Weeks Of Participation Research Articles

Protocol of a cluster-randomised trial to improve adolescent bicycling safety education programme efficacy

IntroductionSecond to motor vehicles, bicycles contribute to more childhood injuries than any other consumer product. Youth bicycling safety education programmes are one avenue of prevention, but despite a plethora of...

Adherence to high-frequency ecological momentary assessment in persons with moderate-to-severe traumatic brain injury.

Ecological momentary assessment (EMA) involves repeated collection of real-time self-report data, often multiple times per day, nearly always delivered electronically by smartphone. While EMA has shown promise for researching internal states, behaviors, and experiences in multiple populations, concerns remain regarding its feasibility in samples with cognitive impairments, like those associated with chronic moderate-to-severe traumatic brain injury (TBI). This study examines adherence to a 7-week high-frequency (5x daily) EMA protocol in individuals with moderate-to-severe TBI, considering changes in response rate over time, as well as individual participant characteristics (memory function, education, injury severity, and age). In the sample of 39 participants, the average overall response rate was 65% (range: 5%-100%). Linear mixed-effects modeling revealed a small but statistically significant linear decay in response rate over 7 weeks of participation. Individual trajectories were variable, as evidenced by the significant effect of random slope. A better response rate was positively associated with greater educational attainment and better episodic memory function (statistical trend), whereas the effects of age and injury severity were not significant. These findings shed light on the potential of EMA in TBI studies but underscore the need for tailored strategies to address individual barriers to adherence.

Efficacy and Safety of Roxadustat for Anemia in Patients Receiving Chemotherapy for Nonmyeloid Malignancies: A Randomized, Open-Label, Active-Controlled Phase III Study.

We evaluated the efficacy and safety of roxadustat, a first-in-class hypoxia-inducible factor prolyl hydroxylase inhibitor, for chemotherapy-induced anemia (CIA) in patients with nonmyeloid malignancies receiving multicycle treatments of chemotherapy. In this open-label, noninferiority phase III study conducted at 44 sites in China, 159 participants age ≥18 years with CIA nonmyeloid malignancy and CIA were randomly assigned (1:1) to oral roxadustat or subcutaneous recombinant human erythropoietin-α (rHuEPO-α) three times a week for 12 weeks. Roxadustat starting dosages were 100, 120, and 150 mg three times a week for participants weighing 40-<50, 50-60, and >60 kg, respectively. rHuEPO-α starting dosage for all participants was 150 IU/kg three times a week. Both roxadustat and rHuEPO-α dosages could be modified. The primary end point was least-squares mean (LSM) change in hemoglobin (Hb) concentration from baseline to the concentration averaged over weeks 9-13. Of the 159 participants randomly assigned, 140 were included in the per-protocol set (roxadustat, n = 78; rHuEPO-α, n = 62). The LSM (95% two-sided CI) change from baseline to weeks 9-13 in Hb concentration was 17.1 (13.58 to 20.71) g/L with roxadustat and 15.4 (11.34 to 19.50) g/L with rHuEPO-α (mean difference [95% CI], 1.7 [-3.39 to 6.84]). The lower bound of the one-sided 97.5% CI for the treatment difference (‒3.4 g/L) was greater than the predefined noninferiority margin of ‒6.6 g/L, establishing noninferiority. Noninferiority was supported by five of six key secondary end points. Rates of adverse events were generally comparable between treatments and consistent with previous findings. Roxadustat was noninferior to rHuEPO-α in treating CIA in participants with nonmyeloid malignancies receiving multicycle treatments of myelosuppressive chemotherapy. The oral formulation of roxadustat may potentially increase compliance.

MERLIN: Two-Year Results of Brolucizumab in Participants with Neovascular Age-Related Macular Degeneration and Persistent Retinal Fluid

PurposeTo report the safety and efficacy of brolucizumab (Beovu®) 6 mg vs. aflibercept (Eylea®) 2 mg administered every 4 weeks in participants with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid after the Week 52 primary endpoint analysis (from Week 52 up to Week 104, post-study termination). DesignMulticenter, randomized, double-masked Phase 3a study. ParticipantsParticipants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-vascular endothelial growth factor treatment). MethodsStudy eyes were randomized 2:1 to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks for 100 weeks, or until study termination. Main Outcome MeasuresAll available efficacy (analysis of noninferiority in mean best-corrected visual acuity [BCVA], central subfield thickness [CST], fluid-free status [no intraretinal fluid and no subretinal fluid]), and safety data up to study termination, including data up to Week 104 for those participants who completed the study prior to its termination. All P values after Week 52 were nominal and reflect observed data for the efficacy analyses. ResultsBrolucizumab 6 mg every 4 weeks was noninferior to aflibercept 2 mg in mean BCVA change from baseline to Week 104 (least squares mean difference, -0.4 Early Treatment Diabetic Retinopathy Study letters; 95% confidence interval [CI], -3.7 to 3.0; P = 0.0169). The proportion of eyes with ≥15-letter loss was 6.2% for brolucizumab and 4.7% for aflibercept. (P = 0.0014), and a greater proportion of eyes were fluid free at Week 104 (52.5% brolucizumab vs. 28.2% aflibercept; 95% CI, 11.9−37.3; P < 0.001) in eyes treated with brolucizumab vs. aflibercept. Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, was 11.5% (0.8% and 2.2%) for brolucizumab vs 6.1% (0% and 0.6%) for aflibercept, respectively. ConclusionsConsistent with 52-week results, brolucizumab 6 mg every 4 weeks was noninferior in mean BCVA change with anatomic outcomes superior to aflibercept 2 mg every 4 weeks from baseline to Week 104 or study termination. The incidence of IOI, including retinal vasculitis and retinal vascular occlusion, was higher with brolucizumab vs. aflibercept; therefore, brolucizumab should not be used more frequently than every 8 weeks following the loading regimen.

Vascular Endothelial Growth Factor-B Blockade with CSL346 in Diabetic Kidney Disease: A Phase 2A Randomized Controlled Trial.

Increased vascular endothelial growth factor B (VEGF-B) expression in patients with diabetic kidney disease (DKD) is associated with increased lipid deposition in glomerular podocytes. Reducing VEGF-B activity in animal models of DKD using an anti-VEGF-B antibody improved histological evidence of glomerular injury and reduced albuminuria; effects attributed to prevention of ectopic lipid deposition in the kidney. CSL346 is a novel humanized monoclonal antibody that binds VEGF-B with high affinity. Targeting VEGF-B in patients with type 2 diabetes mellitus may improve DKD progression markers. An international, randomized, double-blind, placebo-controlled, phase 2a study (NCT04419467) assessed CSL346 (8 mg/kg or 16 mg/kg subcutaneously every 4 weeks for 12 weeks) in participants with type 2 diabetes mellitus and a urinary albumin-to-creatinine ratio (UACR) ≥150 mg/g (17.0 mg/mmol), and eGFR >20 mL/min/1.73m2. Efficacy, safety/tolerability, pharmacokinetics, and pharmacodynamics of CSL346 were evaluated. The primary analysis compared the change from baseline in log-transformed UACR between the two CSL346 dose groups combined versus placebo at Week 16. In total, 114 participants were randomized. CSL346 did not significantly reduce UACR compared with placebo at Week 16 (combined CSL346 group difference from placebo 95% confidence interval]: 4.0% [-14.7, 26.8]). Furthermore, no effect was seen in participant subgroups (degree of kidney impairment or sodium-glucose cotransporter 2 [SGLT2] inhibitor use) or on urinary biomarkers reflecting proximal tubular injury. CSL346 was generally well tolerated; however, diastolic blood pressure was significantly higher with CSL346 16 mg/kg versus placebo from Week 2 onwards, with differences ranging from +3.8 to +5.3 mmHg (P = 0.002 at Week 16). CSL346 did not reduce UACR compared with placebo at 16 weeks in participants with type 2 diabetes mellitus and DKD, and was associated with an increase in diastolic blood pressure.

Return to activity is a multi-faceted variable, not a discrete yes-no

ObjectivesTo develop a patient-reported outcome that allows for tracking of return to activity after injury. By acknowledging that return to activity is not a discrete Yes/No question where participants return to their baseline activity may be unrelated to their treatment a more comprehensive understanding and measurement of the outcome of treatment after injury as it relates to activity participation was developed and evaluated. MethodsItem development and evaluation were undertaken with the final version tested in an ongoing observational clinical trial. Descriptive statistics and test-re-test analysis using intra-class correlation and percent agreement were used. ResultsA 5-item set of questions was identified that assess return to activity from a multi-faceted perspective. The final 5 items record preferred activity, days and hours per week of participation, impact of change in participation in activity, degree of limitation in participation and if it is related to injury or external factors. Over 30% of the population reported that their participation in their preferred activity was no longer active and not related to their injury but other factors demonstrating the importance of documenting more than one variable. ConclusionThe Minnesota Activity Scale provides standardized questions to comprehensively assess return to activity as a marker of treatment effectiveness. Level of evidenceV.

Dulaglutide and Glomerular Hyperfiltration, Proteinuria, and Albuminuria in Youth With Type 2 Diabetes: Post Hoc Analysis of the AWARD-PEDS Study.

To examine changes in glomerular hyperfiltration and other measures of kidney function in youth with type 2 diabetes treated with dulaglutide or placebo. Post hoc analysis was performed on kidney laboratory data from 154 youths (age 10-18 years) with type 2 diabetes enrolled in a completed placebo-controlled glycemic control trial of dulaglutide. Mean estimated glomerular filtration rate (eGFR) decreased from baseline to 26 weeks in participants treated with dulaglutide versus placebo (-5.8 vs. -0.1 mL/min/1.73 m2; P = 0.016). Decreases in eGFR were observed primarily in participants with baseline glomerular hyperfiltration. At 26 weeks, the prevalence of both glomerular hyperfiltration and proteinuria increased with placebo but decreased with dulaglutide (P = 0.014 and 0.004 vs. placebo, respectively). Dulaglutide was associated with attenuated glomerular hyperfiltration and proteinuria in youth with type 2 diabetes. The impact of these changes on the risk of diabetic kidney disease is unclear.

Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial

Retatrutide is a novel triple agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 and glucagon receptors. A 48-week phase 2 obesity study demonstrated weight reductions of 22.8% and 24.2% with retatrutide 8 and 12 mg, respectively. The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF. Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo. The mean relative change from baseline in LF at 24 weeks was −42.9% (1 mg), −57.0% (4 mg), −81.4% (8 mg), −82.4% (12 mg) and +0.3% (placebo) (all P < 0.001 versus placebo). At 24 weeks, normal LF (<5%) was achieved by 27% (1 mg), 52% (4 mg), 79% (8 mg), 86% (12 mg) and 0% (placebo) of participants. LF reductions were significantly related to changes in body weight, abdominal fat and metabolic measures associated with improved insulin sensitivity and lipid metabolism. The ClinicalTrials.gov registration is NCT04881760.

Long-term pain outcomes after serial lidocaine infusion in participants with recent onset of peripheral neuropathic pain: A pilot double-blind, randomized, placebo-controlled trial.

This study investigated the outcomes up to 12 weeks after serial lidocaine infusion for early-onset peripheral neuropathic pain. This pilot double-blind, randomized, 2-arm placebo-controlled trial recruited 50 participants with onset of peripheral neuropathic pain within the past 6 months and randomized them to either receive lidocaine (3 mg/kg) in normal saline (50 mL) intravenous infusion over 1 hour (lidocaine group) once a week for 4 weeks or 50 mL of normal saline infusion (placebo group) once a week for 4 weeks. Twenty-nine participants completed the protocol; 15 participants were assigned to the lidocaine group and 14 to the placebo group. The outcomes were pain intensity assessed using a numerical rating scale (NRS), quality of life assessed using EuroQol-Five Dimensions-Five Levels questionnaire (EQ-5D-5L), psychological function using the Thai version of the 21-item Depression Anxiety Stress Scales (DASS-21), pain medication use, and adverse effects, all assessed at baseline (BL) and again at 4, 8, and 12 weeks following randomization. The reported tramadol use at 8 and 12 weeks following the first infusion was significantly lower in the lidocaine group (P = .023). No other significant between-group differences were observed at any time point or for any other outcome, and no serious adverse events were observed. Multiple lidocaine infusions of 3 mg/kg once a week for 4 weeks in participants with recent onset of peripheral neuropathic pain demonstrated no significant benefits in pain intensity, quality of life, or psychological outcomes. At most, this treatment may result in less tramadol use.

Liraglutide 3.0 mg once daily for the treatment of overweight and obesity in patients hospitalised at a forensic psychiatric department: A 26-week open-label feasibility study.

Overweight and obesity constitute a major concern among patients treated at forensic psychiatric departments. The present clinical feasibility study aimed at investigating the extent to which glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment with once-daily liraglutide 3.0 mg could be a feasible pharmacological treatment of these conditions in patients with schizophrenia spectrum disorders hospitalised in forensic psychiatry. The 26-week, open-label feasibility study included participants aged 18-65 years diagnosed with a severe mental illness and hospitalised at a forensic psychiatric department. At the time of inclusion, all participants fulfilled the indication for using liraglutide as a treatment for overweight and obesity. Participants' baseline examinations were followed by a 26-week treatment period with liraglutide injection once daily according to a fixed uptitration schedule of liraglutide, with a target dose of 3.0 mg. Each participant attended seven visits to evaluate the efficacy and adverse events. The primary endpoint was the number of "completers", with adherence defined as >80% injections obtained in the period, weeks 12-26. Determining whether liraglutide is a feasible treatment was pre-defined to a minimum of 75% completers. Twenty-four participants were included in the study. Sex, male = 19 (79.2%). Mean age: 42.3 [25th and 75th percentiles: 39.1; 48.4] years; body mass index (BMI): 35.7 [31.7; 37.5] kg/m2; glycated haemoglobin (HbA1c): 37 [35; 39] mmol/mol. Eleven out of 24 participants (46%) completed the study. For the completers, the median net body weight loss after 26 weeks of participation was -11.4 kg [-15.4; -5.9]. The net difference in HbA1C and BMI was -2.0 mmol/mol [-4; -1] and -3.6 kg/m2 [-4.7; -1.8], respectively. The weight change and reduction in HbA1c and BMI were all statistically significant from baseline. The study did not confirm our hypothesis that liraglutide is a feasible treatment for a minimum of 75% of the patients initiating treatment with liraglutide while hospitalised in a forensic psychiatric department. The high dropout rate may be due to the non-naturalistic setting of the clinical trial. For the proportion of patients compliant with the medication, liraglutide 3.0 mg was an efficient treatment for overweight.

Protocol for evaluating the effects of the Reducing Cardiometabolic Diseases Risk dietary pattern in the Chinese population with dyslipidaemia: a single-centre, open-label, dietary intervention study

IntroductionCardiometabolic disease (CMD) is the leading cause of mortality in China. A healthy diet plays an essential role in the occurrence and development of CMD. Although the Chinese heart-healthy diet...

Mini-COMET study: Safety and efficacy data after avalglucosidase alfa dosing for ≥ 145 weeks in participants with infantile-onset Pompe disease (IOPD) who had demonstrated clinical decline or sub-optimal response while receiving alglucosidase alfa

Mini-COMET study: Safety and efficacy data after avalglucosidase alfa dosing for ≥ 145 weeks in participants with infantile-onset Pompe disease (IOPD) who had demonstrated clinical decline or sub-optimal response while receiving alglucosidase alfa

A pilot study examining a double-conjugated, retinoid-based skincare regimen for darker, blemish-prone skin.

Retinoids and alpha- and beta hydroxy acids are common components utilized in regimens for blemish-prone skin. However, balancing efficacy and tolerability is often challenging. This pilot study evaluated a double-conjugated retinoid serum specifically formulated for blemish-prone skin (AHARet-SA) in combination with exfoliating peel pads (double-conjugated retinoid, glycolic, lactic, and salicylic acids), a cleanser, mineral-based sunscreen, and a lightweight moisturizer in female participants with mild-to-moderate blemish-prone skin. Fifty-five percent of participants were Fitzpatrick Skin Type (FST) IV and 27% were FST V. Participants used the exfoliating peel pads (3x/week for 8 weeks; 2x/week for 4 weeks) followed by nightly AHARet-SA and a moisturizer (as needed). Improvements in skin were assessed using the 5-point Investigator Global Assessment Scale, and participant satisfaction and tolerability were assessed over 12 weeks. Significant mean improvement from baseline in skin clarity occurred after 4 weeks (14%; p = 0.04) with progressive improvements through week 12 (52%; p = 0.004). Eighty-eight percent of participants reported improvements in the appearance and texture of their skin and fewer blemishes/breakouts. Mild, transient adverse events were reported. A regimen comprised of a double-conjugated serum and exfoliating peel pads formulated for blemish-prone skin led to significant improvements from baseline in skin clarity after 12 weeks in participants with predominately darker skin tones and mild-to-moderate blemish-prone skin.

Further Preclinical Development of a Bio‐therapeutic Against Porphyromonas gingivalis for the control of Systemic and Neuro‐inflammation related Dementia and Alzheimer’s Disease

AbstractAddressing novel mechanisms and effective therapeutic treatments for cognitive decline, Dementia and Alzheimer’s Disease is a major public health need. Keystone Bio have identified that specific virulent strains of Porphyromonas gingivalis (Pg) and the release of specific virulence factors/toxins in the oral cavity as the primary driver/causation of systemic/neuro‐vascular inflammation/degenerative diseases i.e., cognitive decline/dementias/Alzheimer’s disease (Nara et. al 2021). A recent landmark finding was reported in a sub‐cohort analysis from a Phase 2/3 GAIN trial (n = 238) demonstrated that lowering the load of Pg in the mouth leads to a significant improvement of cognitive slowing at both 24 and 48 weeks in participants with mild to moderate AD. Another study showed lowering the load of Pg in the mouth had a favorable effect on AD‐related brain atrophy (https://doi.org/10.1002/alz.12378). Pg OMVs and systemic system diseases has many well‐defined examples such as: cardiometabolic diseases‐ Pg OMVs attenuate insulin induced Akt/GSK‐3_ signaling in hepatic HepG2 cells, thereby causing changes in glucose metabolism in the liver and promoting the development of diabetes and increase vascular permeability by cleaving endothelial cell connexins such as PECAM‐1, thereby promoting cardiovascular diseases.Keystone Bio has further developed both a companion diagnostic (CDx) and a clinical, proof‐of‐concept tested, first generation, safe, efficacious, precision, bio‐therapeutic murine monoclonal antibody (KB‐001) for the diagnosis, treatment and monitoring against the oral bacteria and major virulent factor/toxin of Pg. The antibody engagement is with the later stages of the complex virulent factor/toxin secretion containing outer membrane vesicles from the bacteria thereby interfering/stopping all necessary metabolic, host defense, energy‐producing sources, adherence and biofilm formation and integrity (Nara et. al 2021). The talk will review what now seems like a solid case for causation in the role of virulent/toxin secreting strains of in neuro‐inflammation leading to cognitive decline, dementia, Sporadic Alzheimer’s disease and possibly Parkinson’s.

Efficacy and Safety of Brolucizumab for Diabetic Macular Edema

Despite the effectiveness of existing anti-vascular endothelial growth factor (VEGF) therapies, a need remains for further treatment options to improve response rates and/or reduce injection or monitoring frequency in patients with diabetic macular edema (DME). To evaluate the efficacy and safety of brolucizumab vs aflibercept dosed every 4 weeks in participants with DME. This 52-week, double-masked, phase 3 randomized clinical trial included treatment-naive adults and adults who had previously received anti-VEGF therapy. Data were collected from September 2019 to March 2020, and data were analyzed from April 2020 to February 2021. Brolucizumab, 6 mg, intravitreal injection every 4 weeks or aflibercept, 2 mg, intravitreal injection every 4 weeks. Participants were randomized 2:1 to brolucizumab, 6 mg, or aflibercept, 2 mg. The primary end point was change from baseline in best-corrected visual acuity at week 52. Secondary end points were the proportion of participants with a 2-step improvement or greater from baseline in Diabetic Retinopathy Severity Scale score, the proportion of eyes with absence of both subretinal fluid and intraretinal fluid, change from baseline in central subfield thickness, and safety at week 52. A total of 517 participants were randomized to brolucizumab (n = 346) or aflibercept (n = 171); 299 (57.8%) were male, and the mean (SD) age was 60.7 (10.2) years. Brolucizumab was noninferior to aflibercept in best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letter score) change from baseline at week 52 (brolucizumab, 12.2-letter improvement; aflibercept, 11.0-letter improvement; difference, 1.1; 95% CI, -0.6 to 2.9; noninferiority margin, 4; P < .001). Brolucizumab was superior to aflibercept for the proportion of eyes without subretinal and intraretinal fluid (brolucizumab, 144 of 346 [41.6%]; aflibercept, 38 of 171 [22.2%]; difference, 20.0%; 95% CI, 12.5to 28.6; P < .001) and mean central subfield thickness change from baseline at week 52 (brolucizumab, -237.8 μm; aflibercept, -196.5 μm; difference, -41.4; 95% CI, -58.9 to -23.8; P < .001). Incidence of intraocular inflammation was 4.0% (14 of 346) in the brolucizumab arm and 2.9% (5 of 171) in the aflibercept arm, incidence of retinal vasculitis was 0.9% (3 of 346) and 0.6% (1 of 171), respectively, and incidence of retinal vascular occlusion was 0.3% (1 of 346) and 0.6% (1 of 171). One participant in the brolucizumab arm had retinal artery occlusion. In these study participants with DME, no clinically meaningful differences in visual outcomes were noted between the brolucizumab and aflibercept arms; some superior anatomic improvements were noted in the brolucizumab arm. No new safety concerns were identified. ClinicalTrials.gov Identifier: NCT03917472.

Optec: A Phase 2 Study to Evaluate Outpatient Administration of Teclistamab, a BCMA-Targeting Bispecific Antibody, in Patients with Multiple Myeloma

Background: Teclistamab is the only approved BCMA×CD3 bispecific antibody with a personalized, weight-based dosing schedule for the treatment of triple-class exposed relapsed/refractory multiple myeloma (RRMM). It is FDA approved for patients (pts) of therapy (LOTs), including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. In the pivotal MajesTEC-1 study (Moreau et al NEJM 2022), teclistamab showed deep and durable responses and a manageable safety profile in heavily pretreated pts with RRMM who had limited treatment options. The incidence of all grade cytokine release syndrome (CRS) during the first 2 cycles was 70%. Most pts experienced CRS following step-up doses 1 (42%) or 2 (35%), or the initial treatment dose (24%); 33% of pts experienced recurrent CRS. Most CRS events were grade 1/2 and fully resolved without discontinuation or dose reduction of teclistamab. One (0.6%) case of grade 3 CRS occurred in a pt who pneumonia but resolved in 2 days. No grade 4 or 5 CRS occurred. Tocilizumab is a monoclonal antibody targeting the interleukin-6 receptor (IL-6R) which is used to manage CRS resulting from T-cell redirection therapy. Preclinical data indicate that inhibition of IL-6 signaling prior to teclistamab administration can prevent CRS development without impacting anti-tumor activity (Li et al Ann. Oncol. 2019). In MajesTEC-1, pts who received a single IV dose of tocilizumab before the first teclistamab step-up dose (n=23) showed a reduction in the incidence of all grades of CRS, compared with the overall study population (26% vs 72%). Currently, there are no data on the safety of administering the step-up doses of teclistamab in the outpatient (OP) setting, but OP step-up dosing may make teclistamab more accessible. Therefore, we seek to investigate whether the use of prophylactic tocilizumab can reduce the incidence and severity of CRS associated with teclistamab and allow safe OP administration of the step-up dosing. Methods: This single-arm, non-randomized, multicenter, prospective study (NCT05972135) will evaluate CRS incidence and severity after prophylactic tocilizumab in pts treated with teclistamab in the OP setting. A target of 50 participants will be enrolled with an initial PK/PD safety cohort (n=10). Objectives through end of study include recurrent CRS, grade ≥3 and any grade infections, neurotoxicity including ICANS, neutropenia, febrile neutropenia, and efficacy. Eligible pts are ≥18 years with a documented diagnosis of RRMM who have previously received ≥4 LOTs. Pts with rapidly progressing disease, central nervous system involvement, active infection, or contraindication to tocilizumab will be excluded from the trial. Prior to the treatment phase, pts will participate in a 28-day screening phase to determine study eligibility. During the treatment phase, a single dose of tocilizumab will be administered at 8 mg/kg IV, 2 to 4 hours prior to step-up dose 1 of teclistamab (Cycle 1 Day 1) in an outpatient setting (Figure 1). Teclistamab will then be administered at step-up doses of 0.06 mg/kg subcutaneously (SC) (Cycle 1 Day 1) and 0.3 mg/kg SC (Cycle 1 Days 3-5), followed by 1.5 mg/kg SC (Cycle 1 Day 8), with weekly administration for twelve 28-day cycles or until disease progression or unacceptable toxicity. Teclistamab may be reduced to 1.5 mg/kg SC every two weeks for participants who achieve partial response or better after 6 months of therapy. Safety evaluations will include physical examination, vital sign measurements, neurological examination, assessment of ECOG performance status, and clinical safety laboratory assessments. IVIG is recommended in pts with serum IgG &amp;lt;4 g/L. Follow-up of participants during the study will include monitoring for all adverse events, disease progression, and survival until end of study. By studying the feasibility and safety of administering the step-up dosing schedule in an outpatient setting, teclistamab may become more accessible to pts with RRMM and limited treatment options.

Pegcetacoplan compared with supportive care for 26 weeks for participants with paroxysmal nocturnal hemoglobinuria: a plain language summary

Pegcetacoplan compared with supportive care for 26 weeks for participants with paroxysmal nocturnal hemoglobinuria: a plain language summary

Changes in exhaled volatile organic compounds following indirect bronchial challenge in suspected asthma

BackgroundInhaled mannitol provokes bronchoconstriction via mediators released during osmotic degranulation of inflammatory cells, and, hence represents a useful diagnostic test for asthma and model for acute attacks. We hypothesised that...

1199-P: Timing of Postprandial Peak CGM Glucose in Gestational Diabetes

Background: Current guideline recommendations for management of gestational diabetes mellitus (GDM) recommend capillary testing of blood glucose levels fasting and one-two hours postprandial. Use of intermittently-scanned continuous glucose monitors (isCGM) during pregnancy in women with GDM has the potential to improve fetal outcomes, however there are limited recommendations for their use. Optimal timing of postprandial testing is unknown. Methods: Women with GDM diagnosed after 24 weeks gestation were recruited and randomized to adjunctive use of isCGM versus capillary testing with blinded CGM. In this subanalysis of 8 participants, timing of peak CGM glucose value is compared to recommended 1-hour postprandial capillary value. Food logs and/or meter data from the first two weeks of participation were used for analysis. Results: A total of 265 meals were analyzed. Gestational age at analysis was 29±1.2 weeks. One participant was treated with insulin. Three participants used blinded CGM; 5 used isCGM. Mean peak CGM glucose was 100±11 mg/dL. Mean time to peak was 96±14 minutes. Seventy-four percent of peak glucoses were after one hour. Conclusions: Current recommendations for glucose monitoring may need to be adapted to use of new technology with isCGM. Our data found that if a user only scanned at one hour postprandial, they could miss the peak glucose for the majority of meals. Repeat scanning or retrospective review of isCGM data may be required to determine the timing of a user’s postprandial peaks in relation to glycemic goals. Factors like the lag in CGM glucose compared to capillary testing and meal content should be considered with isCGM use. Disclosure G.O'malley: Research Support; Dexcom, Inc., Abbott Diabetes, Tandem Diabetes Care, Inc., Omnipod, Eli Lilly and Company. M.Kononenko: None. S.J.Ogyaadu: None. C.Levister: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Abbott Diabetes. E.Ellis: None. D.Arumugam: None. L.Vieira: None. C.J.Levy: Advisory Panel; Dexcom, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., T1D Exchange. Funding Abbott Diabetes Care

Real-Time Continuous Glucose Monitoring Reduced Costly Diabetes-Related Events in Adolescents and Young Adults despite Lack of Short-Term Reduction in Hemoglobin A1c

Real-time continuous glucose monitoring (rtCGM) can directly improve patient outcomes, including decreased health care system utilization and associated costs. The purpose of this study was to evaluate the clinical benefits of rtCGM use in a high-risk, under-resourced cohort of adolescents and young adults (AYA) with type 1 diabetes (T1D) who had no prior access to rtCGM. The effects of rtCGM use on hemoglobin A1c (A1c) and the frequency of health care events (i.e., diabetes-related emergency room (ER) visits, hospitalizations, emergency medical services (EMS), and after-hour emergency calls) were evaluated regarding payor costs in 33 AYA with ≥70% rtCGM use. Secondary aims included the evaluation of a phone-based pattern management intervention. The frequency of health care events decreased at 12 and 24 weeks for all participants, and there was no significant difference by treatment group. We estimated that the use of rtCGM in this cohort results in a projected annualized cost-savings of $195,943 to $294,864 or 43–65% per year based on Medicare or list pricing for rtCGM, respectively. Results also revealed improvements in A1c at 12 weeks for all study participants, but this was not maintained at 24 weeks for the phone-based pattern management intervention group. Our findings suggest that rtCGM may be an effective tool for reducing diabetes-related events and underscores the importance of access. Future studies are needed to further examine tailored interventions and support to optimize rtCGM use and glycemic health in high-risk AYA.