Responder Definition Research Articles

Defining responders to altered running footwear based on measures of running economy

This study compared three different ways of defining a responder to a shoe intervention when assessing running economy (RE). Furthermore, we investigated the influence of multiple trials on the classification of responders. This was done using indirect calorimetry to measure RE in thirty-seven runners, in three different running shoes. Over two visits, each participant ran a total of four times in each shoe. Three responder definitions were used to classify participants into responders or non-responders. The strength of each definition was evaluated using a logistic regression analysis with a pseudo r2. The effect of multiple trials was analysed using number of trials defined as responders. Two definitions had similar high McFadden’s Pseudo r-squared (r2 = 0.89, r2 =0.86), being definitions that i) included a coefficient of variation (CV) derived from the literature and ii) a CV calculated by averaging all participants day-to-day CV from the present study. Inconsistent responders were present in 57% of the incidences, meaning that participant showed both responding and non-responding trials for the same shoe condition. For defining responders to a shoe intervention (RE specifically), it is recommended to use a cut-off value based on the literature which is easily available. Furthermore, conducting multiple trials is beneficial as this allows a separation between consistent- and inconsistent responders.

Novel approaches to define responders to interventional treatment in hypertension: insights from the SPYRAL HTN-OFF and HTN-ON MED trials.

Multiple sham-controlled clinical trials have demonstrated significant reductions in both office and 24-h blood pressure (BP) following radiofrequency renal denervation (RDN) in the uncontrolled hypertension population. Notably, the blood pressure response varies widely within individual participants, thus showing a clinical need to identify potential RDN "responders" prior to the procedure. Despite multiple analytic efforts, no single parameter, aside from baseline blood pressure, has been consistently associated with BP reduction following RDN. However, this failure may be due to limitations in empiric definitions of responders. Indeed, commonly applied responder definitions based on the difference between two point-in-time BP measurements are fraught due to visit-to-visit variability in office and 24-h blood pressure endpoints. Several factors should be considered to develop a more clinically useful operational definition of procedural response including relative changes in office and 24-h BP, consideration of the temporal response to RDN, as well as adjustment for baseline BP. The current evidence may provide incentives for future expert consensus to precisely define responders to hypertension treatments.

Predicting blood pressure response to renal denervation based on a new approach.

Identifying predictors of blood pressure (BP) response to renal denervation (RDN) is crucial for patient selection. According to Wilder's principle, baseline BP predicts BP change after any antihypertensive intervention. Thus, any observed BP change after RDN is the sum of the BP change depending on the baseline BP and the specific BP reduction due to RDN. Based on this concept, we propose a new definition of BP responders. In our center, 148 patients with uncontrolled hypertension underwent RDN, and 24-h ambulatory BP (ABP) was measured at baseline, and 6 months after the procedure. The decrease in 24-h systolic BP (SBP) correlated with baseline SBP (P = <0.001, r = -0.374). We determined the RDN-specific effect by subtracting the predicted SBP decrease from the observed SBP decrease. The cohort was divided into RDN responders, neutral responders, and nonresponders. Our study population had a mean age of 59 ± 10.4 years and was 74% male. The RDN-specific (residual) 24-h ABP decreased by -14.9 ± 6.3/-8.2 ± 3.8 mmHg (responder group), 1.0 ± 3.2/0.2 ± 1.9 mmHg (neutral group), and 14.2 ± 10.4/8.3 ± 3.9 mmHg (nonresponder group) 6 months after RDN. Responders had fewer antihypertensive medications (P = 0.018), higher baseline office heart rate (HR) (P = 0.019), higher 24-h ambulatory HR (P = 0.003), lower BMI (P < 0.038), and absence of type 2 diabetes (T2D) (P = 0.020). Our definition of BP responders to RDN separates baseline BP-related changes from RDN-specific changes. Positive predictors for BP response to RDN include low BMI, fewer antihypertensive medications, high baseline office HR, high 24-h ambulatory HR, and absence of T2D.

Symptoms trend in patients with obstructive hypertrophic cardiomyopathy treated with disopyramide

Abstract Background In obstructive hypertrophic cardiomyopathy (HOCM) medical intervention becomes necessary when symptoms coexist, whereas invasive septal reduction therapy (SRT) is indicated in presence of NYHA class &amp;gt;II, although optimized medical therapy. Thus, if SRT is avoided by medical therapy patient should be considered responder. However, due to inconsistency on definition of responders, effectiveness of medical therapy among data are conflicting. In addition, only short follow-up (FU) is available for analyses. Purpose To address this, we conducted a retrospective analysis in two HCM centers, both defining responders based on guidelines recommendations. Methods 62 symptomatic HOCM patients (43% women, age 52±14 years) with LVOTG ≥50 mmHg at rest or during provocation, were recruited from two HCM Italian centers. Disopyramide was added as second-line therapy. Responders were those reaching at least NYHA class II, if &amp;gt;II at baseline and those reaching NYHA class I or with stabilization of symptoms if in NYHA II class at baseline. Results At FU, (mean 4.4 years, IQR 1.1-6.6 years), 47 patients (76%) were responders, whereas 15(24%) patients were no-responders. Changes in NYHA class from baseline to follow-up are reported in the Figure. There were no differences at baseline of clinical and echocardiographic data between responders and no-responders, whereas at FU responders showed a significant lower LVOTG than no-responders (43 ±32 vs 66 ±28 mmHg, respectively, p=0.013), with LVOTG &amp;lt;50 mmHg more represented in responders than in no-responders (75% vs 25%, respectively; p=0.004) (Figure). No side effects indicating discontinuation of the therapy were recorded. Conclusion Patients treated with disopyramide as second-line therapy showed a reduction in symptoms in a quite long-follow-up, avoiding SRT in up to 70% of them. Patients who might benefit the most from the therapy are those who reached LVOTG &amp;lt;50 mmHg during treatment.

Development and Validation of a Patient-Reported Outcome Measure of the Impact of Chronic Hand Eczema on Health-Related Quality of Life: the Hand Eczema Impact Scale (HEIS).

Chronic Hand Eczema (CHE) is an inflammatory skin disease that causes significant impact on health-related quality of life (HRQoL). The Hand Eczema Impact Scale (HEIS) is a new patient-reported outcome(PRO) measure designed to assess the impact of CHE on key domains of HRQoL. This study aimed to develop and evaluate content and psychometric validity of the HEIS. The HEIS was initially developed on the basis of a literature review and concept elicitation interviews. Qualitative cognitive debriefing interviews (n = 20) were conducted with patients with CHE to assess relevance and understanding of items, response options, and recall period. Psychometric properties (item performance, dimensionality, reliability, validity, responsiveness, and estimation of meaningful change thresholds) were then assessed using data (n = 258) from a phase 2b trial (NCT03683719). Cognitive debriefing confirmed all items were understood and relevant to patients. Inter-item correlations (all > 0.50) and confirmatory factor analysis (factor loadings ≥ 0.80) supported unidimensionality of the HEIS score, and mostly provided support for the HEIS Proximal Daily Activity Limitations (PDAL) score, with only one item loading below the prespecified threshold. Item properties and previous qualitative work supported retaining this item in the total score but removed from the HEIS PDAL domain. Internal consistency (Cronbach's alpha ≥ 0.89) and test-retest reliability (intra-class correlation coefficient ≥ 0.79) results were very strong. Strong correlations with concurrent measures (0.66-0.87) and significant differences between severity groups (p < 0.001) supported construct validity. Large effect sizes for mean change scores in participants that improved and significant differences between groups indicated ability to detect change. Anchor-based analyses supported within-individual responder definitions of ≥ 1.3 points for improvements in both HEIS score and HEIS PDAL score (covering three items) and of ≥ 1.5 points for HEIS embarrassment with the appearance of hands (Emb) score (covering two items). The 9-item HEIS is the first CHE-specific PROmeasure developed and validated according to regulatory guidance for assessment of the impact of CHE on key domains of HRQoL. This article provides evidence of strong content and psychometric validity and shows improvements of ≥ 1.3 points in HEIS score and HEIS PDAL score, and improvements of ≥ 1.5 points in HEIS Emb score represent clinically meaningful, important changes. NCT03683719.

Evaluation of validity, reliability and ability to detect change for the Hand Eczema Severity Index (HECSI) and evaluation of HECSI-75 and HECSI-90 as within-patient responder definitions.

The Hand Eczema Severity Index (HECSI) is a Clinician-Reported Outcome measure of the severity of hand eczema (HE). This study aimed to evaluate the validity, reliability and ability to detect change of the HECSI, and the HECSI-75 and HECSI-90 as responder definitions. Analyses were performed using data from a sample of n = 258 patients with Chronic Hand Eczema (CHE) from a Phase 2b, randomised, double-blind, vehicle-controlled trial of delgocitinib cream, pooled across treatment groups. The measurement properties of the HECSI were assessed and the adequacy of the HECSI-75 and HECSI-90 as responder definitions was explored through cross-tabulation. Inter-item correlations provided support for the scoring, whereby items are grouped by areas of the hand. HECSI demonstrated good test-retest reliability with intra-class correlations >0.70. Construct validity was supported by a logical pattern of correlations with concurrent measures and significant differences in HECSI scores across severity groups (p < 0.001). HECSI was responsive with statistically significant improvements over time and with significant differences (p < 0.001) between improved and stable groups. Data provided support for both HECSI-75 and HECSI-90 as within-patient responder definitions. HECSI has strong validity, reliability and ability to detect change as a measure of CHE severity. HECSI-75 and HECSI-90 are appropriate responder definitions.

Implementation of Handling Actions for Health Problems Regarding Food Poisoning

Poisoning is an emergency that can damage cells and some body functions due to the entry of a substance or food that contains poison, originating from toxic materials formed due to the decomposition of food and bacteria. Food poisoning is an illness that occurs after eating food that contains toxins, originating from toxic materials formed as a result of food decay and bacteria. Research purposes is for know knowledge help first on poisoning food. Research Methods this is study descriptive with use approach cross sectional. Retrieval sample done with accidental sampling and collection data use questionnaire knowledge poisoning food with a analysis data using univariate analysis. Results which obtained majority respondent know definition poisoning, sign and symptom poisoning, and management poisoning. Majority respondent not yet know handling dehydration heavy and diarrhea which due to because poisoning.

Harmonizing Heartbeats: The Mosaic of Cardiac Resynchronization Therapy Responders-A Comprehensive Exploration of Diverse Criteria and Predictors.

Background: Heart failure (HF) remains a challenging healthcare issue necessitating innovative therapies like cardiac resynchronization-defibrillation therapy (CRT-D). However, the definition of a CRT-D response lacks uniformity, impeding effective clinical evaluation. This study explores diverse CRT-D responder definitions encompassing functional, echocardiographic and laboratory criteria. Materials & Methods: A single-center study involving 132 CRT-D patients scrutinized responder criteria including NYHA stage, LVEF increase and proBNP decrease. Statistical analyses such as Kaplan-Meier curves and Cox hazard regression were employed to evaluate responder characteristics and survival outcomes. Results: Responder rates varied across criteria, revealing nuanced patient profiles. CRT-D responders defined by NYHA decrease, LVEF increase or proBNP decrease exhibit improved survival rates after 2 and 3 years (p < 0.050). Young age, absence of recent myocardial infarction and normal right ventricular echocardiographic parameters emerge as predictors for positive response. In part, drug-based HF therapy correlates with increased responder rates. Cox regression identified LVEF ≥ 5% and proBNP decrease ≥ 25% as independent predictors of extended survival. Conclusions: CRT-D responder definitions exhibit considerable variability, emphasizing the need for a nuanced patient-centered approach. Factors like right ventricular function, drug therapy, atrial fibrillation and renal function influence responses. This study enriches our understanding of CRT-D response and contributes to the foundation for personalized HF management.

Long-term follow-up study on obstructive hypertrophic cardiomyopathy patients treated with disopyramide: evidences of a notable trend in symptom control within a real-world clinical setting.

In obstructive hypertrophic cardiomyopathy (HOCM), disopyramide is used in patients who remain symptomatic despite β-blockers or verapamil. However, effectiveness of disopyramide therapy has not been clearly established due to inconsistent definition of responders and the insufficient length of follow-ups reported in literature. To address these shortcomings, we have conducted a retrospective analysis from detailed databases with long follow-up, from two HCM Referral Centers. 62 symptomatic HOCM patients (43% women, age 52 ± 14 years) with left ventricular (LV) outflow tract gradient (LVOTG) ≥ 50 mmHg at rest or during provocation, were recruited from two Italian Centers. Disopyramide was added as second-line therapy in the patients in whom symptoms persisted despite classic pharmacologic treatment. Patients in NYHA class > II at baseline who reached NYHA class II or I, and patients in NYHA class II at baseline who reached NYHA class I or symptoms stabilization were defined as responders. At follow-up, (mean 4.4 years, IQR 1.1-6.6 years), 47 patients (76%) were responders, whereas 15 (24%) were no-responders. Responders showed larger LV diastolic volume index (LVEDVi) at baseline as compared to no-responders (61 ± 14 vs. 49 ± 16 ml, respectively, p = 0.018), and, at follow-up, reached lower LVOTG than no-responders (43 ± 32 vs. 66 ± 28 mmHg, respectively, p = 0.013), with a LVOTG <50 mmHg more represented in responders than in no-responders (75% vs. 25%, respectively; p = 0.004). No side effects requiring discontinuation of the therapy were recorded. HOCM patients treated with disopyramide as second-line therapy in a quite long-follow-up showed a significant improvement of symptoms, which avoided SRT in up to 70% of them. Moreover, our data suggest that a larger LVEDVi at baseline identify the subgroup of patients who benefit the most from the therapy in terms of symptoms and reduction of LVOTG below 50 mmHg during treatment. We will discuss specific situations where disopyramide may be preferred over myosin inhibition to ensure that effective therapeutic options are fully considered and not prematurely dismissed.

The Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) scale in patients with axial spondyloarthritis: psychometric properties and clinically meaningful thresholds for interpretation

BackgroundFatigue is an important symptom for most patients with axial spondyloarthritis (axSpA). The FACIT-Fatigue is a 13-item patient-reported outcome (PRO) instrument that has been used in axSpA clinical trials to measure fatigue severity and impact on daily activities. However, the psychometric properties of the FACIT-Fatigue are not fully evaluated across the entire spectrum of axSpA including non-radiographic axSpA (nr-axSpA) and radiographic axSpA (r-axSpA). This study determined: (1) the psychometric properties of the FACIT-Fatigue in nr-axSpA, r-axSpA, and the broad axSpA population and (2) FACIT-Fatigue scores representing meaningful within-patient change (MWPC), meaningful between-group differences, and cross-sectional severity bands.MethodsData from two Phase 3 trials in adults with nr-axSpA (BE MOBILE 1; N = 254) and r-axSpA (BE MOBILE 2; N = 332) were analyzed pooled and separately to assess the psychometric properties of the FACIT-Fatigue. MWPC and meaningful between-group difference estimates were derived using anchor-based and distribution-based methods. Cross-sectional fatigue severity bands were estimated using logistic regression analysis.ResultsThe FACIT-Fatigue presented good internal consistency, adequate convergent and known-groups validity, and was sensitive to change over time across the full axSpA spectrum. A 5–11-point increase in FACIT-Fatigue score was estimated to represent a MWPC, with an 8-point increase selected as the responder definition. A 2.14–5.34-point difference in FACIT-Fatigue score change over a 16-week period was estimated to represent a small-to-medium meaningful between-group difference. FACIT-Fatigue score severity bands were defined as: none or minimal (>40), mild (>30 to ≤40), moderate (>21 to ≤30), and severe (≤21).ConclusionsThese findings support the use of the FACIT-Fatigue as a fit-for-purpose measure to assess fatigue-related treatment benefit in axSpA clinical trials. The proposed score estimates and thresholds can guide FACIT-Fatigue score interpretation across the full axSpA spectrum.Trial registrationClinicalTrials.Gov, NCT03928704. Registered 26 April 2019—Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT03928704. ClinicalTrials.Gov, NCT03928743. Registered 26 April 2019—Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT03928743.

A Review of Current Data on Duration of Effect in Glabellar Lines After Treatment With AbobotulinumtoxinA 50 U.

AbobotulinumtoxinA has become well established as a treatment option for moderate to severe glabellar lines since its first aesthetic approval in 2009. Pivotal trials leading to regulatory approval showed that abobotulinumtoxinA treatment was associated with high responder rates when defined as achievement of none or mild glabellar lines (0 or 1 on the glabellar line severity scale) and a duration of action of up to 5 months. More recently, the goals for treatment of glabellar lines have shifted toward not only achieving a decrease in glabellar line severity but also ensuring that patients are satisfied with their experience. Patients seek an improvement in the appearance of their glabellar lines while maintaining a "natural look," fast onset of effect, and long duration of response. Trial designs have evolved to meet these new targets, including expanding the definition of responders to those having at least 1-grade improvement in the glabellar line severity scale score from baseline coupled with the use of subject satisfaction and psychological well-being questionnaires. The findings demonstrate that abobotulinumtoxinA remains a well-tolerated and consistently effective treatment option associated with a rapid onset of effect, duration of efficacy lasting up to 6 months, and high, long-lasting levels of patient satisfaction.

Development and Validation of a Simple and Multifaceted Instrument, Chronic Constipation-Therapeutic Efficacy and Satisfaction Test, for the Clinical Evaluation of Patients with Chronic Constipation

Introduction: This study evaluated the psychometric properties of the newly developed chronic constipation-therapeutic efficacy and satisfaction test (CC-TEST) among patients with chronic constipation. Methods: Japanese patients with moderate or severe chronic constipation underwent a 4-week remedy. The baseline, 2-week, and 4-week assessments included the CC-TEST, Constipation Scoring System (CSS), Medical Outcome Study Short Form-8 Health Survey (SF-8), and Hospital Anxiety and Depression Scale (HADS). The CC-TEST comprises three domains: (1) symptoms; chronic constipation symptom severity (seven items), defecation status (five items), (2) impact for daily life; dissatisfaction with daily life level (DS; four items), and (3) therapeutic response; therapeutic efficacy measured by patients and medication compliance (four items). Results: Of 201 eligible patients at baseline, 110 completed the 4-week treatment and the survey responses. Cronbach’s α values for the stool, defecation, and abdominal symptom subscales, as well as the total symptom score and DS subscale, showed good internal consistency reliability (0.72–0.80). Pearson’s r for comparisons between corresponding items (CC-TEST symptoms with CSS, and CC-TEST DS with SF-8 physical and mental component summary scores) was significant. After 4 weeks, scores for symptoms, defecation status, and DS items/subscales notably decreased, with a significant effect size (p < 0.005, Cohen’s d; 0.30–1.16). Statistically significant differences emerged between treatment responders and nonresponders using the three responder definitions, in changes in scores for most CC-TEST symptoms, defecation status, and DS items/subscales (p < 0.05). Conclusion: CC-TEST demonstrates commendable reliability, convergent and known-group validity, and responsiveness to treatment effects. As a simple, comprehensive, and versatile patient-reported outcome measure, CC-TEST may be well suited for clinical trials and primary care of Japanese patients with chronic constipation.

Responder analysis using clinically meaningful thresholds: Post hoc analyses from randomized dupilumab clinical trials in patients with prurigo nodularis.

Prurigo nodularis (PN) is an intensely pruritic disease characterized by itchy nodules on the trunk/extremities; it is often accompanied by skin pain and sleep disruption with negative impacts on the quality of life (QoL). The patient-reported outcome (PRO) instruments, Worst Itch-Numeric Rating Scale (WI-NRS), Skin Pain-NRS, Sleep-NRS and Dermatology Life Quality Index (DLQI) have been psychometrically validated and the clinically meaningful within-patient improvement thresholds (responder definition) have been established through data pooled from the two Phase-3 trials (PRIME, NCT04183335 and PRIME2, NCT04202679) of dupilumab in adults with PN uncontrolled on topical therapies. To estimate the proportion of dupilumab-treated patients (vs. placebo) achieving clinically meaningful improvement in itch, skin pain, sleep and QoL, either alone or in combination, from the data pooled from PRIME and PRIME2 trials. The patient-level data pooled from the two Phase-3 trials (N = 311) were used for this post hoc analysis. Thresholds of clinically meaningful within-patient improvement in PRO instrument scores from baseline at Week 24 used for defining responders were 4 (WI-NRS and Skin Pain-NRS), 2 (Sleep-NRS) and 9 points (DLQI). The proportion of dupilumab-treated patients, versus placebo, achieving the thresholds, and the time taken to achieve the thresholds were evaluated for the individual and combination of PROs. Responder rates were significantly higher with dupilumab, versus placebo at Week 24 for WI-NRS (58.8% vs. 19.0%, p < 0.0001), Skin Pain-NRS (49.7% vs. 20.9%, p < 0.0001), Sleep-NRS (42.5% vs. 23.4%, p < 0.0001) and DLQI (64.7% vs. 22.8%, p < 0.0001). Proportion of patients achieving simultaneous improvement in symptoms and QoL (24.8% vs. 6.3%, p < 0.0001) were significantly higher in dupilumab-treated patients versus placebo. The time needed for achieving clinically meaningful improvement in symptoms were significantly lower in dupilumab-treated patients, versus placebo. Significantly greater proportion of dupilumab-treated patients with PN, versus placebo, demonstrated clinically meaningful improvements in PRO measures of symptoms and QoL.

Exploring Definitions and Predictors of Response to Biologics for Severe Asthma

Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. A total of 2,210 patients were included. Responder rate ranged from 80.7% (n= 566 of 701) for exacerbation response to 10.6% (n= 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n= 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio= 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio= 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed.

Development and validation of a quality of life and treatment satisfaction measure in canine osteoarthritis.

Canine osteoarthritis (OA) causes pain and mobility impairment. This can reduce dog quality of life (QoL), owner QoL and owners' satisfaction with, and adherence to, treatments. No existing canine OA-specific instrument assesses all three impacts. This study aimed to develop and psychometrically evaluate an owner-completed canine OA-specific measure of dog QoL, owner QoL and owner treatment satisfaction; the "Canine OA Quality of Life and Treatment Satisfaction Questionnaire" (CaOA-QoL-TS). The CaOA-QoL-TS was developed using a conceptual model derived from a meta-synthesis of published literature followed by cognitive interviews with ten owners of dogs with OA, to evaluate content validity. Based on interview findings, ten items were reworded, four removed, and two added; resulting in 26 items that all owners understood and considered relevant. The recall period and response options were well understood and appropriate to almost all owners. To evaluate its psychometric properties, the CaOA-QoL-TS (draft 26-item version) was administered, across six timepoints in a phase 4 field study, to owners of OA treated dogs, recruited from veterinary practices (N = 93). Inter-item correlations suggested items clustered into three distinct domains: Dog QoL, Owner QoL and Treatment Satisfaction, as hypothesized. Confirmatory factor analysis supported deletion of two items and calculation of the three domain scores, with acceptable model fit. The resulting 24-item CaOA-QoL-TS instrument demonstrated strong internal consistency and good to excellent test-retest reliability. Convergent validity was supported by moderate to strong correlations with concurrent measures. Known groups validity was supported by statistically significant differences between groups categorized by owner global impression of QoL. Ability to detect change was demonstrated through statistically significant improvements over time in Owner and Dog QoL, with larger within-group effect sizes reported for the mean of 'improved' dogs compared to the mean of 'stable' dogs. Only a small sample of dogs worsened throughout the study. Anchor-based analyses supported-0.9 and-1.0-point within-group responder definitions for dog and owner QoL domains, respectively. Findings support the content validity of the CaOA-QoL-TS in canine OA. The 24-item CaOA-QoL-TS is a reliable and valid instrument to measure owner and canine QoL and TS and is sensitive to improvements following OA treatment.

BLOOD PRESSURE RESPONDERS TO RENAL DENERVATION BASED ON A NEW DEFINITION

Objective: Identifying predictors of blood pressure (BP) response to renal denervation (RDN) is an unmet need for patient selection. Any antihypertensive intervention follows the law of the inital value, which means that the baseline BP predicts the BP change, a phenomenon known as Wilder‘s Principle (European Heart Journal, 2015, 36, 576-579). Thus, any observed change in BP after renal denervation is the sum of the change in BP depending on the baseline BP and the specific BP reduction related to RDN. Based on this concept, we propose a new definition of BP responders. Design and method: In our center, a total of 127 patients with uncontrolled hypertension underwent RDN and 24h ambulatory BP was measured at baseline, 6- and 12 months after the procedure. According to the Wilder's principle, the decrease in the 24h ambulatory systolic BP (SBP) was related to the baseline 24h SBP (p=&lt;0.001, r=-0.466, y=69.28–0.52∗x). Subsequently, we calculated the predicated decrease in 24h SBP and subtracted this from the the observed decrease in 24h SBP, thereby getting the specific or residual effect of SBP decrease. According to this RDN specific change of 24h SBP, the study cohort was divided into tertials: RDN responders, neutral responders and non-responders. Results: Our study population with mean of age of 59 years consisted of 74% males and 55% with type 2 Diabetes (T2D). The RDN specific (residual) 24-hour ambulatory blood pressure decreased by -14.4/-8.8mHg (responder group), 1.4/0.4mmHg (neutral group) und 15.7/8.5 mmHg (non-responder group) twelve months after RDN (see table). According to our new definition of BP-responders to RDN, the RDN responder group was characterized only by lower number of antihypertensive medication (p=0.002), low BMI (p&lt;0.001), and the absence of T2D (p=0.013). Conclusions: We propose a new definition of responders to RDN, separating the BP- changes related to the baseline BP from those related to the reduction of the sympathetic nerve activity after RDN. Following this approach, we identified low BMI, less antihypertensive medication and absence of T2D as positive predictors for BP response to renal denervation.

Psychometric evaluation of the near activity visual questionnaire presbyopia (NAVQ-P) and additional patient-reported outcome items.

The Near Visual Acuity Questionnaire Presbyopia (NAVQ-P) is a patient-reported outcome (PRO) measure that was developed in a phakic presbyopia population to assess near vision function impacts. The study refined and explored the psychometric properties and score interpretability of the NAVQ-P and additional PRO items assessing near vision correction independence (NVCI), near vision satisfaction (NVS), and near vision correction preference (NVCP). This was a psychometric validation study conducted using PRO data collected as part of a Phase IIb clinical trial (CUN8R44 A2202) consisting of 235 randomized adults with presbyopia from the US, Japan, Australia, and Canada. Data collected at baseline, week 2, and months 1, 2, and 3 during the 3-month trial treatment period were included in the analyses to assess item (question) properties, NAVQ-P dimensionality and scoring, reliability, validity, and score interpretation. Item responses were distributed across the full response scale for most NAVQ-P and additional PRO items. Confirmatory factor analysis supported the pre-defined unidimensional structure and calculation of a NAVQ-P total score as a measure of near vision function. Item deletion informed by item response distributions, dimensionality analyses, item response theory, and previous qualitative findings, including clinical input, supported retention of 14 NAVQ-P items. The 14-item NAVQ-P total score had excellent internal consistency (α = 0.979) and high test-retest reliability (Intraclass Correlation Coefficients > = 0.898). There was good evidence of construct-related validity for all PROs supported by strong correlations with concurrent measures. Excellent results for known-groups validity and ability to detect change analyses were also demonstrated. Anchor-based and distribution-based methods supported interpretation of scores through generation of group-level and within-individual estimates of meaningful change thresholds. A meaningful within-patient change in the range of 8-15-point improvement on the NAVQ-P total score (score range 0-42) was recommended, including a more specific responder definition of 10-point improvement. The NAVQ-P, NVCI, and NVS are valid and reliable instruments which have the ability to detect change over time. Findings strongly support the use of these measures as outcome assessments in clinical/research studies and in clinical practice in the presbyopia population.

Validation of a scoring algorithm for the clinician-reported outcome tool 'prurigo activity and severity (PAS)' based on clinical studies of dupilumab in adults with prurigo Nodularis.

Prurigo nodularis (PN) also known as chronic prurigo, is a chronic inflammatory skin disease characterized by intensely itchy nodules/lesions which occur due to intensive scratching. PN management is, in part, based on clinician evaluations of PN lesions, which can be supported by clinician-reported outcomes (ClinRO) such as the Prurigo Activity and Severity (PAS) instrument. A 5-item version of PAS was included in recent phase-3 dupilumab PN trials (PRIME [NCT04183335]/PRIME2 [NCT04202679]). The PAS score was derived using the unweighted sum of 3-items of the 5-item PAS (range, 0-11; higher score indicates worse activity and severity): Item 2 (number of lesions), Item 5a (percentage of lesions with excoriations/crusts) and Item 5b (percentage of healed lesions) for use in clinical practice and for communication of treatment benefit to physicians. To evaluate the measurement properties of PAS score and derive within-patient (responder definition) and between-group improvement thresholds for interpreting changes in PAS score in patients with PN. The data source was the pooled treatment group, intention-to-treat (ITT) data from the phase-3 PRIME (NCT04183335) and PRIME2 (NCT04202679) studies evaluating the efficacy of dupilumab in adult patients with PN with ≥20 nodules and severe itch uncontrolled with topical therapies. PAS score reliability, validity and sensitivity to change were evaluated, and anchor- and distribution-based methods were applied to derive meaningful change thresholds. The pooled ITT population included 311 patients (mean age 49.5 years, 65.3% female). Adequate to good psychometric properties were demonstrated for PAS score. The within-patient meaningful improvement threshold was estimated as 3.0 points (absolute change) and 37% (per cent change). A 1.7-point (absolute change) and 20% (per cent change) improvement were estimated to reflect a between-group meaningful change in PAS score. PAS score is a simple, clinically relevant indicator of PN lesion activity and severity supported by suitable psychometric performance.

Steroid responsiveness in alcohol-associated hepatitis is linked to glucocorticoid metabolism, mitochondrial repair, and heat shock proteins.

Alcohol-associated hepatitis (AH) is one of the clinical presentations of alcohol-associated liver disease. AH has poor prognosis, and corticosteroids remain the mainstay of drug therapy. However, ~40% of patients do not respond to this treatment, and the mechanisms underlying the altered response to corticosteroids are not understood. The current study aimed to identify changes in hepatic protein expression associated with responsiveness to corticosteroids and prognosis in patients with AH. Patients with AH were enrolled based on the National Institute on Alcohol Abuse and Alcoholism inclusion criteria for acute AH and further confirmed by a diagnostic liver biopsy. Proteomic analysis was conducted on liver samples acquired from patients with AH grouped as nonresponders (AH-NR, n = 7) and responders (AH-R, n = 14) to corticosteroids, and nonalcohol-associated liver disease controls (n = 10). The definition of responders was based on the clinical prognostic model, the Lille Score, where a score < 0.45 classified patients as AH-R and a score > 0.45 as AH-NR. Primary outcomes used to assess steroid response were Lille Score (eg, improved liver function) and survival at 24 weeks. Reduced levels of the glucocorticoid receptor and its transcriptional co-activator, glucocorticoid modulatory element-binding protein 2, were observed in the hepatic proteome of AH-NR versus AH-R. The corticosteroid metabolizing enzyme, 11-beta-hydroxysteroid dehydrogenase 1, was increased in AH-NR versus AH-R along with elevated mitochondrial DNA repair enzymes, while several proteins of the heat shock pathway were reduced. Analysis of differentially expressed proteins in AH-NR who survived 24 weeks relative to AH-NR nonsurvivors revealed several protein expression changes, including increased levels of acute phase proteins, elevated coagulation factors, and reduced mast cell markers. This study identified hepatic proteomic changes that may predict responsiveness to corticosteroids and mortality in patients with AH.

Development and Psychometric Validation of a Patient-Reported Outcome Measure to Assess the Signs and Symptoms of Chronic Hand Eczema: The Hand Eczema Symptom Diary (HESD).

Chronic Hand Eczema (CHE) is an inflammatory skin disease of the hands. The Hand Eczema Symptom Diary (HESD) is a new patient-reported outcome measure of worst severity of core CHE signs/symptoms. This study aimed to evaluate content and psychometric validity of the HESD. The HESD was developed based on the literature and concept elicitation interviews. Qualitative cognitive debriefing interviews were conducted with CHE patients to assess relevance and understanding of items, response options and recall period. Psychometric properties of the HESD (item performance, dimensionality, reliability, validity, responsiveness and estimation of meaningful change thresholds) were then assessed, first using data from a phase 2b trial (NCT03683719), and confirmed using data from the first 280 participants completing the 16-week treatment phase of a phase 3 trial (NCT04871711). Cognitive debriefing supported item refinement and removal of items and confirmed all items were well understood and relevant to patients. Item properties and dimensionality analyses in the phase 2b data supported removal of additional items, resulting in the 6-item HESD included in the phase 3 trial. Unidimensionality was supported by inter-item correlations (all > 0.70) and Rasch analysis. Internal consistency (Cronbach's alpha = 0.96) and test-retest reliability (IntraclassCorrelationCoefficient > 0.89) results were very strong. Construct validity was supported by moderate correlations with concurrent measures (0.53-0.64) and significant differences between severity groups (p < 0.001). Large effect sizes for mean change scores in participantsthat improved and significant differences between change groups indicatedthe ability to detect change. Anchor-based analyses supported within-individual responder definitions of ≥ 4-points for improvements in 7-day average HESD scores. The HESD is the first CHE-specific, patient-reported outcome measure of CHE signs/symptoms developed and validated in line with regulatory guidance. This article provides evidence of strong content validity and psychometric validity and shows improvements of ≥ 4 points on 7-day average HESD scores represent clinically meaningful, important changes. NCT03683719, NCT04871711.