Relationship Between Clusters of Chronic Conditions and Disability Trajectories

Recent evidence shows that more complex clusters of chronic conditions are associated with poorer health outcomes. Less clear is the extent to which these clusters are associated with different types of disability (basic and instrumental activities of daily living (ADL, IADL) and functional mobility (FM)) over time. This was a longitudinal analysis using the National Health and Aging Trends Study (NHATS) (n = 6,179). Using latent class analysis, we determined the optimal clusters of chronic conditions, then assigned each person to a best-fit class. Next, we used mixed-effects models with repeated measures to examine the effects of group (best-fit class), time (years from baseline), and the group by time interaction on each of the outcomes in separate models over 4 years. We identified 5 chronic condition clusters: “multisystem morbidity” (13.9% of the sample), “diabetes” (39.5%), “osteoporosis” (24.9%), “cardio/stroke/cancer” (4.5%), and “minimal disease” (17.3%). Group by time interaction was not significant for any outcome. For ADL outcome, only time was significant (F3,16249 = 224.72, p < .001). For IADL, both group (F4,5403 = 6.62, p < .001) and time (F3,22622 = 3.87, p = .009) were significant. For FM, both group (F4,5920 = 2.96, p = .02) and time were significant (F3,16381 = 213.41, p < .001). We did not find evidence that any cluster experienced greater increases in disability over time, but all clusters containing multiple chronic conditions had risk of IADL and FM disability. Increased screening for IADL and FM disability could identify early disability and prevent decline.

Endoscopic-Assisted Canal Wall-up Tympanomastoidectomy for Reduction of Residual Cholesteatoma

Introduction The treatment of cholesteatoma is generally surgical, and the major obstacle is the high prevalence of recidivism. The endoscopic ear surgery technique is proposed to minimize this problem. Objectives To utilize endoscopes to visualize and manipulate cholesteatoma residues after microscopic removal Methods Cross-sectional study. Thirty-two patients with cholesteatoma underwent microscopic wall-up mastoidectomy combined with the endoscopic approach. The subjects were assessed for the presence and location of covert disease. Results Of the 32 cases, 17 (53.12%) had residual cholesteatoma in the endoscopic phase. Minimal disease was found, usually fragments of the cholesteatoma matrix. Pars tensa cholesteatomas had more covert disease than pars flaccida cholesteatomas (62.50% vs 43.75%). Posterior recesses (47.05%) and tegmen tympani (41.17%) were the locations with more covert disease (p < 0.05). Conclusion Cholesteatomas of the pars tensa presented more residual disease and were significantly more common in the posterior recesses and tegmen tympani.

Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study

BackgroundIn SELECT-PsA 1, a randomised double-blind phase 3 study, upadacitinib 15 mg and 30 mg were superior to placebo and non-inferior to adalimumab in ≥20% improvement in American College of Rheumatology (ACR) criteria at 12 weeks in patients with psoriatic arthritis (PsA). Here, we report 56-week efficacy and safety in patients from SELECT-PsA 1.MethodsPatients received upadacitinib 15 mg or 30 mg once daily, adalimumab 40 mg every other week for 56 weeks or placebo through week 24 switched thereafter to upadacitinib 15 mg or 30 mg until week 56. Efficacy endpoints included the proportion of patients achieving ≥20%/50%/70% improvement in ACR criteria (ACR20/50/70), ≥75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), minimal disease activity (MDA) and change from baseline in modified total Sharp/van der Heijde Score. Treatment-emergent adverse events per 100 patient years (PY) were summarised.ResultsConsistent with results through week 24, ACR20/50/70, PASI75/90/100 and MDA responses were maintained with upadacitinib through week 56 and were generally numerically higher than with adalimumab; inhibition of radiographic progression was also maintained. Patients who switched from placebo to upadacitinib exhibited comparable improvements at week 56 as patients originally randomised to upadacitinib. The rates of serious adverse events were 9.1 events/100 PY with upadacitinib 15 mg and 12.3 events/100 PY with upadacitinib 30 mg. Two deaths were reported in each of the upadacitinib groups.ConclusionEfficacy across various domains of PsA were maintained with upadacitinib 15 mg and 30 mg through week 56 with no new safety signals observed.

Predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden

Introduction Despite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment. Materials and method We extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application. Results Of 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p<0.001). In the multivariate analysis, the adjusted hazards ratios (HR) for an unfavorable response to TB therapy for extent of involvement, baseline cavitation and persistence (post treatment) were 1.21 (95% CI: 1.01–1.44), 1.73 (95% CI: 1.05–2.84) and 2.68 (95% CI: 1.4–5.12) respectively. A 3+ smear had an HR of 1.94 (95% CI: 0.81–4.64). Further probing into the interaction, among patients with 3+ and 2+ smears, HRs for cavitation were 3.26 (95% CI: 1.33–8.00) and 1.92 (95% CI: 0.80–4.60) while for >2 zones, were 3.05 (95% CI: 1.12–8.23) and 1.92 (95% CI: 0.72–5.08) respectively. Patients without cavitation, zonal involvement <2, and a smear grade less than 2+ had a better prognosis and constituted minimal disease. Conclusion Baseline Cavitation, Opacities occupying >2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting “minimal disease”, had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens.

The natural history of TB disease - a synthesis of data to quantify progression and regression across the spectrum

Background: Prevalence surveys have found a substantial burden of subclinical (asymptomatic but infectious) TB, from which individuals can progress, regress or even persist in a chronic disease state. We aimed to quantify these pathways across the spectrum of TB disease. Methods: We created deterministic framework of TB disease with progression and regression between three states of pulmonary TB disease: minimal (non-infectious), subclinical, and clinical (symptomatic and infectious) disease. We estimated ranges for each parameter by considering all data from a systematic review in a Bayesian framework, enabling quantitative estimation of TB disease pathways. Findings: Twenty-four studies contributed data from 6030 individuals. Results suggested that, after five years, 24.7%(95% uncertainty interval, UI, 21.3%-28.6%) of individuals with prevalent subclinical disease at baseline had either progressed to clinical disease or died from TB, whereas 16.1%(95%UI, 13.8%-18.5%) had recovered after regressing to minimal disease. Over the course of five years 30% (95%UI, 27.2%-32.6%) of the subclinial cohort never developed symptoms. For those with clinical disease at baseline, 39%(95%UI, 35.8%-41.9%) and 10.3%(95%UI, 8.5%-12.4%) had died or recovered from TB, with the remainder in, or undulating between, the three disease states. The ten-year mortality of people with untreated prevalent infectious disease was 38%. Interpretation: Our results show that for people with subclinical disease, classic clinical disease is neither inevitable nor an irreversible outcome. As such, reliance on symptom- based screening means a large proportion of people with infectious disease may never be detected. Funding: TB Modelling and Analysis Consortium and European Research Council

Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study

ObjectivesThis study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range.MethodsAdult HS (age 18–80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1–5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort.Results939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups.ConclusionsUltrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.

Does Disease Activity Influence the Levels of Uric Acid in Psoriatic Arthritis?

Background: Hyperuricemia is not only associated with the development of gout but also with renal and vascular dysfunction. The prevalence of this condition has already been studied in psoriasis, but there are a few studies that have been carried out in psoriatic arthritis (PsA). Some studies have shown an association with metabolic syndrome, while others with the extent of cutaneous involvement, but there are no studies that have evaluated the disease activity with compound indexes. Objective: The aim of the study was to determine if disease activity, measured by different composite scores, influences the levels of uric acid. Method: This was a cross-sectional, observational study, which included 52 PsA patients. Clinical assessments included dactylitis, tender and swollen joint counts, Psoriasis Area and Severity Index, Leeds Enthesis Index, Minimal Disease Activity and Disease Activity for Psoriatic Arthritis. Hyperuricemia was defined as serum uric acid levels ≥ 6mg/dL in females and ≥ 7mg/dL in males. Results: Among the 52 included patients, 55.76% were female. The mean age was 54.9 ± 11.6 years. Hyperuricemia occurred in 26.92%. Demographic data, diet, comorbidities and medication were similar between patients with and without hyperuricemia. Patients with hyperuricemia had higher waist circumference (p <0.0046). There was no difference in disease activity between groups, either in the isolated items or in the composite indexes. There was a significant difference in uric acid levels according to the classification of chronic kidney disease by estimated glomerular filtration rate (p=0.0016). Individuals using leflunomide had significantly lower levels of uric acid than those who were not using (p=0.0071). Conclusion: This study supports the notion that, in PsA, hyperuricemia is more related to metabolic factors than to disease activity.

POS0192 PROGNOSTIC FACTORS ASSOCIATED WITH ACHIEVING MINIMAL DISEASE ACTIVITY IN EARLY PSORIATIC ARTHRITIS PATIENTS

Background:The goal of treat to target strategy (T2T) in psoriatic arthritis (PsA) is attaining remission or minimal disease activity (MDA). The benefits of T2T have been seen recently [1]. But prognostic factors for MDA achievement in PsA patients (pts) at an early-stage hasn’t been studied yet.Objectives:to determine the prognostic factors associated with MDA achievement within 12 months (mos.) of treatment according to T2T strategy in early PsA pts.Methods:77 pts (M/F=36/41) with early active PsA fulfilling the CASPAR criteria were included. Mean age 36.9±10.45 years (yrs.), PsA duration 11.1±10.0 mos., Psoriasis (PsO) duration 82.8±92.1 mos. At baseline (BL) and at 12 mos. of therapy PsA activity by tender joint count (TJC)/68, swelling joint count (SJC)/66, Pain (VAS), Patient global assessment disease activity (PtGA, VAS), CRP mg/l, dactylitis, enthesitis by LEI and plantar fascia, BSA (%), HAQ and fatigue by FACIT (Functional Assessment of Chronic Illness Therapy) Fatigue Scale (Version 4) were evaluated. A score FACIT <30 indicates severe fatigue and > 30 – less fatigue. All pts was given therapy with Methotrexate (MTX) s/c. After 3-9 mos. of ineffectiveness of MTX treatment 29 pts were given biologic DMARDs. By 12 mos. of therapy, the proportion of pts who had reached MDA (5/7) were calculated. Pts were split into 2 groups: MDA + (n=45) and MDA - (n=32). The one-factor model of logistic regression was used to identify a group of features that are associated with MDA achievement. M±SD, Me [Q25; Q75], Min-Max, %, t-test, Pierson-χ2, Manna-Whitney tests, ORs with 95% CI were performed. All p<0.05, were considered to indicate statistical significance.Results:Comparative analysis in both groups and one-factor model of logistic regression showed the following features at BL were associated with MDA achievement: TJC/SJC < 3 (p<0.001), PGA ≤ 20 mm (p<0.001), Pain (VAS) ≤ 15 mm (p<0.001), CRP ≤ 5 mg/l (p< 0.03), HAQ ≤ 0.5 (p< 0.001), FACIT > 30 (p< 0.021), absent of entesitis (p< 0.003), dactylitis (p< 0.029) and nail damage (p< 0.012). Early PsA pts with combination of these features at first visit have more chance to achieve MDA within 12 mos in comparison to PsA pts without them, OR=9.684 [CI 95% 4.6-20.4]. (Figure 1).Conclusion:It is a combination of features at first visit to clinic – TJC, SJC < 3, PGA ≤ 20 mm, pain ≤ 15 mm, CRP ≤ 5 mg/l, HAQ ≤ 0.5, FACIT > 30 points, absent of entesitis, dactylitis and nail PsO - that constitutes a clinical prognostic factors for MDA achievement within 12 mos of T2T strategy in early PsA pts.References:[1]Coates LC, et al. Lancet. 2015 Dec 19;386(10012):2489-98. doi: 10.1016/S0140-6736(15)00347-5Figure 1.The prognostic factors associated with achievement MDA within 12 months in early PsA ptsDisclosure of Interests:None declared