Difference In Percentage Change Research Articles

Efficacy and safety of dupilumab with concomitant topical corticosteroids in Japanese pediatric patients with moderate-to-severe atopic dermatitis: A randomized, double-blind, placebo-controlled phase 3 study

BackgroundWe investigated the efficacy and safety of dupilumab in Japanese patients aged ≥6 months to <18 years old with moderate-to-severe atopic dermatitis not adequately controlled with existing therapies. MethodsIn this randomized, double-blind, phase 3 study, patients received dupilumab (n = 30) or placebo (n = 32) with concomitant topical corticosteroids for 16 weeks, then all patients received dupilumab from 16 to 52 weeks. The primary endpoint was the proportion of patients with ≥75% improvement in Eczema Area and Severity Index (EASI) score from baseline (EASI-75) to Week 16. Key secondary endpoints included changes in EASI score, proportion of patients with investigator global assessment (IGA) scores of 0/1, and changes in worst daily itch numerical rating scale (NRS) scores (evaluated in patients aged ≥6 to <12 years [n = 35]). ResultsAt Week 16, more patients achieved EASI-75 with dupilumab than placebo (43.3% vs 18.8%; P = 0.0304), and the least squares mean (LSM) difference in percent change in EASI scores at Week 16 of dupilumab vs placebo was –39.4% (P = 0.0003). However, no significant difference in the proportion of patients achieving IGA scores of 0/1 at Week 16 with dupilumab versus placebo were seen (10.0% vs 9.4%; P = 0.8476). The percent change in worst daily itch NRS scores at Week 16 was higher with dupilumab (LSM difference: –33.3%; nominal P = 0.0117). Dupilumab was well tolerated; no new safety signals were identified. ConclusionsDupilumab showed consistent efficacy and was well tolerated in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis previously insufficiently controlled with existing therapies.

Factors Influencing Music Therapists' Retention of Clinical Hours with Autistic Clients over Telehealth During the COVID-19 Pandemic.

The 2019 coronavirus disease pandemic influenced music therapists to migrate services to online platforms, though some lost clinical hours during the pandemic when telehealth was not a viable option. This survey study aimed to ascertain factors that helped music-based therapists to continue serving autistic clients over telehealth during the pandemic. We surveyed 193 accredited music therapists located mainly in Canada and the US. In addition to gathering data on general perceptions of telehealth music therapy and Neurologic Music Therapy (NMT), one-way ANOVAs were applied to determine differences in percent-change loss of clinical hours for music therapists: (1) working in different employment settings; (2) serving children, youth, adults, or a mixture of ages; and (3) practicing NMT or not. The general perception of telehealth music therapy was positive, and NMTs believed that the clear protocols and transformation design model were helpful to them in adapting services to telehealth. There were no significant differences in percent-change of clinical hours among music therapists in different employment settings or serving different client age groups. Music therapists who said they practiced within the NMT treatment model lost a significantly lower percentage of clinical hours with autistic clients than those who did not practice NMT. Possible reasons for this result and the need for further research are discussed.

Alirocumab in Pediatric Patients With Heterozygous Familial Hypercholesterolemia

Many pediatric patients with heterozygous familial hypercholesterolemia (HeFH) cannot reach recommended low-density lipoprotein cholesterol (LDL-C) concentrations on statins alone and require adjunct lipid-lowering therapy (LLT); the use of alirocumab in pediatric patients requires evaluation. To assess the efficacy of alirocumab in pediatric patients with inadequately controlled HeFH. This was a phase 3, randomized clinical trial conducted between May 2018 and August 2022 at 43 centers in 24 countries. Pediatric patients aged 8 to 17 years with HeFH, LDL-C 130 mg/dL or greater, and receiving statins or other LLTs were included. Following consecutive enrollment into dosing cohorts, 25 of 99 patients screened for dosing every 2 weeks (Q2W) failed screening; 25 of 104 patients screened for dosing every 4 weeks (Q4W) failed screening. A total of 70 of 74 Q2W patients (95%) and 75 of 79 Q4W patients (95%) completed the double-blind period. Patients were randomized 2:1 to subcutaneous alirocumab or placebo and Q2W or Q4W. Dosage was based on weight (40 mg for Q2W or 150 mg for Q4W if <50 kg; 75 mg for Q2W or 300 mg for Q4W if ≥50 kg) and adjusted at week 12 if LDL-C was 110 mg/dL or greater at week 8. After the 24-week double-blind period, patients could receive alirocumab in an 80-week open-label period. The primary end point was percent change in LDL-C from baseline to week 24 in each cohort. Among 153 patients randomized to receive alirocumab or placebo (mean [range] age, 12.9 [8-17] years; 87 [56.9%] female), alirocumab showed statistically significant reductions in LDL-C vs placebo in both cohorts at week 24. Least squares mean difference in percentage change from baseline was -43.3% (97.5% CI, -56.0 to -30.7; P < .001) Q2W and -33.8% (97.5% CI, -46.4 to -21.2; P < .001) Q4W. Hierarchical analysis of secondary efficacy end points demonstrated significant improvements in other lipid parameters at weeks 12 and 24 with alirocumab. Two patients receiving alirocumab Q4W experienced adverse events leading to discontinuation. No significant difference in adverse event incidence was observed between treatment groups. Open-label period findings were consistent with the double-blind period. The findings in this study indicate that alirocumab Q2W or Q4W significantly may be useful for reducing LDL-C and other lipid parameters and be well tolerated in pediatric patients with HeFH inadequately controlled with statins. ClinicalTrials.gov Identifier: NCT03510884.

(210) Four-Year Surgical and Sexual Function Outcomes of Rezum Therapy Across a Broad Range of Prostate Volumes

Abstract Introduction Benign prostatic hyperplasia (BPH) often leads to the development of lower urinary tract symptoms (LUTS), which can result in significant deterioration in quality of life (QoL). Rezum therapy has demonstrated efficacy in alleviating LUTS secondary to BPH across a broad range of prostate volumes (PVs). However, there is a scarcity of long-term real-world data on Rezum outcomes across a wide range of PVs. Objective To evaluate surgical and sexual function Rezum outcomes over a 4-year period in patients with PVs &amp;lt;30cc, 30-80cc, or &amp;gt;80cc. Methods A retrospective study was conducted on patients from a multiethnic population treated with Rezum between 2017 and 2019. Patients were stratified into three cohorts based on PV: &amp;lt;30cc, 30-80cc, or &amp;gt;80cc. Outcome measures, including International Prostate Symptom Score (IPSS), QoL, International Index of Erectile Function (IIEF)-Erectile and Orgasmic function, maximum urinary flow rate (Qmax), BPH medication usage, adverse events (AEs), and decisional regret scores were collected and compared at baseline and 1-, 3-, 6-, 12-, and/or 48-months follow-up. Results A total of 252 patients were analyzed, with 35 (13.9%), 196 (77.8%), and 21 (8.3%) patients in the 30cc, 30-80cc, and &amp;gt;80cc cohorts, respectively. The &amp;gt;80cc cohort was significantly older (66.9 years [8.1]) than the &amp;lt;30cc cohort (63.4 years [8.5], p = 0.02). The &amp;lt;30cc cohort had a significantly higher baseline IPSS (21 [15-28]) and QoL (5 [4-6]) than the 30-80cc (IPSS 17 [10-23], p = 0.003; QoL 4 [3-5], p=0.02) and &amp;gt;80cc (IPSS 16 [6.5-22.5], p = 0.01; QoL 4 [3-5], p = 0.006) cohorts. The number of injections utilized per lateral prostatic lobe significantly increased with PV (&amp;lt;30cc: 1 injection [0-1] vs 30-80cc: 2 injections [1-2] vs &amp;gt;80cc: 3 injections [2-3.5], p &amp;lt; 0.001). When compared to baseline, the combined cohort saw significant percent changes at 48-months in IPSS (-70.6%, p &amp;lt; .001), QoL (-80%, p &amp;lt; .001), and Qmax (52%, p = 0.003). Within each PV cohort, significant improvements in IPSS and QoL were found at all follow-ups when compared to baseline. Qmax improvements were significant only in the 30-80cc cohort at all follow-ups. There were no significant differences in percent changes in IPSS, QoL, or Qmax between cohorts at 3-, 6-, 12-, or 48-months when compared to baseline. The &amp;lt;30cc and 30-80cc cohorts had significant decreases in BPH medication usage as early as 3-months that remained durable through 48-months (all p &amp;lt; 0.05). The &amp;gt;80cc cohort experienced a significant decrease in BPH medication usage at 3-months but it did not remain durable to 12- or 48-months. No significant differences in postoperative AEs or decision regret scores were observed between cohorts. There were no significant changes in erectile function and orgasmic function at 12-months within cohorts. No significant differences were found in 48-months reoperation rates between the &amp;lt;30cc, 30-80cc, and &amp;gt;80cc cohorts (0% vs 4.9% vs 5%, p = 0.49). Conclusions Rezum effectively improved LUTS secondary to BPH irrespective of PV, with improvements being durable over 4 years. However, patients with PVs &amp;gt;80cc should be counseled on the possibility of continuing their BPH medications following treatment. Disclosure No.

Skeletal muscle mitochondrial capacity in patients with statin-associated muscle symptoms (SAMS)

ObjectiveThe objective of this article is to evaluate near-infrared spectroscopy (NIRS), a non-invasive technique to assess tissue oxygenation and mitochondrial function, as a diagnostic tool for statin-associated muscle symptoms (SAMS).MethodsWe...

1985. A Prospective, Randomized Trial to Assess a Protease Inhibitor–based Regimen Switch Strategy to Manage Integrase Inhibitor–related Weight Gain

Abstract Background Integrase inhibitor (INI)–based antiretroviral (ARV) therapies are associated with greater weight gain than non-nucleoside reverse transcriptase inhibitor– or boosted protease inhibitor–based regimens, disproportionately affecting Black and Hispanic individuals and women. The mechanisms underlying this weight gain are unknown, and there are no prospective, randomized data exploring the impact of switching ARV classes to mitigate or reverse ARV-related weight gain. Methods DEFINE (ClinicalTrials.gov: NCT04442737) is a randomized (1:1), prospective, 48-week, active-controlled, open-label, multicenter phase 4 study evaluating switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) versus continuing INI+TAF/emtricitabine (FTC) in virologically-suppressed HIV-1–infected adults who had ≥10% weight gain while on the INI-based regimen. The primary objective was to assess percent change in body weight from baseline to Week 24 in both arms. The primary endpoint was analyzed using a mixed model for repeated measures in the intent-to-treat set of randomized participants who had received ≥1 dose of study drug. Secondary endpoints included change in body mass index (BMI), waist circumference (WC), efficacy, and safety. Data through Week 24 are reported. Results Overall, 103 adults were randomized to D/C/F/TAF (n=53) or continued INI+TAF/FTC (n=50); 30% were female and 61% were Black/African American, with median 27.0 months virologic suppression on INI+TAF/FTC (Table 1). Discontinuation rates were low and similar between arms. At Week 24, there was no significant difference in percent change in body weight from baseline between the D/C/F/TAF and INI+TAF/FTC arms (Figure). Most participants in each arm had body weight changes of ≤±3% and remained within baseline BMI and WC categories. Percent body weight changes for key subgroups are shown in Table 2. Switching to D/C/F/TAF was safe and well tolerated, and efficacy was maintained.Table 1.Demographics and Baseline Characteristics (ITT Set)BMI, body mass index; D/C/F/TAF, darunavir/cobicistat/emtricitabine/tenofovir alafenamide; FTC, emtricitabine; INI, integrase inhibitor; ITT, intent-to-treat; TAF, tenofovir alafenamide. *One participant in the D/C/F/TAF arm did not have available data. Percent Change From Baseline in Body Weight Over Time for Participants Who Switched to D/C/F/TAF and Those Who Continued Their Current INI+TAF/FTC Regimen (ITT Set) D/C/F/TAF, darunavir/cobicistat/emtricitabine/tenofovir alafenamide; FTC, emtricitabine; INI, integrase inhibitor; ITT, intent-to-treat; LS, least-squares; TAF, tenofovir alafenamide. LS means percent changes in body weight were calculated in the ITT set of randomized participants who had received ≥1 dose of study drug using a mixed model for repeated measures, in which the dependent variable was percent change from baseline in body weight; independent variables were treatment, baseline body mass index, sex, and race (Black/African American vs non–Black/African American); and visits were repeated measures. Participants in the ITT set with baseline records and ≥1 postbaseline record were included. Conclusion There was no significant difference in weight change through 24 weeks after switching from an INI-based regimen to D/C/F/TAF in adults with INI-related weight gain. Additional analyses are ongoing, including follow up through Week 48 and evaluation of changes in biomarkers and body composition (DEXA).Table 2.Percent Change From Baseline in Body Weight at Week 24 Among Key Subgroups (ITT Set)BMI, body mass index; D/C/F/TAF, darunavir/cobicistat/emtricitabine/tenofovir alafenamide; FTC, emtricitabine; INI, integrase inhibitor; ITT, intent-to-treat; TAF, tenofovir alafenamide. Disclosures William R. Short, MD, Gilead Sciences: Advisor/Consultant|ViiV: Advisor/Consultant|ViiV: Honoraria Moti Ramgopal, MD, FACP, FIDSA, AbbVie: Honoraria|Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Honoraria|Janssen Pharmaceuticals: Advisor/Consultant|Janssen Pharmaceuticals: Honoraria|Merck: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Debbie P. Hagins, MD, FAPCR, AAHIVS, Janssen Pharmaceuticals: Advisor/Consultant Johnnie Lee, MD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Richard Bruce Simonson, BS, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Tien-Huei Hsu, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Ping Xu, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds David Anderson, MD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds

FRI681 OsteoboostTm Is Effective In Preserving Bone Strength And Density Of The Spine In Women With Low Bone Mass

Abstract Disclosure: L.D. Bilek: Grant Recipient; Self; Bone Health Technologies. Stock Owner; Self; Bone Health Technologies. L.E. Flores: Employee; Self; Bone Health Technologies. N. Waltman: None. L.R. Mack: None. K. Smith: None. D. Hillstrom: Employee; Self; Bone Health Technologies. M. Griffin: Consulting Fee; Self; Bone Health Technologies. Stock Owner; Self; Bone Health Technologies. L. Yecies: Employee; Self; Bone Health Technologies. Stock Owner; Self; Bone Health Technologies. M. Jaasma: Consulting Fee; Self; Bone Health Technologies. Stock Owner; Self; Bone Health Technologies. Introduction: Fragility fractures result in significant morbidity and mortality, which is of particular concern in postmenopausal women who are at high risk of fractures due to loss of estrogen. Pharmaceutical interventions are effective but have low uptake and adherence and are generally not indicated for patients with osteopenia. Vibration has the potential to prevent bone loss and holds promise as an effective, yet minimal risk, treatment. The Osteoboost, a novel wearable device delivering targeted vibration to the lumbar spine and hips, is designed to improve bone strength and bone density. Thus, this study aims to evaluate the efficacy of a 12-month intervention with the OsteoboostTM on preserving strength of the first lumbar vertebrae in postmenopausal women with low bone mass. Methods: This double-blinded, randomized controlled trial enrolled postmenopausal women with low bone mass who were not taking bone-active medications. Women had a bone density DXA and assessment of thyroid function to screen for eligibility Those who qualified were randomized to receive Osteoboost treatment 5x/week for 12 months with the belt in either the active or sham setting. The sham device created a sound but did not deliver vibration. Compressive strength (N) and volumetric density of the 1st lumbar vertebra (L1) was analyzed using Finite Element Analysis (FEA) of computed tomography (CT) scans of lumbar spine by ON Diagnostics. Results: 126 women (64 Active, 62 Sham) with low bone mass participated in the study, with an average age of 62.1 years (SD ± 5.8) and 60.6 years (± 5.3) in the Active and Sham groups, respectively. Most participants were of White race (98%) and non-Hispanic (96%). There were no significant differences in baseline demographics between the sham and active groups. Intent to treat analysis revealed no significant difference in percent change in vertebral bone strength between the Active and Sham groups over time (baseline to 12 months). When stratified by age category, significant differences in percent change in vertebral bone strength were present in the 50-60 year old category; the Sham group lost 3.4% of their vertebral bone strength compared to a 0.5% loss in the Active group (p=0.018). While bone was preserved in the active group relative to the sham in the women over 60, it was not significant (p=0.20). With analysis of those who met the compliance criterion of 3x/week, the Sham group lost 2.84% compared to 0.48% in the Active group (p=0.014); representing a 5 times greater loss in the Sham group. Additionally, the Osteoboost treatment preserved volumetric bone density of L1, with the Active treatment group losing 0.29% BMD relative to a 1.97% loss in the Sham group; representing a 6.8 times greater loss in the Sham group (p=0.008). Conclusion: The Osteoboost holds promise as a therapeutic intervention for women with low bone mass to prevent decline to osteoporosis and reduce fracture risk. Presentation: Friday, June 16, 2023

The Importance of Timing of Physical Therapy in Relation to Radiation Therapy during Multimodality Breast Cancer Treatment to Maximize Shoulder Range of Motion

Physical therapy (PT) is an effective tool for improving range of motion (ROM) for breast cancer patients to reduce long-term impairment. There is a paucity of data surrounding when PT should be initiated to optimally reduce upper limb disability. We hypothesized that patients who initiated PT early after surgery and before radiation therapy (RT), would experience greater gains in functionality compared to PT during/after RT. Demographic/clinical variables were assessed via retrospective chart review for patients referred to outpatient PT and receiving multimodality treatment for breast cancer between January 2015 and August 2021. Three distinct cohorts were established: patients who received PT and no RT, PT initiated before radiation therapy (pre-RT), and PT initiated during/after RT (d/a RT). The primary endpoint was percent change of total ROM of the ipsilateral shoulder between the first and last PT visits. Secondary endpoints included absolute change in degrees of total ROM of the ipsilateral shoulder between first and last PT visits. Associations between ROM across PT groups and baseline characteristics were evaluated with analysis of variance (ANOVA) testing. Thirty-seven patients were identified, median age 47 years (range 28-76). Higher tumor stage and axillary lymph node dissection were associated with the receipt of RT (p = 0.023, p = 0.003 respectively). Baseline ROM was associated with both percent and absolute improvement in ROM (p = 0.007). Patients receiving no RT demonstrated the greatest mean percent improvement in ROM with PT (84%), compared to the pre-RT and d/a RT cohorts, which demonstrated a 63% and 40% improvement, respectively. In pairwise comparisons, patients in the no RT group and those in the PT pre-RT group both demonstrated a statistically greater improvement in percent change in ROM compared to patients receiving PT d/a RT (no RT 74% vs d/a RT 20%, p = 0.006; pre-RT 59% vs d/a RT 20%, p = 0.045). There was no difference in percent change in ROM between the no RT and pre-RT groups (p = 0.528). On univariate analysis, baseline worse ROM was associated with statistically worse percent change in ROM after PT (p = 0.008), no other baseline characteristics were associated with ROM after PT. When adjusting for baseline ROM, the no RT cohort continued to be associated with improvement in ROM compared to the PT d/a RT group (p = 0.024), while there was no difference in percent change in ROM between patients who received physical therapy pre-RT compared to no RT (p = 0.829). Physical therapy is helpful in improving shoulder ROM at all stages of multimodality breast cancer treatment, however early initiation of PT prior to the start of RT may help maximize range of motion gains.

A comparative intervention trial of deer milk and an oral nutritional supplement efficacy for improving older adults' nutritional status, muscle mass and physical performance

To compare the effectiveness of deer milk (DM) for improving nutritional status, muscle mass and physical performance with that of a commercially available oral nutritional supplement (ONS) in older women. This study was an 11-week randomised, double-blind, parallel group study. Healthy women (N=120) aged 65-80 years, the majority having a body mass index (BMI)<25kg/m2 were recruited. The women were randomly assigned to either 200ml DM or a commercial ONS for 11 weeks. Data on habitual macronutrient intake, nutritional status (Mini Nutrition Assessment-Short Form, MNA-SF; ≤7 malnourished, 8-11at risk of malnutrition, ≥12 normal nutrition), anthropometrics/body composition, and physical performance were collected. Blood samples were collected for metabolic markers. 102 women (DM 45, ONS 57) completed the study, of whom 29% had a dietary protein intake of <1g/kg body weight per day, and 38% at risk of malnutrition. There were no between group differences in percentage change in MNA-SF score and body composition (P>0.05), but a trend for a difference in handgrip strength (DM 11.7±49.8% vs. ONS -2.42±17.9%, P=0.06). Further exploratory analysis showed that there was a trend for a between group difference in percentage change in MNA-SF score, favoring DM (DM 7.72+13.0% vs. ONS 0.63+9.25%, P=0.06) only in women at risk of malnutrition. There was also a between group difference in percentage change in muscle mass (DM 1.68±2.77% vs. ONS -0.18±2.81%, P=0.02) in women with BMI ≥25kg/m2 and in handgrip strength (DM 10.6±23.6% vs. ONS -5.03±18.1%, P<0.01) in women with BMI<25kg/m2. Total cholesterol, LDL and LDL:HDL ratio did not change over time (P>0.05), but there was a between group difference in percentage change in these markers (total cholesterol: DM 3.01±6.97% vs. ONS -2.65±9.92%, P<0.01; LDL: DM 4.22±14.9% vs. ONS -6.05±17.6%, P<0.01; LDL:HDL ratio: DM: 2.27±16.4% vs. ONS:-5.78±18.2%, P=0.02). Baseline nutritional status and BMI may modulate nutritional status, muscle mass and physical performance response to DM (as compared with ONS), suggesting DM may improve nutritional status and physical performance in women at risk of malnutrition and/or with lower BMI, and improve muscle mass in women with a higher BMI. The study was registered with the Australian New Zealand Clinical Trial Registry ACTRN12621000650897p.

The comparable efficacy of denosumab on bone mineral density in rheumatoid arthritis patients with postmenopausal osteoporosis: A retrospective case-control study.

Little is known about differences in the therapeutic efficacy of denosumab in subjects with and without rheumatoid arthritis (RA). This study compares the changes in bone mineral density (BMD) between RA patients and controls without RA who had been treated with denosumab for 2 years for postmenopausal osteoporosis. A total of 82 RA patients and 64 controls were enrolled, who were refractory to selective estrogen receptor modulators (SERMs) or bisphosphonates and completed the treatment of denosumab 60 mg for 2 years. The efficacy of denosumab in RA patients and controls was assessed using areal BMD (aBMD) and T-score of the lumbar spine, femur neck, and total hip. A general linear model with repeated measures analysis of variance was used to determine differences in aBMD and T-score between 2 study groups. No significant differences in percent changes in aBMD and T-scores by denosumab treatment for 2 years at the lumbar spine, femur neck, and total hip were evident between RA patients and controls (P > .05 of all), except T-score of the total hip (P = .034). Denosumab treatment equally increased aBMD at the lumbar spine and T-scores at the lumbar spine and total hip between RA patients and controls without statistical differences, but RA patients showed less improvement in aBMD at the femur neck (ptime*group = 0.032) and T-scores at the femur neck and total hip than controls (ptime*group = 0.004 of both). Changes in aBMD and T-scores after denosumab treatment in RA patients were not affected by previous use of bisphosphonates or SERMs. Differences of T-score at the femur neck among previous bisphosphonate users and aBMD and T-score at the femur neck and T-scores at the total hip were evident. This study revealed that 2 years of denosumab treatment in female RA patients achieved comparable efficacy on BMD to controls at the lumbar spine, but showed somewhat insufficient improvement at the femur neck and total hip.

#3236 CHANGE IN ALBUMINURIA IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS TREATED WITH AVACOPAN

Abstract Background and Aims Urinary albumin:creatinine ratio (UACR) is an important biomarker of active glomerulonephritis, a common complication of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. In most glomerular diseases, high UACR levels and low estimated glomerular filtration rates are associated with the long-term risk of end-stage kidney disease, cardiovascular disease, and death.[1] In the double-dummy, double-blind, controlled ADVOCATE Phase 3 trial, patients were randomized to receive avacopan, an oral C5a receptor (C5aR) antagonist that blocks C5a-mediated neutrophil activation and migration, or a prednisone taper. All patients received background immunosuppression with either cyclophosphamide followed by azathioprine, or rituximab. Primary endpoints were remission at week 26 and sustained remission at week 52. Prespecified secondary endpoints included the evaluation of kidney function.[2] The effect of avacopan on UACR in patients with ANCA-associated vasculitis is described. Method This post hoc analysis compared the time to achieve the maximum mean difference in percent change in UACR from baseline between the avacopan and prednisone taper groups using Kaplan-Meier survival analysis. Change in UACR from baseline was a prespecified secondary endpoint but was not adjusted for multiplicity. This analysis included patients from the ADVOCATE trial with kidney involvement (based on the Birmingham Vasculitis Activity Score) and a UACR of at least 10 mg/g at baseline. Results The baseline geometric mean UACR mg/g (range) in the avacopan group (n = 125) and the prednisone taper group (n = 128) was 433 (20 to 6461) and 312 (11 to 5367), respectively. A statistically significant UACR reduction (based on least-square means) in the avacopan group compared to the prednisone taper group occurred as early as week 2 (−25% vs. 6%, p = 0.0068, difference between groups: −29%, 95% confidence interval (CI) [−45%, −9%]). UACR continued to decrease at week 4 to the maximum difference between the two groups (−40% vs. 0%, p&amp;lt;0.0001, difference between groups: −40%, 95% CI [−53%, −22%]) (Figure 1). UACR was comparable between the two groups by week 13 (−55% vs. −49%, p = 0.3028, difference between groups: −12%, 95% CI [−32%, 13%]). During the 52-week treatment period, 84% (105/125) of patients in the avacopan group achieved a 40% UACR reduction from baseline within a median time of 29 days (95% CI [29, 88]), compared to 83% (106/128) of patients in the prednisone taper group within a median time of 92 days (95% CI [91, 180]) (logrank p = 0.0450) (Figure 2). At week 52, there was a greater overall mean improvement in estimated glomerular filtration rate (eGFR) of 7.6 mL/min/1.73 m2 in the avacopan group compared to 4.6 mL/min/1.73 m2 in the prednisone taper group (p = 0.0432). Conclusion In the ADVOCATE trial, UACR, an important early indicator of improving kidney function, improved three times faster in the avacopan group compared to the prednisone taper group. The rapid reduction in UACR seen in patients with ANCA-associated vasculitis receiving avacopan suggests more rapid control of glomerular inflammation which may have contributed to the observed subsequent greater improvement in eGFR.

Demographic and Clinical Profile of South Asian vs. non-South Asian Patients with Parkinson’s disease (P6-11.003)

<h3>Objective:</h3> To determine differences in demographic and clinical profile of South Asian vs. non-South Asian patients with Parkinson’s disease (PD) undergoing deep brain stimulation (DBS). <h3>Background:</h3> The majority of knowledge of PD has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of such biochemical and genetic discoveries to other ethnically diverse populations are unknown, with the South Asian population being underrepresented in PD research. <h3>Design/Methods:</h3> We performed a retrospective review of South Asian vs. non-South Asian PD patients undergoing STN-DBS between 2017–2022. Demographic data and clinical data were obtained. Pre-operative OFF/ON evaluation (dopamine challenge), neuropsychological testing scores (Dementia Rating Scale-2), motor and non-motor complaints were compared between the two groups using a Student’s T-test or chi-squared test as appropriate. <h3>Results:</h3> We compared data from 9 South Asian and 21 non-South Asian PD patients. Demographic characteristics were not different between the two groups. Alcohol use was less common in the South Asian population with a trend towards significance (88% never used vs. 57%, respectively, p = 0.09). At the pre-DBS evaluation, there was no difference in percent change in Unified Parkinson’s Disease Rating Scale (UPDRS) scores comparing OFF and ON evaluations, nor differences in DRS-2 scores. About 86% of non-South Asian patients complained of tremor pre-DBS, compared with only 44% in the South Asian group (p = 0.02). REM Behavior Disorder (RBD) was also less commonly reported in the South Asian vs. non-South Asian group (0% vs. 43%, respectively, p = 0.02). <h3>Conclusions:</h3> In this pilot study, we found differences in the clinical profile of South Asian vs. non-South Asian PD patients. Larger studies are needed to further examine these differences in the South Asian population which may lead to improved care and treatment in this group of patients. <b>Disclosure:</b> Mr. Srinivasan has nothing to disclose. Dr. Hargreaves has nothing to disclose. Ms. Caputo has nothing to disclose. Jasdeep Hundal has received research support from Rutgers University CAHBIR/BHI. Jasdeep Hundal has received research support from Horizon BCBS. Jasdeep Hundal has received research support from National Cancer Institute (NCI). Jasdeep Hundal has received research support from National Institute of Health/NIA. Dr. Danish has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for medtronic. Dr. Chen has nothing to disclose. Dr. Pal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint. Dr. Pal has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Pal has stock in Baudax Bio. The institution of Dr. Pal has received research support from National Institutes of Health. The institution of Dr. Pal has received research support from Parkinson’s Foundation.

Efficacy of deep brain stimulation for the treatment of anorexia nervosa: a systematic review and network meta-analysis of patient-level data.

Deep brain stimulation (DBS) has been approved as a therapy for movement disorders and obsessive-compulsive disorder. Recently, DBS has been studied in patients with anorexia nervosa (AN), which is a debilitating and life-threatening psychiatric disorder. Several stimulation locations have been tested without a clear indication of the best region. In this systematic review and network meta-analysis, the authors used patient-level data to identify stimulation targets with the greatest evidence for efficacy in increasing body mass index (BMI). A systematic search was performed on or before August 4, 2022, using PubMed/MEDLINE, Ovid, and Scopus. Articles were included if patient-level data were presented, patients were diagnosed with AN and treated with DBS, and 6 months or more of postoperative follow-up data were reported. Quality and risk of bias were assessed with the NIH assessment tools. Patient data were collected and stratified by stimulation location. A network meta-analysis was performed. This review was written in accordance with PRISMA guidelines for systematic reviews. Eleven studies consisting of 36 patients were included. The mean age and BMI at the time of surgery were 38.07 (SD 11.64) years and 12.58 (SD 1.4) kg/m2, respectively. After 6 months of DBS, a significant difference in percentage change in BMI was found between the nucleus accumbens and subcallosal cingulate cortex (SCC) (SMD 0.78; 95% CI 0.10, 1.45) and between the SCC and ventral anterior limb of the internal capsule (SMD -1.51; 95% CI -2.39, -0.62). Similarly, at 9-12 months, a significant difference in percentage change in BMI was found between the SCC and ventral anterior limb of the internal capsule (SMD -1.18; 95% CI -2.21, -0.15). With hierarchical ranking, this study identified SCC as the most supported stimulation location for BMI change at 6 and 9-12 months (P-scores 0.9449 and 0.9771, respectively). Several DBS targets have been tested for AN, and this study identified the SCC as the most supported region for BMI change. However, further studies with blinded on/off periods are necessary to confirm this finding.

Toxicity and efficacy of stereotactic body radiation therapy vs. intensity-modulated radiation therapy for the treatment of locally advanced pancreatic cancer in a phase 3 trial.

713 Background: Locally advanced pancreatic cancer (LAPC) remains one of the deadliest cancers. Radiation is listed as a first line therapy option in treatment guidelines and remains a common treatment for this patient population primarily for local disease control and symptoms. Herein, we performed an exploratory analysis to compare the toxicity and efficacy between patients receiving either stereotactic body radiation therapy (SBRT) or intensity-modulated radiation therapy (IMRT) during the induction phase (prior to randomization) of a Phase 3 trial for localized intra-arterial gemcitabine therapy. Methods: As part of the TIGeR-PaC Phase 3 trial, patients with LAPC and an ECOG of 0-1 underwent an induction phase and were treated with 2 cycles of gemcitabine and nab-paclitaxel prior to receiving SBRT (n=59; 33Gy in 5 Fractions) or IMRT (n=75; 50Gy in 25 fractions) with concurrent PO capecitabine BID Monday-Friday. We performed Mann-Whitney analyses to compare mean percent changes in tumor size (imaging performed prior and 1-month after radiation) and CA 19-9 tumor markers. Adverse event (AE) incidence data during and 2 weeks after completion of the last fraction of radiation was used to compare toxicity via a contingency table. Results: A total of 134 patients across 22 sites (63 male/71 female; median age: 68.5 years) underwent radiation with no significant difference in baseline demographics between SBRT and IMRT patients. The decision for SBRT vs. IMRT was site-driven and not pre-specified by the protocol. Of these, 104 had analyzable imaging data, 50 SBRT and 54 IMRT, with a mean baseline tumor size of 4.3 cm and 4.0 cm (p=0.17), respectively. Pancreatic tumor location included head (n=63), body (n=36), or other (n=5). There was no statistical significance between the mean percent change of tumor size between SBRT (-13.3%) and IMRT (-10.8%; p=0.834). Both arms had similar RECIST partial response (approximately 18% of patients) after treatment. Patients with analyzable CA 19-9 tumor marker data (14 SBRT, 17 IMRT) showed no significant difference in percent change (mean, 9.8%±111%, -40.7%±40%; p=0.262). The SBRT subgroup had significantly less patients drop-out due to clinical deterioration (1 SBRT, 9 IMRT; p=0.025) and experience any AE (26 SBRT, 49 IMRT; p=0.014), gastrointestinal AE (10 SBRT, 33 IMRT; p&lt;0.001), grade 3 or higher AE (6 SBRT, 20 IMRT; p=0.017), and serious AE (2 SBRT, 10 IMRT; p=0.045) p=0.014, 0.017, 0.045, respectively). The main AEs and serious AEs were gastrointestinal events. Conclusions: When compared to IMRT, SBRT demonstrates improved tolerability for treatment of patients with LAPC with comparable clinical efficacy. Clinical trial information: NCT03257033 .

Towards detection of early response in neoadjuvant chemotherapy of breast cancer using Bayesian intravoxel incoherent motion.

The early identification of good responders to neoadjuvant chemotherapy (NACT) holds a significant potential in the optimal treatment of breast cancer. A recent Bayesian approach has been postulated to improve the accuracy of the intravoxel incoherent motion (IVIM) model for clinical translation. This study examined the prediction and early sensitivity of Bayesian IVIM to NACT response. Seventeen female patients with breast cancer were scanned at baseline and 16 patients were scanned after Cycle 1. Tissue diffusion and perfusion from Bayesian IVIM were calculated at baseline with percentage change at Cycle 1 computed with reference to baseline. Cellular proliferative activity marker Ki-67 was obtained semi-quantitatively with percentage change at excision computed with reference to core biopsy. The perfusion fraction showed a significant difference (p = 0.042) in percentage change between responder groups at Cycle 1, with a decrease in good responders [-7.98% (-19.47-1.73), n = 7] and an increase in poor responders [10.04% (5.09-28.93), n = 9]. There was a significant correlation between percentage change in perfusion fraction and percentage change in Ki-67 (p = 0.042). Tissue diffusion and pseudodiffusion showed no significant difference in percentage change between groups at Cycle 1, nor was there a significant correlation against percentage change in Ki-67. Perfusion fraction, tissue diffusion, and pseudodiffusion showed no significant difference between groups at baseline, nor was there a significant correlation against Ki-67 from core biopsy. The alteration in tumour perfusion fraction from the Bayesian IVIM model, in association with cellular proliferation, showed early sensitivity to good responders in NACT. https://clinicaltrials.gov/ct2/show/NCT03501394, identifier NCT03501394.

Denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women: A randomized, double-blind, placebo-controlled, multicenter phase III study.

This study assessed the efficacy, safety, pharmacokinetics (PK), and immunogenicity profiles of a denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women with a high risk of fracture. In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, 448 postmenopausal women aged 50-85 years with osteoporosis were enrolled at 49 centers in China and were randomly assigned (3:1) to receive 60​mg of the denosumab biosimilar (LY06006) or placebo subcutaneously every 6 months for 1 year. Lumbar spine bone mineral density (BMD) change was the primary endpoint. Of the 448 randomized patients, 409 (LY06006, n​=​311; placebo, n​=​98) completed the study. All 448 (100.0%) subjects were included in the intent-to-treat (ITT) trial, 427 (95.3%) were included in the full analysis set (FAS), 408 (91.1%) were included in the per protocol set (PPS), 446 (99.6%) were included in the safety set (SS), and 336 (75.0%) were included in the pharmacokinetics concentration set (PKCs). For the primary endpoint, a 4.71% (95% CI, 3.81%, 5.60%) treatment difference in percent change in lumbar spine BMD from baseline to month 12 was observed in the LY06006 group compared with the placebo group (P​<​0.0001). For the secondary endpoints, LY06006 was associated with increased lumbar spine BMD levels measured at month 6, BMD levels at the femoral neck, total hip, and trochanter measured at months 6 and 12 and reduced serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1​N-peptide (P1NP) levels at months 1, 6, and 12. Safety analysis was based on the safety analysis set (SS), and 264 (78.6%) subjects in the LY06006 group and 83 (75.5%) in the placebo group experienced adverse events (AEs). Most events were mild or moderate and not related to the study drugs. In postmenopausal women with a high risk of fracture, LY06006 increased the BMD and decreased bone resorption; thus, LY06006 might be an effective treatment for osteoporosis. LY06006 was generally safe and well tolerated without unexpected adverse reactions, similar to the reference drug Prolia®. The characteristics of effectiveness and safety were similar to those reported in previous studies. In this multi-center, randomized, double-blind, placebo-controlled phase 3 study, LY06006 showed substantially efficacy to increase BMD and well tolerance without unexpected adverse reactions, which is comparable to the reference drug Prolia ®. The presented results are encouraging and can offer some valuable evidence for the clinical practice.

The effect of calcineurin inhibitors on anthropometric measurements in kidney transplant recipients

BackgroundThis study was designed to investigate the effect of calcineurin inhibitors (CNIs), cyclosporine (CsA), and tacrolimus (Tac) on anthropometrics in kidney transplant recipients.Methods111 of 128 adult kidney transplant recipients who received post-transplant CNIs were included in this retrospective study. Anthropometrics were recorded in the pre-transplant and post-transplant 4-year follow-up periods (1st, 3rd, 6th, 12th, 24th, 36th and 48th months).ResultsCompared to pre-transplant values, significant increases in body weight and body mass index (between 3rd and 48th months), waist and hip circumferences (between 1st and 48th months), waist-to-hip ratio (between 1st and 3rd or 6th months) and neck circumference (between 1st and 12th or 24th months) were observed in both CsA and Tac groups. A significant increase was noted in post-transplant body fat percentage values for the 3rd to 24th months in the CsA group, whereas for the 24th to 48th months in both CsA and Tac groups. Hip circumferences percentage changes from the pre-transplant period to the 1st, 12th and 24th months were significantly higher in CsA than in the Tac group. At each time point, there was no significant difference in percentage changes for other anthropometric parameters between the CsA and Tac groups. De novo diabetes mellitus developed in 8.3% of the CsA group and 19.1% of the Tac group.ConclusionsAfter a successful kidney transplant, anthropometric measurements increase in most recipients. Although the effect of calcineurin inhibitor type on weight gain is unclear, a regression analysis showed that CNI type was not a risk factor for the development of obesity in the 48th month. However, it is helpful to be cautious about its dyslipidemic effect in patients using CsA and the potential hazards of using Tac in patients with a diabetic predisposition.

High-Definition Transcranial Infraslow Pink-Noise Stimulation Can Influence Functional and Effective Cortical Connectivity in Individuals With Chronic Low Back Pain: A Pilot Randomized Placebo-Controlled Study

IntroductionPain can be regarded as an emergent property of multiple interacting, dynamically changing brain networks and thus needs a targeted treatment approach. A novel high-definition transcranial infraslow pink-noise stimulation (HD-tIPNS) technique was developed to modulate the key hubs of the three main nociceptive pathways simultaneously, ie, the pregenual anterior cingulate cortex (pgACC) (descending inhibitory pathway), the dorsal anterior cingulate cortex (dACC) (medial nociceptive pathway), and both somatosensory cortices (S1) (lateral nociceptive pathway). This study aimed to evaluate safety and verify whether a single session of HD-tIPNS may disrupt functional and effective connectivity between targeted cortical regions. Materials and MethodsA pilot double-blind randomized two-arm placebo-controlled parallel trial was conducted. Participants (N = 30) with chronic low back pain were equally randomized to receive a single session of either sham stimulation or HD-tIPNS (targeting the pgACC, dACC, and bilateral S1). Primary outcomes included safety and electroencephalographic measures, and secondary outcomes included pain measures, collected after treatment. A Mann-Whitney U test was used to compare between-group differences in percentage changes with baseline for each outcome measures. A Wilcoxon signed-rank test was used to identify difference in effective connectivity measure before and after HD-tIPNS. ResultsNo serious adverse events were reported. A significant decrease in instantaneous functional connectivity was noted between the pgACC and dACC (U = 47.0, Z = −2.72, p = 0.007) and the pgACC and left S1 (U = 41.0, Z = −2.97, p = 0.003) in the infraslow band after HD-tIPNS when compared with sham stimulation. A significant decrease in instantaneous effective connectivity was noted in the direction of the dACC to the pgACC (Z = −2.10, p = 0.035), in the infraslow band after HD-tIPNS when compared with baseline. No changes in clinical pain measures were detected. ConclusionsHD-tIPNS can safely modulate the functional and effective connectivity between targeted pain-related cortical hubs. Further studies are warranted to evaluate whether repeated exposures to HD-tIPNS can incur clinical benefits through inducing changes in functional and effective connectivity at targeted cortical regions. Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is ACTRN12621001438842.

A Comparison of Functional and Oncologic Outcomes between Partial Nephrectomy and Radiofrequency Ablation in Patients with Chronic Kidney Disease after Propensity Score Matching.

Purpose: This study aimed to compare functional and oncological outcomes between partial nephrectomy (PN) and radiofrequency ablation (RFA) for a small renal mass (SRM, ≤4 cm) in patients with chronic kidney disease (CKD). Materials and Methods: Patients with CKD who underwent either PN or RFA for SRM between 2005 and 2019 were included. Patients were stratified into two categories: CKD stage 2 and CKD stage 3 or higher. We performed propensity score matching (PSM) analysis in patients with CKD stage 2 and CKD stage 3 or higher. We compared the functional and oncological outcomes between two groups according to CKD stage before and after PSM. Results: Among 1332 patients, 1195 patients were CKD stage 2 and 137 patients were CKD stage 3 or higher. After PSM analysis using age, pre-treatment eGFR, and clinical tumor size as matching variables, the PN and RFA groups had 270 and 135 CKD stage 2 patients, respectively, and both had 53 patients each with CKD stage 3 or higher. There were no significant differences in percent change in eGFR at 1 year post-operation between groups in patients with CKD stage 2 and stage 3 or higher. Among all patients with tissue-proven malignancy, the 5-year recurrence-free survival (RFS), cancer-specific survival, and overall survival were significantly higher in the PN group. However, only the 5-year RFS was significantly higher in the PN group after matching. Conclusion: Mortality is low in patients with SRM, and functional outcomes were not significantly different between the two treatments. RFA could be an alternative treatment modality in patients who are poor candidates for surgery.

N-3 fatty acid supplementation mediates lipid profile, including small dense LDL, when combined with statins: a randomized double blind placebo controlled trial

BackgroundEpidemiological and clinical evidence suggests that high-dose intake of omega 3 fatty acids (n-3 FA) have a favorable role in altering serum triglycerides (TG) and non-high density lipoprotein cholesterol (non-HDL-C) when combined with statins in hyperlipidemic patients. Their efficacy in altering low-density lipoprotein cholesterol (LDL-C) particle size is yet to be established.AimThis study evaluated the effects of supplementing 4 g/day Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) on serum blood lipids, including small, dense LDL-C particle concentration, in hyperlipidemic patients receiving stable statin therapy.MethodsIn this randomized, placebo-controlled, double-blind parallel group study, 44 patients on statin therapy for > 8 weeks with non-HDL-C concentrations above 130 mg/dL were randomized into two groups. For 8 weeks, together with their prescribed statin, the intervention group received 4 g/day EPA + DHA (3000 mg EPA + 1000 mg DHA in ethyl ester form) and the placebo group received 4 g/day olive oil (OO). Measurements of serum non-HDL-C, TG, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), LDL-C (including large - LDL I; intermediate - LDL II; and small - LDL III subclasses), very-low-density lipoprotein cholesterol (VLDL-C) concentration, were taken at baseline and post-intervention. Dietary intake was assessed with a weighed intake, 3-day food diary at week 4. Primary outcome measures were percent change in LDL III, non-HDL-C and LDL particle number.ResultsAt the end of treatment, the median percent change in serum LDL III concentration was significantly greater in the n-3 FA group plus atorvastatin compared to placebo (− 67.5% vs − 0%, respectively; P < 0.001). Supplementation with n-3 FA plus atorvastatin led to significant reductions in serum non-HDL-C (− 9.5% vs 4.7%, P < 0.01), TG (− 21.5% vs 6.2%, P < 0.001) and VLDL-C (− 36.9% vs 4.0%, P < 0.001) and TC (− 6.6% vs 2.1%, P < 0.001). Between the groups, no significant difference in percent change in the serum concentration of LDL-C, HDL-C, as well as in the LDL I and LDL II subclasses was observed.ConclusionIn this group of hyperlipidemic patients on a stable statin prescription, OM3 plus atorvastatin improved small dense LDL concentrations, non-HDL-C, VLDL-C and TG to a greater extent than atorvastatin alone. Further studies are warranted in this area.Trial registrationThis trial was retrospectively registered on 23 May 2019 on ClinicalTrials.gov with ID: NCT03961763.