A randomised interventional trial of ω-3-polyunsaturated fatty acids on endothelial function and disease activity in systemic lupus erythematosus

Objective: To determine the clinical effect of dietary supplementation with low-dose ?-3-polyunsaturated fatty acids on disease activity and endothelial function in patients with systemic lupus erythematosus. Methods: A 24-week randomised double-blind placebo-controlled parallel trial of the effect of 3 g of ?-3-polyunsaturated fatty acids on 60 patients with systemic lupus erythematosus was performed. Serial measurements of disease activity using the revised Systemic Lupus Activity Measure (SLAM-R) and British Isles Lupus Assessment Group index of disease activity for systemic lupus erythematosus (BILAG), endothelial function using flow-mediated dilation (FMD) of the brachial artery, oxidative stress using platelet 8-isoprostanes and analysis of platelet membrane fatty acids were taken at baseline, 12 and 24 weeks. Results: In the fish oil group there was a significant improvement at 24 weeks in SLAM-R (from 9.4 (SD 3.0) to 6.3 (2.5), p

Steps to a better Belfast: physical activity assessment and promotion in primary care

BACKGROUND: Low physical activity (PA) levels which increase the risk of chronic disease are reported by two-thirds of the general UK population. Promotion of PA by primary healthcare professionals is advocated but more evidence is needed regarding effective ways of integrating this within everyday practice. This study aims to explore the feasibility of a randomised trial of a pedometer-based intervention, using step-count goals, recruiting patients from primary care. METHOD: Patients, aged 35-75, attending four practices in socioeconomically deprived areas, were invited to complete a General Practice PA Questionnaire during routine consultations. Health professionals invited 'inactive' individuals to a pedometer-based intervention and were randomly allocated to group 1 (prescribed a self-determined goal) or group 2 (prescribed a specific goal of 2500 steps/day above baseline). Both groups kept step-count diaries and received telephone follow-up at 1, 2, 6 and 11 weeks. Step counts were reassessed after 12 weeks. RESULTS: Of the 2154 patients attending, 192 questionnaires were completed (8.9%). Of these, 83 were classified as 'inactive'; 41(10 men; 31 women) completed baseline assessments, with the mean age of participants being 51 years. Mean baseline step counts were similar in group 1 (5685, SD 2945) and group 2 (6513, SD 3350). The mean increase in steps/day was greater in groups 1 than 2 ((2602, SD 1957) vs (748, SD 1997) p=0.005). CONCLUSIONS: A trial of a pedometer-based intervention using self-determined step counts appears feasible in primary care. Pedometers appear acceptable to women, particularly at a perimenopausal age, when it is important to engage in impact loading activities such as walking to maintain bone mineral density. An increase of 2500 steps/day is achievable for inactive patients, but the effectiveness of different approaches to realistic goal-setting warrants further study.

Physical activity assessment in practice: a mixed methods study of GPPAQ use in primary care

Background: Insufficient physical activity (PA) levels which increase the risk of chronic disease are reported by almost two-thirds of the population. More evidence is needed about how PA promotion can be effectively implemented in general practice (GP), particularly in socio-economically disadvantaged communities. One tool recommended for the assessment of PA in GP and supported by NICE (National Institute for Health and Care Excellence) is The General Practice Physical Activity Questionnaire (GPPAQ) but details of how it may be used and of its acceptability to practitioners and patients are limited. This study aims to examine aspects of GPPAQ administration in non-urgent patient contacts using different primary care electronic recording systems and to explore the views of health professionals regarding its use.

Methods: Four general practices, selected because of their location within socio-economically disadvantaged areas, were invited to administer GPPAQs to patients, aged 35-75 years, attending non-urgent consultations, over two-week periods. They used different methods of administration and different electronic medical record systems (EMIS, Premiere, Vision). Participants’ (general practitioners (GPs), nurses and receptionists) views regarding GPPAQ use were explored via questionnaires and focus groups.

Results: Of 2,154 eligible consultations, 192 (8.9%) completed GPPAQs; of these 83 (43%) were categorised as inactive. All practices were located within areas ranked as being in the tertile of greatest socio-economic deprivation in Northern Ireland. GPs/nurses in two practices invited completion of the GPPAQ, receptionists did so in two. One practice used an electronic template; three used paper copies of the questionnaires. End-of-study questionnaires, completed by 11 GPs, 3 nurses and 2 receptionists and two focus groups, with GPs (n = 8) and nurses (n = 4) indicated that practitioners considered the GPPAQ easy to use but not in every consultation. Its use extended consultation time, particularly for patients with complex problems who could potentially benefit from PA promotion.

Conclusions: GPs and nurses reported that the GPPAQ itself was an easy tool with which to assess PA levels in general practice and feasible to use in a range of electronic record systems but integration within routine practice is constrained by time and complex consultations. Further exploration of ways to facilitate PA promotion into practice is needed.

A Longitudinal Study of Stargardt Disease: Quantitative Assessment of Fundus Autofluorescence, Progression and Genotype Correlations

PURPOSE To characterise subtypes of fundus autofluorescence (AF), the progression of retinal atrophy and correlate these findings with genotype in Stargardt Disease. METHODS Full clinical examination and AF imaging was undertaken in 68 patients with Stargardt Disease. The baseline data were compared with those at follow-up. Patients were classified into three AF subtypes: type 1 had a localised low signal at the fovea surrounded by a homogeneous background; type 2 had a localised low signal at the macula surrounded by a heterogeneous background with numerous foci of abnormal signal; type 3 had multiple low signal areas at the posterior pole with a heterogeneous background. At baseline, there were 19 patients with type 1, 41 with type 2, and 8 with type 3. The areas of reduced AF signal were measured and rate of atrophy enlargement (RAE) was calculated as the difference of the atrophy size over time (mm2) divided by the follow-up interval (yrs). Molecular screening of ABCA4 was undertaken. RESULTS The mean follow-up interval was 9.1 years. 42% of type 1 progressed to type 2, and 12% of type 2 progressed to type 3. RAE (mm2/yr) based upon baseline AF subtypes was significantly different; 0.06 in type 1, 0.67 in type 2, and 4.37 in type 3. ABCA4 variants were identified in 57 patients. There was a significant association between AF subtype and genotype. CONCLUSIONS The AF pattern at baseline influences the enlargement of atrophy over time and has genetic correlates. These data are likely to assist in the provision of counselling on prognosis in Stargardt Disease and be valuable for future clinical trials.

Physical activity assessment in cystic fibrosis: A position statement

Background

The aim of this position statement was to inform the choice of physical activity tools for use within CF research and clinical settings.

Methods

A systematic review of physical activity tools to explore evidence for reliability, validity, and responsiveness. Narrative answers to “four key questions” on motion sensors, questionnaires and diaries were drafted by the core writing team and then discussed at the Exercise Working Group in ECFS Lisbon 2013.

Results and summary

Our current position is that activity monitors such as SenseWear or ActiGraph offer informed choices to facilitate a comprehensive assessment of physical activity, and should as a minimum report on dimensions of physical activity including energy expenditure, step count and time spent in different intensities and sedentary time. The DigiWalker pedometer offers an informed choice of a comparatively inexpensive method of obtaining some measurement of physical activity. The HAES represents an informed choice of questionnaire to assess physical activity. There is insufficient data to recommend the use of one diary over another. Future research should focus on providing additional evidence of clinimetric properties of these and new physical activity assessment tools, as well as further exploring the added value of physical activity assessment in CF.

Optical Coherence Tomography for the Monitoring of Neovascular Age-Related Macular Degeneration: A Systematic Review

Topic

To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition.

Traditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests.

Systematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias.

We included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%–93%) and 48% (95% CI, 30%–67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias.

There is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.

The role of Optical Coherence Tomography (OCT) for the diagnosis, monitoring, and guiding of treatment for neovascular Age-related Macular Degeneration (nAMD): an evidence synthesis study

Purpose:To determine the optimal role of OCT in diagnosing and monitoring nAMD (detecting disease activity and the need for further anti-VEGF treatment).
Methods:Systematic review. Major electronic databases and websites were searched. Studies were included if they reported the diagnostic performance of time domain or spectral domain OCT (or selected other tests) against a reference standard of ophthalmologist-interpreted fluorescein angiography in people with newly suspected or previously diagnosed nAMD. Risk of bias was assessed by two independent investigators using QUADAS-2. Summary receiver operating characteristic (SROC) curves were produced for each test given sufficient data.
Results:3700 titles/abstracts were screened, and 120 (3.2%) were selected for full-text assessment. A total of 22 studies were included (17 on diagnosis, 7 monitoring, and 3 both). From 15 studies reporting OCT data, sensitivity and specificity ranged from 59% to 100% and 27% to 100%, respectively.
Conclusions:The reported diagnostic performance of OCT showed large variability. The methodological quality of most studies was sub-optimal.

Randomized comparison of unfractionated heparin with corticosteroids in severe active inflammatory bowel disease

BACKGROUND: Heparin therapy may be effective in steroid resistant inflammatory bowel disease.

AIM: A randomized pilot study, to compare unfractionated heparin as a first-line therapy with corticosteroids in colonic inflammatory bowel disease.

METHODS: Twenty patients with severe inflammatory bowel disease (ulcerative colitis, n=17; Crohn's colitis, n=3) were randomized to either intravenous heparin for 5 days, followed by subcutaneous heparin for 5 weeks (n=8), or high-dose intravenous hydrocortisone for 5 days followed by oral prednisolone 40 mg daily, reducing by 5 mg per day each week (n=12). After 5 days, non-responders in each treatment group were commenced on combination therapy. Response to therapy was monitored by: clinical disease activity (ulcerative colitis: Truelove and Witt Index; Crohn's colitis: Harvey and Bradshaw Index), stool frequency, serum C-reactive protein and alpha1 acid glycoprotein, endoscopic and histopathological grading.

RESULTS: The response rates were similar in both treatment groups: clinical activity index (heparin vs. steroid; 75% vs. 67%; P=0.23), stool frequency (75% vs. 67%; P=0.61), endoscopic (75% vs. 67%; P=0.4) and histopathological grading (63% vs. 50%; P=0.67). Both treatments were well-tolerated with no serious adverse events.

CONCLUSION: Heparin as a first line therapy is as effective as corticosteroids in the treatment of colonic inflammatory bowel disease. Large multicentre randomized comparative studies are required to determine the role of heparin in the management of inflammatory bowel disease.

Learning from Outdoor Webcams: Surveillance of Physical Activity Across Environments

Abstract
Publicly available, outdoor webcams continuously view the world and share images. These cameras include traffic cams, campus cams, ski-resort cams, etc. The Archive of Many Outdoor Scenes (AMOS) is a project aiming to geolocate, annotate, archive, and visualize these cameras and images to serve as a resource for a wide variety of scientific applications. The AMOS dataset has archived over 750 million images of outdoor environments from 27,000 webcams since 2006. Our goal is to utilize the AMOS image dataset and crowdsourcing to develop reliable and valid tools to improve physical activity assessment via online, outdoor webcam capture of global physical activity patterns and urban built environment characteristics.
This project’s grand scale-up of capturing physical activity patterns and built environments is a methodological step forward in advancing a real-time, non-labor intensive assessment using webcams, crowdsourcing, and eventually machine learning. The combined use of webcams capturing outdoor scenes every 30 min and crowdsources providing the labor of annotating the scenes allows for accelerated public health surveillance related to physical activity across numerous built environments. The ultimate goal of this public health and computer vision collaboration is to develop machine learning algorithms that will automatically identify and calculate physical activity patterns.

Accelerated apoptosis in SLE neutrophils cultured with anti-dsDNA antibody isolated from SLE patient serum: a pilot study.

Increased numbers of apoptotic neutrophils are found in SLE, related to disease activity and levels of anti-dsDNA antibody. The mechanism of increased apoptosis is not clear, but anti-dsDNA antibody has been shown to induce apoptosis in neutrophils from normal subjects and in certain cell lines. In this study, polyclonal anti-dsDNA antibody was isolated from the serum of a patient with active SLE, and was shown to substantially accelerate apoptosis in neutrophils from SLE patients as compared with neutrophils from healthy control or rheumatoid arthritis subjects.

The clinical effect of dietary supplementation with omega-3 fish oils and/or copper in systemic lupus erythematosus.

OBJECTIVE: To determine the effect of dietary supplementation with omega-3 fish oils with or without copper on disease activity in systemic lupus erythematosus (SLE). Fish oil supplementation has a beneficial effect on murine models of SLE, while exogenous copper can decrease the formation of lupus erythematosus cells in rats with a hydralazine-induced collagen disease. METHODS: A double blind, double placebo controlled factorial trial was performed on 52 patients with SLE. Patients were randomly assigned to 4 treatment groups. Physiological doses of omega-3 fish oils and copper readily obtainable by dietary means were used. One group received 3 g MaxEPA and 3 mg copper, another 3 g MaxEPA and placebo copper, another 3 mg copper and placebo fish oil, and the fourth group received both placebo capsules. Serial measurements of disease activity using the revised Systemic Lupus Activity Measure (SLAM-R) and peripheral blood samples for routine hematological, biochemical, and immunological indices were taken at baseline, 6, 12, and 24 weeks. RESULTS: There was a significant decline in SLAM-R score from 6.12 to 4.69 (p <0.05) in those subjects taking fish oil compared to placebo. No significant effect on SLAM-R was observed in subjects taking copper. Laboratory variables were unaffected by either intervention. CONCLUSION: In the management of SLE, dietary supplementation with fish oil may be beneficial in modifying symptomatic disease activity.

Colour Doppler ultrasound of the ocular circulation in patients with systemic lupus erythematosus identifies altered microcirculatory haemodynamics

We assessed whether quantitative analysis of Doppler flow velocity waveforms is able to identify subclinical microvascular abnormalities in SLE and whether eigenvector analysis can detect changes not detectable using the resistive index (RI). Fifty-four SLE patients with no conventional cardiovascular risk factors, major organ involvement or retinopathy were compared to 32 controls. Flow velocity waveforms were obtained from the ophthalmic artery (OA), central retinal artery (CRA) and common carotid artery (CA). The waveforms were analysed using eigenvector decomposition and compared between groups at each arterial site. The RI was also determined. The RI was comparable between groups. In the OA and CRA, there were significant differences in the lower frequency sinusoidal components (P <0.05 for each component). No differences were apparent in the CA between groups. Eigenvector analysis of Doppler flow waveforms, recorded in proximity of the terminal vascular bed, identified altered ocular microvascular haemodynamics in SLE. Altered waveform structure could not be identified by changes in RI, the traditional measure of downstream vascular resistance. This analytical approach to waveform analysis is more sensitive in detecting preclinical microvascular abnormalities in SLE. It may hold potential as a useful tool for assessing disease activity, response to treatment, and predicting future vascular complications.

Wegener's granulomatosis and autoantibodies to neutrophil antigens

We report five cases of Wegener's granulomatosis all of whom had clinical and histological evidence of disease activity at presentation and in whom autoantibodies to neutrophil antigens were detected. This test may prove useful for the diagnosis of this serious condition and help to monitor disease activity during treatment.

Plasma IL-6 levels correlate with clinical and ultrasound measures of arthritis in patients with systemic lupus erythematosus

ObjectiveThe objective of this paper is to elucidate the role of specific cytokines in lupus (SLE) arthritis.MethodsFifty SLE and 40 RA patients had an ultrasound (US) scan of their hand as per standardized protocols. US scores were expressed per joint and as a total 'US activity' score, (sum of power Doppler (PD) and grey-scale synovial hypertrophy scores in all joints) and a total erosion score. SLE disease activity was assessed (BILAG and SELENA-SLEDAI). Plasma levels of IL-6, TNF-alpha and BLyS were measured using sandwich ELISA kits (Quantikine kits, R & D).ResultsOn the basis of the US results SLE patients were divided into three groups: erosive arthritis (n?=?20), non-erosive arthritis (n?=?18) and those with a normal US scan (n?=?12). Across the SLE groups plasma IL-6 levels correlated with CRP (p?