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BackgroundUse of antiretroviral drugs (ARVs) for a discrete period for Preventing Mother-to-Child HIV transmission (PMTCT) only may be compared to Structured Treatment Interruption, which has been associated with virologic failure (VF). We sought to determine factors associated with VF among women on Antiretroviral Therapy (ART) but with prior exposure to short-term ARVs for PMTCT.MethodsHIV-infected women presenting for ART initiation in three HIV care clinics in Kisumu County, Kenya were enrolled in the KiBS follow-up study (2010–2013) if they had previously received triple ARVs for PMTCT (Group 1) or short-course ARVs for PMTCT (Group 2) or were ARVs-naïve (Group 3). First-line ART was provided as per 2010 WHO treatment guidelines and viral load (VL) tests were conducted every six months for 24 months. VF was defined as any confirmed VL value ≥400 copies/ml after 6 months of ART initiation. Frequencies and proportions were used in the descriptive analysis while Pearson’s Chi-square/Fisher’s exact test was used to determine the association between VF and eight independent variables. Univariate and Multivariate Cox-proportional regression model was fitted to investigate factors associated with VF.ResultsOut of 284 participants data for 245 were analysed (Group 1: 27; Group 2: 107; Group 3: 111). Majority were aged 25–29 years and over 60% had primary/lesser education. There were 39 (Group 1: 5; Group 2: 16; Group 3: 18) VFs with a total VF incidence of 8.12 [95% CI (5.96, 11.17)] per 1000 Person months of observation (PMOs). Group 2 had the lowest VF incidence. Baseline CD4 3 and initiation/use of TDF/3TC/EFV were associated with virologic failure (VF).ConclusionWomen at risk of VF based on the identified risk factors should be identified and targeted with appropriate intervention. Further studies are needed to verify and understand the mechanisms of association between VF and TDF/3TC/EFV which is a WHO-recommended first-line ART regimen.

Performing a chest drain procedure with a safe technique is a core skill for a medical registrar and arguably the highest risk procedure they are expected to perform at junior level. The competency level of a cohort of registrars who typically rotate every six months is often not known. Little regard is given to this when drawing up on call rotas and training needs are often missed. In this initiative we aimed to address these failings. Methods By way of induction for the general medical registrars beginning a six month post in our hospitals we arranged a short verbal introduction to the group about local processes of how chest procedures within our hospital are performed eg. location of equipment in centralised packs, standardised equipment lists, check lists and use of bedside US and patient information/consent. Over the first two weeks of the run we arranged “one on one” teaching with a Consultant chest physician who taught each registrar according to their needs on realistic mannequins. Three techniques taught: thoracocentesis with an 8 F drainage pack; a small bore 12 F seldinger drain and a surgical 28 F drain drain according to need. Teaching of 32 registrars was completed within a two week time frame in the space of four PA/clinic sessions. Competency was judged at the end of the session and electronic DOPS and feedback from the registrars was obtained. We encouraged further discussion with educational supervisors with regard to ongoing training requirements for individuals. Results and evaluation Attendance was 31/32. 59% had 12 months or less experience as a registrar. 66% were able to perform thoracocentesis and 63% seldinger drain independently. Most others were competent enough to perform with a colleague supervising. Additionally 38% and 25% of registrars were deemed to be able to teach other thoracocentesis and seldinger drains respectively. Learner feedback was extremely positive and self-rated confidence and safety improved from 5–7.6 and 5.2 to 7.7 out of 10 respectively. Responses highly valued the fact this was delivered by a Consultant and identified a need for further bedside chest US training.

To investigate whether hand bone mineral content (BMC) measurement is an outcome measure for RA and whether the early changes in hand BMC predict functional disability.Tender and swollen joints in hands and body, HAQ score, Larsen score on hand radiographs, serum CRP, and hand BMC measurement by DXA were studied every six months for five years in 40 patients with early RA. At the final visit, patients completed the SF-36 and Duruoz hand function questionnaires.All patients completed two years and 29 completed five years' follow up. Hand BMC worsened over the first three years (percentage loss from baseline: mean (SD) -5.5 (7.2), -7.5 (8.4), -9.8 (9.4)) and stabilised over last two years (-9.9 (8.8), -10 (7.8)). Baseline disease activity and function correlated with hand BMC loss at five years (swollen joints in hands: r=-0.38, p=0.043; swollen joints in body: r=-0.47, p=0.01; HAQ: r=-0.52, p=0.004). Percentage change in hand BMC over five years correlated with SF-36 physical function (r=0.61, p0.01), hand function (r=-0.64, p0.01), HAQ score (r=-0.63, p0.01) at five years. Relative risk of bad hand functional outcome at five years was significantly higher for patients with hand BMC loss of/=1.17 g (smallest detectable difference) than for patients with less bone loss within the first six months (OR=6.9, 95% CI 1.3 to 34.5, p0.02).Early loss of hand BMC in patients with RA is a composite marker of disease activity and functional status and can predict poor functional outcome.

It has been little more than a decade since the initial observation of the dose dependent relation between the severity of vitamin A deficiency and childhood mortality,1 quickly followed by the publication of a controlled trial in which children of preschool age, randomised to receive large doses of vitamin A every six months, died at only two thirds (or less) the rate of control subjects.2 3 In the short interval since this trial, an initially sceptical scientific community has declared control of vitamin A deficiency a major international goal4-6 and potentially one of the most cost effective of all health interventions.7 #### Key messages The story did not begin in the 1980s. A host of animal studies and anecdotal clinical reports during the first third of the century, soon after vitamin A was discovered, suggested a close, potentially causal relation between vitamin A status and morbidity and mortality from infection. These are detailed elsewhere.8 For ethical and logistic reasons the observational study1 has never been repeated, though a large number of intervention trials have been carried out. Eight were initially considered to be suitably rigorous for inclusion in an independently commissioned meta-analysis (table 1).9 The results were remarkably similar, particularly given the wide differences in culture, dietary …

Accepted 26 February AIMS—Long acting subcutaneous testosterone pellets are of proved efficacy for the treatment of hypogonadal men, but have not been reported as a treatment modality in adolescent boys. Pharmacodynamic studies of subcutaneous testosterone release have shown prolonged normalisation of testosterone levels for at least four months. Administration of a long acting, safe, effective, and convenient form of treatment is desirable when life- long treatment is indicated. PATIENTS AND METHODS—Eighteen boys (aged 13.9-17.5 years at the start of treatment)—seven with primary hypogonadism, nine with secondary hypogonadism, and two boys being treated with testosterone for tall stature—were given testosterone pellets (8-10 mg/kg) every six months for 18months. Height, weight, pubertal status, and psychosocial parameters were assessed and follicle stimulating hormone, luteinising hormone, testosterone, prolactin, and lipids were measured at 0, 1, 3,6, 12, and 18 months. Bone age was measured at 0 and 12months. RESULTS—In all boys growth velocity continued appropriately for bone age. Puberty continued to progress in all boys and in two boys the amount of virilisation exceeded that seen with previous treatment with intramuscular testosterone. After testosterone administration, follicle stimulating hormone and luteinising hormone suppressed incompletely in the boys with primary hypogonadism. Serum testosterone ranged from 4.3 to 26.7 nmol/l at three months to less than 10nmol/l at six months after implantation. Prolactin and lipid levels were normal throughout the study. By report, there was an improvement in mood and emotional wellbeing. No pellet extrusions occurred in a total of 156 pellet insertions. CONCLUSIONS—All boys preferred this mode of testosterone administration to intramuscular injections. Long acting subcutaneous testosterone pellets are safe, efficacious, well tolerated, and convenient, and result in normal physical growth and improved psychological outlook in adolescent hypogonadal boys. • Continued normal progress of growth and pubertal status occurs with subcutaneous testosterone • Prolonged stable physiological levels of testosterone are maintained for four to six months • Bone age advance is commensurate with change in chronological age • Psychological outlook and self image are reported to be improved • Subcutaneous testosterone is safe, well tolerated, efficacious, and convenient

Standardization of Inflammatory Bowel Disease (IBD) care through participation in the ImproveCareNow (ICN) Network has improved outcomes for pediatric patients with IBD, but under the current care model, our improvements have plateaued. Current ICN model care guidelines recommend health supervision visits every six months. We identified a gap in our practice's ability to ensure either a routine six month follow-up or a rapid follow-up after a disease flare, and a significant number of patients with active disease status during a six month period lacked timely reassessment after interventions or medication changes. Telemedicine provides an alternative method of care delivery to address these gaps, but has had limited use in patients with IBD. A multi-step approach to offer alternative follow-up care options via telemedicine was developed with potential impact on remission rates and quality of life. Short term goals of the pilot were to improve telemedicine access for patients with IBD were to 1) increase the percent of patients with active disease with a follow-up completed within two months of a visit from 40% to 70%, 2) increase the percent of patients with a visit scheduled within two months of their last sick visit from 20% to 70% (interim measure), 3) increase the number of eVisits from zero visits per month to two visits per month during pilot phase, 4) increase electronic communication with patients from zero messages per month to 200 messages per month, 5) no change in complications or adverse events (defined as an unplanned visit or ED (emergency department) encounter within 30 days of an eVisit. The expected outcomes of the e-visit model were to: maintain baseline care standards and health screening capabilities, improve access to care, and provide equivalent care delivery (no increase in the number of unplanned clinical encounters). Using the IHI model for improvement (Plan-Do-Study-Act) we have seen a progressive increase in the rate of patient signups for the electronic medical record patient portal, with a baseline median of 20% per clinic compared with a current median of approximately 70% after six months. We successfully implemented e-messaging in its pilot form among five providers and have seen steady uptake in patient use from 5 patient initiated messages during the first month to 76 messages/month over the past three months. E-visits have replaced a total of 32 visits to date. Medications, nutrition, and disease activity were appropriately screened and managed electronically without the need for a physical office visit by the treating gastroenterologist. Access to care was improved in that all patients completed their e-visits from their homes without missing school or work and did not require a physical office visit. One visit successfully identified worsening of the patient's clinical course and resulted in a scheduled office visit request, but no unplanned office visits or ED visits have occurred. This report represents the first description of telemedicine use in routine clinical care in children with IBD. We anticipate continuing use of this novel mode of health care delivery in pediatrics in an effort to increase the proportion of patients seen for interval follow-up, after IBD diagnosis, or mild flare in an effort to target early treatment changes that should result in improved remission and patient reported outcomes. E-visits are less expensive and time consuming than traditional visits and may serve as an additional method of cost savings by matching care to a patient's individual needs.

OBJECTIVES--To study the functional outcome in patients with rheumatoid arthritis (RA) who tolerate second line drug therapy for five years. METHODS--We enrolled into prospective controlled trials, 190 patients with rheumatoid arthritis who tolerated 'disease modifying' antirheumatic drug therapy for five years. Demographic data were recorded. Disease activity was measured every six months for two years and annually thereafter, using clinical and laboratory variables. Patient function was measured using the modified Health Assessment Questionnaire. The change in each variable was analysed using paired Wilcoxon tests. RESULTS--Patient function improved significantly compared with baseline. The improvement was maximal after one to two years, and thereafter function started to decline slowly. After five years of treatment the patients' function was still significantly better than before treatment had started. There were highly significant improvements in all variables measured to assess disease activity, which remained well controlled throughout the five year period. CONCLUSION--Good control of disease activity and improved function can be achieved long term in approximately 30% of RA patients treated with injectable gold, sulphasalazine or penicillamine.

Elevated CA-125 levels have been reported in some women with endometrial carcinoma. Current follow-up policy for these patients does not involve the use of tumor markers. CA-125 measurements were performed in 28 patients with a diagnosis of endometrial cancer, 14 clinically free of disease and 14 with known disease. Based on the sensitivity (0.64) and specificity (0.93) observed we constructed a model to estimate the predictive value of the assay as a marker in the follow-up of patients who have completed treatment. This model would involve a CA-125 assay every six months for five years in 100 patients with stage I and II disease. Despite the high statistical correlation between the clinical status of the patient and the CA-125 value observed in our study, the positive predictive value would be approximately 24% in such a follow-up protocol where a low prevalence of recurrent malignancy is expected.

OBJECTIVE--To assess the quality of care provided by hospitals for young children with sickle cell disease. DESIGN--Retrospective survey. SETTING--Teaching hospital in London. PATIENTS--31 Children (mean age 4 years 4 months, range 4 months to 7 years 5 months) born with sickle cell disease between 1978 and 1985 identified from Hospital Activity Analysis data, an outpatient diagnostic register, and registers of the haematology department. Eight had been diagnosed on neonatal screening and at least four of these had not been followed up. MAIN OUTCOME MEASURES--Aspects of quality of outpatient care (blood testing, clinic attendance, and prophylactic drug treatment) and family care (adequate support and carers' knowledge about the disease) as assessed by reviewing the notes and administering a semistructured questionnaire to the carers, in relation to a devised list of standards deemed necessary to ensure achievement of the aims of screening. RESULTS--There were 93 outpatient attendances during the previous 12 months, but 13 children had not attended at least every six months and four not at all for more than a year. Only eight children had had three of the blood tests considered to be necessary for good care; three had had none. Prophylactic treatment with penicillin and folic acid was erratic; three children with sickle cell anaemia were not receiving regular prophylactic penicillin. IMPLICATION--Diagnosis of sickle cell disease on neonatal screening must be linked with follow up to ensure optimal management.

Background Most HIV diagnoses in Australia are among gay and bisexual men (GBM), yet less than a quarter of higher-risk GBM are testing at the recommended frequency (3–6 monthly). In the context of a randomised trial of HIV self-testing (FORTH), we examined the predictors of more frequent use of HIV self-testing among higher-risk GBM. Methods Participants in FORTH trial included higher-risk GBM (>5 sexual partners or condomless anal intercourse in the past 3 months). The trial is being conducted over 12 months, and men in the intervention arm receive 4 self-tests (OraSure’s OraQuick home test) at baseline and additional self-tests on request. Using data from the baseline and 6 month surveys, we used logistic regression to examine predictors of using >2 self-tests over 6 months among participants in the intervention arm. Results Of the GBM (n = 154) in the intervention arm, 59% reported in the baseline survey they had condomless anal intercourse with casual partners (CLAIC) in the past 6 months and 56% had a HIV test every six months. Men who reported CLAIC in the past 6 months were more likely to use >2 HIV self-tests in the first 6 months of the trial (odds ratio:2.8,95% CI: 1.2–6.7). No other baseline survey factors were associated with >2 self-tests, including; demographics, testing frequency, likelihood to self-test in the future, and reported testing barriers (the process of getting tested is too much hassle, I don’t like having to return for results, I don’t want to go to a clinic/doctor to get tested). Conclusion These findings indicate men who report sexual risk behaviour are more likely to increase their testing frequency through self-tests, which is a key HIV prevention goal. However there is also a need to ensure the longer window period of the OraQuick self-test is understood to avoid infections being missed. Disclosure of interest statement The research is funded through a NHMRC Program grant from the NHMRC and self-test kits were purchased from OraSure Technologies Inc. (Bethlehem, PA, USA). The Kirby Institute and the Centre for Social Research in Health receive funding from the Australian Government Department of Health.

Background Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of a CAG polyglutamine repeat within the first exon of the huntingtingene. A range of mouse models are currently available for modelling HD, however these models must be characterised to determine their reliability in recapitulating HD symptoms. Knock-in mouse models have been previously shown to demonstrate subtle early cognitive phenotypes, followed by the appearance of motor disturbances which accurately reflect the symptom development of the human disease. Aims We sought to characterise the development of both motor and cognitive symptoms in HdhQ111 heterozygous mice to determine whether they recapitulate the core symptoms of the human disease. Methods The motor phenotype was investigated very three months using a battery of motor tests including; rotarod, balance beam, grip strength, locomotor activity and gait analysis. The cognitive phenotype was explored every six months utilising 9-hole operant boxes and an operant battery of tasks which included; fixed ratio, progressive ratio and the 5-choice serial reaction time task (5CSRTT). Results No significant differences were demonstrated in the fixed or progressive ratio tasks. However, HdhQ111 heterozygous animals were significantly impaired in the 5CSRTT at 6 and 12 months of age. Significant motor problems were observed in HdhQ111 heterozygous animals on the accelerating rotarod from 12 months of age. Balance beam results indicated motor deficits beginning at 9 months of age and additional problems with co-ordination from 12 months of age. No significant differences were observed in grip strength, general locomotor activity or gait analysis. Conclusions Deficits in the 5CSRTT, followed by motor problems which occur later in the disease accurately reflect the human condition and make the HdhQ111 mouse model an ideal model for testing novel therapeutics.

Background Since the description of the efficacy of rituximab (RTX) in treating patients with rheumatoid arthritis (RA), the use of this drug has been extended. Nevertheless, there are not clearly established guidelines to follow after administration of the first cycle. Objectives To systematically review the published evidence to date regarding on the difference in efficacy in the treatment of RA with RTX when it is used with a fixed, every 6 months, or an on-demand pattern. Methods A sensitive search of all published studies on the difference in the efficacy of RTX in RA patients used in a fixed pattern or on-demand was performed in Medline, Embase and Cochrane Central databases since its inception until July 2013. We selected all studies involving adult patients with RA treated with RTX in which intervention was described as treatment with RTX in a fixed pattern, every 6 months, and comparator as the administration of RTX in an on-demand pattern. Any standardized measure of efficacy in RA was considered as outcome measure. Although meta analysis, systematic reviews, clinical trials and cohorts well designed were preferably selected, finally we also included open studies and all studies that showed a methodologically correct subanalysis related to the question even if it had not been its main objective. After removing duplicates, an initial selection by reading titles, a second selection after reading abstracts and, finally, full reading of selected studies, assessing the methodological quality by levels of the Oxford Centre for Evidence Based Medicine Evidence (2001 update) where applicable, was carried out. A manual search of the references of included studies was also performed. Results A total of 1118 citations about the treatment of RA patients with RTX used in a fixed pattern, every 6 months, or in an on-demand one were identified, which were reduced to 52 after removing duplicates and selection by reading titles and abstracts. Of the 52 articles selected, finally only two were included in the review both from the same study. Despite not being able to be included in the review for methodological reasons, four additional studies that had included analysis of several cycles of retreatment with RTX were specially revised. Conclusions The effectiveness of the administration of successive cycles of RTX is equal when is done according to a fixed schedule every 6 months or as decided by the doctor following the patient (level of evidence 2b, grade of recommendation B). However, careful reading of some of the articles not included in the review permits us to conclude that, after a first cycle with RTX, a more efficiency is obtained when close monitoring and treatment by objective is done since 4-6 months of previous cycle. Acknowledgements This work has been funded by the Spanish Society of Rheumatology. Disclosure of Interest A. M. Ortiz Grant/research support: Spanish Society of Rheumatology, M. Rosario Lozano: None declared, C. Martinez Fernandez: None declared, I. Gonzalez-Άlvaro Grant/research support: Spanish Society of Rheumatology DOI 10.1136/annrheumdis-2014-eular.4005

Background Prolia® (denosumab) has shown to be a safe and efficacious therapy for osteoporotic patients in numerous clinical trials. However, few studies have been performed to determine its effectiveness in real world clinical practice. Currently, best practice guidelines state that Prolia® should be administered every six months. This study explores whether deviation from this recommended subcutaneous injection course would have an impact on patient9s bone mineral density (BMD). Objectives The objective of this study is to assess if a delay in administration of Prolia will have a negative impact on the patient9s BMD measured at the lumbar spine and femoral neck, measured 12 months after initiation of Prolia therapy Methods A retrospective cohort study was conducted from August 2012 to August 2013 for all osteoporotic patients who received a minimum of two subcutaneous injections of Prolia® since May 2010. Patients who have only received their first subcutaneous injection and patients without a corresponding BMD score were excluded from the study. Data obtained included age, sex, injection history (number of days between subsequent injections), and BMD of the femoral neck and lumbar spine. Patients were classified into 3 categories: 1) subsequent injection less than five months, 2) between five to seven months, 3) more than seven months after their initial subcutaneous injection. Changes in BMD from a one-year follow-up were obtained and compared. Results Of the study population (n=212), the baseline characteristics were: mean (SD) age 68.78±11.56 years, 91.9% female, 8.1% male. After one year of treatment, BMD scores increased in all three groups for both lumbar spine (37.79%, 15.16%, 18.09%) and femoral neck (8.77%, 5.55%, 8.77%) for patients receiving a subsequent injection less than five months, between five to seven months and more than seven months after their initial injection, respectively. The relationship between drug administration and change in BMD was found to be not statistically significant (p>0.05). Conclusions This study suggest that the efficacy of Prolia® (denosumab), as assessed by BMD measurements at the lumbar spine and femoral neck is not affected by a delay in timing of the subsequent injection. Current best practice is to administer the drug every six months, and although we will continue to strive for this, the preliminary data that we present suggests that there is some flexibility in this timing, especially if a subsequent injection needs to be delayed. A follow-up study with a larger sample size will allow for a more indepth characterization of this relationship. Disclosure of Interest M. Wong-Pack: None declared, A. Kalani: None declared, J. Hordyk: None declared, G. Ioannidis: None declared, R. Bensen: None declared, W. Bensen: None declared, J. Adachi Grant/research support: Amgen, Speakers bureau: Amgen, Astra Zenica, Eli Lilly, GSK, Merck, Novartis, Nycomed, Pfizer, Proctor and Gamble, Roche, Sanofi-Aventis, Wyeth, BMS, A. Lau Grant/research support: Amgen, Roche, Speakers bureau: Amgen, Roche DOI 10.1136/annrheumdis-2014-eular.4744

Background The recommended therapeutic regime for Rituximab (RTX) in Rheumatoid Arthritis (RA), according to prescribing information, includes two 1000-milligram infusions given two weeks apart, every 6 months. However, this is often not the case in clinical practice, since both consensus documents and information from clinical trials consider other alternatives. Objectives Our objective in this study was to analyze the regime of use of RTX in RA in daily clinical practice. Methods This is a retrospective study that includes patients treated with RTX between 1998 and 2013 in a single university hospital. We reviewed medical records and collected demographic data, number of cycles, doses and intervals of RTX administered to the patients, response duration, as well as frequency and reasons of treatment discontinuation. Descriptive analysis was performed using the statistical package Stata v. 12. Results Ninety-three patients were studied, of which 83% were women. Median age at disease onset was 51 years with an interquartile range (IQR) of 39 to 60 years. Median age at the start of treatment with RTX was 60 [IQR: 51-70] years. Out of the 93 patients, 11 had negative rheumatoid factor. The number of cycles of RTX administered to each patient ranged from one to nine. Treatment was discontinued in 33% of the patients. The reasons for discontinuation were inefficacy (16%), adverse effects (7%) and others (10%). RTX was most commonly withdrawn during the first two cycles. The main data related to use of RTX in our study are summarized in the following table. Response duration in males tended to be longer [12 months; IQR: 8-13] than in females [10 months; IQR: 7-12], but this didn9t reach statistical significance (p=0911, Mann-Whitney9s test). Longer response duration was observed in patients with a longer RA history (r =0.24, P=0.001, Pearson9s test). RTX dose per cycle did not modify the response duration (1 vs 2 grams, 9.5 and 10 months respectively). Conclusions Our data show that, in daily clinical practice, RTX is more frequently used on demand, tending to abandon the fixed regime of 2 grams every six months. In addition, we observe a tendency to an increased use of 1 gram cycles with time. This results in cost savings without apparent decrease in healthcare quality. References Martin Mola et al. Grupo de Expertos en Rituximab. Reumatol Clin. 2011;7:30-44 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4562

Background Coping patterns relate to demographic, socioeconomic, clinical, and therapy in patients with chronic diseases. In patients with rheumatic diseases, the evasive pattern is associated with the poorest outcome. Objectives To describe coping patterns in patients with gout and its association with clinical variables and therapeutic adherence. Methods The study includes a large inception cohort of patients with gout (ACR and CGD criteria) attending the Rheumatology departments of two major hospitals started in 2010. Most patients attending these two hospitals are poor and lack of financial support to cover the cost of medical care. Demographic, clinical, biochemical and therapy variables were recorded at baseline and every six months visits. The HAQ, EuROQoL, and Coping and Adherence questionnaires previously developed and validated in our country, were administered to all patients at every visit. Good adherence (GA) was defined by the intake of ≥80% of the doses prescribed. Statistical analysis included the t, Mann Whitney, χ 2 , and Fisher9s tests. Results There were 235 patients with gout (97% males, mean age 47.7±12.6 years and mean disease duration 14.2±10.2 years, 66% tophaceous) with an educational level of 9.4±4.2 years at baseline. Coping patterns were evasive in 70% of the patients whereas 14% and 13% showed a negative emotional pattern + others or a revalorative + direct pattern, respectively. The association between evasive pattern and a lower educational level, more severe disease (number of acute flares, bigger tophi size, HAQ, VAS for pain and general health) was highly significant. Evasive pattern was still the most frequently found in 43% patients that completed the 12th month evaluation. Interestingly, 78% of the patients with evasive pattern in both visits have good therapeutic adherence, but have more severe disease (see table). Conclusions In patients with gout, evasive was the most frequent pattern of coping with the disease found in this study. Factors associated with this pattern include low educational level and severe disease. Interestingly, it does not seem associated with adherence and clinical response to treatment. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2970

Two thirds of women opt to use a vaginal pessary initially to manage the symptoms of pelvic organ prolapse. In the UK most women attend a health care professional at least every six months to change the pessary. This represents a significant burden both economically to the health care system and personally for the woman. Annually there are more than 300 appointments for pessary changes at our hospital. We developed a programme to teach women to self-manage their pessaries with the aim of improving patient experience and reducing outpatient attendances to free up outpatient capacity for new referrals. A physiotherapist was recuited to deliver this programme involving a one to one training session supplemented with written materials and an online video. Women using pessaries were offered the option of self-management. Eighty-eight women aged between 29 to 84 years enrolled in the programme. Sixty-three women (73% of those enrolled) successfully continued with self-management at six months, creating 126 extra outpatient appointment capacity in one year alone. Women self-managing reported higher levels of convenience (94% vs 81%), accessibility (97% vs 73%), support (100% vs. 83%), and comfort (86% vs. 53%) than those attending the hospital for GP practice for pessary change. Self-management appears to be an acceptable option for many women using vaginal pessaries, with personal benefits to the women and economic benefits to the hospital and commissioners.

Objectives The WHAT-ME study (Women’s Health in Apprenticeship Trades-Metalworkers and Electricians) was established because of concerns about risk to the fetus of women welding during pregnancy. Prospective data on work-related health outcomes are also collected. The potential of the study is investigated using ‘new-onset asthma or wheeze’ as an example. Methods Women in registered apprenticeships since 2005 in welding, boiler-making, steam fitting/pipefitting (‘welders’) or electrical trades are invited to join the study. They complete questionnaires on health and exposure at baseline and subsequently every six months. Exposure data are based on the last day at work at each contact, and include information on hazards encountered for each task performed. For the analyses presented here a woman was considered currently working within her trade if working as a welder or electrician at the time of the interview or in the preceding month. Results To date 496 women have signed up, and recruitment is underway across Canada. The results here are from 385 early recruits (mean age 31.6 years) with completed baseline questionnaires: 220 women, analysed here, have also completed the first (6 month) follow-up questionnaire. At baseline more welders (28%) than electricians (18%) were current smokers (p Conclusions Female welders appear at higher risk than female electricians of reporting new-onset asthma or wheeze. The continuing recruitment and follow-up of the cohort will provide increasing power for this analysis and information on tasks within trade will help identify recommendations for prevention.

Background We investigated the age-specific distribution of genital HPV and HSV-2 antibodies among men whose sexual behaviour was confined either to men or to women (fixed) vs men whose sexual behaviour included both sexes (fluid). We hypothesised that fluid men may have more exposure to viral STIs. Methods A total 4123 men from Sao Paulo, Brazil, Cuernavaca, Mexico, and Tampa, USA, aged 18–70 years, reported their sexual behaviour every six months for 2 years. Analysis was restricted to 1412 Brazilian men where fluidity had a much higher prevalence. Genital exfoliated cells for HPV PCR genotyping were collected every 6 months and blood for HSV-2 antibody testing was collected every 12 months. We used chi square and the Cochran-Armitage test to assess associations and age-specific linear trends. Results Of 1292 men at enrollment who provided sexual behaviour information at ≥ 2 time points, those aged 17–24 reported the most fluidity (24%) and those aged 50–70 reported the least (16%) although the linear trend was not significant (p = 0.12). After two years of follow up, HPV prevalence was comparable and stable by age among both fixed and fluid men for any HPV type, oncogenic types, and nononcogenic types. Prevalence of HSV-2 antibodies was higher among fluid than fixed men (65% and 59%, respectively) although not significantly different (p = 0.06). The prevalence of HSV-2 antibodies increased by age among both fixed and fluid men (p for trend Conclusions These data suggest that fluidity is not associated with increased prevalence of HPV and HSV-2. There was no trend for genital HPV by age which might be expected of a highly prevalent viral infection that often escapes immune surveillance; however, age was associated with HSV-2 antibodies as would be expected of a highly prevalent viral infection that less often escapes immune recognition.

Background Patient reported outcomes are an important aspect of outcome evaluation, and supplement the argument for the necessity of these therapies. Objectives To evaluate improvements in RA treated biologic patients’ reported function, quality of life and health status over the course of treatment. Methods The Alberta Biologics Pharmacosurveillance Program captures the clinical efficacy and safety of biologic therapies in RA since 2000. HAQ scores, SF-36 and the EQ-5D are completed every six months. Results Our cohort includes 605 patients (74% female, mean age 43 years). Mean disease activity at baseline was: DAS28 5.73, patient global score 6.8, TJC 4.4 and SJC 3.2. Improvement in the 8 domains of the SF-36 occurred over the first year of treatment and stabilized thereafter (Figure 1). A similar trend occurred in the 5 domains of the EQ-5D. HAQ scores showed improvement in the first year of therapy (mean baseline HAQ 1.59, HAQ at 1 year 0.76), followed by stabilization but began to rise again after 4 years (mean HAQ at 7 years 0.96). Conclusions Health status and quality of life significantly improve with biologic therapy, with the most impressive benefit in the first year of therapy followed by a period of stabilization lasting over 11 years. The worsening of physical function after 4 years is not associated with deterioration in other domains, which is unexpected. Disclosure of Interest None Declared

Background Rituximab is the only currently available B-cell depleting agent, licensed for use in treatment of rheumatoid arthritis (RA).The optimal therapeutic strategy that would give an answer to the question when is the best moment to repeat a course of rituximab, has not yet been clearly defined. In addition to strictly controlled randomized studies, registers show the effectiveness of different therapeutic strategies applied in daily clinical practice. Objectives To assess the efficacy of rituximab in RA when administered every six months in comparison to a longer period between two courses, according to data from the Serbian registry of RA patients (NARASS). Methods 161 RA patients, treated with rituximab are followed to date in NARRAS. Forty of them (33 women and 7 men, mean age 52 years), who received at least three courses of the drug were selected and analyzed. They were divided into two subgroups: subgroup I (SG 1 ) - 26 (65%) patients who received rituximab every six months, and subgroup II (SG 2 ) - 14 (35%) patients with a time period of seven months or more between two courses. Disease activity score (DAS 28 ) was assessed before each course and six months after the third course of rituximab, and compared between two subgroups of patients. The analysis of variance (ANOVA) and Student’s T-test were used for statistical analyses of data. Results Mean disease duration before diagnosis of RA in two subgroups of patients did not differ significantly (SG 1 : SG 2 =12.6: 17.5 months, p=0.85), as well as disease duration from diagnosis to beginning of treatment with rituximab (SG 1 : SG 2 =133.1: 123.6 months, p=0.71). The mean time period between two courses of rituximab for patients in SG 1 was 6.2 months and for patients in SG 2 8.9 months. Analyzing the data for the whole group of 40 patients we have noticed a statistically significant decrease in disease activity six months after the third course of rituximab, compared to the period before treatment (DAS 28 index decreased from 5.87 to 4.47, p 1 compared to SG 2 - mean DAS 28 decreased significantly (p=0.002) from 6.30 (before treatment) to 4.31 (six months after the third course) in SG 1 , and from 5.12 to 4.80 in SG 2 (p=0.057). Conclusions The efficacy of rituximab is better when patients are retreated regularly at six-month intervals, compared to patients who receive the drug with a longer time period between the courses Disclosure of Interest None Declared

Background The role of disease worsening or flares in taking important clinical decisions, such as dose adjustments or treatment change, is poorly understood in patients suffering from severe RA treated with TNF inhibitors over long periods of time. Objectives To determine whether the prevalence of flare episodes can predict the response to anti-TNF treatment over time and the change to second line therapy. Methods In this longitudinal, observational, population-based, cohort study we included a total of 400 patients. Data were retrieved from the National Health Insurance House (NHIH) database (2002-2011). Flare events were defined according to OMERACT criteria as increase in disease activity score DAS28 >3.2 or >0.6 if DAS28 >3.2. Prevalence of flare episodes, DAS28 response rates and EULAR response rates were calculated every six months. Results In our analysis, 379 (94.5%) patients presented 672 flare episodes (prevalence 168% in the analysed population). Conclusions In current clinical practice in Romania, a single flare episode in patients with a MDA should prompt change to second line therapy, including biological agents with other mechanisms. Our real life results, based on data collected before 2012, support OMERACT flares criteria and ACR/EULAR recommendations, emphasizing strict patient evaluation and tight control in the first 1-3 months after anti-TNF treatment initiation. Disclosure of Interest None Declared

Background It remains still unclear whether autoantibodies are useful biomarkers to tailor the choice of biological treatment in rheumatoid arthritis (RA). Objectives The main aim of our study was to identify predictive factors for response to TNF inhibitors in patients with established RA with a special focus on baseline levels of autoantibodies. Methods We performed a prospective observational 12 months study in 90 consecutive active established RA receiving their first anti-TNF agent: adalimumab (33), etanercept (30), infliximab (27). Standard assessments consisted of 28-joint counts, patient reported outcomes, inflammatory tests and activity scores (DAS28-ESR, SDAI) performed every three months, while total and IgA-RF and ACPA every six months. The primary outcome measure was SDAI remission (≤ 3.3). Univariate and multivariate logistic regression models were used to estimate the association between baseline variables and SDAI remission at 12 months, using SPSS-16 software, p Results 39.7% of RA achieved SDAI remission after 12 months of anti-TNFs. Baseline levels of autoantibodies in subgroup analysis were 182.3IU/ml for total RF, 14.4IU/ml for IgA-RF and 75.7 IU/ml for ACPA, respectively. Statistically significant moderate correlation between SDAI remission and baseline IgA-RF (Spearman: r=0.321, p=0.002), as well as weak correlation with ACPA (Sperman: r=0.194, p=0.047) were reported, while no correlation with total initial RF levels (Sperman: r=0.021, p=0.844). Furthermore, patients with baseline levels of total RF ≤100IU/ml (OR 1.09; IC95% 0.45-2.61), ACPA ≤40IU/ml(OR 1.99; IC95% 0.95-4.17) and IgA-RF ≤20IU/ml(OR 5.76; IC95% 1.43-23.23) were more likely to achieve SDAI remission. Conclusions The presence as well as the titer of IgA-RF isotype and ACPA before starting anti-TNFα therapy were significantly correlated with SDAI remission at 12 months. However, this correlation is not strong enough to allow a reliable prediction in individual patients. Disclosure of Interest None Declared

Background Granulomatous polyangiitis (GPA) is a chronic relapsing systemic vasculitis and repeated remission treatment with cyclophosphamide poses long term safety risks. Studies of rituximab (RTX) have reported successful remission in patients with severe and relapsing GPA, however relapses continue to occur in more than half the patients (1,2). Information about repeated RTX therapy in GPA is limited. Objectives To evaluate the efficacy and tolerance of repeated RTX infusions in patients with relapsing GPA, previously treated with cyclophosphamide and other conventional immunosuppressants. Methods A retrospective study of the clinical characteristics, previous treatments, disease activity, relapses and tolerance of RTX in GPA patients who had received RTX as maintenance treatment at our department between 2003 and 2011. Patients had to fulfill ACR and/or CHCC criteria for GPA. Disease activity was measured using BVAS. All patients were followed until Dec 31, 2011. Results In total eleven patients with repeated RTX infusions were identified, six men and five women, all PR3 ANCA-positive. The patients had previously received a mean of 5,6 different immunosuppressants, including cyclophosphamide and steroids. The mean cumulative dose of cyclophosphamide before RTX treatment was 50 g (range 11-105) and the median number of relapses were 3 (range 1-8). The patients have received a median of four (range 2 -11) maintenance RTX infusions (1000 mg x 2) every six months, with a median follow-up of 18 months from the first infusion (range 9-96). During follow-up no relapses have occurred and BVAS (median) dropped from 9 (range 15-4) before first infusion to 0 (range 2-0) after last infusion. 7 of 11 patients were in remission on Dec 31 2011, defined as BVAS=0 and prednisolone Seven infusion reactions have been noted (in three patients), all could continue treatment. Infections were the most frequently reported adverse events; the majority being “common colds”, but seven infections needed treatment with antibiotics and one case of Pneumocystis jiroveci was recorded. Conclusions Rituximab as maintenance treatment in this setting of GPA patients, with a median follow-up time of 18 months and receiving a median of four RTX treatments prevented further relapses, gave a good disease control and enabled reduction of steroids and other immunosuppressants. Rituximab was well tolerated but infections may prove an issue. References N Engl J Med 2010;363:221-32 2. AnnRheumDis 2011Oct. e-pub) Disclosure of Interest None Declared

Background Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, safe and effective in rheumatoid arthritis (RA) patients with inadequate response orintolerant to tumor necrosis factor (TNF) inhibitorshas been approved at dose of 1g fortnightlyevery six months. The SERENA and MIRROR studies have shown that response rates are similar in patients treated with 2x0.5g and 2x1g every six months, but there is no agreement concerning the optimal RTX strategy over time (1.2). Objectives To verify whether RA patientsEULAR responders after the third course of RTX 2x1g achieve the same result after reducing RTX doseto 2x0.5g Methods Among seventy active RA patients with inadequate response to MTX (range 7.5-20 mg/week) and at least one anti-TNF inhibitor treated in our Center since 2007 we selected twenty-one patients that reached a good-moderate EULAR response after treatment with three courses of RTX 2x1g every six months. At the fourth course they were randomly treated with RTX 2x0.5g (group 1: 10 patients, 9 F, mean age 48 years, range 21-68; mean disease duration 9.7±6.2 years, 5 RF + and 6 anti-CCP +, baseline DAS28: 4.62±0.98) or RTX 2x1g (group 2: 11 patients, 8 F, mean age 61 years, range 39-74; mean disease duration 11.1 ± 8.3 years, 9 RF + and 8 anti-CCP +, baseline DAS28: 4.85±1.35) every six months for 52 weeks Results No difference between the two groups in disease duration (p=0.832), baseline DAS28 (p=0.647), percentage of patient RF+ (p=0.055) and anti-CCP+ (p=0.126) are observed. The percentage of patients in low disease activity (LDA) or remission based on DAS28 were similar in both groups after the fourth (70.0% vs 72.8% p=1,0) and fifth course (83.3% vs 66.7% p= 0.545). They maintained the same rate of EULAR response respect baseline (100% vs 90.1% p= 1 after course four and 100% vs 100% after course five). Conclusions In patients responders to three standard doses of RTX, it is possible to reduce the dose to 2x0,5g without affecting response and optimizing the pharmacoeconomic impact. Further studies to evaluate the radiological progression of RA after dose reduction are suggested. References Emery P, et al. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (SERENE). Ann Rheum Dis. 2010;69:1629-35. Rubbert-Roth A, et al . Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR). Rheumatology ( Oxford ). 2010;49:1683-93. Disclosure of Interest None Declared

An experimental vaccine against HIV has resulted in the number of people infected with the virus being a third less than in the placebo group, although the number of cases was small, in results released this week from the first trial to show that vaccination can protect against HIV infection in humans. The phase III trial randomised 16 402 volunteers (aged 18-30) in Thailand to the HIV vaccine or placebo. The volunteers were HIV negative at the start of the trial and were all counselled on protecting themselves against HIV infection before the study and then every six months, for a total of three years. The proof of concept study, which began in 2003, was designed to evaluate the vaccine’s efficacy in preventing …

Aim for one audit every six months of your job. Convey your interest to the consultant in charge of audits or your own educational supervisor at the beginning of your job. If your job is only for six months, the earlier you start the earlier you can finish it. Join an audit team. If you are inexperienced or have limited …

In mid-1997 I went for blood and other tests after an episode of back pain. A monoclonal electrophoretic peak and a spinal lesion of uncertain origin were found. After a few months of further tests I was given a diagnosis of monoclonal gammopathy of uncertain significance (MGUS). I was no longer a subjectively healthy man but a potentially ill person, with considerable anxiety. MGUS is one of those strange noso-logical entities of modern medicine—which is so good at creating “new diseases” without necessarily knowing how to cure them. The medical literature didn't help much. Several small studies reported a cumulative risk of malignant transformation of MGUSs of between 7% and 19%, with the likeliest estimate of annual risk of transformation around 1%, but without clear predictors. > Could a second transplant improve results? I was prescribed blood tests every six months to monitor any such transformation. The years went by, during which my levels of anxiety varied, increasing at times of testing and whenever any personal or work …

Objective To compare blood pressure control, satisfaction, and adherence to drug treatment in patients with treated hypertension followed up by their family physicians either every three months or every six months for three years. Design Randomised equivalence clinical trial. Settings 50 family practices in south eastern Ontario, Canada. Participants 609 patients aged 30-74 years with essential hypertension receiving drug treatment whose hypertension had been controlled for at least three months before entry into the study. Results 302 patients were randomly assigned to follow up every three months and 307 to follow up every six months. Baseline variables in the two groups were similar. As expected, patients in the six month group had significantly fewer visits, but patients in both groups visited their doctor more frequently than their assigned interval. Mean blood pressure was similar in the groups, as was control of hypertension. Patient satisfaction and adherence to treatment were similar in the groups. About 20% of patients in each group had blood pressures that were out of control during the study. Conclusions Follow up of patients with treated essential hypertension every six months is equivalent to follow up every three months. Patient satisfaction and adherence to treatment are the same for these follow up intervals. As about 20% of patients' hypertension was out of control at any time during the study in both groups, the frequency of follow up may not the most important factor in the control of patients' hypertension by family practitioners.

We recently showed that daily supplementation with 1.2 g calcium and 800 IU cholecalciferol over 18 months substantially decreased the risk of hip fractures and other non-vertebral fractures in elderly women living in nursing homes.1 We report the results of a further 18 months of treatment. A total of 3270 mobile elderly women (mean age 84 (SD 6) years) living in 180 nursing homes were enrolled in the study. Half the women received 1.2 g calcium daily in the form of tricalcium phosphate, together with 800 IU (20 μg) cholecalciferol; the other half received a double placebo. All subjects were followed up every six months; biochemical variables were measured at baseline and every year in a subgroup of 52 women. Hip fractures and all non-vertebral fractures were separately analysed using a log …

Sexually active teenage girls should be screened for Chlamydia trachomatis infection every six months, not every 12 months as recommended, according to a study by US researchers published in JAMA (1998;280:521-6). High rates of infection and re-infection put young girls at risk of pelvic inflammatory disease, infertility, and ectopic pregnancy. The study's leader, Dr Gale Burstein, a paediatric and adolescent medicine specialist at Johns Hopkins …

Five times: coincidence or something more serious? {#article-title-2} See Editor's choice The anonymous article below was sent to us by a doctor outlining the concerns he had about the competence of a surgeon he once worked with when he was a junior doctor. We asked four other doctors what the junior should have done, what they would have done had they been approached by the junior, and what the implications are for the regulation of medicine. Perioperative mortality (death within 28 days of an operation) has became a key surgical phrase in the past decade, particularly after the publication of the first report of the confidential inquiry into perioperative deaths. This document detailed a variety of surgical and anaesthetic disasters, and, although it pointed out that many perioperative deaths were and remain unavoidable, there were contributory factors such as inadequate hospital facilities, poor supervision of junior doctors, and inappropriate surgery in severely ill patients. This and subsequent reports, together with regular intradepartmental and interdepartmental audits, have raised the awareness of perioperative mortality. All operative deaths should now be discussed to discover if care could have been improved or death avoided. I have been fortunate to be a surgical trainee in these more enlightened times. Usually, the audits I have attended have had an average of one death every six months from routine general surgery lists (somewhat more from emergency surgery), and even fewer during my five years in specialist training. With one exception: during a six month period on one firm, five patients on routine lists died from a variety of reasons. All of these patients were led to believe that their conditions would be substantially improved if not cured by the surgery, and yet within a matter of days they were dead. I felt at the time that certain questions were overlooked, if not ignored. My polite …

Studies of the effects of different exercise programmes on bone in postmenopausal women have produced different conclusions, but few have targeted elderly women specifically.1 We report a controlled trial of weight bearing exercise in this clinically important population. The study was approved by the local ethics committee. We recruited volunteers by advertising in the local press. After excluding subjects with conditions or drug treatment likely to affect bone, we randomly allocated 118 volunteers (mean age 64.5 (range 60-73) years) to either a group taking calcium supplementation (1000 mg calcium daily, as calcium carbonate) or to an exercise group taking the same calcium supplementation. We monitored compliance with calcium by a tablet count every six months. We asked volunteers in the calcium group taking exercise to attend the University of Dundee's exercise class for people aged over 60 three times weekly for each of three 10 …

Height and weight were measured every six months in a long term prospective study of 66 children with chronic perennial asthma for a mean 13.1 years. There was no evidence of growth retardation on entry into the study. Growth developed along normal lines in all 66 children until about 10 years, and in 35 of these children growth continued along normal lines throughout the whole period of follow up. Thirty children showed the physiological decelerating growth velocity pattern seen in children with delay in the onset of puberty, and one child had an early menarche. The tendency for delay in the onset of puberty was significant for both boys and girls and was noted to be independent of severity of asthma. Once puberty finally began in these children, complete catch up growth resulted in the attainment of the predicted adult height. Long term prophylactic inhalation of beclomethasone dipropionate in 26 children in a dosage up to 600 mcg/day before puberty and 400 mcg/day during puberty was shown not to affect growth. It is concluded that asthma had no direct influence on growth in height but was associated with delay in the onset of puberty. The pre-adolescent physiological deceleration of growth velocity that occurs in these children gives the impression of growth retardation.

General professional training in psychiatry usually requires a minimum of three years' in-service training in senior house officer and registrar posts, leading to membership of the Royal College of Psychiatrists (MRCPsych) by examination. In 1974 the postgraduate dean of this region and his adviser from the Royal College of Psychiatrists set up a psychiatric subcommittee of the regional postgraduate medical committee, to consider and advise on the planning of training in psychiatry in the region. At that time, four clinical tutors ran well-known weekend and week-long block release courses which took place every six months, either at Brookwood psychiatric hospital or at the University of Surrey, in addition to their local teaching responsibilities. These courses were intended to prepare candidates for the professional examination, which occurred twice yearly. In addition one of the tutors had organised a two-term day release basic medical science course for Part A of the Diploma of Psychological Medicine (which be came also suitable for the preliminary MRCPsych examination). Early on, the subcommittee recommended the setting up of a regional two-year day release course (consisting of six seven-week terms), which was designed to equip candidates for the final part of the MRCPsych examination. After two years the entire course was held at St George's Hospital Medical