Meaningful Improvements In Quality Research Articles

Quality of Life Improvement Following Reconstruction of Midtarsal Charcot Foot Deformity: A Five Year Follow-Up

Category:DiabetesIntroduction/Purpose:Previous data has suggested that patients have significant clinical improvement after reconstruction of diabetes-associated Charcot foot arthropathy at one year postoperatively. The purpose of this study is to re-evaluate a cohort of patients who were previously surveyed pre-operatively and 1 year post-operatively following Charcot foot reconstruction to determine if improvements in quality of life measures were sustained at a 5-year interval post-operatively.Methods:Twenty-four patients were contacted to repeat the Short Musculoskeletal Function Assessment (SMFA) 5 years after their index Charcot foot reconstruction. The same cohort of patients had completed the SMFA pre-operatively and at 1 year post-operatively. The response to items were summated to establish scores on the dysfunction and bother indices. The scores were then standardized to range from 0 to 100 with use of the published scoring formula. Poorer function is indicated by higher scores. Descriptive statistics were utilized to analyze the differences between the preoperative and five year data for the group. Sixteen of the initial 24 study patients (66.6%) were successfully contacted and completed the SMFA survey at five years postoperatively; 2 of the 16 had subsequently undergone amputation.Results:Fourteen patients who had previously completed the SMFA preoperatively and 1 year postoperatively after Charcot foot reconstruction in a circular frame were contacted and again completed the SMFA instrument. Improvement was noted in all domains measured by the SMFA between preoperative scores and five years postoperative scores; there was a 17-point decrease in the SMFA standardized functional index and a 3.6-point decrease in bother index. Similarly, when looking at individual domains, there was a 8.7-point decrease in difficulty with daily activities, 4-point improvement in emotion, and 5.7-point improvement in mobility. There was a statistically significant improvement in difficulty with daily activities at five years (p = 0.037), All other domains assessed by the SMFA demonstrated improvement between the two time periods, but did not reach significance due to the limited sample size.Conclusion:Successful correction of non-plantigrade midtarsal Charcot foot arthropathy is associated with a clinically meaningful improvement in health-related quality of life at both one and five years postoperatively, including independence with daily activities. This further supports the modern paradigm shift towards operative correction of this deformity.

Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial

Elexacaftor plus tezacaftor plus ivacaftor is a triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be generally safe and efficacious in people with cystic fibrosis aged 12 years or older with at least one F508del-CFTR allele. We aimed to assess the magnitude and durability of the clinical effects of this triple combination regimen in people with cystic fibrosis homozygous for the F508del-CFTR mutation. We conducted a multicentre, randomised, double-blind, active-controlled, phase 3b trial of elexacaftor plus tezacaftor plus ivacaftor at 35 medical centres in Australia, Belgium, Germany, and the UK. Eligible participants were those with cystic fibrosis homozygous for the F508del-CFTR mutation, aged 12 years or older with stable disease, and with a percent predicted FEV1 of 40-90% inclusive. After a 4-week run-in period, in which participants received tezacaftor 100 mg orally once daily and ivacaftor 150 mg orally every 12 h, participants were randomly assigned (1:1) to receive 24 weeks of either elexacaftor 200 mg orally once daily plus tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h (elexacaftor plus tezacaftor plus ivacaftor group) or tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h (tezacaftor plus ivacaftor group). Randomisation was stratified by percent predicted FEV1, age at screening visit, and whether the participant was receiving CFTR modulators at the time of the screening visit. Patients, investigators, and sponsor's study execution team were masked to treatment assignment. The primary endpoint was the absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score from baseline (ie, at the end of the tezacaftor plus ivacaftor run-in period) up to and including week 24. The key secondary endpoint was the absolute change from baseline in percent predicted FEV1 up to and including week 24; other secondary endpoints were the absolute change from baseline in sweat chloride concentrations up to and including week 24, and safety and tolerability. All endpoints were assessed in all randomised patients who had received at least one dose of their assigned regimen. This study is registered with ClinicalTrials.gov, NCT04105972. Between Oct 3, 2019, and July 24, 2020, 176 participants were enrolled. Following the 4-week tezacaftor plus ivacaftor run-in period, 175 participants were randomly assigned (87 to the elexacaftor plus tezacaftor plus ivacaftor group and 88 to the tezacaftor plus ivacaftor group) and dosed in the treatment period. From baseline up to and including week 24, the mean CFQ-R respiratory domain score increased by 17·1 points (95% CI 14·1 to 20·1) in the elexacaftor plus tezacaftor plus ivacaftor group and by 1·2 points (-1·7 to 4·2) in the tezacaftor plus ivacaftor group (least squares mean treatment difference 15·9 points [95% CI 11·7 to 20·1], p<0·0001), the mean percent predicted FEV1 increased by 11·2 percentage points (95% CI 9·8 to 12·6) in the elexacaftor plus tezacaftor plus ivacaftor group and by 1·0 percentage points (-0·4 to 2·4) in the tezacaftor plus ivacaftor group (least squares mean treatment difference 10·2 percentage points [8·2 to 12·1], p<0·0001), and the mean sweat chloride concentration decreased by 46·2 mmol/L (95% CI 43·7 to 48·7) in the elexacaftor plus tezacaftor plus ivacaftor group and by 3·4 mmol/L (1·0 to 5·8) in the tezacaftor plus ivacaftor group (least squares mean treatment difference -42·8 mmol/L [-46·2 to -39·3], nominal p<0·0001). Most participants (70 [80%] in the elexacaftor plus tezacaftor plus ivacaftor group and 74 [84%] in the tezacaftor plus ivacaftor group) had adverse events that were mild or moderate in severity; serious adverse events occurred in five (6%) of 87 participants in the elexacaftor plus tezacaftor plus ivacaftor group and 14 (16%) of 88 participants in the tezacaftor plus ivacaftor group. One (1%) participant in the elexacaftor plus tezacaftor plus ivacaftor group discontinued treatment due to an adverse event of anxiety and depression. Two (2%) participants in the tezacaftor plus ivacaftor group discontinued treatment due to adverse events of psychotic disorder (n=1) and obsessive-compulsive disorder (n=1). The elexacaftor plus tezacaftor plus ivacaftor regimen was safe and well tolerated, and led to significant and clinically meaningful improvements in respiratory-related quality of life and lung function, as well as improved CFTR function, changes that were durable over 24 weeks and superior to those seen with tezacaftor plus ivacaftor in this patient population. Vertex Pharmaceuticals.

Impact of Risankizumab on PASI90 and DLQI0/1 Duration in Moderate-to-Severe Psoriasis: A Post Hoc Analysis of Four Phase 3 Clinical Trials.

IntroductionNovel therapies have allowed psoriasis patients to achieve high levels of skin clearance and meaningful improvements in health-related quality of life measures; however, duration of these outcomes has not been evaluated. This study aimed to estimate the duration of Psoriasis Area and Severity Index (PASI) 90 and Dermatology Life Quality Index (DLQI) 0/1 among patients with moderate-to-severe psoriasis receiving risankizumab and other treatments.MethodsPooled data from four phase 3 randomized clinical trials of risankizumab were used to estimate the number and proportion of days with PASI90 and DLQI0/1 during the 1-year post-baseline period with an area-under-the-curve approach. Patients were classified into five cohorts on the basis of their treatment experience during the follow-up period: risankizumab (RISA) only, RISA followed by re-randomization to RISA or placebo (RISA and RISA/PBO), adalimumab (ADA) followed by re-randomization to ADA or RISA (ADA and ADA/RISA), ustekinumab (UST) only, and placebo followed by risankizumab (PBO/RISA).ResultsA total of 2101 patients were included in this analysis. Mean age was 47.5 years, 70% were males, and mean duration since psoriasis diagnosis was 18.6 years. Patients treated with RISA only throughout the study period experienced the longest PASI90 [245.7 days (67% over 1 year)] and DLQI0/1 [213.7 (59%)] duration. Patients treated with PBO/RISA [156.8 (43%)] and UST only [154.2 (42%)] experienced the shortest PASI90 duration. Similarly, patients treated with PBO/RISA experienced the shortest DLQI0/1 duration during the 52-week study period [90.5 (25%)].ConclusionPatients with moderate-to-severe psoriasis treated with risankizumab exhibited longer durations of PASI90 and DLQI0/1 than patients treated with other therapies.Trial RegistrationClinicalTrials.gov identifiers: UltIMMa-1 (NCT02684370), NCT02684357 (UltIMMa-2), IMMvent (NCT02694523), IMMhance (NCT02672852).Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00660-3.

The Relationship Between Reductions in WHO Risk Drinking Levels During Treatment and Subsequent Healthcare Costs for the ACTIVE Workgroup.

Abstinence has historically been considered the target outcome for alcohol use disorder (AUD) treatment, yet recent work has found drinking reductions after AUD treatment, as measured by World Health Organization (WHO) risk drinking levels, are associated with meaningful improvements in functioning, physical health, and quality of life. This study extends previous analyses of AUD treatment outcomes by estimating the association between changes in WHO risk drinking levels (very high, high, medium, and low, based on average daily alcohol consumption) and healthcare costs. Secondary data analysis of the COMBINE study, a multisite randomized clinical trial of acamprosate, naltrexone and behavioral interventions for AUD. Generalized gamma regression models were used to estimate relationships between WHOrisk drinking level reductions over the course of treatment and healthcare costs in the year after treatment (N = 964) and up to 3 years following treatment (N = 651). SustainedWHOrisk drinking reductions of 2 or more levels throughout treatment were associated with 52.0% lower healthcare costs ( P < 0.001) in the year following treatment, and 44.0% lower costs ( P < 0.0025) over 3 years. A reduction of exactly 1 level was associated with 34.8% lower costs over 3 years, which was not significant ( P = 0.05). Cost reductions were driven by lower inpatient behavioral health and emergency department utilization. Reduction in WHO risk drinking levels of at least 2 levels was associated with lower healthcare costs over 1 and 3 years. Our results add to literature showing drinking reductions are associated with improvement in health.

Dupilumab Provides Rapid and Sustained Clinically Meaningful Responses in Adults with Moderate-to-severe Atopic Dermatitis.

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a realworld setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo-controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p < 0.0001) achieved improvement in signs (Eczema Area and Severity Index ≤ 7), symptoms (worst itch score ≤ 4), or quality of life (Dermatology Life Quality Index ≤5), representative of minimal/clear atopic dermatitis. All 3 endpoints, indicative of no/minimal atopic dermatitis, were achieved by 44.3% of dupilumab-treated vs 10.2% placebo patients (p < 0.0001) and sustained through 1 year. Dupilumab treatment provided sustained clinically meaningful improvement in signs, symptoms, and quality of life in adults with moderate-to-severe atopic dermatitis.

Categorized Hematologic Response to Pegcetacoplan and Correlations with Quality of Life in Patients with Paroxysmal Nocturnal Hemoglobinuria: Post Hoc Analysis of Data from Phase 1b, Phase 2a, and Phase 3 Trials

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a complement-mediated, hematologic disease characterized by hemolysis, anemia, and fatigue that impairs quality of life. Pegcetacoplan (PEG), a C3-inhibitor recently approved by the Food and Drug Administration for treatment of PNH, controls intravascular hemolysis (IVH) and prevents extravascular hemolysis (EVH). The PADDOCK and PALOMINO trials demonstrated PEG's improvement of key hematologic and clinical parameters, including hemoglobin (Hb) level and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score. The PEGASUS trial demonstrated that PEG was more effective than eculizumab (ECU) in improving these parameters in PNH patients with suboptimal response to prior ECU treatment.Aims: This post hoc analysis categorized hematologic response to PEG in 3 trials: PADDOCK (phase 1b, open-label, two-cohort [NCT02588833]), PALOMINO (phase 2a, open-label, single-cohort [NCT03593200]), and PEGASUS (phase 3, randomized, open-label, active-comparator controlled [NCT03500549]).Methods: PADDOCK and PALOMINO included adult complement inhibitor-naïve patients, while PEGASUS included adult patients with Hb <10.5 g/dL despite ≥3 months of ECU treatment. PADDOCK was a multiple ascending dose pilot study of 2 cohorts: cohort 1 received a suboptimal PEG dose (180 mg/day subcutaneously [SQ]) for 28 days; cohort 2 received a PEG dose of 270-360 mg/day SQ for up to one year. Patients could be enrolled in both cohorts. PALOMINO patients received a PEG dose of 270-360 mg/day SQ for up to one year. PEGASUS comprised a 4-week run-in period where patients received both ECU (continued dosing regimen) and PEG (1080 mg SQ twice-weekly), 16-week randomized controlled period (PEG or ECU monotherapy), and 32-week open-label period (PEG monotherapy) including a 4-week run-in period for the ECU-to-PEG group.Hematologic response category was assessed at Days 113/337 for patients in the combined PADDOCK/PALOMINO trials (N=24) via manual categorization by two independent, blinded observers. Categorization was assessed at Weeks 16/48 for PEGASUS patients (N=80) using SAS 9.4M5. Statistical significance for hematologic response categories within arms at Week 16 vs. 48, and between arms at Week 48, was evaluated using Wilcoxon-Mann-Whitney and Chi-square testing. FACIT-Fatigue scores for PEGASUS patients, summarized using descriptive statistics, were also correlated to hematologic response category.Response categories were defined per the following criteria (Risitano A, et al., Front Immunol, 2019;10:1157): complete- no transfusions required, stable Hb (normal range), no evidence of hemolysis (lactate dehydrogenase [LDH]≤1.5×upper limit of normal [ULN] U/L, absolute reticulocyte count [ARC]≤150,000/µL); major- no transfusion, normal Hb, but with evidence of hemolysis (LDH>1.5×ULN U/L and/or ARC>150,000/µL); good- no transfusions, but with chronic mild anemia or evidence of hemolysis; partial- chronic moderate anemia and/or occasional transfusions (<3 units/6 months); minor- regular transfusions required (3-6 units/6 months); no response- regular and frequent transfusions required (>6 units/6 months).PADDOCK/PALOMINO patients missing data at an assessment timepoint, or PEGASUS patients missing data within 6 weeks prior to an assessment timepoint, were not evaluated.Results: Most PADDOCK/PALOMINO patients achieved at least a good hematologic response at Days 113 and 337 (Table 1). At Week 48, most patients in both PEGASUS arms achieved a good/major/complete hematologic response (inter-arm p=0.4390), with a significant increase in the percent of ECU-to-PEG patients achieving at least a good response after switching to PEG at Week 16 (Week 16 vs. 48: intra-arm p<0.0001; Table 1). In PEGASUS, patients with better response categories had higher FACIT-Fatigue scores when compared to the rest of the cohort (Week 16: p<0.001, Week 48: p=0.028; Table 2).Conclusions: In post hoc analyses of PADDOCK, PALOMINO, and PEGASUS trial data, a substantial proportion of patients achieved and maintained good, major, or complete hematologic responses to PEG, suggesting that PEG can lead to sustained improvements in hematologic parameters. PEGASUS data also demonstrated correlation of improved hematologic response category with clinically meaningful improvements in quality of life, as measured by FACIT-Fatigue. [Display omitted] DisclosuresRisitano: Jazz: Other: Lecture fees, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees; Biocryst: Membership on an entity's Board of Directors or advisory committees; RA Pharma: Research Funding; Amyndas: Consultancy; Samsung: Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Research Funding, Speakers Bureau; Alnylam: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Research Funding, Speakers Bureau; F. Hoffmann-La Roche Ltd.: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Lecture fees, Speakers Bureau; Apellis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Speakers Bureau. Wong: Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Apellis Pharmaceuticals: Research Funding, Speakers Bureau; Alexion: Consultancy, Honoraria, Research Funding, Speakers Bureau. Al-Adhami: Apellis Pharmaceuticals: Current Employment. Chen: Apellis Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Peffault De Latour: Swedish Orphan Biovitrum AB: Consultancy, Honoraria; Apellis Pharmaceuticals: Consultancy, Honoraria; Alexion Pharmaceuticals: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.

Efficacy and Safety of Fitusiran Prophylaxis, an siRNA Therapeutic, in a Multicenter Phase 3 Study (ATLAS-INH) in People with Hemophilia A or B, with Inhibitors (PwHI)

IntroductionHemophilia A and B are rare bleeding disorders characterized by ineffective clot formation due to impaired thrombin generation as a result of deficiency of FVIII or FIX, respectively. Fitusiran is a subcutaneously (SC) administered investigational siRNA therapeutic targeting antithrombin to restore thrombin generation and rebalance hemostasis in people with hemophilia A or B, with or without inhibitors. Here, we present the safety and efficacy of fitusiran prophylaxis for PwHI in a phase 3 study (ATLAS-INH; NCT03417102).MethodsThe ATLAS-INH study is a randomized, open-label Phase 3 study designed to evaluate the efficacy and safety of fitusiran in PwHI. Eligible males ≥12 years receiving on-demand treatment with bypassing agents (BPA) were randomized in a 2:1 ratio to receive once monthly 80 mg SC fitusiran prophylaxis or continue with on-demand BPA. The primary endpoint is annualized bleeding rate (ABR) in PwHI on fitusiran prophylaxis compared to those on BPA on-demand in the efficacy period. The secondary endpoints include spontaneous ABR, joint ABR, and quality of life (QoL) measured by Haem-A-QoL.Results57 subjects were randomized into the study. Mean (range) age of the study participants at screening was 28.4 (13-63) yrs. Statistical significance was achieved for primary and all secondary endpoints with significant reduction in ABRs of treated bleeds: all, spontaneous and joint bleeds for fitusiran vs on-demand BPA arm (Table 1). A total of 25 patients in fitusiran arm (65.8%) had zero treated bleeding events. Efficacy of fitusiran prophylaxis treatment was seen in both hemophilia A and hemophilia B patients with inhibitors. Statistical significance was also achieved for improvement in physical health domain score, with a difference (95% CI) of -28.72 (-39.07 to -18.37, p-value <0.0001) as well as overall HRQoL and between fitusiran and on-demand BPA arms.Overall, 38 patients (92.7%) in the fitusiran arm and 11 patients (57.9%) in the on-demand BPA arm experienced at least 1 treatment emergent adverse event (TEAE). A total of 13 treatment emergent serious adverse events (TESAEs) were reported in 7 patients (17.1%) in the fitusiran arm and 8 TESAEs were reported in 5 patients (26.3%) in the on-demand BPA arm. All TESAEs were reported in 1 patient each; in the fitusiran prophylaxis arm these included events of device related infection, hematuria, spinal vascular disorder, subclavian vein thrombosis, thrombosis, acute cholecystitis, chronic cholecystitis and asymptomatic COVID-19. One patient (2.4%) in the fitusiran arm experienced TEAEs that resulted in study drug discontinuation (spinal vascular disorder and thrombosis). There were no fatal TEAEs reported.ConclusionsThis Phase 3 study demonstrated the efficacy of the 80 mg monthly subcutaneous prophylaxis dose of fitusiran in people with hemophilia A or B with inhibitors. Specifically, fitusiran significantly reduced bleeding with a median ABR of zero and significant proportion of people with zero bleeds, resulting in a meaningful improvement in health-related quality of life. Reported TESAEs were generally consistent with what is anticipated in an adult and adolescent population with severe hemophilia A or B with inhibitors, or with the previously identified risks of fitusiran. A revised fitusiran dosing regimen with reduced dose and dose frequency is currently being evaluated in ongoing clinical studies. [Display omitted] DisclosuresYoung: Genentech/Roche, Grifols, and Takeda: Research Funding; Apcintex, BioMarin, Genentech/Roche, Grifols, Novo Nordisk, Pfizer, Rani, Sanofi Genzyme, Spark, Takeda, and UniQure: Consultancy. Kavakli: Roche: Consultancy, Other: Clinical Trial Support; Novo Nordisk A/S: Consultancy, Other: Clinical Trial Support; Takeda: Consultancy, Other: Clinical Trial Support. Poloskey: Sanofi: Current Employment, Current equity holder in publicly-traded company. Qui: Sanofi: Current Employment, Current equity holder in publicly-traded company. Kichou: Sanofi: Current Employment, Current equity holder in publicly-traded company. Andersson: Sanofi: Current Employment, Current equity holder in publicly-traded company; WEST advisory committee member: Membership on an entity's Board of Directors or advisory committees. Mei: Sanofi: Current Employment, Current equity holder in publicly-traded company. Rangarajan: Sanofi: Other: Advisory Board; Pfizer: Other: Advisory Board; Reliance Life Sciences: Consultancy; Takeda: Other: Advisory Board, Conference Support, Speakers Bureau.

S509 Plecanatide Provided Clinically Meaningful Improvements in Health-Related Quality of Life in Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation: A Post-Hoc Analysis

S509 Plecanatide Provided Clinically Meaningful Improvements in Health-Related Quality of Life in Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation: A Post-Hoc Analysis

Changes in Product Use and Quality of Life After Patch Testing in Children With Allergic Contact Dermatitis: A Follow-up Survey.

Patch testing is the standard to diagnose allergic contact dermatitis (ACD). This study assessed the value of patch testing for product changes and quality of life in children with ACD. In this cross-sectional survey, we used a questionnaire to follow up with families of ACD patients about changes since patch testing and counseling preferences. Eligible participants were 18 years or younger during expanded series or personalized patch tests at the Washington University School of Medicine from 2007 to 2020. Of the 43 enrolled participants, most were positive for multiple allergens (63%) and changed personal products after patch testing (71%). Only 26% of the families consistently read product labels before patch testing, compared with 66% after. Patients saw a mean relative reduction of 49% in severity of rash (8.2-4.2 of 10), 46% in interference with activities (5.7-3.1), and 51% in self-consciousness (7.0-3.4) since patch testing. Families gave favorable feedback for counseling on products to avoid (9.4 of 10 average rating of usefulness), product recommendations (8.5 of 10), and chemical names (7.9 of 10). Patch testing can lead to meaningful improvements in quality of life for most children with ACD. Counseling related to positive patch test results should include discussion of specific products to use and avoid.

186. Persistent sleep disturbance after spine surgery is associated with failure to achieve meaningful improvements in pain and health related quality of life

<h3>BACKGROUND CONTEXT</h3> The relationship between biopsychosocial factors (the interaction of biologic factors, behavioral factors, and social factors that affect overall health) and quality of life is well established in spine surgery patients. Sleep hygiene is an important component of wellbeing and is closely linked to mental health. Despite the importance of sleep hygiene and the strong association between poor sleep and mental health disorders, little is known about how sleep disturbance (SD) in patients with spine conditions correlates with validated health-related quality-of-life (HRQOL) measures or the degree to which SD changes after surgery. <h3>PURPOSE</h3> Our objectives were to determine the (1) prevalence of SD among patients presenting for spine surgery at a large academic medical center; (2) correlation between SD and HRQOL scores; and (3) association between postoperative SD resolution and short-term HRQOL. We hypothesized that SD would be significantly correlated with HRQOL in patients undergoing elective spine surgery. In addition, we hypothesized that postoperative resolution of SD would be significantly associated with improved HRQOL. <h3>STUDY DESIGN/SETTING</h3> The current study is a retrospective review of these prospectively collected data from patients who presented for spine surgery at an academic medical center. <h3>PATIENT SAMPLE</h3> Eligible patients were English-speaking, were aged 18 years or older, had undergone elective surgery for degenerative lumbar or cervical spine disease or for correction of spinal deformity, and had completed preoperative and immediate postoperative assessments. Of 1,193 patients enrolled, we included the 508 (43%) who met our inclusion criteria. Of these, 226 (44%) had complete 1-year follow-up. Participants' mean age was 60 years (standard deviation, 13 years), and most were non-Hispanic (98%), and White (73%). All participants were treated at the same center by 5 fellowship-trained, board-certified spine surgeons with 6–26 years in practice. We found no significant differences in age (P = 0.98), sex (P = 0.73), or prevalence of SD (P = 0.17) between included and excluded patients. <h3>OUTCOME MEASURES</h3> Participants completed an assessment before surgery of sociodemographic and clinical information. Sociodemographic information comprised age, sex, race/ethnicity, highest educational attainment, annual household income, and relationship status. Highest educational attainment was categorized as less than 4-year college degree; 4-year college degree; or post-graduate degree. Annual household income was categorized as <$30,000; $30,000–$80,000; or >$80,000. Relationship status was used to determine whether a participant lived alone or with a partner. Clinical information was presence of comorbid conditions, current use of opioid medication, and presence of intraoperative and/or postoperative complications. Participants completed assessments of their health and wellness before and after surgery. After surgery, assessments were completed during the immediate postoperative period (6–12 weeks) and at 6, 12, and 24 months. These assessments were the Oswestry Disability Index (ODI) or the Neck Disability Index (NDI) and the Patient-Reported Outcome Measurement Information System (PROMIS-29) health domains. <h3>METHODS</h3> Using preoperative PROMIS SD scores, we grouped participants as having no sleep disturbance (score <55), mild disturbance (score, 55–60), moderate disturbance (score 60–70), or severe disturbance (score, 70). For the final analysis, we collapsed these categories into no/mild and moderate/severe. Pearson correlation tests were used to assess correlations between SD and HRQOL measures. Regression analysis (adjusting for age, sex, comorbidities, current opioid use, and occurrence of complications) was used to estimate the effect of postoperative resolved or continuing SD on HRQOL scores and the likelihood of achieving clinically meaningful improvements in HRQOL. Alpha = 0.05. <h3>RESULTS</h3> Preoperative SD was reported by 127 participants (25%). SD was significantly correlated with worse ODI/NDI values and worse scores in all PROMIS health domains (all, P < 0.001). At the immediate postoperative assessment, SD had resolved in 80 of 127 participants (63%). Compared with participants who reported no preoperative SD, those with ongoing SD were significantly less likely to achieve clinically meaningful improvements in Pain Interference (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.28, 0.84), Physical Function (OR, 0.32; 95% CI, 0.13, 0.82), and Satisfaction with Participation in Social Roles (OR, 0.57; 95% CI, 0.37, 0.80). <h3>CONCLUSIONS</h3> One-quarter of spine surgery patients reported preoperative SD of at least moderate severity. Poor preoperative sleep quality and ongoing postoperative sleep disturbance were significantly associated with worse scores on several HRQOL measures. These results highlight the importance of addressing patients' sleep disturbance both before and after surgery. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

27394 Dupilumab provides clinically meaningful improvement in atopic dermatitis (AD) signs, symptoms, and quality of life in children with severe AD: Results from the LIBERTY AD PEDS phase 3 clinical trial

Background: Patients with atopic dermatitis (AD) suffer from a multidimensional disease burden. We report clinically meaningful improvements in AD signs, symptoms, and quality of life in children treated with FDA-approved doses of dupilumab.

HIV Associated Neurocognitive Disorders Subsidence Through Citalopram Addition in Anti-retroviral Therapy (HANDS-CARE): A Concept Note.

There is a pressing need to effectively manage HIV Associated Neurocognitive Disorders (HAND) in sub-Saharan Africa (SSA) where the burden is among the highest in the world. Contemporary approaches based on the use of Highly Active Antiretroviral Therapy (HAART) alone are inadequate interventions for HAND, especially in SSA where there is limited availability of the required combinations of HAART for effective central nervous system penetration and where many currently prescribed agents, including efavirenz, have neurotoxicity as a major drawback. This article reviews data supporting the rationale for additive citalopram in antiretroviral therapy as a latent approach to abate HAND. It proposes the conduct of a HIV Associated Neurocognitive Disorders Subsidence through Citalopram addition in Anti-Retroviral therapy (HANDS-CARE) pilot feasibility trial (RCT) to assess whether the adjunctive use of citalopram, a widely prescribed serotonergic antidepressant, will lead to a meaningful improvement in neurocognitive functioning and quality of life in patients with HAND who are receiving HAART. A preliminarily feasible and efficacy-suggesting HANDS-CARE trial could generate statistical, clinical and operational data necessary to design and conduct a future definitive RCT. If successful, this intervention will be applicable to resource-limited settings as well as developed countries. Effective management of HAND will improve the quality of life of HIV patients, and reduce the cost of managing the disease.

Co-produced capability framework for successful patient and staff partnerships in healthcare quality improvement: results of a scoping review

BackgroundInternationally, patient and public involvement (PPI) is core policy for health service quality improvement (QI). However, authentic QI partnerships are not commonplace. A lack of patient and staff capability to...

Disease Milestones through Bibliometeric Analysis of Top 100 Cited Articles in Multiple Myeloma

Background:Multiple Myeloma (MM) accounts for 1.6% of all cancers and 5-10% of hematologic malignancies in the United States. Novel therapeutic agents have raised the overall survival from 1-2 years to 7-8 years with meaningful improvement in quality of life. Ongoing clinical trials have significantly contributed to the favorable disease outcomes, however many of these interventions still remain unknown to clinicians. The significance of citation analysis lies in the fact that clinicians often modify their management strategy based on research published in high impact journals. In this article, our main objective is to assist medical professionals working in the field to identify the most influential research published on MM.Materials and methods:We conducted a bibliographic analysis on the Web of Science (WOS). Included journals were those listed in the Science Citation Index Expanded, without specific restrictions on the journals. We retrieved the articles for analysis by typing “Multiple Myeloma” into WOS search box and conducted this data search in Title setting with application of English language filter on 07-25-2017.Results: We identified 27,718 articles published between 1901 and 2017, ranked the articles on the basis of citation frequency from highest to lowest and thereafter shortlisted the top 100 cited articles. The most cited article received 2404 citations. Top 100 cited articles were published between 1990 and 2007. In our analysis, we found that highest number of articles were published in the year 2007 (Table 1). 44 out of 100 articles were published in journals with impact factor (IF) greater than 20. The journal with highest number of publications (36%) was BLOOD (IF 13.16). The country with leading number of publication on MM was the United States of America (77%), followed by France (20%), Italy (15%), and the United Kingdom (15%) (Table 2). The production of these 100 articles originated from 50 centers, the most significant contributors out of which were VA Boston Healthcare system and Harvard University each with 36% of total articles, followed by Dana-Farber with 34% of the total articles. Anderson KC., was found to be most frequently cited common author with his contributions amounting up to 26% of the total (Table 3). Maximum studies were found to be categorized under the title of hematology (40%), followed by general internal medicine (29%) and oncology (27%).Discussion:MM research has gone through milestones in areas including disease staging, pathogenesis and management. Seven articles focused on staging, 29 on disease pathogenesis and 51 on treatment. Two of the top ten most cited articles were aimed at staging. Clinical staging was proposed by Durie BGM et al., although the most cited article in our list is no longer the primary staging system. Current classification of MM is based on revised international staging system and disease cytogenetics. Second most frequently encompassed category was disease pathogenesis. Over the years, understanding of pathogenesis has laid the foundation for development of novel therapeutic agents. Among the top 100 cited articles, only 7 studies were focused on bortezomib containing regimens, whereas none of them included carfilzomib or Ixazomib based novel therapeutic regimens. This shows that articles with high frequency of citations mostly consist of early-published articles. Among the top 100 list, only two articles were from 2012 (latest year on the list). To capture important and latest research, a second search was carried out with strategy to limit articles published during last five years.Conclusion:A bibliographic analysis of top cited articles published focused on disease staging, pathogenesis and management. Search limited to last five years (2012-2017) portrayed different results from our original search. None of the studies in the last 5 years list were included in the original list due to less number of total citations received. Recent studies focused on latest developments including therapeutic agents such as novel proteasome inhibitors (carfilzomib, Ixazomib) and monoclonal antibodies (daratumumab, eculizumab) among others. Hence we can infer that top cited article set the stage with deeper understating about MM and helped make solid foundations for the latest developments in the field. We continue to expect ground breaking discoveries be shared through medical scientific literature. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effects of Staff Training on Nursing Home Residents’ End-Of-Life Care: A Randomized Controlled Trial

ObjectivesThis trial examines the effects of end-of-life training on long-term care facility (LTCF) residents' health-related quality of life (HRQoL) and use and costs of hospital services. DesignA single-blind, cluster randomized (at facility level) controlled trial (RCT). Our training intervention included 4 small-group 4-hour educational sessions on the principles of palliative and end-of-life care (advance care planning, adverse effects of hospitalizations, symptom management, communication, supporting proxies, challenging situations). Training was provided to all members of staff. Education was based on constructive learning methods and included resident cases, role-plays, and small-group discussions. Setting and participantsWe recruited 324 residents with possible need for end-of-life care due to advanced illness from 20 LTCF wards in Helsinki. MethodsPrimary outcome measures were HRQoL and hospital inpatient days per person-year during a 2-year follow-up. Secondary outcomes were number of emergency department visits and cost of all hospital services. ResultsHRQoL according to the 15-Dimensional Health-Related Quality-of-Life Instrument declined in both groups, and no difference was present in the changes between the groups (P for group .75, adjusted for age, sex, do-not-resuscitate orders, need for help, and clustering). Neither the number of hospital inpatient days (1.87 vs 0.81 per person-year) nor the number of emergency department visits differed significantly between intervention and control groups (P for group .41). The total hospital costs were similar in the intervention and control groups. Conclusions and ImplicationsOur rigorous RCT on end-of-life care training intervention demonstrated no effects on residents’ HRQoL or their use of hospitals. Unsupported training interventions alone might be insufficient to produce meaningful care quality improvements.

Microbial water quality improvement associated with transitioning from intermittent to continuous water supply in Nagpur, India

Nearly half a billion people living in Indian cities receive their drinking water from an intermittent water supply (IWS), which can be associated with degraded water quality and risk of waterborne disease. The municipal water supply in Nagpur, India is transitioning from intermittent to continuous supply in phases. We conducted cross-sectional sampling to compare microbial water quality under IWS and continuous water supply (CWS) in Nagpur. In 2015 and 2017, we collected 146 grab samples and 90 large-volume dead-end ultrafiltration (DEUF) samples (total volume: 6,925 liters). In addition to measuring traditional water quality parameters, we also assayed DEUF samples by droplet digital PCR (ddPCR) for waterborne pathogen gene targets. At household taps served by IWS, we detected targets from enterotoxigenic E. coli, Shigella spp./enteroinvasive E. coli, norovirus GI and GII, adenovirus A-F, Cryptosporidium spp., and Giardia duodenalis. We observed a significant increase in the proportion of grab samples positive for culturable E. coli (p = 0.0007) and DEUF concentrates positive for waterborne pathogen gene targets (p = 0.0098) at household taps served by IWS compared to those served by CWS. IWS continues to be associated with fecal contamination, and, in this study, with increased prevalence of molecular evidence of waterborne pathogens. These findings add mounting evidence that, despite the presence of piped on premise infrastructure, IWS is less likely to meet the requirements for safely-managed drinking water as defined by the Sustainable Development Goals. Importantly, these findings demonstrate the transition from IWS to CWS in Nagpur is yielding meaningful improvements in microbial water quality.

Selection Criteria for Lung Transplantation: Controversies and New Developments.

Lung transplantation is an accepted therapeutic option for end-stage lung diseases. The imbalance between limited availability and vast need of donor organs necessitates careful selection of recipient candidates, ensuring the best possible utilization of the scarce resource of organs. Nonetheless, possible lung transplant candidates who could experience a meaningful improvement in survival and quality of life should not be excluded solely based on the complexity of their case. In this review, controversial issues or difficult limitations for lung transplantation, and new developments in recipient selection criteria, are discussed, which may help broaden recipient eligibility for lung transplantation without compromising long-term outcomes.

The Long-Term Impact of Levodopa/Carbidopa Intestinal Gel on 'Off'-time in Patients with Advanced Parkinson's Disease: A Systematic Review.

IntroductionLevodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in levodopa-responsive patients with advanced Parkinson’s disease (PD) when other treatments have not given satisfactory results. Reduction in ‘off’-time is a common primary endpoint in studies of LCIG, and it is important to assess the durability of this response. This systematic literature review was conducted to qualitatively summarise the data on the long-term effects of LCIG therapy on ‘off’-time.MethodsStudies were identified by searching PubMed, EMBASE and Ovid on 30 September 2019. Studies were included if they reported on patients with PD, had a sample size of ≥ 10, LCIG was an active intervention and ‘off’-time was reported for ≥ 12 months after initiation of LCIG treatment. Randomised clinical trials, retrospective and prospective observational studies, and other interventional studies were included for selection. Data were collected on: ‘off’-time (at pre-specified time periods and the end of follow-up), study characteristics, Unified Parkinson’s Disease Rating Scale (UPDRS) II, III and IV total scores, dyskinesia duration, quality of life scores, non-motor symptoms and safety outcomes.ResultsTwenty-seven studies were included in this review. The improvement in ‘off’-time observed shortly after initiating LCIG was maintained and was statistically significant at the end of follow-up in 24 of 27 studies. ‘Off’-time was reduced from baseline to end of follow-up by 38–84% and was accompanied by a clinically meaningful improvement in quality of life. Stratified analysis of ‘off’-time demonstrated mean relative reductions of 47–82% at 3–6 months and up to 83% reduction at 3–5 years of follow-up. Most studies reported significant improvements in activities of daily living and motor complications. Most frequent adverse events were related to the procedure or the device.ConclusionIn one of the largest qualitative syntheses of published LCIG studies, LCIG treatment was observed to provide a durable effect in reducing ‘off’-time.Infographic Video Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01747-1.

Problem-solving skills training in adult cancer survivors: Bright IDEAS-AC.

e24109 Background: Cancer patients experience significant distress throughout treatment and especially during transition back to normal life with greater burden on socially disadvantaged patients and those with medical comorbidities. Patient stressors can interfere with their ability to make reasoned and timely decisions about survivorship care and lead to poor quality of life and low physical and social functioning. This pilot effectiveness-implementation study examined the impact and feasibility of offering the Bright IDEAS system of Problem-Solving Skills Training (PSST) to adult cancer survivors to help them and their caregivers cope more successfully with decision making and distress. Methods: Patients with breast (21), prostate (9) or colorectal (20) cancer who completed their definitive cancer treatment within the last 6 months and had their cancer survivorship visit were recruited from two regional cancer centers and affiliated community oncology clinics. Patients with an NCCN distress level &gt; 2 were randomly assigned to either care as usual (CAU) or 8 weekly PSST sessions provided by a trained therapist in person or remotely. Patients were invited but not required to include a supportive other (n = 17). Patient and caregiver assessments at baseline (T1), end of intervention/3 months (T2), and 3 months post intervention/6 months (T3) focused on problem-solving skills (SPSI-25), distress (HADS) and quality of life (FACT). We also collected healthcare utilization data. We compared outcome changes T1-T2 and T1-T3, by study arm, using t-tests. Multivariate regression analysis identified subgroups of patients with positive and negative responses to skills training. Results: Average age of the participants was 63 years (45 to 87) with racial and ethnic distributions representative of the local population (88% white). Two thirds were women (n = 32), one third of the patients were recruited and received therapy fully remotely due to COVID-19-related protocol changes. Patients who received PSST reported a reduction in dysfunctional problem-solving style and improvement in constructive style while problem-solving skills of CAU patients trended in the opposite direction. Patients in the PSST arm also reported significant reduction in anxiety and depression and improvement in cancer-specific quality of life (p &lt; 0.05) that was sustained at 6 months. Patients in the PSST arm reported lower use of hospital and ED services compared to CAU patients (p = 0.07). Better improvement in outcomes was driven by lower problem-solving skills at baseline. Conclusions: Despite the logistical complexity of running a clinical trial during quarantine, patients and caregivers in the PSST arm demonstrated meaningful improvement in distress and quality of life. The evidence from this pilot study will help guide development of a future multi-site randomized clinical trial of the effect of PSST on cancer survivorship care and outcomes. Clinical trial information: NCT03567850.

Implementing an Evidence-Based Bundle to Reduce Early Labor Admissions and Increase Adherence to Labor Arrest Guidelines: A Quality Improvement Initiative.

At many hospitals, the cesarean birth rate among nulliparous term singleton vertex (NTSV) pregnancies is higher than World Health Organization benchmarks. Reducing NTSV cesarean birth is a national quality imperative. The aim of this initiative was to implement an evidence-based bundle at an urban community teaching hospital in at least 50% of labors in 60 days in order to reduce early labor admissions and increase adherence to evidence-based labor management guidelines shown to decrease cesarean birth. Chart audits, root-cause analysis, and staff engagement informed bundle development. An early labor triage guide, labor walking path, partograph, and pre-cesarean checklist were implemented to drive change. Four Rapid Cycle Plan Do Study Act cycles were conducted over 8 weeks. The bundle was implemented in 58% of births. The bundle reduced early labor admissions labor from 41% to 25%. Team knowledge reflecting current guidelines in labor management increased 35% and 100% of cesareans for labor arrest met criteria. Patient satisfaction scores exceeded 98%. Implementing an evidenced-based bundle was effective in reducing early labor admissions and increasing utilization of and adherence to labor management guidelines. Implementation of evidence-based bundles has the potential to achieve meaningful quality improvements in maternity care.