A comparative analysis exposes an amplification delay distinctive to SARS-CoV-2 Omicron variants of clinical and public health relevance.

Mutations in the SARS-CoV-2 genome may negatively impact a diagnostic test, have no effect, or turn into an opportunity for rapid molecular screening of variants. Using an in-house FDA Emergency Used Authorized RT-qPCR-based COVID-19 diagnostic assay, we combined sequence surveillance of viral variants and computed PCR efficiencies for mismatched templates. We found no significant mismatches for the N, E, and S set of assay primers until the Omicron variant emerged in late November 2021. We found a single mismatch between the Omicron sequence and one of our assay's primers caused a >4 cycle delay during amplification without impacting overall assay performance. Starting in December 2021, clinical specimens received for COVID-19 diagnostic testing that generated a Cq delay greater than 4 cycles were sequenced and confirmed as Omicron. Clinical samples without a Cq delay were largely confirmed as the Delta variant. The primer-template mismatch was then used as a rapid surrogate marker for Omicron. Primers that correctly identified Omicron were designed and tested, which prepared us for the emergence of future variants with novel mismatches to our diagnostic assay's primers. Our experience demonstrates the importance of monitoring sequences, the need for predicting the impact of mismatches, their value as a surrogate marker, and the relevance of adapting one's molecular diagnostic test for evolving pathogens.

Suprachoroidal Retinal prostheses, longterm stability and safety results

Purpose : To report the longterm safety and stability of two suprachoroidal retinal prosthesis trials (NCT01603576, NCT03406416), comprising of seven patients, with followup ranging from two to nine years. Methods : Three patients with retinitis pigmentosa were implanted with our prototype 24 channel suprachoroidal retinal prosthesis in May-August 2012. One patient had the entire device removed following the trial in 2014 for a medical reason unrelated to the device. The other two patients had the intraocular array left in situ and the percutaneous connector removed, as planned. Ocular followup has continued since that time, albeit interrupted due to the Covid 19 pandemic. Four patients with retinitis pigmentosa were implanted with our second generation 44 channel fully implantable device in February to August 2018. They continue to use the device in the home enviroment. Ocular assessments including clinical examination, colour fundus photographs and optical coherence tomography (OCT) have been used to assess stability of the devices and retinal health longitudinally in patients (P) 1-7. Results : Electrode to retina distance OCT measurements over two to nine years, calculated by comparing group means, showed an increase over time. (Wilcoxon, p=0.03) In the prototype trial, the increase appeared linked to fibrosis and stimulation, with no progression once devices were inactivated, in the second generation trial, it seemed primarily due to passive fibrosis. Retinal thickness OCT measurements showed a slow reduction in central retinal thickness, as expected, due to progression of dystrophic disease. (Wilcoxon, p=0.11) Device position compared to the optic nerve head (ONH) was calculated and three patients demonstrated some temporal movement. P1 position returned to baseline over seven years, P2 stabilised over three months and P6 had a temporary choroidal effusion event which settled spontaneously. Function of the four Generation two fully implantable devices remains stable. Conclusions : Using fundus photography and OCT measurements we demonstrate that retinal prostheses implanted in the suprachoroidal space for up to nine years are overall stable in position and cause mild progressive fibrosis in the suprachoroidal space. Longterm assessment of the changes in the retina are all consistent with the underlying retinal dystrophy. This provides further evidence of the safety of the suprachoroidal surgical approach for retinal prostheses.

Health trajectories of frail, older people while cocooning during the covid-19 pandemic

Background: Cocooning, i.e. staying at home and reducing interaction with others, was a key part of the strategy to protect older people during the COVID-19 pandemic. Unfortunately, there are concerns this has had a negative impact on the physical and mental wellbeing of those who have been isolated. Methods: We completed a survey of 150 patients (55% female, mean age 79.8 years, averageClinical Frailty Scale 4.8) attending ambulatory medical services in a large university hospital. Questions were focused on: access to healthcare services, mental health, physical health, and attitudes to COVID-19 restrictions. Results: Almost 40% reported that their mental health was 'worse' or 'much worse' while cocooning, while over 40% reported a decline in their physical health. Over 57% had a scheduled healthcare-related visit cancelled while cocooning, most frequently hospital outpatient appointments. Worryingly, almost 1/6 reported not seeking medical attention for an illness that they would usually. Of these, half did not as they were worried about catching COVID and 46% did not as this service was not currently available to them. Conclusion: The COVID-19 pandemic and lack of access to essential services, both medical and social, has had a devastating impact on older people. This is evident in both the acute presentations to hospital and the longer-term impact it has had on health and function. It is important that in the future clear policies are in place to enable older people to access care when they need it.

IMPROVING INPATIENT INFLUENZA VACCINATION RATES—THE VALUE OF AN ELECTRONIC PATIENT RECORD REMINDER SYSTEM

Background Influenza vaccination, particularly for vulnerable, older adults, will have added importance this winter given the possibility of further waves of COVID-19 pandemic. Previous interventions at the study site noted poor awareness on the need for inpatient Influenza vaccination1. This study examines a vaccination reminder process using an electronic patient record (EPR) to identify high-priority eligible inpatients. Methods The study site is a 900-bed university teaching hospital with all clinical notes accessed via an EPR. We included a convenience sample of 750 adults aged≥50 years (mean age 75.9 +/− 0.4 years, 48% female) and high-priority for influenza vaccination (Age > 65 years and/or length of stay (LOS) >30 days) from October 1st 2020 to January 12th 2021. A live electronic dashboard identified eligible inpatients for vaccination, prompting vaccination reminders to the clinical teams via the antimicrobial pharmacist. Data was collected retrospectively. Logistic regression models reporting odds ratios were used to assess the association of these reminders with vaccine uptake. Results Over one third (35%, 264/750) of high-priority patients received the Influenza vaccine while inpatients, including 40% aged ≥80 years. The reminder was sent on 41% (305/750) of patients and was associated with an almost 50% higher likelihood of vaccination after adjusting for other covariates (Odds Ratio 1.48 (95% CI 1.00–2.20);p = 0.048). Other factors independently associated with vaccination were advancing age (Odds Ratio 2.69 (95% CI 1.12–6.47) for age ≥ 80 years);LOS (4% higher likelihood of vaccination for every additional day in hospital) and admission under geriatric medicine (Odds Ratio 3.71 (95% CI 2.45–5.62) when compared to other specialities). Conclusion Our study shows relatively low uptake of inpatient Influenza vaccination and strategies to improve uptake are required. Reminders sent to clinical teams using the EPR appear to be an effective means of increasing Influenza vaccination and should be considered as part of this year’s inpatient vaccination drive.

THE ‘WISH TO DIE’ AMONGST OLDER PEOPLE IN IRELAND IN THE CONTEXT OF THE DYING WITH DIGNITY BILL

Background ‘Wish to Die’ (WTD) involves thoughts of or wishes for one’s own death or that one would be better off dead. Assisted dying is the act of deliberately providing medical assistance to another person who wishes to end their own life. Currently, in Ireland, it is illegal to provide such assistance to people with WTD or suicidal ideation. However, a new bill that would legalise assisted dying for those with terminal illnesses, the Dying with Dignity Bill 2020, is due to be considered by lawmakers in Ireland in the coming months. In order to inform discussion around this complex issue, we examine the prevalence and longitudinal course of WTD in a large population-representative sample of older people. Methods To define WTD, participants were asked: ‘In the last month, have you felt that you would rather be dead?’ Depressive symptoms were measured using the CES-D. Mortality data were compiled by linking administrative death records to individual-level survey data from the study. Results At Wave 1, 3.5% of participants (279/8,174) reported WTD. Both persistent loneliness (OR 5.73 (95% CI 3.41–9.64)) and depressive symptoms (OR 6.12 (95% CI 4.33–8.67)) were independently associated with WTD. Of participants who first reported WTD at Wave 1 or 2, 72% did not report WTD when reassessed after 2 years, and the prevalence of depressive symptoms (−44%) and loneliness (−19%) was more likely to decline in this group at follow-up. Fifteen per cent of participants expressing WTD at Wave 1 died during a 6-year follow-up. Conclusion WTD amongst community-dwelling older people is frequently transient and is strongly linked with the course of depressive symptoms and loneliness. An enhanced focus on improving access to mental health care and addressing social isolation in older people should therefore be a public health priority, particularly in the current context of the Covid-19 pandemic.

Physical and mental health of older people while cocooning during the COVID-19 pandemic.

BACKGROUND: Cocooning or shielding, i.e. staying at home and reducing face-to-face interaction with other people, was an important part of the response to the COVID-19 pandemic for older people. However, concerns exist regarding the long-term adverse effects cocooning may have on their physical and mental health. AIM: To examine health trajectories and healthcare utilization while cocooning in a cohort of community-dwelling people aged ≥70 years. DESIGN: Survey of 150 patients (55% female, mean age 80 years and mean Clinical Frailty Scale Score 4.8) attending ambulatory medical services in a large urban university hospital. METHODS: The survey covered four broad themes: access to healthcare services, mental health, physical health and attitudes to COVID-19 restrictions. Survey data were presented descriptively. RESULTS: Almost 40% (59/150) reported that their mental health was 'worse' or 'much worse' while cocooning, while over 40% (63/150) reported a decline in their physical health. Almost 70% (104/150) reported exercising less frequently or not exercising at all. Over 57% (86/150) of participants reported loneliness with 1 in 8 (19/150) reporting that they were lonely 'very often'. Half of participants (75/150) reported a decline in their quality of life. Over 60% (91/150) agreed with government advice for those ≥70 years but over 40% (61/150) reported that they disliked the term 'cocooning'. CONCLUSIONS: Given the likelihood of further restrictions in coming months, clear policies and advice for older people around strategies to maintain social engagement, manage loneliness and continue physical activity and access timely medical care and rehabilitation services should be a priority.