Nebulised interferon beta-1a (SNG001) in the treatment of viral exacerbations of COPD.

BACKGROUND: Respiratory viral infections are major drivers of chronic obstructive pulmonary disease (COPD) exacerbations. Interferon-ß is naturally produced in response to viral infection, limiting replication. This exploratory study aimed to demonstrate proof-of-mechanism, and evaluate the efficacy and safety of inhaled recombinant interferon-ß1a (SNG001) in COPD. Part 1 assessed the effects of SNG001 on induced sputum antiviral interferon-stimulated gene expression, sputum differential cell count, and respiratory function. Part 2 compared SNG001 and placebo on clinical efficacy, sputum and serum biomarkers, and viral clearance. METHODS: In Part 1, patients (N = 13) with stable COPD were randomised 4:1 to SNG001 or placebo once-daily for three days. In Part 2, patients (N = 109) with worsening symptoms and a positive respiratory viral test were randomised 1:1 to SNG001 or placebo once-daily for 14 days in two Groups: A (no moderate exacerbation); B (moderate COPD exacerbation [i.e., acute worsening of respiratory symptoms treated with antibiotics and/or oral corticosteroids]). RESULTS: In Part 1, SNG001 upregulated sputum interferon gene expression. In Part 2, there were minimal SNG001-placebo differences in the efficacy endpoints; however, whereas gene expression was initially upregulated by viral infection, then declined on placebo, levels were maintained with SNG001. Furthermore, the proportion of patients with detectable rhinovirus (the most common virus) on Day 7 was lower with SNG001. In Group B, serum C-reactive protein and the proportion of patients with purulent sputum increased with placebo (suggesting bacterial infection), but not with SNG001. The overall adverse event incidence was similar with both treatments. CONCLUSIONS: Overall, SNG001 was well-tolerated in patients with COPD, and upregulated lung antiviral defences to accelerate viral clearance. These findings warrant further investigation in a larger study. TRIAL REGISTRATION: EU clinical trials register (2017-003679-75), 6 October 2017.

Patient-reported daily functioning after SARS-CoV-2 vaccinations in autoimmune neuromuscular diseases.

BACKGROUND AND PURPOSE: There are concerns for safety regarding SARS-CoV-2 vaccines for patients with autoimmune neuromuscular disease. We compared daily functioning using disease-specific patient-reported outcome measures (PROMs) before and after SARS-CoV-2 vaccinations. METHODS: In this substudy of a prospective observational cohort study (Target-to-B!), patients with myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and idiopathic inflammatory myopathy (IIM) vaccinated against SARS-CoV-2 were included. Surveys of daily functioning (Myasthenia Gravis Activities of Daily Living, Inflammatory Rasch-Built Overall Disability Scale, Multifocal Motor Neuropathy Rasch-Built Overall Disability Scale, and Health Assessment Questionnaire-Disability Index) were sent before first vaccination and every 60 days thereafter for up to 12 months. Regression models were constructed to assess differences in PROM scores related to vaccination, compared to scores unrelated to vaccination. We also assessed the proportion of patients with deterioration of at least the minimal clinically important difference (MCID) between before first vaccination and 60 days thereafter. RESULTS: We included 325 patients (median age = 59 years, interquartile range = 47-67, 156 [48%] female sex), of whom 137 (42%) had MG, 79 (24%) had CIDP, 43 (13%) had MMN, and 66 (20%) had IIM. PROM scores related to vaccination did not differ from scores unrelated to vaccination. In paired PROMs, MCID for deterioration was observed in three of 49 (6%) MG patients, of whom none reported a treatment change. In CIDP, MCID for deterioration was observed in eight of 29 patients (28%), of whom two of eight (25%) reported a treatment change. CONCLUSIONS: SARS-CoV-2 vaccination had no effect on daily functioning in patients with autoimmune neuromuscular diseases, confirming its safety in these patients.

Pediatric asthma exacerbation and COVID-19 pandemic: Impacts, challenges, and future considerations.

OBJECTIVE: Asthma, a common disease among children and adolescents, poses a great health risk when ignored; therefore, a thorough follow-up to prevent exacerbations is emphasized. The aim of the present study is to investigate asthma exacerbation in children during the Coronavirus disease 2019 (COVID-19) era. DATA SOURCES: This narrative review has been done by searching the PubMed and Embase databases using Asthma, COVID-19, Pandemic, and Symptom flare up as keywords. STUDY SELECTIONS: Studies related to asthma exacerbation in COVID-19 pandemic were included. RESULTS: Based on studies, controlled or mild to moderate asthma has not been considered a risk factor for COVID-19 severity and has not affected hospitalization, intensive care unit (ICU) admission, and mortality. Surprisingly, emergent and non-emergent visits and asthmatic attacks decreased during the pandemic. The three main reasons for decreased incidence and exacerbation of asthma episodes in the COVID-19 era included reduced exposure to environmental allergens, increasing the acceptance of treatment by pediatrics and caregivers, and decreased risk of other respiratory viral infections. Based on the available studies, COVID-19 vaccination had no serious side effects, except in cases of uncontrolled severe asthma, and can be injected in these children. Also, there was no conclusive evidence of asthma exacerbation after the injection of COVID-19 vaccines. CONCLUSION: Further studies are recommended to follow the pattern of asthma in the post-pandemic situation and to become prepared for similar future conditions.

Duration of α-1 adrenergic antagonist administration after low-dose-rate brachytherapy for prostate cancer.

BACKGROUND: Urinary dysfunction is an adverse event of low-dose-rate brachytherapy (LDR-BT) in patients with prostate cancer. We aimed to examine the time to α-1 adrenergic antagonist withdrawal after LDR-BT initiation. METHODS: We retrospectively evaluated 1663 patients who underwent LDR-BT at our hospital during 2004-2022. RESULTS: Overall, 1485/1663 (89.3%) patients were able to stop using α-1 adrenergic antagonists, 1111 (66.8%) of them within 1 year of LDR-BT. Risk factors for prolonged time to withdrawal were age ≥70 years, taking agents for lower urinary tract symptoms prior to LDR-BT, an International Prostate Symptom Score ≥8, an Overactive Bladder Symptom Score ≥3 and a residual urine volume ≥20 ml. Of the patients who were able to stop taking α-1 adrenergic antagonists, 357/1485 (24.0%) required resumption, 218 (61.1%) of whom did so between 1 and 3 years after LDR-BT. This period matched the period of transient worsening of the urinary symptom score. Finally, multivariable analysis identified supplemental external beam radiotherapy and an Overactive Bladder Symptom Score ≥3 as independent risk factors for α-1 adrenergic antagonist resumption. CONCLUSIONS: Withdrawal of α-1 adrenergic antagonists was possible in 66.8% of patients within 1 year of LDR-BT. Our results suggest that patients who are older or have pre-treatment LUTS may have prolonged deterioration of urinary dysfunction after treatment. Resumption of α-1 adrenergic antagonists 1-3 years after treatment may be associated with urinary symptom flares, and close attention is necessary for patients with supplemental external beam radiotherapy and a high pretreatment Overactive Bladder Symptom Score.

Pulse versus non-pulse corticosteroid therapy in patients with acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Corticosteroids are commonly used for the treatment of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF); however, the optimal initial dose of corticosteroids remains uncertain due to a lack of sufficient evidence. We evaluated whether the administration of a pulse dose of corticosteroids resulted in improved survival outcomes compared with conventional non-pulse dose of corticosteroids. METHODS: We retrospectively analysed 238 patients with AE-IPF treated with corticosteroids at a tertiary referral hospital between January 2013 and December 2021. Based on whether a pulse dose of corticosteroids (methylprednisolone of ≥250 mg/day or equivalent) was administered within 7 days of hospitalization for AE-IPF, the patients were divided into the pulse and non-pulse regimen groups. The survival outcomes were compared between the two groups using multivariable regression and propensity score-matched analyses. RESULTS: Among the 238 patients, 59 patients received pulse dose of corticosteroids, whereas 179 patients received conventional non-pulse dose of corticosteroids. After adjusting for the confounding factors related to the baseline clinical and radiographic severity, compared with the conventional non-pulse regimen, the pulse regimen of corticosteroids did not reduce the risk of mortality at the 3-month (aHR 0.84, 95% CI 0.45-1.38) or 12-month (aHR 0.96, 95% CI 0.60-1.25) follow-ups. Propensity score-matched analysis revealed similar results. CONCLUSION: The survival outcomes of patients with AE-IPF who received a pulse dose of corticosteroids did not differ from those of patients who received conventional non-pulse dose of corticosteroids. Further prospective studies are required to establish the optimal initial dose of corticosteroids for the treatment of AE-IPF.

Differential Diagnosis of Suspected Chronic Obstructive Pulmonary Disease Exacerbations in the Acute Care Setting: Best Practice.

Patients with chronic obstructive pulmonary disease (COPD) may suffer from acute episodes of worsening dyspnea, often associated with increased cough, sputum, and/or sputum purulence. These exacerbations of COPD (ECOPDs) impact health status, accelerate lung function decline, and increase the risk of hospitalization. Importantly, close to 20% of patients are readmitted within 30 days after hospital discharge, with great cost to the person and society. Approximately 25% and 65% of patients hospitalized for an ECOPD die within 1 and 5 years, respectively. Patients with COPD are usually older and frequently have concomitant chronic diseases, including heart failure, coronary artery disease, arrhythmias, interstitial lung diseases, bronchiectasis, asthma, anxiety, and depression, and are also at increased risk of developing pneumonia, pulmonary embolism, and pneumothorax. All of these morbidities not only increase the risk of subsequent ECOPDs but can also mimic or aggravate them. Importantly, close to 70% of readmissions after an ECOPD hospitalization result from decompensation of other morbidities. These observations suggest that in patients with COPD with worsening dyspnea but without the other classic characteristics of ECOPD, a careful search for these morbidities can help detect them and allow appropriate treatment. For most morbidities, a thorough clinical evaluation supplemented by appropriate clinical investigations can guide the healthcare provider to make a precise diagnosis. This perspective integrates the currently dispersed information available and provides a practical approach to patients with COPD complaining of worsening respiratory symptoms, particularly dyspnea. A systematic approach should help improve outcomes and the personal and societal cost of ECOPDs.

Effects of indoor environments and outdoor air pollutants in residential areas on acute exacerbation in patients with severe asthma.

This study aimed to determine the effects of indoor environment (IE) and outdoor air pollutants (OAPs) in residential areas on acute exacerbation (AE) in patients with severe asthma. A total of 115 participants were recruited. To characterize IE, we used structured questionnaires and estimated OAP concentrations using a land-use regression model. Participants who were exposed to passive smoking and lived in houses where the kitchen and living room were not separated showed a significantly higher rate of AE (p = 0.014 and 0.0016, respectively). The mean concentration of PM2.5 in residential areas during the last 3 years was significantly higher in participants with AE than that in those without AE (19.8 ± 3.1 vs. 21.0 ± 2.5 µg/m3, p = 0.033). Moreover, the serum level of 8-hydroxy-2'-deoxyguanosine significantly increased in participants with AE compared to those without AE (56.9 ± 30.0 vs. 94.7 ± 44.5 ng/mL, p = 0.0047) suggesting enhanced oxidative stress in those with AE.

Associations Between Urological Chronic Pelvic Pain Syndrome Symptom Flares, Illness Impact, and Health Care Seeking Activity: Findings From the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study.

PURPOSE: Most studies on interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome use typical or average levels of pelvic pain or urological symptom intensity as their outcome, as both are associated with reduced quality of life. Symptom exacerbations or "flares" have also been found to be associated with reduced quality of life, but no studies, to our knowledge, have investigated whether these associations are independent of typical pelvic pain levels and thus might be useful additional outcome measures (or stated differently, whether reducing flare frequency even without reducing mean pain intensity may be important to patients). MATERIALS AND METHODS: We used screening visit and weekly run-in period data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study to investigate associations between flare frequency and multiple measures of illness impact and health care seeking activity, independent of typical nonflare and overall pelvic pain levels. RESULTS: Among the 613 eligible participants, greater flare frequency was associated with worse condition-specific illness impact (standardized ß coefficients=0.11-0.68, P trends < .0001) and health care seeking activity (odds ratios=1.52-3.94, P trends .0039 to < .0001) in analyses adjusted for typical nonflare and overall pelvic pain levels. Experiencing ≥1/d was also independently associated with worse general illness impact (standardized ß coefficients=0.11-0.25). CONCLUSIONS: Our findings suggest that flare frequency and possibly other flare characteristics may be worth considering as additional outcome measures in urological chronic pelvic pain syndrome research to support the development of new preventive and therapeutic flare strategies.

Clustering of gout-related comorbidities and their relationship with gout flares: a data-driven cluster analysis of eight comorbidities.

OBJECTIVES: To study the aggregation of multiple comorbidities in people with gout and explore differences in prognosis of gout flares among different subgroups. METHODS: Hierarchical clustering was performed to identify homogeneous subgroups among 2639 people with gout using eight comorbidities. A one-year follow-up of acute gout flares in 463 of these people was conducted; the incidence and the timing of gout flares in each cluster were assessed to explore prognosis of gout flares. Binary logistic regression was applied to assess factors associated with gout flares. RESULTS: In baseline study, we identified five subgroups (C1-C5). C1 (n = 671, 25%) was characterized by isolated gout with few comorbidities. C2 (n = 258, 10%) were all obese. Almost all people in C3 (n = 335, 13%) had diabetes (99.7%). All people in C4 (n = 938, 36%) had dyslipidemia. C5 (n = 437, 17%) had the highest proportion of cardiovascular disease (CVD, 53%), chronic kidney disease (CKD, 56%), and cancer (7%). In follow-up study, C5 had the highest incidence (71.9%) and earliest onset (median 3 months) of gout flares. C2 had the lowest incidence (52.1%) and the latest onset (median 10 months) of gout flares. The highest relative risk for gout recurrent was seen for C5 (OR = 2.09). Other factors associated with the risk of gout flares were age at diagnosis of gout, duration of gout, presence of tophi, and smoking ≥ 20 cigarettes/day. CONCLUSIONS: We clustered people with gout into five groups with varying comorbidities. People with CVD, CKD, and cancer had the highest risk of gout flares and should receive comprehensive care.

Evaluation of Exacerbation and Symptom-Free Time in Patients with COPD.

In clinical practice, clinicians mainly focus on Chronic Obstructive Pulmonary Disease (COPD) exacerbations and symptoms, while patients may prefer to evaluate periods free of COPD exacerbations and deteriorated symptoms. The latter would suit the positive health approach that centralizes people and their beliefs. We aimed to identify patient characteristics and health outcomes relating to: 1) COPD exacerbation-free days; 2) days with no more symptoms than usual; and 3) combined COPD exacerbation and comorbid flare-up-free days (i.e. chronic heart failure, anxiety, depression flare-ups) using negative binomial regression analyzes. Data were obtained from two self-management intervention trials including COPD patients with and without comorbidities. 313 patients (mean age 66.0 years, 63.6% male, 68.7% comorbidity) were included. Better baseline chronic respiratory questionnaire (CRQ) fatigue (incidence rate ratio (IRR) = 1.03 (95% CI 1.01-1.05), p = 0.02) and mastery scores (IRR = 1.03 (95% CI 1.00-1.06), p = 0.04) and fewer courses of antibiotics (IRR = 0.95 (95% CI 0.94-0.96), p < 0.01) were related to more COPD exacerbation-free days. Additionally, better baseline CRQ fatigue (IRR = 1.05 (95% CI 1.00-1.10), p = 0.04) and mastery scores (IRR = 1.06 (95% CI 1.00-1.12), p = 0.04), fewer courses of antibiotics (IRR = 0.94 (95% CI 0.91-0.96), p < 0.01), and improved CRQ dyspnea scores over 12 months of follow-up (IRR = 1.07 (95% CI 1.01-1.12), p < 0.01) were correlated to more days free of deteriorated symptoms. Less baseline dyspnea (modified Medical Research Council score) (IRR = 0.95 (95% CI 0.92-0.98), p < 0.01) and fewer courses of antibiotics (IRR = 0.94 (95% CI 0.93-0.95), p < 0.01) were associated with more combined COPD exacerbation and comorbid flare-up-free days. Healthcare professionals should be aware that less fatigue and better mastering of COPD relate to more exacerbation and symptom-free time in COPD patients.

Systemic glucocorticoid use and the occurrence of flares in psoriatic arthritis and psoriasis: a systematic review.

OBJECTIVES: The use of systemic glucocorticoids (SGCs) is traditionally discouraged in the treatment of PsA and psoriasis due to the risk of psoriatic flares. However, despite this recommendation, SGCs are frequently prescribed for these patients. In this study we reappraise the old paradigm that SGCs are contra-indicated in the treatment of PsA and psoriasis. METHODS: A systematic search of MEDLINE, EMBASE and the Cochrane Library databases was performed in November 2019 to identify articles on any SGC use compared with no use in the PsA and psoriasis population. Topical glucocorticoid treatment was excluded. Our two primary outcomes focused on the prescribing characteristics and the occurrence of any type of flare. RESULTS: Our search yielded 4922 articles, and of these 21 full-text articles were eligible for inclusion. There were 11 retro- and prospective cohorts involving a total of 4,171,307 patients. Of these, 6727 (37.82%) of the patients with PsA and 1 460 793 (35.17%) of the patients with psoriasis were treated with any type of SGC. Ten observational/interventional studies did not report an increased risk or occurrence of psoriatic flares related to SGC use. CONCLUSION: Our results indicate that SGCs are frequently prescribed for PsA and psoriasis patients. The occurrence of psoriatic flares appears to be low upon SGC exposure. In patients with a clear indication for SGCs, e.g. in need of rapid anti-inflammatory therapy or bridging of therapies, the use of SGCs should be considered in view of the low risk of skin flaring. It remains of importance to weigh risks for short- and long-term SGC-related side effects in clinical decision making.

Evaluation of flare rate and reduction strategies for bDMARDs in juvenile idiopathic arthritis: real world data from a single-centre cohort.

This study aimed to determine the flare rate (FR) in a cohort of Juvenile Idiopathic Arthritis (JIA) patients with tapered or abruptly discontinued biologic disease-modifying anti-rheumatic drugs (bDMARDs) and to identify predictors of flare. This retrospective observational study included 191 bDMARD dose-reduction events in patients with JIA followed-up at a referral hospital during the period 2000-2019. FR was analysed according to reduction strategies. To identify predictors of flare, Kaplan-Meier and Cox-regression models were plotted at 6 months (6 m), 12 months (12 m) and 24 months (24 m) following tapering (TP) or withdrawal (WD). 165 episodes of TP and 71 episodes of WD were included; 45 episodes where treatment was withdrawn after TP were included in both strategies. FR after TP was 13.4% at 6 m and increased up to 26.6% at 12 m and 51.4% at 24 m. After WD, FR was higher, 52.1% of events had a flare at 6 m and 67.6% at 12 m. Previous TP did not increase time in remission after WD of bDMARDs in the Kaplan-Meier analysis. Factors associated with flares were identified after TP at 6 m: female sex, higher number of previous bDMARDs and longer time on bDMARD treatment were positively associated with flares. Polyarticular subtype and younger age at diagnosis were associated with flares at 12 and 24 m after TP. No factors were identified in multivariable analysis after WD. TP is a successful strategy to maintain remission with lower bDMARD doses. Previous TP of bDMARDs does not seem to increase time in remission after WD.

Does Pollen Trigger Urological Chronic Pelvic Pain Syndrome Flares? A Case-Crossover Analysis in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network.

PURPOSE: We sought to determine whether pollen triggers urological chronic pelvic pain syndrome flares. MATERIALS AND METHODS: We assessed flare status every 2 weeks for 1 year as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain case-crossover analysis of flare triggers (NCT01098279). Flare symptoms, flare start date and exposures in the 3 days before a flare were queried for the first 3 flares and at 3 randomly selected nonflare times. These data were linked to daily pollen count by date and the first 3 digits of participants' zip codes. Pollen count in the 3 days before and day of a flare, as well as pollen rises past established thresholds, were compared to nonflare values by conditional logistic regression. Poisson regression was used to estimate flare rates in the 3 weeks following pollen rises past established thresholds in the full longitudinal study. Analyses were performed in all participants and separately in those who reported allergies or respiratory tract disorders. RESULTS: Although no associations were observed for daily pollen count and flare onset, positive associations were observed for pollen count rises past medium or higher thresholds in participants with allergies or respiratory tract disorders in the case-crossover (OR 1.31, 95% CI 1.04-1.66) and full longitudinal (RR 1.23, 95% CI 1.03-1.46) samples. CONCLUSIONS: We found some evidence to suggest that rising pollen count may trigger flares of urological chronic pelvic pain syndrome. If confirmed in future studies, these findings may help to inform flare pathophysiology, prevention and treatment, and control over the unpredictability of flares.

Comparisons of Efficacy and Safety between Triple (Inhaled Corticosteroid/Long-Acting Muscarinic Antagonist/Long-Acting Beta-Agonist) Therapies in Chronic Obstructive Pulmonary Disease: Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND: Various combinations of inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA), and long-acting beta-agonist (LABA) have been used as triple therapy for stable chronic obstructive pulmonary disease (COPD). OBJECTIVE: Our study was conducted to answer whether there were significant differences among various combinations in efficacy, for reducing exacerbation or mortality, and in safety, for increasing cardiovascular events or pneumonia. METHOD: We searched parallel-group randomized controlled trials (RCTs) comparing ICS/LAMA/LABA with other inhaled drugs in patients with stable COPD for at least 12 weeks in PubMed, EMBASE, the Cochrane Library, and clinical trial registries from inception to December 31, 2019. We conducted a network meta-analysis with Bayesian statistics using a random-effects model with heterogeneous variance structure (PROSPERO, CRD42019126757). RESULTS: Nine different combinations of ICS/LAMA/LABA were identified in 21 RCTs containing 29,892 patients with moderate to very severe COPD. We could not find any significant evidence suggesting a better treatment for reducing total exacerbations or all-cause mortality among ICS/LAMA/LABA combinations. There were also no significant differences in moderate to severe exacerbation, COPD-related mortality, or cardiovascular disease-related mortality among ICS/LAMA/LABA combinations, and the risk of major adverse cardiovascular events was not different. A significantly lower risk of pneumonia was found in fluticasone propionate (FP)/glycopyrrolate/salmeterol (SAL) than FP/tiotropium/SAL {median odds ratio [OR] (95% credible interval [CrI]) = 0 [0-0.72]} and FP/umeclidinium/SAL {median OR (95% Crl) = 0 [0-0.97]}. CONCLUSION: There were no significant differences in clinical outcomes, including acute exacerbation and all-cause mortality among various ICS/LAMA/LABA combinations in patients with moderate to very severe COPD.

Long-term follow-up of 89 patients with giant cell arteritis: a retrospective observational study on disease characteristics, flares and organ damage.

The objective of the study is to investigate the clinical characteristics and long-term prognosis including flares and organ damage in patients with giant cell arteritis (GCA) from a tertiary referral centre and compare these features in different subgroups. In this retrospective observational study, patients with GCA who were followed up in our vasculitis clinic between 1998 and 2018 were evaluated by a predefined protocol. Patients with and without cranial symptoms were compared for clinical and laboratory features, flares and permanent damage findings. Vasculitis Damage Index and Large Vessel Vasculitis Index of Damage were used for damage assessment. Records of 89 patients (median follow-up time 46 months) were analysed; mean time to diagnosis after initial symptom was longer in patients with acute vision loss (11 ± 4 vs. 4.8 ± 1.1 months p = 0.002). EGG (n = 19) was younger (63 ± 2 vs. 69 ± 1 years old p = 0.01); had higher mean CRP (141.8 ± 107.3 vs. 76.6 ± 67.9 mg/dL p = 0.023) and ESR (120.8 ± 25.1 vs. 99.3 ± 24.3 mm/h p = 0.004) at diagnosis. PET-CT detected large vessel vasculitis in 42/48 (87.5%) cases of the entire cohort. Thirty-one patients had flares and proportion of flared patients was significantly higher in patients with cranial symptoms. At least one damage item (DI) was present in 54 (60.7%) patients. The development of damage was found to be associated with flares. Evaluation of our cohort revealed the importance of early diagnosis for prevention of vision loss in GCA. Patients without cranial symptoms were younger, present with higher inflammatory response and for these, PET-CT was the main diagnostic tool. Relapse rate was higher in patients with cranial symptoms. Flares and accompanying corticosteroid treatment may contribute to organ damage in GCA.

Evaluation of the Level of Physical Activity and Muscle Strength of Quadriceps in Patients Hospitalized for E-COPD: A Longitudinal Study.

Physical inactivity and peripheral muscle dysfunction are considered two of the main contributors to hospitalizations due to exacerbation and, above all, predictors of mortality for these requirements in patients with COPD. Therefore, longitudinal studies are needed to determine the impact of exacerbations during hospitalization on these two factors, especially after three months of hospital discharge. The objectives of the present study were to assess the level of physical activity in daily life (PADL) and isometric muscle strength of the quadriceps in patients hospitalized for exacerbation of COPD and to verify changes after 3 months of hospital discharge. This is a longitudinal observational study that assessed the PADL level with an accelerometer, after 24 h of the hospitalization and the beginning of the drug treatment and assessed the quadriceps muscle strength with a manual dynamometer, after 72 h of hospitalization, in 32 patients with COPD (66 ± 7.61 years), in addition to repeating both assessments with 30 days of hospital discharge and after 3 months of follow-up. Cognition, dyspnea, general health, physical performance and lung function were assessed to characterize the sample. As main results, there was increase in active time (344 ± 260 - 447 ± 199 min; p = 0.04) and number of steps (4.241 ± 374 - 6.216 ± 400 steps; p = 0.02) after three months. In addition, inactive time showed significant reduction 30 days after hospital discharge (1.151 ± 249 - 1.065 ± 198 min; p = 0.02). The level of physical activity showed significant improvement due to the increase in active time and number of steps after three months of hospital discharge and to the reduction of inactive time 30 days after hospital discharge.

Comparisons of exacerbations and mortality among LAMA/LABA combinations in stable chronic obstructive pulmonary disease: systematic review and Bayesian network meta-analysis.

BACKGROUND: Only few randomized controlled trials (RCTs) for head-to-head comparison have been conducted between various combinations of long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs). Our study was conducted to compare acute exacerbation and all-cause mortality among different LAMA/LABA regimens using Bayesian network meta-analysis (NMA). METHODS: We searched Medline, EMBASE, and the Cochrane library (search date: July 1, 2019). We included parallel-group RCTs comparing LAMA/LABA combinations with other inhaled drugs in the stable COPD for ≥ 48 weeks. Two different network geometries were used. The geometry of network (A) had nodes of individual drugs or their combination, while that of network (B) combined all other treatments except LAMA/LABA into each drug class. This study was prospectively registered in PROSPERO; CRD42019126753. RESULTS: We included 16 RCTs involving a total of 39,065 patients with stable COPD. Six combinations of LAMA/LABA were identified: tiotropium/salmeterol, glycopyrrolate/indacaterol, umeclidinium/vilanterol, tiotropium/olodaterol, aclidinium/formoterol, and glycopyrrolate/formoterol. We found that umeclidinium/vilanterol was associated with a lower risk of total exacerbations than other LAMA/LABAs in the NMA using network (A) (level of evidence: low or moderate). However, the significant differences were not present in the NMA of network (B). There were no significant differences among the LAMA/LABA combinations in terms of the number of moderate to severe exacerbations, all-cause mortality, major adverse cardiovascular events, or pneumonia. CONCLUSIONS: The present NMA including all available RCTs provided that there is no strong evidence suggesting different benefits among LAMA/LABAs in patients with stable COPD who have been followed up for 48 weeks or more. TRIAL REGISTRATION: This study was prospectively registered in PROSPERO; CRD42019126753.

A longitudinal analysis of urological chronic pelvic pain syndrome flares in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

OBJECTIVE: To describe the frequency, intensity and duration of urological chronic pelvic pain syndrome symptom exacerbations ('flares'), as well as risk factors for these features, in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Epidemiology and Phenotyping longitudinal study. PARTICIPANTS AND METHODS: Current flare status ('urological or pelvic pain symptoms that are much worse than usual') was ascertained at each bi-weekly assessment. Flare characteristics, including start date, and current intensity of pelvic pain, urgency and frequency (scales of 0-10), were assessed for participants' first three flares and at three randomly selected times when they did not report a flare. Generalized linear and mixed effects models were used to investigate flare risk factors. RESULTS: Of the 385 eligible participants, 24.2% reported no flares, 22.9% reported one flare, 28.3% reported 2-3 flares, and 24.6% reported ≥4 flares, up to a maximum of 18 during the 11-month follow-up (median incidence rate = 0.13/bi-weekly assessment, range = 0.00-1.00). Pelvic pain (mean = 2.63-point increase) and urological symptoms (mean = 1.72) were both significantly worse during most flares (60.6%), with considerable within-participant variability (26.2-37.8%). Flare duration varied from 1 to 150 days (94.3% within-participant variability). In adjusted analyses, flares were more common, symptomatic, and/or longer-lasting in women and in those with worse non-flare symptoms, bladder hypersensitivity, and chronic overlapping pain conditions. CONCLUSION: In this foundational flare study, we found that pelvic pain and urological symptom flares were common, but variable in frequency and manifestation. We also identified subgroups of participants with more frequent, symptomatic, and/or longer-lasting flares for targeted flare management/prevention and further study.

True cytomegalovirus colitis is a poor prognostic indicator in patients with ulcerative colitis flares: the 10-year experience of an academic referral inflammatory bowel disease center.

Background and aims: The impact of cytomegalovirus (CMV) colitis on long-term outcomes of ulcerative colitis (UC) flares remains controversial. Methods: A total of 257 UC patients with moderate-to-severe flares were observed for a mean follow-up of 41.2 months. CMV colitis was defined as histopathologic confirmation of CMV inclusions obtained from macroscopic endoscopic lesions in patients with UC flares. An independent gastrointestinal pathologist prospectively reviewed all specimens. A poor outcome was defined as any of hospitalization, colectomy or death during the follow-up period. Results: The prevalence of CMV colitis was 14% (36/257) over the 10-year study period (2007-2016). When compared to the controls, patients with CMV colitis were characterized by older age, higher disease activity, endoscopic deep ulcerations and more frequent use of immunosuppressive drugs (all p < .05). In total, 57 outcome events (50 hospitalizations, seven colectomies) were observed among the study population (44.7% in patients with CMV colitis vs. 18.9% in controls). The cumulative probability of a poor outcome was significantly greater in the patients with CMV colitis than in the controls (log-rank test p < .001). In a multivariable analysis, CMV colitis remained as an independent predictor of a poor outcome (hazard ratio; 2.27; 95% confidence interval: 1.12-4.60). Despite a generally favorable response to antiviral therapy (79%), the risk of recurrent CMV colitis remained quite high (57%). Most of the recurrences developed within 8 months (75%). Conclusions: True CMV colitis is a poor prognostic indicator among patients with UC flares. An effective strategy for managing recurrent CMV colitis is urgently needed (KCT0003296).

Impact and risk factors of non-adherence to 5-aminosalicylates in quiescent ulcerative colitis evaluated by an electronic management system.

BACKGROUND AND OBJECTIVE: To determine the impact of non-adherence to 5-Aminosalicylates (5-ASA) on the risk of flares and to identify risk factors of non-adherence. METHODS: Observational, cohort study of ulcerative colitis (UC) patients in clinical remission at least 6 months on 5-ASA monotherapy maintenance prescribed by an electronic management program. Adherence was considered when 80% of the prescribed 5-ASA had been dispensed at the pharmacy. The study analyzed the existence and degree of 5-ASA adherence, disease course, UC phenotypic expression, and 5-ASA dose and regimen, and consumption of non-UC chronic drugs during 2-year follow-up. RESULTS: The study included 274 patients, 49% males with a median age of 38 (27-49) years old. Overall, 41% of patients were non-adherent to 5-ASA. Risk of flares was reduced in the adherent group (36% vs 54%; OR = 0,484; p = 0,004), mainly the mild ones (26% vs 38%; OR = 0,559; p = 0,031). Non-adherence was associated with younger age at diagnosis (32 (26-45) vs 41.5 (21-50), p = 0.000) and no-consumption of other chronic treatments (1.1 vs 2.1; OR = 1709; p = 0,048). CONCLUSION: Non-adherence to 5-ASA evaluated by the pharmaceutical management system was at 41% with a higher risk of relapse. Younger patients and patients who do not receive non-UC chronic treatments showed lower adherence rate.