Lebrikizumab monotherapy impacts on quality of life scores through improved itch and sleep interference in two Phase 3 trials.

BACKGROUND: Lebrikizumab improved itch, interference of itch on sleep, and quality of life (QoL) in patients with moderate-to-severe atopic dermatitis (AD), in two Phase 3 trials at 16 weeks compared to placebo. OBJECTIVES: We assess improvements in itch and sleep interference due to itch and their impact on QoL measurements after treatment. METHODS: Data were analyzed from ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) in patients with moderate-to-severe AD. QoL was evaluated using Dermatology Life Quality Index (DLQI) at Week 16 in patients (>16 years of age) who were itch responders/non-responders (defined as ≥4-point improvement in Pruritus Numeric Rating Scale) or Sleep-Loss Scale responders/non-responders (defined as ≥2-point improvement in itch interference on sleep). RESULTS: In ADvocate1 and ADvocate2, significantly greater proportions of itch responders had a clinically meaningful improvement in measures related to QoL (DLQI scores (0/1), ≤5 DLQI total score and ≥4-point DLQI improvement) compared to itch non-responders. In both studies, a significantly greater proportion of Sleep-Loss Scale responders, reported a DLQI score of (0/1), DLQI total score of ≤5 and DLQI improvement of ≥4 points compared to Sleep-Loss Scale non-responders. CONCLUSIONS: Improvement in itch and sleep interference due to itch is associated with improvement in the QoL of patients after treatment with lebrikizumab for moderate-to-severe AD.ClinicalTrials.gov registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).

Lebrikizumab in Uncontrolled Asthma: Reanalysis in a Well-Defined Type 2 Population.

BACKGROUND: LAVOLTA (L)I, LII, and ACOUSTICS were randomized, placebo-controlled, Phase 3 trials of lebrikizumab, a monoclonal antibody targeting IL-13 in patients with uncontrolled asthma. Failure to demonstrate efficacy may have been related to patient selection in those trials. OBJECTIVE: To assess the efficacy in a well-defined subpopulation of patients with elevated blood eosinophil counts and a minimum number of prior asthma exacerbations. We performed an additional analysis in a subpopulation of patients with elevated FeNO and prior exacerbations. METHODS: Adult (LI and LII) and adolescent patients (aged 12-17 years weighing ≥40 kg, ACOUSTICS) with uncontrolled asthma received lebrikizumab (125 mg, n = 832; or 37.5 mg, n = 829) or placebo (n = 833) subcutaneously every 4 weeks. Post hoc analysis of the annualized adjusted exacerbation rate (AER) was performed in a subpopulation of patients with baseline blood eosinophils of 300 cells/µL or greater and history of one or more exacerbations. In this subpopulation, there were 227 patients in the placebo group, 222 in the lebrikizumab 37.5-mg group, and 217 in the lebrikizumab 125-mg group. We summarized safety in patients who received at least one dose of lebrikizumab using adverse events. RESULTS: Lebrikizumab significantly reduced AER compared with placebo in adults (AER reduction: 125 mg [38%]; and 37.5 mg [41%]) and adolescents (AER reduction:125 mg [59%]; 37.5 mg [64%]) with baseline blood eosinophils of 300 cells/µL or greater and one or more exacerbations. Most adverse events were mild or moderate in severity and did not lead to treatment discontinuation. CONCLUSION: Lebrikizumab significantly reduced asthma exacerbations in a subpopulation of patients with elevated blood eosinophils, elevated FeNO, and a history of asthma exacerbation.

Assessing Itch Severity: Content Validity and Psychometric Properties of a Patient-Reported Pruritus Numeric Rating Scale in Atopic Dermatitis.

BACKGROUND: Pruritus, or itch, is a key symptom of atopic dermatitis (AD); as such, mitigating itch is an important outcome of AD treatment. This study explored the content validity and measurement properties of the Pruritus Numeric Rating Scale (Pruritus NRS), a novel single-item scale for assessing itch severity in clinical trials of AD treatments. METHODS: In this mixed-methods study, qualitative interviews were conducted with 21 people with moderate-to-severe AD (n = 15 adult, n = 6 adolescent) to develop a conceptual model of the patient experience in AD and explore the content validity of the Pruritus NRS. Data collected daily from adults with moderate-to-severe AD enrolled in a phase 2b study (NCT03443024) were used to assess the Pruritus NRS' psychometric performance, including reliability, construct validity, and responsiveness. Meaningful within-patient change (MWPC) thresholds were also determined using anchor-based methods. RESULTS: Qualitative findings highlighted the importance of itch in AD, including severity, persistence, frequency, and daily life interference. Patient debriefing of the Pruritus NRS indicated that the scale was relevant, appropriate, and interpreted as intended. Trial data supported overall good psychometric properties. MWPC was defined as a 3-point improvement in Pruritus NRS score, a finding supported by qualitative data. CONCLUSIONS: The Pruritus NRS provides a valid and reliable patient-reported measure of itching severity in patients with moderate-to-severe AD, and can detect change, indicating it is fit-for-purpose to evaluate the efficacy of AD treatments in this population. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03443024.

[Synergistic Benefits of Pollution and Carbon Reduction from Air Pollution Control in Hebei Province from 2013 to 2020].

Recently, China has been facing the dual challenges of air pollution control and carbon emission reduction. Pollution and carbon reduction have become a breakthrough point for green socio-economic transformation. Air pollutant and CO2 emission inventories provide a tool for monitoring pollution and carbon reduction; however, there have been some problems in previous studies, including incomplete species coverage, different source classifications, and narrow time scales. Based on the unified emission source classification system and estimation method, an emission inventory was developed for Hebei Province from 2013 to 2020, and the emission trends, structure change, driving force, synergistic benefits, and spatial distribution were analyzed. Hebei Province achieved a balance during the study period in socio-economic development and anthropogenic emission control. SO2 emissions decreased rapidly during the "Ten Atmospheric Measures" period. VOCs and NH3 emissions reduction were more significant during the "Blue Sky Defense War" period. The decrease rates of NOx and PM2.5 emissions were relatively stable, and CO2 emissions increased slightly. The coal-fired treatment effectively reduced the air pollutant and CO2 emissions and strengthening the emission standards for key industries reduced SO2, NOx, and PM2.5 emissions; however, the VOCs emission control requires improvement. Power and residential sources achieved co-reduction of air pollutants and CO2 and reducing residential coal optimized the energy structure, thereby leading to greater synergistic benefits in the residential source. The key pollution and carbon reduction areas in Hebei Province were Shijiazhuang, Tangshan, Handan, Baoding, and Langfang. The methods and conclusions in this study can provide technical and decision-making references for regional pollution and carbon reduction efforts.

Utilizing biochar to decorate nanoscale FeS for the highly effective decontamination of Se(IV) from simulated wastewater.

Selenium (Se) as an essential nutrient for human beings at trace concentrations, the allowable concentration for the human is only 40 µg/L. Iron sulfide (FeS) nanoparticles have been applied for excessive of selenium (Se) remediation in surface water and groundwater. In this study, FeS nanoparticles were anchored onto biochar (BC) to reduce agglomeration of FeS and prepared into the composite of FeS-BC by pyrolysis to economically and efficiently remove Se(IV) from simulated wastewater based on the excellent performance of FeS and the low cost of BC. Characterizations presented the uniform anchorage of FeS on the BC surface to prevent agglomeration. The results of batch experiments revealed that the removal of Se(IV) by FeS-BC nanomaterials significantly depended on the pH value, with the maximum removal of ∼174.96 mg/g at pH 3.0. A pseudo-second-order kinetic model well reflected the kinetic removal of Se(IV) in pure Se(IV) solution with different concentration, as well as the coexistence of K+, Ca2+, Cl-, and SO42- ions. The presence of K+ ions significantly inhibited the removal of Se(IV) with the increase of K+ ion concentration compared with the effect of the other three ions. SEM-EDS and XPS analyses indicated that the removal process was achieved through adsorption by surface complexation, and reductive precipitation of Se(IV) into Se0 with the electron donor of Fe(II) and S(-II) ions. The FeS-BC nanomaterial exhibited an excellent application prospect in the remediation of Se(IV).

A fusion learning method to subgroup analysis of Alzheimer's disease.

Uncovering the heterogeneity in the disease progression of Alzheimer's is a key factor to disease understanding and treatment development, so that interventions can be tailored to target the subgroups that will benefit most from the treatment, which is an important goal of precision medicine. However, in practice, one top methodological challenge hindering the heterogeneity investigation is that the true subgroup membership of each individual is often unknown. In this article, we aim to identify latent subgroups of individuals who share a common disorder progress over time, to predict latent subgroup memberships, and to estimate and infer the heterogeneous trajectories among the subgroups. To achieve these goals, we apply a concave fusion learning method to conduct subgroup analysis for longitudinal trajectories of the Alzheimer's disease data. The heterogeneous trajectories are represented by subject-specific unknown functions which are approximated by B-splines. The concave fusion method can simultaneously estimate the spline coefficients and merge them together for the subjects belonging to the same subgroup to automatically identify subgroups and recover the heterogeneous trajectories. The resulting estimator of the disease trajectory of each subgroup is supported by an asymptotic distribution. It provides a sound theoretical basis for further conducting statistical inference in subgroup analysis.

Evaluating vehicular exhaust and evaporative emissions via VOC measurement in an underground parking garage.

Vehicular emissions, including both tailpipe exhaust and evaporative emissions, are major anthropogenic sources of volatile organic compounds (VOCs) in urban cities. Current knowledge on vehicle tailpipe and evaporative emissions was mainly obtained via laboratory tests on very few vehicles under experimental conditions. Information on fleet gasoline vehicles emission features under real-world conditions is lacking. Here, VOC measurement was conducted in a large residential underground parking garage in Tianjin, China, to reveal the feature of the exhaust and evaporative emissions from real-world gasoline vehicle fleets. The VOC concentration in the parking garage was on average 362.7 ± 87.7 µg m-3, significantly higher than that in the ambient atmosphere at the same period (63.2 µg m-3). Aromatics and alkanes were the mainly contributors on both weekdays and weekends. A positive correlation between VOCs and traffic flow was observed, especially in the daytime. Source apportionment through the positive matrix factorization model (PMF) revealed that the tailpipe and evaporative emissions accounted for 43.2% and 33.7% of VOCs, respectively. Evaporative emission contributed 69.3% to the VOCs at night due to diurnal breathing loss from numerous parked cars. In contrast, tailpipe emission was most remarkable during morning rush hours. Based on the PMF results, we reconstructed a vehicle-related VOCs profile representing the combination of the tailpipe exhaust and evaporative emission from fleet-average gasoline vehicles, which could benefit future source apportionment studies.

COVID-19 pandemic-related depression and anxiety under lockdown: The chain mediating effect of self-efficacy and perceived stress.

Objective: In early March 2022, the highly contagious Omicron variant rapidly emerged in Shanghai. This study aimed to explore the prevalence and associated factors of depression and anxiety in isolated or quarantined populations under lockdown. Methods: A cross-sectional study was conducted between May 12 and 25, 2022. The depressive and anxiety symptoms, perceived stress, self-efficacy and perceived social support in the 167 participants under isolated or quarantined were examined using the Patient Health Questionnaires-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7), the Perceived Stress Scale-10 (PSS-10), the General Self-Efficacy Scale (GSES) and the Perceived Social Support Scale (PSSS). Data on demographic information were also collected. Findings: The prevalence of depression and anxiety in isolated or quarantined populations was estimated to be 12 and 10.8%, respectively. Higher education level, being healthcare workers, being infected, longer duration of segregation and higher perceived stress level were identified as risk factors for depression and anxiety. Furthermore, the relationship between perceived social support and depression (anxiety) was mediated not only by perceived stress but also the chain of self-efficacy and perceived stress. Conclusion: Being infected, higher education level, longer duration of segregation and higher perceived stress were associated with higher levels of depression and anxiety among isolated or quarantined populations under lockdown. The formulation of psychological strategies that promote one's perceived social support and self-efficacy as well as reduce perceived stress is supposed to be drawn.

Early improvements in signs and symptoms predict clinical response to baricitinib in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Early prediction of therapeutic response can optimize treatment strategies in atopic dermatitis (AD). Baricitinib is approved for moderate-to-severe AD in Europe, Japan and other countries. OBJECTIVES: To identify early clinical improvements that can reliably predict a later clinical response to baricitinib in adults with moderate-to-severe AD. METHODS: Using data from one topical corticosteroid combination study [BREEZE-AD7 (NCT03733301)] and data pooled from two monotherapy studies [(BREEZE-AD1 (NCT03334396) and BREEZE-AD2 (NCT03334422)], we calculated the sensitivity and specificity, along with the positive predictive value (PPV) and negative predictive value (NPV), of predefined changes in single and combined clinical scores at weeks 2, 4 and 8, to predict clinical response at week 16. Clinical response was defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI 75), ≥ 4-point improvement in Itch Numeric Rating Scale (Itch NRS ≥ 4), or a combination of both. RESULTS: Composite predictors had higher predictive accuracy for week 16 response outcomes than did single parameters. This was evident as early as week 4 for the combination of EASI 50 or Itch NRS ≥ 3 and of validated Investigator Global Assessment for AD (vIGA-AD) score ≤ 2 or Itch NRS ≥ 3 (sensitivity 87-100%; NPV 68-100%). The predictive accuracy of these composite clinical predictors for week 16 response outcomes was highest at week 8 (sensitivity 92-100%; NPV 80-100%). At both weeks 4 and 8, EASI 50 or Itch NRS ≥ 3 had higher sensitivity and NPV than did vIGA-AD score ≤ 2 or Itch NRS ≥ 3. CONCLUSIONS: Improvement in signs and symptoms early during treatment with baricitinib 4 mg once daily predicts clinical response at week 16, providing a tool for dermatologists when choosing treatment strategies for patients with moderate-to-severe AD.

Robust analyses for radiographic progression in rheumatoid arthritis.

Demonstrating inhibition of the structural damage to joints as a statistically significant difference in radiographic progression as measured by the van der Heijde modified Total Sharp Score (mTSS) is a common objective in trials for rheumatoid arthritis treatments. The frequently used analysis of the covariance model with missing data imputed using linear extrapolation (analyses of covariance, ANCOVA+LE) may not be ideal for long-term extension studies or for paediatric studies. The random coefficient (RC) model may represent a better alternative.A two-arm (active treatment and placebo) setting with a week 44 study period was considered. RC model, ANCOVA+LE and ANCOVA with last observation carried forward imputation were compared under different scenarios in bias, root mean square error (RMSE), power and type I error rate.The RC model outperformed ANCOVA+LE in metrics measuring bias, RMSE, power and type I error rate under the evaluated scenarios. ANCOVA and RC provide similar performance when there are no missing data. With missing data, RC+observed (OBS) provides similar or better results than ANCOVA+LE in power and bias.Our simulations support that RC is both a more sensitive and a more precise alternative to the commonly used ANCOVA+LE as a primary method for analysing mTSS in long-term extension and paediatric studies with a higher likelihood of missing data. The RC model can provide a reference at time points with missing data by estimating a slope; mTSS change by one unit change in time. ANCOVA+LE is recommended as a sensitivity analysis.

One-quarter of COVID-19 patients developed PTSD symptoms: A one-year longitudinal study.

This study investigated the longitudinal development of PTSD symptoms and respiratory sequelae among COVID-19 patients one year after hospital discharge. The cumulative occurrence of probable PTSD in COVID-19 survivors (n = 329) was 26.7%, which significantly decreased over the 12-month period (23.1% to 4.3%). Non-severe patients showed marked improvement in all four clusters of PTSD symptoms at 12 months compared to 3 months, while severe patients only showed improvements in re-experiencing and numbing symptoms. Moreover, being female and having respiratory sequelae increased the risk for chronic PTSD. Psychological interventions are required for COVID-19 patients during long-term convalescence.

Maintained improvement in physician- and patient-reported outcomes with baricitinib in adults with moderate-to-severe atopic dermatitis who were treated for up to 104 weeks in a randomized trial.

BACKGROUND: Patients who completed the originating studies, BREEZE-AD1 (NCT03334396), BREEZE-AD2(NCT03334422), and BREEZE-AD7 (NCT03733301), were eligible for enrollment in the multicenter,phase-3, long-term extension study BREEZE-AD3 (NCT03334435). METHODS: At week 52, responders and partial responders to baricitinib 4 mg were re-randomized (1:1) into the sub-study to dose continuation (4 mg, N = 84), or dose down-titration (2 mg, N = 84). Maintenance of response was assessed from week 52 to 104 of BREEZE-AD3. Physician-rated outcomes included vIGA-AD (0,1), EASI75, and mean change from baseline in EASI. Patient-reported outcomes included DLQI, P OEM total score, HADS, and from baseline: WPAI (presenteeism, absenteeism, overall work impairment, daily activity impairment) and change from baseline in SCORAD itch and sleep loss. RESULTS: With continuous treatment with baricitinib 4 mg, efficacy was maintained up to week 104 in vIGA-AD (0,1), EASI75, EASI mean change from baseline, SCORAD itch, SCORAD sleep loss, DLQI, P OEM, HADS, and WPAI (all scores). Patients down-titrated to 2 mg maintained most of their improvements in each of these measures. CONCLUSION: The sub-study of BREEZE AD3 supports flexibility in baricitinib dosing regimens. Patients who continued treatment with baricitinib 4 mg and down-titrated to 2 mg maintained improvements in skin, itch, sleep, and quality of life for up to 104 weeks.

[Railway Emission Trends in China Based on Fuel Life Cycle Analysis].

Railway transportation is one of the main modes of modern transportation. Under the dual constraints of air quality improvement and carbon neutrality achievement, clarifying the emission trend of CO2 and pollutants in railway transportation is of great significance for pollution and carbon reduction in the transport sector. In this study, the CO2 and pollutant emission characteristics of Chinese railways from 2001 to 2018 were analyzed based on the fuel life cycle method. Then, railway emission trends from 2019-2030 were assessed combined with scenario analysis. The results showed that with the advancement of railway electrification, the use of new diesel locomotives, and the continuous upgrading of fuel standards, the total CO2 and pollutant emissions in the fuel life cycle of railway transportation showed an upward and downward trend, respectively. In 2018, the total emissions of CO2, NOx, CO, BC, and SOx from railway transportation were 3780.29×104t, 11.98×104t, 3.94×104t, 0.20×104t, and 3.08×104t, respectively. Accelerating the improvement of power structure and reducing unit energy consumption were the best single control strategies to reduce railway emissions of CO2, SOx, NOx, BC, and CO, respectively. Under the comprehensive scenario of actively responding to railway pollution and carbon reduction, the emission reduction rates of CO2, NOx, CO, BC, and SOx could reach 35%, 37%, 39%, 32%, and 45%, respectively. The stagnation of power structure reform or the railway electrification process will lead to a significant increase in total emissions of railway transportation. Therefore, the pollution and carbon reduction of railway transportation requires continuous attention.

[Evolution and Characteristics of Full-process Vehicular VOCs Emissions in Tianjin from 2000 to 2020].

Vehicle emissions are an important source of anthropogenic volatile organic compound (VOCs) emissions in urban areas and are commonly quantified using vehicle emission inventories. However, most previous studies on vehicle emission inventories have incomplete emission factors and emission processes or insufficient consideration of meteorological parameters. Based on the localized full-process emission factors attained from tested data and previous studies, a method to develop a monthly vehicular VOC emission inventory of full process for the long-term was established, which covered exhaust and evaporative emissions (including running loss, diurnal breathing loss, hot soak loss, and refueling emission). Then, the method was used to develop a full-process vehicular VOC emission inventory in Tianjin from 2000 to 2020. The results showed that the total vehicular VOC emissions in Tianjin rose slowly and then gradually decreased. In 2020, the total emissions were 21400 tons. The light-duty passenger vehicles were the dominant contributors and covered 75.00% of the total emissions. Unlike the continuous decline in exhaust emissions, evaporative emissions showed an inverted U-shaped trend with an increasing contribution to total emissions yearly, accounting for 31.69% in 2020. Monthly emissions were affected by both vehicle activity and emission factors. VOC emissions were high in autumn and winter and low in spring and summer. During the COVID-19 epidemic in 2020, vehicle activity was limited by closure and control, making VOC emissions significantly lower than those during the same period in previous years. The method and data in this study can provide technical reference and a decision-making basis for air pollution prevention and control.

Efficacy of downtitration or treatment withdrawal compared with continuous dosing after successful treatment with baricitinib in patients with moderate-to-severe atopic dermatitis in a randomized substudy from the long-term extension study BREEZE-AD3.

BACKGROUND: Baricitinib, an oral, selective Janus kinase 1/2 inhibitor, demonstrated long-term efficacy in moderate-to-severe atopic dermatitis in an ongoing double-blind, phase III, long-term extension study, BREEZE-AD3 (NCT03334435). OBJECTIVES: To evaluate the efficacy and safety of downtitration and treatment withdrawal in a substudy of BREEZE-AD3. METHODS: The substudy included patients (N = 526) treated with baricitinib 4 mg or 2 mg at entry into BREEZE-AD3 who achieved a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD®) scale score of 0 (clear), 1 (almost clear) or 2 (mild) at week 52. Patients treated with baricitinib 4 mg were rerandomized to baricitinib 4 mg (continuous dosing), baricitinib 2 mg (downtitration) or placebo (treatment withdrawal, 4-mg cohort), and patients treated with baricitinib 2 mg were rerandomized to baricitinib 2 mg (continuous dosing), baricitinib 1 mg (downtitration), or placebo (treatment withdrawal, 2-mg cohort). After 16 weeks, we assessed the proportion of patients with vIGA-AD® 0/1, vIGA-AD® 0/1/2, vIGA-AD® ≥ 3 (loss of response; criterion to readminister the original baricitinib dose) and for patients who were readministered the original baricitinib dose, we assessed the proportion of patients who recaptured vIGA-AD® 0/1/2 within 16 weeks of treatment readministration (patients in the continuous dosing maintained the same dose). RESULTS: For the continuous dosing, downtitration, and treatment withdrawal groups 51%, 45% and 30% of patients in the 4-mg cohort achieved vIGA-AD® 0/1 and 87%, 61% and 50% of patients achieved vIGA-AD® 0/1/2, respectively. For the 2-mg cohort, the respective proportions of patients were 48%, 42% and 25% for vIGA-AD® 0/1 and 92%, 71% and 45% for vIGA-AD® 0/1/2. The respective proportions of patients with vIGA-AD® ≥ 3 were 39%, 49% and 56% in the 4-mg cohort and 41%, 41% and 64% in the 2-mg cohort. Of those who were readministered the original baricitinib dose, the proportions of patients who recaptured vIGA-AD® 0/1/2 among the continuous dosing, downtitration, and treatment withdrawal groups were 80%, 85% and 88% in the 4-mg cohort and 90%, 56% and 86% in the 2-mg cohort, respectively. CONCLUSIONS: Baricitinib allows flexibility for patients to downtitrate or stop treatment. For patients who downtitrated treatment, the majority maintained efficacy through 16 weeks. Most patients who lost efficacy with downtitration or treatment withdrawal achieved clinically relevant efficacy upon readministration of their original dose.

Patient Disease Trajectories in Rheumatoid Arthritis Patients Treated with Baricitinib 4-mg in Four Phase 3 Clinical Studies.

INTRODUCTION: We sought to identify and compare treatment response groups based on individual patient responses (rather than group mean response) over time on the Clinical Disease Activity Index (CDAI) for rheumatoid arthritis (RA), in patients treated with baricitinib 4-mg in 4 phase 3 studies. METHODS: Trajectory subgroups were identified within each study using growth mixture modeling. Following grouping, baseline characteristics and disease measures were summarized and compared. RESULTS: In each study, three response trajectories were identified. In the three studies of patients naïve to biological disease-modifying anti-rheumatic drugs (bDMARDs) patients had, on average, high disease activity, as measured by CDAI. In these studies, a group of rapid responders (65-71% of patients) had the lowest baseline CDAI scores and achieved mean CDAI ≤ 10 by week 16. Gradual responders (10-17%) had higher baseline CDAI, but generally achieved low disease activity (CDAI ≤ 10) by week 24. A group of partial responders (18-22%) had higher baseline CDAI and did not achieve mean CDAI ≤ 10. In bDMARD-experienced patients, the subgroups were rapid responders, who achieved mean CDAI ≤ 10 (42% of patients); partial responders, with mean CDAI decrease of ~ 15 points from baseline (42% of patients); and limited responders (15% of patients). Changes in modified total sharp score (mTSS; assessed only in biologic-naïve patients) were below the smallest detectable difference at 24/52 weeks for > 90% of patients in each group, excepting partial responders in RA-BEGIN (≥ 75% no detectable change). CONCLUSION: In patients receiving baricitinib 4-mg, lower baseline CDAI was generally associated with rapid response, while higher baseline CDAI scores were generally seen for patients who either reached treatment targets more gradually, or who had a partial or limited response. Maintenance of response was observed with continued baricitinib treatment in all response groups and generally included maintenance of mTSS.

Baricitinib is an oral agent widely approved for the treatment of moderately to severely active rheumatoid arthritis). Although baricitinib (and other agents) have demonstrated efficacy at the population level, treatment responses vary considerably between individual patients. This study assessed four baricitinib phase 3 clinical studies and categorized patient responses into response groups based on the Clinical Disease Activity Index (CDAI) using a growth mixture model. We then evaluated baseline characteristics and corresponding disease measures within the response groups. In patients with no prior treatment with biological disease-modifying anti-rheumatic drugs (bDMARDs), 65­71% of patients had rapid responses to treatment, while smaller groups had gradual (10­17%) or partial (18­22%) responses. In patients with prior bDMARD experience, rapid and partial responders each comprised 42% of patients while 15% had limited response. Gradual responders generally had higher baseline CDAI versus rapid responders, but achieved low disease activity (LDA) by 24, versus 12 weeks for rapid responders. Across response groups, patients who continued treatment generally maintained their response up to 52 weeks, and where joint erosion was assessed (in bDMARD-naïve patients), generally saw maintenance of joints during continued therapy. The identification of a gradual responder group, which demonstrated good response but required more time to achieve LDA, is relatively novel and should be considered when setting treatment expectations, particularly in patients with high baseline disease activity. In addition, in bDMARD-experienced patients, many patients did not achieve LDA but maintained a substantial partial response with continued therapy.

Comparison of CO2, NOx, and VOCs emissions between CNG and E10 fueled light-duty vehicles.

In China, natural gas (NG) is the main vehicle fuel after gasoline and diesel, and the number of NG vehicles ranks first in the world. At present, there are many studies on the conventional gaseous pollutants and particulate matter of NG vehicles, but very few studies on their VOCs. In this study, the chassis dynamometer is used to test CNG/E10 bi-fuel light-duty vehicles, analyze the advantages of CNG in CO2, fuel thermal efficiency, and cost, and discuss its disadvantages in NOx emission. Most importantly, the emission characteristics and ozone formation potential of VOCs in the exhaust of CNG vehicles were analyzed in the study. Compared with E10, CNG fuel can reduce CO2 emission by about 20 %, improve thermal efficiency by about 13 %, and save fuel costs by about 50 %. However, it will increase NOx and NO2 emissions by about 10 % and 13 % respectively. As for VOCs, the emission factor of VOCs from CNG fuel is about 54 % of E10 fuel. The VOCs group with the highest proportion in the exhaust of CNG-fueled vehicles is alkanes, >80 %. while the alkanes and alkenes with the highest proportion in E10 fuel are 30 % and 23 % respectively. C2 VOCs emitted by CNG account for >70 %, while C2 VOCs emitted by E10 are <60 %, followed by C4 VOCs, about 10 % - 30 %. The OFPs of VOCs in CNG exhaust is about 13.7 % of E10. Alkenes contribute the most to ozone, and the OFPs of alkenes in CNG and E10 vehicle exhaust accounts for about 55.3 % and 78.8 % of TVOCs respectively. The results of this study are helpful to improve people's understanding of the environmental value of using NG vehicles.

Baricitinib 2 mg for the treatment of atopic dermatitis in North America: Long-term efficacy and patient-reported outcomes.

To address the need for long-term efficacy and patient-reported outcomes (PROs) data for patients with atopic dermatitis (AD) treated with baricitinib 2 mg, a study was conducted to evaluate the efficacy of baricitinib 2 mg in adult patients with moderate-to-severe AD. Data presented here provided efficacy and outcomes data for patients treated for 52 weeks. Patients who participated in the originating study, BREEZE-AD5 (NCT03435081), and met additional eligibility criteria could enroll in the multicenter, open-label, Phase 3, long-term extension study BREEZE-AD6 (NCT03559270). Patients received baricitinib 2 mg for the duration of BREEZE-AD6. In BREEZE-AD6, the proportion of patients who achieved a 75% improvement in the Eczema Area and Severity Index (EASI75) and validated Investigator Global Assessment for AD (vIGA-AD™) of 0 (clear) or 1 (almost clear) were assessed through 52 weeks, in addition to several PROs. At week 52, the proportion of patients treated with baricitinib 2 mg daily achieving EASI75 was 48.6% (70/144), and 31.3% (45/144) of patients achieved a vIGA-AD score of 0 or 1 (clear or almost clear). Improvements in PROs such as SCORing Atopic Dermatitis (SCORAD, itch and sleep) scores, Dermatology Life Quality Index (DLQI) total score, and DLQI ≤5 response were observed, and these responses were sustained through 52 weeks. Long-term efficacy of baricitinib in patients with AD was demonstrated by both clinician and patient-reported outcome measures.

Improvements in itch and sleep following treatment with baricitinib in combination with topical corticosteroids are associated with better quality of life and productivity in adult patients with moderate-to-severe atopic dermatitis: a post hoc analysis from BREEZE-AD7

Background: Treatment with baricitinib in combination with topical corticosteroids previously showed greater improvements in itch and sleep versus placebo in adults with moderate-to-severe AD. Objectives: To assess whether improvements in itch and sleep translate to greater quality of life (QoL), productivity and treatment benefit in AD. Materials & Methods: In this post hoc analysis with data from BREEZE-AD7 (NCT03733301), itch and sleep improvements at Week 16 were defined by ≥4-point improvements in the Itch Numeric Rating Scale and ≥1.5 decreases in the number of night-time awakenings since baseline, respectively. Dermatology Life Quality Index, Work Productivity and Activity Impairment-AD and Patient Benefit Index (PBI) scores were compared in patients with and without improvements. Proportions were analysed using logistic regression with non-responder imputation. Changes from baseline were calculated using ANCOVA, with last observation carried forward. Least square mean PBI scores were assessed using ANOVA. Results: More patients with itch improvement versus no itch improvement reported no impact of AD on QoL (28.4% vs. 6.0%). Daily activity impairment was lower in patients with itch improvement (-39.6% vs. -15.6%). A greater proportion of patients with sleep improvement versus no sleep improvement had no AD-related impact on QoL (24.1% vs. 1.5%). Patients with sleep improvement had less daily activity impairment (-35.0% vs. -18.5%). Patients with itch and sleep improvements experienced greater treatment benefit. Conclusion: Patients with AD who experienced clinically meaningful improvements in itch and sleep following treatment had significantly better QoL, productivity and treatment benefit. Addressing these symptoms is important to achieving meaningful and patient-relevant improvements in well-being.