Estimation of mortality rate ratios for chronic conditions with misclassification of disease status at death.

Estimation of mortality rates and mortality rate ratios (MRR) of diseased and non-diseased individuals is a core metric of disease impact used in chronic disease epidemiology. Estimation of mortality rates is often conducted through retrospective linkage of information from nationwide surveys such as the National Health Interview Survey (NHIS) and death registries. These surveys usually collect information on disease status during only one study visit. This infrequency leads to missing disease information (with right censored survival times) for deceased individuals who were disease-free at study participation, and a possibly biased estimation of the MRR because of possible undetected disease onset after study participation. This occurrence is called "misclassification of disease status at death (MicDaD)" and it is a potentially common source of bias in epidemiologic studies. In this study, we conducted a simulation analysis with a high and a low incidence setting to assess the extent of MicDaD-bias in the estimated mortality. For the simulated populations, MRR for diseased and non-diseased individuals with and without MicDaD were calculated and compared. Magnitude of MicDaD-bias depends on and is driven by the incidence of the chronic disease under consideration; our analysis revealed a noticeable shift towards underestimation for high incidences when MicDaD is present. Impact of MicDaD was smaller for lower incidence (but associated with greater uncertainty in the estimation of MRR in general). Further research can consider the amount of missing information and potential influencers such as duration and risk factors of the disease.

Incidence of Parkinson's disease in Germany based on prevalence data from 70 million patients of the statutory health insurance.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor system manifestations and psychiatric symptoms. The aim of this study was to estimate the age- and sex-specific incidence of PD in Germany using an illness-death model and a corresponding partial differential equation (PDE) based on prevalence and mortality data. METHODS: Based on a PDE that describes the dynamics in an illness-death model, the age- and sex-specific incidence of PD in Germany was estimated using published prevalence and mortality rates. Prevalence rates were provided by the Central Institute for Statutory Health Insurance (Zi) for the period from 2010 to 2019. Parkinson's related mortality was estimated based on comparable population data from Norway. Bootstrapping was used for incidence estimation (median of 5000 samples) and to obtain 95% confidence intervals to interpret the accuracy of the incidence estimation. RESULTS: Men had higher incidences of PD than women at all ages. The highest incidences (median of 5000 bootstrap samples) for both groups were estimated for the age of 85 years with an incidence of 538.49 per 100,000 person-years (py) in men and 284.09 per 100,000 py in women, with an increasing width of bootstrapping 95% CIs showing greater uncertainty in the estimation at older ages. CONCLUSION: The illness-death model and the corresponding PDE, which describes changes in prevalence as a function of mortality and incidence, can be used to estimate the incidence of PD as a chronic disease. As overestimation of incidence is less likely with this method, we found incidence rates of Parkinson's disease that are suitable for further analyses with a lower risk of bias.

Beneficial effects associated to a healthy lifestyle in systemic lupus erythematosus: A cross-sectional study.

OBJECTIVE: To assess whether a healthy lifestyle is associated to beneficial effects on various systemic lupus erythematosus (SLE) health domains. METHODS: In a cross-sectional study, Mediterranean Diet Adherence Score (MEDAS), physical activity energy expenditure (PAEE), and smoking status were assessed by questionnaires, along with clinical parameters and various health domains including Systemic Lupus Disease Activity Score (SLEDAI), Depression Scale (CES-D), Fatigue Severity (FSS), functional status (FFbH), physical and mental quality of life (PCS, MCS). Lifestyle choices were assessed with respect to health domains by linear regression modeling. Additionally, SLE patients with a healthy lifestyle (MEDAS ≥ 4, ≥ 1 h sport per week, no smoking) were compared to those without by Wilcoxon's signed-rank test. RESULTS: 49 of 145 SLE patients (44.3 ± 31.7 years, 87.6% female) followed a healthy lifestyle and showed a higher physical quality of life (ß = 4.5 (95%-CI 1.5-7.9) p = 0.01), lower depression (ß = -5.0 (-8.2 to -0.2) p = 0.02) and lower fatigue (ß = -0.8 (-1.5 to -0.2) p = 0.01) independently of SLE disease activity. Furthermore, dsDNA-antibodies were lower (146 ± 540 vs 266 ± 146 U/mL, p = 0.049). In a more detailed analysis, physical activity had the highest impact on the various health domains when compared to smoking or diet adherence, which was consistent even after adjusting for multiple potential confounders. Each 1,000 kcal of weekly PAEE was associated to a 1.8 (0.9-2.6) point increase in the PCS (p = 0.0001), a 0.2 (0.03-0.4) point decrease in the CES-D (p = 0.01) and a 2.8 (1.2-4.4) point increase in the FFbH (p = 0.0006). CONCLUSION: A healthy lifestyle, especially physical activity is associated with beneficial effects including quality of life, depression and fatigue in SLE.

Estimating incidence of type 1 and type 2 diabetes using prevalence data: the SEARCH for Diabetes in Youth study.

BACKGROUND: Incidence is one of the most important epidemiologic indices in surveillance. However, determining incidence is complex and requires time-consuming cohort studies or registries with date of diagnosis. Estimating incidence from prevalence using mathematical relationships may facilitate surveillance efforts. The aim of this study was to examine whether a partial differential equation (PDE) can be used to estimate diabetes incidence from prevalence in youth. METHODS: We used age-, sex-, and race/ethnicity-specific estimates of prevalence in 2001 and 2009 as reported in the SEARCH for Diabetes in Youth study. Using these data, a PDE was applied to estimate the average incidence rates of type 1 and type 2 diabetes for the period between 2001 and 2009. Estimates were compared to annual incidence rates observed in SEARCH. Precision of the estimates was evaluated using 95% bootstrap confidence intervals. RESULTS: Despite the long period between prevalence measures, the estimated average incidence rates mirror the average of the observed annual incidence rates. Absolute values of the age-standardized sex- and type-specific mean relative errors are below 8%. CONCLUSIONS: Incidence of diabetes can be accurately estimated from prevalence. Since only cross-sectional prevalence data is required, employing this methodology in future studies may result in considerable cost savings.

A population-based projection of psoriatic arthritis in Germany until 2050: analysis of national statutory health insurance data of 65 million German population.

The population-based prevalence of psoriatic arthritis (PsA) is still unclear and not well described globally. The aim of this study was to conduct a population-based prevalence projection and provide long-term future estimations of PsA patients in Germany until 2050, using the illness-death model and based on historical data. We analyzed the national statutory health insurance data of 65 million population in the German Institute for Medical Documentation and Information between January 2009 and December 2012. We constructed an estimation of the PsA burden among the German population using the relevant epidemiological parameters to project the numbers of patients with PsA in Germany until 2050 under five possible scenarios by varying the incidence and mortality. The overall conservatively estimated prevalence of PsA in Germany in 2019 was 0.31% (95% CI 0.28-0.36%). Women contribute a higher prevalence than men in all five scenarios. In the assumed scenarios with increased incidence, the prevalence of PsA at 60 years of age could rise from 1% in 2019 to more than 3% in 2050 for both genders, with the increase particularly pronounced for women, reaching around 3.5%. However, in the assumed scenarios with decreasing incidence, the prevalence curve may flatten and begin a decreasing trend from 2035 to 2050 for both genders, achieving a prevalence of less than 1% in 2050. Our research is to generate assumed population-based data on PsA in Germany that can serve as a reference for public health stakeholders to prepare an optional intervention. We would expect worryingly high numbers in the coming decades if preventive strategies are not implemented. In the long term, it will be necessary to implement preventive strategies to identify predictors and treat psoriasis symptoms early in order to delay or even prevent the transition of psoriasis to PsA.

Estimation of migraine prevalence considering active and inactive states across different age groups.

BACKGROUND: Migraine is a very common headache disorder on the population level, characterized by symptomatic attacks (activity). For many people with migraine, the migraine symptoms intermittently or permanently cease during their lifetime (inactive migraine). The current diagnostic classification of migraine considers two states: active migraine (having migraine symptoms within the last year) and not having active migraine (including both individuals with inactive migraine and those who never had migraine). Defining a state of inactive migraine that has gone into remission may better capture the trajectories of migraine across the lifespan and contribute to a better understanding of its biological processes. We aimed to quantify the prevalence of never, active, and inactive migraine separately, using modern prevalence and incidence estimation methodology to better describe the complexity of migraine trajectories at the population level. METHODS: Using a multistate modeling approach, data from the Global Burden of Disease (GBD) study, and results from a population-based study, we estimated the transition rates by which individuals moved between migraine disease states and estimated prevalences of never, active and inactive migraine. We used data from the GBD project and a hypothetical cohort of 100,000 people with a starting age of 30 and 30 years of follow-up, both in Germany and globally, stratified by sex. RESULTS: In Germany, the estimated rate of transition from active to inactive migraine (remission rate) increased after the age of 22.5 in women and 27.5 in men. The pattern for men in Germany was similar to the one observed on the global level. The prevalence of inactive migraine among women reaches 25.7% in Germany and 16.5% globally at age 60. For men, the inactive migraine prevalence estimates at the same age were 10.4% in Germany and 7.1% globally. CONCLUSIONS: Considering an inactive migraine state explicitly reflects a different epidemiological picture of migraine across the lifecourse. We have demonstrated that many women of older ages may be in an inactive migraine state. Many pressing research questions can only be answered if population-based cohort studies collect information not only on active migraine but also on inactive migraine states.

Productivity-adjusted life years lost due to type 2 diabetes in Germany in 2020 and 2040.

AIMS/HYPOTHESIS: Type 2 diabetes can lead to reduced productivity during working age. We aimed to estimate productive life years lost associated with type 2 diabetes on the individual and population level in Germany in 2020 and 2040, while accounting for future trends in mortality. METHODS: Based on a mathematical projection model, we estimated age- and sex-specific productivity losses associated with type 2 diabetes during working age (20-69 years) in Germany in 2020 and 2040. Productivity losses in terms of excess mortality (years of life lost, YLL) and reductions in labour force participation, presenteeism and absenteeism (years of productivity lost, YPL) were summed to calculate productivity-adjusted life years (PALY) lost. Input data for the projection were based on meta-analyses, representative population-based studies and population projections to account for future trends in mortality. RESULTS: Compared with a person without type 2 diabetes, mean PALY lost per person with type 2 diabetes in 2020 was 2.6 years (95% CI 2.3, 3.0). Of these 2.6 years, 0.4 (95% CI 0.3, 0.4) years were lost due to YLL and 2.3 (95% CI 1.9, 2.6) years were lost due to YPL. Age- and sex-specific results show that younger age groups and women are expected to lose more productive life years than older age groups and men. Population-wide estimates suggest that 4.60 (95% CI 4.58, 4.63) million people with prevalent type 2 diabetes in 2020 are expected to lose 12.06 (95% CI 10.42, 13.76) million PALY (1.62 million years due to YLL and 10.44 million years due to YPL). In 2040, individual-level PALY lost are projected to slightly decrease due to reductions in YLL. In contrast, population-wide PALY lost are projected to increase to 15.39 (95% CI 13.19, 17.64) million due to an increase in the number of people with type 2 diabetes to 5.45 (95% CI 5.41, 5.50) million. CONCLUSIONS/INTERPRETATION: On the population level, a substantial increase in productivity burden associated with type 2 diabetes was projected for Germany between 2020 and 2040. Efforts to reduce the incidence rate of type 2 diabetes and diabetes-related complications may attenuate this increase.

Association between HIV infection and hypertension: a global systematic review and meta-analysis of cross-sectional studies.

BACKGROUND: Improved access to effective antiretroviral therapy has meant that people living with HIV (PLHIV) are surviving to older ages. However, PLHIV may be ageing differently to HIV-negative individuals, with dissimilar burdens of non-communicable diseases, such as hypertension. While some observational studies have reported a higher risk of prevalent hypertension among PLHIV compared to HIV-negative individuals, others have found a reduced burden. To clarify the relationship between HIV and hypertension, we identified observational studies and pooled their results to assess whether there is a difference in hypertension risk by HIV status. METHODS: We performed a global systematic review and meta-analysis of published cross-sectional studies that examined hypertension risk by HIV status among adults aged > 15 (PROSPERO: CRD42019151359). We searched MEDLINE, EMBASE, Global Health and Cochrane CENTRAL to August 23, 2020, and checked reference lists of included articles. Our main outcome was the risk ratio for prevalent hypertension in PLHIV compared to HIV-negative individuals. Summary estimates were pooled with a random effects model and meta-regression explored whether any difference was associated with study-level factors. RESULTS: Of 21,527 identified studies, 59 were eligible (11,101,581 participants). Crude global hypertension risk was lower among PLHIV than HIV-negative individuals (risk ratio 0.90, 95% CI 0.85-0.96), although heterogeneity between studies was high (I2 = 97%, p < 0.0001). The relationship varied by continent, with risk higher among PLHIV in North America (1.12, 1.02-1.23) and lower among PLHIV in Africa (0.75, 0.68-0.83) and Asia (0.77, 0.63-0.95). Meta-regression revealed strong evidence of a difference in risk ratios when comparing North American and European studies to African ones (North America 1.45, 1.21-1.74; Europe 1.20, 1.03-1.40). CONCLUSIONS: Our findings suggest that the relationship between HIV status and prevalent hypertension differs by region. The results highlight the need to tailor hypertension prevention and care to local contexts and underscore the importance of rapidly optimising integration of services for HIV and hypertension in the worst affected regions. The role of different risk factors for hypertension in driving context-specific trends remains unclear, so development of further cohorts of PLHIV and HIV-negative controls focused on this would also be valuable.

European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance.

BACKGROUND/OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. METHODS: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. RESULTS: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. CONCLUSIONS: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.

Factors detrimental to work productivity and daily activities in systemic lupus erythematosus patients - Analysis of the German LuLa study.

OBJECTIVE: The aim of this study was to identify factors associated with impaired work productivity and impaired daily activities in patients with systemic lupus erythematosus (SLE). METHODS: The LuLa study is a longitudinal patient-reported study. Beyond sociodemographic data, work productivity, daily activities and fatigue, several other clinical outcome parameters (e.g. mental health-related quality of life and physical functioning, disease activity, damage and pain) were surveyed with validated questionnaires. The effects of confounders on work productivity (WPAI 2) and daily activity domains (WPAI 4) were studied by multivariate regression analysis. RESULTS: A total of 585 patients completed the questionnaire of whom 259 were employed and analysed. The median impairment in work productivity (WPAI 2) was 20% (Q1-3 0-40), and the median impairment in daily activities (WPAI 4) was 30% (Q1-3 10-50%). Multivariate regression analysis revealed that fatigue, pain, disease activity and health-related quality of life affected WPAI 2 and 4. Furthermore, we observed distinct synergistic effects of fatigue, disease activity and pain on both work productivity and daily activities: a higher impact of fatigue was associated with the reported extent of pain or disease activity. CONCLUSION: In employed patients with SLE, impaired work productivity and impaired daily activities were frequently reported. Fatigue, pain, disease activity and health-related quality of life demonstrated a detrimental impact, with a synergistic effect of fatigue, disease activity and pain. Hence, both optimized pain management and targeted immunomodulatory therapy are important for preserving active participation in life among patients with fatigue.

Delayed diagnosis adversely affects outcome in systemic lupus erythematosus: Cross sectional analysis of the LuLa cohort.

OBJECTIVE: Despite increased physician's awareness and improved diagnostic and serological testing in the recent years, the interval between the initial symptoms and the diagnosis of Systemic lupus erythematosus (SLE) is still very long. Our aim was to study this delay and its association to the outcome of the disease. METHODS: Information on demographics, onset of first symptoms, first physicians visit and time of diagnosis was assessed by self-reported questionnaires among SLE patients in Germany (LuLa cohort, n = 585) in the year 2012. Disease activity (Systemic Lupus Activity Questionnaire; SLAQ), disease related damage (Brief Index of Lupus Damage; BILD), health related quality of life (Short Form 12) and fatigue (FSS) were chosen as proxies for outcome. Linear regression analysis was used to analyze the association of the delay in diagnosis to the outcome, adjusted for age, disease duration and sex. RESULTS: Mean duration between the onset of symptoms and the diagnosis of SLE was 47 months (SD 73). The longer the time to diagnosis, the higher the disease activity (ß = 0.199, p < 0.0001), the disease-related damage (ß = 0.137, p = 0.002) and fatigue (ß 0.145, p = 0.003) and the lower the health-related quality of life (physical ß = -0.136, p = 0.004, mental ß = -0.143, p = 0.004). CONCLUSION: In systemic lupus erythematosus, longer time to diagnosis was associated with worse outcome. Concepts in care with the intention to shorten the time to diagnosis are needed to improve the long-term outcome of the disease.

Associations of site-specific CD4+-T-cell hypomethylation within CD40-ligand promotor and enhancer regions with disease activity of women with systemic lupus erythematosus.

OBJECTIVE: To comprehensively assess associations of site-specific CD4+-T-cell hypomethylation of the CD40-Ligand gene (CD40L) with disease activity of women with systemic lupus erythematosus (SLE). METHODS: CpG-sites within the DNA of the promotor and two enhancer regions (n = 22) of CD40L were identified and numbered consecutively. The rate of methylated DNA in isolated CD4+-T-cells of women with SLE were quantified for each methylation site by MALDI-TOF. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Associations of site-specific methylation rates with the SLEDAI scores were assessed by linear regression modelling. P values were adjusted according to Bonferroni-Holm as indicated. RESULTS: 60 female SLE patients participated in the study (age 45.7 ± 11.1 years, disease duration 17.0 ± 8.3 years). Significant associations to the SLEDAI were noted for CpG22 hypomethylation of the promotor (ß = -40.1, p = 0.017, adjusted p = 0.027), trends were noted for CpG17 hypomethylation of the promotor (ß = -30.5, p = 0.032, adjusted p = 0.6), and for CpG11 hypermethylation of the second enhancer (ß = 15.0, p = 0.046, adjusted p = 0.8). CONCLUSION: Site-specific hypomethylation of the CD40L promotor in CD4+-T-cells show associations with disease activity in female SLE patients.

Methyl donor micronutrients, CD40-ligand methylation and disease activity in systemic lupus erythematosus: A cross-sectional association study.

OBJECTIVE: Hypomethylation of CD40-ligand (CD40L) in T-cells is associated with increased disease activity in systemic lupus erythematosus (SLE). We therefore investigated possible associations of dietary methyl donors and products with CD40L methylation status in SLE. METHODS: Food frequency questionnaires were employed to calculate methyl donor micronutrients in 61 female SLE patients (age 45.7 ± 12.0 years, disease duration 16.2 ± 8.4 years) and compared to methylation levels of previously identified key DNA methylation sites (CpG17 and CpG22) within CD40L promotor of T-cells using quantitative DNA methylation analysis on the EpiTYPER mass spectrometry platform. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Linear regression modelling was used. P values were adjusted according to Benjamini & Hochberg. RESULTS: Amongst the micronutrients assessed (g per day), methionine and cysteine were associated with methylation of CpG17 (ß = 5.0 (95%CI: 0.6-9.4), p = 0.04; and ß = 2.4 (0.6-4.1), p = 0.02, respectively). Methionine, choline, and cysteine were additionally associated with the mean methylation of the entire CD40L (ß = 9.5 (1.0-18.0), p = 0.04; ß = 1.6 (0.4-3.0), p = 0.04; and ß = 4.3 (0.9-7.7), p = 0.02, respectively). Associations of the SLEDAI with hypomethylation were confirmed for CpG17 (ß=-32.6 (-60.6 to -4.6), p = 0.04) and CpG22 (ß=-38.3 (-61.2 to -15.4), p = 0.004), but not the mean methylation of CD40L. Dietary products with the highest impact on methylation included meat, ice cream, white bread, and cooked potatoes. CONCLUSIONS: Dietary methyl donors may influence DNA methylation levels and thereby disease activity in SLE.

Diabetes free life expectancy and years of life lost associated with type 2 diabetes: projected trends in Germany between 2015 and 2040.

BACKGROUND: Type 2 diabetes (T2D) causes substantial disease burden and is projected to affect an increasing number of people in coming decades. This study provides projected estimates of life years free of type 2 diabetes (T2D) and years of life lost ([Formula: see text]) associated with T2D for Germany in the years 2015 and 2040. METHODS: Based on an illness-death model and the associated mathematical relation between prevalence, incidence and mortality, we projected the prevalence of diagnosed T2D using currently available data on the incidence rate of diagnosed T2D and mortality rates of people with and without diagnosed T2D. Projection of prevalence was achieved by integration of a partial differential equation, which governs the illness-death model. These projected parameters were used as input values to calculate life years free of T2D and [Formula: see text] associated with T2D for the German population aged 40 to 100 years in the years 2015 and 2040, while accounting for different assumptions on future trends in T2D incidence and mortality. RESULTS: Assuming a constant incidence rate, women and men at age 40 years in 2015 will live approximately 38 years and 33 years free of T2D, respectively. Up to the year 2040, these numbers are projected to increase by 1.0 years and 1.3 years. Assuming a decrease in T2D-associated excess mortality of 2% per year, women and men aged 40 years with T2D in 2015 will be expected to lose 1.6 and 2.7 years of life, respectively, compared to a same aged person without T2D. In 2040, these numbers would reduce by approximately 0.9 years and 1.6 years. This translates to 10.8 million and 6.4 million [Formula: see text] in the German population aged 40-100 years with prevalent T2D in 2015 and 2040, respectively. CONCLUSIONS: Given expected trends in mortality and no increase in T2D incidence, the burden due to premature mortality associated with T2D will decrease on the individual as well as on the population level. In addition, the expected lifetime without T2D is likely to increase. However, these trends strongly depend on future improvements of excess mortality associated with T2D and future incidence of T2D, which should motivate increased efforts of primary and tertiary prevention.

Differentiating rheumatoid and psoriatic arthritis: a systematic analysis of high-resolution magnetic resonance imaging features-preliminary findings.

BACKGROUND: Because of overlapping phenotypical presentations, the diagnostic differentiation of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) remains challenging. Thus, this study aimed to examine the diagnostic value of distinct imaging features obtained by high-resolution 3-T MRI for the diagnostic differentiation. MATERIALS AND METHODS: Seventeen patients with PsA and 28 patients with RA were imaged at high resolution using 3-T MRI scanners and a dedicated 16-channel hand coil. All images were analyzed according to the outcome measures in rheumatology clinical trials' (OMERACT) RAMRIS (Rheumatoid Arthritis Magnetic Resonance Imaging Score) and PsAMRIS (Psoriatic Arthritis Magnetic Resonance Imaging Score) for the presence and intensity of synovitis, flexor tenosynovitis, bone edema, bone erosion, periarticular inflammation, bone proliferation, and joint space narrowing. Next, odds ratios (OR) were calculated to determine the strength of the associations between these imaging features, demographic characteristics, and the outcome RA vs. PsA. RESULTS: PsA could be differentiated from RA by extracapsular inflammatory changes (PsAMRIS sub-score "periarticular inflammation"), with low odds for the presence of RA (OR of 0.06, p < 0.01) at all metacarpophalangeal (MCP) joints. A prediction model informed by the items that were strongest associated with the presence of RA or PsA demonstrated excellent differentiating capability with an area under the curve of 98.1%. CONCLUSION: High-resolution imaging is beneficial for the identification of relevant imaging features that may assist the clinical differentiation of inflammatory conditions of the hand. At the MCP level, extracapsular inflammatory changes were strongly associated with PsA and may consequently allow the imaging differentiation of PsA and RA.

Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities.

OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). CONCLUSIONS: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.

Association between autoantibody level and disease activity in rheumatoid arthritis is dependent on baseline inflammation.

OBJECTIVES: It is still controversial whether autoantibody (AAb) serum levels have a value for response monitoring in rheumatoid arthritis (RA). Therefore, we retrospectively investigated a real-life outpatient RA cohort to determine which factors are associated with change in serum AAb levels and RA disease activity. The primary goal of the study was to determine predictors for changes in DAS28 and autoantibodies over time and identify traits of non-rituximab treated patients, which would define strong association of disease activity with changes in AAb-levels. METHODS: Seventy-eight patients with seropositive RA were monitored for DAS28, CRP, ESR, anti-cyclic citrullinated peptides (CCP), anti-mutated citrullinated vimentin (MCV), and rheumatoid factor (RF). Using linear mixed regression modelling, factors influencing DAS28 and serum AAb were determined. Patients showing above (good correlators) and below (bad correlators) average correlation of serum AAb with DAS28 were further characterised. RESULTS: In non-rituximab treated patients (88.5%), associations of changes in AAb and DAS28 were strengthened with more morning stiffness (p=0.002), DMARD use (p=0.02), tender joints (p=0.01), swollen joints (p<0.01), higher ESR (p<0.01) and VAS (p<0.001) at baseline. Decrease of anti-CCP was also predicted by longer disease duration (-4.4 U/ml per year disease duration, p=0.048) and/or no erosions (-2.0 U/ml/month, p<0.01) at baseline, whereas erosive disease predicted an increase (+1.4 U/ml/month, p=0.015) in anti-CCP. Conversely, patients with erosive disease showed a trend to decrease RF (-1.9 U/ml/month, p=0.06). CONCLUSIONS: In non-rituximab treated RA patients, the association between disease activity and change in autoantibody levels is not static, but strengthens with increase in signs of inflammation (ESR, VAS, swollen joints, tender joints, morning stiffness) at baseline. Therefore, studies of changes in AAb need to consider baseline inflammation as confounder.

2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus.

OBJECTIVE: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. RESULTS: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. CONCLUSION: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.

Analysing detection of chronic diseases with prolonged sub-clinical periods: modelling and application to hypertension in the U.S.

BACKGROUND: We recently introduced a system of partial differential equations (PDEs) to model the prevalence of chronic diseases with a possibly prolonged state of asymptomatic, undiagnosed disease preceding a diagnosis. Common examples for such diseases include coronary heart disease, type 2 diabetes or cancer. Widespread application of the new method depends upon mathematical treatment of the system of PDEs. METHODS: In this article, we study the existence and the uniqueness of the solution of the system of PDEs. To demonstrate the usefulness and importance of the system, we model the age-specific prevalence of hypertension in the US 1999-2010. RESULTS: The examinations of mathematical properties provide a way to solve the systems of PDEs by the method of characteristics. In the application to hypertension, we obtain a good agreement between modeled and surveyed age-specific prevalences. CONCLUSIONS: The described system of PDEs provides a practical way to examine the epidemiology of chronic diseases with a state of undiagnosed disease preceding a diagnosis.

New ways of estimating excess mortality of chronic diseases from aggregated data: insights from the illness-death model.

BACKGROUND: Recently, we have shown that the age-specific prevalence of a disease can be related to the transition rates in the illness-death model via a partial differential equation (PDE). The transition rates are the incidence rate, the remission rate and mortality rates from the 'Healthy' and 'Ill' states. In case of a chronic disease, we now demonstrate that the PDE can be used to estimate the excess mortality from age-specific prevalence and incidence data. For the prevalence and incidence, aggregated data are sufficient - no individual subject data are needed, which allows application of the methods in contexts of strong data protection or where data from individual subjects is not accessible. METHODS: After developing novel estimators for the excess mortality derived from the PDE, we apply them to simulated data and compare the findings with the input values of the simulation aiming to evaluate the new approach. In a practical application to claims data from 35 million men insured by the German public health insurance funds, we estimate the population-wide excess mortality of men with diagnosed type 2 diabetes. RESULTS: In the simulation study, we find that the estimation of the excess mortality is feasible from prevalence and incidence data if the prevalence is given at two points in time. The accuracy of the method decreases as the temporal difference between these two points in time increases. In our setting, the relative error was 5% and below if the temporal difference was three years or less. Application of the new method to the claims data yields plausible findings for the excess mortality of type 2 diabetes in German men. CONCLUSIONS: The described approach is useful to estimate the excess mortality of a chronic condition from aggregated age-specific incidence and prevalence data. TRIAL REGISTRATION: The article does not report the results of any health care intervention.