The top 10 research priorities in psoriatic arthritis: a James Lind Alliance Priority Setting Partnership.

OBJECTIVES: To identify and prioritize the top 10 research questions for PsA. METHODS: The British Psoriatic Arthritis Consortium (BritPACT) formed a Priority Setting Partnership (PSP) comprising of people living with PsA, carers and clinicians, supported by the James Lind Alliance (JLA). This PSP followed the established three-stage JLA process: first, an online survey of people living with PsA, carers and clinicians to identify PsA questions, asking, 'What do you think are the most important unanswered questions in psoriatic arthritis research?' The questions were checked against existing evidence to establish 'true uncertainties' and grouped as 'indicative questions' reflecting the overarching themes. Then a second online survey ranked the 'true uncertainties' by importance. Finally, a workshop including people living with PsA and clinician stakeholders finalized the top 10 research priorities. RESULTS: The initial survey attracted 317 respondents (69% people living with PsA, 15% carers), with 988 questions. This generated 46 indicative questions. In the second survey, 422 respondents (78% people living with PsA, 4% carers) prioritized these. Eighteen questions were taken forward to the final online workshop. The top unanswered PsA research question was 'What is the best strategy for managing patients with psoriatic arthritis including non-drug and drug treatments?' Other top 10 priorities covered diagnosis, prognosis, outcome assessment, flares, comorbidities and other aspects of treatment (https://www.jla.nihr.ac.uk). CONCLUSION: The top 10 priorities will guide PsA research and enable PsA researchers and those who fund research to know the most important questions for people living with PsA.

Research priorities to reduce the impact of musculoskeletal disorders: a priority setting exercise with the child health and nutrition research initiative method.

Involving research users in setting priorities for research is essential to ensure the outcomes are patient-centred and maximise its value and impact. The Musculoskeletal Disorders Research Advisory Group Versus Arthritis led a research priority setting exercise across musculoskeletal disorders. The Child Health and Nutrition Research Initiative (CHNRI) method of setting research priorities with a range of stakeholders was used, involving four stages and two surveys, to: (1) gather research uncertainties, (2) consolidate these, (3) score uncertainties against importance and impact, and (4) analyse scoring for prioritisation. 213 people responded to the first survey and 285 people to the second, representing clinicians, researchers, and people with musculoskeletal disorders. Key priorities included developing and testing new treatments, better treatment targeting, early diagnosis, prevention, and better understanding and management of pain, with an emphasis on understanding underpinning mechanisms. We present a call to action to researchers and funders to target these priorities.

Musculoskeletal training: are GP trainees exposed to the right case mix for independent practice?

Musculoskeletal conditions are common in general practice, but clinicians express poor self confidence in dealing with them. Training in general practice relies on clinical exposure to a range of presentations in order to gain competence. It has been suggested that trainees are exposed to a different case mix from qualified general practices (GPs), due to seeing more minor illness and less chronic disease and that this may be responsible in part for their subsequent lack of confidence. The aims of this study were to analyse the case mix of musculoskeletal conditions encountered by general practice trainees and to compare this to the overall population consulting behaviour. This is a prospective observational study. Thirteen general practices in North East England were recruited. Musculoskeletal disorders encountered by 13 GP trainees (7 junior and 6 senior) were prospectively recorded using a handheld diary. Disorders were classified according to working diagnosis or body region if diagnosis was unclear. Musculoskeletal (MSK) disorders comprised 17 % of consultations, and the distribution of diagnoses of these was in proportion to epidemiological studies of MSK disorders in the UK as they present in primary care. Back pain was the most frequent label with 141 (29 %) consultations with a further 43 (9 %) for neck pain. Inflammatory arthritis accounted for the same number 43 (9 %). Individual joint problems were 115 (24 %) with knee being most common. A specific diagnosis was more likely to be applied when symptoms were more distal and less likely when axial. Trainees are exposed to the same spectrum of MSK disorders as are present in the population as a whole. Case mix does not appear to be a significant factor in low confidence levels in dealing with MSK disorders.

Paracetamol: not as safe as we thought? A systematic literature review of observational studies.

OBJECTIVES: We conducted a systematic literature review to assess the adverse event (AE) profile of paracetamol. METHODS: We searched Medline and Embase from database inception to 1 May 2013. We screened for observational studies in English, which reported mortality, cardiovascular, gastrointestinal (GI) or renal AEs in the general adult population at standard analgesic doses of paracetamol. Study quality was assessed using Grading of Recommendations Assessment, Development and Evaluation. Pooled or adjusted summary statistics were presented for each outcome. RESULTS: Of 1888 studies retrieved, 8 met inclusion criteria, and all were cohort studies. Comparing paracetamol use versus no use, of two studies reporting mortality one showed a dose-response and reported an increased relative rate of mortality from 0.95 (0.92 to 0.98) to 1.63 (1.58 to 1.68). Of four studies reporting cardiovascular AEs, all showed a dose-response with one reporting an increased risk ratio of all cardiovascular AEs from 1.19 (0.81 to 1.75) to 1.68 (1.10 to 2.57). One study reporting GI AEs reported a dose-response with increased relative rate of GI AEs or bleeds from 1.11 (1.04 to 1.18) to 1.49 (1.34 to 1.66). Of four studies reporting renal AEs, three reported a dose-response with one reporting an increasing OR of ≥30% decrease in estimated glomerular filtration rate from 1.40 (0.79 to 2.48) to 2.19 (1.4 to 3.43). DISCUSSION: Given the observational nature of the data, channelling bias may have had an important impact. However, the dose-response seen for most endpoints suggests a considerable degree of paracetamol toxicity especially at the upper end of standard analgesic doses.

Primary care approaches to musculoskeletal multiple-site joint pain pharmacological therapy: a survey of general practitioners.

Chronic multiple-site joint pain (MSJP) due to osteoarthritis and soft tissue disorders is common in people over 50 years old and associated with poor outcomes. This study examined current pharmacological approaches to MSJP management in primary care. One hundred and fifty general practitioners (GPs) attending an educational seminar participated in an electronic survey (mean response rate 96%). Most GPs reported treating multiple painful joints concurrently (78%) compared with focusing on a single joint (21%). The majority believed there was no difference in analgesia for different disorders when selecting paracetamol (84%), non-steroidal anti-inflammatory drugs (NSAID)/COX-2 inhibitors (57%) or opioids (70%). When optimising therapy, intra-class optimisation (increase NSAID dose 41%, change to another NSAID/COX-2 inhibitor 30%) was preferred to inter-class step up therapy (add opioid 23%, change to opioid 6%). For NSAID gastrointestinal intolerance, the preference was to add a gastro-protective agent (74%). There is a need to better characterise MSJP and examine optimal pharmacotherapy regimens.

Paediatric musculoskeletal learning needs for general practice trainees: achieving an expert consensus.

BACKGROUND: Paediatric musculoskeletal (pMSK) disorders are common in clinical practice, but training in their recognition and management is suboptimal at both undergraduate and postgraduate level. Exposure to pMSK conditions is variable in GP training, and there is no standardised curriculum for what GPs should know about pMSK medicine. AIM: To attain expert agreement on the gold standard of pMSK skills and knowledge required at completion of GP training. DESIGN AND SETTING: Modified Delphi process followed by consensus group meeting and focus groups. METHODS: Two iterative rounds of Delphi process conducted by email, followed by a face-to-face meeting of stakeholders. Items with >80% agreement included in final curriculum statement. Member checking by GPs conducted through focus group meetings. RESULTS: A curriculum covered by 12 overarching statements was developed, with positive feedback from GP educators on the feasibility of delivering the curriculum and usefulness of the items. CONCLUSION: The introduction of expert-derived learning needs to the GP curriculum on pMSK medicine should help with improving the recognition and management of children with MSK disorders.

Drug-free gel containing ultra-deformable phospholipid vesicles (TDT 064) as topical therapy for the treatment of pain associated with osteoarthritis: a review of clinical efficacy and safety.

BACKGROUND: Many patients with osteoarthritis (OA) experience side effects with available systemic therapies, some of which can be life threatening. The widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs), often without prescription, is concerning given their potential risks. New treatments for OA are therefore required. This review discusses evidence supporting the use of TDT 064, a drug-free, topical gel containing ultra-deformable phospholipid vesicles (Sequessome * vesicles), for OA-associated pain. SCOPE: Preclinical and clinical studies investigating TDT 064 in patients with OA-associated knee pain were identified in searches of PubMed and congress abstracts. FINDINGS: The ultra-deformable phospholipid vesicles (sequessome vesicles) in TDT 064 pass through the skin intact to reach the synovial space within the joint. The mechanism of action is not yet certain, but the phospholipid-based structure of these ultra-deformable phospholipid vesicles, and the observation that they localize to the cartilage surface, support biolubrication as a possible mechanism of action of TDT 064. Data from randomized, phase III studies in OA knee pain in which TDT 064 was used as the drug-free vehicle control for IDEA-033 (ketoprofen in ultra-deformable phospholipid vesicles) demonstrate a marked and consistent response to TDT 064 in terms of pain, stiffness, and function. In a 12 week study of >1300 patients, the effects of TDT 064 on pain and function were statistically noninferior to those of oral celecoxib, and superior to oral placebo. TDT 064 was well tolerated in all studies, and adverse events were typically mild-to-moderate effects on the skin. CONCLUSIONS: Evidence from clinical studies supports the use of TDT 064 as a drug-free topical treatment for patients with OA. Further experience with TDT 064, particularly among patients with comorbidities or NSAID contraindications, will provide more information on its potential use.

Doctors likely to encounter children with musculoskeletal complaints have low confidence in their clinical skills.

OBJECTIVE: To assess self-rated confidence in pediatric musculoskeletal (pMSK) clinical assessment in trainees and experienced doctors in primary care and selected secondary care specialties to whom children with MSK problems are likely to present. STUDY DESIGN: Attendees at programmed postgraduate teaching sessions within a health care region of the United Kingdom completed an anonymous questionnaire to self-rate confidence in pMSK assessment compared with other bodily systems and describe exposure to MSK teaching. RESULTS: Respondents (n = 346) were qualified from 23 different medical schools (United Kingdom and 9 non-United Kingdom) and included trainees in Primary Care (n = 75), Pediatrics (n = 39), Emergency (n = 39), Orthopedics (n = 40), and experienced doctors in Primary Care (n = 93), and Pediatrics (n = 60). Self-rated confidence in pMSK assessment was low; the majority had "no" or "some" confidence (21% and 53%, respectively). Conversely, most respondents were confident "in most aspects" or "very confident" for cardiovascular, respiratory, and abdominal systems. pMSK ranked lowest below all other systems. Most respondents (92%) recalled some teaching of adult MSK medicine, mostly at undergraduate level. Fewer (51%) recalled any teaching of pMSK medicine. CONCLUSIONS: Self-rated confidence in pMSK assessment was lowest, compared with other bodily systems, within doctors to whom children with MSK problems are likely to present. Core clinical skills are learnt at undergraduate level, and this study reflects poor levels of pMSK training which needs to be addressed.