Risk of myocardial infarction with use of selected nonsteroidal anti-inflammatory drugs in spondyloarthritis patients

BACKGROUND: Spondyloarthritis (SpA) is associated with increased risk of myocardial infarction (MI); the risk may be due to the underlying inflammatory disease, or also due to medications that increase MI risk, such as certain non-steroidal anti-inflammatory drugs (NSAIDs). OBJECTIVES: 1. To describe the risk of myocardial infarction (MI) among patients with spondyloarthritis who are prescribed NSAIDs 2. To compare the pattern of MI risk with specific NSAID use among spondyloarthritis patients with the pattern of risk among patients with osteoarthritis (OA) METHODS: Nested case-control studies were performed using 1994–2015 data from The Health Improvement Network (THIN). Underlying cohorts included adult patients with incident SpA or OA had >1 NSAID prescriptions and no history of MI. In each cohort, we matched cases of incident MI to four controls without MI. NSAID use was categorized as: (A) current (prescription end 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 244,399, there were 115 and 6287 MI cases, respectively. After adjustment, among SpA subjects, current diclofenac use was associated with an OR of 3.05 (95% CI 1.48–6.29; Table 2) for MI. Naproxen use was not associated with any increase (adjusted OR 1.25, 95% CI 0.56–2.78). A ratio of ORs for SpA/diclofenac relative to OA/diclofenac was 2.35 (1.10–4.90).2019-06-12T00:00:00

Association of Tramadol Use With Risk of Hip Fracture.

Several professional organizations have recommended tramadol as one of the first-line or second-line therapies for patients with chronic noncancer pain and its prescription has been increasing rapidly worldwide; however, the safety profile of tramadol, such as risk of fracture, remains unclear. This study aimed to examine the association of tramadol with risk of hip fracture. Among individuals age 50 years or older without a history of hip fracture, cancer, or opioid use disorder in The Health Improvement Network (THIN) database in the United Kingdom general practice (2000-2017), five sequential propensity score-matched cohort studies were assembled, ie, participants who initiated tramadol or those who initiated one of the following medications: codeine (n = 146,956) (another commonly used weak opioid), naproxen (n = 115,109) or ibuprofen (n = 107,438) (commonly used nonselective nonsteroidal anti-inflammatory drugs [NSAIDs]), celecoxib (n = 43,130), or etoricoxib (n = 27,689) (cyclooxygenase-2 inhibitors). The outcome was incident hip fracture over 1 year. After propensity-score matching, the included participants had a mean age of 65.7 years and 56.9% were women. During the 1-year follow-up, 518 hip fracture (3.7/1000 person-years) occurred in the tramadol cohort and 401 (2.9/1000 person-years) occurred in the codeine cohort. Compared with codeine, hazard ratio (HR) of hip fracture for tramadol was 1.28 (95% confidence interval [CI] 1.13 to 1.46). Risk of hip fracture was also higher in the tramadol cohort than in the naproxen (2.9/1000 person-years for tramadol, 1.7/1000 person-years for naproxen; HR = 1.69, 95% CI 1.41 to 2.03), ibuprofen (3.4/1000 person-years for tramadol, 2.0/1000 person-years for ibuprofen; HR = 1.65, 95% CI 1.39 to 1.96), celecoxib (3.4/1000 person-years for tramadol, 1.8/1000 person-years for celecoxib; HR = 1.85, 95% CI 1.40 to 2.44), or etoricoxib (2.9/1000 person-years for tramadol, 1.5/1000 person-years for etoricoxib; HR = 1.96, 95% CI 1.34 to 2.87) cohort. In this population-based cohort study, the initiation of tramadol was associated with a higher risk of hip fracture than initiation of codeine and commonly used NSAIDs, suggesting a need to revisit several guidelines on tramadol use in clinical practice. © 2020 American Society for Bone and Mineral Research

Disulfiram use is associated with lower risk of COVID-19: A retrospective cohort study.

Funder: British Heart FoundationFunder: VA Boston Healthcare SystemFunder: Dana-Farber Cancer InstituteFunder: VA Cooperative Studies ProgramFunder: National Institutes of HealthFunder: Harvard Medical SchoolEffective, low-cost therapeutics are needed to prevent and treat COVID-19. Severe COVID-19 disease is linked to excessive inflammation. Disulfiram is an approved oral drug used to treat alcohol use disorder that is a potent anti-inflammatory agent and an inhibitor of the viral proteases. We investigated the potential effects of disulfiram on SARS-CoV-2 infection and disease severity in an observational study using a large database of clinical records from the national US Veterans Affairs healthcare system. A multivariable Cox regression adjusted for demographic information and diagnosis of alcohol use disorder revealed a reduced risk of SARS-CoV-2 infection with disulfiram use at a hazard ratio of 0.66 (34% lower risk, 95% confidence interval 24-43%). There were no COVID-19 related deaths among the 188 SARS-CoV-2 positive patients treated with disulfiram, in contrast to 5-6 statistically expected deaths based on the untreated population (P = 0.03). Our epidemiological results suggest that disulfiram may contribute to the reduced incidence and severity of COVID-19. These results support carefully planned clinical trials to assess the potential therapeutic effects of disulfiram in COVID-19

Risk Factors for Diagnosis of Psoriatic Arthritis, Psoriasis, Rheumatoid Arthritis, and Ankylosing Spondylitis : A Set of Parallel Case-control Studies

Funding Information: This work was supported in part by the National Institutes of Health (NIH), Grant K23 AR063764, to the principal investigator AO, and internal funds from the University of Pennsylvania. MD was supported by the NIH, Grant K23 AR06912701. 1E. Meer, BA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; 2T. Thrastardottir, MPH, T.J. Love, MD, PhD, Department of Medicine/Rheumatology, University of Iceland and Landspitali, Reykjavik, Iceland; 3X. Wang, MD, Y. Chen, PhD, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; 4M. Dubreuil, MD, Department of Medicine/Rheumatology, Boston University, Boston, Massachusetts, USA; 5J.M. Gelfand, MD, MSCE, Department of Biostatistics, Epidemiology and Informatics, and Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; 6A. Ogdie, MD, MSCE, Department of Biostatistics, Epidemiology and Informatics, and Department of Medicine/ Rheumatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. JMG has served as a consultant for BMS, Boehringer Ingelheim, Lilly, Janssen Biologics, Novartis, UCB (DSMB), Neuroderm (DSMB), Dr. Reddy’s Labs, Pfizer, and Sun Pharma, receiving honoraria; receives research grants (to the Trustees of the University of Pennsylvania) from AbbVie, Boehringer Ingelheim, Janssen, Novartis, Celgene, Ortho Dermatologics, and Pfizer; and received payment for continuing medical education work related to psoriasis that was supported indirectly by Lilly, Ortho Dermatologics, and Novartis. JMG is a co-patent holder of resiquimod for treatment of cutaneous T-cell lymphoma, is a Deputy Editor for the Journal of Investigative Dermatology, receiving honoraria from the Society for Investigative Dermatology, and is a member of the Board of Directors for the International Psoriasis Council, receiving no honoraria. TJL has received reimbursement from Celgene for speaking about guidelines for the treatment of psoriatic arthritis. AO has served as a consultant for AbbVie, Amgen, BMS, Celgene, Corrona, Global Health Living Foundation, Janssen, Lilly, Novartis, Pfizer, and Takeda, and has received grants to the University of Pennsylvania from Pfizer and Novartis and to Forward from Amgen; her husband has received royalties from Novartis. EM, TT, MD, XW, and YC declare no conflicts of interest relevant to this article. Address correspondence to Dr. A. Ogdie, University of Pennsylvania, Division of Rheumatology, 3400 Civic Center Blvd., Philadelphia, PA 19104, USA. Email: [email protected]. Accepted for publication July 16, 2021. Publisher Copyright: © 2022 The Journal of Rheumatology.Objective. To compare potential risk factors for the diagnosis of psoriatic arthritis (PsA), psoriasis (PsO), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Methods. Four parallel case-control studies were conducted within The Health Improvement Network using data between 1994 and 2015. Patients with PsA, PsO, RA, or AS were identified using validated code lists and matched to controls on age, sex, practice, and year. Risk factors were selected in the time prior to diagnosis. Multivariable logistic regression models were constructed for each disease using automated stepwise regression to test potential risk factors. Results. Patients with incident PsA (n = 7594), PsO (n = 111,375), RA (n = 28,341), and AS (n = 3253) were identified and matched to 75,930, 1,113,345, 283,226, and 32,530 controls, respectively. Median diagnosis age was 48 (IQR 38–59), 43 (IQR 28–60), 60 (IQR 48–71), and 41 (IQR 32–54) years, respectively. In multivariable models, there were some shared and some differing risk factors across all 4 diseases: PsA was associated with obesity, pharyngitis, and skin infections; PsA and PsO were associated with obesity and moderate alcohol intake; PsA and AS were associated with uveitis; and PsA and RA were associated with preceding gout. Both RA and AS were associated with current smoking, former moderate drinking, anemia, osteoporosis, and inflammatory bowel disease. All shared former or current smoking as a risk factor; statin use was inversely associated with all 4 diseases. Conclusion. Shared and different risk factors for PsA, PsO, RA, and AS were identified. Statin use was inversely associated with all 4 conditions.Peer reviewe

The Smoking Paradox in the Development of Psoriatic Arthritis among Psoriasis Patients – A Population-Based Study

Objectives: Smoking is strongly associated with an increased risk of psoriatic arthritis (PsA) in the general population, but not among psoriasis patients. We sought to clarify the possible methodologic 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 psoriasis patients. 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 7,057 developed incident PsA. Smoking was associated with an increased risk of PsA in the general population (RR, 1.27; 95% CI, 1.19-1.36), but with a decreased risk among psoriasis patients (RR 0.91; 95% CI, 0.85-0.99). 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 RRs = ~1.50), it could reverse the biased estimate of effect of smoking among psoriasis patients (RR=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 psoriasis patients. Conditioning on a causal intermediate variable (psoriasis) can reverse the association between smoking and PsA, explaining the smoking paradox for the risk of PsA among psoriasis patients

Enhancing the hospice curriculum within the family medicine clerkship

BACKGROUND: Medical schools are improving end-of-life (EOL) care curricula; however, students rarely practice EOL communication skills in a safe learning environment. OBJECTIVE: Our objective was to study which curriculum improves students\u27 ability to discuss hospice care. METHODS: We conducted a study of six family medicine clerkship blocks; three taught with a didactic curriculum (A) and three with an interactive curriculum (B). RESULTS: Students reported improvement in their skill and comfort in discussing hospice care in both groups. Subjectively more students commented on the instructiveness of curriculum B due to role-plays. CONCLUSION: A variety of curricular methods helped students\u27 confidence and self-reflection around hospice discussions in a comfortable environment

Comparison of the drug retention and reasons for discontinuation of tumor necrosis factor inhibitors and interleukin-6 inhibitors in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study

Background This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of either tumor necrosis factor inhibitors (TNFi) or interleukin-6 inhibitors (IL-6i) in patients with elderly-onset rheumatoid arthritis (EORA). Methods Patients with rheumatoid arthritis (RA) enrolled in a Japanese multicenter observational registry between 2011 and 2020 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding by indication for treatment with TNFi or IL-6i, a propensity score based on multiple baseline characteristics variables was used to compare the drug retention and causes for discontinuation between TNFi and IL-6i. Adjusted cumulative incidence of drug discontinuation for each reason was compared between the two groups using the Fine-Gray model. Results Among a total of 9,550 patients in the registry, 674 TNFi and 297 IL-6i initiators with EORA were identified. Age, the proportion of females, disease duration, and baseline disease activity at the time of TNFi or IL-6i initiation were similar between the two groups. After adjusting for differences in baseline characteristics between the two groups, overall drug discontinuation was significantly lower in the IL-6i as compared to the TNFi (HR = 0.71, 95%CI = 0.59-0.86, p < 0.001). The adjusted cumulative incidence of discontinuation due to lack of effectiveness was lower with the IL-6i (HR = 0.46, 95%CI = 0.33-0.63, p < 0.001) while those due to adverse events (HR = 0.82, 95%CI = 0.56-1.18, p = 0.28) or achievement of clinical remission (HR = 1.09, 95%CI = 0.62-1.91, p = 0.76) were similar between the two groups. Conclusions In EORA patients initiating a TNFi or IL-6i, significantly higher drug retention was observed with IL-6i. Discontinuation due to lack of effectiveness was significantly less frequent in IL-6i while discontinuations due to adverse event or achievement of clinical remission were similar between the two groups

Diabetes incidence in psoriatic arthritis, psoriasis and rheumatoid arthritis: a UK population-based cohort study.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageThe objective of this study was to evaluate the incidence of diabetes among patients with PsA and RA in the general population.We conducted a cohort study using an electronic medical records database representative of the UK general population (1986-2010). We estimated hazard ratios (HRs) for incident diabetes in PsA, psoriasis and RA cohorts compared with age- and sex-matched comparison cohorts without the corresponding conditions, adjusting for BMI, smoking, alcohol use, co-morbidities and glucocorticoids at baseline.Cohorts included 4196 persons with PsA, 59 281 with psoriasis and 11 158 with RA, with mean follow-up times of 5.9, 5.8 and 5.5 years, respectively. Incidence rates for diabetes were 7.3, 6.4 and 6.3 cases per 1000 person-years among individuals with PsA, psoriasis and RA, respectively. Age- and sex-matched HRs for diabetes were 1.72 (95% CI 1.46, 2.02) in PsA, 1.39 (95% CI 1.32, 1.45) in psoriasis and 1.12 (95% CI 1.01, 1.25) in RA. After adjustment for BMI, smoking and alcohol, the HRs were attenuated substantially (1.43, 1.24 and 1.00, respectively). With further adjustment for baseline glucocorticoid use and co-morbidities, the HRs were 1.33 (1.09, 1.61) in PsA, 1.21 (1.15, 1.27) in psoriasis and 0.94 (0.84, 1.06) in RA.This general population study suggests an increased incidence of diabetes in PsA and RA, which is substantially explained by obesity and lifestyle factors. These findings support the importance of managing such factors in PsA and RA patients.NIAMS P60AR047785 National Heart, Blood and Lung Institute R01 HL089744 NIH K24-AR064310 Boston University School of Medicin