Fish oil: what the prescriber needs to know

There is a general belief among doctors, in part grounded in experience, that patients with arthritis need nonsteroidal anti-inflammatory drugs (NSAIDs). Implicit in this view is that these patients require the symptomatic relief provided by inhibiting synthesis of nociceptive prostaglandin E(2), a downstream product of the enzyme cyclo-oxygenase (COX), which is inhibited by NSAIDs. However, the concept of 'safe' NSAIDs has collapsed following a multiplicity of observations establishing increased risk for cardiovascular events associated with NSAID use, especially but not uniquely with the new COX-2-selective NSAIDs. This mandates greater parsimony in the use of these agents. Fish oils contain a natural inhibitor of COX, reduce reliance on NSAIDs, and reduce cardiovascular risk through multiple mechanisms. Fish oil thus warrants consideration as a component of therapy for arthritis, especially rheumatoid arthritis, in which its symptomatic benefits are well established. A major barrier to the therapeutic use of fish oil in inflammatory diseases is ignorance of its mechanism, range of beneficial effects, safety profile, availability of suitable products, effective dose, latency of effects and instructions for administration. This review provides an evidence-based resource for doctors and patients who may choose to prescribe or take fish oil

Pelatihan Penerapan Teknologi Fiber Glass pada Perahu Tradisional di Desa Karangsong

Potential of marine fisheries in our country is very big, one of them in Indramayu. However, the people who tend to still use the traditional way of making or repairing boats resulted in utilization is not optimal. Karangsong fundamental problem is the inability of traditional fishing boats as a means of providing the arrest. An alternative form of boat made of fiberglass are very worthy to be a technological solution. Fiberglass technology has long been known, but its use by fishermen in the village of Indramayu especially Karangsong not optimal. Therefore, the need for training on the application of fiberglass technology. The program is expected to make the fishing communities get added value and simplify the process of making a boat that is necessary to improve the productivity of the fishermen. The method is performed in the implementation of this program for surveying, socialization programs to the community in the village Karangsong, preparation tools and place, giving General knowledge of fiberglass materials, training design boat design, the development of the use of resin, boat making, evaluation and monitoring. Result of this activity is increased knowledge about fiberglass fishing communities around and start applying fiberglass technology for repair and manufacture of traditional boats

Mild autonomic dysfunction in primary Sjögren's syndrome: a controlled study

Introduction The aim of this study was to compare cardiovascular autonomic nervous system function in patients with primary Sjögren's syndrome (pSS) with that in control individuals, and to correlate the findings with autonomic symptoms and the presence of exocrine secretory dysfunction. Methods Twenty-seven female patients with pSS and 25 control individuals completed the COMPASS (Composite Autonomic Symptom Scale) self-reported autonomic symptom questionnaire. Beat-to-beat heart rate and blood pressure data in response to five standard cardiovascular reflex tests were digitally recorded using a noninvasive finger pressure cuff and heart rate variability was analyzed by Fourier spectral analysis. Analysis was performed by analysis of variance (ANOVA), multivariate ANOVA and repeated measures ANOVA, as indicated. Factor analysis was utilized to detect relationships between positive autonomic symptoms in pSS patients. Results Multiple, mild autonomic disturbances were observed in pSS patients relating to decreased heart rate variability, decreased blood pressure variability and increased heart rate, which were most evident in response to postural change. There was a strong trend toward an association between decreased heart rate variability and increased severity of the secretomotor, orthostatic, bladder, gastroparesis and constipation self-reported autonomic symptom cluster identified in pSS patients. This symptom cluster was also associated with fatigue and reduced unstimulated salivary flow, and therefore may be an important component of the clinical spectrum of this disease. Conclusion There was evidence of mild autonomic dysfunction in pSS as measured with both cardiovascular reflex testing and self-reported symptoms. Pathogenic autoantibodies targeting M3 muscarinic receptors remain a strong candidate for the underlying pathophysiology, but practical assays for the detection of this autoantibody remain elusive.Fin ZJ Cai, Sue Lester, Tim Lu, Helen Keen, Karyn Boundy, Susanna M Proudman, Anne Tonkin and Maureen Rischmuelle

Prevalence, correlates and clinical usefulness of antibodies to RNA polymerase III in systemic sclerosis: a cross-sectional analysis of data from an Australian cohort

Extent: 13p.INTRODUCTION: The prevalence of antibodies to RNA polymerase III (anti-RNAP) differs among systemic sclerosis (SSc) cohorts worldwide. Previously reported associations of anti-RNAP include diffuse cutaneous disease, tendon friction rubs and renal crisis, with recent reports suggesting a close temporal association between malignancy and SSc disease onset among patients with anti-RNAP. METHODS: Patients with SSc were tested for the presence of anti-RNAP at recruitment into the Australian Scleroderma Cohort Study. We used univariate and multivariable methods to identify and quantify clinical and laboratory correlates of anti-RNAP in SSc. Diagnostic testing procedures were used to determine the usefulness of these antibodies in estimating the likelihood of clinically important outcomes. RESULTS: There were 451 patients with mean ± standard deviation age and disease duration at recruitment of 58.1 ± 12.4 and 11.6 ± 10.0 years, respectively; 151 (33.5%) patients were recruited within 5 years of diagnosis of SSc. Overall, 69 (15.3%) patients had anti-RNAP. Univariate associations of anti-RNAP were diffuse disease (75.4% vs. 20.9%, P < 0.0001), joint contractures (73.9% vs. 30.1%, P < 0.0001), greater highest-recorded modified Rodnan skin score (20.6 ± 12.4 vs. 10.1 ± 7.9, P < 0.0001), synovitis (31.9% vs. 19.9%, P = 0.03), myositis (2.9% vs. 0.5%, P = 0.05), systemic hypertension (59.4% vs. 39.7%, P = 0.002), renal crisis (24.6% vs. 1.8%, P < 0.0001) and malignancy diagnosed within 5 years of onset of SSc skin disease (13.3% vs. 3.9%, P = 0.01). In multiple regression analysis, after adjustment for other covariates, anti-RNAP were independently associated with renal crisis (odds ratio (OR) 3.8, 95% confidence interval (CI) 1.2 to 11.5, P = 0.02; positive predictive value (PPV) 24.6%, negative predictive value (NPV) 98.2%), diffuse disease (OR 6.4, 95% CI 2.9 to 13.8, P < 0.0001; PPV 75.4%, NPV 20.9%), joint contractures (OR 2.5, 95% CI 1.2 to 5.3, P = 0.02; PPV 73.9%, NPV 69.9%) and malignancy diagnosed within 5 years of onset of SSc skin disease (OR 4.2, 95% CI 1.3 to 13.4, P = 0.01; PPV 13.3%, NPV 96.1%). CONCLUSIONS: Anti-RNAP status is a clinically useful prognostic marker in SSc and enables clinicians to identify patients at high risk of developing renal crisis, synovitis, myositis and joint contractures. Patients with anti-RNAP also have an increased risk of malignancy within a 5-year timeframe before or after onset of SSc skin changes.Mandana Nikpour, Pravin Hissaria, Jillian Byron, Joanne Sahhar, Maree Micallef, William Paspaliaris, Janet Roddy, Peter Nash, Alan Sturgess, Susanna Proudman and Wendy Steven

Risk factors for development of pulmonary arterial hypertension in Australian systemic sclerosis patients: Results from a large multicenter cohort study

Published online: 27 September 2016Background: Pulmonary arterial hypertension (PAH) is the leading cause of mortality in patients with systemic sclerosis (SSc). We sought to determine the incidence, prevalence and risk factors for PAH development in a large Australian SSc cohort. Methods: PAH was diagnosed on right heart catheterisation (mPAP >25 and PAWP <15 mmHg at rest). Patients with PH secondary to interstitial lung disease (ILD; defined as abnormal HRCT scan and FVC < 60 %) were excluded. Summary statistics, chi-square tests, univariate and multivariable logistic regression along with post-estimation diagnostics were used to determine the associations of different combinations of risk factors with PAH. Results: Among 1579 SSc patients, 8.4 % (132 patients) were diagnosed with PAH over a mean (±SD) follow-up of 3.2 (±2.5) years. The incidence of PAH in this cohort was 0.7 % per annum. Of these, 68.9 % had limited disease subtype (lcSSc). In multivariable regression analysis, the presence of anti-centromere antibody (ACA) (OR 1.6, 95 % CI 1.1-2.5, p = 0.03), oesphageal stricture (OR 2.0, 95 % CI 1.2-3.3, p = 0.006), calcinosis (OR 1.9, 95 % CI 1.2-2.9, p = 0.003), sicca symptoms (OR 1.6, 95 % CI 1.1-2.5, p = 0.03), mild ILD (OR 2.3, 95 % CI 1.5-3.7, p < 0.001) and digital ulcers (OR 1.6, 95 % CI 1.0-2.4, p = 0.03) were predictive of PAH. This model had an area under the curve of 0.7 and concordance of 91.8 %. When analysed by disease subtype, the presence of calcinosis (OR 2.2, 95 % CI 1.4-3.7, p = 0.01), sicca symptoms (OR 2.6, 95 % CI 1.5-4.6, p = 0.001), mild ILD (OR 2.3, 95 % CI 1.4-3.8, p = 0.001) and digital ulcers (OR 1.9, 95 % CI 1.2-3.7, p = 0.01) were predictive of PAH in lcSSc; and oesophageal stricture (OR 4.4, 95 % CI 1.9-10.5, p = 0.001), mild ILD (OR 2.8, 95 % CI 1.2-6.8, p = 0.02) and ACA (OR 5.2, 95 % CI 1.8-14.8, p = 0.002) were predictive of PAH in dcSSc. Conclusions: The incidence and prevalence of PAH in this cohort are 0.7 % per annum and 8.4 %, respectively. The clinical-serologic risk factors for PAH differ based on disease subtype. In both subtypes, mild ILD is associated with PAH, suggesting the possibility of common pathogenic mechanisms underlying both of these disease manifestations. This model identifies a subset of patients at an appreciably higher risk of developing PAH, who should be screened and would in future, benefit from preventative therapies.Kathleen Morrisroe, Molla Huq, Wendy Stevens, Candice Rabusa, Susanna M. Proudman, Mandana Nikpour and the Australian Scleroderma Interest Group (ASIG

Cardiac arrhythmias and conduction defects in systemic sclerosis

Signs and symptoms of arrhythmias or conduction defects are frequently reported in patients with SSc. These rhythm disorders may have several origins (i.e. related to primary heart involvement, pericardial disease, valvular regurgitation or pulmonary arterial hypertension) and may negatively affect the overall prognosis of these patients. It is therefore important to identify patients at high risk for cardiac arrhythmias with a complete cardiological evaluation and to identify the underlying heart disease, including SSc-related myocardial involvement. In addition, some therapeutic options in SSc patients may differ from those recommended in other population

A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee

INTRODUCTION: AMG 108 is a fully human, immunoglobulin subclass G2 (IgG2) monoclonal antibody that binds the human interleukin-1 (IL-1) receptor type 1, inhibiting the activity of IL-1a and IL-1b. In preclinical studies, IL-1 inhibition was shown to be beneficial in models of osteoarthritis (OA). The purpose of this two-part study was to evaluate the safety and pharmacokinetics (PK; Part A) and clinical effect (Part B) of AMG 108 in a double-blind, placebo-controlled, multiple-dose study in patients with OA of the knee. METHODS: In Part A, patients received placebo or AMG 108 subcutaneously (SC; 75 mg or 300 mg) or intravenously (IV; 100 mg or 300 mg) once every 4 weeks for 12 weeks; in Part B, patients received placebo or 300 mg AMG 108 SC, once every 4 weeks for 12 weeks. The clinical effect of AMG 108 was measured in Part B by using the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index pain score. RESULTS: In Part A, 68 patients were randomized, and 64 received investigational product. In Part B, 160 patients were randomized, and 159 received investigational product. AMG 108 was well tolerated. Most adverse events (AEs), infectious AEs, serious AEs and infections, as well as withdrawals from the study due to AEs occurred at similar rates in both active and placebo groups. One death was reported in an 80-year-old patient (Part A, 300 mg IV AMG 108; due to complications of lobar pneumonia). AMG 108 serum concentration-time profiles exhibited nonlinear PK. The AMG 108 group in Part B had statistically insignificant but numerically greater improvement in pain compared with the placebo group, as shown by the WOMAC pain scores (median change, -63.0 versus -37.0, respectively). CONCLUSIONS: The safety profile of AMG 108 SC and IV was comparable with placebo in patients with OA of the knee. Patients who received AMG 108 showed statistically insignificant but numerically greater improvements in pain; however, minimal, if any, clinical benefit was observed. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov with the identifier NCT00110942.Stanley B Cohen, Susanna Proudman, Alan J Kivitz, Francis X Burch, John P Donohue, Deborah Burstein, Yu-Nien Sun, Christopher Banfield, Michael S Vincent, Liyun Ni, and Debra J Zac

A comparison of the predictive accuracy of three screening models for pulmonary arterial hypertension in systemic sclerosis

Introduction: There is evidence that early screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) improves outcomes. We compared the predictive accuracy of two recently published screening algorithms (DETECT 2013 and Australian Scleroderma Interest Group (ASIG) 2012) for SSc-associated PAH (SSc-PAH) with the commonly used European Society of Cardiology/European Respiratory Society (ESC/ERS 2009) guidelines. Methods: We included 73 consecutive SSc patients with suspected PAH undergoing right heart catheterization (RHC). The three screening models were applied to each patient. For each model, contingency table analysis was used to determine sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values for PAH. These properties were also evaluated in an ‘alternate scenario analysis’ in which the prevalence of PAH was set at 10%. Results: RHC revealed PAH in 27 (36.9%) patients. DETECT and ASIG algorithms performed equally in predicting PAH with sensitivity and NPV of 100%. The ESC/ERS guidelines had sensitivity of 96.3% and NPV of only 91%, missing one case of PAH; these guidelines could not be applied to three patients who had absent tricuspid regurgitant (TR) jet. The ASIG algorithm had the highest specificity (54.5%). With PAH prevalence set at 10%, the NPV of the models was unchanged, but the PPV dropped to less than 20%. Conclusions: In this cohort, the DETECT and ASIG algorithms out-perform the ESC/ERS guidelines, detecting all patients with PAH. The ESC/ERS guidelines have limitations in the absence of a TR jet. Ultimately, the choice of SSc-PAH screening algorithm will also depend on cost and ease of application