Baseline Characteristics and Maintenance Therapy Choice on Symptom Control, Reliever Use, Exacerbation Risk in Moderate-Severe Asthma: A Clinical Modelling and Simulation Study.

INTRODUCTION: Although some factors associated with asthma symptom deterioration and risk of exacerbation have been identified, these are not yet fully characterised. We conducted a clinical modelling and simulation study to understand baseline factors affecting symptom control, reliever use and exacerbation risk in patients with moderate-severe asthma during follow-up on regularly dosed inhaled corticosteroid (ICS) monotherapy, or ICS/long-acting beta2-agonist (LABA) combination therapy. METHODS: Individual patient data from randomised clinical trials (undertaken between 2001 and 2019) were used to model the time course of symptoms (n = 7593), patterns of reliever medication use (n = 3768) and time-to-first exacerbation (n = 6763), considering patient-specific and extrinsic factors, including treatment. Model validation used standard graphical and statistical criteria. Change in symptom control scores (Asthma Control Questionnaire 5 [ACQ-5]), reduction in reliever use and annualised exacerbation rate were then simulated in patient cohorts with different baseline characteristics and treatment settings. RESULTS: Being a smoker, having higher baseline ACQ-5 and body mass index affected symptom control scores, reliever use and exacerbation risk (p < 0.01). In addition, low forced expiratory volume in 1 s percent predicted, female sex, season and previous exacerbations were found to contribute to a further increase in exacerbation risk (p < 0.01), whereas long asthma history was associated with more frequent reliever use (p < 0.01). These effects were independent from the underlying maintenance therapy. In different scenarios, fluticasone furoate (FF)/vilanterol was associated with greater reductions in reliever use and exacerbation rates compared with FF or fluticasone propionate (FP) alone or budesonide/formoterol, independently from other factors (p < 0.01). CONCLUSIONS: This study provided further insight into the effects of individual baseline characteristics on treatment response and highlighted significant differences in the performance of ICS/LABA combination therapy on symptom control, reliever use and exacerbation risk. These factors should be incorporated into clinical practice as the basis for tailored management of patients with moderate-severe asthma.

In this study we quantified how individual baseline patient characteristics at the start of treatment influence the response to regular maintenance medication. Specifically, using computer modelling and simulations based on data from individual patients enrolled into clinical trials in moderate­severe asthma, we predicted how much reliever inhaler they need, how well they rate their asthma control, and how likely an asthma attack (exacerbation) is to occur within the next 12 months. Simulation scenarios were then implemented to evaluate opportunities to improve and personalise real-life management of patients in clinical practice. Considering symptom control level, reliever use and other patient-specific factors at the start of treatment, we assessed how well maintenance therapy with inhaled corticosteroids/bronchodilators contributes to symptom improvement and/or reduction in the risk of asthma attacks. These scenarios show that current smokers, people with higher asthma symptom scores, who are obese, and have a longer history of asthma tend to use their reliever inhalers more often. Moreover, this was linked to a higher risk of having an asthma attack and worse symptom control. This pattern appears to compensate in most cases for the effect of the same baseline factors on symptom control. Switching patients who are not responding well to initial treatment with the inhaled corticosteroid, fluticasone propionate, to fluticasone furoate/vilanterol resulted in a significantly greater reduction in reliever inhaler use and risk of asthma attack, compared with those switched to budesonide/formoterol. These findings highlight the importance of tailored choices for optimal management of patients with moderate­severe asthma.

Effectiveness of Lactoferrin in the Treatment of Anemia in Chronic Kidney Disease: A Single-Center Pilot Study.

Background: Anemia occurs in majority of patients with chronic kidney disease despite adequate dialysis and iron replete status. This study was done to evaluate the effects of lactoferrin with or without iron supplementation for the treatment of anemia in patients with chronic kidney disease (CKD). Materials and Methods: In this prospective, observational, single-center, single-arm pilot study, adult patients aged >18 years, having stage 5 CKD (estimated glomerular filtration rate [eGFR] <15 ml/min/1.73 m2), and who had anemia (hemoglobin [Hb] <10 g/dl; transferrin saturation [Tsat] >20%) were included. Patients were treated with 100 mg of oral lactoferrin twice a day for one month with or without iron supplementation. Patients had been on stable erythropoietin doses for ≥1 month prior to inclusion in the study. We report on the improvement in Hb levels and effect on inflammatory markers from baseline at four weeks. Results: A total of 46 CKD patients having anemia were included. Patients had a mean age of 39.3 years, and a majority were men (69.6%). Improvement in the mean (SD) Hb level (g/dl) was observed from baseline (8.18 [1.19]) to Week 2 (8.54 [1.57]), which attained significance at Week 4 (8.96 [1.93]; P < 0.001; mean difference: -0.76; 95% confidence interval [CI]: -1.291 to - 0.2383). The improvement in Hb was higher in women than in men (P = 0.48) and in patients receiving lactoferrin with iron supplementation than in those receiving lactoferrin alone (P = 0.14). There was a non-significant decrease in the erythrocyte sedimentation rate (P = 0.14) and a non-significant increase in C-reactive protein (P = 0.54) level. Conclusion: Oral lactoferrin therapy was effective in improving hemoglobin levels in patients with advanced CKD and anemia. The effects of lactoferrin therapy on inflammatory markers remain uncertain.

Screening type 2 Diabetes mellitus among Indians using inflammatory biomarkers.

Diabetes is a metabolic disorder associated with chronic inflammation; pre-diabetes phase promotes to inflammatory mechanism then finally progress to diabetes and its associated complications. Therefore, it is of interest to investigate the changes in inflammatory biomarkers Evidence that inflammatory markers play a role in the development as well as severity of Type 2 diabetes mellitus (T2DM). This study has been designed to decipher the involvement of Tumor Necrosis Factor (TNFα), Interleukin-6 (IL-6), Nesfatin-1 and Blood sugar in the etiopathogenesis of T2DM. This retrospective observational study analyzed patient records from our hospital, focusing on those with diabetes or pre-diabetes. Glycosylated hemoglobin, inflammatory biomarkers, Fasting Blood Glucose, and Post-Prandial Blood Glucose were assessed. SPSS 28 facilitated statistical analysis; utilizing Bivariate Correlation assessed the relationship between inflammatory biomarkers and diabetes status (glycosylated hemoglobin). In the pre-diabetic vs. diabetic groups, significant differences exist in IL-6 (p=0.0344), TNF-α (p=0.041), Nesfatin-1 (p=0.0485), fasting blood glucose (p=0.036), and 2h post-prandial blood glucose (p=0.048). IL6 (AUC=0.729, p<0.001), TNF (AUC=0.761, p<0.001), and Nesfatin1 (AUC=0.892, p<0.001) show moderate discriminative power. PP (AUC=0.992, p<0.001) and hbA1c (AUC=0.993, p<0.001) exhibit excellent discriminatory ability. Correlations: IL6 with TNF (r=0.672, p<0.001) and Nesfatin1 (r=0.542, p<0.001); TNF with Nesfatin1 (r=0.591, p<0.001), hbA1c (r=0.683, p<0.001), and PP (r=0.367, p<0.001); Nesfatin1 with PP (r=0.594, p<0.001) and hbA1c (r=0.800, p<0.001). Age has a negative correlation with hbA1c (r=-0.119, p=0.086). Thus, data shows a significant association between inflammatory markers, blood glucose levels, and the progression from pre-diabetes to diabetes.

General practitioner and patient perspectives on intranasal corticosteroids for allergic rhinitis: Treatment duration and obstacles to adherence, findings from a recent survey.

Background and objective: Currently, there are no guideline recommendations for the duration of intranasal corticosteroid (INCS) treatment for allergic rhinitis (AR). We aimed to catalogue real-world AR-INCS prescription patterns. Materials and methods: This multicenter, non-interventional, cross-sectional study used online general practitioner (GP) and patient surveys from 4 countries. Eligible GPs had 3-35 years of practical experience, regularly prescribed INCSs for AR treatment, and had managed ≥5 patients with AR per month according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in the previous year. Eligible patients with AR were non-pregnant females or males, aged 18-65 years, previous AR-INCS users (≥12 months), and receiving GP-prescribed AR therapy. Survey participants were from countries with 15-50% AR prevalence and mostly prescription-only INCS use of ≥100 million units annually (Brazil, Mexico, Spain, Thailand). GP surveys and GP-completed patient record forms (PRFs) gathered AR-care and INCS-use data over 10 months; each GP completed patient record forms (PRFs) for 3 patients with AR under their care. The patient survey reflected actual AR-INCS experience, treatment duration, and adherence factors from patient perspectives. The target sample size was 75 GPs, 75 patients, and ≥30 respondents per country. Results: From 900 GP-PRFs, the mean GP-recommended AR-INCS durations reported were 8.4 (Brazil), 8.3 (Mexico), 5.4 (Spain), and 6.4 (Thailand) weeks. From 300 patient surveys, mean reported INCS recommended durations were 6.4 (Brazil), 5.1 (Mexico), 4.0 (Spain), and 4.9 (Thailand) weeks; reported actual use durations were 6.2, 4.8, 3.6, and 6.4 weeks, respectively. The most frequent GP-PRF-reported factors influencing AR-INCS treatment duration were symptom severity (76-85%), symptom recurrence (49-73%), and existing comorbidities (33-57%). The most frequent GP-PRF-reported obstacles to adherence included forgetting to take medication regularly (54-100%), subsiding symptoms (42-91%), and being unable to continue activities (33-51%). Subsiding symptoms (36-53%) and reaching the prescription duration end (20-51%) were most frequent obstacles reported by the patient survey. Patients from all surveyed countries indicated that they visited the GP, a different physician, or a pharmacy for assistance with symptom recurrence; some patients also self-medicated. Conclusions: Real-world AR-INCS prescription durations vary between countries and actual use tends to be shorter than prescribed. Understanding underlying factors may support appropriate AR-INCS use. The study was not powered to statistically compare intercountry differences; hence, comparisons have not been drawn, and the small sample may not reflect a complete picture of clinical practice and patients with AR in each country.

Linking IL-6 and hsCRP among Indian patients with myocardial infarction.

The association between serum interleukin-6 (IL-6) and highly sensitive C - reactive protein (hsCRP) as predictors of the risk factors for Myocardial Infarction. The study included a total of 50 patients with Myocardial Infarction, aged between 25 to 74 years. The levels of hsCRP were measured using the immunoturbidimetry method, while Interleukin 6 was estimated using the sandwich ELISA method. Statistical analysis was conducted using SPSS version 21.0, with p values calculated using Quartile ratio, ANOVA unpaired t-test, and Kaplan-Meier Curve Method. A p-value of less than 0.05 was considered statistically significant. All participants underwent a questionnaire, physical examination, medical history assessment, and laboratory tests. The results of the study showed that there was a significant correlation between IL-6 and hsCRP levels in the Quartile groups, as well as with lipid profiles. The Kaplan-Meier method also demonstrated a significant association between IL-6 and hsCRP levels in participants. The comparison of biomarkers further supported these findings. Thus, data shows that elevated levels of hsCRP and IL-6 could serve as valuable diagnostic markers for predicting Acute Myocardial Infarction. Our study strongly suggests that IL-6 could be a powerful marker in evaluating the Myocardial Infarction.

A network meta-analysis of the association between patient traits and response to regular dosing with ICS plus short-acting ß2-agonist reliever or ICS/formoterol reliever only in mild asthma.

INTRODUCTION/BACKGROUND: Mild asthma treatment recommendations include intermittent inhaled corticosteroid (ICS)/formoterol dosing or regular ICS dosing with short-acting ß2-agonist reliever. Due to the heterogeneity of asthma, identification of traits associated with improved outcomes to specific treatments would be clinically beneficial. AIMS/OBJECTIVES: To assess the impact of patient traits on treatment outcomes of regular ICS dosing compared with intermittent ICS/formoterol dosing, a systematic literature review (SLR) and network meta-analysis (NMA) was conducted. Searches identified randomised controlled trials (RCTs) of patients with asthma aged ≥12 years, containing ≥1 regular ICS dosing or intermittent ICS/formoterol dosing treatment arm, reporting traits and outcomes of interest. RESULTS: The SLR identified 11 RCTs of mild asthma, of 14,516 patients. A total of 11 traits and 11 outcomes of interest were identified. Of these, a feasibility assessment indicated possible assessment of three traits (age, baseline lung function, smoking history) and two outcomes (exacerbation rate, change in lung function). The NMA found no significant association of any trait with any outcome with regular ICS dosing relative to intermittent ICS/formoterol dosing. Inconsistent reporting of traits and outcomes between RCTs limited analysis. CONCLUSIONS: This is the first systematic analysis of associations between patient traits and differential treatment outcomes in mild asthma. Although the traits analysed were not found to significantly interact with relative treatment response, inconsistent reporting from the RCTs prevented assessment of some of the most clinically relevant traits and outcomes, such as adherence. More consistent reporting of respiratory RCTs would provide more comparable data and aid future analyses.

Adiponectin and HbA1c levels among Indian patients with diabetes mellitus.

Adiponectin is closely related to glucose metabolism and newly diagnosed type 2 diabetes mellitus (T2DM), and other kinds of diabetes linked to the risk of T2DM. Therefore, it is of interest to report the correlation between adiponectin levels and glycosylated hemoglobin (HbA1c) as a diagnostic marker of T2DM and healthy control. Total 210 participants were included of IPD & OPD healthy controls with glycosylated hemoglobin levels under 6% were included. Blood samples, collected using sterile clot activator or plain vials, were stored at -20°C. The biomarker score that comprised significant differences in age, gender distribution, and metabolic indicators are seen between the diabetes (n=105) and control (n=105) groups. Increase in both Adiponectin and HbA1c% Mean±SD (6.86±0.23, p<0.0001; 22.71±2.01; p<0.0001) is indicative of deteriorating glycaemic control and an accompanying rise in inflammatory response. Positively correlate adiponectin levels with HbA1c levels (r2=0.398; p<0.0001), suggesting a link between inflammatory response and glucose control. Lower adiponectin levels are statistically associated with diabetes. Diabetes and adiponectin were negatively correlated and positive linear relationship between HbA1c and adiponectin levels. Adiponectin may be a significant factor useful in understanding the pathophysiology; they are likely to be straight forward instruments for predicting future risk of diabetes.

Comprehensive workflow and its validation for simulating diffuse speckle statistics for optical blood flow measurements.

Diffuse optical methods including speckle contrast optical spectroscopy and tomography (SCOS and SCOT), use speckle contrast (κ) to measure deep blood flow. In order to design practical systems, parameters such as signal-to-noise ratio (SNR) and the effects of limited sampling of statistical quantities, should be considered. To that end, we have developed a method for simulating speckle contrast signals including effects of detector noise. The method was validated experimentally, and the simulations were used to study the effects of physical and experimental parameters on the accuracy and precision of κ. These results revealed that systematic detector effects resulted in decreased accuracy and precision of κ in the regime of low detected signals. The method can provide guidelines for the design and usage of SCOS and/or SCOT instruments.

Genetic diversity, population structure analysis and codon substitutions of Indicine Badri cattle using ddRAD sequencing.

The present study was carried out on 96 animals representing three distinct colour variants of Badri cattle to investigate the genetic diversity, population structure and substitution mutations in the genetic codons due to single nucleotide variations. The DNA samples of 96 Badri cows were genotyped using a double digestion restriction associated DNA (ddRAD) sequencing approach. A standardized bioinformatics pipeline was employed to identify single nucleotide polymorphisms (SNPs), initially detecting 7,168,552 SNPs through alignment with the Bos indicus reference genome assembly. Subsequent stringent quality filtration yielded 65,483 high-confidence SNPs for downstream analysis. Genetic diversity analysis of the Badri cattle population resulted in average values of 0.145, 0.088, and 0.091 for Shannon's diversity Index (I), Simpson's Diversity (h), and Simpson's Unbiased Diversity (uh), respectively. Genetic similarities between the black and brown, black and grey, and brown and grey Badri variants were found to be 0.9972, 0.9980 and 0.9970, respectively. Tajima's D diversity value was observed to be significant and positive for 99.29% of high-confidence SNPs (65,483). STRUCTURE analysis showed admixture among the three Badri colour variants, suggesting a lack of genetic differentiation. Annotation of high-confidence SNPs regarding genetic codon changes indicated maximum substitutions in the GGC with GGT (22 occurrences), followed by AAC to AGC (20 occurrences), GAA to TAA (19 occurrences) and CAA to CAG (19 occurrences). The study concludes there are genetic similarities among colour variants, lack of rare alleles, balancing selection, sudden population contraction and genetic codon substitutions within the Badri cattle population. Insights derived from SNP data analysis hold potential significance for conservation initiatives and breed improvement programs for indicine cattle.

Systematic literature review of traits and outcomes reported in randomised controlled trials of asthma with regular dosing of inhaled corticosteroids with short-acting ß2-agonist reliever, as-needed ICS/formoterol, or ICS/formoterol maintenance and reliever therapy.

INTRODUCTION: Asthma treatments based solely on diagnostic label do not benefit patients equally. To identify patient traits that may be associated with improved treatment response to regular inhaled corticosteroid (ICSs) dosing with short-acting ß2-agonist reliever or ICS/formoterol-containing therapy, a systematic literature review (SLR) was conducted. METHODS: Searches of databases including MEDLINE and Embase identified randomised controlled trials (RCTs) of patients with asthma, aged ≥12 years, published 1998-2022, containing ≥1 regular ICS dosing or ICS/formoterol-containing treatment arm, and reporting patient traits and outcomes of interest. Relevant data was extracted and underwent a feasibility assessment to determine suitability for meta-analysis. RESULTS: The SLR identified 39 RCTs of 72,740 patients and 90 treatment arms, reporting 11 traits and 11 outcomes. Five patient traits (age, body mass index, FEV1, smoking history, asthma control) and five outcomes (exacerbation rate, lung function, asthma control, adherence, time to first exacerbation) were deemed feasible for inclusion in meta-analyses due to sufficient comparable reporting. Subgroups of clinical outcomes stratified by levels of patient traits were reported in 16 RCTs. CONCLUSION: A systematic review of studies of regular ICS dosing with SABA or ICS/formoterol-containing treatment strategies in asthma identified consistent reporting of five traits and outcomes, allowing exploration of associations with treatment response. Conversely, many other traits and outcomes, although being potentially relevant, were inconsistently reported and limited subgroup reporting meant analyses of treatment response for subgroups of traits was not possible. We recommend more consistent measurement and reporting of clinically relevant patient traits and outcomes in respiratory RCTs.

Meta-analysis and cost-effectiveness analysis of intranasal corticosteroid treatment in allergic rhinitis with ocular symptoms.

BACKGROUND: Intranasal corticosteroid (INCS) has a beneficial effect on ocular symptoms in allergic rhinitis (AR). To our knowledge, the cost-effectiveness of available INCS for AR with ocular symptoms is yet to be demonstrated. OBJECTIVE: To evaluate the cost-effectiveness of INCSs including Budesonide (BANS), Mometasone furoate (MFNS), Triamcinolone (TANS), and Fluticasone furoate (FFNS) on ocular symptoms associated with AR in the Thai context. METHODS: The percentage of effectiveness in improving total ocular symptoms score (TOSS) was derived from the result of a meta-analysis that estimated the SMD of each INCS treatment compared to placebo as clinical input parameters. A cost-effectiveness analysis based on a decision-tree model to assess one-year costs and outcomes from a Thai societal perspective. The outcomes were to compare incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analyses (PSA) were also conducted to capture parameter uncertainties. RESULTS: 13 eligible RCTs with a total of 3,722 patients with SAR were included in the analysis. The percentage of effectiveness of FFNS, MFNS, TANS, and BANS was 59.89%, 45.60%, 24.89%, and 16.00%, respectively. The ICER of FFNS, MFNS, and TANS is THB-6,539.92, 4,593.83, and 1,401.24 compared to BANS. CECA result showed the probability of using FFNS is considered cost-effective in 87.50% of cases from zero value followed by MFNS (0.80%), TANS (5.40%), and BANS (6.30%). With a threshold greater than THB20,000, FFNS is considered a cost-effective strategy. CONCLUSIONS: FFNS is a cost-effective option compared to alternative INCSs in Thailand for treating AR with ocular symptoms.

Validation of secretory Immunoglobulin A (IgA) for early and efficient diagnosis of Pseudomonas aeruginosa lung infection.

Pseudomonas aeruginosa is a gram-negative bacterium that is considered to be a major causal organism of nosocomial infection. This study brought data-specific evidence to reveal the efficacy of secretory Immunoglobulin A (IgA) measurement in diagnosing pulmonary P. aeruginosa infection and claims its validation as a diagnostic marker. This study has included controls and patients of Pseudomonas and grouped them into four, namely, controls, chronic cases, intermittent cases, and negative group. The last group, that is, the "Negative" group, is the ones who had a history of infection but currently showed negative blood culture. The level of sIgA was quantified in all the patients and the controls and then their status of pulmonary infection was determined by their blood culture. ANOVA and Pearson Chi-Square were employed for showing the association between sIgA and pulmonary infection. The mean value of salivary sIgA has been found the highest in chronic cases followed by Intermittent cases and Negative Infections. The boxplot diagram showed several parameters of sIgA quantification in each group and control. ANOVA and Pearson Chi-square (P<0.005) tests showed a significant association between sIgA level in saliva and pulmonary infection of P. aeruginosa. The ROC curve was plotted to determine the cut-off value of sIgA (sIgA≧13.09 U/ml) for efficient clinical diagnosis of pulmonary P. aeruginosa infection. The study has validated statistically that quantification of salivary sIgA can be used in clinical practice for early diagnosis of pulmonary infection of P. aeruginosa.

Anatomical Modeling and Optimization of Speckle Contrast Optical Tomography.

Traditional methods for mapping cerebral blood flow (CBF), such as positron emission tomography and magnetic resonance imaging, offer only isolated snapshots of CBF due to scanner logistics. Speckle contrast optical tomography (SCOT) is a promising optical technique for mapping CBF. However, while SCOT has been established in mice, the method has not yet been demonstrated in humans - partly due to a lack of anatomical reconstruction methods and uncertainty over the optimal design parameters. Herein we develop SCOT reconstruction methods that leverage MRI-based anatomical head models and finite-element modeling of the SCOT forward problem (NIRFASTer). We then simulate SCOT for CBF perturbations to evaluate sensitivity of imaging performance to exposure time and SD-distances. We find image resolution comparable to intensity-based diffuse optical tomography at superficial cortical tissue depth (~1.5 cm). Localization errors can be reduced by including longer SD-measurements. With longer exposure times speckle contrast decreases, however, noise decreases faster, resulting in a net increase in SNR. Specifically, extending exposure time from 10µs to 10ms increased SCOT SNR by 1000X. Overall, our modeling methods provide anatomically-based image reconstructions that can be used to evaluate a broad range of tissue conditions, measurement parameters, and noise sources and inform SCOT system design.

A comprehensive workflow and its validation for simulating diffuse speckle statistics for optical blood flow measurements.

Diffuse optical methods including speckle contrast optical spectroscopy and tomography (SCOS and SCOT), use speckle contrast (κ) to measure deep blood flow. In order to design practical systems, parameters such as signal-to-noise ratio (SNR) and the effects of limited sampling of statistical quantities, should be considered. To that end, we have developed a method for simulating speckle contrast signals including effects of detector noise. The method was validated experimentally, and the simulations were used to study the effects of physical and experimental parameters on the accuracy and precision of κ. These results revealed that systematic detector effects resulted in decreased accuracy and precision of κ in the regime of low detected signals. The method can provide guidelines for the design and usage of SCOS and/or SCOT instruments.

Serum Expression Level of MicroRNA-122 and its Significance in different Stages of Hepatitis B Virus Infection.

This study aims to determine the serum expression level of miRNA-122 and its significance in the different stages of Hepatitis B virus infection. The study subjects were recruited and grouped for Hepatitis B associated with Chronic Hepatitis B infection, hepatic sclerosis, hepatocellular carcinoma, and healthy controls were also considered. Venous blood was collected from the participants including the controls and routine blood tests and quantification of miRNA-122 were done and analyzed in each case of hepatitis B infection and compared with that of healthy controls. The miRNA-122 was determined, which came to be highest in patients with Chronic Hepatitis B while patients with hepatic sclerosis and patients with hepatocellular carcinoma showed a subsequent number of copies. The number of copies of miRNA-122 in the CHB, hepatic sclerosis, and HCC group was significantly higher than in the healthy control. The quantification of miRNA-122 and subsequently plotting the ROC curve has shown that miRNA-122 can be considered as a biomarker of hepatitis B for screening and diagnosis purposes.

A network meta-analysis of the association between patient traits and response to regular dosing with ICS/long-acting ß2-agonist plus short-acting ß2 agonist reliever or maintenance and reliever therapy for asthma.

INTRODUCTION: Current treatment for moderate-severe asthma with inhaled corticosteroid (ICS)-based therapy can follow two strategies: a single inhaler maintenance and reliever therapy (MART) regimen, or regular dosing with ICS/long-acting ß2-agonist used as maintenance therapy plus a separate short acting ß2-agonist reliever inhaler. It would be clinically useful to understand the potential of patient traits to influence regular dosing or MART treatment outcomes. OBJECTIVES: A systematic literature review (SLR) and meta-analysis was conducted to identify specific patient traits that may predict improved clinical outcomes with regular dosing or MART. RESULTS: The SLR identified 28 studies in patients with moderate-severe asthma assessing regular dosing or MART treatments and reporting the traits and outcomes of interest. Network meta-regressions found no significant difference in the relative efficacy of regular dosing as compared with MART on any of the clinical outcomes (exacerbation rate, time to first exacerbation, FEV1, reliever use and adherence) for any of the patient traits (baseline lung function, baseline ACQ, age, BMI, and smoking history) evaluated. However, some trends towards traits influencing treatment efficacy were identified. Inconsistent reporting of traits and outcomes was observed between trials. CONCLUSIONS: The analysed patient traits evaluated in this study were associated with similar efficacy for the analysed outcomes to either regular dosing or MART; however, trends from the data observed encourage future analyses for possible identification of additional traits, or a combination of traits, that may be of interest. More comparable reporting of clinically important traits and outcomes would improve future analyses.

Assessing the Effects of Changing Patterns of Inhaled Corticosteroid Dosing and Adherence with Fluticasone Furoate and Budesonide on Asthma Management.

INTRODUCTION: Pharmacological asthma management focuses on the use of inhaled corticosteroid (ICS)-containing therapies, which reduce airway inflammation and provide bronchoprotection, improving symptom control and reducing exacerbation risk. ICS underuse due to poor adherence is common, leading to poor clinical outcomes including increased risk of mortality. This article reviews efficacy versus systemic activity profiles for various adherence patterns and dosing regimens of fluticasone furoate (FF)-containing and budesonide (BUD)-containing asthma therapies in clinical trials and real-world studies. METHODS: We performed a structured literature review (1 January 2000-3 March 2022) and mathematical modelling analysis of FF-containing and BUD-containing regular daily dosing in patients with mild-to-severe asthma, as-needed BUD/formoterol (FOR) in mild asthma, and BUD/FOR maintenance and reliever therapy (MART) dosing in moderate-to-severe asthma, to assess efficacy (bronchoprotection) and systemic activity (cortisol suppression) profiles of dosing patterns of ICS use in multiple adherence scenarios. RESULTS: A total of 22 manuscripts were included in full-text review and 18 in the model simulations. Focusing on FF-containing or BUD-containing treatments at comparable adherence rates, regular daily FF or FF/vilanterol (VI) dosing provided more prolonged bronchoprotection and fewer systemic effects than daily BUD, daily BUD/FOR, or BUD/FOR MART dosing, especially in low adherence scenarios. In model simulations and the real-world setting, FF/VI generally provided longer bronchoprotection, lower systemic activity, and greater clinical benefits over BUD/FOR as well as consistently higher adherence. CONCLUSION: In this literature review and modelling analysis, FF/VI was found to show clinical advantages on asthma control over BUD/FOR. These findings have implications for helping clinicians select the most suitable inhaled therapy for their patients with asthma.

Park Area and Physical Activity Among Children and Adolescents: Findings From the Healthy Communities Study.

BACKGROUND: There is currently a nationwide effort to bring parks and green spaces within a 10-minute walk of the home. We examined the association between park area within 1 km of a child's residence and self-reported park-specific physical activity (PA) along with accelerometer-derived moderate to vigorous physical activity (MVPA). METHODS: A subsample of K through eighth-grade youth (n = 493) from the Healthy Communities Study reported whether they engaged in park-specific PA during the last 24 hours and wore an accelerometer for up to 7 days. Park area was defined as the percentage of park land in a 1 km Euclidean buffer around the participant's residence, categorized into quintiles. Analysis consisted of logistic and linear regression modeling with interaction effects that controlled for clustering within communities. RESULTS: Regression models estimated greater park-specific PA for participants in the fourth and fifth quintiles of park land. Age, sex, race ethnicity, and family income were unrelated to park-specific PA. Accelerometer analysis indicated that total MVPA was unrelated to park area. Older children (ß = -8.73, P < .001) and girls (ß = -13.44, P < .001) engaged in less MVPA. Seasonality significantly predicted both park-specific PA and total MVPA. CONCLUSION: Increasing park area is likely to improve youth PA patterns, lending support for the 10-minute walk initiative.

Evaluation of Lung Functions, Blood Pressure, and Hearing Deterioration in Tile Setters.

INTRODUCTION: Tile setters in construction industries are exposed to a potent risk of silicosis as they are constantly exposed to crystalline silica dust during concrete finishing, cutting and fixing of the ceramic tiles. The noise produced by instruments used in tile settings may lead to noise-induced hearing loss. Noise above the permissible limit of 85 dB may lead to autonomic changes and alteration in blood pressure. These facts gave us an impetus to evaluate the pulmonary functions, blood pressure and hearing deterioration in tile setters and correlate these parameters for their present functional status with duration of exposure to tile cutting profession. METHODS: The pulmonary functions were evaluated with spirometer, autonomic status by recording the blood pressure and hearing loss by calculating the Hearing Deterioration Index (HDI) for hearing loss. RESULTS: There was significant decline in forced vital capacity (FVC), forced expiratory volume 1 sec (FEV1) and forced expiratory volume 1% (FEV1%) in tile setters. The decline in FVC, FEV1 and FEV1% was significantly higher in subjects with exposure of more than five years. There was increased systolic and diastolic blood pressure in those having more than five years of exposure in the tile setting profession as compared to less than five years. There was a positive correlation between years of service in the tile setting profession as well as sound exposure level with HDI and blood pressure in our subjects. CONCLUSION: Prolonged exposure to the tile setting profession may lead to compromised lung function, hypertension and hearing deterioration in tile setters.