Pragmatic implementation science to assess lipid optimization in peripheral artery disease: Design and conduct of the randomized optimize PAD-1 trial

Background: Underutilization of proven therapies in peripheral artery disease (PAD) remains a critical problem. Implementation science aims to improve this, but few trials exist. We describe a randomized trial designed with pragmatic elements in PAD patients. Method(s): OPTIMIZE PAD-1 was designed to evaluate the efficacy of a multidisciplinary vascular care team using an intensive lipid reduction program in PAD patients versus usual care. The primary endpoint is low density lipoprotein-cholesterol (LDL-C) reduction at 12 months. A second objective is to assess the impact of a structured quality assurance program (EQuIP) on variability in 6-minute walk test (6MWT) distance. Due to COVID-19, pragmatic aspects were introduced, including virtual consent/recruitment, home-based subject conducted lab testing, and virtually monitored homebased 6MWT. Result(s): A total of 114 subjects with PAD were recruited over ~18 months at the University of Colorado and randomized to algorithm-driven lipid management by a multidisciplinary vascular care team with pharmacist support or to usual care (Figure). Subjects were also randomized to 6MWT conducted by site versus EQuIP staff. Potential participants and clinical events during follow up were identified via electronic medical records. Adjustments to enable remote study conduct were successfully implemented. Conclusion(s): Pragmatic randomized trials in PAD patients are feasible to strengthen implementation science.

Humoral and T- cell response to multiple COVID-19 booster vaccinations in people with MS

Introduction: People with multiple sclerosis (PwMS) treated with anti-CD20 therapies and fingolimod are less likely to successfully produce a humoral response to COVID-19 vaccines 1 and 2. Objective(s): To measure the humoral and/or cellular response to COVID-19 booster vaccinations in a cohort of PwMS who were previously seronegative after their initial COVID vaccine course. Aim(s): To determine whether there is a benefit of COVID-19 booster vaccinations for people with MS who are known to have had an attenuated response to initial vaccines. Method(s): We studied a cohort of PwMS all of whom were seronegative for anti-SARS-CoV-2 spike protein IgG after the 1st and 2nd COVID-19 vaccines, including PwMS treated with ocrelizumab (n=53), fingolimod (n=15), other DMTs (n=9) and no DMT (n=2). Dried blood spot +/- whole blood samples were obtained from participants at 2-8 weeks after their 3rd (n=79) and 4th (n=40) COVID-19 vaccines. Samples were used to measure anti-SARS-CoV-2 spike protein IgG (ELISA) and T-cell response (IFN-g release assay measured on whole blood). Result(s): Overall 27/79 (34%) who were seronegative after COVID vaccine 2 seroconverted after vaccine 3. Seroconversion rates were 17% for PwMS treated with ocrelizumab, 47% for fingolimod and 100% for other DMTs. A further 2/30 (7%) of those who remained seronegative after vaccine 3 seroconverted after vaccine 4. Anti-SARS-CoV-2 T-cell responses were measurable in 26/40 (65%) after vaccine 3 and 13/19 (68%) after vaccine 4 but were conspicuously absent in people treated with fingolimod. Overall, 75% of participants showed either humoral or cellular response after receiving 4 COVID vaccinations. PwMS with laboratory evidence of prior COVID-19 infection had higher measurable T-cell responses. Conclusion(s): Booster vaccinations for COVID-19 are associated with incremental benefits in measurable immunity in those with attenuated responses to the initial vaccine course. Overall, three quarters of those who were seronegative after COVID vaccines 1 & 2 had a measurable immune response after COVID vaccine 4. This data supports the use of booster vaccinations in pwMS at risk of attenuated vaccine response.

Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Shedding and Predictors of Viral Culture Positivity on Vaccinated Healthcare Workers With Mild Coronavirus Disease 2019.

In this prospective cohort of 30 vaccinated healthcare workers with mild Omicron variant infection, we evaluated viral culture, rapid antigen test (RAT), and real-time reverse-transcription polymerase chain reaction (RT-PCR) of respiratory samples at days 5, 7, 10, and 14. Viral culture was positive in 46% (11/24) and 20% (6/30) of samples at days 5 and 7, respectively. RAT and RT-PCR (Ct ≤35) showed 100% negative predictive value (NPV), with positive predictive values (PPVs) of 32% and 17%, respectively, for predicting viral culture positivity. A lower RT-PCR threshold (Ct ≤24) improved culture prediction (PPV = 39%; NPV = 100%). Vaccinated persons with mild Omicron infection are potentially transmissible up to day 7. RAT and RT-PCR might be useful tools for shortening the isolation period.

Tetraplegia following intervention for a massive pulmonary embolism months after severe COVID-19 pneumonia

Context: Hypercoagulability is a known phenomenon during acute COVID-19 infection. Studies have demonstrated higher levels of d-dimer, fibrinogen, and fibrinogen degradation products. Also evidence of vascular endothelial damage associated with this infection. Finding(s): 59 y/o man with new C5 complete tetraplegia admitted to rehab 9 months after acute SARs CoV-2 pneumonia. He required hospitalization, but recovered after a couple of weeks, ultimately returning to work. However, 6 months later he started having episodes of dizziness. He presented emergently 7 months later with severe dyspnea and chest tightness. He was diagnosed with a massive saddle pneumonia embolism, source: left femoral, popliteal, and tibial deep venous thrombosis. Treatment included tissue plasminogen activator (TPA) intervention and 2 days later experienced acute onset of lower extremity weakness. Imaging revealed a C2-T11 epidural hematoma with cord compression. Conclusion/Clinical Relevance: Post covid-19 disease syndrome(s), such as long haulers, have prolonged symptoms for months. Therefore, Covid-19 disease could be associated with a prolonged hypercoagulable state in some cases. Research data reporting the rates of thrombosis after acute infection are limited. This case stands out because the patient had no risk factors for VTE besides his age. He was a thin, nonsmoker, not acutely ill, active, working fulltime in a non-sedentary occupation, and had no previous personal nor family history for VTE. In regard to post rehab disposition the patient's wife was identified as the anticipated caregiver, however she never fully recovered and the patient was discharged to a skilled nursing facility.

Multiple sclerosis and COVID-19: Assessing risk perception, patient behaviors and access to disease-modifying therapies.

BACKGROUND: Following the outbreak of COVID-19, global healthcare systems have had to rapidly adapt. People with multiple sclerosis (pwMS) were required to make decisions about their individual risk and consequent work and social behaviors. This study aimed to evaluate risk perception and patterns of shielding behavior amongst pwMS at the onset of the COVID-19 pandemic and the subsequent impact on patients' employment and access to disease modifying therapies (DMTs). METHODS: Postal surveys were sent to 1690 people within a UK population-based MS cohort during the first wave of the COVID-19 pandemic. Patients were surveyed on: (i) perceived vulnerability to COVID-19; (ii) isolation behavior; (iii) interruption to DMT; (iv) employment status; (v) level of satisfaction with their current working arrangement. RESULTS: Responses were received from 1000 pwMS. Two thirds of patients reported isolating at home during the first wave of the pandemic. This behavior was associated with increased age (p<0.0001), higher disability (p<0.0001) and use of high-efficacy DMTs (p = 0.02). The majority of patients reported feeling vulnerable (82%) with perceived vulnerability associated with higher EDSS (p<0.0001) and receiving a high-efficacy DMT (p = 0.04). Clinician-defined risk was associated with shielding behavior, with those at high-risk more likely to self-isolate/shield (p<0.0001). Patients on high-efficacy DMTs were more likely to have an interruption to their treatment (50%) during the first wave of the pandemic. Most pwMS experienced a change to their working environment, and most were satisfied with the adjustments. CONCLUSION: This study highlights the risk perception, social behavioral practices and changes to treatment experienced by pwMS during the first wave of the COVID-19 pandemic in a large, well-described UK cohort. The results may help inform management of pwMS during future pandemic waves.

CARACTERIZAÇÃO DA INFECTIVIDADE DA VARIANTE ÔMICRON E PREDITORES DE POSITIVIDADE DE CULTURA VIRAL EM PROFISSIONAIS DE SAÚDE COM COVID-19 LEVE

Introdução A variante Ômicron do vírus SARS-CoV-2 (B.1.1.529) foi designada uma variante preocupante (VOC) devido à alta transmissibilidade e capacidade de escapar da imunidade natural e induzida por vacina. Objetivo Caracterizar a duração da infectividade da variante Ômicron em indivíduos vacinados com sintomas leves de COVID-19. Método Estudo transversal com 30 indivíduos vacinados com COVID-19 para avaliar a duração da infectividade da Ômicron comparando o isolamento viral com o teste rápido de antígeno (RAT) e os valores de Ct da reação em cadeia da polimerase em tempo real (RT-PCR) de amostras respiratórias nos dias 5, 7, 10 e 14 a partir do início dos sintomas. Resultados O crescimento viral foi observado em 46% (11/24) das amostras dos indivíduos vacinados no dia 5 dos sintomas e 20% (6/30) no dia 7, nenhuma amostra teve isolamento viral no dia 10. A carga de RNA viral permaneceu detectável em 97% (29/30) e 57% (17/30) dos participantes nos dias 10 e 14, respectivamente. Entre as amostras com isolamento viral, todas (n = 17) foram RAT e RT-PCR positivas. Por outro lado, amostras sem isolamento viral (n = 97) foram RAT e RT-PCR positivas em 36 (37%) e 83 (86%), respectivamente. RAT e RT-PCR evidenciaram sensibilidade global e valores preditivos negativos de 100%, porém, RAT apresentou 63% de especificidade global e 32% de valor preditivo positivo (VPP), enquanto RT-PCR evidenciou menor especificidade (14%) e VPP (17%) para predizer a infectividade. Conclusão Indivíduos vacinados imunocompetentes com infecção por Ômicron ainda podem transmitir o vírus no 7° dia de sintomas, portanto, é altamente improvável que estejam transmitindo o vírus infeccioso no dia 10. Testes rápidos de antígeno podem ser usados para estimar a duração da infectividade dos casos de Ômicron. Ag. Financiadora Instituto todos pela saúde do Banco Itaú.

The Impact of Pandemic Management Strategies on Staff Mental Health, Work Behaviours, and Resident Care in One Long-Term Care Facility in British Columbia: A Mixed Method Study

Context: To slow the spread of COVID-19 within the Canadian long-term residential care (LTRC) sector, a series of pandemic management strategies were introduced, including restricted visitation and single site employment. These strategies were enacted to prevent and control infection, resulting in unknown impact on direct care staff and staff capacity to deliver quality care or service. Objective: To explore staff reports of outcomes associated with LTRC pandemic management strategies, particularly their impact on LTRC staff mental health, work behaviours and quality of care or service provision. Method: This was a case study using mixed methods including a longitudinal survey and interviews with staff from one LTRC site in British Columbia. Survey data from 68 staff who participated in both survey times were analyzed using regressions with relative weight analysis. Semi-structured interviews were conducted with 26 LTRC staff and analyzed using content analysis. Findings: Survey data demonstrated that staff perceived the sick time policy and staffing levels as the most inadequate pandemic management strategies. Survey data also showed the visitation policy, the sick time policy and the single site employment policy were most significantly associated with negative outcomes to staff mental health, work behaviours and quality of care or service delivery. Qualitative data suggested connections between these policies and inadequate staffing levels and heavy workloads. Limitations: The study design along with the low response rate and the small sample size limits the generalizability of the findings to other settings. Implications: The development and implementation of pandemic management strategies must be informed by and give consideration to working conditions of LTRC staff including long standing systemic issues such as staffing shortages and heavy workloads. © 2022 The Author(s).

An international, interlaboratory ring trial confirms the feasibility of an extraction-less "direct" RT-qPCR method for reliable detection of SARS-CoV-2 RNA in clinical samples.

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is used worldwide to test and trace the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). "Extraction-less" or "direct" real time-reverse transcription polymerase chain reaction (RT-PCR) is a transparent and accessible qualitative method for SARS-CoV-2 detection from nasopharyngeal or oral pharyngeal samples with the potential to generate actionable data more quickly, at a lower cost, and with fewer experimental resources than full RT-qPCR. This study engaged 10 global testing sites, including laboratories currently experiencing testing limitations due to reagent or equipment shortages, in an international interlaboratory ring trial. Participating laboratories were provided a common protocol, common reagents, aliquots of identical pooled clinical samples, and purified nucleic acids and used their existing in-house equipment. We observed 100% concordance across laboratories in the correct identification of all positive and negative samples, with highly similar cycle threshold values. The test also performed well when applied to locally collected patient nasopharyngeal samples, provided the viral transport media did not contain charcoal or guanidine, both of which appeared to potently inhibit the RT-PCR reaction. Our results suggest that direct RT-PCR assay methods can be clearly translated across sites utilizing readily available equipment and expertise and are thus a feasible option for more efficient COVID-19 coronavirus disease testing as demanded by the continuing pandemic.

113 The invaluable introduction of a cancer care coordinator into the lung cancer team

Introduction: The Trust successfully applied for funding for a temporary cancer care co-ordinator post from the cancer alliance. The role adapted over the 9 month secondment to best meet the needs of the service. Methods: This post has developed to become part admin and part nursing support. Admin tasks include: the tracking of patients throughout their pathway;pre-booking of oncology slots to speed up the patient pathway;adding alerts to patient's electronic records so that they are flagged to the lung cancer nursing team if they present to hospital as an emergency. Our cancer care co-ordinator offers holistic needs assessments (HNA) for all patients newly diagnosed with lung cancer or mesothelioma. As her confidence and competence has grown, this has expanded such that she now offers HNAs at multiple points throughout the pathway. In addition to this she answers telephone calls, refers on as appropriate and has helped maintain the support group during the COVID pandemic. Results: The number of holistic needs completed have increased 8-fold since the post commenced with further expansion of the service happening currently. By taking on some of the admin roles previously completed by the LCNS, the nursing team have been able to expand their nurse-led clinics. This role has also increased the capacity of the whole team to support patients living with and beyond cancer. Tracking of patients has meant that we have a more robust system of following patients through the pathway, ensuring timely appointments and treatment and preventing patients being lost to follow-up. This has enhanced patient care and patient feedback has been good. Conclusion: The impact this role has made to the lung cancer service is invaluable and has enabled improvements to our service to be made. The process of making this a substantive post within our Trust is underway. Disclosure: No significant relationships.

Performance of at-home self-collected saliva and nasal-oropharyngeal swabs in the surveillance of COVID-19.

Background: SARS-CoV-2 quickly spreads in the worldwide population, imposing social restrictions to control the infection, being the massive testing another essential strategy to break the chain of transmission. Aim: To compare the performance of at-home self-collected samples - saliva and combined nasal-oropharyngeal swabs (NOP) - for SARS-CoV-2 detection in a telemedicine platform for COVID-19 surveillance. Material and methods: We analyzed 201 patients who met the criteria of suspected COVID-19. NOP sampling was combined (nostrils and oropharynx) and saliva collected using a cotton pad device. Detection of SARS-COV-2 was performed by using the Altona RealStar® SARS-CoV-2 RT-PCR Kit 1.0.  Results: There was an overall significant agreement (κ coefficient value of 0.58) between saliva and NOP. Considering results in either sample, 70 patients positive for SARS-CoV-2 were identified, with 52/70 being positive in NOP and 55/70 in saliva. This corresponds to sensitivities of 74.2% (95% CI; 63.7% to 83.1%) for NOP and 78.6% (95% CI; 67.6% to 86.6%) for saliva. Conclusion: Our data show the feasibility of using at-home self-collected samples (especially saliva), as an adequate alternative for SARS-CoV-2 detection. This new approach of testing can be useful to develop strategies for COVID-19 surveillance and for guiding public health decisions.

SARS-CoV-2 in a stream running through an underprivileged, underserved, urban settlement in São Paulo, Brazil: A 7-month follow-up.

COVID-19 pandemic has led to concerns on the circulation of SARS-CoV-2 in the environment, its infectivity from the environment and, the relevance of transmission via environmental compartments. During 31 weeks, water samples were collected from a heavily contaminated stream going through an urban, underprivileged community without sewage collection. Our results showed a statistically significant correlation between cases of COVID-19 and SARS in the community, and SARS-CoV-2 concentrations in the water. Based on the model, if the concentrations of SARS-CoV-RNA (N1 and N2 target regions) increase 10 times, there is an expected increase of 104% [95%CI: (62-157%)] and 92% [95%CI: (51-143%)], respectively, in the number of cases of COVID-19 and SARS. We believe that differences in concentration of the virus in the environment reflect the epidemiological status in the community, which may be important information for surveillance and controlling dissemination in areas with vulnerable populations and poor sanitation. None of the samples were found infectious based cultures. Our results may be applicable globally as similar communities exist worldwide.

Torquetenovirus in saliva: A potential biomarker for SARS-CoV-2 infection?

Torquetenovirus (TTV) is present in biological fluids from healthy individuals and measurement of its titer is used to assess immune status in individuals with chronic infections and after transplants. We assessed if the titer of TTV in saliva varied with the presence of SARS-CoV-2 in the nasopharynx and could be a marker of COVID-19 status. Saliva from 91 individuals positive for SARS-CoV-2 in nasal-oropharyngeal samples, and from 126 individuals who were SARS-CoV-2-negative, all with mild respiratory symptoms, were analyzed. Both groups were similar in age, gender, symptom duration and time after symptom initiation when saliva was collected. Titers of TTV and SARS-CoV-2 were assessed by gene amplification. Loss of smell (p = 0.0001) and fever (p = 0.0186) were more prevalent in SARS-CoV-2-positive individuals, while sore throat (p = 0.0001), fatigue (p = 0.0037) and diarrhea (p = 0.0475) were more frequent in the SARS-CoV-2 negative group. The saliva TTV and nasal-oropharyngeal SARS-CoV-2 titers were correlated (p = 0.0085). The TTV level decreased as symptoms resolved in the SARS-CoV-2 infected group (p = 0.0285) but remained unchanged in the SARS-CoV-2 negative controls. In SARS-CoV-2 positive subjects who provided 2-4 saliva samples and in which TTV was initially present, the TTV titer always decreased over time as symptoms resolved. We propose that sequential TTV measurement in saliva is potentially useful to assess the likelihood of symptom resolution in SARS-CoV-2-positive individuals and to predict prognosis.

An international, inter-laboratory ring trial confirms the feasibility of an open source, extraction-less "direct" RT-qPCR method for reliable detection of SARS-CoV-2 RNA in clinical samples (preprint)

RT-qPCR is used world-wide to test and trace the spread of SARS-CoV-2. Extraction-less or direct RT-PCR is an open-access qualitative method for SARS-CoV-2 detection from nasopharyngeal (NP) or oral pharyngeal (OP) samples with the potential to generate actionable data more quickly, at a lower cost, and with fewer experimental resources than full RT-qPCR. This study engaged ten global testing sites, including laboratories currently experiencing testing limitations due to reagent or equipment shortages, in an international inter-laboratory ring trial. Participating labs were provided a common protocol, common reagents, aliquots of identical pooled clinical samples and purified nucleic acids, and used their existing in-house equipment. We observed 100% concordance across labs in the correct identification of all positive and negative samples, with highly similar Ct values observed. The test also performed well when applied to locally collected patient NP samples, provided the viral transport media did not contain charcoal or guanidine, both of which appeared to potently inhibit the RT-PCR reaction. Our results suggest that open access, direct RT-PCR assays are a feasible option for more efficient COVID-19 testing as demanded by the continuing pandemic.

Saliva as a Reliable Sample for COVID-19 Diagnosis in Paediatric Patients (preprint)

Saliva has been described a less invasive and easy to handle sample, compared to nasopharyngeal swabs (NPS), in the diagnosis of COVID-19 in adults. Although the advantages of using saliva is still more evident in paediatric patients, little is now about its sensitivity in this group. The aim of this study was to compare the performance of saliva to that of NPS in the detection of SARS-CoV-2 in paediatric patients with mild symptoms. This study evaluated saliva samples from children with suspected COVID-19 who attended public healthcare services of Araraquara, Sao Paulo, Brazil. Children were asked to spit into a sterile container for collection of about 1ml of saliva after the NPS collection. SARS-COV-2 detection was performed by using the Altona RealStar(R) SARS-CoV-2 RT-PCR Kit 1.0. The sample consisted of 50 patients, in which 27 were girls (54%) and 23 were boys (46%). Ten were positive for SARS-CoV-2 in at least one sample collected. The mean age was 10.24 {+/-} 3.52 years old and saliva was collected after 4.76 {+/-} 1.31 days from the symptoms. Saliva and NPS have showed the same performance in the SARS-CoV-2 detection (k = 0.865, P < 0.001). In conclusion, saliva is a reliable alternative sample for COVID-19 diagnosis in paediatric population.

Supporting small languages together: The history and impact of the International Conference on Language Documentation (Formula presented) Conservation series

The International Conference on Language Documentation (Formula presented) Conservation series, or ICLDC, has, since its inception in 2009, become the flagship conference for the field of language documentation. Every two years, conference attendees gather at the University of Hawai‘i at Mānoa to share their experiences working on diverse topics related to the preservation of underrepresented languages worldwide. Attendees come from a range of backgrounds: Indigenous language communities, language activism organizations, K–12 school systems, as well as students and faculty from colleges and universities. They represent dozens of countries and hundreds of languages, and they have one goal in mind: supporting small languages together. In this paper, we trace the history of the ICLDC series since the first iteration and discuss the scope of its impact on the field of language documentation and conservation according to conference attendees. We also look ahead to the changes that the covid-19 pandemic will bring to the structure of the conference in 2021 and beyond. © 2020. All Rights Reserved.

Implementation of multidisciplinary telehealth CF clinics

Background: The COVID-19 pandemic entered the USA in early 2020. As of March 16, our local CF infrastructure came to a complete halt. Clinic cancellations, minimum staff coverage, and stay-at-home recommendations were enacted. The CF center decreased from 25 clinic visits per week to 4 or less. Two significant barriers to implementing telehealth management occurred: 1) absence of institutional telehealth infrastructure;and 2) hybrid nature of the CF center team with university faculty and hospital staff, resulting in the adoption of different pandemic work and management schedules. Consequently, the CF team had to test and implement a viable and effective telehealth model to maintain adequate patient management. The SMART Aim was to implement a meaningful, remote, multidisciplinary care management for people with CF from 0% to 80% by May 31, 2020. Methods: Using the Model for Improvement, the ambulatory in-person care process was adapted for telehealth visits. The team focused on minimizing gaps in communication and information sharing to address reduced working schedules and difficulties in accessing medical information from home. The team utilized plan-do-study-act cycles to test and adapt pre-visit planning (PVP), preparation of patient/family (P/F), visit note sharing, testing of off-the-shelf remote communication tools, including texting (iOS and Android messaging, WhatsApp, etc), and video apps (Google's Duo & Meet, FaceTime, Zoom, Doxy.me, Spike, and Jitsi Meet). Data collection included the number of scheduled visits, visits converted to telehealth, pre-visit contacts, completed visits, reschedules, “no answers,” and telehealth visits carried out with single (provider only) or with multiple members of the team. We used an informal survey to assess staff satisfaction and an email survey to determine P/F satisfaction. Results: Changes in processes occurred using rapid-cycle testing. PVP allowed the team to coproduce P/F preference for contact and specific instructions about the upcoming telehealth visit. Having the MD make the call first allowed the ability to control and proceed with the visit by phone or video-based (offered on diverse formats) with direct feedback from the P/F. The use of group messaging during the telehealth visit helped the team with patient management. The sequential discipline calls increased the likelihood of connecting with the P/F. Barriers for P/F included limited broadband access, limited knowledge of video app solutions, and lack of cellular service. Team's obstacles included limited availability (reduced staffing) and institutional restrictions on working from home. Since adopting the MD telephone/video visit method with team participation via group messaging and calling P/F sequentially, team participation reached 89%. Staff satisfaction was reported as positive. P/F survey indicated 100% agreed it was not a burden to receive multiple calls, and 100% agreed it was helpful to speak to other CF team members during the call period. Conclusions: A multidisciplinary telehealth visit process was tested, adapted, and found to meet patients' and team members' needs. Institutional barriers can be overcome by brainstorming and testing new ideas. Future steps include assessing reliability and gaps in management and outcomes.