Validation of a patient-reported outcome measure for giant cell arteritis.

OBJECTIVES: GCA is systemic vasculitis manifesting as cranial, ocular or large vessel vasculitis. A prior qualitative study developed 40 candidate items to assess the impact of GCA on health-related quality of life (HRQoL). This study aimed to determine final scale structure and measurement properties of the GCA patient reported outcome (GCA-PRO) measure. METHODS: Cross-sectional study included UK patients with clinician-confirmed GCA. They completed 40 candidate items for the GCA-PRO at times 1 and 2 (3 days apart), EQ-5D-5L, ICECAP-A, CAT-PROM5 and self-report of disease activity. Rasch and exploratory factor analyses informed item reduction and established structural validity, reliability and unidimensionality of the final GCA-PRO. Evidence of validity was also established with hypothesis testing (GCA-PRO vs other PRO scores, and between participants with 'active disease' vs those 'in remission') and test-retest reliability. RESULTS: The study population consisted of 428 patients: mean (s.d.) age 74.2 (7.2), 285 (67%) female; 327 (76%) cranial GCA, 114 (26.6%) large vessel vasculitis and 142 (33.2%) ocular involvement. Rasch analysis eliminated 10 candidate GCA items and informed restructuring of response categories into four-point Likert scales. Factor analysis confirmed four domains: acute symptoms (eight items), activities of daily living (seven items), psychological (seven items) and participation (eight items). The overall scale had adequate Rasch model fit (χ2 = 25.219, degrees of freedom = 24, P = 0.394). Convergent validity with EQ5D-5L, ICECAP-A and Cat-PROM5 was confirmed through hypothesis testing. Internal consistency and test-retest reliability were excellent. CONCLUSION: The final GCA-PRO is a 30-item, four-domain scale with robust evidence of validity and reliability in measuring HRQoL in people with GCA.

Measuring the impact of steroid therapy on health-related quality of life in patients with rheumatic diseases: international development of a glucocorticoid treatment-specific patient-reported outcome measure.

OBJECTIVES: Glucocorticoids (GCs) ('steroids') are used to treat rheumatic diseases but adverse effects are common. We aimed to explore the impact of GC therapy on health-related quality of life (HRQoL), to inform the development of a treatment-specific patient-reported outcome measure (PROM) for use in clinical trials and practice. METHODS: Semi-structured qualitative interviews were conducted with patients from the UK, USA and Australia, treated for a rheumatic condition with GCs in the last 2 years. Purposive sampling was used to select participants with a range of demographic and disease features. An initial conceptual framework informed interview prompts and cues. Interviews elicited GC-related physical and psychological symptoms and salient aspects of HRQoL in relation to GC therapy. Interview data were analysed inductively to develop initial individual themes and domains. Candidate questionnaire items were developed and refined. RESULTS: Sixty semi-structured qualitative interviews were conducted (UK n = 34, USA n = 10, Australia n = 16). The mean age was 58 years; 39/60 were female; and 18 rheumatic diseases were represented. Some 126 individual themes were identified and organized into six domains: physical symptoms; psychological symptoms; psychological impact of steroids; impact of steroids on participation; impact of steroids on relationships; and benefits of steroids. Candidate questionnaire items were tested and refined by piloting with patient research partners, iterative rounds of cognitive interviews and linguistic translatability assessment, informing a draft questionnaire. CONCLUSION: We describe an international qualitative study to develop candidate items for a treatment-specific PROM for patients with rheumatic diseases. A future survey will enable the validation of a final version of the PROM.

Patient perceptions of health-related quality of life in giant cell arteritis: international development of a disease-specific patient-reported outcome measure.

OBJECTIVES: GCA is a large vessel vasculitis (LVV) presenting with headache, jaw claudication, musculoskeletal and visual involvement. Current treatment is glucocorticoids and anti-IL-6 tocilizumab in refractory disease. The objective of this study was to explore the impact of GCA and its treatment on people's health-related quality of life (HRQoL), to inform the development of a disease-specific patient-reported outcome measure (PROM) for use in clinical trials and practice. METHODS: Participants from the UK and Australia, with biopsy- or imaging-confirmed GCA, were interviewed to identify salient aspects of HRQoL in relation to GCA and its treatment. Purposive sampling included a range of demographic and disease features (cranial, LVV-GCA and visual involvement). Inductive analysis identified individual themes of importance, then domains. Candidate questionnaire items were developed from the individual themes, refined by piloting, cognitive interviews and a linguistic translatability assessment. RESULTS: Thirty-six interviews were conducted to saturation with participants with GCA from the UK (25) and Australia (11). Mean age was 74 years, 23 (63.9%) were female, 13 (36.1%) had visual loss and 5 (13.9%) had LVV-GCA. Thirty-nine individual themes within five domains were identified: physical symptoms; activity of daily living and function; participation; psychological impact; and impact on sense of self and perception of health. Sixty-nine candidate items were developed from individual themes; piloting and refinement resulted in a 40-item draft questionnaire. CONCLUSION: This international qualitative study underpins the development of candidate items for a disease-specific PROM for GCA. The draft questionnaire is now ready for psychometric testing.

Reducing arthritis fatigue impact: two-year randomised controlled trial of cognitive behavioural approaches by rheumatology teams (RAFT).

OBJECTIVES: To see if a group course delivered by rheumatology teams using cognitive-behavioural approaches, plus usual care, reduced RA fatigue impact more than usual care alone. METHODS: Multicentre, 2-year randomised controlled trial in RA adults (fatigue severity>6/10, no recent major medication changes). RAFT (Reducing Arthritis Fatigue: clinical Teams using CB approaches) comprises seven sessions, codelivered by pairs of trained rheumatology occupational therapists/nurses. Usual care was Arthritis Research UK fatigue booklet. Primary 26-week outcome fatigue impact (Bristol RA Fatigue Effect Numerical Rating Scale, BRAF-NRS 0-10). Intention-to-treat regression analysis adjusted for baseline scores and centre. RESULTS: 308/333 randomised patients completed 26 week data (156/175 RAFT, 152/158 Control). Mean baseline variables were similar. At 26 weeks, the adjusted difference between arms for fatigue impact change favoured RAFT (BRAF-NRS Effect -0.59, 95% CI -1.11 to -0.06), BRAF Multidimensional Questionnaire (MDQ) Total -3.42 (95% CI -6.44 to -0.39), Living with Fatigue -1.19 (95% CI -2.17 to -0.21), Emotional Fatigue -0.91 (95% CI -1.58 to -0.23); RA Self-Efficacy (RASE, +3.05, 95% CI 0.43 to 5.66) (14 secondary outcomes unchanged). Effects persisted at 2 years: BRAF-NRS Effect -0.49 (95% CI -0.83 to -0.14), BRAF MDQ Total -2.98 (95% CI -5.39 to -0.57), Living with Fatigue -0.93 (95% CI -1.75 to -0.10), Emotional Fatigue -0.90 (95% CI -1.44, to -0.37); BRAF-NRS Coping +0.42 (95% CI 0.08 to 0.77) (relevance of fatigue impact improvement uncertain). RAFT satisfaction: 89% scored > 8/10 vs 54% controls rating usual care booklet (p<0.0001). CONCLUSION: Multiple RA fatigue impacts can be improved for 2 years by rheumatology teams delivering a group programme using cognitive behavioural approaches. TRIAL REGISTRATION NUMBER: ISRCTN52709998.

Patient preferences for psychological support in inflammatory arthritis: a multicentre survey.

OBJECTIVES: Inflammatory arthritis (IA) can lead to anxiety, depression, pain and fatigue. Psychological support can improve quality of life and self-management; and European and American guidelines recommend support be offered. This study examined patient views on psychological support for their IA. METHODS: A questionnaire designed by researchers, patient partners and clinicians was administered to 2280 patients with IA. RESULTS: 1210 patients responded (53%): 74% women; mean age 59 years (SD 12.7); patient global 5 (2.3); disease duration <5 years (41%), 5-10 (20%), >10 (39%). Only 23% reported routinely being asked about social and emotional issues by a rheumatology professional, but 46% would like the opportunity to discuss psychological impact. If offered, 66% of patients reported they would use a self-management/coping clinic (63% pain management, 60% occupational therapy, 48% peer support groups, 46% patient education, 46% psychology/counselling). Patients want support with managing the impact of pain and fatigue (82%), managing emotions (57%), work and leisure (52%), relationships (37%) and depression (34%). Preferences are for support to be delivered by the rheumatology team (nurse 74%, doctor 55%) and general practitioners (GPs) (51%). Only 6% of patients stated that social and emotional issues were not relevant. CONCLUSIONS: Demand for psychological support is high; however, less than a quarter of patients reported being asked about social and emotional issues, suggesting a gap between needs and provision. The preference is for delivery from rheumatology clinicians and GPs, and research should establish whether they have the skills and resources to meet patients' needs.

Biologic interventions for fatigue in rheumatoid arthritis.

BACKGROUND: Fatigue is a common and potentially distressing symptom for patients with rheumatoid arthritis (RA), with no accepted evidence-based management guidelines. Evidence suggests that biologic interventions improve symptoms and signs in RA as well as reducing joint damage. OBJECTIVES: To evaluate the effect of biologic interventions on fatigue in rheumatoid arthritis. SEARCH METHODS: We searched the following electronic databases up to 1 April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Controlled Trials Register, the National Research Register Archive, The UKCRN Portfolio Database, AMED, CINAHL, PsycINFO, Social Science Citation Index, Web of Science, and Dissertation Abstracts International. In addition, we checked the reference lists of articles identified for inclusion for additional studies and contacted key authors. SELECTION CRITERIA: We included randomised controlled trials if they evaluated a biologic intervention in people with rheumatoid arthritis and had self reported fatigue as an outcome measure. DATA COLLECTION AND ANALYSIS: Two reviewers selected relevant trials, assessed methodological quality and extracted data. Where appropriate, we pooled data in meta-analyses using a random-effects model. MAIN RESULTS: We identified 32 studies for inclusion in this current review. Twenty studies evaluated five anti-tumour necrosis factor (anti-TNF) biologic agents (adalimumab, certolizumab, etanercept, golimumab and infliximab), and 12 studies focused on five non-anti-TNF biologic agents (abatacept, canakinumab, rituximab, tocilizumab and an anti-interferon gamma monoclonal antibody). All but two of the studies were double-blind randomised placebo-controlled trials. In some trials, patients could receive concomitant disease-modifying anti-rheumatic drugs (DMARDs). These studies added either biologics or placebo to DMARDs. Investigators did not change the dose of the latter from baseline. In total, these studies included 9946 participants in the intervention groups and 4682 participants in the control groups. Overall, quality of randomised controlled trials was moderate with a low to unclear risk of bias in the reporting of the outcome of fatigue. We downgraded the quality of the studies from high to moderate because of potential reporting bias (studies included post hoc analyses favouring reporting of positive result and did not always include all randomised individuals). Some studies recruited only participants with early disease. The studies used five different instruments to assess fatigue in these studies: the Functional Assessment of Chronic Illness Therapy Fatigue Domain (FACIT-F), Short Form-36 Vitality Domain (SF-36 VT), Visual Analogue Scale (VAS) (0 to 100 or 0 to 10) and the Numerical Rating Scale (NRS). We calculated standard mean differences for pooled data in meta-analyses. Overall treatment by biologic agents led to statistically significant reduction in fatigue with a standardised mean difference of -0.43 (95% confidence interval (CI) -0.38 to -0.49). This equates to a difference of 6.45 units (95% CI 5.7 to 7.35) of FACIT-F score (range 0 to 52). Both types of biologic agents achieved a similar level of improvement: for anti-TNF agents, this stood at -0.42 (95% CI -0.35 to -0.49), equivalent to 6.3 units (95% CI 5.3 to 7.4) on the FACIT-F score; and for non-anti-TNF agents, it was -0.46 (95% CI -0.39 to -0.53), equivalent to 6.9 units (95% CI 5.85 to 7.95) on the FACIT-F score. In most studies, the double-blind period was 24 weeks or less. No study assessed long-term changes in fatigue. AUTHORS' CONCLUSIONS: Treatment with biologic interventions in patients with active RA can lead to a small to moderate improvement in fatigue. The magnitude of improvement is similar for anti-TNF and non-anti-TNF biologics. However, it is unclear whether the improvement results from a direct action of the biologics on fatigue or indirectly through reduction in inflammation, disease activity or some other mechanism.

Jaw claudication and jaw stiffness in giant cell arteritis: secondary analysis of a qualitative research dataset.

Objective: Jaw symptoms can be a vital clue to the diagnosis of GCA. Guidelines recommend more intensive treatment if jaw claudication is present. We sought to explore how patients with GCA described their jaw symptoms. Methods: We carried out a secondary, qualitative analysis of interview data from 36 participants from the UK (n = 25) and Australia (n = 11), originally collected in order to develop a patient-reported outcome measure for GCA. In all cases, GCA had been confirmed by biopsy/imaging. Interview transcripts were organized within QSR NVivo 12 software and analysed using template analysis. Themes were refined through discussion among the research team, including a patient partner. Results: Twenty of 36 participants reported jaw symptoms associated with GCA. The median age of these 20 participants was 76.5 years; 60% were female. Five themes were identified: physical sensations; impact on function; impact on diet; symptom response with CSs; and attribution to other causes. Physical sensations included ache, cramp, stiffness and 'lockjaw'. Functional impacts included difficulty in eating/chewing, cleaning teeth, speaking or opening the mouth. Dietary impacts included switching to softer food. Response to CSs was not always immediate. Jaw symptoms were initially mis-attributed by some participants to arthritis, age or viral illnesses; or by health-care professionals to a dental cavity, ear infection or teeth-grinding. Conclusion: Jaw symptoms in GCA are diverse and can lead to diagnostic confusion with primary temporomandibular joint disorder, potentially contributing to delay in GCA diagnosis. Further research is needed to determine the relationship of jaw stiffness to jaw claudication.

Non-pharmacological interventions for fatigue in rheumatoid arthritis.

BACKGROUND: Fatigue is a common and potentially distressing symptom for people with rheumatoid arthritis with no accepted evidence based management guidelines. Non-pharmacological interventions, such as physical activity and psychosocial interventions, have been shown to help people with a range of other long-term conditions to manage subjective fatigue. OBJECTIVES: To evaluate the benefit and harm of non-pharmacological interventions for the management of fatigue in people with rheumatoid arthritis. This included any intervention that was not classified as pharmacological in accordance with European Union (EU) Directive 2001/83/EEC. SEARCH METHODS: The following electronic databases were searched up to October 2012, Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; AMED; CINAHL; PsycINFO; Social Science Citation Index; Web of Science; Dissertation Abstracts International; Current Controlled Trials Register; The National Research Register Archive; The UKCRN Portfolio Database. In addition, reference lists of articles identified for inclusion were checked for additional studies and key authors were contacted. SELECTION CRITERIA: Randomised controlled trials were included if they evaluated a non-pharmacological intervention in people with rheumatoid arthritis with self-reported fatigue as an outcome measure. DATA COLLECTION AND ANALYSIS: Two review authors selected relevant trials, assessed risk of bias and extracted data. Where appropriate, data were pooled using meta-analysis with a random-effects model. MAIN RESULTS: Twenty-four studies met the inclusion criteria, with a total of 2882 participants with rheumatoid arthritis. Included studies investigated physical activity interventions (n = 6 studies; 388 participants), psychosocial interventions (n = 13 studies; 1579 participants), herbal medicine (n = 1 study; 58 participants), omega-3 fatty acid supplementation (n = 1 study; 81 participants), Mediterranean diet (n = 1 study; 51 participants), reflexology (n = 1 study; 11 participants) and the provision of Health Tracker information (n = 1 study; 714 participants). Physical activity was statistically significantly more effective than the control at the end of the intervention period (standardized mean difference (SMD) -0.36, 95% confidence interval (CI) -0.62 to -0.10; back translated to mean difference of 14.4 points lower, 95% CI -4.0 to -24.8 on a 100 point scale where a lower score means less fatigue; number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 4 to 26) demonstrating a small beneficial effect upon fatigue. Psychosocial intervention was statistically significantly more effective than the control at the end of the intervention period (SMD -0.24, 95% CI -0.40 to -0.07; back translated to mean difference of 9.6 points lower, 95% CI -2.8 to -16.0 on a 100 point scale, lower score means less fatigue; NNTB 10, 95% CI 6 to 33) demonstrating a small beneficial effect upon fatigue. For the remaining interventions meta-analysis was not possible and there was either no statistically significant difference between trial arms or findings were not reported. Only three studies reported any adverse events and none of these were serious, however, it is possible that the low incidence was in part due to poor reporting. The quality of the evidence ranged from moderate quality for physical activity interventions and Mediterranean diet to low quality for psychosocial interventions and all other interventions. AUTHORS' CONCLUSIONS: This review provides some evidence that physical activity and psychosocial interventions provide benefit in relation to self-reported fatigue in adults with rheumatoid arthritis. There is currently insufficient evidence of the effectiveness of other non-pharmacological interventions.

The Brazilian health system: history, advances, and challenges.

Brazil is a country of continental dimensions with widespread regional and social inequalities. In this report, we examine the historical development and components of the Brazilian health system, focusing on the reform process during the past 40 years, including the creation of the Unified Health System. A defining characteristic of the contemporary health sector reform in Brazil is that it was driven by civil society rather than by governments, political parties, or international organisations. The advent of the Unified Health System increased access to health care for a substantial proportion of the Brazilian population, at a time when the system was becoming increasingly privatised. Much is still to be done if universal health care is to be achieved. Over the past 20 years, there have been other advances, including investments in human resources, science and technology, and primary care, and a substantial decentralisation process, widespread social participation, and growing public awareness of a right to health care. If the Brazilian health system is to overcome the challenges with which it is presently faced, strengthened political support is needed so that financing can be restructured and the roles of both the public and private sector can be redefined.

Health conditions and health-policy innovations in Brazil: the way forward.

Brazil is a large complex country that is undergoing rapid economic, social, and environmental change. In this Series of six articles, we have reported important improvements in health status and life expectancy, which can be ascribed largely to progress in social determinants of health and to implementation of a comprehensive national health system with strong social participation. Many challenges remain, however. Socioeconomic and regional disparities are still unacceptably large, reflecting the fact that much progress is still needed to improve basic living conditions for a large proportion of the population. New health problems arise as a result of urbanisation and social and environmental change, and some old health issues remain unabated. Administration of a complex, decentralised public-health system, in which a large share of services is contracted out to the private sector, together with many private insurance providers, inevitably causes conflict and contradiction. The challenge is ultimately political, and we conclude with a call for action that requires continuous engagement by Brazilian society as a whole in securing the right to health for all Brazilian people.

Remotely delivered cognitive-behavioural and personalized exercise interventions to lessen the impact of fatigue: a qualitative evaluation.

Objectives: Fatigue can be a disabling symptom of inflammatory rheumatic diseases. LIFT (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomized Trial) is a randomized trial of remotely delivered cognitive-behavioural approach or personalized exercise programme interventions, compared with usual care. The aim of this nested qualitative study was to evaluate participants' experiences of taking part in the intervention, including their ideas about future service delivery. Methods: Semi-structured telephone interviews were conducted with a subgroup of LIFT participants to discuss their views and experiences of the interventions. Results: Forty-three participants (30 women) from six sites who had participated in the cognitive-behavioural approach (n = 22) or personalized exercise programme (n = 21) interventions took part. Five themes were identified in the thematic analysis. In the theme 'not a miracle cure, but a way to better manage fatigue', LIFT could not cure fatigue; however, most felt better able to manage after participating. Participants valued 'building a therapeutic relationship' with the same therapist throughout the intervention. In 'structure, self-monitoring and being accountable', participants liked the inclusion of goal-setting techniques and were motivated by reporting back to the therapist.After taking part in the interventions, participants felt 'better equipped to cope with fatigue'; more confident and empowered. Lastly, participants shared ideas for 'a tailored programme delivered remotely', including follow-up sessions, video calling, and group-based sessions for social support. Conclusion: Many participants engaged with the LIFT interventions and reported benefits of taking part. This suggests an important future role for the remote delivery of fatigue self-management.

Therapists' experiences of remotely delivering cognitive-behavioural or graded-exercise interventions for fatigue: a qualitative evaluation.

Objective: Fatigue is a challenging feature of all inflammatory rheumatic diseases. LIFT (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomized Trial) included remotely delivered personalized exercise programme (PEP) or cognitive-behavioural approach (CBA) interventions. The aim of this nested qualitative evaluation was to understand rheumatology health professionals' (therapists') perspectives of delivering the interventions in the LIFT trial. Methods: A subgroup of therapists who had delivered the personalized exercise programme (PEP) and cognitive-behavioural approach (CBA) interventions took part in semi-structured telephone interviews. Results: Seventeen therapists (13 women and 4 men) who delivered PEP (n = 8) or CBA (n = 9) interventions participated. Five themes were identified. In 'The benefits of informative, structured training', therapists described how they were able to practice their skills, and the convenience of having the LIFT manual for reference. When 'Getting into the swing of it', supporting patients gave therapists the confidence to tailor the content of the manual to each patient. Clinical supervision supported therapists to gain feedback and request assistance when required. In 'Delivering the intervention', therapists reported that patients valued the opportunity to talk about their fatigue and challenge their beliefs. In 'Challenges in delivering the LIFT intervention', therapists struggled to work in partnership with patients who lacked motivation or stopped engaging. Finally, in 'LIFT developing clinical skills', therapists gained confidence and professional satisfaction, seeing patients' fatigue improve over time. Conclusion: The findings support the provision of training for rheumatology health professionals to remotely deliver fatigue-management interventions. Insights from these trials can be used to better improve clinical practice and service provision.

Patient Perceptions of Physical Activity After a Diagnosis of Giant Cell Arteritis: Analysis of Multinational Qualitative Data.

OBJECTIVE: To explore patient perceptions of physical activity in giant cell arteritis (GCA). METHODS: This was a multinational qualitative study, analyzing interview data collected from participants from the UK (n = 25) and Australia (n = 11) with a definitive diagnosis of GCA from imaging or biopsy. Interview transcripts were analyzed using thematic analysis to identify themes related to physical activity. This was secondary analysis of data collected to explore health-related quality of life in people with GCA. RESULTS: A total of 108 individual codes pertaining to physical activity were identified. These were grouped into 2 overarching themes: barriers to and facilitators of physical activity, each with 4 subthemes. Barriers were categorized into physical symptoms (including visual loss, fatigue, weakness, pain, and stiffness), perceptions of personal capability (including poor stamina, confidence, and mobility), negative perceptions of physical activity, and negative consequences. Facilitators of physical activity were categorized into external facilitators (including motivation from health care professionals and support groups), access to appropriate facilities, personal strategies (including pacing and goal-setting), and personal facilitators (including internal motivation to improve symptoms, and positive reinforcement). CONCLUSION: A range of barriers and facilitators to physical activity were identified in relation to GCA. Future work could include development of an intervention to support physical activity in patients with GCA; ideally this intervention should be underpinned by an appropriate behavioral change framework and codesigned with patients.

Global Health Diplomacy (GHD) and the integration of health into foreign policy: Towards a conceptual approach.

Since the end of the Cold War, health has gone from a peripheral concern in foreign policy negotiations to a prominent place on the global political agenda. While the rise of health onto the foreign policy agenda is by now old news, the driving forces behind its expansion into new political spheres remain understudied and undertheorized. This article builds on empirical findings from a four-country study of the integration of health into foreign policy, and proposes a conceptual approach to GHD to improve understanding of the conditions under which health is successfully positioned on the foreign policy agenda. Our approach consists of three dimensions: features of institutions and the interest various actors represent in GHD; the ideational environment in which GHD operates; and issue characteristics of the specific health concern entering foreign policy. Within each dimension, we identify specific variables that, in combination, make up the explanatory power of the proposed approach. The proposed approach does not relate to, or build upon, a single social sciences, public health, or international relations (IR) theory, but can be seen as a heuristic device to identify dimensions and variables that may shape why certain health issues rise onto the foreign policy agenda.

Self-management of fatigue in rheumatoid arthritis: a randomised controlled trial of group cognitive-behavioural therapy.

OBJECTIVES: To investigate the effect of group cognitive behavioural therapy (CBT) for fatigue self-management, compared with groups receiving fatigue information alone, on fatigue impact among people with rheumatoid arthritis (RA). METHODS: Two-arm, parallel randomised controlled trial in adults with RA, fatigue ≥ 6/10 (Visual Analogue Scale (VAS) 0-10, high bad) and no recent change in RA medication. Group CBT for fatigue self-management comprised six (weekly) 2 h sessions, and consolidation session (week 14). Control participants received fatigue self-management information in a 1 h didactic group session. Primary outcome at 18 weeks was the impact of fatigue measured using two methods (Multi-dimensional Assessment of Fatigue (MAF) 0-50; VAS 0-10), analysed using intention-to-treat analysis of covariance with multivariable regression models. RESULTS: Of 168 participants randomised, 41 withdrew before entry and 127 participated. There were no major baseline differences between the 65 CBT and 62 control participants. At 18 weeks CBT participants reported better scores than control participants for fatigue impact: MAF 28.99 versus 23.99 (adjusted difference -5.48, 95% CI -9.50 to -1.46, p=0.008); VAS 5.99 versus 4.26 (adjusted difference -1.95, 95% CI -2.99 to -0.90, p<0.001). Standardised effect sizes for fatigue impact were MAF 0.59 (95% CI 0.15 to 1.03) and VAS 0.77 (95% CI 0.33 to 1.21), both in favour of CBT. Secondary outcomes of perceived fatigue severity, coping, disability, depression, helplessness, self-efficacy and sleep were also better in CBT participants. CONCLUSIONS: Group CBT for fatigue self-management in RA improves fatigue impact, coping and perceived severity, and well-being. TRIAL REGISTRATION: ISRCTN 32195100.

Toxicity of boron and vanadium nanoparticles on Danio rerio embryos - Phenotypical, biochemical, and behavioral alterations.

Engineered nanoparticles (NPs) are emerging contaminants of concern and it is important to understand their environmental behavior and ecological risks to exposed organisms. Despite their ubiquitous presence in the environment, there is little information about the hazards of certain NPs, such as boron (BNPs) and vanadium (VNPs). The aim of the present research was to investigate the effects of commercial BNPs and VNPs (80 to 100 nm) to zebrafish embryos, at different levels of biological organization. A range of nominal concentrations for both NPs (0, 0.01, 0.1, 1, and 10 mg/L) was tested. Due to the presence of triton X-100 in the NPs' stock dispersions, an additional control group was included (0.001% triton X-100). Survival, hatching, and malformations of embryos were assessed for 96 hours (h) exposure. Locomotor behavior was evaluated at 120 h. Furthermore, embryos were exposed to 0, 1, and 10 mg/L of NPs to evaluate a set of biomarker responses after 96 h: cholinesterase (ChE) and glutathione S-transferase (GST) activities, total glutathione (TG) and energy budgets levels. VNPs induced malformations (10 mg/L), hyperactivity (10 mg/L), erratic swimming (0.01 mg/L), altered swimming pattern (>0.01 mg/L), delayed hatching (10 mg/L) and altered biochemical responses involved in antioxidant defense (GST and TG at >1 mg/L), neurotransmission (ChE at 10 mg/L) and energy metabolism (lipids at >1 mg/L and carbohydrates at 10 mg/L). BNPs caused malformations (10 mg/L), affected swimming pattern (>0.01 mg/L), induced erratic swimming (10 mg/L) and decreased TG content and GST activity (>1 mg/L). At the same concentrations, VNPs affected a greater number of endpoints than BNPs, demonstrating a greater toxicity to zebrafish embryos. The present study shows that BNPs and VNPs may affect aquatic organisms, albeit at relatively great non-environmentally relevant concentrations, reinforcing the importance of the risk assessment of different NPs.

Group cognitive-behavioural programme to reduce the impact of rheumatoid arthritis fatigue: the RAFT RCT with economic and qualitative evaluations.

BACKGROUND: Fatigue is a major problem in rheumatoid arthritis (RA). There is evidence for the clinical effectiveness of cognitive-behavioural therapy (CBT) delivered by clinical psychologists, but few rheumatology units have psychologists. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of a group CBT programme for RA fatigue [named RAFT, i.e. Reducing Arthritis Fatigue by clinical Teams using cognitive-behavioural (CB) approaches], delivered by the rheumatology team in addition to usual care (intervention), with usual care alone (control); and to evaluate tutors' experiences of the RAFT programme. DESIGN: A randomised controlled trial. Central trials unit computerised randomisation in four consecutive cohorts within each of the seven centres. A nested qualitative evaluation was undertaken. SETTING: Seven hospital rheumatology units in England and Wales. PARTICIPANTS: Adults with RA and fatigue severity of ≥ 6 [out of 10, as measured by the Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scale (BRAF-NRS)] who had no recent changes in major RA medication/glucocorticoids. INTERVENTIONS: RAFT - group CBT programme delivered by rheumatology tutor pairs (nurses/occupational therapists). Usual care - brief discussion of a RA fatigue self-management booklet with the research nurse. MAIN OUTCOME MEASURES: Primary - fatigue impact (as measured by the BRAF-NRS) at 26 weeks. Secondary - fatigue severity/coping (as measured by the BRAF-NRS); broader fatigue impact [as measured by the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ)]; self-reported clinical status; quality of life; mood; self-efficacy; and satisfaction. All data were collected at weeks 0, 6, 26, 52, 78 and 104. In addition, fatigue data were collected at weeks 10 and 18. The intention-to-treat analysis conducted was blind to treatment allocation, and adjusted for baseline scores and centre. Cost-effectiveness was explored through the intervention and RA-related health and social care costs, allowing the calculation of quality-adjusted life-years (QALYs) with the EuroQol-5 Dimensions, five-level version (EQ-5D-5L). Tutor and focus group interviews were analysed using inductive thematic analysis. RESULTS: A total of 308 out of 333 patients completed 26 weeks (RAFT, n/N = 156/175; control, n/N = 152/158). At 26 weeks, the mean BRAF-NRS impact was reduced for the RAFT programme (-1.36 units; p < 0.001) and the control interventions (-0.88 units; p < 0.004). Regression analysis showed a difference between treatment arms in favour of the RAFT programme [adjusted mean difference -0.59 units, 95% confidence interval (CI) -1.11 to -0.06 units; p = 0.03, effect size 0.36], and this was sustained over 2 years (-0.49 units, 95% CI -0.83 to -0.14 units; p = 0.01). At 26 weeks, further fatigue differences favoured the RAFT programme (BRAF-MDQ fatigue impact: adjusted mean difference -3.42 units, 95% CI -6.44 to - 0.39 units, p = 0.03; living with fatigue: adjusted mean difference -1.19 units, 95% CI -2.17 to -0.21 units, p = 0.02; and emotional fatigue: adjusted mean difference -0.91 units, 95% CI -1.58 to -0.23 units, p = 0.01), and these fatigue differences were sustained over 2 years. Self-efficacy favoured the RAFT programme at 26 weeks (Rheumatoid Arthritis Self-Efficacy Scale: adjusted mean difference 3.05 units, 95% CI 0.43 to 5.6 units; p = 0.02), as did BRAF-NRS coping over 2 years (adjusted mean difference 0.42 units, 95% CI 0.08 to 0.77 units; p = 0.02). Fatigue severity and other clinical outcomes were not different between trial arms and no harms were reported. Satisfaction with the RAFT programme was high, with 89% of patients scoring ≥ 8 out of 10, compared with 54% of patients in the control arm rating the booklet (p < 0.0001); and 96% of patients and 68% of patients recommending the RAFT programme and the booklet, respectively, to others (p < 0.001). There was no significant difference between arms for total societal costs including the RAFT programme training and delivery (mean difference £434, 95% CI -£389 to £1258), nor QALYs gained (mean difference 0.008, 95% CI -0.008 to 0.023). The probability of the RAFT programme being cost-effective was 28-35% at the National Institute for Health and Care Excellence's thresholds of £20,000-30,000 per QALY. Tutors felt that the RAFT programme's CB approaches challenged their usual problem-solving style, helped patients make life changes and improved tutors' wider clinical practice. LIMITATIONS: Primary outcome data were missing for 25 patients; the EQ-5D-5L might not capture fatigue change; and 30% of the 2-year economic data were missing. CONCLUSIONS: The RAFT programme improves RA fatigue impact beyond usual care alone; this was sustained for 2 years with high patient satisfaction, enhanced team skills and no harms. The RAFT programme is < 50% likely to be cost-effective; however, NHS costs were similar between treatment arms. FUTURE WORK: Given the paucity of RA fatigue interventions, rheumatology teams might investigate the pragmatic implementation of the RAFT programme, which is low cost. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52709998. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 57. See the NIHR Journals Library website for further project information.

Rheumatoid arthritis (RA) is a lifelong inflammatory condition affecting multiple joints, with fatigue as a major consequence. Cognitive­behavioural therapy (CBT) helps patients work out links between symptoms, behaviours and thoughts driving those behaviours (e.g. why someone pushes on when exhausted), and understanding these links helps patients make changes. A CBT programme for groups of RA patients, facilitated by a psychologist, reduces fatigue impact. However, few rheumatology teams have psychologists. The study tested whether or not rheumatology nurses and occupational therapists (OTs) could facilitate the programme [named RAFT, i.e. Reducing Arthritis Fatigue by clinical Teams using cognitive­behavioural (CB) approaches] after brief training. The study compared the RAFT programme with usual care for RA fatigue (i.e. a short discussion of an arthritis fatigue booklet). All 333 patients received usual care, and then half of the patients were allocated (by chance) to also attend the seven-session RAFT programme. The study compared the RAFT programme with usual care for effects on fatigue, quality of life, cost and value for money. In addition, the rheumatology nurse and OT RAFT tutors were interviewed for their views on the RAFT programme. The study found that patients' fatigue impact was reduced by both the RAFT programme and usual care at 6 months and 2 years, but patients undertaking the RAFT programme improved significantly more than those receiving usual care alone. Differences were seen for improvements in fatigue impact, fatigue coping, emotional fatigue and living with fatigue. Patients were very satisfied with the RAFT programme and attended most of the sessions. The study found no significant difference between the NHS costs of the RAFT programme and usual care. Neither the RAFT programme nor usual care changed quality of life; therefore, standard value-for-money tests showed no difference between them. Tutors found that the CB questioning approach of the RAFT programme was different from their usual problem-solving style, but helped patients make life changes, and the new CB skills improved tutors' wider clinical practice. In conclusion, the trial has shown that the RAFT programme has a small to medium effect on reducing fatigue impact in patients with RA and is a potentially low-cost intervention that can be delivered by rheumatology nurses and OTs rather than a psychologist.

Pharmaceutical Services in Mozambique: foreign aid in public provision of medicines. / Assistência Farmacêutica em Moçambique: a ajuda externa na provisão pública de medicamentos.

This article examines the activities of national and international actors in Pharmaceutical Services (PS) in Mozambique from 2007 to 2012, focusing on the public provision of HIV/Aids, malaria and tuberculosis medicines. It describes how PS functions in the country, what actors are involved in this area and the relations among them, pursuing salient issues in the modus operandi of partners in cooperation. The methodology combines literature review, document survey and analysis and interviews. The theoretical and analytical framework was given by the policy analysis approach, focusing on the role of the State and its interrelations with other actors in foreign aid in PS, and also by the networks approach. It was concluded that the interactions among the actors involved is complex and characterised by operational fragmentation and overlapping of activities between entities, centralised medicine procurement in the hands of few agents, bypassing of national structures and disregard for the strengthening needed to bolster national health system autonomy. Despite some advances in the provision and availability of medicines for these diseases, external dependence is strong, which undermines the sustainability of PS in Mozambique.

Este artigo analisa a ação de atores nacionais e internacionais na Assistência Farmacêutica (AF) em Moçambique, no período de 2007 a 2012, com foco na provisão pública de medicamentos para HIV/Aids, malária e tuberculose. Descreve-se o funcionamento da AF no país; os atores que atuam nesse âmbito e as relações entre eles; discutem-se questões relevantes sobre o modus operandi dos parceiros de cooperação. A metodologia combinou: revisão bibliográfica, levantamento e análise documental e entrevistas. O marco teórico e analítico utilizou a análise de políticas públicas com foco no papel do Estado e suas inter-relações como os demais atores na ajuda externa na área farmacêutica e a abordagem de redes. Conclui-se que a interação entre os atores envolvidos é complexa, caraterizada pela fragmentação operacional e sobreposição de atividades entre diversos entes; centralização da aquisição de medicamentos na mão de poucos agentes; by pass das estruturas nacionais e desconsideração do necessário fortalecimento do sistema nacional de saúde para a construção de sua autonomia. A despeito de alguns avanços na provisão e disponibilidade de medicamentos para essas doenças, existe forte dependência externa nesse âmbito, o que obstaculiza a sustentabilidade da AF em Moçambique.

Política externa e saúde no Brasil (1995-2010): uma análise da diplomacia de saúde brasileira - da Aids ao 'Fome Zero' / Brazil's foreign policy and health (1995-2010): A policy analysis of the Brazilian health diplomacy - from AIDS to 'Zero Hunger'

RESUMO Este artigo analisa como a saúde entrou na política externa brasileira entre 1995 e 2010 e apoiou a posição internacional do País, utilizando o enfoque de análise de políticas. Essa questão raramente é examinada na literatura brasileira sobre diplomacia da saúde. A partir de revisão de literatura, análise documental e entrevistas com atores-chave, examinamos as políticas impulsionadas por complexos processos históricos de mudança no Brasil. Há importantes inter-relações entre política externa e política social, incluindo saúde. Durante os governos Lula (2003-2010), a internacionalização das políticas domésticas brasileiras, vinculadas à cooperação Sul-Sul, teve papel central. A saúde na agenda da política externa foi um importante suporte à crescente presença internacional do Brasil. Esses desenvolvimentos foram possibilitados pelo ativismo e comprometimento de diversos atores estatais e não estatais, que atuaram em dois níveis: advocacia nacional e transnacional e atividades coordenadas entre representantes do governo, incluindo diplomatas, e atores da sociedade civil. O principal argumento deste estudo é que as políticas nacionais e internacionais são interrelacionadas nesse processo, e a dinâmica doméstica e o engajamento societal são essenciais, mas não suficientes: escolhas governamentais são também determinantes. Os arranjos institucionais e políticos mudaram em diferentes conjunturas e são constantemente propensos a conflitos e mudanças.

ABSTRACT This article analyses, from a policy analysis approach, how health entered Brazilian foreign policy between 1995 and 2010 and supported the country's international position, which is rarely explored in the literature on Brazilian health diplomacy. By drawing on literature review, document analysis and key-actor interviews, we examined policies triggered by far-reaching and complex historical change processes in Brazil. We find significant interrelationships between foreign policy and social policy, including health. The internationalization of Brazilian domestic policies, and South-South cooperation, played a central role during Lula governments (2003-2010). Health found its way into the foreign policy agenda to support Brazil's growing international presence. These developments were made possible by the activism and engagement of several of State and non-State actors working on two levels: national and transnational advocacy, and coordinated activities of government representatives, including Brazilian diplomats, and civil society activists. The main argument of this study is that national and international policies are intertwined in this process and that domestic dynamics and societal engagement are essential but more is needed: governmental choices are also determinant. Institutional arrangements and policies shift in different conjunctures and are constantly prone to conflicts and change.

Multinational Qualitative Research Study Exploring the Patient Experience of Raynaud's Phenomenon in Systemic Sclerosis.

OBJECTIVE: Raynaud's phenomenon (RP) is the most common manifestation of systemic sclerosis (SSc). RP is an episodic phenomenon, not easily assessed in the clinic, leading to reliance on self-report. A thorough understanding of the patient experience of SSc-RP is essential to ensuring that patient-reported outcome (PRO) instruments capture domains important to the target patient population. We report the findings of an international qualitative research study investigating the patient experience of SSc-RP. METHODS: Focus groups of SSc patients were conducted across 3 scleroderma centers in the US and UK, using a topic guide and a priori purposive sampling framework devised by qualitative researchers, SSc patients, and SSc experts. Focus groups were audio recorded, transcribed, anonymized, and analyzed using inductive thematic analysis. Focus groups were conducted until thematic saturation was achieved. RESULTS: Forty SSc patients participated in 6 focus groups conducted in Bath (UK), New Orleans (Louisiana), and Pittsburgh (Pennsylvania). Seven major themes were identified that encapsulate the patient experience of SSc-RP: physical symptoms, emotional impact, triggers and exacerbating factors, constant vigilance and self-management, impact on daily life, uncertainty, and adaptation. The interrelationship of the 7 constituent themes can be arranged within a conceptual map of SSc-RP. CONCLUSION: We have explored the patient experience of SSc-RP in a diverse and representative SSc cohort and identified a complex interplay of experiences that result in significant impact. Work to develop a novel PRO instrument for assessing the severity and impact of SSc-RP, comprising domains/items grounded in the patient experiences of SSc-RP identified in this study, is underway.