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Background Many patients with rheumatoid arthritis (RA) do not attain remission/low disease activity, remaining in a moderate disease activity state (MDAS) with ongoing disability and impaired quality of life (QoL). If patients in persistent MDAS with poor future outcomes could be prospectively identified, they could arguably be treated more intensively. We evaluated baseline factors predicting function (Health Assessment Questionnaire-Disability Index [HAQ-DI] scores) and QoL (3-level EuroQol-5 dimensions questionnaire [EQ-5D-3L] index scores) at 12 months in patients with RA in persistent MDAS in a real-world setting. Methods Patients with persistent MDAS (Disease Activity Score for 28-joint count based on erythrocyte sedimentation rate [DAS28-ESR] 3.2–5.1 on at least two consecutive outpatient appointments over 12 months) were identified retrospectively from Guy’s Hospital RA Centre and analysed in two groups: (1) biologic naïve at baseline or (2) receiving/ever received biologics. The baseline timepoint was the second-visit MDAS DAS28-ESR score; the endpoint was the closest visit to 12 months. Linear regression analyses evaluated relationships between baseline variables and (1) 12-month HAQ-DI scores, (2) 12-month rank-transformed EQ-5D-3L index scores, (3) 12-month changes in HAQ-DI scores, and (4) 12-month changes in EQ-5D-3L index scores. Results The analysis included 207 biologic-naïve and 188 biologic-experienced patients. All patients had moderate disability (mean HAQ-DI 1.21 and 1.46) and impaired QoL (mean EQ-5D-3L index scores 0.52 and 0.50). Many reported moderate/severe pain (93 and 96%) and showed little change in HAQ-DI and EQ-5D-3L index scores over 12 months. In both biologic-naïve and biologic-experienced groups, multivariate analysis revealed a significant association between baseline HAQ-DI scores and endpoint HAQ-DI scores (β = 0.67, P P P P P = 0.004, respectively). Baseline EQ-5D-3L index scores were significantly associated with 12-month changes in EQ-5D-3L index scores in both groups (β = − 0.73, P P = 0.003, respectively). Conclusions Patients with RA in persistent MDAS experience substantial ongoing physical disability, poor QoL, and pain. HAQ-DI is an important predictor of future disability and reduced QoL, supporting current national recommendations to measure HAQ-DI in routine care.

Background/Aims It became apparent at a session at the BSR Annual Conference 2019 that some CCGs restrict the prescription of high cost drugs (HCDs) beyond three drugs for people with rheumatoid arthritis (RA). We were interested to explore the efficacy of HCDs beyond the third choice in our own service. Methods All patients in our service who are being considered for HCDs, are discussed at a multi-disciplinary team meeting comprising of seven consultants and eight nurses. The HCD decision is recorded in the minutes of the meeting which were scrutinised to identify patients who had received four or more HCDs. We began at March 2017, the launch of JAK inhibitors, in the expectation that few people would have had four HCDs before that time. The medical records were reviewed for the order of HCDs given and for evidence of efficacy and toxicity. The response to each drug choice was graded as: responder; partial responder and failure (primary non-responder or toxicity). Results From a database of 2,673 patients with RA, 542 patients were taking HCDs, thirty-two of those had received four or more of these drugs. Eleven of the thirty-two patients had tried four HCDs, seven had received five HCDs, ten patients had six, one patient had seven HCDs, two had tried eight and one patient had received nine HCDs. The response rates for each choice of drug are shown in table 1. Many patients responded to their fourth, fifth and sixth choice of HCD. If there was a restriction of three HCDs in our service, thirty-three prescriptions for drugs that patients have responded to, would not have been made. Conclusion Many patients responded to their fourth or subsequent HCD. Thus, there is no clinical justification in restricting the use of HCDs below at least six choices. Additionally, this data suggests that only small numbers of patients are prescribed more than four HCDs. Therefore lifting this limitation would have little cost implication. P141 Table 1:HCD Response RateHCD Choice*123456>6Responder12 (38%)10 (31%)10 (31%)12 (44%)14 (58%)6 (60%)1 (14%)Partial Responder5 (16%)1 (3%)7 (22%)5 (19%)4 (17%)1 (10%)1 (14%)Failure15 (47%)21 (66%)15 (47%)10 (37%)6 (25%)3 (30%)5 (71%)n =3232322724107*Switches to biosimilars were not regarded as a change. Disclosure D. Walker: Honoraria; Gilead Sciences Ltd, Ely Lilly Pharmaceuticals, Pfizer Pharmaceutical. Grants/research support; Gilead Sciences Ltd. S. Robinson: None. J. Barry: Corporate appointments; Gilead Sciences Ltd. P. Punter: Corporate appointments; Gilead Sciences Ltd. S. Kearns: Corporate appointments; Gilead Sciences Ltd. I. Goff: None.

Current guidelines for the management of rheumatoid arthritis (RA) recommend early treatment and a treat-to-target goal of remission or low disease activity. Over the past decade, this approach has been extremely successful in reducing disease activity and joint damage in patients with RA. At the same time, however, overall patient perception of well-being appears to have decreased with respect to outcome measures considered important by patients themselves, such as pain, fatigue, physical function and quality of life. The timely and effective use of patient-reported outcomes (PROs) should encourage healthcare professionals (HCPs) to focus more on the impact of RA on patients and how patients are feeling. This would facilitate shared decision making between patients and HCPs, ultimately leading to a more patient-centered approach, improved patient care and optimal health outcomes. Importantly, PROs provide information about individual patients that complements information provided by physical assessment and composite scores, and can also be used to guide patient care, such as determining whether a clinic visit is needed or whether management modifications are necessary. This is particularly important for patients who do not achieve the target of remission or low disease activity with pharmacological treatment. A number of validated PRO questionnaires are available, but how and which PROs should be incorporated into rheumatology clinical practice as part of the decision-making process is still controversial. Combining PROs with digital technology, such as computer adaptive tests, electronic PRO systems, web-based platforms and patient dashboards, could further aid PRO integration into daily rheumatology clinical practice.

Objectives: Access to biologic DMARDs for RA is often restricted to those with severe disease. This systematic review aimed to identify prognostic factors in patients with moderate disease activity who may be at risk of disease progression and poor clinical outcomes. Methods: MEDLINE, Embase and Cochrane databases were searched (final search 22 September 2017), and data from patients with moderate disease [28-joint DAS (DAS28) >3.2–≤5.1] were included. Studies were evaluated according to the measure(s) of progression/poor outcome used: radiographic, disease activity or other indicators. Results: The searches identified 274 publications, of which 30 were selected for data extraction. Fourteen studies were prioritized, because they specifically analysed patients with moderate RA. Nine studies reported radiographic progression outcomes for 3241 patients, three studies reported disease activity progression for 1516 patients, and two studies reported other relevant outcomes for 2094 patients. Prognostic factors with consistent evidence for progression/poor outcome prediction were as follows: DAS28 ≥ 4.2, the presence of anti-CCP antibodies, and power Doppler ultrasound score ≥1. Some predictors were specific to either disease activity or radiographic progression. Conclusion: Several criteria used in standard clinical practice were identified that have the potential to inform the selection of patients with moderate RA who are at greater risk of a poor outcome. A combination of two or more of these factors might enhance their predictive potential. Further work is required to derive clinical decision rules incorporating these factors.

Introduction Various factors play a role in the development of erectile dysfunction (ED). Aim To provide a descriptive comparison of erectile function response for tadalafil on-demand (PRN) and once-daily (OAD) dosing regimens in patients with common comorbid conditions, treatments, or risk factors that can be considered when treating ED. Methods In total, 17 PRN and 4 OAD placebo-controlled studies were included in the integrated database in these pooled analyses. Data were analyzed from patients treated with placebo, tadalafil 10 mg (low dose), and 20 mg (high dose) for the PRN studies and placebo, tadalafil 2.5 mg (low dose), and 5 mg (high dose) for the OAD studies. Main Outcome Measures The effects of tadalafil were measured using the International Index of Erectile Function administered from baseline to week 12. A descriptive comparison of the efficacy of tadalafil PRN vs OAD was examined in the clinical populations. Results Baseline characteristics of 4,354 men were comparable between the PRN and OAD groups, with differences seen only in the variables of race, body mass index (BMI) of at least 30 kg/m2, and alcohol use. Tadalafil was efficacious at improving erectile function for all clinical populations, except for the low-dose OAD group, which demonstrated a weaker effect vs placebo than the high-dose OAD group, and the low- and high-dose PRN groups vs placebo for patients with BMI of at least 30 kg/m2 for patients without a cardiovascular disorder, smokers, patients with ED duration shorter than 1 year, and patients without previous phosphodiesterase type 5 inhibitor use. Tadalafil was efficacious for patients with or without diabetes mellitus, arterial hypertension, hyperlipidemia, and alcohol use at baseline. Conclusion Tadalafil OAD and PRN regimens showed efficacy in patients with ED. No clinical populations of patients with ED seemed to benefit overwhelmingly from one dose regimen over the other.

Circulating insulin-like growth factor-I (IGF-I) levels have been shown to be related to risk of prostate cancer in epidemiologic studies. While specific genetic loci responsible for interindividual variation in circulating IGF-I levels in normal men have not been identified, candidate genes include those involved in the growth hormone (GH)–IGF-I axis such as the hypothalamic factors GH releasing hormone (GHRH) and somatostatin and their receptors. To investigate the role of the GH–IGF-I axis on in vivo prostate carcinogenesis and neoplastic progression, we generated mice genetically predisposed to prostate cancer (the TRAMP model) to be homozygous for lit, a mutation that inactivates the GHRH receptor (GHRH-R) and reduces circulating levels of GH and IGF-I. The lit mutation significantly reduced the percentage of the prostate gland showing neoplastic changes at 35 weeks of age (P=0.0005) and was also associated with improved survival (P

The Climbie Report 2003 has suggested radical reforms in relation to how child protection services are organised out of hours. The impact of this will be felt in Emergency Duty Teams throughout the UK leading those involved in commissioning child protection services to ask whether the generic emergency duty team is the most appropriate model for dealing with all social services emergencies out of normal working hours.

The protein product of the immediate-early gene c-fos is expressed rhythmically in the shell region of the suprachiasmatic nucleus (SCN), the mammalian circadian clock. Recently, we found that exposure to an entraining light pulse caused a suppression of Fos expression in the SCN shell in rats. To study the hypothesis that suppression of Fos in the shell is a correlate of photic entrainment, we used rats that were treated with the retinal neurotoxin monosodium glutamate (MSG) during the neonatal period. In spite of retinal degeneration, MSG-treated rats entrained normally and displayed light-induced suppression of Fos within the SCN shell. These results support the view that light-induced suppression of Fos within the SCN shell is a cellular correlate of photic entrainment.

Introduction. Irukandji syndrome is because of envenoming by a number of small jellyfish. It results in a delayed onset of generalized pain, sweating hypertension, and tachycardia. There is no antivenom. Case report. A 44-year-old healthy male was stung while swimming in NE Australia. He rapidly developed Irukandji syndrome. He had a rapid deterioration in conscious level because of an intracerebral hemorrhage. He developed left ventricular failure with an elevated troponin (34 mcg/L, N < 0.4) requiring inotropic support. He progressed to brain death and died on day 13 poststing. Nematocysts recovered from the patient skin were consistent with a large Carukia barnesi. Discussion. This is the first case of a death because of Irukandji syndrome where the jellyfish Carukia barnesi has been demonstrated to the causative creature.

There has been a recent explosion in knowledge regarding the central role of the immune system in the pathogenesis of psoriasis. Originally felt to be primarily a disorder of keratinocyte hyperproliferation, it has recently been classified as a T cell-mediated, autoimmune disease. Type 1 cytokines released predominantly from activated T lymphocytes are now considered to cause the psoriatic phenotype, including the epidermal and vascular changes. Armed with this new knowledge, pharmaceutical and biotechnology companies have developed more specific, immunologically directed interventions. These newer agents aim to be both more effective in clearing a condition that is associated with much morbidity and to be more selective, resulting in fewer toxic side effects than current therapies. This article gives an overview of the newer immunotherapeutic approaches from the points of view of safety, efficacy and mechanisms of action. The review also outlines the steps involved in the immune response leading to psoriasis and considers how each step could offer a target for therapeutic intervention. Infliximab, etanercept, alefacept and efalizumab are considered in detail.

Background This multicenter, randomized, double-blind, double-dummy, placebo-controlled trial primarily evaluated the efficacy of tadalafil once-daily (OaD) or on-demand (“pro-re-nata”; PRN) treatment, started early post-nsRP. Secondary outcome-measures on quality-of-life (QoL) and treatment satisfaction are reported. Methods Patients, aged