ULTRASOUND GUIDED INJECTIONS of HYADD4 for KNEE OSTEOARTHRITIS IMPROVES PAIN and FUNCTIONAL OUTCOMES at 3 and 6 MONTHS WITHOUT CHANGES in SYNOVIAL FLUID VOLUMES

Background: Prior studies have demonstrated improved accuracy and efficacy when Intra-articular (IA) therapeutics are injected using ultrasound (US) guidance. There is also growing evidence that many patients with knee oste-oarthritis (OA) exhibit a pro-infammatory catabolic synovial fuid (SF) profile. However, it is not known if temporary clinical improvement in pain and function after IA Hyaluronic acid (HA) injections is associated with changes in SF volumes. Objectives: The purpose of this study was to determine if IA HA injections delivered using US directed needle visualization with an external pneumatic compression device would result in improved clinical outcomes for knee OA at 3 and 6 months, and if this was associated with a reduction in the amount of knee synovial fuid (SF) measured on US. Methods: 49 eligible subjects with symptomatic Knee OA, BMI < 40 and KL radiographic rating of II or III OA were consented for this open label prospective IRB approved Investigator Initiated SF OA biomarker study (HS 3179, NCT 04093232). All standing radiographs were reviewed by a fellowship-trained MSK radiologist. 36 subjects had adequate aspirated SF volumes of > 500 mcl for biomarker analysis and therefore were eligible to receive two IA injections of HYADD4, 24 mg/3ml (Fidia Farmaceutici S.p.A. Italy) 7 days apart by a MSK US certifed Rheumatologist. An external pneumatic compression device and US visualized needle insertion ensured injections were delivered into the intra-syn-ovial space. Despite COVID-19 restrictions, 34 patients (17 women and 17 men) between 35 and 78 years of age returned for 3 month evaluations and 30 had evaluations at 6 months. The following clinical variables were measured: Western Ontario and McMaster Universities Index (WOMAC) total scores, Visual Analog Pain Scale (VAS, 0-10), PCS scores on the SF-36 health survey questionnaires (physical function/bodily pain and general health), 6-min-ute walking distance in meters (6 MWD), and measured SF depth before and after an external pneumatic compression device was infated to 100 mmHg to facilitate aspiration by increasing available SF volumes under positive presure. The SF depth was measured on the recorded US image (GE logiq e) as the largest anechoic region selected for aspiration on either the lateral (n= 30) or medial (n=4) compartment. SF and simultaneous peripheral blood samples were centrifuged and cryopreserved at-80 o C within 45 minutes of aspiration for future analysis. Statistical differences between baseline values compared to those levels at 3 and 6 months were determined using a paired ANOVA test with p <0.05 signifcance. Results: Improvements over baseline values were observed at 3 and 6 months respectively, after IA HA injections in WOMAC (40%, 40%), VAS (45%, 51%) and PCS (15%, 18%) all p< 0.0001. The 6 WWD improved by 7 % at 3 months (p< 0.007) but was not statistically improved at 6 months. US measured SF depth at baseline was 3.2 ± 2.2 mm before infation and 6.4 + 3.7 mm after infation of the pneumatic external compressioin device but statistical differences in SF depth were not observed at 3 and 6 months. Conclusion: Despite improvements in WOMAC, VAS scores, and PCS scores on the SF 36 at 3 and 6 months after US guided knee injections with an HA product, a statistically signifcant reduction in the amount of US measured SF was not observed. The 6 MWD improved at 3 months but was not statistically different from the baseline distance by 6 months. IA injections using US needle visualization confrmed that the product was delivered into the synovial space with 100 % accuracy which might have resulted in improved efficacy results in this study compared to prior IA HA studies injected without US or using different HA products. In the future, we hope SF biomarkers may identify which individual OA patients will likely achieve the greatest beneft with IA HA injections and to determine if this is associated with a reduction in catabolic pro-infammatory proteins.

Sf-36 mental component score trajectories do not show a strong impact of the COVID-19 pandemic in current and former smokers

Background: CDC recommended increased social distancing in order to reduce virus transmission during the COVID-19 pandemic. This included physical isolation for older adults at elevated risk for COVID-19 due to age and chronic medical conditions such as lung disease. While social distancing is effective at reducing the spread of COVID-19, the secondary negative impact of isolation and reduction in social resources is likely to impact vulnerable older adults with medical risk factors such as a history of heavy smoking and chronic lung disease. In this study we will examine the impact of pandemic on longitudinal change in SF-36 Mental Component Score. Methods: COPDGene is a longitudinal study of current and former smokers with at least a 10 pack-year smoking history. The study has included 3 visits (Baseline, Phase 2 at 5-years, and Phase 3 at 10-years), during which quality of life was assessed using the SF-36. Phase 3 in-person visits were interrupted by COVID-19 in March 2020. SF-36 was included in virtual visits conducted from March-October of 2020 using telephony and online surveys. We examined vectors of change in MCS across the 3 timepoints employing group-based trajectory models (SAS Proc Traj) to identify group membership and the probability of the observed MCS given group memberships. Each model used baseline and 5-year data in the same way. The first model used phase 3 data collected in-person (PRE) and the second used phase 3 data collected during the pandemic (DURING). Trajectory membership was compared using demographic profiles of participants pre- vs post-pandemic. Results: Figure 1 shows the trajectories identified for each group. The PRE group (n=2,242) included 4 trajectories: 1) 68% began high (MCS=56.1) and continued to be high across 10 years, 2) 15% began low (MCS=38.8) and improved, 3) 11.0% began high (MCS=51.4) and decreased and 4) 6.4% began low (MCS=30.0%) and remained low. The DURING group included three trajectories with the majority of observations beginning high (MCS=54.5) and remaining high, and two other groups that duplicated the pattern of PRE groups 2 and 3. The most consistent predictors of group membership in both PRE and DURING were age, MMRC and 6 minute walk at both baseline and year 10 follow-up (p<0.0001 in all cases). Conclusions: Trajectories of change in mental-health related quality of life do not reflect a large negative impact of the COVID- 19 pandemic in this large sample of older current and former smokers with and without COPD.

Do established infection prevention and control measures prevent spread of SARS-CoV-2 to the hospital environment beyond the patient room?

The role of the hospital environment in the transmission of infection is well described. With an emerging infection whose mode of transmission is under investigation, strict infection prevention and control measures, including patient isolation, hand hygiene, personal protective equipment that is doffed on exiting the patient room, and environmental cleaning should be implemented to prevent spread. Environmental testing demonstrated that COVID-19 patients contaminated the patient area (11/26, 42.3% of tests) but contamination of general ward areas was minimal (1/30, 3%) and the virus was detected after cleaning on one item only (1/25, 4%) which was noted to be in disrepair.

Clinical Trials and Tribulations in the COVID-19 Era.

Advances in treating and preventing Alzheimer disease and other neurocognitive disorders of aging arise from rigorous preclinical and clinical research, with randomized controlled treatment trials as the last and definitive test. The COVID-19 pandemic has greatly disrupted ongoing interventional studies and researchers are scrambling to find ways to safely continue this critical work amidst rapidly shifting guidelines from sponsors, institutions, and state and federal guidelines. Here the authors describe novel approaches and work-flow adaptations to study visits, drug delivery and interim and endpoint safety and outcomes assessments to avoid sacrificing years of preparation and substantial financial investments, to work in the best interest of participants and their caregivers, and to continue on the path toward discovering disease-modifying treatments for the millions of individuals impacted by major neurocognitive disorders.