Western Institutional Review Board Research Articles

Platform Design for Optical Screening and Conditioning for Injury Resilience.

Musculoskeletal injuries (MSKIs) among active duty soldiers result in more than 10 million limited duty days each year and account for more than 70% of the medically nondeployable population. Overuse injuries in lower limbs from running, foot marching long distances with heavy loads, and lifting heavy objects are the most common types of injuries in the military. Physical training and rehabilitation exercises for greater resiliency through aerobic, muscle strength, endurance, and agility conditioning programs can prevent or reduce the effects of MSKIs if Soldiers adhere to proper biomechanics and training techniques. We are introducing a three-dimensional (3D) camera-based platform for Optical Screening and Conditioning for Injury Resilience (OSCIR) that is designed to identify and correct high-risk movement patterns based on quantifiable biomechanical measurements in clinical or field settings. Our goal is to improve resilience to MSKI by offering greater access to quality of movement skills in warfighters through an autonomous device that can be used in Sports Medicine and Reconditioning Team (SMART) clinics and High-Intensity Tactical Training (HITT) sites. OSCIR fuses four pairs of Kinect Azure cameras into a concise footprint to achieve suitable sampling rates and an unobstructed field of view for accurate dynamic movement tracking using a custom point cloud solution. We designed a unique multistage 3D joint tracking algorithm architecture to methodically isolate the human body point cloud from the background, identify individual limb segments, and perform iterative joint optimization at the global and local joint levels. We evaluated the feasibility of our prototype system among N = 12 control participants (6 M/6 F; 21-37 years) in compliance with the Western Institutional Review Board (Tracking #20225920, approved on November 4, 2022). Five task-specific MSKI outcome metrics identified by end-user physical therapists and athletic trainers as indicators for movement quality were assessed across 7 lower-extremity exercises derived from standardized MSK assessment/conditioning batteries used in the military. Data were recorded concurrently by OSCIR and a reference standard Vicon motion capture system for validating system accuracy. Task-specific MSKI indicators for knee flexion and hip flexion range of motion achieved an average error of 4.05 ± 2.34°, while 3D position-based postural outcomes of left-right foot distance, left-right hand distance, and step length obtained mean absolute errors of 2.58 ± 2.30 cm. Results support the feasibility of our system in achieving outcomes that are comparable to currently accepted laboratory standards. Our study describes the integration process for a 3D camera-based clinical system for MSKI conditioning and rehabilitation. The impact of our system will enable key stakeholders in the military to manage MSKIs in warfighters by automating key assessment and rehabilitation test batteries; making tests more readily accessible, and interpretations more accurate by providing objective biomechanical measures. OSCIR is undergoing turn-key design features to serve as a screening tool for warfighters to readily assess susceptibility to MSKI or as a training platform to help guide exercise techniques to achieve resiliency against future injuries.

Improving Neurological Health in Aging Via Neuroplasticity-Based Computerized Exercise: Protocol for a Randomized Controlled Trial.

Our current understanding of how computerized brain training drives cognitive and functional benefits remains incomplete. This paper describes the protocol for Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE), a randomized controlled trial in healthy older adults designed to evaluate whether brain training improves cholinergic signaling. INHANCE evaluates whether 2 computerized training programs alter acetylcholine binding using the vesicular acetylcholine transporter ligand [18F] fluoroethoxybenzovesamicol ([18F] FEOBV) and positron emission tomography (PET). In this phase IIb, prospective, double-blind, parallel-arm, active-controlled randomized trial, a minimum of 92 community-dwelling healthy adults aged 65 years and older are randomly assigned to a brain training program designed using the principles of neuroplasticity (BrainHQ by Posit Science) or to an active control program of computer games designed for entertainment (eg, Solitaire). Both programs consist of 30-minute sessions, 7 times per week for 10 weeks (35 total hours), completed remotely at home using either loaned or personal devices. The primary outcome is the change in FEOBV binding in the anterior cingulate cortex, assessed at baseline and posttest. Exploratory cognitive and behavioral outcomes sensitive to acetylcholine are evaluated before, immediately after, and 3 months following the intervention to assess the maintenance of observed effects. The trial was funded in September 2019. The study received approval from the Western Institutional Review Board in October 2020 with Research Ethics Board of McGill University Health Centre and Health Canada approvals in June 2021. The trial is currently ongoing. The first participant was enrolled in July 2021, enrollment closed when 93 participants were randomized in December 2023, and the trial will conclude in June 2024. The study team will be unblinded to conduct analyses after the final participant exits the study. We expect to publish the results in the fourth quarter of 2024. There remains a critical need to identify effective and scalable nonpharmaceutical interventions to enhance cognition in older adults. This trial contributes to our understanding of brain training by providing a potential neurochemical explanation of cognitive benefit. ClinicalTrials.gov NCT04149457; https://clinicaltrials.gov/ct2/show/NCT04149457. DERR1-10.2196/59705.

Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer’s disease: a randomized, controlled clinical trial

BackgroundEvidence links lifestyle factors with Alzheimer’s disease (AD). We report the first randomized, controlled clinical trial to determine if intensive lifestyle changes may beneficially affect the progression of mild cognitive impairment (MCI) or early dementia due to AD.MethodsA 1:1 multicenter randomized controlled phase 2 trial, ages 45-90 with MCI or early dementia due to AD and a Montreal Cognitive Assessment (MoCA) score of 18 or higher. The primary outcome measures were changes in cognition and function tests: Clinical Global Impression of Change (CGIC), Alzheimer’s Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating–Sum of Boxes (CDR-SB), and Clinical Dementia Rating Global (CDR-G) after 20 weeks of an intensive multidomain lifestyle intervention compared to a wait-list usual care control group. ADAS-Cog, CDR-SB, and CDR-Global scales were compared using a Mann-Whitney-Wilcoxon rank-sum test, and CGIC was compared using Fisher’s exact test. Secondary outcomes included plasma Aβ42/40 ratio, other biomarkers, and correlating lifestyle with the degree of change in these measures.ResultsFifty-one AD patients enrolled, mean age 73.5. No significant differences in any measures at baseline. Only two patients withdrew. All patients had plasma Aβ42/40 ratios <0.0672 at baseline, strongly supporting AD diagnosis. After 20 weeks, significant between-group differences in the CGIC (p= 0.001), CDR-SB (p= 0.032), and CDR Global (p= 0.037) tests and borderline significance in the ADAS-Cog test (p= 0.053). CGIC, CDR Global, and ADAS-Cog showed improvement in cognition and function and CDR-SB showed significantly less progression, compared to the control group which worsened in all four measures. Aβ42/40 ratio increased in the intervention group and decreased in the control group (p = 0.003). There was a significant correlation between lifestyle and both cognitive function and the plasma Aβ42/40 ratio. The microbiome improved only in the intervention group (p <0.0001).ConclusionsComprehensive lifestyle changes may significantly improve cognition and function after 20 weeks in many patients with MCI or early dementia due to AD.Trial registrationApproved by Western Institutional Review Board on 12/31/2017 (#20172897) and by Institutional Review Boards of all sites. This study was registered retrospectively with clinicaltrials.gov on October 8, 2020 (NCT04606420, ID: 20172897).

Prevalence of Antibodies to COVID-19 Due to Infection or Vaccination in US Adults.

-Determine the seroprevalence of SARS-CoV-2 infection and vaccination in a population applying for life insurance. -This is a cross-sectional study of 2584 US life insurance applicants, to determine the seroprevalence of antibodies to COVID-19. This convenience sample was selected on two consecutive days April 25-26, 2022. -For COVID-19, 97.3% are seropositive, and 63.9% have antibodies to nucleocapsid protein, a marker of prior infection. An additional, 33.7% have been vaccinated with no serologic evidence of infection. -Serum and urine samples from a nationwide group of insurance applicants for routine risk assessment were collected. The examination of applicants typically occurs, in their homes, their place of employment, or a clinic. The paramedic exam occurs 7-14 days after the insurance application. Before the exam, an office assistant calls the applicant and inquires if they have been in contact with a person with SARS-CoV-2, been ill within the last 2 weeks, felt sick, or recently had a fever. If the applicant answers yes, the exam is rescheduled. Before sample collection, the applicant reads and signs a consent form to release medical information and testing. Next, the examiner records the applicant's blood pressure, height, and weight. Then, a blood and a urine sample are collected and sent with the consent form to our laboratory via Federal Express. On April 25-26, 2022, we tested 2584 convenience samples from adult insurance applicants for the presence of antibodies to nucleocapsid and spike proteins from SARS-CoV-2. As a standard practice, we reported the client-specified test profile results to our life insurance carriers. In contrast, the COVID-19 test results were only available to the authors. Patient and Public Involvement.-There was no patient involvement in study design, reporting of results, or journal publication selection. There was patient consent to publish de-identified study results. No public involvement occurred in the creation or completion of the study. The authors thank the participants in this study for approving the use of their blood samples to further society's understanding of the SARS-CoV-19 pandemic. Ethics Review.-Western Institutional Review Board reviewed the study design and determined it to be exempt under the Common Rule and applicable guidance. Therefore, it is exempt under 45 CFR § 46.104(d)(4) from using de-identified study samples for epidemiologic investigation, WIRB Work Order #1-1324846-1. In addition, all test subjects had signed a consent allowing research of their blood and urine samples with the removal of personally identifiable information. -The combined seroprevalence for antibodies to nucleocapsid, a marker of prior infection, and antibodies to spike protein, an indicator of either previous infection or vaccination, was 97.3%. Higher infection rates occur in younger vs older age groups, with a non-statistical difference for vaccinated and acquired natural immunity. For the age group 16-84, the total estimated seroprevalence of COVID-19 in the US is 249 million cases. -The US population has widespread immune resistance to current variants of COVID-19 due to prior infection or vaccination. The infectivity of new variants and silent disease, independent of previous infection or vaccination, are the driving force behind the sporadic increase in clinical SARS-CoV-2 cases.

The effect of oral guaifenesin on pediatric chronic rhinitis: A pilot study

ObjectivesTo investigate the effectiveness of guaifenesin in the relief of nasal symptoms in children with chronic rhinitis (CR). We hypothesized that guaifenesin use over a 14-day study period would improve subjective nasal complaints in pediatric patients with chronic rhinitis, as measured by the SinoNasal-5 (SN-5) survey. We also hypothesized improvement in nasal volume and cross-sectional area with guaifenesin. Study designRandomized, placebo-controlled, parallel group, masked clinical trial. MethodsThe study consisted of a 14-day, randomized, placebo-controlled, parallel group, masked clinical trial of oral guaifenesin for CR in children aged 7–18 years. A 2:1 ratio of subjects on active medication to placebo was used. The study was approved by the Western Institutional Review Board. On initial enrollment and at the conclusion of therapy, the SN-5 was completed by parents, acoustic rhinometry measurements performed, and mucus sampling for rheology was obtained. Results30 subjects were enrolled in the study, with 20 receiving guaifenesin and 10 placebo. Treatment with guaifenesin for 14 days produced a significant mean change towards clinical improvement in SN-5 scores compared with placebo (p = 0.013). There was no significant difference in quality of life assessment scores between the two groups or in any of the acoustic rhinometry parameters. Many of the study subjects had difficulty producing a mucus sample sufficient for analysis. ConclusionsBased upon our pilot data, it appears that guaifenesin treatment may produce objective improvements in pediatric patients with CR. Further research with larger samples sizes, inclusion of children younger than 6, and biophysical mucus analyses is warranted. Level of evidenceLevel 2b.

Breakthrough COVID-19 Infections in Patients with Hematologic Malignancies during the Omicron (B.1.1.529) Surge: Data from the Patient-Reported Leukemia & Lymphoma Society National Registry

INTRODUCTION We have previously observed that many patients with B-cell derived hematologic malignancies fail to produce protective levels of anti-spike antibodies or anti-spike T-cells in response to SARS-CoV-2 mRNA vaccination. We attempted to understand if these results indicated that such patients may be vulnerable to COVID-19 infections. METHODS The patient-reported LLS National Registry was used to identify patients who had COVID-19 infections including those whose infections occurred after vaccination (breakthrough infections or BTIs) and correlate the BTI with the level of anti-spike antibodies prior to the infection (NCT04806295, NCT04794387). The cohort consisted primarily of patients with chronic lymphocytic leukemia (43%) and other B-cell derived non-Hodgkin lymphomas (35%). Patients self-reported data on demographic variables, vaccine type(s) and dates of administration, date of COVID-19 infection, diagnostic method to detect the infection, and hospitalization date. Anti-spike antibody levels were assessed using the Roche Elecsys semi-quantitative assay. This study was approved by the Western Institutional Review Board, and participants provided informed consent electronically. This survey was conducted on February 17, 2022. RESULTS 2707 patients who were vaccinated, predominately with SARS-CoV-2 mRNA vaccines, responded to the survey. 295 out of 2707 (10.9%) patients reported BTIs (Figure 1). 80% of BTIs occurred during December 2021 to February 2022, a timing that coincided with the Omicron surge in the general US population. Of the 295 patients who had BTIs, 133/1177 (11.3%), 155/1464 (10.6%), and 7/66 (10.6%) of the patients had 2, 3 or 4 vaccinations, respectively. Among the 866 patients who had three vaccinations and anti-spike antibody analysis, 70 (8.1%) had BTIs. Compared to the population of patients that had three vaccinations who did not develop BTIs, 14/166 (8.2%) and 33/429 (7.6%) patients who had BTIs had undetectable (<0.8 U/mL) or very high levels (>2500 U/mL) of anti-spike antibodies, respectively. There was a moderate association between anti-spike antibody levels and time between 3rd vaccination and BTI (r2 = 0.064, P = 0.03; median values 114 to 138 days for non-detectable and maximum anti-spike levels, respectively). Hospitalizations were reported by 19 of 295 (6.4%) patients. Ten of these patients had anti-spike antibody analysis done after vaccination and prior to the BTI. 100% (10/10) of these patients had anti-spike antibody levels below detectable levels (N = 7) or low anti-spike antibody levels (range : 42-167 U/mL). Nine out of these ten patients had BTIs during the Omicron surge. CONCLUSIONS AND FUTURE DIRECTIONS Approximately 10% of patients with hematologic malignancies that had two to four SARS-CoV-2 vaccines reported a BTI during the Omicron surge. The percentage of BTIs was similar regardless of the anti-spike antibody level prior to the infection. In contrast, hospitalization due to a BTI was only found in patients with no detectable anti-spike antibodies or antibody levels previously known to be associated with poor neutralizing antibody levels. Further analysis is on-going to determine if these trends also occur during the BA.5 surge. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparison of Reverse and Anatomic Total Shoulder Arthroplasty in Patients With an Intact Rotator Cuff and No Previous Surgery.

This study's purpose is to compare clinical and radiographic outcomes of primary anatomic total shoulder arthroplasty (aTSA) and primary reverse total shoulder arthroplasty (rTSA) patients with osteoarthritis (OA) and an intact rotator cuff with no previous history of shoulder surgery using a single platform TSA system at a minimum follow-up of 2 years. A total of 370 aTSA patients and 370 rTSA patients matched for age, sex, and length of follow-up from an international multi-institutional Western Institutional Review Board approved registry with a minimum 2-year follow-up were reviewed for this study. All patients had a diagnosis of OA, an intact rotator cuff, and no previous shoulder surgery. All patients were evaluated and scored preoperatively and at latest follow-up using six outcome scoring metrics and four active range of motion measurements. Mean follow-up was 41 months, and the mean age was 73 years. Preoperatively, the rTSA patients had lower outcome metrics and less motion. Postoperatively, aTSA and rTSA patients had similar clinical outcomes, motion, and function, with the only exception being greater external rotation in aTSA exceeding the minimal clinically important difference. Pain relief was excellent, and patient satisfaction was high in both groups. Humeral radiolucent lines were similar in both groups (8%). Complications were significantly higher with aTSA (aTSA = 4.9%; rTSA = 2.2%; P = 0.045), but revisions were similar (aTSA = 3.2%; rTSA = 1.4%; P = 0.086). At a mean of 41 month follow-up, primary aTSA and rTSA patients with OA and an intact rotator cuff with no previous history of shoulder surgery had similar clinical and radiographic outcomes. Greater external rotation was noted in aTSA patients at follow-up. However, aTSA patients had a significantly greater rate of complications compared with rTSA patients. rTSA is a viable treatment option in patients with an intact rotator cuff and no previous shoulder surgery, offering similar clinical outcomes with a lower complication rate. Level III.

Effect of 3-Dimensional, Virtual Reality Models for Surgical Planning of Robotic Prostatectomy on Trifecta Outcomes: A Randomized Clinical Trial.

Planning complex operations such as robotic-assisted radical prostatectomy requires surgeons to review 2-dimensional magnetic resonance imaging (MRI) cross-sectional images to understand 3-dimensional (3D), patient-specific anatomy. We sought to determine surgical outcomes for robotic-assisted radical prostatectomy when surgeons reviewed 3D, virtual reality (VR) models for operative planning. A multicenter, randomized, single-blind clinical trial was conducted from January 2019 to December 2020. Patients undergoing robotic-assisted laparoscopic radical prostatectomy were prospectively enrolled and randomized to either a control group undergoing usual preoperative planning with prostate biopsy results and MRI only or to an intervention group where MRI and biopsy results were supplemented with a 3D VR model. The primary outcome measure was margin status, and secondary outcomes were oncologic control, sexual function and urinary function. Ninety-two patients were analyzed, with trends toward lower positive margin rates (33% vs 25%) in the intervention group, no significant difference in functional outcomes and no difference in traditional operative metrics (p >0.05). Detectable postoperative prostate specific antigen was significantly lower in the intervention group (31% vs 9%, p=0.036). In 32% of intervention cases, the surgeons modified their operative plan based on the model. When this subset was compared to the control group, there was a strong trend toward increased bilateral nerve sparing (78% vs 92%), and a significantly lower rate of postoperative detectable prostate specific antigen in the intervention subset (31% vs 0%, p=0.038). This randomized clinical trial demonstrated patients whose surgical planning involved 3D VR models have better oncologic outcomes while maintaining functional outcomes.

Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations.

3535 Background: Approximately 20% of colorectal cancer (CRC) has an activating mutation in the PIK3CA oncogene. PIK3CA codes for the catalytic subunit of phosphoinositide 3-kinase alpha (PI3Kα), which ultimately activates the AKT and mammalian target of rapamycin (mTOR) pathway. The PI3Kα inhibitor alpelisib has been approved for breast cancer where a single PIK3CA activating mutation is sufficient for response. However, two activating mutations (multi-hit) in the PIK3CA allele substantially increases PI3Kα signaling compared to single hot spot mutations and results in exceptional response to PI3Kα inhibition. We aimed to identify the prevalence of PIK3CA multi-hit mutations in CRC to identify patients potentially susceptible to PI3K inhibitors. Methods: Tissue-based comprehensive genomic profiling (CGP) was performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified, CAP (College of American Pathologists)-accredited laboratory (Foundation Medicine Inc., Cambridge, MA, USA) on all-comers during the course of routine clinical care from 2013-2021. Approval was obtained from the Western Institutional Review Board (Protocol No. 20152817). Hybrid capture was carried out for at least 324 cancer-related genes, including PIK3CA. Results: We identified 48,836 patients with advanced CRC who underwent Foundation Medicine testing and 846 (1.7%) patients with multi-hit PIK3CA mutations. Additional clinical and molecular data was available for 41,154 of these patients of which 710 (1.7%) had multi-hit PIK3CA and 7627 (19%) had any deleterious PIK3CA mutation . The local colon tumor was used for sequencing in 70% of cases and a separate site in 30% of cases. Patients with PIK3CA multi-hit mutations were 53% male with a median age of 60 (interquartile range 50-70). The microsatellite status was available for 697 of 710 patients with multi-hit PIK3CA and 123/697 (18%) were microsatellite instability-high. The Table outlines the genes with cooccurring mutations of &gt;10% prevalence for multi-hit PIK3CA CRC, including the clinically relevant mutations in KRAS (65%) and BRAF (13%). The four most common PIK3CA variants were H1047R (9.8%), E545K (9.2%), E542K (9.0%) and R88Q (7.1%). The most common variant pair was E542K with E545K in 4.7% of multi-hit cases. Conclusions: Double-hit mutations in PIK3CA are seen in 1.7% of advanced CRC patients and may represent a subset of patients that may have enhanced sensitivity to PI3K inhibitors. Given the high prevalence of CRC in the United States and worldwide this represents a clinically meaningful prevalence of multi-hit PIK3CA. Future investigation on the clinical utility of PI3K inhibitors may be warranted in multi-hit PIK3CA CRC.[Table: see text]

Impact of methicillin‐resistant Staphylococcus aureus polymerase chain reaction nasal swabs on vancomycin utilisation in patients admitted to the intensive care unit with respiratory infections

AbstractBackgroundMethicillin‐resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) screening has a negative predictive value as high as 96% for pneumonia. Using nasal PCR, care providers can detect the presence or absence of MRSA earlier and potentially decrease the duration of vancomycin therapy in patients with negative results.AimsThe primary objective was to assess the impact of MRSA nasal PCR on vancomycin length of therapy in patients admitted to the intensive care unit (ICU) with respiratory infections.MethodsThis was a retrospective, quasi‐experimental, uncontrolled before—after study, comparing patients receiving screening versus those who did not. Patients over the age of 18, admitted to ICU with respiratory infections who received at least one dose of vancomycin were included in this study. This investigation received exemption from the South Nassau Communities Hospital and Western Institutional Review Board (reference number SNCH‐E14) and was conducted in accordance with the tenets espoused in the Declaration of Helsinki.ResultsA total of 77 patients, 22 in the study group and 55 in the comparator group were included in the analysis. There was a reduction in median length of vancomycin therapy in the MRSA PCR group compared to the unscreened group (1.7 days vs. 6 days, IQR: 4.15 vs. 4.8, p &lt; 0.001). There was a reduction in median vancomycin levels performed (3 levels vs. 1 level, p = 0.619).ConclusionsThe use of nasal PCR screening for MRSA was associated with a reduction in median vancomycin length of therapy for patients admitted to the ICU with respiratory infections.

Rise in Blood Pressure Observed Among US Adults During the COVID-19 Pandemic

Rise in Blood Pressure Observed Among US Adults During the COVID-19 Pandemic

Sars-Cov-2 Antibody Levels in Blood Cancer Patients after a Third Sars-Cov-2 “Booster” Vaccination - Observational Data from the LLS National Registry

Immunosuppressed patients may be at high risk for breakthrough COVID-19 infection despite SARS-CoV-2 vaccination, due to an inadequate or negligible antibody response. Based on data from the Leukemia & Lymphoma Society (LLS) National Registry, 25% of patients with hematologic malignancies do not produce anti-Spike protein antibodies in response to mRNA vaccines, with B-cell malignancy patients at highest risk (Greenberger et al, 2021, Cancer Cell, on-line). While studies of T-cell immunity, antibody cocktails, and booster vaccinations are underway, some patients have elected to receive an additional “booster” vaccination after a full course of SARS-CoV-2 vaccination. The LLS National Registry (NCT04794387) has collected Patient Reported Outcomes and serology from 3300 patients with hematologic malignancies. This study was approved by the Western Institutional Review Board, and participants provided informed consent electronically.As of July 2021, the Registry includes 24 patients who obtained a 3 rd vaccination after full vaccination with mRNA vaccines. Twenty of these patients were seronegative >14 days post 2 nd vaccination (as measured by the Roche Elecsys assay). Four patients had low positive serology results. All patients were nucleocapsid antibody negative.Patient ages ranged from 51-79 years. Eleven had chronic lymphocytic leukemia (CLL), 7 non-Hodgkin's lymphoma (NHL), 5 Waldenstrom's macroglobulinemia (WM), and 1 multiple myeloma (MM). Six patients were not currently on anti-B cell therapy, 11 had received anti-CD20 therapy (8 within the last 6 months), 6 had received Bruton's tyrosine kinase (BTK) inhibitors within the last 6 months, and 1 patient had recently received chemotherapy. The booster vaccinations were obtained between April and June 2021, 21 to 114 days after completing the initial vaccination series between January and April 2021. Serology was performed 12-61 days post-booster vaccination. Fifteen patients received a heterologous adenovirus vaccine. Four patients received a heterologous mRNA vaccine, 5 patients received a homologous mRNA vaccine. Descriptive results are shown on the following table.All patients (4) who had some level of antibody response to the initial vaccines had an augmented antibody response after a booster (i.e. sero-enhanced). Patients who had prior anti-CD20 often failed to seroconvert after booster vaccination. Only 2 of 8 patients who received anti-CD20 antibody treatment in the 6 months prior to vaccination seroconverted after booster vaccination. Two out of 3 seronegative patients receiving anti-CD20 therapy in the last 2 years (but > 6 months) seroconverted after the booster. One patient with follicular lymphoma who received anti-CD20 therapy in 2019 remained seronegative despite a prolonged duration without therapy. Of the 6 seronegative patients taking BTK inhibitors, 3 seroconverted after the booster. Two of the 3 remaining seronegative patients were taking concomitant anti-CD20 therapy. Of the 4 seronegative patients not currently taking anti-B cell therapy, 3 seroconverted while one patient who currently required intravenous immunoglobulin remained seronegative. A patient currently receiving chemotherapy also did not respond to a booster.In this limited set of patients there was no evident pattern of antibody response amongst patients who received homologous versus heterologous vaccine nor between disease types. While anti-CD20 therapy appeared to reduce antibody response to booster vaccination, there was substantial heterogeneity. Although many patients with B-cell malignancies did not mount a robust response to full mRNA vaccine series, several patients demonstrated an antibody response to the booster vaccination.Clinical trials are needed to further understand who can benefit from a booster strategy as well as define the safety of the approach. The LLS Registry includes collection of Electronic Health Records, which will allow us to more specifically evaluate timing and dosage of boosters, the influence of prior therapeutics, as well as health and safety outcomes to better guide patients and physicians through the COVID-19 pandemic. [Display omitted] DisclosuresNo relevant conflicts of interest to declare. OffLabel Disclosure:Booster vaccination (after full vaccination) using BNT162b2, mRNA-1273, or Ad26.COV2.S

An Intervention by and for Transgender Women Living With HIV: Study Protocol for a Two-Arm Randomized Controlled Trial Testing the Efficacy of "Healthy Divas" to Improve HIV Care Outcomes.

Introduction: Transgender women (assigned “male” at birth but who do not identify as male) are disproportionately impacted by HIV and experience unique barriers and facilitators to HIV care engagement. In formative work, we identified culturally specific and modifiable barriers to HIV treatment engagement among transgender women living with HIV (TWH), including prioritizing transition-related healthcare over HIV treatment, avoiding HIV care settings due to gender-related and HIV stigma, concerns about potential drug interactions with hormones, and inadequate social support. Grounded in the investigators' Models of Gender Affirmation and Health Care Empowerment, we developed the Healthy Divas intervention to optimize engagement in HIV care among TWH at risk for treatment failure and consequential morbidity, mortality, and onward transmission of HIV.Methods and Analysis: We conducted a 2-arm randomized controlled trial (RCT) of the intervention's efficacy in Los Angeles and San Francisco to improve engagement in care among TWH (N = 278). The primary outcome was virologic control indicated by undetectable HIV-1 level (undetectability = < 20 copies/mL), at baseline and follow-up assessment for 12 months at 3-month intervals.Ethics and Dissemination: This study was approved by University of California, San Francisco Institutional Review Board (15-17910) and Western Institutional Review Board (20181370). Participants provided informed consent before enrolment in the study. We are committed to collaboration with National Institutes of Health officials, other researchers, and health and social services communities for rapid dissemination of data and sharing of materials. The results will be published in peer-reviewed academic journals and scientific presentations. We will make our results available to researchers interested in transgender health to avoid unintentional duplication of research, as well as to others in health and social services communities, including HIV clinics, LGBT community-based organizations, and AIDS service organizations.Clinical Trial Registration: Clinicaltrials.gov, identifier NCT03081559.

COVID-19 Vaccination Is Safe and Effective in Patients With Inflammatory Bowel Disease: Analysis of a Large Multi-institutional Research Network in the United States

COVID-19 Vaccination Is Safe and Effective in Patients With Inflammatory Bowel Disease: Analysis of a Large Multi-institutional Research Network in the United States

18. SOSHI-APE: Sources of Sexual Health Information for Adolescents and Preferences for Education

<h3>Background</h3> Adolescents may receive information about sexual health topics from a variety of different sources, such as school, family, healthcare professionals, peers, and media sources such as television, books, and the internet. Despite this variety, there is little information on where adolescents actually do receive information on these topics. The objective of this study was to identify the sources from which adolescents receive information about sexual health topics, how useful they find this information, and their preferred sources for education. <h3>Methods</h3> We conducted a survey of adolescents aged 14-21 about the sources from which they received sexual health information. Adolescents were recruited through online and in-person advertising at an adolescent-specific obstetrics and gynecology clinic. Descriptive statistics were calculated using Statistical Package for the Social Sciences (SPSS) v25.0. This study was approved by the Western Institutional Review Board #2017-030. <h3>Results</h3> The survey was completed by 196 adolescents. The average age of respondents was 16.0 years, 82.1% identified as female, and respondents were racially diverse (Table 1). School was the most common source of information on almost all sexual health topics: STIs (67.9%), condoms (50.5%), sex (40.8%), consent (40.3%), abortion (34.7%), pregnancy (33.7%), and birth control (32.7%), with the exception of lesbian, gay, bisexual, transgender, and queer (LGBTQ) issues, which respondents most commonly learned about from friends (24.5%). Parents and friends were also reported as highly common sources of sexual health information (Figure 1). Information about sex was much less commonly obtained from media sources, although the internet was one of the main sources of information about LGBTQ issues (10.2%) and abortion (9.7%). Across all topics, respondents rated the information that they received to be somewhat or very useful (75-85.7%). The main sources from which respondents would have preferred to receive information were school, healthcare professionals, or parents, with the exception of LGBTQ issues, which they would have preferred to learn about from school, parents, or friends. <h3>Conclusions</h3> The results of this descriptive study suggest that adolescents receive most of their information about sexual health from school, parents, or friends, with the exception of LGBTQ issues and abortion. The accuracy of information from family, friends, and the internet may vary and adolescents should be made aware of this. Although healthcare professionals were an uncommon source of sexual health information, respondents identified them as one of their main preferred sources. These findings indicate a need for more education on sexual health topics during healthcare encounters.

Impact of the Coronavirus Disease 2019 Pandemic on Gastrointestinal Procedures and Cancers in the United States: A Multicenter Research Network Study

Impact of the Coronavirus Disease 2019 Pandemic on Gastrointestinal Procedures and Cancers in the United States: A Multicenter Research Network Study

The Association of Long-term Macrolide Therapy and Nontuberculous Mycobacterial Culture Positivity in Patients With Bronchiectasis

The Association of Long-term Macrolide Therapy and Nontuberculous Mycobacterial Culture Positivity in Patients With Bronchiectasis

The Opioid Epidemic Within the COVID-19 Pandemic: Drug Testing in 2020.

The convergence of the opioid epidemic and the coronavirus disease 2019 (COVID-19) pandemic has created new health care challenges. The authors analyzed changes in clinical drug testing patterns and results at a national clinical laboratory, comparing data obtained before and during the pandemic. Testing for prescription and illicit drugs declined rapidly during the pandemic, with weekly test volumes falling by approximately 70% from the baseline period to the trough (the week beginning March 29) before rising in subsequent weeks. Among individuals tested, positivity increased by 35% for non-prescribed fentanyl and 44% for heroin during the pandemic. Positivity for non-prescribed fentanyl increased significantly among patients positive for other drugs: by 89% for specimens positive for amphetamines; 48% for benzodiazepines; 34% for cocaine; and 39% for opiates (P < 0.01 for all comparisons). These findings suggest significant increases in dangerous drug combinations. Positivity for non-prescribed use of many other drugs remained consistent or declined for some drugs, relative to pre-pandemic patterns. Models adjusting for potential confounding variables, including medication-assisted treatment and treatment at a substance use disorder facility indicated that the risk for non-prescribed fentanyl positivity rose by more than 50% during the pandemic. In summary, these findings demonstrate decreased drug testing overall, with increased positivity for high-risk drugs and dangerous drug combinations. The convergence of the drug abuse epidemic and COVID-19 pandemic has led to an increased need for health care and public health resources dedicated to supporting vulnerable patients and addressing the underlying causes of these disturbing trends.

Self-Administered Behavioral Skills-Based At-Home Virtual Reality Therapy for Chronic Low Back Pain: Protocol for a Randomized Controlled Trial.

BackgroundChronic pain is one of the most common and debilitating health conditions. Treatments for chronic low back pain typically focus on biomedical treatment approaches. While psychosocial treatments exist, multiple barriers prevent broad access. There is a significant unmet need for integrative, easily accessible, non-opioid solutions for chronic pain. Virtual reality (VR) is an immersive technology allowing innovation in the delivery of behavioral pain treatments. Behavioral skills-based VR is effective at facilitating pain management and reducing pain-related concerns. Continued research on these emerging approaches is needed.ObjectiveIn this randomized controlled trial, we seek to test the efficacy of a self-administered behavioral skills-based VR program as a nonpharmacological home-based pain management treatment for people with chronic low back pain (cLBP).MethodsWe will randomize 180 individuals with cLBP to 1 of 2 VR programs: (1) EaseVRx (8-week skills-based VR program); or (2) Sham VR (control condition). All participants will receive a VR headset to minimize any biases related to the technology’s novelty. The Sham VR group had 2D neutral content in a 3D theater-like environment. Our primary outcome is average pain intensity and pain-related interference with activity, stress, mood, and sleep. Our secondary outcomes include patient-reported physical function, sleep disturbance, pain self-efficacy, pain catastrophizing, pain acceptance, health utilization, medication use, and user satisfaction. We hypothesize superiority for the skills-based VR program in all of these measures compared to the control condition. Team statisticians blinded to treatment assignment will assess outcomes up to 6 months posttreatment using an approach suitable for the longitudinal nature of the data.ResultsThe study was approved by the Western Institutional Review Board on July 2, 2020. The protocol (NCT04415177) was registered on May 27, 2020. Recruitment for this study was completed in July 2020, and data collection will remain active until March 2021. In total, 186 participants were recruited. Multiple manuscripts will be generated from this study. The primary manuscript will be submitted for publication in the winter of 2020.ConclusionsEffectively delivering behavioral treatments in VR could overcome barriers to care and provide scalable solutions to chronic pain’s societal burden. Our study could help shape future research and development of these innovative approaches.Trial RegistrationClinicalTrials.gov NCT04415177; https://clinicaltrials.gov/ct2/show/NCT04415177International Registered Report Identifier (IRRID)RR1-10.2196/25291

Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial

Background: Treatment options for outpatients with COVID-19 could reduce morbidity and prevent SARS-CoV-2 transmission.Methods: In this randomized, double-blind, three-arm (1:1:1) placebo-equivalent control trial conducted remotely throughout the United States, adult outpatients with laboratory-confirmed SARS-CoV-2 infection were recruited. Participants were randomly assigned to receive HCQ (400mg BID x1day, followed by 200mg BID x9days) or placebo-equivalent (ascorbic acid) and AZ (500mg, then 250mg daily x4days) or placebo-equivalent (folic acid), stratified by risk for progression to severe COVID-19 (high-risk vs. low-risk). Self-collected mid-turbinate nasal swabs for SARS-CoV-2 PCR, FLUPro symptom surveys, EKGs and vital signs collected daily. Primary endpoints were: (a) 14-day progression to lower respiratory tract infection (LRTI), 28-day COVID-19 related hospitalization, or death; (b) 14-day time to viral clearance; secondary endpoints included time to symptom resolution (ClinicalTrials.gov: NCT04354428). Due to the low rate of clinical outcomes, the study was terminated for operational futility.Findings: Between 15th April and 27th July 2020, 231 participants were enrolled and 219 initiated medication a median of 5.9 days after symptom onset. Incident LRTI occurred in six participants (two control, four HCQ/AZ) and COVID-19 related hospitalization in nine (four control, two HCQ, three HCQ/AZ). There were no deaths. Median time to clearance was 5 days (95% CI=4-6) in HCQ, 6 days (95% CI=4-8) in HCQ/AZ, and 8 days (95% CI=6-10) in control. HCQ but not HCQ/AZ had faster time to viral clearance (HR=1.62, 95% CI=1.01-2.60, p=0.047 & HR=1.25, 95% CI=0.75-2.07, p=0.39) compared to control. Among 197 participants who met the COVID-19 definition at enrollment, time to symptom resolution did not differ by group.Interpretation: Neither HCQ nor HCQ/AZ shortened the clinical course of outpatients with COVID-19, and HCQ, but not HCQ/AZ, had only a modest effect on SARS-CoV-2 viral shedding. HCQ and HCQ/AZ are not effective therapies for outpatient treatment of SARV-CoV-2 infection.Trial Registration Number: ClinicalTrials.gov: NCT04354428Funding: The COVID-19 Early Treatment Study was funded by the Bill & Melinda Gates Foundation (INV-017062) through the COVID-19 Therapeutics Accelerator. University of Washington Institute of Translational Health Science (ITHS) grant support (UL1 TR002319), KL2 TR002317, and TL1 TR002318 from NCATS/NIH funded REDCap. The content is solely the responsibility of the authors and does not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated. PAN and MJA were supported by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program. Conflict of Interest: Declaration of interests: CJ reports grants from BMGF for conduct of the study, and grants from CDC and NIH outside of the submitted work. HSK reports funding from NIH. PAN and MJA have a potential financial relationship with AliveCor related to QT assessment using the device, however the investigators would receive no financial benefit for use of the technology for patients at Mayo Clinic or for its use in the current study. AB reports consulting for Gates Ventures and grants from BMGF and NIH outside of the submitted work. HYC reports consulting for BMGF, Pfizer, Ellume, and Merck, and grants from Gates Ventures, NIH, CDC, BMGF, DARPA, Apple Inc., Sanofi-Pasteur, and Roche-Genentech, outside of the submitted work. Ethical Approval: Study visits were conducted via Health Insurance Portability and Accountability Act (HIPAA)-compliant telemedicine. The Western Institutional Review Board (WIRB) approved this study with reliance agreements with collaborating institutions.