Risk of myocardial infarction with use of selected non-steroidal anti-inflammatory drugs in patients with spondyloarthritis and osteoarthritis.

OBJECTIVES: Spondyloarthritis (SpA) is associated with an increased risk of myocardial infarction (MI) due to underlying inflammation and possibly due to medications such as certain non-steroidal anti-inflammatory drugs (NSAIDs). We sought to describe MI risk among patients with SpA who were prescribed NSAIDs, and to compare the pattern of risk in SpA with that in osteoarthritis (OA). METHODS: Nested case-control studies were performed using The Health Improvement Network (THIN). Underlying cohorts included adults with incident SpA or OA who had >1 NSAID prescription and no history of MI. Within each cohort, we matched each MI case to four controls without MI. NSAID use was categorised as: (a) current (prescription date 0-180 days prior to index date), (b) recent (181-365 days) or (c) remote (>365 days). We performed conditional logistic regression to compare the odds of current or recent NSAID use relative to remote use of any NSAID, considering diclofenac and naproxen specifically. RESULTS: Within the SpA cohort of 8140 and the OA cohort of 244 339, there were 115 and 6287 MI cases, respectively. After adjustment, current diclofenac use in SpA was associated with an OR of 3.32 (95% CI 1.57 to 7.03) for MI. Naproxen was not associated with any increase (adjusted OR 1.19, 95% CI 0.53 to 2.68). A ratio of ORs for SpA/diclofenac relative to OA/diclofenac was 2.64 (95% CI 1.24 to 5.58). CONCLUSIONS: MI risk in SpA is increased among current users of diclofenac, but not naproxen. The MI risk with diclofenac in SpA appears to differ from that in OA.

Smoking paradox in the development of psoriatic arthritis among patients with psoriasis: a population-based study.

OBJECTIVES: Smoking is associated with an increased risk of psoriatic arthritis (PsA) in the general population, but not among patients with psoriasis. We sought to clarify the possible methodological mechanisms behind this paradox. METHODS: Using 1995-2015 data from The Health Improvement Network, we performed survival analysis to examine the association between smoking and incident PsA in the general population and among patients with psoriasis. We clarified the paradox using mediation analysis and conducted bias sensitivity analyses to evaluate the potential impact of index event bias and quantify its magnitude from uncontrolled/unmeasured confounders. RESULTS: Of 6.65 million subjects without PsA at baseline, 225 213 participants had psoriasis and 7057 developed incident PsA. Smoking was associated with an increased risk of PsA in the general population (HR 1.27; 95% CI 1.19 to 1.36), but with a decreased risk among patients with psoriasis (HR 0.91; 95% CI 0.84 to 0.99). Mediation analysis showed that the effect of smoking on the risk of PsA was mediated almost entirely through its effect on psoriasis. Bias-sensitivity analyses indicated that even when the relation of uncontrolled confounders to either smoking or PsA was modest (both HRs=~1.5), it could reverse the biased effect of smoking among patients with psoriasis (HR=0.9). CONCLUSIONS: In this large cohort representative of the UK general population, smoking was positively associated with PsA risk in the general population, but negatively associated among patients with psoriasis. Conditioning on a causal intermediate variable (psoriasis) may even reverse the association between smoking and PsA, potentially explaining the smoking paradox for the risk of PsA among patients with psoriasis.

Obesity Paradox in Recurrent Attacks of Gout in Observational Studies: Clarification and Remedy.

OBJECTIVE: Obesity is strongly associated with incident gout risk, but its association with the risk of recurrent gout attacks has been null or weak, constituting an obesity paradox. We sought to demonstrate and overcome the methodologic issues associated with the obesity paradox for risk of recurrent gout attacks. METHODS: Using the Multiple Risk Factor Intervention Trial database, we decomposed the total effect of obesity into its direct and indirect (i.e., mediated) effects using marginal structural models. We also estimated the total effect of body mass index (BMI) change from baseline among incident gout patients. RESULTS: Of 11,816 gout-free subjects at baseline, we documented 408 incident gout cases, with 132 developing recurrent gout attacks over a 7-year followup period. The adjusted odds ratio (OR) for incident gout among obese individuals was 2.6, whereas that for recurrent gout attacks among gout patients was 0.98 (i.e., the obesity paradox). These ORs correlated well with the ORs for the indirect and direct effects of obesity on the risk of recurrent gout attacks (2.83 and 0.98, respectively). Compared with no BMI change, the OR of increasing versus decreasing >5% of baseline BMI was 0.61 and 1.60 for recurrent gout attacks, respectively (P for trend < 0.01), suggesting a dose-response association. CONCLUSION: The obesity paradox for the risk of recurrent gout attacks is explained by the absence of the direct effect, which is often measured in conventional analyses and misinterpreted as the intended total effect of interest. In contrast, the BMI change analysis correctly estimated the intended total effect of BMI, and revealed a dose-response relationship.

Skin cancer education for massage therapists: a novel approach to the early detection of suspicious lesions.

Studies indicate that with training, nonmedical health professionals may be able to successfully recognize lesions suspicious for skin cancer and thereby assist with early detection of suspicious lesions. We present the results of a study aimed at assessing the efficacy of a 4-h continuing education program designed to educate massage therapists about skin cancer detection and prevention. Prior to and after the administration of the course, surveys were administered to attendees to gauge their ability to identify skin cancer and their comfort level with counseling clients with suspicious lesions. Our study suggests that while many massage therapists are educated on skin cancer and have experience referring patients for suspicious lesions, a 4-h educational session may not be sufficient to improve sensitivity of detection.

Skin cancer education among massage therapists: a survey at the 2010 meeting of the American Massage Therapy Association.

Massage therapists encounter skin on a daily basis and have a unique opportunity to recognize potential skin cancers. The purpose of this study was to describe the skin cancer education provided to massage therapists and to assess their comfort regarding identification and communication of suspicious lesions. An observational retrospective survey study was conducted at the 2010 American Massage Therapy Association Meeting. Sixty percent reported receiving skin cancer education during and 25% reported receiving skin cancer education after training. Massage therapists who examine their own skin are more likely to be comfortable with recognizing a suspicious lesion and are more likely to examine their client's skin. Greater number of clients treated per year and greater frequency of client skin examinations were predictors of increased comfort level with recognizing a suspicious lesion. Massage therapists are more comfortable discussing than identifying a potential skin cancer. Massage therapists may be able to serve an important role in the early detection of skin cancer.

QCT measures of bone strength at the thoracic and lumbar spine: the Framingham Study.

We used volumetric quantitative computed tomography (QCT) scans to evaluate volumetric bone density (vBMD), geometry, and strength in the thoracic (T8 to T10) and lumbar (L3 to L5) spine and determined how these parameters varied with age, sex, and spinal region. Participants included 690 participants of the Framingham Study, 40 to 87 years old (mean, 61 years). In both women and men, trabecular vBMD declined with age similarly for lumbar and thoracic regions, whereas cortical vBMD and integral vBMD, vertebral strength, and compressive force declined more at the lumbar spine than thoracic spine (interaction, p < 0.01). Notably, in men, cortical vBMD increased (ß = 0.0004, p = 0.01), and vertebral strength did not change (ß = 1.9305, p = 0.66) at the thoracic spine with age. In both women and men, vertebral cross-sectional area increased less and the factor-of-risk increased more with age at the lumbar than at the thoracic region (interaction, p < 0.01). For example, in women, the factor-of-risk for forward flexion increased (worsened) with age 6.8-fold more in the lumbar spine (ß = 0.0157), compared with the thoracic spine (ß = 0.0023). vBMD and vertebral strength declined more and the factor-of-risk increased more with age in women than men (interaction, p < 0.01). For instance, integral vBMD for the lumbar spine declined 36% from 40 to 75 years of age in women compared with 18% in men. There was little or no age-related change in the forces applied to the thoracic vertebrae in either women or men. Age-related changes were greater in the lumbar spine than in the thoracic region and greater in women than men. Whereas women lost bone density and strength at both the thoracic and lumbar spine, in men, vertebral strength declined only at the lumbar spine. Our study confirms the importance of evaluating determinants of vertebral strength in both the thoracic and lumbar spine and in both women and men to understand mechanisms underlying the structural failure of vertebral bodies with aging.

The PLIN4 variant rs8887 modulates obesity related phenotypes in humans through creation of a novel miR-522 seed site.

PLIN4 is a member of the PAT family of lipid storage droplet (LSD) proteins. Associations between seven single nucleotide polymorphisms (SNPs) at human PLIN4 with obesity related phenotypes were investigated using meta-analysis followed by a determination if these phenotypes are modulated by interactions between PLIN4 SNPs and dietary PUFA. Samples consisted of subjects from two populations of European ancestry. We demonstrated association of rs8887 with anthropometrics. Meta-analysis demonstrated significant interactions between the rs8887 minor allele with PUFA n3 modulating anthropometrics. rs884164 showed interaction with both n3 and n6 PUFA modulating anthropometric and lipid phenotypes. In silico analysis of the PLIN4 3'UTR sequence surrounding the rs8887 minor A allele predicted a seed site for the human microRNA-522 (miR-522), suggesting a functional mechanism. Our data showed that a PLIN4 3'UTR luciferase reporter carrying the A allele of rs8887 was reduced in response to miR-522 mimics compared to the G allele. These results suggest variation at the PLIN4 locus, and its interaction with PUFA as a modulator of obesity related phenotypes, acts in part through creation of a miR-522 regulatory site.