A Placebo-Controlled, Single-Blind Extension Study Evaluating The Safety And Efficacy Of Lorecivivint In Subjects With Structurally Advanced Osteoarthritis Of The Knee (Oa-07): Radiographic And Pain Outcomes At 24 And 30 Month

Purpose: Knee osteoarthritis (OA) is a common joint disorder associated with pain, disability, and joint damage. An unmet need remains for safe, efficacious treatments for symptoms and disease modification. Lorecivivint (LOR), a novel intra-articular (IA) CLK/DYRK inhibitor thought to modulate Wnt and inflammatory pathways, has previously appeared safe, demonstrated patient-reported outcome (PRO) improvements compared with placebo (PBO), and maintenance of radiographic medial joint space width (mJSW). A LOR trial, OA-11, enrolled participants with structurally advanced (mJSW 1.5-4 mm) knee OA. OA-11 did not meet its primary endpoint;however, greater treatment effects were observed in subjects with less advanced/earlier (Kellgren Lawrence [KL] grade 2) OA. Additionally, the COVID pandemic potentially confounded pain reporting and expected mJSW progression. An ongoing 4-year extension study, OA-07 (NCT04520607), continues to evaluate LOR safety and efficacy with primary and secondary efficacy outcomes of mJSW (mm) and Pain Numerical Rating Scale (NRS [0-10]) respectively. Data up to 30 months from this study are reported. Method(s): Subjects who completed OA-11, a 13-month Phase 3 LOR trial, were enrolled into OA-07, an extension study designed to evaluate safety and efficacy of long-term LOR treatment. During the single-blinded Year 1 of OA-07, subjects received repeat injection according to their randomized treatment received in OA-11 (LOR or PBO). In Year 2 and annually thereafter, all subjects (LOR and PBO) received an open-label 0.07 mg IA LOR injection. OA-07 commenced in July 2020 and is planned to continue over a 4-year period with clinic visits every six months. Result(s): 277 subjects (mean age 61.0 +/- 8.2 years, BMI 31.8 +/- 4.9 kg/m2, female 62.8%, KL3 45.5%, 67.1% bilaterally symptomatic, mean baseline mJSW 2.63 +/- 0.69 mm, 68.6% mJSW < 3 mm) were enrolled. LOR appears safe and well-tolerated, consistent with its previously observed safety profile. At 24 months, the LOR treatment arm shows reduced mJSW loss compared to placebo, LOR -0.13 (+/- 0.06) mm (n=103) vs. PBO -0.22 (+/- 0.05) mm (n=112) (DELTA=0.10 mm, 95% CI [-0.05, 0.25], P=0.199, Figure 1A) for Full Analysis Set (FAS) and LOR +0.02 (+/- 0.07) mm (n=61) vs. PBO -0.15 (+/- 0.07) mm (n=63) (DELTA=0.17 mm, 95% CI [-0.02, 0.37], P=0.077, Figure 1B) for KL2. Average change from OA-07 baseline to 24 months in Pain NRS is -0.25 (+/- 0.19) for LOR (n=121) compared to 0.11 (+/- 0.19) for placebo (n=130) (DELTA=-0.36, 95% CI [-0.89, 0.17], P=0.179, Figure 2A). For WOMAC Function, LOR (n=96) change from baseline was -5.33 (+/- 1.84) vs PBO (n=104) -0.43 (+/-1.76), (DELTA=-4.90, 95% CI [-9.92, 0.13], P=0.056, Figure 2B);for WOMAC Pain, LOR (n=96) change from baseline of -4.80 (+/-1.87) vs PBO (n=106) 0.38 (+/-1.78), (DELTA=-5.18, 95% CI [-10.28, -0.08], P=0.047, Figure 2C). At 30 months (Figure 2A), unblinded IA injection of LOR (n=60) shows additional Pain NRS improvements with change from OA-07 baseline of -0.57 (+/-0.39) and cross-over to LOR from PBO (n=76) shows an improvement of -0.37 (+/-0.26). Larger improvements in PROs were observed in the KL2 subgroup, with month 24 improvements for LOR over PBO (DELTA= -0.48 (95% CI -1.20, 0.23), P=0.183 in Pain NRS, (DELTA -6.05 (95% CI -12.87, 0.78), P=0.082 in WOMAC Function, and (DELTA -6.58 (95% CI -13.18, 0.02), P=0.051, in WOMAC Pain. Conclusion(s): LOR continues to appear safe and well tolerated. A potential benefit of LOR 0.07 mg compared with PBO in mJSW is observed 12 months after OA-07 baseline injection. Potential LOR benefit compared to PBO is also seen across PROs. Within this structurally advanced knee OA cohort, both mJSW and PROs treatment effects appear enhanced in earlier/ less advanced KL2 knee OA subjects relative to those with more advanced KL3 graded knees. This study is ongoing. [Formula presented] [Formula presented]Copyright © 2023

Profiles of COVID-19 vaccine hesitancy by race and ethnicity in eastern Pennsylvania.

BACKGROUND: Throughout US history, chronic and infectious diseases have severely impacted minority communities due to a lack of accessibility to quality healthcare and accurate information, as well as underlying racism. These fault lines in the care of minority communities in the US have been further exacerbated by the rise of the COVID-19 pandemic. This study examined the factors associated with COVID-19 vaccine hesitancy by race and ethnicity, particularly among African American and Latinx communities in Eastern Pennsylvania (PA). METHODS: Survey data was collected in July 2021 in Philadelphia, Scranton, Wilkes-Barre, and Hazleton, PA. The 203 participants (38.7% Black, 27.5% Latinx) completed the 28-question survey of COVID-19 vaccination attitudes in either English or Spanish. RESULT: Out of the 203 participants, 181 participants met all the inclusion criteria, including completed surveys; of these participants, over three-fifths (63.5%) were acceptant of the COVID-19 vaccine whereas the remainder (36.5%) were hesitant. Binary logistic regression results showed that age, concern for vaccine efficacy, race, knowledge on the vaccine, and belief that the COVID-19 virus is serious significantly influenced COVID-19 vaccine hesitancy. Minorities were more likely to be hesitant toward vaccination (OR: 2.8, 95% CI: 1.1, 6.8) than non-Hispanic whites. Those who believed the COVID-19 vaccine was ineffective (OR: 8.3, 95% CI: 3.8, 18.2), and that the virus is not serious (OR: 8.3, 95% CI: 1.1, 61.8) showed the greatest odds of hesitancy. CONCLUSIONS: Minority status, age less than 45 years, misinformation about seriousness of COVID-19 illness, and concern about vaccine efficacy were contributing factors of COVID-19 vaccine hesitancy. Therefore, understanding and addressing the barriers to COVID-19 vaccination in minority groups is essential to decreasing transmission and controlling this pandemic, and will provide lessons on how to implement public health measures in future pandemics.

Implementation of Expanded Syphilis Screening in Planned Parenthood Northern California Family Planning Health Centers

BACKGROUND: California is experiencing record increases in all reportable sexually transmitted infections (STIs), with particularly dramatic rises in prenatal and congenital syphilis. In response, Planned Parenthood Northern California (PPNorCal) Health Centers implemented expanded screening protocols in Fall 2018 which include HIV/chlamydia/gonorrhea/syphilis co-screening for any patient with a positive pregnancy test and HIV/syphilis co-screening for all patients. METHOD(S): This analysis explores (1) protocol implementation barriers and facilitators, (2) lessons learned, and (3) perceived impact of COVID-19 on implementation. Twelve clinical and four leadership PPNorCal staff interviews were conducted. Due to time constraints, each interview question was not answered by every interviewee. Recrutiment prioritized health centers in counties with high syphilis morbidity. Thematic analysis was conducted to identify primary themes and a secondary thematic analysis per theme identified sub-themes. RESULT(S): Frequently identified facilitators included patient education/communication (12/16;75%), workflow (11/16;69%), and staff education/communication (11/16;69%). Frequently identified barriers included patient willingness (11/16;69%), patient education/communication (9/16;56%), staff education/communication (9/16;56%), and workflow (9/16;56%). When stratifying by staff level, leadership identified staff communication/education more frequently for both facilitators and barriers, while clinical staff discussed patient communication/education. 93% (13/14) of respondents stated protocols were effective in increasing syphilis screening and case identification;100% (12/12) reported a positive impact on patient care. With regard to staff workload, 42% (5/12) noted increases, 25% (3/12) reported improvements over time, and 33% (4/12) reported no impact. Finally, 86% (13/15) reported a decrease in screening during the COVID-19 pandemic. CONCLUSION(S): Expanded STI screening protocols may increase screening and case identification, resulting in positive impacts on patient care, as was attested to unanimously by interviewees. Workload increases may occur, with potential improvement over time. Consideration of patient and staff education/communication, patient willingness, and workflow may lend to successful implementation of such protocols in family planning clinics.

Assessing the Profile of Unvaccinated COVID-19 Individuals in African American and Latinx Communities in Eastern Pennsylvania (preprint)

Background: Throughout US history, chronic and infectious diseases have severely impacted minority communities due to lack of accessibility to quality healthcare, accurate information, and underlying racism. These fault lines in the care of minority communities in the US have been further exposed by the rise of COVID-19 pandemic. This study examined the factors associated with COVID-19 vaccine hesitancy among African American and Latinx communities in Eastern Pennsylvania (PA). Methods: Survey data was collected in July 2021 in Philadelphia, Scranton, Wilkes-Barre, and Hazleton, PA. The 203 participants (38.7% Black, 27.5% Latinx) completed the 28-question survey of COVID-19 vaccination attitudes in either English or Spanish. Results: Out of a total of 181 participants that met inclusion criteria of completed surveys, results indicate that 63.5% (n=115) were acceptant of the COVID-19 vaccine whereas the remainder 36.5% (n=66) were hesitant. Binary logistic regression results showed that age, concern for vaccine efficacy, race, knowledge on the vaccine, and belief that the COVID-19 virus is serious significantly influenced COVID vaccine hesitancy. Minorities were more likely to be hesitant toward vaccination (OR: 2.77, 95% CI: 1.13, 6.79) than non-Hispanic whites. Those who believed the COVID vaccine was ineffective (OR: 8.29, 95% CI: 3.78,18.2), and that the virus is not serious (OR: 8.28, 95% CI: 1.11, 61.8) showed the greatest odds of hesitancy. Conclusions: Contributing factors of vaccine hesitancy in minority communities were age, concern for vaccine efficacy, and education. Understanding and addressing the barriers to COVID-19 vaccination in minority groups is essential to decreasing transmission and controlling this pandemic.