Absolute Score Changes Research Articles

Changes in depression symptom profile with gender-affirming hormone use in transgender persons

BackgroundWomen show higher prevalence of depression and different symptomatology than men, possibly influenced by sex hormones. Many transgender persons, who face a high risk of depression, use Gender-Affirming Hormone Therapy (GAHT), but the impact of GAHT on depressive symptom profiles is unknown. MethodsThis study examined depressive symptoms in transgender persons before GAHT and after 3- and 12 months of GAHT. We used the Inventory of Depressive Symptomatology-Self Report to assess depressive symptoms, exploratory factor analysis (EFA) to assess symptom clusters, and linear mixed models to assess changes in symptom clusters. ResultsThis study included 110 transmasculine (TM) and 89 transfeminine (TF) participants. EFA revealed four symptom clusters: mood, anxiety, lethargy, and somatic symptoms. Changes in total depressive symptoms significantly differed between TM and TF groups. After 3 months of GAHT, TM participants reported improvement in lethargy (−16 %; 95%CI: −29 %; −2 %), and after 12 months TF participants reported worsening in low mood (24 %; 95%CI: 3 %; 51 %), but absolute score changes were modest. Neither group showed changes in anxiety or somatic symptoms. LimitationsThis study had limited sample sizes at 12 months follow-up and did not include relevant biological or psychosocial covariates. DiscussionChanges in depressive symptoms after GAHT use differ in TM and TF persons: TM persons report slight improvements in lethargy, whereas TF persons report a slight increase in low mood. Starting GAHT represents a significant life event with profound social and physical effects, and further research should assess social and biological effects of GAHT on mood-related symptoms.

Impact of rater change on data variability in ADAS‐Cog and CDR assessments

AbstractBackgroundThe past decade has seen numerous research trial failures in Alzheimer’s Disease. The CDR and ADAS‐Cog are the two most frequently used primary outcome measures of memory and cognition in clinical trials of Alzheimer’s Disease (AD). Given the high number of failed AD trials in recent years, data reliability of these measures is paramount. In an effort to minimize data variability and increase data quality, study designs often require the same rater assesses the subject/caregiver at each study visit. However, the impact of rater change on data reliability of these measures is largely unknown. This analysis investigates the impact of rater change on data variability in these measures.MethodData from 13 multinational clinical trials of early symptomatic and mild to moderate AD were analyzed. ADAS‐Cog and CDR assessments conducted by site raters were arranged according to visit sequence and divided into two groups: Rater Change (different raters administered subject’s consecutive visits) and No Rater Change (same rater administered consecutive visits). Visit‐to‐visit absolute score changes for CDR‐SB and ADAS‐Cog Total Score were calculated, and frequency distributions were evaluated.ResultWelch corrected, two sample t‐tests were conducted to compare score changes between rater change groups. For CDR, the Rater Change group showed a higher mean visit‐to‐visit score change (mean = 1.26, SD = 1.32) compared to the No Rater Change (mean = 1.02, SD = 1.13) group. The Rater Change group also showed a higher mean score change on ADAS‐Cog (mean = 4.44, SD: 3.77 and mean ‐ 4.06, SD = 3.50, for Rater Change and No Rater Change Groups, respectively). These group differences reached significance for both ADAS‐Cog (t = ‐7.2925, df = 9769.1, p < .001) and CDR (t = ‐11.228, df = 6122.7, p < .001).ConclusionThe analysis indicates significantly different score changes when there is a rater change between visits than not for both CDR and ADAS‐Cog assessments. These findings highlight the importance of rater consistency in reducing variability in an effort to improve data quality in AD trials.

Comparable Minimally Important Differences and Responsiveness of Brief Pain Inventory and PEG Pain Scales across 6 Trials

The 3-item pain intensity (P), interference with the enjoyment of life (E), and interference with general activity (G), or PEG, has become one of the most widely used measures of pain severity and interference. The minimally important differences (MID) and responsiveness of the PEG are essential metrics for solidifying its role in research and clinical care. The current study aims to establish the MID and responsiveness of the PEG by synthesizing data from 1,710 participants across 6 controlled trials. MIDs were estimated using absolute score changes among individuals reporting their pain was “a little better” on a retrospective global change anchor as well as distribution-based estimates using standard deviation thresholds and 1 and 2 standard errors of measurement. Responsiveness was assessed using standardized response means, area under the curve, and treatment effect sizes. MID estimates for the PEG ranged from 0.60 to 1.1 when using 0.35 SD, and 0.78 to 1.22 using 1 standard error of measurement. MID estimates using the global anchor had somewhat more variability but most estimates ranged from 1.0 to 1.75. Responsiveness effect sizes were generally large (>.80) for standardized response means and moderate (>.50) for treatment effect. Similarly, the most area under the curve values demonstrated an acceptable level of scale responsiveness (≥.70). Importantly, MID estimates and responsiveness of the PEG and BPI scales were largely comparable when aggregating data across trials. Our synthesis indicates that 1 point is a reasonable MID estimate on these 0- to 10-point pain scales, with 2 points being an upper bound. PerspectiveThis article synthesizes data from 6 clinical trials to establish the minimally important difference (MID) and responsiveness of the 3-item PEG pain scale. The PEG demonstrated good responsiveness, and 1 to 2 points proved to be reasonable estimates for the lower and upper bounds of the MID.

Computed tomography-based assessment of radiographic progression in spine and sacroiliac joints after pregnancy in women with radiographic axial spondyloarthritis.

Mechanical stress are one of the pathogenesis of axial spondyloarthritis (axSpA). During pregnancy, the mechanical overload on the spine and pelvis increases due to gravid uterus. We aimed to investigate whether pregnancy affects radiographic progression in patients with radiographic axSpA (r-axSpA) based on computed tomography (CT) evaluations. This retrospective study included women with r-axSpA aged 19-49 years who underwent at least two CT evaluations of the whole spine and/or sacroiliac joints (SIJs) at intervals of 2-4 years. To compare radiographic progression after delivery, we classified the patients into two groups: delivery group and controls. The delivery group was restricted to women who had the first CT ∼2 years before delivery and the second CT ∼2 years after delivery. The CT Syndesmophyte Score (CTSS) (0-522) and SIJ scores (0-40) were used to evaluate spinal syndesmophytes and erosion, joint space narrowing, and sclerosis of the SIJs. A total of 21 women in the delivery group and 38 women in the control group were included. The median (Q1-Q3) CTSS at baseline in the delivery group and controls was 19 (16-23) and 20 (13.25-27.75), and the median progression was 1 (0-3) and 0 (0-1) during the median 2.9-year follow-up, respectively. The median (Q1-Q3) SIJ score at baseline in the delivery group and controls was 13 (8-22) and 11 (6-22), and the median progression was 1.5 (0-3) and 1 (0-2), respectively. Using cut-off 0.5, 52.9, and 61.9% of r-axSpA patients and 39.3 and 44.4% of controls showed progression of whole spine and SIJs, respectively. However, no difference in proportion of spinal and SIJ progression and absolute score changes per time point was observed between two groups. Moreover, the SIJ score changes were comparable according to the delivery method. Pregnancy and delivery do not affect the radiographic progression of the spine and SIJs in women with r-axSpA assessed by CT.

The Effects of Postoperative Physician Phone Calls for Hand and Wrist Fractures: A Prospective, Randomized Controlled Trial.

BackgroundIn this study, we sought to determine if postoperative physician phone calls following hand and wrist fracture surgery improve patient outcomes, satisfaction, and treatment adherence.MethodologyWe prospectively enrolled 24 consecutive adult patients who underwent outpatient surgery for isolated hand and wrist fractures at a single, metropolitan, safety-net hospital over one year to receive an additional physician phone call starting on postoperative day one. We measured preoperative and postoperative Brief Michigan Hand Questionnaire (bMHQ) composite score, overall satisfaction on a five-point Likert scale, compliance with treatment recommendations, presence of complications, discharge instructions reading level, and clarity of discharge and follow-up instructions. The surgical team was blinded to the treatment arm.ResultsThe bMHQ score improved 26% after surgery; however, there was no difference in absolute score change between groups (12.2 vs. 6.5, p = 0.69). Most patients were satisfied throughout all stages of care, but postoperative satisfaction did not differ between groups (1.4 vs. 2.5, p = 0.21). There was a stronger correlation between patient hand function and satisfaction starting one month after surgery (R2 = 0.502, p = 0.002) than preoperatively (R2 = 0.252, p = 0.029). Immediately following surgery, most patients stated that discharge instructions were clear, and the average readability was below the average patient education level. Despite this, 13% removed their splint or Kirschner wires, 67% did not follow up within a week of recommendation, 62% did not complete postoperative treatment, and 33% had complications.ConclusionsPostoperative phone calls by physicians did not improve compliance with recommendations, patient-rated outcome measures, or clinical outcomes among our hand and wrist fracture patient population.

Minimal Clinically Important Difference for PROMIS Physical Function and Pain Interference in Patients Following Surgical Treatment of Distal Radius Fracture

We estimated the minimal clinically important difference (MCID) for the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) and Pain Interference (PI) computer adaptive tests (CATs) following surgical treatment of distal radius fracture (DRF). Adult patients surgically treated between November 2017 and November 2020 for isolated DRF were identified. Demographic and patient-reported outcome data were extracted from the electronic health record. Outcomes of interest were the PROMIS PF and PI CATs. Inclusion criteria were met if: (1) PROMIS PF and PI scores were available at preoperative and postoperative visits; and (2) a postoperative clinical anchor question asking about overall response to treatment was answered. An anchor-based MCID estimate was determined by calculating the average absolute score change in PROMIS PF and PI for patients who indicated a mild change to the anchor question. A distribution-based MCID estimate was also calculated using the standard error of measurement and effect sizes of change. The changes in PROMIS PF and PI scores were significantly different between patients who gave responses of much change (n= 73), mild change (n= 51), and no change (n= 19) to the clinical anchor question. The average score changes in the mild change group for PROMIS PF and PI were 5.2 (SD, 3.7) and 6.8 (SD, 4.3) points, respectively, representing the anchor-based MCID estimates. The PROMIS PI anchor-based estimate was moderately correlated with the preoperative score (r=-0.41), time between visits (r=-0.39), and age (r= 0.30). The distribution-based MCID estimates were 3.8 (SD, 1.3) and 3.7 (SD, 1.3) points for the PROMIS PF and PI, respectively. The MCIDs were estimated as 5.2 and 6.8 for the PROMIS PF and PI CATs, respectively, following surgery for DRF. As reports continue to publish a consistent range of MCID values, researchers can be confident in these values and begin using them across a broader spectrum of conditions treated by hand surgeons.

Phototherapy for atopic dermatitis: Systematic review and network meta-analysis of randomized controlled trials.

Phototherapies could represent an efficient option for the treatment of atopic dermatitis (AD), but the evidences available for clinical choices were contradictory. This study aimed to evaluate the efficacy of different phototherapies on AD. This systematic review and network meta-analysis included randomized controlled trials (RCTs) through searching keywords from PubMed, EMBASE, and the Cochrane library. We summarized different phototherapy types and scoring systems. Scoring Atopic Dermatitis (SCORAD) absolute score changes were estimated by mean differences (MDs) and standard deviations (SDs) and then included in the network meta-analysis. The effect sizes of comparison of different phototherapies were presented as MDs and 95% confidence intervals (CIs). Egger's test was used to evaluate publication bias. Eleven RCTs were included in the systematic review and 4 studies in the network meta-analysis. Based on the pooled estimates, medium-dose ultraviolet A1 (UVA1) cold light was superior to medium-dose UVA1 (MD 8.92; 95% CI: 5.60-12.24) but no significant difference between high-dose (UVA1) and medium-dose UVA1 cold light (MD 0.66; 95% CI: -5.57to6.90). Publication bias was not supported by Egger's test (P=.168). Due to possible long-term adverse effects of high-dose UVA1, medium-dose UVA1 cold light appears to be the superior form for AD.

Associations of Common Depression Treatment Metrics With Patient-centered Outcomes.

Various metrics predicated on Patient Health Questionnaire-9 (PHQ-9) scores denote depression "response" or "remission" over time, but few have been empirically validated. We compare the associations of depression response and remission metrics with concomitant clinical improvement in patient-centered outcomes (PCOs). Secondary analysis of PHQ-9 and PCO data from the treatment arm (n=906) of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) trial. We conducted univariate correlations between 9 depression treatment metrics and 4 PCOs. For each PCO, we specified a multivariate linear fixed-effects regression model with penalized LASSO (least absolute shrinkage and selection operator) variable selection that included parameters for each incremental absolute PHQ-9 decrease between 0 and 16 points. Model predictive properties were assessed using a split sample analysis. There was a notable variation in depression improvement rates across metrics. Each metric was significantly associated with PCOs in univariate analyses. In the multivariate models, the cumulative likelihood of PCO improvement was most improved by absolute PHQ-9 score decreases of 7-9 and 14-16 points. The multivariate models showed greater area under the curve (0.671-0.804) in out-of-sample predictions of PCO changes than the univariate models (0.529-0.649). Choice of depression response metric impacts observed response and remission rates, though PCOs tend to improve with depression improvement regardless of metric choice. Absolute incremental PHQ-9 score decreases are broadly associated with an increased likelihood of favorable PCO scores. Our findings support a novel PHQ-9 metric defined by an absolute score change of 8 points or greater.

Predictors of Poststroke Aphasia Recovery: A Systematic Review-Informed Individual Participant Data Meta-Analysis.

The factors associated with recovery of language domains after stroke remain uncertain. We described recovery of overall-language-ability, auditory comprehension, naming, and functional-communication across participants' age, sex, and aphasia chronicity in a large, multilingual, international aphasia dataset. Individual participant data meta-analysis of systematically sourced aphasia datasets described overall-language ability using the Western Aphasia Battery Aphasia-Quotient; auditory comprehension by Aachen Aphasia Test (AAT) Token Test; naming by Boston Naming Test and functional-communication by AAT Spontaneous-Speech Communication subscale. Multivariable analyses regressed absolute score-changes from baseline across language domains onto covariates identified a priori in randomized controlled trials and all study types. Change-from-baseline scores were presented as estimates of means and 95% CIs. Heterogeneity was described using relative variance. Risk of bias was considered at dataset and meta-analysis level. Assessments at baseline (median=43.6 weeks poststroke; interquartile range [4-165.1]) and first-follow-up (median=10 weeks from baseline; interquartile range [3-26]) were available for n=943 on overall-language ability, n=1056 on auditory comprehension, n=791 on naming and n=974 on functional-communication. Younger age (<55 years, +15.4 Western Aphasia Battery Aphasia-Quotient points [CI, 10.0-20.9], +6.1 correct on AAT Token Test [CI, 3.2-8.9]; +9.3 Boston Naming Test points [CI, 4.7-13.9]; +0.8 AAT Spontaneous-Speech Communication subscale points [CI, 0.5-1.0]) and enrollment <1 month post-onset (+19.1 Western Aphasia Battery Aphasia-Quotient points [CI, 13.9-24.4]; +5.3 correct on AAT Token Test [CI, 1.7-8.8]; +11.1 Boston Naming Test points [CI, 5.7-16.5]; and +1.1 AAT Spontaneous-Speech Communication subscale point [CI, 0.7-1.4]) conferred the greatest absolute change-from-baseline across each language domain. Improvements in language scores from baseline diminished with increasing age and aphasia chronicity. Data exhibited no significant statistical heterogeneity. Risk-of-bias was low to moderate-low. Earlier intervention for poststroke aphasia was crucial to maximize language recovery across a range of language domains, although recovery continued to be observed to a lesser extent beyond 6 months poststroke.

Arthroscopic Correction of Sports-Related Femoroacetabular Impingement in Competitive Athletes: 2-Year Clinical Outcome and Predictors for Achieving Minimal Clinically Important Difference.

Background:A growing body of literature supports surgical intervention for femoroacetabular impingement (FAI) in young, active athletes. However, factors likely to influence results in this cohort are less clearly defined.Purpose:To quantify changes in validated patient-reported outcome measures (PROMs) and determine whether differences in baseline athlete demographic characteristics, intraoperative findings, and surgical techniques are associated with achieving improved outcomes and minimal clinically important difference (MCID) after arthroscopic management of sports-related FAI.Study Design:Case series; Level of evidence, 4.Methods:Data were prospectively collected from competitive athletes who underwent hip arthroscopy between January 2009 and February 2017. Athletes who underwent primary arthroscopic correction of sports-related FAI with labral repair were included providing they had a Tönnis grade ≤1 and a lateral center-edge angle ≥20°, excluding significant articular cartilage injury and lateral rim dysplasia. The modified Harris Hip Score, Western Ontario and McMaster Universities Osteoarthritis Index, University of California Los Angeles activity scale, and 36-Item Short Form Health Survey were used to measure outcomes at the 2-year follow-up. MCID was measured using 3 methods: a mean change method, a distribution-based method, and the percentage of possible improvement (POPI) method. Multivariate regression models were used to assess a number of diagnostic and surgical variables associated with good outcome and achieving MCID at follow-up.Results:At 2-year follow-up, statistically significant improvements were observed for all PROMs (P < .001 for all), and 84% of athletes continued to play sport. Higher preoperative PROM scores reduced the likelihood of achieving MCID; however, returning to play was the strongest predictor of reaching MCID in this athletic cohort. Using absolute score change (mean change or distribution method) to calculate MCID was less accurate owing to ceiling effects and dependence on preoperative PROM scores.Conclusion:Athletes undergoing arthroscopy for sports-related FAI can expect a successful outcome and continued sports participation at 2 years postoperatively. The majority of athletes will achieve MCID. The POPI method of MCID calculation was more applicable to higher functioning athletic cohorts. Reduced preoperative PROM scores and the ability to return to sport increased the likelihood of achieving MCID in this population.

“RADIOLOGICALASSESSMENT OF OSTEOMEATAL UNIT VARIATIONS IN CHRONIC RHINOSINUSITIS AND NASAL POLYPOSIS– A STUDY IN A TERTIARY CARE HOSPITAL”.

The osteomeatalunit plays an important role in the development of chronic rhinosinusitis with nasal polyposis. Fifty patients were studied. Most were Caucasian and had moderate/severe allergic rhinitis symptoms. Mean Age was 36 (6 14.5) years. Rhinoseptoplasty was associated with improvement in all QOL scores irrespective of turbinate Intervention (P &lt; 0.001). Analysis of covariance was conducted to control for potential confounders. There was no difference Between the groups in absolute score changes for Nasal Obstruction Symptom Evaluation-Portuguese (NOSE-p) (250.5 vs. 247.6; P 5 0.723), Rhinoplasty Outcome Evaluation (ROE) (47 vs. 44.8; P 5 0.742), and all World Health Organization Quality Of Life Scale-Abbreviated (WHOQOL-brief) score domains (P &gt; 0.05). There were no differences between the groups regarding Presence of the complications. Surgical duration was higher in the EPIT group (212 minutes 6 7.8 vs. 159.1 6 5.6; P? 0.001). Fifty patients were studied. Most were Caucasian and had moderate/severe allergic rhinitis symptoms. Mean Age was 36 (6 14.5) years. Rhinoseptoplasty was associated with improvement in all QOL scores irrespective of turbinate Intervention (P &lt; 0.001). Analysis of covariance was conducted to control for potential confounders. There was no difference Between the groups in absolute score changes for Nasal Obstruction Symptom Evaluation-Portuguese (NOSE-p) (250.5 vs. 247.6; P 5 0.723), Rhinoplasty Outcome Evaluation (ROE) (47 vs. 44.8; P 5 0.742), and all World Health Organization Quality Of Life Scale-Abbreviated (WHOQOL-brief) score domains (P &gt; 0.05). There were no differences between the groups regarding Presence of the complications. Surgical duration was higher in the EPIT group (212 minutes 6 7.8 vs. 159.1 6 5.6; P? 0.001). Fifty patients were studied. Most were Caucasian and had moderate/severe allergic rhinitis symptoms. Mean Age was 36 (6 14.5) years. Rhinoseptoplasty was associated with improvement in all QOL scores irrespective of turbinate Intervention (P &lt; 0.001). Analysis of covariance was conducted to control for potential confounders. There was no difference Between the groups in absolute score changes for Nasal Obstruction Symptom Evaluation-Portuguese (NOSE-p) (250.5 vs. 247.6; P 5 0.723), Rhinoplasty Outcome Evaluation (ROE) (47 vs. 44.8; P 5 0.742), and all World Health Organization Quality Of Life Scale-Abbreviated (WHOQOL-brief) score domains (P &gt; 0.05). There were no differences between the groups regarding Presence of the complications. Surgical duration was higher in the EPIT group (212 minutes 6 7.8 vs. 159.1 6 5.6; P? 0.001). Fifty patients were studied. Most were Caucasian and had moderate/severe allergic rhinitis symptoms. Mean Age was 36 (6 14.5) years. Rhinoseptoplasty was associated with improvement in all QOL scores irrespective of turbinate Intervention (P &lt; 0.001). Analysis of covariance was conducted to control for potential confounders. There was no difference Between the groups in absolute score changes for Nasal Obstruction Symptom Evaluation-Portuguese (NOSE-p) (250.5 vs. 247.6; P 5 0.723), Rhinoplasty Outcome Evaluation (ROE) (47 vs. 44.8; P 5 0.742), and all World Health Organization Quality Of Life Scale-Abbreviated (WHOQOL-brief) score domains (P &gt; 0.05). There were no differences between the groups regarding Presence of the complications. Surgical duration was higher in the EPIT group (212 minutes 6 7.8 vs. 159.1 6 5.6; P? 0.001). Materials and Methods Observational Descriptive Study Design. Medical Records Department and CT Archives of Radiology Department, Father Muller Medical College Hospital(FMMCH), Mangalore. Three months after approval from ethics committee, data extraction period was from 29-09-2018 to 20-05-2020. Inclusion Criteria: All age group patients with chronic rhinosinusitis and nasal polyposis who underwent FESS in FMMCH, Mangalore from 29-09-2018 to 20-05-2020. Exclusion Criteria: Patients with Malignancy of nose and PNS, road traffic accident cases and Revision nasal surgery cases. Result and Discussion: In our study, 16(10.4%) patients were ≤20 years old, 32(20.8%) patients were 21-30 years old, 34(22.1%) patients were 31-40 years old, 28(18.2%) patients were 41-50 years old, 22(14.3%) patients were 51-60 years old, 14(9.1%) patients were 61-70 years old,7(4.5%) patients were 71-80 years old and 1(0.6%) patient was 81-90 years old. There were 70(45.5%) female patients and 84(54.5%) male patients. For complete disease clearance and safe performance of endoscopic sinus surgery a thorough knowledge of the CT scan of the paranasal sinuses is a necessary requirement in modern the modern endoscopic sinus surgery era. Hence a better understanding of the anatomy of the osteomeatal complex plays a vital role in the outcome of endoscopic sinus surgery performed for chronic rhinosinusitis. Conclusion: We concluded in our study that deviated nasal septum was seen in 83% of our patients which was the most common anatomical variant followed by concha bullosa, aggernasi, haller cell and paradoxical middle turbinate. The most common attachment of the uncinate process was to the lamina papyracea.

CONGENITAL MUSCULAR DYSTROPHIES: P.326Minimal clinically important difference for the Motor Function Measure in patients with congenital muscular dystrophy and congenital myopathy

To determine the minimal clinically important difference (MCID) for the motor function measure (MFM-32) in congenital muscular dystrophy and congenital myopathy patient an observational, retrospective, multicentric study was conducted on 85 congenital muscular dystrophy or congenital myopathy patients, aged 5 to 22 years at the national institute of neurological disorders and stroke of the national institutes of health and 2 French departments of paediatric physical medicine and rehabilitation. Data were collected if at least 2 MFMs were performed (MFM1 and MFM2) within 8 to 36 months of each other and if during MFM2 parents or patients were asked to provide their perceived change in functional status or strength since MFM1. Patients were divided in 3 groups according to their overall assessment of disease evolution: deterioration, stability or improvement. Absolute score changes between MFM1 and MFM2 total score (TS) and each subscore (D1, D2 and D3) were calculated for each patient. The mean score change of each group of patient reported disease evolution was provided and then groups were compared to determine if the difference was statistically significant. The MCID was calculated. Mean scores changes for D1, D2 and TS improved for patients reporting improvement (respectively 2,4±5,6; 2,1±13,3 and 2,5±7,2) and declined for patients reporting deterioration (-3,2±8,1; -1,3±15,7 and -1,3±7,2) or stability (-1,2±7,4; -2,2±10,5 and -1,5±10). The mean score for D3 was stable or improved in all patients, even if they reported an overall deterioration. The MCID was consecutively calculated for D1, D2 and TS. When designing clinical trials in congenital onset neuromuscular diseases, the use of MCID for MFM should be considered as a chief outcome measure to determine if a given intervention effects not only statistically significant change but also clinically meaningful improvements.

Habit, a Feasibility Trial to Improve Hydroxyurea Adherence, Improves Quality of Life in Youth with Sickle Cell Disease

Background: Daily hydroxyurea (HU) adherence is often suboptimal for youth with sickle cell disease (SCD). Adolescence is a critical time to improve HU adherence as youth assume greater responsibility for medication self-management. While QOL is higher among youth prescribed HU compared to those who are not,1little is known about how participation in an intervention to improve HU adherence is related to self- and parent-proxy reported QOL.Methods: We conducted a 2-site randomized controlled feasibility trial with 2:1 randomization, “Hydroxyure Adherence for Personal Best in Sickle Cell Treatment: HABIT,” to estimate the effect of a community health worker (CHW) intervention for youth-parent dyads, augmented by tailored text messages, on HU adherence in youth 10-18 years of age with SCD.2 The secondary outcomes, reported here, were: generic QOL (PedsQL; total score and 4 subscales); disease-specific QOL (PedsQL SCD Module; total score and 9 additional subscales), and youth-parent concordance regarding self-management responsibility (Sickle Cell Family Responsibility Scale, adapted from the Diabetes Family Responsibility Questionnaire). Each outcome was measured at 0, 3 and 6 months. Descriptive statistics were used to profile each measure including a Cronbach alpha to assess scale reliability in this sample. A minimally clinically important difference (MCID) was computed for each total and subscale score as a criterion to assess clinically meaningful improvements. A linear individual growth model incorporating group assignment and time was used to examine the difference in each outcome over time. Where outcomes achieved statistical significance (p<0.05), we compared the intervention group's absolute score change from 0 to 6 months to the MCID to assess a clinically meaningful change. Data were analyzed using SAS 9.4 (Cary, NC) statistical software.Results: Of 48 eligible dyads, 28 (youth age 14.3±2.6 years, 50% Hispanic) participated (18 intervention dyads, 10 control dyads), with 10.7% attrition. The intervention was feasible (58% enrolled), acceptable to dyads and demonstrated a trend to HU adherence improvement at 4 months.3 Cronbach alphas ranged between 0.71 and 0.97 for parent and youth measures. Incorporating group assignment and time, intervention youth reported improved generic QOL total score (p=0.04; change 9.2 [95% CI 5.7, 12.7]) and its emotional subscale (p=0.034; change 14.4 [95% CI 10.2, 18.6]), 3 disease-specific QOL subscales: worry I (p=0.009; 26.1 [95% CI 18.0, 34.2), emotions (p=0.01; change 33.0 [95% CI 23.8, 42.2]), and communication I (p=0.048; change 15.3 [95% CI 8.5, 22.1]), and a trend for improved dyad concordance regarding self-management responsibility at 3 months (p=0.07; change 1.6 [95% CI 1.0, 2.2]). In each case, score improvement exceeded its MCID. No differences were found in parent-proxy reported QOL measures.Conclusions: HABIT improved two generic and three disease-specific youth-reported QOL outcomes in the psychosocial domain. Whether QOL improvement stemmed from greater HU adherence, CHW support and/or improved dyad self-management concordance is uncertain. These findings add to a growing body of research examining effects of interventions on QOL outcomes in youth with SCD. To confirm these findings, a multi-site HABIT randomized controlled trial powered to test intervention efficacy is planned.

Partial inferior turbinectomy in rhinoseptoplasty has no effect in quality-of-life outcomes: A randomized clinical trial.

Evaluate the impact of endoscopic partial inferior turbinectomy (EPIT) associated with primary rhinoseptoplasty on quality-of-life outcomes (QOL), complications, and surgical duration. Randomized clinical trial. Individuals with nasal obstruction aged ≥ 16 years who were candidates for functional and aesthetics primary rhinoseptoplasty were evaluated from March 2014 through May 2015. Eligible participants were randomly allocated to rhinoseptoplasty with or without EPIT (excision of one-third of the inferior turbinates). Fifty patients were studied. Most were Caucasian and had moderate/severe allergic rhinitis symptoms. Mean age was 36 ( ± 14.5) years. Rhinoseptoplasty was associated with improvement in all QOL scores irrespective of turbinate intervention (P < 0.001). Analysis of covariance was conducted to control for potential confounders. There was no difference between the groups in absolute score changes for Nasal Obstruction Symptom Evaluation-Portuguese (NOSE-p) (-50.5 vs. -47.6; P = 0.723), Rhinoplasty Outcome Evaluation (ROE) (47 vs. 44.8; P = 0.742), and all World Health Organization Quality of Life Scale-Abbreviated (WHOQOL-bref) score domains (P > 0.05). There were no differences between the groups regarding presence of the complications. Surgical duration was higher in the EPIT group (212 minutes ± 7.8 vs. 159.1 ± 5.6; P ? 0.001). Turbinate reduction through EPIT during primary rhinoseptoplasty did not improve short-term general and specific QOL outcomes. The use of EPIT increases surgical time considerably without improving QOL scores. There was no difference in postoperative incidence of complications, suggesting that EPIT is a safe technique. 1b. Laryngoscope, 128:57-63, 2018.

T38 - Preliminary Model For The Genetic Prediction Of Clozapine Response

Background Despite its clinical utility, the antipsychotic clozapine (CLZ) has not yet had a promising pharmacogenetic test developed for prediction of response. In the past 20 years, multiple genetic variants (e.g. dopamine, serotonin) have been suggested to be associated with CLZ response. Arranz et al (2000) proposed a model to predict response, but it was not replicated in independent samples. Since then, no other studies have sought to create a genetic panel predicting response to CLZ. Thus, we reinitiated the effort to develop a genetic model for CLZ response incorporating the most promising findings from our group’s repository of CLZ response studies. Methods Our sample consisted of 151 Caucasian subjects with schizophrenia (SCZ) (DSM-III) treated with CLZ for six months. Response was assessed using the Brief Psychiatric Rating Scale (BPRS), and evaluated using absolute score change and binary response (Kane et al. 1988 criteria), with baseline score as a covariate. A total of 99 polymorphisms were tested from a range of candidate genes. Variants showing at least a nominal statistical trend (p Results Four markers from genes encoding for dopamine D2 receptor (DRD2), serotonin-6 receptor (5-HT6), brain-derived neurotrophic factor (BDNF), and neurexin-1 (NRXN1) were included in the model. We observed a statistically significant association between genetic risk score with BPRS score change (p=0.000039, Adjusted R^2=0.565) and binary response (p=0.004, Nagelkerke R^2=0.097) assuming a linear increase in response for each additional risk allele. The model had an accuracy of 62%, a sensitivity of 70%, and a specificity of 47%. The model was not significantly associated with response in the independent CATIE European Caucasian subsample treated with other antipsychotics (p=0.10). Discussion We have developed a preliminary genetic model for CLZ response that includes genes with strong rationale for involvement. NRXN1 is a synaptic membrane cell-adhesion protein that has been suggested to modulate NMDA receptor activity, which is indirectly regulated by CLZ. The 5-HT6 receptor is involved in neurite growth and has lower expression in the hippocampus of SCZ patients compared to healthy controls. It mediates cognitive function, anxiety, and positive symptom improvement in animal models of SCZ. The model does not appear to generalize to other antipsychotics. For CLZ response prediction per se, replication in independent studies of CLZ response in SCZ is required to confirm the validity of these findings.

Enoximone coupled to very low dose dobutamine echocardiography detects myocardial viability in akinetic and dyskinetic post-myocardial infarcted areas

Dobutamine and enoximone stimulate independently inotropic reserve by increasing intracellular cyclic adenosine monophosphate. The potential of enoximone (0.75 mg/kg body weight over 10 minutes) followed by very low dose (2.5 μg/kg/min) dobutamine echocardiography to predict recovery of ventricular function in akinetic and dyskinetic postinfarcted areas was studied. We enrolled 22 patients with previous Q-wave myocardial infarction and regional wall motion abnormalities related to left anterior descending arterial disease, left ventricular ejection fraction <40%, and all scheduled for myocardial revascularization. A 10 μg/kg/min dobutamine test was performed 48 hours before the study protocol. Test images obtained at peak of pharmacodynamic effects were compared with those obtained at 4 months after myocardial revascularization. We used a 16-segment ventricular model and a 5-grade scoring system. Resting regional myocardial dysfunction graded ≥2 was present in 267 of 352 segments evaluated. Contractile reserve (decrease in resting wall motion score ≥2 grades) at peak effect of enoximone infusion was present in 34 of 112 severely hypokinetic, 42 of 117 akinetic, and 14 of 38 dyskinetic segments. The inotropic reserve evaluated after very low dose dobutamine was observed in 34 of 112 severely hypokinetic, 49 of 117 akinetic, and 20 of 38 dyskinetic segments. After revascularization, recovery of function was observed in 31 of 112 severely hypokinetic, 49 of 117 akinetic, and 21 of 38 dyskinetic segments. Overall, there was a significant correlation between absolute score changes of segments which were abnormal at baseline (n = 267) to enoximone peak effects (r = 0.49, p <0.001) to predict absolute changes after revascularization; after dobutamine there was progress toward identity (r = 0.62, p <0.001) and the difference was significant among correlation slopes of dobutamine alone, enoximone alone, and enoximone plus very low dose dobutamine echocardiograophy (0.45 ± 0.04, 0.51 ± 0.04, and 0.63 ± 0.04, respectively, F = 5.25, p = 0.005). Therefore, enoximone followed by very low dose dobutamine may assess myocardial viability of postinfarcted akinetic and dyskinetic areas. This test may be useful when evaluating patients with more severe cardiac failure and/or life-threatening arrhythmias.

Four-month test-retest reliability of the MMPI-2 with normal male clergy.

This investigation examined the test-retest coefficients and absolute score changes with the Basic, Supplementary, and Content scales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Participants were 111 active male clergy who were not receiving mental health services at the time of their participation and who completed the MMPI-2 on two occasions separated by 4 months. A repeated measures multivariate analysis of variance for the three groups of scales revealed nonsignificant changes in mean T scores. In general, the test-retest coefficients obtained were similar to those reported in the MMPI-2 manual by Butcher, Dahlstrom, Graham, Tellegen, and Kaemmer (1989) and by Spiro, Butcher, Levenson, Aldwin, and Bosse (1993). Increases or decreases of 3 to 6 T-score points were observed for the majority of the scales, and instances in which T-score changes exceeded 10 points were observed on every scale. In sum, the test-retest reliability of the majority of MMPI-2 scales, as represented in this nonclinical sample, appears acceptable and compares favorably with the original MMPI.

Benign Prostatic Hyperplasia Specific Health Status Measures in Clinical Research: How Much Change in the American Urological Association Symptom Index and the Benign Prostatic Hyperplasia Impact Index is Perceptible to Patients?

Purpose We assessed the relationship between changes in scores for the American Urological Association (AUA) symptom index and benign prostatic hyperplasia (BPH) impact index with patient global ratings of improvement in a large Veterans Affairs trial comparing different pharmacological therapies for BPH. Materials and Methods The primary analyses compared absolute score changes from baseline with global ratings of improvement at 13 weeks for 1,218 men. Results Subjects who rated themselves as being slightly improved had a mean decrease in AUA symptom index and BPH impact index scores of 3.1 and 0.4 points, respectively. However, the baseline scores strongly influenced this relationship. Conclusions These data provide guidance for investigators using the AUA symptom index and BPH impact index as outcome measures.