Wayne Gulliver

Meta-analysis of tumor necrosis factor inhibitors and glucocorticoids on bone density in rheumatoid arthritis and ankylosing spondylitis trials.

To examine the impact of antirheumatic drugs on bone mineral density (BMD) in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis using a systematic review.

Higher Dietary Choline and Betaine Intakes Are Associated with Better Body Composition in the Adult Population of Newfoundland, Canada.

Background Choline is an essential nutrient and betaine is an osmolyte and methyl donor. Both are important to maintain health including adequate lipid metabolism. Supplementation of dietary choline and betaine increase muscle mass and reduce body fat in animals. However, little data is available regarding the role of dietary choline and betaine on body composition in humans. Objective To investigate the association between dietary choline and betaine intakes with body composition in a large population based cross-sectional study. Design A total of 3214 subjects from the CODING (Complex Disease in Newfoundland population: Environment and Genetics) study were assessed. Dietary choline and betaine intakes were computed from the Willett Food Frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry following a 12-hour fast. Major confounding factors including age, sex, total calorie intake and physical activity level were controlled in all analyses. Result Significantly inverse correlations were found between dietary choline and betaine intakes, with all obesity measurements: total percent body fat (%BF), percent trunk fat (%TF), percent android fat (%AF), percent gynoid fat (%GF) and anthropometrics: weight, body mass index, waist circumference, waist-to-hip ratio in both women and men (r range from -0.13 to -0.47 for choline and -0.09 to -0.26 for betaine, p<0.001 for all). Dietary choline intake had stronger association than betaine. Moreover, obese subjects had the lowest dietary choline and betaine intakes, with overweight subjects in the middle, and normal weight subjects consumed the highest dietary choline and betaine (p<0.001). Vice versa, when subjects were ranked according to dietary choline and betaine intakes, subjects with the highest intake of both had the lowest %TF, %AF, %GF, %BF and highest %LM among the groups in both sexes. Conclusion Our findings indicate that high dietary choline and betaine intakes are significantly associated with favorable body composition in humans.

Beneficial association of serum ghrelin and peptide YY with bone mineral density in the Newfoundland population

BackgroundGhrelin and peptide YY (PYY) are appetite regulating hormones secreted from the gastrointestinal tract (gut). Aside from their known effect on energy homeostasis, accumulating data indicates that these gut hormones also affect bone metabolism. However, data regarding the influence of ghrelin and PYY on bone density in humans is very limited, and the results are inconclusive. Therefore, this study was designed to investigate the potential association between circulating ghrelin and PYY with bone density indices in the general population.MethodsA total of 2257 adult subjects from the CODING (Complex Diseases in the Newfoundland Population: Environment and Genetics) study participated in this investigation. Acylated ghrelin and total PYY were measured in serum after a 12-hour fasting, with the Enzyme- Linked Immunosorbent Assay (ELISA) method. Bone mineral density was measured by dual-energy X-ray absorptiometry at the spine, femoral neck, and total hip. Multiple regression analyses adjusting for age, BMI, physical activity, smoking, and alcohol consumption were employed to analyze the association between serum ghrelin and PYY with bone mineral density parameters.ResultsSignificant positive associations of ghrelin concentration with L2-L4 BMD, L2-L4 Z-score, femoral neck BMD, femoral neck Z-score, total hip BMD, and total hip Z-score were found in women. No significant correlations between ghrelin and bone density indices were present in men. After dividing the female group into pre-menopausal and post-menopausal, ghrelin was positively correlated with femoral neck Z-score, and total hip Z-score in pre-menopausal women and L2-L4 BMD, and Z-score in post-menopausal group. Moreover, no significant association was discovered between serum PYY and bone density at any site.ConclusionOur results suggest a beneficial association of circulating ghrelin concentration with bone density in women at the population level. This association is independent of major confounding factors including BMI, physical activity, age, alcohol consumption, and smoking. Effect of menopause on this association seemed to be site specific. However, PYY does not seem to be associated with bone density parameters.

Think beyond the Skin: 2014 Canadian Expert Opinion Paper on Treating to Target in Plaque Psoriasis

Objective: Explore the feasibility of Treat to Target in the area of psoriasis as seen in other therapeutic areas such as hypertension, hyperlipidemia, diabetes and rheumatoid arthritis. Methods: Review validated, measurable targets for psoriasis, including physician global assessment (PGA), psoriasis area and severity index (PASI) and dermatology life quality index (DLQI). Examine principles brought forth in the published European consensus on psoriasis and develop a Canadian consensus on Treat to Target in psoriasis. Results: As PASI and DLQI are not routinely used in the community setting, we are recommending target at a PGA of zero (clear). Conclusion: Recommend that the target is a PGA of zero (clear) as it provides a simple and measurable result that the patient and physician can clearly understand.

Update on alefacept safety.

Background: Alefacept has been demonstrated in clinical trials to be an effective, safe, and well-tolerated treatment strategy when used alone or in combination with other antipsoriatic therapies in patients with chronic plaque psoriasis. Objective: AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational, Canadian phase IV registry evaluating the efficacy and safety of alefacept, alone or in combination with other antipsoriatic therapies, in patients with psoriasis. Methods: Patients with chronic plaque psoriasis were treated with at least one course of alefacept followed by an off-treatment period, typically lasting 12 or more weeks. Prospective follow-up was at least 60 weeks, depending on when patients presented for retreatment. Safety data collected throughout the study included the incidence of serious adverse events (SAEs), dosing suspensions, and withdrawals owing to adverse events. Results: Twelve SAEs were reported in psoriasis patients treated with at least one course of alefacept, with only one considered to be possibly related to the study drug. Approximately one-quarter of patients missed at least one dose of alefacept during the course of the study. A total of 291 doses of alefacept were missed, representing almost 4% of the total doses administered in this group of patients. Low CD4+ count was the most frequent reason for missed doses; however, no patient had persistently low CD4+ counts requiring permanent discontinuation of alefacept treatment. Seven patients in the AWARE registry discontinued treatment with alefacept, with the most common reason being patient request. Conclusion: The AWARE study supports the safety of alefacept used alone or in combination with other antipsoriatic therapies, in a broad population of real-world chronic plaque psoriasis patients in Canada.

Psoriasis Patients Treated With Biologics and Methotrexate Have a Reduced Rate of Myocardial Infarction: A Collaborative Analysis Using International Cohorts.

Psoriasis is a chronic inflammatory skin condition characterised by the formation of red scaly plaques on the skin. It is an autoimmune disease cause by the dysregulation of cytokines controlling the inflammatory pathways, a mechanism likely contributing to various comorbidities observed in patients with psoriasis. Cardiovascular disease is one comorbidity observed more frequently in the psoriasis patient population. Biologic treatments specifically target the dysregulation of cytokines in the inflammation pathway and have shown to be an effective treatment for moderate to severe psoriasis where other systemic treatments have failed. More recently, biologics have been shown to reduce the incidence of myocardial infarction in patients with psoriasis compared to patients treated with topical agents. In the present study, 4 international psoriasis patient cohorts are combined and analyzed to examine the effect that biologic or methotrexate treatment has on reducing the incidence of myocardial infarction. Both methotrexate and biologic treatments were found to lower the incidence of myocardial infarction in moderate to severe psoriasis patient populations.

Do Biologics Protect Patients With Psoriasis From Myocardial Infarction? A Retrospective Cohort

Background: Psoriasis is a chronic immune-mediated inflammatory disorder that affects approximately 2% to 3% of the population, which translates to 17 million in North America and Europe and approximately 170 million people worldwide. Although psoriasis can occur at any age, most cases develop before age 40 years. Some larger studies have noted bimodal age at onset with the first peak occurring at approximately age 30 years and the second peak at around 55 to 60 years, but most patients have a younger age of onset (15-30 years). Psoriasis is associated with multiple comorbidities, decreased quality of life, and decreased longevity of life. Two recent systematic reviews and a meta-analysis concluded that psoriasis patients are at increased risk of major adverse cardiovascular events. Multiple studies confirm that many of the comorbidities found in patients with psoriasis are also important risk factors for cardiovascular disease, stroke, diabetes mellitus, hypertension, hyperlipidemia, obesity, and metabolic syndrome. Methods: We conducted a retrospective cohort study using charts from a dermatology clinic combined with an administrative database of patients with moderate to severe psoriasis in Newfoundland and Labrador, Canada. We examined the role of clinical predictors (age of onset of psoriasis, age, sex, biologic use) in predicting incident myocardial infarction (MI). Results: Logistic regression revealed that age of onset (odds ratio [OR], 8.85; P = .005), advancing age (OR, 1.07; P < .0001), and being male (OR, 3.64; P = .018) were significant risk factors for the development of MI. Neither biologic therapy nor duration of biologic therapy were statistically significant risk factors for the development of MI. Our study found that in patients with psoriasis treated with biologics, there was a nonsignificant trend in reduced MI by 78% (relative risk, 0.18; 95% confidence interval, 0.24-1.34; P = .056). Conclusion: Our study demonstrated a trend toward decreased MI in patients with moderate to severe psoriasis on biologics. Patients with an early age of onset of psoriasis (<25 years) were nearly 9 times more likely to have an MI. Clinicians should consider appropriate cardiovascular risk reduction strategies in patients with psoriasis.

Neoral® in the Treatment of Psoriasis: Consensus Treatment Guidelines

Background: The efficacy of cyclosporine in the treatment of psoriasis is well-recognized. A new microemulsion formulation of cyclosporine, Neoral®, has become available and will replace the original formulation, Sandimmune®. Objectives: In view of the new clinical experience with Neoral and changes in clinical practice, an expert panel was convened to review the treatment guidelines and make new recommendations for its use in the treatment of psoriasis. Results: Compared with the original formulation, Neoral is more rapidly absorbed and there is less intra- and interpatient variation in bioavailability. In clinical trials, Neoral had a faster onset of action than Sandimmune at equal doses; efficacy and safety profiles were comparable. Conclusion: Neoral is indicated in patients with severe psoriasis in whom systemic therapy is justified. Careful baseline clinical and laboratory evaluation is mandatory prior to initiation of Neoral therapy. The therapeutic goal is to maintain substantial improvement with the lowest possible dose of cyclosporine. If possible, intermittent therapy is preferable. Guidelines for monitoring and management of adverse effects are presented.

Peptide T exhibits a well-defined structure in fluorinated solvent at low temperature

The structure of Peptide T was determined by solution NMR spectroscopy, under strong structure‐inducing conditions: 40% hexafluoro‐2‐propanol aqueous solution at 5 °C. Under these conditions it was possible to detect medium‐range NOEs for the first time for this peptide. This allowed a much better‐defined structure to be determined for Peptide T in comparison with earlier NMR and computational studies. Peptide structures consistent with the experimental restraints were generated using a restrained MD simulation with a full empirical force field. Residues 4–8 of Peptide T take on a well‐defined structure with a heavy atom RMSD of 0.78 Å. The structure is stabilized by hydrogen bonding to side‐chain oxygen atoms of Thr 4 and Thr 8, as well as backbone hydrogen bonding between residues 5 and 7 that forms this region into a classic γ‐turn. Copyright

Hidradenitis Suppurativa: A Novel Model of Care and an Integrative Strategy to Adopt an Orphan Disease

Unnecessary investigations, inappropriate treatment, worsening disease, and frustration for both patients and health care professionals are the hallmarks of hidradenitis suppurativa (HS) management. In light of a new treatment algorithm and biologic therapies made available to patients, an HS model of care is outlined in this article. The recommendations and management strategy presented here have been developed to help address the currently unmet needs of this patient population. The patient-centred model of care and disease management strategies were developed through the guidance and recommendations of HS medical experts in Newfoundland and Labrador. This article lays the foundation for the resources and steps required to change the status of this orphan disease and firmly embed patients with HS within a coordinated and integrative system of care.