Short-term Trials Research Articles

The effect of empagliflozin on right ventricular function in heart failure patients with reduced ejection fraction: analysis from the randomized empire hf clinical trial

Abstract Background Reverse remodeling of the left ventricle (LV) has been proposed as a key mechanism to the cardio-protective effects of sodium-glucose-transporter-2 (SGLT2) inhibitors in patients with heart failure and reduced ejection fraction (HFrEF). Deterioration of the right ventricular (RV) function is associated with poor outcome, whereas improvement in RV dysfunction has been correlated with improved outcomes in HFrEF patients. The impact of SGLT2 inhibitors on the RV remains unclear. Purpose The aim of this post-hoc study of the Empire HF trial was to investigate the effect of Empagliflozin on RV function assessed by echocardiography in patients with HFrEF after 12 weeks of treatment compared to placebo. Methods The Empire HF trial was a double-blind, placebo-controlled, randomized clinical trial, in which 190 stable HFrEF patients with a LV ejection fraction (LVEF) ≤40% were randomized (1:1) to receive Empagliflozin 10 mg once daily or matching placebo for 12 weeks. Echocardiographic images were analysed blinded to treatment allocation. Exploratory outcomes were changes in right ventricular function. Statistical analyses were performed using mixed-effects linear models adjusted for age, sex and baseline variables. Results Baseline characteristics were well balanced between the two groups; mean age 64 (SD±11) years; males: 85%; mean LVEF 29 (SD±8) %, RV free wall strain (RVFWS): -16.7 (SD±6)%, NYHA-functional class II: 78% and ischemic HFrEF etiology: 51%. No significant between-group differences were detected in RV free wall strain (RVFWS), tricuspid annular plane systolic excursion (TAPSE) or S’ RV free wall (all P>0.05), Figure 1. When stratified into baseline tertiles of RVFWS, patients in the lowest tertile showed a significant improvement in the Empagliflozin group compared to placebo (treatment effect: -4.4 % [95% CI: -8.0 to -0.8]; P=0.018), Figure 2. There was no correlation between the effect of Empagliflozin on RVFWS in the lowest RVFWS tertile and other changes such as LVEF (P=0.845), plasma volume (P=0.710) or weight loss (P=0.639). Conclusion In this randomized, short-term trial, Empagliflozin did exert a significant effect on RV function in stable HFrEF patients in the overall study population, but notably improved RVFWS in patients in the lowest tertile of RVFWS at baseline after 12 weeks of treatment. Additional research is required to confirm these explorative findings, and to better understand the impact of SGLT2i on RV function and identify patients who could potentially experience therapeutic and prognostic benefits by RV improvement.

The Effects of Bitter Melon (Mormordica charantia) on Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Research indicates that bitter melon could be useful in the management of dyslipidemia. Still, there is disagreement concerning the findings. This systematic study was undertaken to clarify the impact of consuming bitter melon on lipid profile. The databases Web of Science, Cochrane Library, PubMed, and Scopus were queried from inception until February 9, 2023. The study assessed triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. The effect sizes were calculated using weighted mean differences (WMDs) and 95% confidence intervals (CIs). Eight randomized controlled trials (RCTs) with a total of 423 participants were included. Bitter melon consumption resulted in a significant decrease in plasma concentrations of TC (WMD; -9.71 mg/dL; CI: -17.69 to -1.74, p = 0.01) and TG (WMD; -10.24 mg/dL; CI: -19.92 to -0.56, p = 0.03), while bitter melon did not significantly lower blood LDL-C (WMD; -8.66 mg/dL; CI: -19.83 to 2.50, p = 0.12) and HDL-C concentrations (WMD; 0.54 mg/dL; CI: -2.38 to 3.45, p = 0.71). Subgroup analysis showed a significant decrease in TC and LDL-C and an increase in HDL-C at a dose of ≤ 2000 mg/day and an intervention period of ≤ 8 weeks. Also, the greatest impact of LDL-C and HDL-C was seen in diabetic and prediabetic people. Bitter melon supplementation positively impacts TC and TG levels. The limitations of this study were short-term trials (less than 3 months).

Potassium limits productivity in intensive cereal cropping systems in Southeast Asia.

Potassium (K) has received little attention as a potential yield-limiting factor in cropping systems. Here we investigated the K status in intensive cereal cropping systems in Indonesia, which are representative of many other Southeast Asian countries. Our analysis included nutrient input-output balance, leaf nutrient status, long- and short-term fertilizer trials, and farmer surveys. We revealed that soil K levels alone are insufficient to meet plant requirements, and current fertilizer applications are inadequate to prevent K deficiencies and large negative annual soil K balances in farmer fields (average -62 kgK ha-1). On-farm fertilizer trials indicated that nearly 80% of rice crops and 70% of maize crops achieved higher yields with the application of K fertilizer. Addressing K limitations will require an enhanced capacity to predict crop responses to K fertilizer, together with long-term, flexible fertilizer and crop residue management strategies. Furthermore, similar K limitations have probably emerged in other regions globally due to intensive cropping with insufficient K replenishment, which must be addressed to close yield gaps on existing farmland.

Pressure-induced piezoelectric response for mitigating membrane fouling in surface water treatment: Insights from continuous operation and biofouling characterization

Organic fouling and biofouling represents a critical challenge encountered by the membrane-based water treatment process. Herein, a piezoelectric PVDF membrane (PEM), capable of generating electrical responses to hydraulic pressure stimuli, was synthesized and employed for mitigating the fouling in surface water treatment. The surface-hydrophobilized PEM demonstrated sensitive and enhanced underwater output performance in response to increasing transmembrane pressure (TMP) during constant-flux filtration, with signals reaching up to ∼800 mV at a TMP of ∼80 kPa. This in-situ piezoelectric response significantly reduced TMP growth in both short-term (1 h) and long-term (15 days) filtration trials, demonstrating a strong capability to mitigate membrane fouling. Moreover, continuous piezoelectric stimulation effectively inhibited microbial activity and the accumulation of extracellular polymeric substances (EPS) on PEM surface, surpassing the dominant electrokinetic repulsion mechanisms observed in short-term trials. Microbial community analysis suggests that this evolution is primarily due to the targeted impact of piezoelectric stimulation on microbial metabolic behavior. The piezoelectric-induced electrical microenvironment inhibited the growth of microbes associated with high EPS production while promoting the proliferation of electrically active microbes involved in biopolymer digestion. In addition, the PEM demonstrated enhanced permeate quality throughout the filtration process, with DOC and UV254 removal rates increasing from 11.7 % and 15.6 % initially to 28.6 % and 19.5 % by the 15th day, respectively. Given the performance and self-powered capability of PEM compared to current electrified antifouling methods that require an external power supply, these attributes are anticipated to hold practical significance in developing innovative and energy-efficient strategies for mitigating both organic fouling and biofouling.

Possible Data-Generating Models of Longitudinal Continuous Outcomes and Intercurrent Events to Investigate Estimands

We aim to explore data-generating models to jointly simulate outcomes and intercurrent events for randomized clinical trials to enable the investigation of estimands. We develop four possible data-generating models for the joint distribution of longitudinal continuous clinical outcomes and intercurrent events under the scenario where they are observable: a selection model, a pattern-mixture mixed model, a shared-parameter model, and a joint model of longitudinally observed outcomes and a survival model for intercurrent events. We present a case study in a short-term depression trial with repeated measurements of continuous outcomes and two types of intercurrent events, and evaluate the potential and challenges of such data-generating models. Simulating randomized trials with outcomes and intercurrent events is a complex undertaking. We found that the four possible data-generating models can simulate different types of intercurrent events and associated longitudinal outcomes. They can be used to emulate envisaged patterns of intercurrent events and outcomes informed by prior available trial data or expectations. Model and parameter choice for a given application require further development. The four possible data-generating models could be used to investigate different estimands and their properties in-depth in the design stage. Thereby they are useful tools for the selection of estimands a priori.

IPECAD Modeling Workshop 2023 Cross Comparison Challenge on Cost-Effectiveness Models in Alzheimer’s Disease

Decision-analytic models assessing the value of emerging Alzheimer's disease (AD) treatments are challenged by limited evidence on short-term trial outcomes and uncertainty in extrapolating long-term patient-relevant outcomes. To improve understanding and foster transparency and credibility in modeling methods, we cross-compared AD decision models in a hypothetical context of disease-modifying treatment for mild cognitive impairment (MCI) due to AD. A benchmark scenario (US setting) was used with target population MCI due to AD and a set of synthetically generated hypothetical trial efficacy estimates. Treatment costs were excluded. Model predictions (10-year horizon) were assessed and discussed during a 2-day workshop. Nine modeling groups provided model predictions. Implementation of treatment effectiveness varied across models based on trial efficacy outcome selection (CDR-SB, CDR-global, MMSE, FAQ) and analysis method (observed severity transitions, change from baseline, progression hazard ratio, or calibration to these). Predicted mean time in MCI ranged from 2.6-5.2 years for control strategy, and from 0.1-1.0 years for difference between intervention and control strategies. Predicted quality-adjusted life-year gains ranged from 0.0-0.6 and incremental costs (excluding treatment costs) from -US$66,897 to US$11,896. Trial data can be implemented in different ways across health-economic models leading to large variation in model predictions. We recommend 1) addressing the choice of outcome measure and treatment effectiveness assumptions in sensitivity analysis, 2) a standardized reporting table for model predictions, and 3) exploring the use of registries for future AD treatments measuring long-term disease progression to reduce uncertainty of extrapolating short-term trial results by health economic models.

Phase 2 Trial of Anti-TL1A Monoclonal Antibody Tulisokibart for Ulcerative Colitis

BackgroundTulisokibart is a tumor necrosis factor–like cytokine 1A (TL1A) monoclonal antibody in development for the treatment of moderately to severely active ulcerative colitis. A genetic-based diagnostic test was designed to identify patients with an increased likelihood of response.MethodsWe randomly assigned patients with glucocorticoid dependence or failure of conventional or advanced therapies for ulcerative colitis to receive intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10) or placebo. Cohort 1 included patients regardless of status with respect to the test for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response. The primary analysis was performed in cohort 1; the primary end point was clinical remission at week 12. Patients with a positive test for likelihood of response from cohorts 1 and 2 were combined in prespecified analyses.ResultsIn cohort 1, a total of 135 patients underwent randomization. A significantly higher percentage of patients who received tulisokibart had clinical remission than those who received placebo (26% vs. 1%; difference, 25 percentage points; 95% confidence interval [CI], 14 to 37; P<0.001). In cohort 2, a total of 43 patients underwent randomization. A total of 75 patients with a positive test for likelihood of response underwent randomization across both cohorts. Among patients with a positive test for likelihood of response (cohorts 1 and 2 combined), clinical remission occurred in a higher percentage of patients who received tulisokibart than in those who received placebo (32% vs. 11%; difference, 21 percentage points; 95% CI, 2 to 38; P=0.02). Among all the enrolled patients, the incidence of adverse events was similar in the tulisokibart and placebo groups; most adverse events were mild to moderate in severity.ConclusionsIn this short-term trial, tulisokibart was more effective than placebo in inducing clinical remission in patients with moderately to severely active ulcerative colitis. (Funded by Prometheus Biosciences, a subsidiary of Merck; ARTEMIS-UC ClinicalTrials.gov number, NCT04996797.)

Opicapone for the treatment of early wearing-off in levodopa-treated Parkinson’s disease: pooled analysis of patient level data from two randomized open-label studies

BackgroundThe wearing-off phenomenon is a key driver of medication change for patients with Parkinson’s disease (PD) treated with levodopa. Common first-line options include increasing the levodopa dose or adding a catechol-O-methyltransferase (COMT) inhibitor, but there are no trials comparing the efficacy of these approaches. We evaluated the effectiveness of adjunct opicapone versus an additional 100 mg levodopa dose in PD patients with early wearing-off using pooled data from 2 randomized studies.MethodsThe ADOPTION study program included two similarly designed 4-week, open-label studies conducted in South Korea (NCT04821687) and Europe (NCT04990284). Patients with PD, treated with 3–4 daily doses of levodopa therapy and with signs of early wearing-off were randomized (1:1) to adjunct opicapone 50 mg or an additional dose of levodopa 100 mg. Patient-level data from the two studies were pooled.ResultsThe adjusted mean [SE] change from baseline to week 4 in absolute OFF time (key endpoint) was − 62.8 min [8.8] in the opicapone group and − 33.8 min [9.0] in the levodopa 100 mg group, the difference significantly favoring opicapone (− 29.0 [− 53.8, − 4.2] min, p = 0.02). Significant differences in the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale Part III subscore (− 4.1 with opicapone vs − 2.5 with levodopa 100 mg), also favored opicapone (− 1.7 [− 3.3, − 0.04], p < 0.05). Dyskinesia was the most frequently reported adverse event (opicapone 7.2% vs. levodopa 100 mg 4.2%).ConclusionsIn these short-term trials, introducing adjunct opicapone was more effective at reducing OFF time than adding another 100 mg levodopa dose in PD patients with early signs of wearing-off.

Dairy effluent applications to a pasture enhance soil fertility and microbial activity without impacting soil bacterial and fungal community composition

Farm dairy effluents (FDE) from washing the milking parlor contain manure, urine, and chemicals and constitute a large amount of wastewater. Applying FDE as soil fertilizers to pastures can enhance forage yield and improve soil nutrient status. Since the dairy industry is increasingly attempting to maximize returns through better utilization of forage with lesser inputs, there is demand for a supply of FDE as fertilizers. Nevertheless, the impact of this practice on soil microbiota remains largely unexplored. It must be studied before large-scale soil disposal to avoid diminishing microbial diversity or enhancing pathogen abundance. This study evaluated the effects of applying lagoon-stored (Lagoon) and raw dairy effluents (Raw) at a rate of 50 kg N ha−1 in four equal doses, in comparison to urea fertilization, on soil fertility and the activity, abundance, and community structure of soil microbiota. Raw was obtained after solid separation, and Lagoon corresponds to the Raw stationed in a two-lagoon system. Microbial activity was assessed as basal respiration, potentially mineralizable N, potential nitrification activity, and enzymatic activities. The catabolic activity of the microbial community was evaluated using Biolog Ecoplates™. Bacterial and fungal community composition and diversity were analyzed through amplicon sequencing of 16S rRNA and ITS2. The application of FDE benefited soil fertility and microbial activity. Lagoon had the most potent effects on soil available P and extractable K+, Na+, Mg2+ and Ca2+. Soil treated with Raw displayed higher microbial activities, such as dehydrogenase, basal respiration, urease, and potentially mineralizable N, than the other treatments. FDE did not significantly alter the microbial composition, abundance, or functional diversity. In conclusion, in this short-term trial, despite changes in soil chemical properties and microbial activity, the composition and diversity of the bacterial and fungal communities remained unaffected by FDE irrigation.

A systematic review of the psychometric properties of the Leicester Cough Questionnaires based on the COSMIN guidelines

BackgroundChronic cough affects around 10 % of the general adult population, impairing all aspects of quality of life. Research questionWhat are the Leicester Cough Questionnaire's psychometric properties? Study design and methodsElectronic searches of PubMed, CINAHL, and ScienceDirect databases were conducted from inception until October 1rst 2022. All full-text articles, published in French or English, aimed at evaluating the LCQ's content validity or psychometric properties were included. The COSMIN Risk of Bias checklist was applied to assess their methodological quality and results. Results were qualitatively summarised and rated by a modified GRADE approach. Results40 studies were included accounting for 8731 adults, subject to cough or a respiratory condition. Chronic cough (>8 weeks) was the most represented. The LCQ's total score is relevant and comprehensible for the assessment of the impact of cough on QoL. The original 3-factor model showed a satisfactory model fit. Good convergent validity was found for the total and physical domain scores. These scores demonstrate good internal consistency and test retest reliability, with some variability noted and they are responsive to change. Recent estimates of MID thresholds were 1.7 and 0.4 for total and domain scores respectively. The quality of the studies is globally poor. InterpretationThe LCQ is a valid outcome to assess the intra-individual impact of cough on QoL and to detect large changes in quality of life mainly in a short-term clinical trial setting. Clinical trial registrationThe protocol was registered with PROSPERO (CRD42022355191).

Prospective Clinical Trial Demonstrating the Efficacy of Hyaluronic Acid Filler for the Improvement of Atrophic Facial Scars up to 2 years.

Hyaluronic acid (HA) filler longevity has been studied for wrinkles. However, its long-term use for treating atrophic facial scars has not yet been analyzed in long-term prospective studies. Analyze the safety and duration of a HA filler for the use in atrophic scars. Fifteen subjects received VYC-17.5L in atrophic scars on 1 randomized cheek and saline on the other, with 1 optional touch-up treatment and crossover after the short-term trial. Grading for this long-term extension was done on Day 720, using the Global Aesthetic Improvement Scale (GAIS) and the Quantitative Global Scarring Grading System. On Day 720, a live blind evaluator rated the VYC-17.5L assigned side as having significant reduction in scar severity (-7.2 [t(22) = -6.01, p = .00009]) and number of scars (-8.8 [t(22) = -6.25, p = .00006]) as compared with baseline. There was no significant difference in the results from Day 120 to Day 720. Ninety-two percent (11/12) of subjects reported improvement (GAIS), were satisfied with the treatment, thought it looked natural, and had fewer side effects than expected. There were no persistent or late-onset side effects. VYC-17.5L improved rolling atrophic facial scars, and the results were sustained throughout the 2-year trial without side effects.

Modelling changes in whole body and fillet fatty acid composition of Atlantic salmon with changing levels of dietary omega-3 intake

In this study, a fatty acid dilution model was coupled with a dynamic nutrient demand model to provide an integrated model capable of predicting the whole-body and fillet lipid and fatty acid levels of Atlantic salmon (Salmo salar) following a change in dietary fatty acid profile. Based on knowledge of the initial fish and dietary fatty acid compositions, diet digestible energy density, the water temperature and duration of feeding, the model demonstrated that it was possible to predict a range of parameters, including the growth, feed utilisation, whole-body and fillet (Norwegian Quality Cut; NQC) total lipid, and fatty acid levels of the fish. The model was validated against five separate experiments, including two farm-based trials with harvest size fish. Validation experiments involved fish ranging in size (initial weights to final weights) from 138 g/fish to 5138 g/fish and running for durations of between 66 and 323 days. For the laboratory experiments, prediction of growth, feed utilisation and fatty acid deposition proved to be highly predictable (R2 > 0.998). Fatty acid profiles from both short and long-term cage trials were also highly predictable. Despite the reduced level of weight change in the short-term cage trial, and the higher variability that was observed in growth performance, the fatty acid deposition still showed high levels of correlation (R2 > 0.996), between the modelled and measured fatty acid levels in the fish fillet. Departure from linearity was more evident in the long-term cage trial, but correlation still exceeded R2 > 0.995 for all treatments. Prediction of whole-body and NQC total lipid levels was less accurate, with correlations being R2 = 0.962 and R2 = 0.909 respectively. Model outputs were generally more accurate with greater weight change and/or experiment duration. The outcome of this study shows that the model developed here provides a useful tool for the estimation of the fatty acid composition of Atlantic salmon following a change in dietary fatty acid composition. This could help assist in the more judicious use of dietary long-chain omega-3 fatty acids for commercial salmon farming.

Short-Term Memory Capacity Predicts Willingness to Expend Cognitive Effort for Reward.

We must often decide whether the effort required for a task is worth the reward. Past rodent work suggests that willingness to deploy cognitive effort can be driven by individual differences in perceived reward value, depression, or chronic stress. However, many factors driving cognitive effort deployment-such as short-term memory ability-cannot easily be captured in rodents. Furthermore, we do not fully understand how individual differences in short-term memory ability, depression, chronic stress, and reward anticipation impact cognitive effort deployment for reward. Here, we examined whether these factors predict cognitive effort deployment for higher reward in an online visual short-term memory task. Undergraduate participants were grouped into high and low effort groups (n HighEffort = 348, n LowEffort = 81; n Female = 332, n Male = 92, M Age = 20.37, Range Age = 16-42) based on decisions in this task. After completing a monetary incentive task to measure reward anticipation, participants completed short-term memory task trials where they could choose to encode either fewer (low effort/reward) or more (high effort/reward) squares before reporting whether or not the color of a target square matched the square previously in that location. We found that only greater short-term memory ability predicted whether participants chose a much higher proportion of high versus low effort trials. Drift diffusion modeling showed that high effort group participants were more biased than low effort group participants toward selecting high effort trials. Our findings highlight the role of individual differences in cognitive effort ability in explaining cognitive effort deployment choices.

A review of prospective studies regarding percutaneous peripheral nerve stimulation treatment in the management of chronic pain.

Conventionally, peripheral nerve stimulation (PNS) for treatment of chronic pain has involved a two-stage process: a short-term (e.g., 7days) trial and, if significant pain relief is achieved, a permanent PNS system is implanted. A percutaneous PNS treatment is now available where a coiled lead may be implanted for up to 60days with the goal of producing sustained relief. In the present review, published prospective trials using percutaneous PNS treatment were identified and synthesized. The collected evidence indicates that percutaneous PNS treatment for up to 60days provides durable clinically significant improvements in pain and pain interference. Similar efficacy across diverse targets and etiologies supports the broad applicability for use within the chronic pain population using this nonopioid technology.

When cardiovascular medicines should be discontinued.

An integral component of the practice of medicine is focused on the initiation of medications, based on clinical practice guidelines and underlying trial evidence, which usually test the addition of novel medications intended for life-long use in short-term clinical trials. Much less attention is given to the question of medication discontinuation, especially after a lengthy period of treatment, during which patients age gets older and diseases may either progress or new diseases may emerge. Given the paucity of data, clinical practice guidelines offer little to no guidance on when and how to deprescribe cardiovascular medications. Such decisions are often left to the discretion of clinicians, who, together with their patients, express concern of potential adverse effects of medication discontinuation. Even in the absence of adverse effects, the continuation of medications without any proven effect may cause harm due to drug-drug interactions, the emergence of polypharmacy, and additional preventable spending to already strained health systems. Herein, several cardiovascular medications or medication classes are discussed that in the opinion of this author group should generally be discontinued, either for the prevention of potential harm, for a lack of benefit, or for the availability of better alternatives.

Cost-effectiveness of empagliflozin as add-on to standard of care for chronic kidney disease management in the United Kingdom

Objective The sodium-glucose co-transporter-2 inhibitor empagliflozin was approved for treatment of adults with chronic kidney disease (CKD) on the basis of its demonstrated ability to slow CKD progression and reduce the risk of cardiovascular death. This analysis was performed to assess the cost-effectiveness of empagliflozin plus standard of care (SoC) vs SoC alone in the treatment of CKD in the UK. Methods A comprehensive, patient-level CKD progression model that simulates the evolution of risk factors for disease progression based on CKD-specific equations and clinical data was used to project a broad range of CKD-related complications. Patient baseline characteristics, distribution across Kidney Disease Improving Global Outcomes (KDIGO) health states, and changes in estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (uACR), and other parameters while on treatment were derived from the EMPA-KIDNEY trial. UK cost and utilities/disutilities were sourced from the literature. Univariate and probabilistic sensitivity analyses were conducted. Annual discounting of 3.5% was applied on costs and outcomes. Results Over a 50-year horizon, SoC resulted in per-patient costs, life years, and QALYs of £95,930, 8.55, and 6.28, respectively. Empagliflozin plus SoC resulted in an incremental gain in life years (+1.04) and QALYs (+0.84), while decreasing per-patient costs by £6,019. Empagliflozin was more effective and less costly (dominant) with a net monetary benefit of £22,849 at the willingness-to-pay threshold of £20,000. Although treatment cost was higher for empagliflozin, this was more than offset by savings in kidney replacement therapy. Empagliflozin remained highly cost-effective in patients with and without diabetes, and across scenario and sensitivity analyses. Limitations This analysis is limited by reliance on short-term clinical trial data and by uncertainties in modelling CKD progression. Conclusions Empagliflozin as an add-on to SoC for treatment of adults with CKD represents cost-effective use of UK National Health Service (NHS) resources.

Cough Response to High-Dose Inhaled Corticosteroids in Patients with Chronic Cough and Fractional Exhaled Nitric Oxide Levels ≥ 25ppb: A Prospective Study.

This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.

171 Current limitations to implement fiber in U.S. sow and nursery diets, and nutritional strategies to support ideal fiber profile

Abstract The importance of fiber in swine nutrition is increasingly recognized, and the consequences of insufficient dietary fiber can be significant. Consequently, U.S. production nutritionists have begun exploring the incorporation of fiber into their nutrition programs. However, incorporating fiber into diets is not without challenges. Analytical capabilities for assessing fiber content have improved, yet accessing accurate data remains a hurdle. Furthermore, the cost of analysis limits the ability of nutritionists to utilize these advanced methods for ingredient analysis. The lack of information around fiber requirements in the diet may be due to the insufficient methodology that has historically been available to measure the indigestible fraction of the diet. In the nursery phase, research findings on the effects of fiber have been mixed, likely influenced by the health status of the animals. Short-term growth performance trials may not fully capture the benefits of fiber, and more comprehensive, long-term studies focusing on health-related parameters are lacking. Similarly, research on sow nutrition faces challenges due to the limitations of barn structures and feed lines. Sow trials typically involve only a small number of treatments, often requiring before- and after- assessments. Moreover, the benefits of fiber are more apparent in later reproductive cycles, necessitating prolonged research efforts. Given the limited phases in sow diets, primarily lactation and gestation, conducting sow research is both challenging and costly. Evidence from European literature and recent U.S. studies suggests that the total dietary fiber and the level of soluble, fermentable fiber have a crucial role in swine diets, particularly for sows and piglets. However, the availability and affordability of such fiber types in the U.S. are limited. The majority of fiber-rich ingredients in the U.S. consist mostly of insoluble fiber. To address this limitation, technological advancements will be needed to transform available fiber sources into the desired fiber constructs, rather than relying solely on fiber-rich ingredients. A stimbiotic, which encourages fiber fermentation, may be key to achieving the desired fiber profile. The addition of a stimbiotic has been shown to increase the digestibility of fiber. It also increases the capacity of the beneficial microbiome to break down and ferment fiber, which leads to an increase in the production of volatile fatty acids (acetic, propionic and butyric). In conclusion, U.S. swine nutritionist must explore alternative dietary strategies to capturing the ideal fiber composition. Key word: fiber, nursery, sow

Gut Microbiome Response to the Reduction of Diet Induced Obesity by Vitamin B1 Supplementation

Dietary deficiencies in vitamins such as thiamine (Vitamin B1) produce a range of deleterious health effects and can occur even in developed countries. We’ve hypothesized that a physiological deficiency in thiamine can exacerbate conditions like obesity, diabetes, and fatty liver that are associated with consumption of high fat diets rich in soybean oil (SO) and that one or more of these conditions might be associated with changes in the composition of the gut microbiota. We first evaluated the short-term effect of thiamine deficiency on the gut microbial composition in fecal pellets from C57BL/6N male mice. Mice provided a thiamine regime of 1 mg/kg of low-fat diet for 4 weeks showed marked decreases in fecal community diversity and are characterized by “missing”’ microbes compared to animals provided a standard low-fat thiamine diet (5 mg/kg). Combined with a LC/MS metabolomic analysis these data confirmed changes in the microbiome are coincident with changes of physiological levels of thiamine in the mice. To test the effect of thiamine availability directly on obesity, a separate cohort of C57BL/6N male mice were fed either a low-fat chow (OSD) or an obesogenic soybean oil high fat diet (SO-HFD), with or without supplementation with a thiamine analog (640 mg/kg of diet). Over an 18-week period we found that animals on the SO-HFD with the added thiamine analog gained ~40% less weight compared to animals on the SO-HFD only. Longitudinal sampling of fecal pellets at week 0, 10, 16 and 18 demonstrate major shifts in the microbial composition and diversity over time for animals in all four diet groups. A nested PERMANOVA of Bray-Curtis dissimilarities confirmed the microbiome differences between the SO-HFD and OSD diet (adonis, p = 0.001) and with and without the thiamine analog supplementation (adonis, p = 0.009) at week 16. Measures of microbial diversity show significant increases in diversity for animals consuming the thiamine analog (Kruskall-Wallis, q &lt; 0.05), consistent with the trend observed in the short-term diet trial. Taxonomic classifications for species (ASVs) that significantly increased in these animals are primarily in the Lachnospiraceae family from the Bacillota (Firmicutes) phylum. Together, these data identify major compositional and inferred functional changes to the microbiome in response to the SO-HFD diet as well as thiamine supplementation that may contribute to the observed differences in body weight gain. Funding: The Thiamine Advocacy Foundation. Acknowledgements: UCR Genomics Core. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Changes in soil bacterial community structure in a short-term trial with different silicate rock powders

BackgroundThe use of rock powders in soil has emerged as a nature-based technology to improve soil properties relevant to crop development and for atmospheric carbon dioxide removal (CDR) via enhanced rock weathering (ERW). Although modeling this process is crucial, the soil microbiome has been identified as the main reason why several experimental and field results do not fit the geochemical and kinetic theoretical models. Here, the hypothesis that the bacterial community structure is modulated by the application of different silicate rock powders was tested. One phonolite, three basalt variations and one granite, as well as KCl treatments, were applied to a Ferralsol cultivated with Brachiaria in short-term pedogeochemical experiments and assessed after 1 (1M), 4 (4M) and 8 (8M) months.ResultsThe main changes in soil bacterial structure were observed at 8M and found to be modulated according to rock type, with petrochemistry and mineralogy acting as the main drivers. The content of microbial biomass carbon tended to decrease over time in the Control and KCl treatments, especially at 4M, while the rock treatments showed constant behavior. The sampling time and treatment affected the richness and diversity indices. The Si, Ca and Fe from mafic minerals were the main chemical elements related to the soil bacterial changes at 8M.ConclusionsThe type (acidity) of silicate rock powder modulated the soil bacterial community (SBC) in a pot experiment with tropical soil. The specificity of the SBC for each rock type increased with time until the end of the experiment at 8 months (8M). The carbon content in the microbial biomass was lower in the rock powder treatments in the first month (1 M) than in the control and KCl treatments and was equal to or higher than that in the 8 M treatment. This result illustrates the challenge of modeling rock powder dissolution in soil since the soil medium is not inert but changes concurrently with the dissolution of the rock.Graphical