RECOMMENDATIONS ON HANDLING MEDICINE SHORTAGE: LEARNING FROM HYDROXYCHLOROQUINE 2020 CRISIS FOR SLE PATIENTS

BackgroundEarly 2020, short supply of hydroxychloroquine sulfate (HCQ) – then claimed as effective for treatment of COVID-19 in several countries - raised significant concerns for those who use HCQ for chronic diseases including SLE. In April 2020, Lupus Europe launched a survey to quantify the access gap, as well as the anxiety expressed by patients confronted with this outage. 2422 patients responded with an average level of anxiety about access to HcQ of 6.45 on a maximum of 10. After supply issues were resolved, a follow up survey (Aug-Sept 2020 – 1854 answers) showed a significantly reduced anxiety of 4.15. A second follow up survey (Nov 2021 -Feb 2022 - 2255 answers) showed a further reduction to 3.54. Importantly, a core group of 6.2-13.7% of patients remains extremely anxious (scoring 9 or 10) about supply of their medication, substantially more than in Portugal (3.5%) and Finland (0%), where supply remained fair at the heat of the crisis.ObjectivesTo provide consensus on how communication should be conducted to minimize the impact of medicine shortages on patient anxiety.MethodsThe Patient Advisory Network (PAN) of Lupus Europe established an extensive list of potential elements of a more effective communication on shortages, that could help reduce patient anxiety. 20 statements were derived from those elements and proposed to PAN members and Lupus Europe member organisations. 101 answers were collected from 17 countries. For each country, the individual ratings of all participants were averaged to assign an individual vote for each country on each statement. Consensus amongst the 17 countries was then considered as obtained if 14 or more of the 17 countries agreed or strongly agreed with statements.Results9 out of the 20 statements reached consensus:1. Lupus specialists should (a) clarify alternative medication existing and its difference versus current treatments, (b) clarify appropriate emergency procedures and (c) clarify to the patients how to handle a short supply.2. Specialists and Hospitals should establish alternative supply mechanisms to guarantee minimum availability.3. pharmaceutical industry should (a) provide all information to all stakeholders and (b) help create emergency supply routes to ensure that no patient is left without his/her medication for a sustained period of time.4. National authorities should help patients with demonstrated need have priority access to limited supply quantities through a simple process.5. Hospitals should communicate (by email or postal mail) information on the shortage, how to handle it and how to access emergency supply routes. The same number agreed with Health authorities performing that same communication.6. pharmaceutical industry should avoid diverting products from one country to another if that would reduce supply below normal consumption level.7. Patient organisations should stop the rumors that can quickly spread though social media.8. pharmacists should be better equipped in terms of data (on the reasons and clear timelines for resolution as well as alternatives or recommendations for patients facing shortages)9. GP's should clarify alternative medication and appropriate emergency procedures.ConclusionShortages of medicine create an anxiety that can be long lasting. Even when supply is re-established, the fear remains. For this reason, establishing an effective communication system is necessary to reassure patients when short term shortages are taking place, and is key to avoid fast spreading anxiety relating to this concern. In this process, patient associations, physicians, industries and all the stakeholders should be involved.Reference[1]Cornet A, Andersen J, Tani C, Mosca M. Hydroxychloroquine availability during COVID-19 crisis and its effect on patient anxiety. Lupus Sci Med. 2021 Apr;doi: 10.1136/lupus-2021-000496Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Risk factors for hospital-acquired infection during the SARS-CoV-2 pandemic.

OBJECTIVE: To evaluate risk factors for hospital-acquired infection (HAI) in patients during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, including historical and concurrent cohorts. DESIGN: Retrospective cohort. SETTING: Three Missouri hospitals, data from 1st January 2017 to 30th September 2020. PARTICIPANTS: Patients aged ≥18 years and admitted for ≥48 h. METHODS: Univariate and multi-variate Cox proportional hazards models incorporating the competing risk of death were used to determine risk factors for HAI. A-priori sensitivity analyses were performed to assess the robustness of the urine-, blood- and respiratory-culture-based HAI definition. RESULTS: The cohort included 254,792 admissions, with 7147 (2.8%) HAIs (1661 blood, 3407 urine, 2626 respiratory). Patients with SARS-CoV-2 had increased risk of HAI (adjusted hazards ratio 1.65, 95% confidence interval 1.38-1.96), and SARS-CoV-2 infection was one of the strongest risk factors for development of HAI. Other risk factors for HAI included certain admitting services, chronic comorbidities, intensive care unit stay during index admission, extremes of body mass index, hospital, and selected medications. Factors associated with lower risk of HAI included year of admission (declined over the course of the study), admitting service and medications. Risk factors for HAI were similar in sensitivity analyses restricted to patients with diagnostic codes for pneumonia/upper respiratory infection and urinary tract infection. CONCLUSIONS: SARS-CoV-2 was associated with significantly increased risk of HAI.

Anti-SARS- CoV- 2 vaccines do not induce a hypercoagulable state in healthy individuals

Background: Anti-SARS- CoV- 2 adenoviral-vectored- DNA vaccines have been linked to a rare but serious thrombotic post-vaccine complication called the vaccine-induced immune thrombotic thrombocytopenia (VITT). VITT has raised concerns regarding the possibilities of increased thrombotic risk and/thrombocytopenia after anti-COVID- 19 vaccines. Aim(s): To investigate whether anti-SARS- CoV- 2 vaccines can cause subclinical coagulation activation and increased thrombin generation leading to a hypercoagulable state. Method(s): The study included 567 healthcare personnel from two hospitals in Norway. Of these, 521 were recruited 11-57 days post-vaccination with the first dose of ChAdOx1-S (Vaxzevria, AstraZeneca, UK) vaccine, and 46 were recruited prospectively prior vaccination with an mRNA vaccine, either elasomeran (Spikevax, Moderna, n = 38) or tozinameran (Comirnaty, Pfize-BioNTech, n = 8). In the latter group, samples were acquired before and 1-2 weeks after vaccination. In addition to pre-vaccination samples, 56 unvaccinated blood donors were recruited as controls (total n = 102). Thrombin generation, D-dimer and free tissue factor pathway inhibitor antigen (free TFPI) were analyzed. Result(s): None of the participants developed thrombosis/VITT or thrombocytopenia (platelet count < 100.109/L) after vaccination. There were no significant differences in D-dimer, free TFPI or the parameters of thrombin generation between the two vaccine groups and the controls (Table 1). No differences in thrombin generation or free TFPI between the ChAdOx1-S group and the mRNA group, the median D-dimer level was slightly higher in the ChAdOx1-S group, but both were within the normal range (Table 2). Thrombin generation, D-dimer and free TFPI showed no changes after mRNA vaccination compared with baseline. Conclusion(s): Anti-COVID- 19 vaccines, both ChAdOx1-S and mRNA, were not associated with significant increase in thrombin generation, D-dimer or free TFPI compared with controls. Neither significant differences were observed between ChAdOx1-S and mRNA vaccines nor changes after mRNA vaccines compared with baseline levels. Our results are reassuring in the sense that no subclinical activation in the coagulation system was observed with these vaccines. (Table Presented).

A Self-Guided App-Based Adaptive Coping Skills Training Intervention for Patients with Cardiorespiratory Failure: The Blueprint Pilot RCT

Rationale: Cardiorespiratory diseases are common causes of persistent psychological distress symptoms. To fill this gap, we developed Blueprint, a month-long mobile app-based adaptive coping skills training intervention based on lessons learned about intervention delivery and population targeting from a multicenter RCT of a hybrid telephone- and web-based intervention (Figure). However, Blueprint requires further testing before broader use. Methods: The objectives were to (1) Optimize the usability of the new Blueprint system by incorporation of features based on lessons learned and (2) Test two Blueprint iterations vs. usual care in a pilot 3-arm RCT with 3-month follow up among a targeted sample of 45 patients. Usability was assessed using the Systems Usability Scale (SUS). The two Blueprint iterations differed by their response to weekly changes in Hospital Anxiety and Depression Scale (HADS) scores within the app (app-based response with additional digital content vs. therapist response). The key inclusion criterion was hospitalization in an ICU or stepdown unit with a need for cardiorespiratory support (e.g., ventilation, vasopressors) plus a HADS total score ≥8 just after arrival home. Method of minimization was used to balance across strata (ICU service, baseline HADS, age). The 1-month HADS score was the primary outcome, with secondary outcomes at 1 and 3 months including HADS, Post-Traumatic Stress Scale (PTSS), and physical symptoms (PHQ-10) Results: Usability testing was performed among 5 patients asked to perform core tasks in the Blueprint app. The mean (SD) SUS score was 83.5 (9.5), exceeding the benchmark target of 80. Subsequently, the RCT was initiated. A total of 1,133 were screened, 416 (37%) appeared to be eligible, 229 (55%) were approached, 65 (28%) consented, and 45 (69%) randomized in a 1:1:1 ratio by group. A total of 19 (29%) were excluded post-consent for low baseline HADS scores. To date, 25 have completed the trial and 20 are still active in the protocol. The relatively high refusal rate reflects the conduct of the RCT by the study team completely by distance via telephone and SMS texting (including screening and consenting) during the COVID pandemic. Conclusion: We successfully transformed an adaptive coping skills intervention into a highly usable, fully self-guided, mobile app-based version called Blueprint that delivers content responsive to weekly changes in psychological distress symptoms. We reached the target sample size and follow-up for the RCT continues. We anticipate completion by January 2022 with full results ready for presentation by the time of ATS 2022.

Mobile Mindfulness Intervention to Reduce Emotional Distress and Burnout in Frontline Healthcare Workers: The LIFT-HCW Pilot RCT

Background: The COVID-19 pandemic has led to extremely high levels of emotional distress and burnout amongst frontline healthcare workers. Rapidly deployable and scalable interventions are desperately needed to help combat the burgeoning mental health crisis among frontline healthcare works. Methods: We designed a prospective, randomized, waitlist-controlled pilot study assessing the impact of a mobile mindfulness app (LIFT) among nurses working in COVID-19 units. Participants were randomized in a 2:1 fashion to receive access to mobile mindfulness content (intervention) or to a waitlist to receive access to mobile mindfulness content outside the study period (control). All patients completed a survey that includes the Patient Health Questionairre-9 (PHQ-9), The General Anxiety Disorder-7 (GAD-7), the Perceived Stress Scale-4 (PSS-4), and the Maslach Burnout Index (MBI) at baseline (T1) and at the end of the study period (28 days after enrollment, T2). Primary outcomes are feasibility as assessed by the number of participants completing all 4 weeks of mindfulness therapy as well as the total number of daily mindfulness sessions completed. Secondary outcomes included change in PHQ-9, GAD-7, PSS-4, and MBI scores from T1 to T2. Results: Enrollment began in May of 2021. To date 82 participants have been enrolled and randomized, 56 to intervention and 24 to waitlist, with a target enrollment of 100. Median PHQ-9 scores in each group were 8 (IQR 6-11.25) and 7 (IQR 5-10) indicating moderate amounts of emotional distress in each group. Enrollment and follow-up are ongoing, with enrollment planned to be completed in December 2021. Conclusions: We have successfully enrolled 82 participants in an ongoing randomized, waitlist-controlled trial testing the clinical impact of a mobile mindfulness intervention on emotional distress and burnout in frontline healthcare workers. Final results will be presented at ATS International Meeting.

A health and lifestyle framework for management of post covid-19 syndrome based on evidence-informed management of post-polio syndrome: a narrative review

Post covid-19 syndrome includes symptoms common to post-polio syndrome, i.e. weakness;fatigue and pain like myalgic encephalomyelitis/chronic fatigue syndrome;breathlessness;and cognitive disturbances. We conducted a narrative review to establish the basis for an evidence-informed health and lifestyle framework, that underlies the management of post-polio syndrome, as a prototype for managing post covid-19 syndrome. Multi-morbidity, the non-communicable diseases (NCDs) and their risk factors, is strongly associated with SARS-CoV-2 susceptibility and poor outcomes including death. Poliomyelitis survivors may exhibit debilitating sequelae decades after infection, thus their presentations are often confounded by limitations associated with NCDs and their risk factors. An evidence-informed health and lifestyle framework is described. Its three levels of analysis and intervention include: (1) health status;(2) lifestyle practices (smoking;nutrition;weight;sedentariness, activity/exercise;sleep;stress);and (3) the three levels of the WHO's International Classification of Functioning, Disability and Health (body structures and function consistent with the conventional biomedical approach;activity;and participation). Maximising health practices of covid-19 survivors, like poliomyelitis survivors, augments function, and strengthens immunity and patients' capacities to heal, repair, and recover;as well as reduce manifestations of NCDs and their risk factors. Avenues for future research are proposed to complement findings from clinical trials.

Adherence to inhaled corticosteroids in asthma (ARICA): A randomized controlled pilot study

Background: ARICA (AdheRence to Inhaled Corticosteroids in Asthma) is a comprehensive inhaled corticosteroid (ICS) adherence intervention designed to remediate each patient's unique reason for not taking their ICS as prescribed. Objective: The primary objective was to evaluate the feasibility and acceptability of implementing ARICA in a health system. Methods: 29 Black adults who self-reported ICS nonadherence, had uncontrolled persistent asthma, and a Duke Primary Care provider visit within the past 3 years were randomly assigned to intervention (N=15) or control (N=14) in a waitlist randomized controlled pilot trial. Participants were assigned to 1-3 ARICA components based on adherence barriers selected by participants;including, an asthma selfmanagement program, financial assistance referral program, and/or objective feedback on asthma control. All participants received weekly texts and emails dispelling asthma myths. Activities were delivered virtually due to COVID-19. Primary outcomes were feasibility (e.g., process outcomes) and acceptability (e.g., patient exit interviews) measured at 12 weeks. Secondary asthma (e.g., ACT) and adherence outcomes (e.g., DOSEnonadherence) were measured. Results: Most participants were female (N=27, 93%), nonsmokers (N=26, 70%), poorly controlled with ACT <15 (N=14, 48%), and mean age 49.8. Most (N=14, 93%) completed all assigned intervention components and reported mean 4.8 of 5 on Weiner feasibility, acceptability, and appropriateness of intervention. The intervention group had a greater and statistically significant improvement in ACT (Δ-3.5, CI 6.0,0.96) and Marks AQLQ (Δ 11.5, CI 5.5,17.4) when compared to changes in the control ACT (Δ-2.5, CI-5.2,0.05) and Marks AQLQ (Δ5.7, CI-1.3,12.8), respectively. The improvement in ACT in the intervention group was clinically significant. The intervention group also reported a greater and statistically significant decrease in degree of nonadherence (DOSE Δ 0.74, CI 0.2,1.3) than control (DOSE Δ 0.36, CI-0.04,0.75) and a greater decrease in the number of adherence barriers identified in the intervention group (Δ 2.1, CI 1.2,3.0) versus control group (Δ1.6, CI 0.3,3.0). The study was not powered to assess a statistically significant change between groups. Conclusion: The implementation of ARICA in a cohort of Black adults was feasibly deployed in a health system and acceptable to participants. There was a trend in improvement in asthma control and asthma quality of life and a decrease in nonadherence and barriers to adherence.