OBJECTIVES: Previous ecological data suggest a decline in the need for joint replacements in RA patients following the introduction of TNF inhibitor (TNFi) therapy, although patient-level data are lacking. Our primary aim was to estimate the association between TNFi use and subsequent incidence of total hip replacement (THR) and total knee replacement.

METHODS: A propensity score matched cohort was analysed using the British Society for Rheumatology Biologics Registry (2001-2016) for RA data. Propensity score estimates were used to match TNFi users to similar conventional synthetic DMARD users (with replacement) using a 1:1 ratio. Weighted multivariable Cox regression was used to estimate the impact of TNFi on study outcomes. Effect modification by baseline age and disease severity were investigated. Joint replacement at other sites was also analysed. An instrumental variable sensitivity analysis was also performed.

RESULTS: The matched analysis contained a total of 19 116 patient records. Overall, there was no significant association between TNFi use vs conventional synthetic DMARD on rates of THR (hazard ratios = 0.86 [95% CI: 0.60, 1.22]) although there was significant effect modification by age (P < 0.001). TNFi was associated with a reduction in THR among those >60 years old (hazard ratio = 0.60 [CI: 0.41, 0.87]) but not in younger patients. No significant associations were found for total knee replacement or other joint replacement.

CONCLUSION: Overall, no association was found between the use of TNFi and subsequent incidence of joint replacement. However, TNFi was associated with a 40% relative reduction in THR rates among older patients.

OBJECTIVE: To investigate time-trends and cumulative incidence of joint surgery among patients with psoriatic arthritis (PsA) compared with the general population.

METHODS: In this nationwide register-based cohort study, The Danish National Patient Registry was used to identify incident PsA patients. The 5-year incidence rates (IR) and incidence rate ratios (IRR) of joint surgery were calculated in four calendar-period defined cohorts. Each patient was matched with ten non-PsA individuals from the general population cohort (GPC). The cumulative incidences of any joint and joint-sacrificing surgery, respectively, were estimated using the Aalen-Johansen method.

RESULTS: From 1996 to 2017, 11 960 PsA patients (mean age 50 years; 57% female) were registered. The IRR of any joint surgery was twice as high for PsA patients compared with GPCs across all calendar periods. Among patients with PsA, 2, 10 and 29% required joint surgery at 5, 10 and 15 years after diagnosis. The risk of surgery in PsA patients diagnosed at 18-40 years was higher (22%) than in GPC 60+ year old (20%) after 15 years of follow-up.

CONCLUSIONS: The use of joint surgery among PsA patients remained around twofold higher from 1996 to 2012 compared with GPC. After 15 years of follow-up, nearly 30% of the PsA patients had received any surgery, and even a person diagnosed with PsA at the age of 18-40 years had a higher risk of surgery than GPCs of 60+ year old. Thus, the high surgical rates represent an unmet need in the current treatment of PsA.

BACKGROUND: Monitoring disease activity over time is a prerequisite for clinical practice and research. Valid and reliable outcome measurement instruments (OMIs) and staging systems provide researchers and clinicians with benchmark tools to assess the primary and secondary outcomes of interventional trials and to guide treatment selection properly.

OBJECTIVES: To investigate inter-rater reliability and agreement in instruments currently used in hidradenitis suppurativa (HS), with dermatologists experienced in HS as the rater population of interest.

METHODS: In a prospective completely balanced design, 24 patients with HS underwent a physical examination by 12 raters (288 assessments) using nine instruments. The results were analysed using generalized linear mixed models.

RESULTS: For the staging systems, the study found good inter-rater reliability for Hurley staging in the axillae and gluteal region, moderate inter-rater reliability for Hurley staging in the groin and for Physician's Global Assessment, and fair inter-rater reliability for refined Hurley staging and the International HS Severity Scoring System. For all the tested OMIs, the observed intervals for limits of agreement were very wide relative to the ranges of the scales.

CONCLUSIONS: The very wide intervals for limits of agreement imply that substantial changes are needed in clinical research in order to rule out measurement error. The results illustrate a difficulty, even for experienced HS experts, to agree on the type and number of lesions when evaluating disease severity. The apparent caveats call for global efforts, such as the HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) to reach consensus on how best to measure physical signs of HS reliably in randomized trials. What's already known about this topic? Without valid and reliable instruments to measure outcomes, researchers and clinicians lack the necessary benchmarks to assess primary and secondary end points of interventional trials properly. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Several outcome measure instruments exist for HS, but their validation is generally incomplete or of relatively low methodological quality. What does this study add? Using a prospective completely balanced design this study examined inter-rater reliability with HS-experienced dermatologists as the rater population of interest. The study did not find very good reliability for any included instrument or lesion counts. This study illustrates the difficulty in finding agreement on the type and number of HS lesions, even among experts. The results question whether physical signs are best measured by a traditional physician lesion count instrument. What are the clinical implications of this work? For staging, Hurley staging and physician global visual analogue scale proved to be acceptable instruments in terms of inter-rater reliability. For the instruments designed to measure changes in health status, our study illustrates how difficult it is, even for experts, to measure the physical signs of HS using a simple rater counting. Consequently, other assessment methods of physicals signs, such as ultrasound evaluation, require consideration.

METHOD:
Questionnaires from 19,898 women in The Danish Nurse Cohort in 1993 were linked to registries on hospitalizations, death causes and migration until Dec 2016. Cancer risk by tobacco and alcohol was estimated using Cox proportional hazards models.

RESULTS:
16,106 nurses, aged >44 years (mean = 56), were eligible for analysis. Throughout 23 years (mean follow-up = 18.8 years) overall cancers counted 4,968. Of these, 1,897, 2,231, 1,407 and 579 events were smoking-related, alcohol-related, breast cancers and gynecological cancers. Increased risks of overall, smoking-related, and breast cancer were observed for current smoking and excess alcohol intake (>14 units/week), separately, compared to never smoking and light drinking (1-7 units/week) respectively. Moderate drinking (8-14 units/week) increased the risk of alcohol-related and breast cancer. Additional risk increases were observed among smokers drinking alcohol above light levels for overall, smoking-related, alcohol-related and breast cancer (HR = 1.40, 95% CI:1.30-1.51, HR = 1.72, 95% CI:1.52-1.94, HR = 1.33, 95% CI:1.26-1.40, HR = 1.32, 95% CI:1.15-1.53, respectively), compared to non-smokers drinking lightly. These risks increased further for smokers drinking above moderate levels (HR = 1.49, 95% CI:1.36-1.63, HR = 1.97, 95% CI:171.-2.26, HR = 1.40, 95% CI:1.22-1.60, HR = 1.33, 95% CI:1.12-1.57, respectively). No significant associations were found for gynecological cancer.

CONCLUSIONS:
Smoking and alcohol, both separately and combined, increased risks of overall, smoking-related, alcohol-related and breast cancer; combined use resulted in incremental risk increases. Co-use of smoking and alcohol represent an extensive threat to public health; thus, prevention could benefit from combined targeting.

Background: Evidence on the association between road traffic noise and diabetes risk is sparse and inconsistent with respect to how confounding by air pollution was treated. Objectives: In this study, we aimed to examine whether long-term exposure to road traffic noise over 25 years is associated with incidence of diabetes, independent of air pollution. Methods: A total of 28,731 female nurses from the Danish Nurse cohort (>44 years old at recruitment in 1993 or 1999) were linked to the Danish National Diabetes Register with information on incidence of diabetes from 1995 until 2013. The annual mean weighted levels of 24-h average road traffic noise (L
_den) at nurses’ residences from 1970 until 2013 were estimated with the Nord 2000 method and annual mean levels of particulate matter (PM) with diameter <2.5 and 10 nm (PM
_2.5 and PM
₁₀), nitrogen dioxide (NO
₂), and nitrogen oxide (NO
_x) with the Danish AirGIS modeling system. Co
_x proportional hazards regression models were used to examine the association between residential LdenLden in four different exposure windows (1-, 5-, 10-, and 25-years) and the incidence of diabetes, adjusted for lifestyle factors and air pollutants. Results: Of 23,762 nurses free of diabetes at the cohort baseline, 1,158 developed diabetes during a mean follow-up of 15.2 years. We found weak positive associations between 5-y mean exposure to LdenLden (per 10 dB increase) and diabetes incidence in a crude model [hazard ratio (HR): 1.07; 95% confidence interval (CI): 0.99, 1.12], which attenuated in a model adjusted for lifestyle factors (HR:1.04; 95% CI: 0.97, 1.12), and reached unity after additional adjustment for PM
_2.5 (HR: 0.99; 0.91, 1.08). In analyses by level of urbanization, we found a positive association between noise and diabetes in urban areas (HR:1.27; 95% CI: 0.98, 1.63) that was unchanged after adjusting for PM
_2.5 (HR: 1.25; 95% CI: 0.97, 1.62), but we found no apparent association in provincial (HR: 1.02; 95% CI: 0.88, 1.18) or rural areas (HR: 0.97; 95% CI: 0.87, 1.08). Conclusion: In the nationwide cohort of Danish nurses 44 years of age and older, we found no association between long-term exposure to road traffic noise and diabetes incidence after adjustment for PM
_2.5 but found suggestive evidence of an association limited to urban areas.

BACKGROUND: Few studies have examined the relationship between eating frequency and long-term change in body weight, and the results have been inconsistent.

OBJECTIVE: We examined the associations between eating frequency and 6-y changes in body mass index (BMI; in kg/m2), fat mass, fat-free mass, body fat percentage, and waist circumference.

METHODS: The study consisted of Danish men (n = 1080) and women (n = 1044) aged 35-67 y with repeated measures of eating frequency, adiposity, and covariates during 11 y. Multiple linear regression was used to assess the associations between baseline eating frequency and subsequent change in BMI, fat mass, fat-free mass, fat percentage, and waist circumference, as well as the association between initial change in eating frequency and subsequent change in the same outcomes.

RESULTS: Total baseline eating frequency was not associated with change in outcomes. However, when separately examining regular meals and snacks, each additional daily meal was associated with a subsequent 6-y change in BMI of -0.14 (95% CI: -0.27, -0.00). Similar tendencies of inverse associations were found for change in fat mass (P = 0.04), fat-free mass (P = 0.07), and waist circumference (P = 0.05). We found no association between initial change in total eating frequency and subsequent change in outcomes. However, each additional daily regular meal after 5 y was associated with a subsequent 6-y change in BMI of -0.16 (95% CI: -0.30, -0.01). Inverse associations were also seen for fat (P = 0.04) and fat-free mass (P = 0.05). In contrast, an increase in daily frequency of snacking was associated with an increase in fat mass (P = 0.04) and fat percentage (P = 0.02).

CONCLUSIONS: Our results indicate that total frequency of eating has little or no influence on adiposity among middle-aged Danish men and women. Consumption of regular meals, but not snack consumption, showed a weak inverse association with longitudinal gains in BMI.