Patient Centricity: Design and Conduct of Clinical Trials in Orphan Diseases: Third of Three Sets of Expanded Proceedings from the 2020 ISCTM Autumn Conference on Pediatric Drug Development

This article expands on a session, titled "Patient Centricity: Design and Conduct of Clinical Trials in Orphan Diseases," that was presented as part of a two-day meeting on Pediatric Drug Development at the International Society for Central Nervous System (CNS) Clinical Trials and Methodology (ISCTM) Autumn Conference in Boston, Massachusetts, in October 2020. Speakers from various areas of pediatric drug development addressed a variety of implications of including children in drug development programs, including implications for rare/orphan diseases. The speakers have written summaries of their talks. The session's lead Chair was Dr. Joan Busner, who wrote introductory and closing comments. Dr. Simon Day, regulatory consultant, outlined some of the past mistakes that have plagued trials that did not consult with patient groups in the early design phase. Dr. Atul Mahableshwarkar provided an industry perspective of a recent trial that benefited from the inclusion of patient input. Drs. Lucas Kempf and Maria Sheean provided regulatory input from the perspectives of the United States (US) Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively. Dr. Judith Dunn outlined a novel approach for assessing and rank ordering patient and clinician clinical meaningfulness and the disconnect that may occur. Dr. Busner provided closing comments, tied together the presented issues, and provided a synopsis of the lively discussion that followed the session. In addition to the speakers above, the discussion included two representatives from patient advocacy groups, as well as an additional speaker who described the challenges of conducting a pediatric trial in the US and European Union (EU), given the often competing regulatory requirements. This article should serve as an expert-informed reference to those interested and involved in CNS drug development programs that are aimed at children and rare diseases and seek to ensure a patient-centric approach.Copyright © 2023, Matrix Medical Communications. All rights reserved.

Assessment of Disease Activity in Adolescent Patients with Chronic Inflammatory Diseases after Vaccination against Covid-19ata University Hospital in Manaus

Objectives: Chronic Inflammatory Immune-mediated Diseases (CIMD) can cause pain and severe discomfort to the patient, leading to significant reductions in his/her quality of life. Vaccination against COVID-19 has proven to be an efficient method in preventing cases and serious repercussions. However, there is insufficient evidence on the safety of these vaccines in the CIMD population. Objective(s): To assess disease activity in adolescent patients with CIMD after vaccination against SARS-CoV-2. Method(s): Observational, longitudinal, ambidirectional study with follow-up of groups of adolescent patients with CIMDwho received the vaccine provided by the National Immunization Program -Pfizer/BioNTech. Sociodemographic and clinical disease activity data were collected before and after each vaccine dose. Data were stored through an online platform (REDCap). This study is associated to the SAFER Project from the Brazilian Society of Rheumatology and was approved by the local Research Ethics Committee. Result(s): Nineteen adolescents aged between 12 and 17 years were included, all of whom met the inclusion/exclusion criteria. Of the total, 31.6% have Juvenile Idiopathic Arthritis (JIA)-14.33 +/- 2.25 years of age, whose subtypes included persistent oligoarticular JIA (16.7%), Polyarticular Rheumatoid Factor (RF) negative (33.3%), Polyarticular RF positive (16.7%) and Systemic (33.3%);68.4% have Systemic Lupus Erythematosus (SLE) -14.77 +/- 1.96 years of age. Regarding JIA patients, at inclusion, the mean disease activity assessed by the physician was 3 +/- 3.83 and 3.25 +/- 3.77 as assessed by the patient. After the 1st dose, the mean activity assessed by the physician was 2.8 +/- 3.9 and after the 2nd dose it was 3 +/- 4.24. Themean activity after the first dose as assessed by the patient was 3.2 +/- 3.96, and after the 2nd dose it was 2.8 +/- 3.11. In the SLE patients, at inclusion, the mean degree of disease activity was 1.92 +/- 1.83 and of the SLEDAI-2 K was 4.67 +/- 5.14. After the 1st dose, the mean disease activity was 1.11 +/- 1.96, and after the 2nd dose, it was 2.25 +/- 2.76. After the 1st dose, the SLEDAI-2 K was 1.11 +/- 1.76, and after the 2nd dose it was 4.25 +/- 5.28. No reports of worsening of disease activity after the vaccine were found. Conclusion(s): The vaccination proved not to contribute to worsening of clinical activity of rheumatic diseases in adolescents, without significant changes in SLE assessment indices and in the personal and medical assessment of JIA patients.

Attitudes amidst the pandemic: Virtual delivery of care in an adult cystic fibrosis population

Background: The COVID-19 pandemic has altered how we deliver care to people with cystic fibrosis (CF) across the spectrum of disease severity. Because of lockdowns and avoiding exposure to COVID-19 by limiting inperson clinic visits, clinical care has pivoted from standard practices to virtual care in combination with in-person traditional visits. This approach has allowed patients to be monitored and treated in a timely manner. Such virtual visits have the advantage of reducing the time commitment for clinic visits because the patient does not have to travel to and from the hospital, but virtual care lacks the ability to conduct a physical examination and to obtain objective and standardized testing of key measurements known to be associated with health outcomes in CF. The objective of this study was to evaluate the attitude of patients to virtual delivery of care and their comfort level with such care. Method(s): This is a prospective, cross-sectional survey of adults with CF who are followed at St. Michael's Adult CF Center in Toronto, Canada. An online survey was created using SurveyMonkey to assess attitudes toward and satisfaction with virtual care. The survey was emailed to participants and included the Canadian CF Registry ID;a reminder email sent a week later. Baseline demographic and clinical data were obtained from the Canadian CF Registry and presented as median (range) or proportions as appropriate. Questions using a 3-point Likert scale will be categorized into agree, neutral, and disagree. Result(s): A total of 210 participants (53.0% female) completed the survey (median age 37.8, range 19.2-78.9). Median age of diagnosis was 2.2, 95.7% were Caucasian, 76.0% had completed post-secondary education, 63.0% were employed and 11.0% were students, 75% were pancreatic insufficient, 39.0% had CF-related diabetes, and 12.4% were post lung-transplant. Median percentage predicted forced expiratory volume in 1 second was 65.8% (range 17.9-126.9%), and median body mass index was 23.6 kg/m2 (range 15.5-45.7 kg/m2). Eighty-one percent of respondents had had a virtual visit before completing the survey. Sixty percent of respondents felt that in-person visits were the preferred way of completing a medical assessment, and 27.0% preferred virtual visits. Seventy-three percent felt it was important for the virtual visit to occur at the booked time, 59.0% had concerns that their lung function was not assessed during virtual visits, 46.0% felt they were losing the benefits of allied health team assessments with virtual visits, and 40.0% worried that their health would decline if primarily seen virtually. Just over half of respondents wanted to continue with virtual visits in some capacity after the pandemic. The optimal proportion of in-person visits was felt to be 50.0%. More than 85% of respondents were comfortable with technology (phone or computer) and had reliable access to the Internet to conduct virtual visits. Seventy percent of people would like to have access to a home spirometer, but cost was a barrier. Conclusion(s): From the patient's perspective, in-person visits were still the preferred way to complete a medical assessment, which seemed to be driven by concerns over lack of methods for assessment, particularly lung function, and access to the multidisciplinary team. Home spirometers, if freely available, might increase comfort with virtual appointments.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Clinical and quality of life assessment in patients with latex allergy during COVID-19 pandemic: Possible protective role of continuous latex immunotherapy

Background: During Covid-19 pandemic, the massive use of Personal Protective Equipment could provoke severe adverse reactions in latex allergy patients and could negatively affect their quality of life. Method(s): The observational single-centre present study was carried out on 67 adult subjects with a latex allergy diagnosis followed by Allergy Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS of Rome. All data were collected from January 2020 to December 2020. All patients underwent to a survey focused on their clinical and psychological conditions during Covid-19 pandemic. For the evaluation of the degree of well-being, we used SF-36 questionnaire (Short-Form 36-Item Health Survey). The aim of our study is: (a) to evaluate the incidence of allergic reactions in patients with latex allergy during the SARS-CoV- 2 pandemic;(b) to evaluate the protective role of continuous latex ITS during this period;(c) to evaluate quality of life of natural rubber latex allergy (NRLA) patients during the pandemic. Result(s): 67 patients (9 males and 58 females, mean age of 45.9 +/- 11.4 years) suffered from latex allergy were included in the present study. We recorded among our patients 13 cases (34.2%) of urticarial/ angioedema (U/A), 9 cases (23.6%) of respiratory symptoms (RS;dyspnoea, shortness of breath, wheezing) and 7 cases (18.4%) of anaphylaxis. In patients undergone continuous ITS, we observed less cases of U/A (p < 0.001), RS (p < 0.001), anaphylaxis (p = 0.003), hospitalizations (p = 0.014) and a lower therapy administration. We compared the results of SF-36 questionnaire in patients undergone continuous and not continuous latex ITS with a significance differences score between these two groups. Conclusion(s): The pandemic challenged the capacity of healthcare systems to provide adequate management of NRLA patients and in this context, we performed a survey to monitor their health status. During the pandemic, the risk of latex exposure was significant increased considering the possibility of direct skin contact, airborne exposure, contamination of food and medical evaluations. Our study is the first that investigated the clinical and quality of life effects of Covid-19 pandemia in NRLA patients demonstrating the importance of SLIT adherence also in this complex period. (Table Presented).

'How shall we handle this situation?' Social workers' discussions about risks during the COVID-19 pandemic in Swedish elder care

Within a context where New Public Management [NPM] has become increasingly influential in shaping everyday working practices, social workers often handle risks in their everyday work using formalised bureaucratic procedures, among other strategies. As the COVID-19 pandemic progressed, rapid changes occurred in Swedish elder care that social workers were required to address in their everyday work. Intra-professional case conferences amongst social workers provide one opportunity to discuss individual viewpoints and obtain suggestions from colleagues on how to proceed with a case. These discussions have so far received little scholarly attention. In this study we used a data set consisting of 39 audio-recorded case conferences to analyse social workers' intra-professional discussions about risks during the COVID-19 pandemic. In the case conferences, social workers discussed the risks that were accentuated by the pandemic, such as the risk of spreading COVID-19 to clients, the risk of unmet care needs amongst clients, risks related to accountability, and the risks pertaining to blurred boundaries between different organisations. The collegial discussions in case conferences included opportunities for social workers to use their collective professional experience and competency to establish creative solutions 'on the go' and to discuss various ways of handling and balancing different risks while continuing to carry out their work in the changing and unknown situation. Our findings highlight the importance of collegial support in social work in dealing with accentuated risks during the pandemic.Copyright © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

The Stem Cell Unrelated Donor Search during Covid19

Background In Stem Cell Transplants approximately two thirds of donors are identified and used from unrelated donor registries. In January 2020, we considered the impact that Covid19 infections and restrictions would have on donor availability. We identified that we needed to change our practice to ensure we could continue the SCT procedures which are critical for patients. Methods In January 2020, the Joint United Kingdom Blood Transfusion and Transplantation Service Professional Advisory committee (JPAC) changed the Tissue and cell donor selection guidelines. The risk and restrictions of Covid19 caused significant challenges including logistical issues for product delivery. Donor deferrals at medical assessments increased from 14% to 29% and overall activity in the UK was 75% of usual provision. Best practice was established and agreed with the donor registries. As per NICE guidelines, cryopreservation of all stem cell products was recommended with fresh donations considered according to patient condition. Back up donors were identified where possible. All donors were tested for Covid 19 on day of medical and harvest to ensure effective screening. We carried out 58 stem cell procedures from unrelated donors in 2020 and 56 in 2021. This activity is comparable to previous years. We secured stem cell products from Germany, USA, Korea, Poland, Turkey, Greece, Switzerland, the Netherlands and the UK. We analysed our data to assess if any delays occurred. Ethical approval was not required for this service evaluation. Results SCT activity was maintained throughout Covid19 with only postponement of elective SCT's which was assessed to be in the patient's best interest. Discussion We were able to adapt our practice to the benefit of our patients in unique and challenging circumstances. Conclusion We implemented measures which enabled BMT activity to continue throughout the acute Covid19 period despite challenges with new variants and further restrictions.

Parental Experience of Healthcare Access during the Covid-19 Pandemic

Aims Many paediatric emergency departments (PED) reported an unexpected increase in attendances during summer 2021;most of these children were stated to have minor illnesses and were discharged with reassurance. The primary objective of our questionnaire was to obtain parental perspective of how changes to local acute paediatric healthcare services in response to Covid-19 had impacted upon accessing care for their children. Additional objectives aimed to identify if parents were more worried about their child's health in view of the pandemic, understand parents' ideas of how children should be assessed when unwell, and explore how parents felt remote consultations could be improved. Methods A questionnaire comprised of Likert scale, multiple choice and free-text questions was developed to explore the study aiSeveral iterations of the questionnaire were test-run with parents prior to roll-out. The project was registered with the Trust's Quality Improvement team. A total of 88 families presenting to the paediatric emergency department and local urgent treatment centres completed the questionnaire between 26th October and 31st December 2021. Excluded were families for whom a translator was needed for their medical assessment. A thematic analysis was performed using NVivo, and quantitative analysis performed using PRISM statistical software. Results 68.2% of parents had sought medical advice outside of the PED prior to presentation, either in the community and/or online. 20.5% of respondents sought healthcare input from two or more sources prior to attending PED. Figure 1 outlines the responses to Likert-scale questions. Statistical analysis of the responses in relation to of age of child, number of children in the family and whether English was the family's first language was performed. Confidence of phone/video assessments and English/non-English as first language approached statistical significance (p=0.059). No other comparisons were statistically significant. Analysis of free-text responses identified key themes regarding the parental expectation of how children should be reviewed when unwell, and how parents thought remote consultations can be improved. An outline of the identified themes and a selection of responses are outlined in Figure 2. Conclusion The questionnaire identified that parents had still been able to access healthcare during the pandemic when they felt their child was unwell. Parents reported concerns of their children becoming sick with Covid-19, but still felt confident managing minor illnesses at home. The increasing volume of remote assessments in primary care was a necessary adjustment during the pandemic which is likely to be embraced as a more permanent model of service. Many parents recognised the benefit of remote consultations for non-urgent issues. However, a key theme from the questionnaire was the lack of parental confidence in remote (particularly phone) consultations;parents were more likely to still seek a face-to-face assessment in PED if they felt they couldn't communicate their child's signs and symptoms over the phone. As local networks embrace a more remote model of working to deliver some urgency and emergency care it is necessary to identify the cohorts of patients who may still attend PED, and plan how better to provide clinical reviews for them in the community.

Collecting data from a social network as a new method to explore recurrent corneal erosions syndrome

Purpose : Collecting medical data for clinical research studies needs tremendous perseverance. Yet, patients post a lot of their own personal health data on social media and share their experiences through international virtual support groups. Recurrent epithelial erosion (RCE) induces recurrent pain while reducing patients' quality of life. We report data of RCE patients who belong to an international English-speaking support group hosted by a social network. We aimed at better defining patients' symptomatology and the subjective efficacy of proposed treatments, and subsequently compared our results with literature. Methods : We designed a 24-question questionnaire consisting in three parts: demographics, clinical data and therapies. The treatments' efficacy to prevent RCE was scored through a semi-quantitative 4-gradescale (from 'no effect? to 'very efficient'). In May 2021, we posted a 6-month ephemeral hyperlink on the RCE support group forum (Facebook, Meta®) pointing at our questionnaire Results : The RCE group included 1856 members. We harvested 257 complete responses (13.8%;222 women and 35 men;average age =42+/-12 y). Responders were mostly North Americans (n=152;59.1%), and Caucasian (n=214;83.3%). Fewer than one-third of RCEs were attested by a corneal subspecialist MD (n=70;27.2%), whereas 91.8% were referred to a health care professional (n=236). The predominant symptom was acute awakening pain (n=198;77.0%). RCE significantly impaired patients' quality of life (n=176;68.4%). Daily wearing of an anti-Covid-19 surgical mask may have increased the frequency of episodes (n=41;16.0%). Among surgical procedures, manual debridement was the most performed (n=56;21.8%), effective in a third of patients (n=17;30.3%). PTK was performed in one-fifth of patients (n=52;20.2%), effective in two-thirds (n=31;59.6%). 176 patients (68.4%) were treated with hypertonic gel, which, according to the patients was the most efficient medical treatment d (n=103;58.5%;p<0.0001). Conclusions : To our knowledge, this is the first real-life study involving patients with RCE, and the second collecting data through a social network in ophthalmology. Our results are consistent with previous retrospective or prospective reports based on medical records despite responder selection bias. The use of social networks to collect real life data seems to be promisingly reliable as a medical evaluation tool.

Clinical Impact of SARS-CoV2 Pandemic in the Diagnosis of Early-Stage Thoracic Tumours

Introduction: Cancer healthcare has been affected by Coronavirus disease 2019 (COVID-19) pandemic, interfering the normal function of oncology units and increasing diagnostic delay. Nevertheless, the rising incidence of respiratory infections led to an increase in medical consultations and chest imaging explorations. The aim of the study was to assess whether the increase in medical evaluations in the context of the pandemic led to an increase in the detection of early-stage thoracic tumours. Methods: We performed a retrospective single-institution study, collecting data from patients diagnosed with thoracic tumours between March, 1, 2020 and December, 31, 2021. We analysed their demographic and clinical data, symptoms at diagnosis and those who were diagnosed due to SARS-CoV-2 infection. Results: A total of 378 patients were analysed. Main results are shown in Table-1. Only 5.3% of newly diagnosed thoracic tumours were related to a suspected or confirmed SARS-CoV-2 infection. However, these patients were not diagnosed at earlier stages (p = 0.414). When we evaluated symptoms at diagnosis, we found that asymptomatic patients presented in earlier stages (p <0.000, Figure-1), being the majority incidental findings during the follow-up of oncological and non-oncological pathologies. Regarding symptomatic patients, most presented as locally advanced or metastatic diseases and no changes have been observed in the pattern of presentation compared to studies prior to the pandemic. [Formula presented] Conclusions: COVID-19 pandemic did not seem to increase thoracic tumours diagnosis in our study. Lung cancer diagnosed in patients due to SARS-CoV-2 infection was not detected in earlier stages. Clinical presentation was similar to previous reported outside COVID-19 pandemic. Nevertheless, we find that asymptomatic patients diagnosed incidentally presented more frequently in localized stages in comparison with symptomatic patients. [Formula presented] Keywords: COVID19, Lung Cancer, Diagnosis

Catatonia Associated With Cerebral Venous Thrombosis in a COVIDPositive Adolescent

BACKGROUND: Catatonia is a psychomotor syndrome characterized by abnormal movements and decreased responsiveness. Diagnosis is made by observing or eliciting at least 3 of the following 12 criteria: stupor, catalepsy, waxy flexibility, mutism, negativism, posturing, mannerism, stereotypy, agitation, grimacing, echolalia, and echopraxia. It is commonly associated with psychiatric disorders but can also be secondary to a medical condition, more commonly neurologic or metabolic conditions. CASE DESCRIPTION: Patient was a 17-year-old female brought in by her guardian for evaluation at a psychiatric assessment center following a month of regressive behavior and concerns of possible hallucinations. While at the assessment center, the patient began hyperventilating and had 3 seizures. She was transferred to a nearby hospital and continued to seize, becoming hypoxic and requiring intubation. Computed tomography was unremarkable;urine drug testing was positive for THC and benzodiazepines. The patient was transferred to the intensive care unit of a children's hospital. She continued to have poverty of speech, decreased responsiveness, and disorganized behavior after extubation. Child psychiatric services was consulted for these concerns, and differential included psychotic disorder and catatonia, either secondary to psychiatric or medical cause. Patient underwent extensive medical evaluation, which was overall unremarkable, to rule out medical causes (including electroencephalography, cerebrospinal fluid studies, complete blood counts, C-reactive protein, and anti-NMDA antibodies). She did test positive for COVID, which resulted in delay of brain magnetic resonance imaging (MRI) being obtained. She had partial response to lorazepam challenge, and scheduled doses of lorazepam were started after. Bush Francis Catatonia Scale scores did lower partially with scheduled lorazepam, but full resolution of symptoms was not observed. MRI done on day 10 showed findings suspicious for superior sagittal thrombosis. Brain magnetic resonance venography showed superior sagittal and bilateral transverse venous thrombosis. The patient was started on anticoagulation therapy and discharged from hospital with the recommendation of psychiatry and neurology outpatient follow-up. She did not follow up with neurology but did have slow resolution of symptoms per outpatient psychiatry records. DISCUSSION: Catatonia typically results in resolution of symptoms with treatment of underlying cause along with benzodiazepines or electroconvulsive therapy. It is commonly associated with psychiatric disorders, but it is important to evaluate for medical causes as well, especially when there are concerning signs/symptoms. In this patient, there was only a partial response to benzodiazepines, but further improvement with anticoagulation therapy. This along with no previous psychiatric history supports an underlying medical cause. This patient had no history of health conditions associated with hyper-coagulopathies. However, COVID has been associated with risk for arterial and venous thromboembolic complications.

TRENDS IN HYSTERECTOMY FOR PROLAPSE: AN ANALYSIS OF THE EFFECT OF THE COVID-19 PANDEMIC

Introduction: The COVID-19 pandemic has had a considerable and evolving impact on delivery of surgical care to patients. During the early stages of the pandemic, resource scarcity was experienced by many healthcare systems. This led to the implementation of a surgical moratorium on elective surgeries in New York State between the months of March through June 2020. Certain specialties, specifically those performing elective surgeries, experienced significant strain and transformation. Objective: This study aims to describe perioperative and intraoperative characteristics of patients undergoing hysterectomy for pelvic organ prolapse (POP) with and without concomitant urogynecology procedures between 2019-2021 at a multi-hospital healthcare system that experienced significantly strain and a subsequent moratorium on elective surgery during the first peak of the pandemic. Methods: This is a retrospective cohort analysis of all patients in a multi-hospital healthcare system in New York City who underwent hysterectomy for POP from August 19th, 2019 through August 11th, 2021. Cases were identified using procedural and diagnostic codes for hysterectomy and POP, respectively. Patients were separated into three cohorts based on dates corresponding to phases of the COVID-19 pandemic. The 'early peak' was defined from March through June 2020, coinciding with the New York State moratorium. The primary outcome was the stage of POP for patients undergoing surgery. Secondary outcomes included concomitant urogynecologic procedures, route of surgery, time from indication to procedure, length of inpatient stay, and utilization of pre-operative medical assessment/clearance (POMA). Results: A total of 253 cases were included: 106 (41.90%), 15 (5.93%), and 132 (52.17%) patients in the 'pre-pandemic','early peak pandemic', and 'stable pandemic' groups, respectively. Although not statistically significant, vaginal hysterectomy approach was performed less frequently during the 'early peak pandemic' and 'stable pandemic' cohorts (P = 0.0544). The 'early peak pandemic' cohort had significantly more stage IV POP compared to other cohorts (P = 0.0021). Rates of concomitant urogynecology procedures including slings, anterior or posterior repair, or apical repair did not differ between the cohorts. Further, cystoscopy was utilized intraoperatively more frequently in the 'stable pandemic' cohort (P = 0.0272). Time from surgical indication to operation was also significantly different with patients most frequently waiting at least 3 months in the 'early peak pandemic' group (P = 0.0132). Length of inpatient stay did not demonstrate a significant difference (P = 0.3982). The most frequent postoperative complication was transient voiding dysfunction, and this was observed more commonly in the 'stable pandemic' cohort (P = 0.0236), though overall no cases were complicated by persistent voiding dysfunction or urinary retention requiring surgical intervention in any group. Conclusions: In late spring 2020, when the moratorium was lifted, surgical volume returned to pre-peak numbers. However, time from booking to day of surgery remained significantly longer during and after the 'peak'. There was a statistically significant increase in patients with stage IV POP during the 'early peak' and 'stable' pandemic periods. There was a statistically significant increase in use of precautionary measures peri and intra-operatively during the 'peak' and 'stable pandemic' periods with significant increases in use of POMA performed outpatient by anesthesia and an increased utilization of intraoperative cystoscopy.

THEMES AND CHALLENGES OF END OF LIFE CARE FOR COVID-19 PATIENTS REQUIRING NON-INVASIVE RESPIRATORY SUPPORT

Introduction The COVID-19 pandemic created new challenges due to the high numbers and the high symptom burden of end-of-life patients on respiratory support. Methods We conducted an audit of end-of-life patients on the respiratory HDU wards at Whipps Cross Hospital between 17/09/2020-30/01/2021. Results 84 patients receiving respiratory support (in the form of CPAP and HFNT) died during that time at a mean age of 77 (95% CI 67-87) and median of 79 years. All but one death, which followed a cardiac arrest, were expected. The most common clinical indicator for a patient approaching end-of-life was hypoxia on respiratory support, which was documented in 36 (43%) patients, followed by terminal agitation in 27 (32%) patients. Objections to the medical assessment of terminal illness were raised by 3 families and in 1 case the patient had conflicting wishes. The average time between recognition of a terminal deterioration and death was 1.4 days with a median of 2 days. 29 (35%) patients did not have a specialist palliative care review primarily due to the rapid patient deterioration. 25 (30%) patients were not visited by a relative due to the infection risk. 72 (86%) patients were weaned off respiratory support and those who continued did so due to a medical or patient decision. Despite most patients (82%) receiving continuous subcutaneous infusions with an opiate and benzodiazepine most patients had persistent terminal symptoms: 51 (74%) on infusions had agitation and 38 (55%) were persistently breathlessness. Discussion This data highlights some of the major difficulties faced in caring for patients with COVID on respiratory support and approaching end of life. With the inevitably persisting nature of this pandemic and the possibility of future pandemics still present, it is vital to be able to offer guidance and multidisciplinary input to ensure comfort and dignity for these patients.

Understanding the Health care Needs of Migrant Children in Government Custody

Background: There are increasing numbers of immigrant children held in government custody at the US-Mexico border and across the US. Further, anti-immigrant policies and the US COVID-19 pandemic response exacerbated detention conditions under the Trump administration. Thus, there is a greater need to identify the health concerns and challenges clinicians face when caring for these children. Methods: A national cross-sectional 66- question online survey was distributed from October 2020 to January 2021 through national pediatric and migrant health listservs including the Academy of Pediatrics (AAP). The reported total number of listserv members was 6200, but the degree of redundancy among these groups was not able to be assessed. Clinicians were asked about care delays, health problems encountered, and resources needed while caring for children under government custody. “Children in government custody” was defined as children (0-17 years) who currently or previously (in the past 5 years) were under the custody of the US Immigration Customs Enforcement, Customs Border Protection and/or the Office of Refugee and Resettlement. Results: Eightytwo clinicians responded and cared for children clinically. Thirty four cared for children who were in government custody. About 1/3 of this subset of respondents noted care delays while in custody and delays in establishing primary care after custody release. The two main health issues seen were a lack of routine health maintenance and traumatic exposures. Most commonly, children were behind on vaccinations and needed mental health screening. Exposure to violence was the most common traumatic exposure. Furthermore, 47% of clinicians felt that their current resources were inadequate and requested legal assistance and mental health support. Importantly, 58% of respondents were not aware of or were unsure of the Centers for Disease Control and Prevention domestic refugee health guidelines for the care of migrant children and adults. Conclusion: Children who experience detention have significant healthcare needs, many of which clinicians do not feel equipped to address. The reported health complications emphasize the need for policy measures, such as those recommended by the AAP, namely, the provision of evidence-based medical evaluations, trauma-informed care, and family-centered medical homes with comprehensive primary care and embedded mental health and legal support systems. Child detention should end. If present, children should be released to ORR shelters with pediatric clinicians providing healthcare and oversite until children can be safely released to vetted legal guardians and established in medical homes. This process should be swift with improved integration of detainment and post-detainment healthcare. Clinicians can be supported with training on immigrant screening guidelines. Of note, the low response rate and inability to distinguish between ICE, CBP, and ORR on the survey limits these results. Nonetheless, these findings support further research and recommendations for policy changes to improve the health and well-being of newly-arrived immigrant children.

Updated principles of prevention, diagnosis and treatment of COVID-19 in children in Poland - recommendations for paediatricians and family medicine doctors

Since late 2021, we have observed a significant increase in the proportion of children infected with SARS-CoV-2. The course of the disease in children is usually sparsely symptomatic or asymptomatic. However, the predominance of new virus variants makes children more likely to become symptomatically ill and require hospitalisation. This paper aims to update recommendations for managing a child with COVID-19 in out- and inpatient settings. Current options for prevention and antiviral treatment are discussed, noting the limited availability of therapy for children. In most children with COVID-19, the basis for treatment remains symptomatic and supportive therapy and measures to reduce SARS-CoV-2 infection spread.

Managing urinary catheters in residential facility patients

Introduction & Objectives: Residential aged care facility (RACF) patients require complex care, with many needing urinary catheters. As part of Aged Care Quality Standards, facilities are expected to provide appropriate catheter management. Hospital transfers for simple catheter management burdens both Patients and health care systems. Additionally, during the COVID 19 pandemic, transfers to ED for simple catheter issues unnecessarily stresses an already strained healthcare system. Visiting geriatric services provide an alternative for RACF patients. We assessed the trends of ED presentations and referrals to visiting geriatric services for catheter related concerns before and during 2020. Methods: We assessed the electronic medical records of a tertiary teaching hospital for RACF patients with catheter related issues who were transferred to ED and those who were referred to the visiting geriatric services from 2018 to 2020. Exclusion criteria included patients who received a urinary catheter for indications other than a primary urinary tract pathology or where further assessment was required. Flushing, repositioning, or changing of a catheter was deemed suitable as management by nursing staff at RACF. Non-urgent medical assessment was deemed suitable for visiting geriatric services. Results: A total of 399 catheter related issues were managed over the included timeframe, with 129 in 2018, 126 in 2019 and 144 in 2020. Presentations to the ED accounted for 70 (54.3%), 61 (48.4%), and 56 (38.9%) of all presentations in 2018, 2019, and 2020 respectively. The remainder were managed by visiting geriatric services. Out of all catheters related issues, visiting geriatric services managed proportionately more presentations over each sequential year. Subgroup analysis of patients presenting to the ED (total 188) showed that, 115 (61.2%) were suitable for management by RACF staff. A further 34 (18.1%) were deemed suitable for visiting geriatric services. Across all three years, 79.3% of presentations were deemed safe to manage outside of the ED. Furthermore, a total of 211 were patients referred to visiting geriatric services. Of these, 25 (11.8%) were ultimate referred to hospital. Conclusions: During the COVID-19 pandemic in 2020, ED presentations for simple catheter issues reduced with subsequent increase in referrals to visiting geriatric services. This reduces not only financial costs or risks of delirium and falls, but also use of ED resources. However, given 79.3% of ED presentations were deemed safe to manage in the community with or without visiting geriatric services, and only 11.8% of those managed by visiting geriatric services were referred to the ED, there is ongoing unnecessary expenditure for these cases. Further collaboration between ED, urology and geriatric medicine can further streamline this process to identify appropriate residents to be managed in RACF.

Virtual cardiac rehabilitation during the COVID-19 pandemic: a tertiary site experience

Background: The COVID-19 pandemic resulted in the abrupt suspension of centre-based cardiac rehabilitation (CR). Multidisciplinary virtual CR (VCR) with the use of digital, telephone, and video communication was implemented for continued care access. Exercise therapy was delivered through synchronous video-supervised sessions, pre-recorded sessions, and self-directed physical activity. Purpose: To describe patient characteristics, completion rates, and safety outcomes in a real-world VCR population. Methods: Prospective observational study of a tertiary academic CR program. VCR was implemented at pandemic onset (March 2020). Patients who were enrolled in, and either completed or dropped out, during the study period were included. Completers were defined as completing 6 months of virtual enrolment and an exit assessment. Risk was defined by the AACPVR 2020 risk categorization. Adverse cardiovascular events were defined as a patient-initiated event requiring medical assessment and stratified as exercise or non-exercise related. Continuous variables are presented as means and SD or medians and IQR. Student's t-test was used for between group comparisons. Categorical variables are presented as n (%) and compared using the χ2 test or Fischer's exact test. A p-value <0.05 was considered significant. Results: Between March 13th, 2020, and August 31st, 2021, 222 [mean age 61.8 years (SD, 12.6) 77% male], were enrolled and discharged from the VCR program (Table 1). There were 160 completers and 62 non-completers (completion rate 72%). Among the non-completers 26 attended the MD intake assessment only. The remaining 36 completed a median of 85 days (IQR 25-197). This cohort included 21 (9%) high-risk and 35 (16%) moderate risk patients. Those at moderate risk were more likely to be non-completers and those at low risk were more likely to be completers (Table 1). Two exercise and 17 non-exercise adverse events were observed (median clinical surveillance 217 days [IQR 205-240]) (Table 2). Exercise related adverse events included neurally mediated syncope during a synchronous video exercise session in a low risk patient. This was responded to as per centre developed virtual safety protocols. A second syncope related to heart block occurred in a moderate risk patient during independent physical activity and required permanent pacemaker insertion. Both patients completed the program. Three non-exercise adverse cardiac events resulted in cessation of participation included one death and two heart failure hospitalizations (Table 2). One stroke and 13 emergency department visits for cardiac symptoms occurred in completers. Conclusion: Real world VCR is feasible, including in those at moderate to high risk. Modest completion rates and a low exercise related adverse event rate were observed. Synchronous video exercise sessions with video monitoring and safety protocols may improve response to adverse exercise related events. (Table Presented).

eP455: Fetal ultrasound presentation and neonatal diagnosis of Freeman-Sheldon syndrome in son of previously undiagnosed adult male

Background: Freeman-Sheldon syndrome [distal arthrogryposis type 2A (OMIM #193700), DA2A, Freeman-Burian syndrome] is a rare autosomal dominant multiple pterygium syndrome caused by alterations in MYH3. The phenotypic features, particularly of the face, are distinct and easily recognizable, and the diagnosis can be confirmed with molecular gene analysis. Fetal ultrasound imaging may provide important diagnostic clues to facilitate the diagnostic process. Informed consent and parental permission were provided by the parents. Case presentation: The infant’s mother presented for a Maternal Fetal Medicine genetic counseling telehealth appointment (due to COVID-19 pandemic restrictions) as a G7P2132, 32-year old female who had insulin-dependent diabetes and thrombocytosis. Her partner was a 24-year old male with a history of hearing loss, a V-shaped palate, and a lower lip cleft. Gestational age was 14 4/7 weeks and the indications were: increased nuchal translucency, paternal complex medical history, maternal G6PD heterozygote, and recurrent pregnancy loss. During the genetic counseling session, the following were addressed: 1) Maternal heterozygote status for G6PD indicated that if the fetus was male, there was a 50% chance he would be affected with G6PD-deficiency;2) Increased nuchal translucency on fetal ultrasound (US) with measurement at 98th percentile is associated with an increased risk of chromosomal abnormalities, microdeletion/duplications, and Noonan syndrome. The patient reportedly had low risk cell-free DNA but results were not available to the counselor at the time of consult. The option for additional genetic screening and diagnostic testing was declined;3) Three first trimester pregnancy losses with the father of this baby (FOB) were addressed, and parents deferred chromosome analyses at the time;4) Mother shared FOB’s complex history of bilateral sensorineural hearing loss, V-shaped cleft palate, lower lip cleft, and micrognathia. However, father was not present during the telehealth encounter. Mother was counseled regarding the possibility of an autosomal dominant condition with the potential risk to the pregnancy of up to 50%. It was recommended that the FOB have a clinical genetics evaluation, which could potentially provide a specific diagnosis and inform recurrence risk and management guidance. Follow-up MFM genetic counseling telephone visit occurred with the mother at 31 6/7 weeks gestation due to multiple congenital anomalies evident on fetal ultrasound. A 25 week fetal ultrasound revealed hypotelorism and a thickened nuchal translucency. A repeat study at 29 weeks revealed a V-shaped palate with a possible cleft, micrognathia, and midline mandibular cleft. FOB’s history was revisited. It was determined that he had 3 previous “no shows” to Genetics clinic appointments and did not pursue evaluation after the last counseling appointment. Again, it was emphasized that in order to best make a diagnosis for the family, an affected person would need to undergo a thorough evaluation, including medical and family history review, physical examination, and any indicated genetic testing. The parents were comfortable with the likelihood that the baby had the same condition as the father, but variable expressivity and broad range pf phenotypic presentation were explained. Recommendations for postnatal evaluation of the infant and pertinent genetic testing were provided. Consultative Genetics evaluation of the infant at 2 days of age revealed a short, broad forehead with supraorbital fullness leading to a horizontal brow indentation;mask-like facial appearance;hypotelorism;very deep set eyes with blepharophimosis;deep, creased nasal bridge;small, upturned nose with hypoplastic alae and narrow nares;microstomia with pursed lips;glossoptosis;micrognathia;2 deep vertical chin creases;short neck with excess nuchal skin;inverted and wide spaced nipples;clenched hands with 5th digits overlying 4th and 2nd overlying 3rd, bilaterally;bilateral vertical talus;2nd toes longer and overlying rd toes;clinodactyly of 4th and 5th toes bilaterally;and deep gluteal crease with no visible sinus. There were no evident contractures. The father has a complex history with no medical assessments prior to age 18. He reported that he did “not look like anyone else” in his family. He has a diagnosis of autistic spectrum disorder, a submucous cleft, vision issues, hearing loss necessitating a hearing aid on the left, and a history of cholesteatomas and of mastoidectomy. On brief examination, he had a mask-like face, blepharophimosis, left microphthalmia, left esotropia, narrowing of his midface, deep vertical crease on the mandibular region, microstomia, broad great toes, single flexor creases on the thumbs, and contracture of right thumb. Maxillofacial CT of the infant revealed hypoplastic mandibular body, ramus, and condyles bilaterally with micrognathia and retrognathia;hypoplastic maxilla bilaterally;and enophthalmos with retracted appearance of globes in the bony orbits bilaterally. Multiple facial bone abnormalities were seen, including microsomia, micrognathia, retrognathia, orbital hypotelorism and enophthalmos Genetic testing was performed via a custom Whole Exome Slice at GeneDx laboratories and included the MYH3 and TNNI2 genes. Results revealed a heterozygous pathogenic change in MYH3 (c.2015 G>A;p. R6724) consistent with the diagnosis of Freeman-Sheldon syndrome. Conclusion: The presentation of “midline mandibular cleft” on fetal ultrasound was the most specific prenatal finding. This is a very rare fetal finding. Thus, it should prompt further evaluation to assess for true clefting versus ridging or creasing. Additionally, targeted assessment for other findings or clinical clues for Freeman-Sheldon syndrome, such as contractures, “windmill vane” hand, and mouth size, could aid in the differential diagnosis considerations and the diagnostic process. Admittedly, these are position and quality dependent, and are challenging to assess even in ideal situations. The phenotype of the father was immediately recognizable. However, due to COVID-19 pandemic restrictions, prior to the infant’s birth, only telehealth visits were conducted and the father’s participation was by telephone. This limited the ability to narrow the differential diagnosis without visualization of his distinct phenotypic features. Finally, missed opportunities to diagnose the father prior to this pregnancy occurred. Many clinics send “no show” letters to referring providers and patients, as we do. Emphasizing the importance of diagnosis prior to pregnancy for individuals concerned about having a genetic disorder should be considered as part of the information shared in these letters.

Patient Perceptions of Drive Through Medical Treatment Facilities During the COVID-19 Pandemic

Study Objectives: The cumulative burden of the COVID-19 virus on the US healthcare system is substantial. To help mitigate this burden, novel solutions including tele-health and dedicated screening facilities have been utilized. However, there is limited data on the efficacy of such models and none assessing patient comfort levels with these changes in health care delivery. The aim of our study was to evaluate patients’ perceptions of a drive through medical treatment system in the setting of the COVID-19 pandemic. Methods: In response to the COVID-19 pandemic, NMCP’s emergency department established a drive-through medical evaluation facility (DMEF) in proximity to the emergency department. The DMEF was designed to allow full evaluation of patients to include: vital signs, complete medical history, clinician physical examination, limited point-of-care testing and medication distribution. All patients presenting to the emergency department with symptoms of potential COVID etiology and deemed non-critical were directed to the DMEF for initial evaluation. Patients were surveyed about their experience following their visit. An anonymous questionnaire consisting of 5 questions, utilizing a 5-point Likert scale was distributed via electronic tablet. Results: A total of 827 responses were obtained over two months. Three quarters of respondents believed care received was similar to that in a traditional emergency department. Overall positive impression of the drive-thru was 86.6%, and 95% believed that it was more convenient. Conclusion: Overall the drive-thru medical system was perceived as more convenient than the emergency department, and is viewed as a positive experience. While a dramatic change in the delivery model of medical care, if such systems are able to provide comparable levels of care, they may represent a viable option for sustained and surge health care delivery.

Home Pulse Oximetry Monitoring for Patients With Suspected COVID-19: A Pilot Assessment of Patient Engagement and Compliance

Study Objectives: Patients infected with SARS-CoV-2 who are evaluated in the emergency department but well enough to go home are still at risk for clinical deterioration. They may benefit from a program to monitor oxygen levels at home using portable pulse oximeter devices. Our study aims to evaluate patient engagement in and compliance with a home pulse oximetry monitoring program. The results of this study will be important to inform development and operationalization of remote patient monitoring programs. Methods: This was a single center, prospective pilot study of patients who presented to the ED or urgent care for symptoms consistent with SARS-CoV-2 infection and were considered to have some risk of clinical deterioration and thus could benefit from home SpO2 monitoring. Subjects were given a portable pulse oximeter and diary. They were instructed to perform readings at rest and with exertion twice daily for 14 days. Patients also recorded the presence or absence of symptoms associated with COVID-19 and whether they required additional medical care due to worsening symptoms. Subjects were contacted daily to obtain the recorded data. If contact could not be made with 3 attempts on each of 3 successive days, the subject was considered lost to follow up. The primary outcome of interest was patient engagement in the program defined as completion of the entire 14-day assessment. Secondary outcomes included patient compliance with performing the SpO2 readings and the proportion of subjects who had worsening clinical status requiring medical evaluation. Patient compliance was calculated as a percentage of completed readings out of the total number of possible readings. The difference in engagement and compliance rates between COVID-positive and COVID-negative patients was calculated using the Pearson Chi-squared test and Mann-Whitney U test, respectively. Results: Fifty patients were enrolled in the study with 3 screen failures. The remaining 47 were included in the final analysis. All patients received a qualitative test for detection of SARS-CoV-2;27 (57.4%) patients tested positive. Overall, engagement in the program was 46.8% with no significant difference between COVID- positive and COVID-negative groups (48.15% vs 45 %, p = 0.831). Median compliance was 42.9% (IQR 22.22 78.57) with compliance of 50.0% (IQR 20 - 85.71) and 42.86% (IQR 22.92 - 76.44) for COVID-positive and COVID-negative groups, respectively (p= 0.838). A total of 4 patients required additional medical care during the study period. Of those, two sought medical attention after advisement by the study team members due to decreasing SpO2 levels. Conclusion: Our study demonstrated that there was limited engagement and compliance in a 14-days home pulse oximetry monitoring program. A positive SARS-CoV-2 test did not predict a higher likelihood of engagement or compliance. Our program was helpful in detecting worsening SpO2 levels in two patients who sought medical care and were admitted for further management. These results support the use of home pulse oximetry monitoring;however, design of programs should focus on increasing patient engagement and compliance.

Predictors of Hospitalization Due to Coronavirus Disease 2019 (COVID-19) at a Veterans Affairs Medical Center

Background. During the COVID-19 pandemic, the Veterans Affairs Long Beach Healthcare System (VALB HCS) saw a surge of patients with a positive SARS-CoV-2 test. There is a lack of guidance on triaging patients with COVID-19 in the clinical literature. To address this need, our study evaluated factors that predicted hospitalization of patients due to COVID-19. Methods. This was a retrospective cohort study of patients with a positive SARSCoV-2 test and medical evaluation at the VALB HCS between August 1 and December 31, 2020. SARS-CoV-2 positive patients admitted to the hospital for a non-COVID-19 related diagnosis were excluded. At the time of initial evaluation, demographic, clinical, and laboratory data, and PCR cycle threshold were collected and compared between patients admitted to the hospital and those managed in the community. A multiple logistic regression analysis was conducted to evaluate predictors for hospitalization due to COVID-19. Results. Of 748 patients, 94 were admitted to the hospital and 654 were community-managed. The outcomes from the logistic regression analysis indicated that the model explained 58.8% of variance and was a significant predictor of hospitalization (X2 [8, 737] = 277.5, p< 0.0001). Patients with self-reported shortness of breath (OR=12.14, 95% CI=6.43-22.92) or diarrhea (OR=2.78, 95% CI=1.33-5.84) were more likely to be hospitalized, whereas patients with sore throat (OR=0.095, 95% CI=0.017-0.53) or body ache (OR=0.42, 95% CI=0.20-0.89) were less likely to be hospitalized than patients not having such symptoms. Every unit increase in patients' age and temperature increased the likelihood of hospitalization by 7.6% and 62.7%, respectively. Every unit increase in patients' diastolic pressure and SpO2% decreased the likelihood of hospitalization by 6.1% and 3.6%, respectively. Conclusion. Our findings indicate that patients with shortness of breath, diarrhea, temperature, and old age were more likely to be hospitalized due to COVID-19. The results may help providers in clinical decision making regarding whether to admit the patient or not. These findings may be especially helpful when hospital bed availability is limited.