Is family history a predictor of response to tumour necrosis factor inhibitors in spondyloarthritis? A Swedish nationwide cohort study.

Objective: To determine whether a family history of spondyloarthritis (SpA) is associated with clinical presentation at the start of tumour necrosis factor inhibitor (TNFi) treatment, or predictive of TNFi drug survival and treatment response in patients with SpA.Method: Family history of SpA in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and undifferentiated SpA (uSpA) from the Swedish Rheumatology Quality register starting a TNFi as their first biologic in 2006-2018 was assessed through national registers. Clinical characteristics at treatment start were compared by family history status. We used Cox regression to estimate hazard ratios for drug discontinuation, and analysed treatment response at 3 and 12 months with linear regression. Multiple imputation was used to address missing data.Results: We included 9608 patients. Patients with family history had an earlier age at onset and longer disease duration at TNFi treatment start, but did not differ regarding disease activity and presence of SpA manifestations. Hazard ratios for drug discontinuation were 1.08 [95% confidence interval (CI) 0.89-1.31] for AS patients with a family history of AS, 1.02 (95% CI 0.89-1.18) for PsA patients with a family history of PsA, and 1.11 (95% CI 0.85-1.45) for uSpA patients with a family history of uSpA, after adjusting for demographic, socioeconomic, and SpA-related factors. Treatment response at 3 and 12 months was similar between groups.Conclusion: Family history of SpA was not found to be associated with clinical presentation at the start of TNFi treatment, nor was it associated with drug survival or treatment response in SpA patients starting a first TNFi.

Maternal and infant pregnancy outcomes in women with psoriatic arthritis: a Swedish nationwide cohort study.

OBJECTIVE: Studies on pregnancy outcomes in psoriatic arthritis (PsA) are scarce and typically of small size. Available studies have reported conflicting results. The aim of this study was to describe maternal and infant pregnancy outcomes among women with PsA compared with women without PsA. DESIGN: Nationwide cohort study. SETTING: Nationwide Swedish registers. POPULATION: A total of 41 485 singleton pregnancies in 1997-2014, of which 541 pregnancies were identified with PsA exposure and 40 944 pregnancies were unexposed. METHODS: By linkage of national health and population register data, we obtained information on individual pregnancies and compared outcomes among pregnancies with PsA and non-PsA pregnancies. Relative risks were estimated by odds ratios (ORs) with 95% CIs using a generalised linear regression model with generalised estimating equations. Adjustments were made for maternal factors and calendar year of birth. MAIN OUTCOME MEASURES: Maternal and infant pregnancy outcomes. RESULTS: Pregnancies to women with PsA had increased risks of preterm birth (adjusted OR 1.63; 95% CI 1.17-2.28), elective and emergency caesarean deliveries (adjusted OR 1.47; 95% CI 1.10-1.97 and adjusted OR 1.43; 95% CI 1.08-1.88, respectively) compared with non-PsA pregnancies. No increased risks were observed for pre-eclampsia, stillbirth or other infant outcomes apart from preterm birth. CONCLUSION: The majority of women with PsA have uneventful pregnancies with respect to adverse outcomes. In the present study, we found increased risks of preterm birth and caesarean delivery compared with non-PsA pregnancies. TWEETABLE ABSTRACT: Women with psoriatic arthritis have uneventful pregnancies but are at increased risk of preterm birth and caesarean delivery.

Acute ghrelin changes food preference from a high-fat diet to chow during binge-like eating in rodents.

Ghrelin, an orexigenic hormone released from the empty stomach, provides a gut-brain signal that promotes many appetitive behaviours, including anticipatory and goal-directed behaviours for palatable treats high in sugar and/or fat. In the present study, we aimed to determine whether ghrelin is able to influence and/or may even have a role in binge-like eating behaviour in rodents. Accordingly, we used a palatable scheduled feeding (PSF) paradigm in which ad lib. chow-fed rodents are trained to 'binge' on a high-fat diet (HFD) offered each day for a limited period of 2 hours. After 2 weeks of habituation to this paradigm, on the test day and immediately prior to the 2-hour PSF, rats were administered ghrelin or vehicle solution by the i.c.v. route. Remarkably and unexpectedly, during the palatable scheduled feed, when rats normally only binge on the HFD, those injected with i.c.v. ghrelin started to eat more chow and chow intake remained above baseline for the rest of the 24-hour day. We identify the ventral tegmental area (VTA) (a key brain area involved in food reward) as a substrate involved because these effects could be reproduced, in part, by intra-VTA delivery of ghrelin. Fasting, which increases endogenous ghrelin, immediately prior to a palatable schedule feed also increased chow intake during/after the schedule feed but, in contrast to ghrelin injection, did not reduce HFD intake. Chronic continuous central ghrelin infusion over several weeks enhanced binge-like behaviour in palatable schedule fed rats. Over a 4-week period, GHS-R1A-KO mice were able to adapt and maintain large meals of HFD in a manner similar to wild-type mice, suggesting that ghrelin signalling may not have a critical role in the acquisition or maintenance in this kind of feeding behaviour. In conclusion, ghrelin appears to act as a modulating factor for binge-like eating behaviour by shifting food preference towards a more nutritious choice (from HFD to chow), with these effects being somewhat divergent from fasting.

Rheumatoid Arthritis and Risk of Malignant Lymphoma: Is the Risk Still Increased?

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas with a strong correlation with RA disease severity. Given the changes in RA therapy over recent decades, this study was undertaken to assess whether lymphoma risk remains increased, and if so, to explore risk predictors and lymphoma subtypes. METHODS: We identified 12,656 cases of incident RA in the Swedish Rheumatology Quality Register 1997-2012 and obtained information on therapy and inflammatory activity during the first year after diagnosis. Each patient was matched to 10 population comparator subjects. Through linkage to the Swedish Cancer Register, lymphomas, including subtypes, were identified. We assessed hazard ratios (HRs) using Cox regression. RESULTS: Overall, the HR for lymphoma was increased in RA, to 1.6 (95% confidence interval [95% CI] 1.2-2.1). Taking RA duration into account, risks did not appear to have declined over successive calendar years of RA diagnosis. Neither use of methotrexate the first year after RA diagnosis nor ever use of tumor necrosis factor inhibitors (TNFi) increased lymphoma risk (HR 0.9 [95% CI 0.4-1.9]). Use of oral corticosteroids the first year after RA diagnosis was associated with a reduced risk (HR 0.5 [95% CI 0.3-0.9]). Inflammatory activity during the first year after RA diagnosis did not predict future lymphoma risk. Chronic lymphocytic leukemia occurred less frequently, and Hodgkin's lymphoma occurred more frequently, in RA patients than in the general population. CONCLUSION: The average lymphoma risk in recently diagnosed RA is similar in magnitude to that reported in historical cohorts. Standard antirheumatic treatment including TNFi did not predict future lymphoma risk. Distribution of lymphoma subtypes warrants further investigation.

Ankylosing spondylitis, psoriatic arthritis, and risk of malignant lymphoma: a cohort study based on nationwide prospectively recorded data from Sweden.

OBJECTIVE: Data on lymphoma risk in ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are scarce. This study was undertaken to assess the risk of lymphoma in AS and PsA overall and in relation to therapies, including tumor necrosis factor inhibitor (TNFi), for which lymphoma risks are a concern. METHODS: Through the Swedish National Patient Register we assembled nationwide prevalence cohorts of patients with AS (n = 8,707) and patients with PsA (n = 19,283) for whom data were obtained between 2001 and 2010. Each cohort member was matched to 5 population comparator subjects. Linkage with the nationwide Cancer Register identified all lymphomas recorded from 2001 to 2010. Through the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden [ARTIS]), we identified patients exposed to TNFi in the AS cohort (n = 1,908) and the PsA cohort (n = 2,605) before lymphoma diagnosis. Hazard ratios (HRs) for lymphoma were estimated by Cox regression. Crude incidences of lymphoma in TNFi-exposed and TNFi-naive patients were compared. RESULTS: For AS patients, the HR of having lymphoma versus the general population was 0.9 (95% confidence interval [95% CI] 0.5-1.6) (14 lymphomas). For PsA patients, the corresponding HR was 1.2 (95% CI 0.9-1.7) (45 lymphomas). For PsA patients treated with methotrexate and/or sulfasalazine, the HR of having lymphoma was 1.7 (95% CI 1.0-3.1). The numbers and incidence of lymphoma were not materially different in TNFi-exposed versus TNFi-naive AS and PsA patients, although the numbers of lymphomas were small. CONCLUSION: In contrast to rheumatoid arthritis, the average risks of lymphoma in AS or PsA are not elevated, although increased risks in a subset of PsA patients cannot be excluded. Our findings indicate that TNFi does not affect the risk of lymphoma in AS or in PsA.

Visual and cerebral sequelae of very low birth weight in adolescents.

OBJECTIVE: To describe the visual functions and relate them to MRI findings and the intellectual level in adolescents born with very low birth weight (VLBW). DESIGN: Population-based case-control study. PATIENTS: 59 15-year-old VLBW adolescents and 55 sex and age-matched controls with normal birth weight. MAIN OUTCOME MEASURES: Objective clinical findings (visual acuity, stereo acuity and cycloplegic refraction) were recorded. Structured history taking was used to identify visual difficulties. The intellectual level was assessed with the Wechsler Intelligence Scale for Children (WISC). All VLBW adolescents underwent MRI of the brain. RESULTS: Significant differences were found between the VLBW adolescents and controls regarding visual acuity (median -0.11 and -0.2, respectively; p=0.004), stereo acuity (median 60'' and 30'', respectively; p<0.001), prevalence of astigmatism (11/58 and 0/55, respectively; p<0.001) and in full-scale IQ (mean IQ 85 and 97, respectively; p<0.001) and performance IQ (mean 87 and 99, respectively; p=0.002). The structured history also revealed a borderline significant difference between the groups (mean problems 0.46 and 0.15 respectively; p=0.051). 30% (17/57) of the VLBW adolescents had abnormal MRI findings and performed worse in all tests, compared with both the VLBW adolescents without MRI pathology and the normal controls. CONCLUSION: This study confirms previous observations that VLBW adolescents are at a disadvantage regarding visual outcome compared with those with normal birth weight. In 47%, visual dysfunction was associated with abnormal MRI findings and in 33% with learning disabilities. The adolescents with abnormal MRI findings had more pronounced visual and cognitive dysfunction. The findings indicate a cerebral causative component for the visual dysfunction seen in the present study.

Use of gloves among dentists in Sweden--a 3-year follow-up study.

150 community dentists and 200 private general dental practitioners in southern Sweden were asked about the frequency of glove use in dental practice and related issues. This was a 3-year follow-up study. 76% of the community GDPs and 29% of the private GDPs used gloves regularly in all patient treatment. The group consisted mostly of female and younger dentists. Dentists never using gloves at all were older, male private practitioners. Difficulties to adjust using gloves and mostly non-risk-clientele were the two main reasons for dentists not to use gloves regularly. Skin complaints related to glove use seems to have increased from 1988 to 1991. Cross-infection-risk by HIV from patient was assessed as low although the main reason for most dentist to use gloves regularly was the contemporary debate about AIDS and HIV in media.

Use of gloves among dentists in Sweden.

This study among 191 public and private dentists in the Malmöhus County of southern Sweden showed that 77% of the community dentists (n = 167) and 54% of the private dentists (n = 24) used gloves regularly as infection precaution during extraction. For surgery these figures were 90% and 54% respectively. These were low figures considering the several general recommendations from both the Swedish National Board of Health and Welfare and local community authorities to dental personnel to use gloves regularly during procedures with known risk of blood contact. The survey showed that 61% (n = 167) of the public dentists and 4% (n = 24) of the private dentists used gloves regularly during all patient treatment. High cost for gloves was no major obstacle for not using them regularly but rather discomfort and old habits (79% of the answers). 21% of the dentists had experienced local infections of their hands due to patient contact, puncture wounds being the most common cause. Most of the dentists using gloves had been influenced by the general HIV/AIDS discussion in news media (65%; n = 114).