratios (RRs) and 95% confidence intervals (CIs). Pearson's correlations were used to determine the relationship between intervention effect size and the results of both the TDF and BCT coding. RESULTS: Eight studies were included (n = 2071 patients). Compared with usual care, intervention patients were more likely to have discontinued BZRA use at 6 months (eight studies, RR = 2.73, 95% CI = 1.84-4.06) and 12 months post-intervention (two studies, RR = 3.41, 95% CI = 2.22-5.25). TDF domains 'knowledge', 'memory, attention and decision processes', 'environmental context and resources' and 'social influences' were identified as having been included in every intervention. Commonly identified BCTs included 'information about health consequences', 'credible source' and 'adding objects to the environment'. There was no detectable relationship between effect size and the results of either the TDF or BCT coding. CONCLUSION: Brief interventions delivered in primary care are more effective than usual care in reducing and discontinuing long-term benzodiazepine/Z-drug use.

Composition of airway bacterial community correlates with chest HRCT in adults with bronchiectasis.

BACKGROUND AND OBJECTIVE: In bronchiectasis (BE) not caused by cystic fibrosis, chronic, polymicrobial airway infection contributes to the underlying pathogenesis of disease. There is little information on whether bacterial community composition relates to clinical status. We determined the relationship between bacterial community composition, chest high-resolution computed tomography (HRCT) scores and clinical markers in BE. METHODS: A subgroup of BE patients from a previous cross-sectional study were analysed. Spontaneously expectorated sputum was analysed using culture-independent sequencing on the Roche 454-FLX platform covering the V1-V3 region of the 16S rRNA marker gene. Chest HRCT scans, multiple breath washout, spirometry and blood inflammatory markers were collected. Spearman's rank (r) correlation coefficient was used to assess relationships. RESULTS: Data from 21 patients were analysed (mean (SD) age: 64.0 (7.7); female : male 14:7; mean (SD) forced expiratory volume in 1 s (FEV1 ): 76.5 (17.2)). All bacterial community composition metrics (bacterial richness, diversity, evenness and dominance) correlated with percentage BE score, with more severe HRCT abnormality relating to lower bacterial richness, evenness and diversity (range r = -0.47 to -0.66; P < 0.05). Inflammation (C-reactive protein and white cell count) was greater in patients with lower diversity and richness (range r = -0.44 to -0.47; P < 0.05). Bacterial community characteristics did not correlate with lung function. CONCLUSION: This is the first study to indicate a relationship between bacterial community characteristics by 16S rRNA marker gene sequencing, structural damage as determined by chest HRCT and clinical measures in BE. The association between loss of diversity and chest HRCT severity suggests that bacterial dominance with pathogenic bacteria may contribute to disease pathology.

The clinical and cost effectiveness of adapted dialectical behaviour therapy (DBT) for bipolar mood instability in primary care (ThrIVe-B programme): a feasibility study.

BACKGROUND: In bipolar spectrum disorder, some individuals experience ongoing, frequent fluctuations in mood outside of affective episodes. There are currently no evidence-based psychological interventions designed to address this. This feasibility study is a phase II evaluation of a dialectical behavioural therapy-informed approach (Therapy for Inter-episode mood Variability in Bipolar [ThrIVe-B]). It seeks to examine the feasibility and acceptability of a future definitive trial evaluating the clinical and cost effectiveness of the ThrIVe-B programme. METHODS/DESIGN: Patients will be randomised 1:1 to either treatment as usual only (control arm) or the ThrIVe-B intervention plus treatment as usual (intervention arm). Follow-up points will be at 3, 6, 9 and 15 months after baseline, with 9 months as the primary end point for the candidate primary outcome measures. We aim to recruit 48 individuals meeting diagnostic criteria for a bipolar spectrum disorder and reporting frequent mood swings outside of acute episodes, through primary and secondary care services and self-referral. To evaluate feasibility and acceptability, we will examine recruitment and retention rates, completion rates for study measures and feedback from participants on their experience of study participation and therapy. DISCUSSION: Proceeding to a definitive trial will be indicated if the following criteria are met: (1) trial participation does not lead to serious negative consequences for our participants; (2) any serious concerns about the acceptability and feasibility of the trial procedures can be rectified prior to a definitive trial; (3) follow-up data at 9 months are available for at least 60% of participants; (4) at least 60% of patients in the ThrIVe-B arm complete treatment. TRIAL REGISTRATION: ISRCTN, ISRCTN54234300 . Registered on 20 July 2017.

Direct Analysis of Oil Additives by High-Field Asymmetric Waveform Ion Mobility Spectrometry-Mass Spectrometry Combined with Electrospray Ionization and Desorption Electrospray Ionization.

The analysis of corrosion inhibitors in the presence and absence of an oil matrix is reported using electrospray ionization (ESI) and desorption electrospray ionization (DESI), hyphenated with miniaturized high-field asymmetric waveform ion mobility spectrometry (FAIMS) and mass spectrometry (MS). The target analytes were successfully ionized in solution by ESI and directly from steel surfaces using DESI ambient ionization at levels ≥0.0004% w/w (4 ppm) in oil. Differences in the mass spectral profiles observed for the additive/oil mixture are attributed to differences between the ESI and DESI ionization processes. The use of FAIMS improved selectivity for ESI generated analyte ions through reduction in the chemical noise resulting from the oil matrix. DESI enabled the direct, rapid, native state interrogation of oil samples on steel surfaces without sample pretreatment, and the hyphenation of DESI with the miniaturized FAIMS enhanced the relative analyte responses of the surface-active corrosion inhibitors.

Policy on palliative care in the WHO European region: an overview of progress since the Council of Europe's (2003) recommendation 24.

BACKGROUND: With the goal of achieving greater unity and coherence, the Council of Europe developed a national palliative care (PC) policy framework-Recommendation (2003) 24. Although directed at member states, the policy spread to the wider World Health Organisation (WHO) European Region. This article aims to present the current situation relating to national PC health policies in European countries. METHODS: A cross-sectional survey was conducted in 53 European countries of the WHO European Region. Relevant data reported (i) the existence of official documents concerning the provision of PC; (ii) the role of health departments and policymakers in the evaluation of PC provision and (iii) the availability of financial resources for PC provision. RESULTS: In total, 46/53 (87%) EU and non-EU countries responded. PC legislation is established in 20 (71%) EU and nine (50%) non-EU countries. A total of 12 (43%) EU countries possess a PC plan or strategy in comparison with six (33%) non-EU countries. Individuals from Departments of Health and designated policymakers have established collaborative PC efforts. Quality systems have been initiated in 15 (54%) EU and four (22%) non-EU countries. Significant differences were not found in the reporting of payments for PC services between European regions. CONCLUSION: An improvement in national PC policy in both EU and non-EU countries was observed. Future priorities include potential initiatives to improve relationships with policymakers, establish quality control programmes and ensure financial support for PC.

The financial burden of out of pocket prescription drug expenses in Canada.

Pharmaceutical expenditures account for approximately 15.9 % of total health expenditures in Canada. Unlike hospital and physician services, in which costs are universally covered, most pharmacological therapy does not fall under the umbrella of 'medically necessary' services set out by the Canada Health Act, and therefore is funded through a mix of public and private plans. Little is known about the actual financial burden experienced by Canadians from out-of-pocket drug expenditures (OOPDE). This paper examines the burden of OOPDE in Canada. 1.1 % of Canadian households exceed our catastrophic threshold (9 %) of the drug budget share. Additionally, 2.6 and 8.2 % of households exceed lower thresholds of 6 and 3 % respectively. We find an inverse relationship between household income and the burden of OPPDE. Low-income households have the highest likelihood of being in the 'catastrophic' drug expenditure category. This finding suggests that a vulnerable population of 'working poor' are likely to be experiencing disproportionate financial burden because they are not eligible for public assistance programs. Seniors experience the highest burden of OPPDE when compared to other age groups. We also find that there is significant interprovincial variation in the burden of OOPDE, which partly reflects different provincial government drug coverage policies.

Legal barriers in accessing opioid medicines: results of the ATOME quick scan of national legislation of eastern European countries.

CONTEXT: Overregulation of controlled medicines is one of the factors contributing to limited access to opioid medicines. OBJECTIVES: The purpose of this study was to identify legal barriers to access to opioid medicines in 12 Eastern European countries participating in the Access to Opioid Medication in Europa project, using a quick scan method. METHODS: A quick scan method to identify legal barriers was developed focusing on eight different categories of barriers. Key experts in 12 European countries were requested to send relevant legislation. Legislation was quick scanned using World Health Organization guidelines. Overly restrictive provisions and provisions that contain stigmatizing language and incorrect definitions were identified. The selected provisions were scored into two categories: 1) barrier and 2) uncertain, and reviewed by two authors. A barrier was recorded if both authors agreed the selected provision to be a barrier (Category 1). RESULTS: National legislation was obtained from 11 of 12 countries. All 11 countries showed legal barriers in the areas of prescribing (most frequently observed barrier). Ten countries showed barriers in the areas of dispensing and showed stigmatizing language and incorrect use of definitions in their legislation. Most barriers were identified in the legislation of Bulgaria, Greece, Lithuania, Serbia, and Slovenia. The Cypriot legislation showed the fewest total number of barriers. CONCLUSION: The selected countries have in common as main barriers prescribing and dispensing restrictions, the use of stigmatizing language, and incorrect use of definitions. The practical impact of these barriers identified using a quick scan method needs to be validated by other means.