OBJECTIVE: The optimal duration of immunosuppressive (IS) treatment for lupus nephritis (LN) remains uncertain. We assessed the prevalence and predictors of IS tapering and discontinuation (D/C) in LN patients.
METHODS: Data from 137 inception cohort LN patients were analyzed. We examined determinants of flares during tapering and after IS D/C, D/C achievement and time to D/C, and adverse long-term outcomes applying logistic and linear regression models.
RESULTS: IS tapering was attempted in 111 (81%) patients, and D/C was achieved in 67.5%. Longer time to achieve complete renal response (CR) (OR : 1.07, p= 0.046) and higher SLEDAI-2K at tapering initiation (OR : 2.57, p= 0.008) were correlated with higher risk of renal flares during tapering. Persistent hydroxychloroquine use (≥2/3 of follow-up) (OR : 0.28, p= 0.08) and lower SLEDAI-2K 12 months before IS D/C (OR : 1.70, p= 0.013) decreased the risk of post-D/C flares. Adverse outcomes (>30% eGFR decline, chronic kidney disease, end-stage renal disease, death) at the end of follow-up (median124 months) were more frequent in patients with flares during IS tapering (53% vs 16%, p< 0.0038) but did not differ between IS D/C achievers and non-achievers. In proliferative LN, differences mirrored those in entire cohort, except for time to D/C, which occurred 20 months earlier in membranous vs proliferative LN (β-coef=-19.8, p= 0.014).
CONCLUSIONS: Earlier CR achievement and lower SLEDAI-2K at tapering initiation prevent flares during IS tapering, while persistent hydroxychloroquine use and lower SLEDAI-2K 12 months before IS D/C prevent post-D/C flares. Flares during tapering increase the risk of unfavorable long-term outcomes. Earlier IS D/C is feasible in membranous LN.

OBJECTIVE: To quantify the variation, triggers and impact on quality of life of symptom flares in women with chronic pelvic pain (CPP).
METHODS: Cross-sectional questionnaire within the Translational Research in Pelvic Pain clinical cohort study.
METHODS: Women with CPP, with subgroups of women with endometriosis (EAP), interstitial cystitis/bladder pain syndrome (BPS), comorbid endometriosis and interstitial cystitis/bladder pain syndrome (EABP), and those with pelvic pain without endometriosis or interstitial cystitis/bladder pain syndrome (PP).
METHODS: A total of 100 participants.
METHODS: Descriptive and comparative analysis from flares questionnaire.
METHODS: The prevalence, characteristics and triggers of short, medium and long symptom flares in CPP.
RESULTS: We received 100 responses of 104 questionnaires sent. Seventy-six per cent of women with CPP have ever experienced symptom flares of at least one length (short, medium and/or long). Flares are associated with painful and non-painful symptoms. There is large variation for the frequency, duration, symptoms and triggers for flares. Over 60% of participants reported flares as stopping them from doing things they would usually do, >80% reported thinking about symptoms of flares and >80% reported flares being bothersome.
CONCLUSIONS: Flares are prevalent and clinically very important in CPP. More research is needed to elucidate the mechanisms and characteristics underlying flares. Clinical practice should include an enquiry into flares with the aim of finding strategies to lessen their burden.

UNASSIGNED: Exploring (1) pre-exercise and acute movement-evoked pain (AMEP) during an outdoor walking program in individuals with knee osteoarthritis (OA); and (2) comparing baseline physical performance and AMEP flares initiated by walking between participants with either a higher or lower attendance rate.
UNASSIGNED: Individuals with knee OA were prescribed a 24-week walking program, including one unsupervised walk and two supervised walk classes per week. Participants self-reported knee pain on a numerical rating scale (NRS; 0-10) before and after each supervised class. Mixed-effects models were used to investigate trajectories over time for pre-exercise pain and AMEP change (post-minus pre-exercise pain; positive value indicates flare-up). Baseline physical performance (6 tests) and AMEP flares were compared between participants with higher (attending ≥70% of supervised classes) and lower attendance rates.
UNASSIGNED: Of 24 participants commencing the program, 7 (29%) withdrew. Over 24 weeks, pre-exercise pain improved by 1.20 NRS (95% CI -1.41 to -0.99), with estimated largest per class improvements during the first 8 weeks (-0.05 (-0.06 to -0.03) and plateauing around 20-weeks. The AMEP was estimated to improve by 0.19 NRS (95% CI -0.38 to -0.004) over 24-weeks, with improvements plateauing around 12-weeks. Participants with lower attendance (n ​= ​11) scored poorer on all physical performance tests and experienced a slight increase in AMEP during the first two weeks of the program.
UNASSIGNED: Participants improved in pre-exercise pain and AMEP in the first 20 and 12 weeks, respectively. Despite supervision, physical performance and AMEP flares may have contributed to lower attendance.
UNASSIGNED: 12618001097235.

UNASSIGNED: Hidradenitis suppurativa (HS) is a chronic skin condition with recurrent, debilitating flares. Although the majority of patients with HS endorse flares, there is a lack of research regarding HS experts\' flare management practices and perspectives.
UNASSIGNED: An anonymous online survey was distributed through an HS expert listserv. Board-certified dermatologists who saw 1 or more HS patient(s) per month were eligible for participation.
UNASSIGNED: A total of 35 responses were collected; 97.1% self-identified as HS experts. Therapies used for HS flares by more than two-thirds of the respondents included systemic antibiotics (100%), nonprescription pain relievers (91.4%), intralesional triamcinolone injections (91.4%), prescription pain relievers (71.4%), oral corticosteroids (68.6%), and warm compresses (68.6%). The top 3 dermatologist-reported barriers that patients face in accessing care during flares include lack of clinic appointment availability (88.6%), distance that patients have to travel to reach clinic (85.7%), and lack of transportation for patients (62.9%).
UNASSIGNED: Overall, this study highlights variations in the ways that HS experts manage flares. Many of the treatment modalities used by the majority of respondents are not part of the official North American guidelines. Further prospective studies and expert consensus guidelines are needed to standardize the approach to flare management.

BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. PsA disease involves flares, which are associated with increased joint inflammation and tissue remodeling. There is a need for identifying biomarkers related to PsA disease activity and flares to improve the management of PsA patients and decrease flares. The tissue turnover imbalance that occurs during the inflammatory and fibro-proliferative processes during flares leads to an increased degradation and/or reorganization of the extracellular matrix (ECM), where increased proteolysis plays a key role. Hence, protease-mediated fragments of inflammatory and tissue-remodeling components could be used as markers reflecting flares in PsA patients.
METHODS: A broad panel of protease-mediated biomarkers reflecting inflammation and tissue remodeling was measured in serum and synovial fluid (SF) obtained from PsA patients experiencing flares (acutely swollen joint[s], PsA-flare). In serum, biomarker levels assessed in PsA-flare patients were compared to controls and in early-diagnosed PsA patients not experiencing flares (referred to as PsA without flare). Furthermore, the biomarker levels assessed in SF from PsA-flare patients were compared to the levels in SF of osteoarthritis (OA) patients.
RESULTS: In serum, levels of the PRO-C3 and C3M, reflecting formation and degradation of the interstitial matrix, were found significantly elevated in PsA-flare compared to controls and PsA without flare. The remodeling marker of the basement membrane, PRO-C4, was significantly elevated in PsA-flare compared to PsA without flare. The inflammation and immune cell activity related markers, CRPM, VICM, and CPa9-HNE were significantly elevated in PsA-flare patients compared to controls and PsA without flare. In addition, VICM (AUC = 0.71), CPa9-HNE (AUC = 0.89), CRPM (AUC = 0.76), and PRO-C3 (AUC = 0.86) showed good discriminatory performance for separating PsA-flare from PsA without flare. In SF, the macrophage activity marker, VICM, was significantly elevated whereas the type II collagen formation marker, PRO-C2, was significantly reduced in the PsA-flare compared to OA. The combination of five serum markers reflecting type III and IV collagen degradation (C3M and C4M, respectively), type III and VI collagen formation (PRO-C3 and PRO-C6, respectively), and neutrophil activity (CPa9-HNE) showed an excellent discriminatory performance (AUC = 0.98) for separating PsA-flare from PsA without flares.
CONCLUSIONS: The serum biomarker panel of C3M, C4M, PRO-C3, PRO-C6, and CPa9-HNE reflecting synovitis, enthesitis, and neutrophil activity may serve as novel tool for quantitatively monitoring flares in PsA patients.

BACKGROUND: The ability to predict rheumatoid arthritis (RA) flares between clinic visits based on real-time, longitudinal patient-generated data could potentially allow for timely interventions to avoid disease worsening.
OBJECTIVE: This exploratory study aims to investigate the feasibility of using machine learning methods to classify self-reported RA flares based on a small data set of daily symptom data collected on a smartphone app.
METHODS: Daily symptoms and weekly flares reported on the Remote Monitoring of Rheumatoid Arthritis (REMORA) smartphone app from 20 patients with RA over 3 months were used. Predictors were several summary features of the daily symptom scores (eg, pain and fatigue) collected in the week leading up to the flare question. We fitted 3 binary classifiers: logistic regression with and without elastic net regularization, a random forest, and naive Bayes. Performance was evaluated according to the area under the curve (AUC) of the receiver operating characteristic curve. For the best-performing model, we considered sensitivity and specificity for different thresholds in order to illustrate different ways in which the predictive model could behave in a clinical setting.
RESULTS: The data comprised an average of 60.6 daily reports and 10.5 weekly reports per participant. Participants reported a median of 2 (IQR 0.75-4.25) flares each over a median follow-up time of 81 (IQR 79-82) days. AUCs were broadly similar between models, but logistic regression with elastic net regularization had the highest AUC of 0.82. At a cutoff requiring specificity to be 0.80, the corresponding sensitivity to detect flares was 0.60 for this model. The positive predictive value (PPV) in this population was 53%, and the negative predictive value (NPV) was 85%. Given the prevalence of flares, the best PPV achieved meant only around 2 of every 3 positive predictions were correct (PPV 0.65). By prioritizing a higher NPV, the model correctly predicted over 9 in every 10 non-flare weeks, but the accuracy of predicted flares fell to only 1 in 2 being correct (NPV and PPV of 0.92 and 0.51, respectively).
CONCLUSIONS: Predicting self-reported flares based on daily symptom scorings in the preceding week using machine learning methods was feasible. The observed predictive accuracy might improve as we obtain more data, and these exploratory results need to be validated in an external cohort. In the future, analysis of frequently collected patient-generated data may allow us to predict flares before they unfold, opening opportunities for just-in-time adaptative interventions. Depending on the nature and implication of an intervention, different cutoff values for an intervention decision need to be considered, as well as the level of predictive certainty required.

UNASSIGNED: Clinical decision support systems (CDSSs) embedded in electronic medical records (EMRs), also called electronic health records, have the potential to improve the adoption of clinical guidelines. The University of Alberta Inflammatory Bowel Disease (IBD) Group developed a CDSS for patients with IBD who might be experiencing disease flare and deployed it within a clinical information system in 2 continuous time periods.
UNASSIGNED: This study aims to evaluate the impact of the IBD CDSS on the adherence of health care providers (ie, physicians and nurses) to institutionally agreed clinical management protocols.
UNASSIGNED: A 2-period interrupted time series (ITS) design, comparing adherence to a clinical flare management protocol during outpatient visits before and after the CDSS implementation, was used. Each interruption was initiated with user training and a memo with instructions for use. A group of 7 physicians, 1 nurse practitioner, and 4 nurses were invited to use the CDSS. In total, 31,726 flare encounters were extracted from the clinical information system database, and 9217 of them were manually screened for inclusion. Each data point in the ITS analysis corresponded to 1 month of individual patient encounters, with a total of 18 months of data (9 before and 9 after interruption) for each period. The study was designed in accordance with the Statement on Reporting of Evaluation Studies in Health Informatics (STARE-HI) guidelines for health informatics evaluations.
UNASSIGNED: Following manual screening, 623 flare encounters were confirmed and designated for ITS analysis. The CDSS was activated in 198 of 623 encounters, most commonly in cases where the primary visit reason was a suspected IBD flare. In Implementation Period 1, before-and-after analysis demonstrates an increase in documentation of clinical scores from 3.5% to 24.1% (P<.001), with a statistically significant level change in ITS analysis (P=.03). In Implementation Period 2, the before-and-after analysis showed further increases in the ordering of acute disease flare lab tests (47.6% to 65.8%; P<.001), including the biomarker fecal calprotectin (27.9% to 37.3%; P=.03) and stool culture testing (54.6% to 66.9%; P=.005); the latter is a test used to distinguish a flare from an infectious disease. There were no significant slope or level changes in ITS analyses in Implementation Period 2. The overall provider adoption rate was moderate at approximately 25%, with greater adoption by nurse providers (used in 30.5% of flare encounters) compared to physicians (used in 6.7% of flare encounters).
UNASSIGNED: This is one of the first studies to investigate the implementation of a CDSS for IBD, designed with a leading EMR software (Epic Systems), providing initial evidence of an improvement over routine care. Several areas for future research were identified, notably the effect of CDSSs on outcomes and how to design a CDSS with greater utility for physicians. CDSSs for IBD should also be evaluated on a larger scale; this can be facilitated by regional and national centralized EMR systems.

OBJECTIVE: To evaluate whether ultrasound findings of monosodium urate (MSU) crystal deposition predict frequent gout flares in index joints over 12 months.
METHODS: This single-center study enrolled people with at least one gout flare involving the MTP1, ankle or knee joint. The most painful or most frequently joint was identified as index joint for analysis. All participants were started on urate-lowering therapy and had an ultrasound scan of the index joints at the baseline visit. OMERACT scores (for tophus, double contour sign and aggregates) were used to analyze whether ultrasound scores predicted frequent (≥2) gout flares in the index joint over 12 months.
RESULTS: Frequent flares were significantly higher in those with ultrasound findings in all index joints (MTP1: tophus: 85.0% vs 46.0%, P < 0.001, aggregates: 78.8% vs 59.0%, P < 0.01; ankle: tophus: 54.6% vs 20.8%, P < 0.001; aggregates: 60.0% vs 35.9%, P < 0.05; knee: tophus: 68.4% vs 28.6%, P < 0.05). For the MTP1, for each 1-point increase in tophus score, the odds of frequent gout flares increased by 5.19 [(95%CI: 1.26-21.41), 7.91 [(95%CI: 2.23-28.14), and 13.79 [(95%CI: 3.79-50.20)] fold respectively. For the ankle, a tophus score of 3 markedly improved the prediction of the frequent flares [OR= 9.24 (95%CI=2.85-29.91)]. Semi-quantitative sum scores were associated with frequent flares with an OR (95%CI) of 13.66 (3.44-54.18), P < 0.001 at the MTP1, 7.05 (1.98-25.12), P < 0.001 at the ankle.
CONCLUSIONS: Ultrasound features of MSU crystal deposition at the MTP1 and knee predict subsequent risk of frequent gout flares in the same joints following initiation of urate-lowering therapy, with the highest risk in those with high tophus scores.

Generalised pustular psoriasis(GPP) is a rare, potentially life-threatening variant of psoriasis with acute onset, widely spread pustular lesions on an inflamed base associated with a systemic inflammatory state. In the setting of the current COVID-19 pandemic, flares in pustular psoriasis have been reported, however these flares leading to mortality in SARS-CoV-2 infected patients is hitherto unreported. We present two cases of GPP flare following SARS-CoV-2 infection with fatal outcome. A 20 year old male, known case of GPP since 5 years presented with an exacerbation of his existing disease for 2 months. He had received methotrexate, cyclosporine, acitretin, apremilast, infliximab and secukinumab in the past. He was admitted and started on inj. methotrexate (subcutaneous) and cap. acitretin. During admission, he developed COVID-19 associated severe acute respiratory distress syndrome(ARDS). Despite timely intervention with life-saving measures, the patient could not be saved. The second case was a 52-year-old female, a case of GPP on treatment for the last 10 years, being maintained on cap. acitretin and cyclosporine. She also developed ARDS due to COVID infection. Despite being on acitretin for GPP and the appropriate management of severe COVID infection, her condition worsened and she expired within one day of admission. Both of our patients were not vaccinated against COVID-19. Awareness of potential risk of mortality in patients of GPP getting co-infected by COVID-19 is thus essential for dermatologists.

Prevention of asthma exacerbations and reduction of systemic corticosteroid burden remain unmet needs in asthma. US asthma guidelines recommend concomitant short-acting β2-agonist (SABA) and inhaled corticosteroid (ICS) as an alternative reliever at step 2. The Food and Drug Administration approved a pressurized metered-dose inhaler containing albuterol and budesonide for as-needed treatment or prevention of bronchoconstriction and for reducing exacerbation risk in patients with asthma aged ≥18 years. This combination is approved for use as a reliever with or without maintenance therapy, but it is not indicated for maintenance therapy (or for single maintenance and reliever therapy). Intervening with as-needed SABA-ICS during the window of opportunity to reduce inflammation during loss of asthma control can reduce exacerbation risk, by exerting both genomic and nongenomic anti-inflammatory effects. We propose that the use of albuterol-budesonide rather than albuterol as a reliever to manage episodic symptoms driven by acute bronchoconstriction and airway inflammation can improve outcomes. This combination approach, shown to decrease asthma exacerbations and oral corticosteroid burden in patients with moderate-to-severe asthma, represents a paradigm shift for asthma treatment in the United States. Further safety and efficacy studies should provide evidence that this type of reliever should be standard of care.