Prescription of non-steroidal anti-inflammatory drugs for patients with inflammatory arthritis decreases with the initiation of tumour necrosis factor inhibitor therapy: results from the ICEBIO registry.

OBJECTIVE: To study the impact of tumour necrosis factor-α inhibitor (TNFi) therapy on the use of non-steroidal anti inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) in Iceland. METHOD: This registry cohort study used data from the nationwide database on biologics in Iceland (ICEBIO) and the Icelandic Prescription Medicines Register on disease activity, and filled prescriptions for NSAIDs, to study the period from 2 years before to 2 years after initiation of a first TNFi. Five randomly selected individuals from the general population matched on age, sex, and calendar time for each patient served as comparators. RESULTS: Data from 940 patients and 4700 comparators were included. Patients with arthritis were prescribed 6.7 times more defined daily doses of NSAIDs than comparators (149 vs 22 per year). After TNFi initiation, NSAID use decreased to a mean of 85 DDD per year, or by 42% in RA, 43% in PsA, and 48% in axSpA. At TNFi initiation, the quintile of axSpA patients who used most NSAIDs reported significantly worse pain (mean ± sd 66 ± 21 vs 60 ± 23 mm), global health (70 ± 20 vs 64 ± 23 mm), and Health Assessment Questionnaire score (1.21 ± 0.66 vs 1.02 ± 0.66) than the other patients, whereas no significant differences were observed in the groups with peripheral arthritis. CONCLUSION: Patients with inflammatory arthritides requiring TNFi therapy use more NSAIDs than matched comparators, and consumption decreased following TNF initiation. Patient-reported measures are not associated with high NSAID use in patients with peripheral arthritis.

Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.

OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Treatment as Prevention for Hepatitis C (TraP Hep C) - a nationwide elimination programme in Iceland using direct-acting antiviral agents.

A nationwide programme for the treatment of all patients infected with hepatitis C virus (HCV) was launched in Iceland in January 2016. By providing universal access to direct-acting antiviral agents to the entire patient population, the two key aims of the project were to (i) offer a cure to patients and thus reduce the long-term sequelae of chronic hepatitis C, and (ii) to reduce domestic incidence of HCV in the population by 80% prior to the WHO goal of HCV elimination by the year 2030. An important part of the programme is that vast majority of cases will be treated within 36 months from the launch of the project, during 2016-2018. Emphasis is placed on early case finding and treatment of patients at high risk for transmitting HCV, that is people who inject drugs (PWID), as well as patients with advanced liver disease. In addition to treatment scale-up, the project also entails intensification of harm reduction efforts, improved access to diagnostic tests, as well as educational campaigns to curtail spread, facilitate early detection and improve linkage to care. With these efforts, Iceland is anticipated to achieve the WHO hepatitis C elimination goals well before 2030. This article describes the background and organization of this project. Clinical trial number: NCT02647879.

Small joint involvement in psoriatic arthritis is associated with onycholysis: the Reykjavik Psoriatic Arthritis Study.

OBJECTIVES: Psoriasis and psoriatic arthritis (PsA) are associated with nail changes. Recent reports suggest that nail changes may be a part of the enthesitis of PsA and that they predict the onset of arthritis among patients with psoriasis, but they have not reported on subclasses of nail changes. However, earlier reports suggested that onycholysis is the nail change most strongly associated with PsA. If nail changes in PsA are a sign of enthesitis, they might be associated with small joint disease in general and the objective of this study was to test this hypothesis. METHODS: A total of 154 patients recruited through the Reykjavik Psoriatic Arthritis Study had a joint, skin, and nail evaluation. Associations with small joint disease were tested using univariate analysis, and confirmed in a multivariate model. RESULTS: Onycholysis had a strong association with small joint involvement [odds ratio (OR) 3.42, 95% confidence interval (CI) 1.41-8.92], while other types of nail changes did not. The number of swollen joints and shorter disease duration were also associated with small joint disease. CONCLUSIONS: Onycholysis is associated with small joint disease in PsA. Future studies of PsA should report the subtypes of nail changes. Longitudinal studies are needed to determine whether onycholysis predicts PsA.

Peripheral blood T cell responses to keratin peptides that share sequences with streptococcal M proteins are largely restricted to skin-homing CD8(+) T cells.

The association of psoriasis with Streptococcus pyogenes throat infections suggests a potential antigenic target for the T cells that are known to infiltrate psoriatic skin. Streptococcal M protein share an extensive sequence homology with the human epidermal keratins. Keratin 17 (K17), while being mostly absent from uninvolved skin, is up-regulated in psoriatic lesions. Consequentially, M-protein-primed T cells may recognize up-regulated keratin epitopes via molecular mimicry. Using in vitro lymphocyte culture and cytokine flow cytometry we demonstrate that HLA-Cw*0602(+) psoriasis patients had significant CD8(+) T cell interferon (IFN)-gamma responses to peptides from the K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. These responses were about 10 times more frequent in the skin-homing cutaneous lymphocyte-associated antigen-expressing (CLA(+)) subset of CD8(+) T cells. CD4(+) T cells showed only borderline responses. CLA(+) CD8(+) T cells from Cw6(+) non-psoriatic individuals responded to some M6 peptides but rarely to K17 peptides. Cw6(-) psoriasis patients showed a response that was intermediate between Cw6(+) patients and controls. These findings indicate that psoriatic individuals have CD8(+) T cells that recognize keratin self-antigens and that epitopes shared by streptococcal M proteins and human keratins may be targets for the CD8(+) T cells that infiltrate psoriatic skin lesions.

Thermal hazards in mastoid surgery: an evaluation of instruments and irrigation techniques.

Study of the mechanical properties of three commonly used mastoid drills disclosed major differences in their power and potential for heat production. Based on available information regarding heat tolerance of neural tissue, all drills were found capable of producing hazardous temperature elevations. After testing several irrigation techniques, continuous and copious suction irrigation was found to be most effective in preventing bone heating.

Thermal hazard during mastoid surgery.

Torque speed characteristics of two mastoid drills were measured. Potential temperature elevations in temporal bones were calculated from these measurements. Measured temperature elevations in temporal bones drilled without irrigation agreed well with predictions. Irrigation was demonstrated to be of critical importance in minimizing thermal hazard from mastoid drills.