A qualitative study into the barriers and facilitators to effective communication with people with age-related hearing loss in community pharmacy settings

Introduction: One in six adults are affected by hearing loss, and this number increases with age.(1) Inadequate communication is a barrier to the delivery of effective care for people with hearing loss.(2) Communication regarding medicines is particularly relevant to the pharmaceutical care of older people who are more likely to be living with hearing loss, have multiple comorbidities and experience polypharmacy, a risk factor for adverse drug events. This study sought to explore factors that facilitate and impede communication with people with age-related hearing loss (presbycusis) in the community pharmacy, to provide a base upon which to identify solutions/ interventions to improve these interactions. Aim(s): To explore the barriers and facilitators to effective communication with people with age-related hearing loss in the community pharmacy setting. Method(s): This qualitative study consisted of semistructured interviews with people with age-related hearing loss (presbycusis), older people (>50 years old) without hearing loss, and focus groups and interviews with community pharmacists, conducted between March - June 2022. Participants were recruited purposively via advert and snowballing. Interviews and focus groups were conducted using Microsoft Teams or Zoom;two interviews were held by telephone. Data was analysed using the framework method. Result(s): Sixteen people with age-related hearing loss and three older people without hearing loss took part. Eight community pharmacists took part across two focus groups and one interview. Four main themes were identified. The first was 'grappling with the environment'. This theme reflects the multitude of environmental barriers to communication and person-centred pharmaceutical care such as heavy workload, time constraints, lack of privacy, noise levels and Covid-19 safety measures on communication. The second was 'promoting acknowledgment and inclusion of hearing loss in the pharmacy'. This theme captures the perception among patients that their hearing loss is not relevant to the community pharmacy setting and that more could be done to signify that a pharmacy recognises the needs of those with hearing loss. Third, 'patient perceptions and use of community pharmacy services'. This theme highlights the awareness and perceptions of the role of the pharmacy that is, primarily or exclusively as a place to collect prescriptions and the limited interaction with pharmacy personnel. The final theme was 'differing perceptions of patients and pharmacists about communication'. This theme articulates the varying patient-provider perceptions about communication and levels of awareness among pharmacists about the key facilitators to communication. Conclusion(s): This study garnered rich insights about the experiences of accessing and providing pharmaceutical care for people with age-related hearing loss within the community pharmacy setting. However, due to the Covid- 19 pandemic, data collection was chiefly conducted online and the findings cannot be considered reflective of the experiences of older people facing digital exclusion. There is clearly a need to improve pharmacists' awareness of, access to and implementation of strategies, adaptations, and assistive technologies to facilitate communication with people with hearing loss. Future research should identify interventions to support the implementation of strategies/adaptations that are tailored to the needs of people with hearing loss and pharmacists in order to engender hearing-friendly community pharmacies.

The Changing Impact of Vaccines in the Covid-19 Pandemic: A Modeling Study

Background: Much of the world's population had already been infected with COVID-19 by the time that the Omicron variant emerged at the end of 2021, but the scale of the Omicron wave was larger than any that had come before or since, and left a global imprinting of immunity which changed the COVID landscape. In this study, we explore the changing value of vaccines in a landscape of dynamic immunity and rapidly evolving variants of concern. Method(s): We use Covasim, an established agent-based model of COVID-19 enhanced with detailed intra-host dynamics. First, we simulate a vaccine trial over March 2020 - April 2022 within a population resembling that of South Africa, and estimate how both vaccine efficacy (reduction in the risk of severe disease for vaccinated vs unvaccinated individuals) and efficiency (number of doses needed to avert a death) change as the population experiences waves of wild-type, Beta, Delta, and Omicron infections. Next, we introduce six hypothetical variants starting from February 2022 and evaluate the impact of (a) the existing set of vaccines, and (b) vaccines specifically targeted to the new variants. Result(s): We estimate that within our simulated population, vaccine efficacy against severe disease decreased from 80% to 20% in the wake of the first wave of wild-type COVID-19, then increased back to ~70% over the latter half of 2020 as population immunity waned. This pattern repeated following each subsequent wave of infections, with vaccine efficacy falling to its lowest (10%) in the immediate wake of the Omicron wave in December 2021. The efficiency of vaccination decreases over time at an increasing rate: at peak efficiency, fewer than 100 doses would have been required to avert a single death, but by the end of January 2022, we estimate that nearly 4,000 doses would be required to avert a single death. We find that variant-chasing vaccines will only add value above pre-existing vaccines if we can shorten the window between variant introduction and vaccine deployment to under three weeks, an impossible time-frame without significant NPI use. Conclusion(s): Although the vaccines have proven to be remarkably effective, our work demonstrates that the population immunity acquired over the first two years of the pandemic significantly reduced the impact per dose of doses delivered after this time. Next-generation vaccines to fight future COVID variants and/or other respiratory diseases must be delivered rapidly at scale for vaccine strategies to be maximally effective.

fvWillingness to Vaccinate Children against COVID-19 Declined During the Pandemic

Objectives To document the level of vaccine hesitancy in caregivers' of children younger than 12 years of age over the course of the pandemic in Pediatric Emergency Departments (ED). Study design Ongoing multicenter, cross-sectional survey of caregivers presenting to 19 pediatric EDs in the USA, Canada, Israel, and Switzerland during first months of the pandemic (phase1), when vaccines were approved for adults (phase2) and most recently when vaccines were approved for children (phase3). Results Willingness to vaccinate rate declined over the study period (59.7%, 56.1% and 52.1% in the three phases). Caregivers who are fully vaccinated, who have higher education, and those worried their child had COVID-19 upon arrival to the ED, were more likely to plan to vaccinate in all three phases. Mothers were less likely to vaccinate early in the pandemic, but this hesitancy attenuated in later phases. Older caregivers were more willing to vaccinate, and caregivers of older children were less likely to vaccinate their children in phase 3. During the last phase, willingness to vaccinate was lowest in those who had a primary care provider but did not rely on their advice for medical decisions (34%). Those with no primary care provider and those who do and rely on their medical advice, had similar rates of willingness to vaccinate (55.1% and 52.1%, respectively). Conclusions COVID-19 vaccine hesitancy is widespread and growing over time, and public health measures should further try to leverage identified factors associated with hesitancy in order to enhance vaccination rates among children.

Right care, right now: QR code bank to enable clinical staff to access healthcare resources

Historically, information such as protocols and treatment pathways from specialist teams were shared with ward staff in paper format which proved cumbersome and difficult to update. Improvements were made with the addition of an intranet site, where protocols could be stored and accessed by clinical staff, however it was recognised that navigating the intranet site was not always straightforward and took up precious nursing time. The tissue viability team at the Royal United Hospitals NHS Foundation Trust (RUH) considered how such information might be made more readily available to clinicians. Inspired by widespread increased use of QR codes in public places during the COVID-19 pandemic, the team produced a poster containing multiple QR codes, enabling clinical staff to have instant access to wound care protocols as soon as the information was needed.Copyright © 2023, OmniaMed Communications Ltd. All rights reserved.

Willingness to vaccinate children against COVID-19 declined during the pandemic.

OBJECTIVES: To document the level of vaccine hesitancy in caregivers' of children younger than 12 years of age over the course of the pandemic in Pediatric Emergency Departments (ED). Study design Ongoing multicenter, cross-sectional survey of caregivers presenting to 19 pediatric EDs in the USA, Canada, Israel, and Switzerland during first months of the pandemic (phase1), when vaccines were approved for adults (phase2) and most recently when vaccines were approved for children (phase3). RESULTS: Willingness to vaccinate rate declined over the study period (59.7%, 56.1% and 52.1% in the three phases). Caregivers who are fully vaccinated, who have higher education, and those worried their child had COVID-19 upon arrival to the ED, were more likely to plan to vaccinate in all three phases. Mothers were less likely to vaccinate early in the pandemic, but this hesitancy attenuated in later phases. Older caregivers were more willing to vaccinate, and caregivers of older children were less likely to vaccinate their children in phase 3. During the last phase, willingness to vaccinate was lowest in those who had a primary care provider but did not rely on their advice for medical decisions (34%). Those with no primary care provider and those who do and rely on their medical advice, had similar rates of willingness to vaccinate (55.1% and 52.1%, respectively). CONCLUSIONS: COVID-19 vaccine hesitancy is widespread and growing over time, and public health measures should further try to leverage identified factors associated with hesitancy in order to enhance vaccination rates among children.

Technical challenges of modelling real-life epidemics and examples of overcoming these.

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the importance of mathematical modelling in informing and advising policy decision-making. Effective practice of mathematical modelling has challenges. These can be around the technical modelling framework and how different techniques are combined, the appropriate use of mathematical formalisms or computational languages to accurately capture the intended mechanism or process being studied, in transparency and robustness of models and numerical code, in simulating the appropriate scenarios via explicitly identifying underlying assumptions about the process in nature and simplifying approximations to facilitate modelling, in correctly quantifying the uncertainty of the model parameters and projections, in taking into account the variable quality of data sources, and applying established software engineering practices to avoid duplication of effort and ensure reproducibility of numerical results. Via a collection of 16 technical papers, this special issue aims to address some of these challenges alongside showcasing the usefulness of modelling as applied in this pandemic. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

The Royal Society RAMP modelling initiative.

Normally, science proceeds following a well-established set of principles. Studies are done with an emphasis on correctness, are submitted to a journal editor who evaluates their relevance, and then undergo anonymous peer review by experts before publication in a journal and acceptance by the scientific community via the open literature. This process is slow, but its accuracy has served all fields of science well. In an emergency situation, different priorities come to the fore. Research and review need to be conducted quickly, and the target audience consists of policymakers. Scientists must jostle for the attention of non-specialists without sacrificing rigour, and must deal not only with peer assessment but also with media scrutiny by journalists who may have agendas other than ensuring scientific correctness. Here, we describe how the Royal Society coordinated efforts of diverse scientists to help model the coronavirus epidemic. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

Statistical and agent-based modelling of the transmissibility of different SARS-CoV-2 variants in England and impact of different interventions.

The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and the agent-based model Covasim, in June 2021, to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B.1.177 and Delta to be 65-90% more transmissible than Alpha. Using these estimates in Covasim (calibrated 1 September 2020 to 20 June 2021), in June 2021, we found that due to the high transmissibility of Delta, resurgence in infections driven by the Delta variant would not be prevented, but would be strongly reduced by delaying the relaxation of restrictions by one month and with continued vaccination. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

Compositional modelling of immune response and virus transmission dynamics.

Transmission models for infectious diseases are typically formulated in terms of dynamics between individuals or groups with processes such as disease progression or recovery for each individual captured phenomenologically, without reference to underlying biological processes. Furthermore, the construction of these models is often monolithic: they do not allow one to readily modify the processes involved or include the new ones, or to combine models at different scales. We show how to construct a simple model of immune response to a respiratory virus and a model of transmission using an easily modifiable set of rules allowing further refining and merging the two models together. The immune response model reproduces the expected response curve of PCR testing for COVID-19 and implies a long-tailed distribution of infectiousness reflective of individual heterogeneity. This immune response model, when combined with a transmission model, reproduces the previously reported shift in the population distribution of viral loads along an epidemic trajectory. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

Rule-based epidemic models.

Rule-based models generalise reaction-based models with reagents that have internal state and may be bound together to form complexes, as in chemistry. An important class of system that would be intractable if expressed as reactions or ordinary differential equations can be efficiently simulated when expressed as rules. In this paper we demonstrate the utility of the rule-based approach for epidemiological modelling presenting a suite of seven models illustrating the spread of infectious disease under different scenarios: wearing masks, infection via fomites and prevention by hand-washing, the concept of vector-borne diseases, testing and contact tracing interventions, disease propagation within motif-structured populations with shared environments such as schools, and superspreading events. Rule-based models allow to combine transparent modelling approach with scalability and compositionality and therefore can facilitate the study of aspects of infectious disease propagation in a richer context than would otherwise be feasible.

DELIRIUM IN COVID-19: COMMON AND CLINICALLY SIGNIFICANT: EXPERIENCES FROM THE NIGHTINGALE HOSPITAL EXETER

Background Delirium is an independent predictor of mortality in patients admitted with community-acquired pneumonia (Pieralli, 2014), but significance and incidence in Covid-19 infection has not been established. The Nightingale Hospital Exeter (NHE) as a multidisciplinary team model, managed 242 patients with Covid-19 from November 2020 to February 2021. This study identifies the delirium incidence, outcome, premorbid function and demographics of this cohort. Methods Electronic records were retrospectively reviewed for keywords ‘Delirium’, ‘Hyperactive’, ‘Hypoactive’, ‘Confused’ and ‘Muddled’. Patients were categorised as Hyperactive, Hypoactive or Confused/non-specified. Prior functional support (independent, package of care, residential or nursing care) and presence of pre-established neurological conditions (including dementia) were noted. Results 242 patients were included, average age 84 years (range 59–102). Of these patients, 130 (54%) developed delirium (29 (22%) hyperactive, 37 (28%) hypoactive, 2 (1%) mixed and 62 (48%) ‘confused’/non-specified). Of those with delirium, 56 (43%) were previously living independently and 51 (39%) were living at home with a package of care. 60 (46%) of those diagnosed had no pre-existing neurological condition, 32% had underlying dementia. There were 37 deaths at NHE (mortality 15%), 73% of these patients had delirium during their admission compared to 50% of those who survived. Conclusions Over half this cohort developed delirium, a high proportion of whom had been living independently prior to admission with no pre-existing neurological condition, emphasising how common delirium is in patients with Covid-19. In a comparable cohort with pneumonia (mean age 82 years, range 65–99) 25% developed delirium, and it was an independent predictor of in-hospital mortality (Pieralli, 2014). The fact that 73% of all patients who died developed delirium suggests it may have important prognostic implications, and both this and the high incidence indicate further work is required to fully understand how to prevent and manage delirium in Covid-19.

Modelling the impact of reopening schools in the UK in early 2021 in the presence of the alpha variant and with roll-out of vaccination against SARS-CoV-2.

Following the resurgence of the COVID-19 epidemic in the UK in late 2020 and the emergence of the alpha (also known as B117) variant of the SARS-CoV-2 virus, a third national lockdown was imposed from January 4, 2021. Following the decline of COVID-19 cases over the remainder of January 2021, the question of when and how to reopen schools became an increasingly pressing one in early 2021. This study models the impact of a partial national lockdown with social distancing measures enacted in communities and workplaces under different strategies of reopening schools from March 8, 2021 and compares it to the impact of continual full national lockdown remaining until April 19, 2021. We used our previously published agent-based model, Covasim, to model the emergence of the alpha variant over September 1, 2020 to January 31, 2021 in presence of Test, Trace and Isolate (TTI) strategies. We extended the model to incorporate the impacts of the roll-out of a two-dose vaccine against COVID-19, with 200,000 daily vaccine doses prioritised by age starting with people 75 years or older, assuming vaccination offers a 95% reduction in disease acquisition risk and a 30% reduction in transmission risk. We used the model, calibrated until January 25, 2021, to simulate the impact of a full national lockdown (FNL) with schools closed until April 19, 2021 versus four different partial national lockdown (PNL) scenarios with different elements of schooling open: 1) staggered PNL with primary schools and exam-entry years (years 11 and 13) returning on March 8, 2021 and the rest of the schools years on March 15, 2020; 2) full-return PNL with both primary and secondary schools returning on March 8, 2021; 3) primary-only PNL with primary schools and exam critical years (years 11 and 13) going back only on March 8, 2021 with the rest of the secondary schools back on April 19, 2021 and 4) part-rota PNL with both primary and secondary schools returning on March 8, 2021 with primary schools remaining open continuously but secondary schools on a two-weekly rota-system with years alternating between a fortnight of face-to-face and remote learning until April 19, 2021. Across all scenarios, we projected the number of new daily cases, cumulative deaths and effective reproduction number R until April 30, 2021. Our calibration across different scenarios is consistent with alpha variant being around 60% more transmissible than the wild type. We find that strict social distancing measures, i.e. national lockdowns, were essential in containing the spread of the virus and controlling hospitalisations and deaths during January and February 2021. We estimated that a national lockdown over January and February 2021 would reduce the number of cases by early March to levels similar to those seen in October 2020, with R also falling and remaining below 1 over this period. We estimated that infections would start to increase when schools reopened, but found that if other parts of society remain closed, this resurgence would not be sufficient to bring R above 1. Reopening primary schools and exam critical years only or having primary schools open continuously with secondary schools on rotas was estimated to lead to lower increases in cases and R than if all schools opened. Without an increase in vaccination above the levels seen in January and February, we estimate that R could have increased above 1 following the reopening of society, simulated here from April 19, 2021. Our findings suggest that stringent measures were integral in mitigating the increase in cases and bringing R below 1 over January and February 2021. We found that it was plausible that a PNL with schools partially open from March 8, 2021 and the rest of the society remaining closed until April 19, 2021 would keep R below 1, with some increase evident in infections compared to continual FNL until April 19, 2021. Reopening society in mid-April, without an increase in vaccination levels, could push R above 1 and induce a surge in infections, but the effect of vaccination may be able to control this in future depending on the transmission blocking properties of the vaccines.

Modelling the potential impact of mask use in schools and society on COVID-19 control in the UK.

As the UK reopened after the first wave of the COVID-19 epidemic, crucial questions emerged around the role for ongoing interventions, including test-trace-isolate (TTI) strategies and mandatory masks. Here we assess the importance of masks in secondary schools by evaluating their impact over September 1-October 23, 2020. We show that, assuming TTI levels from August 2020 and no fundamental changes in the virus's transmissibility, adoption of masks in secondary schools would have reduced the predicted size of a second wave, but preventing it would have required 68% or 46% of those with symptoms to seek testing (assuming masks' effective coverage 15% or 30% respectively). With masks in community settings but not secondary schools, the required testing rates increase to 76% and 57%.

Exploring overcrowding trends in an inner city emergence department in the UK before and during COVID-19 epidemic.

BACKGROUND: The COVID-19 pandemic and the associated lockdowns have caused significant disruptions across society, including changes in the number of emergency department (ED) visits. This study aims to investigate the impact of three pre-COVID-19 interventions and of the COVID-19 UK-epidemic and the first UK national lockdown on overcrowding within University College London Hospital Emergency Department (UCLH ED). The three interventions: target the influx of patients at ED (A), reduce the pressure on in-patients' beds (B) and improve ED processes to improve the flow of patents out from ED (C). METHODS: We collected overcrowding metrics (daily attendances, the proportion of people leaving within 4 h of arrival (four-hours target) and the reduction in overall waiting time) during 01/04/2017-31/05/2020. We then performed three different analyses, considering three different timeframes. The first analysis used data 01/04/2017-31/12-2019 to calculate changes over a period of 6 months before and after the start of interventions A-C. The second and third analyses focused on evaluating the impact of the COVID-19 epidemic, comparing the first 10 months in 2020 and 2019, and of the first national lockdown (23/03/2020-31/05/2020). RESULTS: Pre-COVID-19 all interventions led to small reductions in waiting time (17%, p < 0.001 for A and C; an 9%, p = 0.322 for B) but also to a small decrease in the number of patients leaving within 4 h of arrival (6.6,7.4,6.2% respectively A-C,p < 0.001). In presence of the COVID-19 pandemic, attendance and waiting time were reduced (40% and 8%; p < 0.001), and the number of people leaving within 4 h of arrival was increased (6%,p < 0.001). During the first lockdown, there was 65% reduction in attendance, 22% reduction in waiting time and 8% increase in number of people leaving within 4 h of arrival (p < 0.001). Crucially, when the lockdown was lifted, there was an increase (6.5%,p < 0.001) in the percentage of people leaving within 4 h, together with a larger (12.5%,p < 0.001) decrease in waiting time. This occurred despite the increase of 49.6%(p < 0.001) in attendance after lockdown ended. CONCLUSIONS: The mixed results pre-COVID-19 (significant improvements in waiting time with some interventions but not improvement in the four-hours target), may be due to indirect impacts of these interventions, where increasing pressure on one part of the ED system affected other parts. This underlines the need for multifaceted interventions and a system-wide approach to improve the pathway of flow through the ED system is necessary. During 2020 and in presence of the COVID-19 epidemic, a shift in public behaviour with anxiety over attending hospitals and higher use of virtual consultations, led to notable drop in UCLH ED attendance and consequential curbing of overcrowding. Importantly, once the lockdown was lifted, although there was an increase in arrivals at UCLH ED, overcrowding metrics were reduced. Thus, the combination of shifted public behaviour and the restructuring changes during COVID-19 epidemic, maybe be able to curb future ED overcrowding, but longer timeframe analysis is required to confirm this.

Mathematical modeling as a tool for policy decision making: Applications to the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of mathematical modeling in advising scientific bodies and informing public policy making. Modeling allows a flexible theoretical framework to be developed in which different scenarios around spread of diseases and strategies to prevent it can be explored. This work brings together perspectives on mathematical modeling of infectious diseases, highlights the different modeling frameworks that have been used for modeling COVID-19 and illustrates some of the models that our groups have developed and applied specifically for COVID-19. We discuss three models for COVID-19 spread: the modified Susceptible-Exposed-Infected-Recovered model that incorporates contact tracing (SEIR-TTI model) and describes the spread of COVID-19 among these population cohorts, the more detailed agent-based model called Covasim describing transmission between individuals, and the Rule-Based Model (RBM) which can be thought of as a combination of both. We showcase the key methodologies of these approaches, their differences as well as the ways in which they are interlinked. We illustrate their applicability to answer pertinent questions associated with the COVID-19 pandemic such as quantifying and forecasting the impacts of different test-trace-isolate (TTI) strategies.

PNS162 An Initial Framework to Describe and Classify Integrated Scientific Advice Procedures: Trends and Developments

Objectives: To develop a framework to compare integrated scientific advice (ISA) procedures, which are services available to companies to seek advice on a technology’s evidence generation plans from multiple stakeholders including regulators, health technology assessment (HTA) bodies, payers and patients. Methods: Information on key aspects of European and North American ISA procedures were obtained in a desk review of websites, public domain sources and interviews with agency representatives. Using this information, an analytical framework was developed in an internal workshop to describe and classify the procedures. Available ISA procedures were compared using the framework, and current trends and developments identified including COVID-19 impact. Results: The framework classified the characteristics of ISA procedures into five categories: Eligibility and Type of Procedure, Process for Procedure, Briefing Book Requirements, Meeting Advice Deliberations, and Advice Reporting & Follow-up. When comparing procedures, similarities identified included a general focus of scope on clinical and economic (HTA bodies) advice, and a formal meeting between agency and company. Key differences included variation in procedure eligibility and timelines. General trends included increased demand for ISA and resulting agency capacity issues, plus impacts of COVID-19, leading to changes in existing procedure processes and development of new offerings, including: prioritisation of COVID-19-related or therapeutically-critical technologies, acceleration of processes (e.g. new fast-track options), change of meetings to virtual format and more detailed submission requirements, such as companies needing to submit patient-reported outcomes and post-launch evidence plans. Conclusions: The initial framework provides an attempt to describe and classify ISA procedures to support comparisons and the value of seeking advice. Current trends in ISA include a shift towards accelerated procedures, pragmatic approaches to deal with demands on agency capacity and implications of COVID-19. Further research needs to be performed to validate the framework to enable comparison and assess the differential value of ISA procedures.

A case of severe thrombocytopenia in a patient with COVID-19 receiving continuous venovenous hemodialysis

Introduction: Thrombocytopenia is a rare complication of renal replacement therapy with most of the cases reported in intermittent hemodialysis patients. There is limited data regarding the incidence of thrombocytopenia caused by continuous renal replacement therapy (CRRT). We report a case of thrombocytopenia in patient treated with CRRT for severe AKI from COVID-19 sepsis unrelated to heparin. Case Description: A 73-year female with history of type 2 diabetes mellitus was admitted for Coronavirus Disease 2019 (COVID-19) pneumonia. Patient developed acute hypoxic respiratory failure requiring mechanical ventilation despite treatment with hydroxychloroquine, azithromycin and convalescent plasma. Hospital course was complicated by septic shock and acute kidney injury with serum creatinine rising from a baseline of 0.8 mg/dl. Continuous veno-venous hemodialysis (CVVHD) without any anticoagulation was initiated due to severe fluid overload. Significant thrombocytopenia below 50,000/mm3 was noted 2 days after CVVHD treatment. Patient received multiple antibiotics and heparin drip before CVVHD and platelet counts were above 150,000/ mm3. Heparin induced thrombocytopenia (HIT) was ruled out with negative serotonin release assay and platelet counts remain low despite the discontinuation of all potential agents. Disseminated intravascular coagulopathy was excluded based on coagulation tests. Platelet counts finally went up to 160,000/mm3 on subsequent CVVHD holidays and again dropped to 70,000/mm3 after CVVHD was resumed. Discussion: The rate of rise in platelet count more than 150,000/mm3 in 2 days after cessation of CVVHD supports the diagnosis of thrombocytopenia caused by CVVHD. Although the exact mechanisms remain unclear, previous studies suggested that the mechanical destruction of platelets by the hemofilter or allergic reaction to dialyzer membrane as some of the reasons. Some studies have found that severe decline (more than 50%) in platelet count was associated with increased mortality and decreased rate of renal recovery. Thrombocytopenia on CVVHD unrelated to HIT is an under-acknowledged complication. Understanding the multiple etiologies of thrombocytopenia will help prevent the excessive use of blood products, fluid overload state and the potential clotting issue of CVVHD due to transfusion.

The use of ace inhibitors and ARBS in patients admitted for COVID-19

Background: Angiotensin converting enzyme (ACE 2) receptor has been implicated as an entry point for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) causing pandemic coronavirus disease 2019 (COVID-19). Experts have postulated the potential benefits of using ACEI/ARB to reduce the severity of acute lung injury and as the treatment of hypertension in COVID-19. However, there is limited data in showing the renal outcomes after the use of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in COVID-19 patients. Methods: This is a retrospective, single center study of 300 patients diagnosed with COVID-19 confirmed by real-time reverse transcription polymerase chain reaction. Four groups were divided based on ACEI/ARB exposure. Group 1 (n=51 patients;17%) were initiated on ACEIs/ARBs during hospitalization, group 2 (n=58 patients;19%) were on ACEIs/ARBS at home and discontinued, group 3 (n=76 patients;25%) were on ACES/ ARBS at home and continued during hospitalization and group 4 (n=116 patients;38%) were never treated with ACEIs/ARBS. The primary end points including the incidence of AKI using KDIGO definition, hyperkalemia, the necessity of dialysis and the secondary end points being the length of total hospital stays, the recovery rate, mortality rate were compared between group 1,2,3 with 4 using adjusted odd ratios (ORs). Results: In group 1, the use of ACEI/ARB has 4 times higher risk of developing AKI than the control group 4 (P= 0.001, 95% CI of 1.70-9.59). and is 4.6 times for stage 2 or above AKI (P= 0.001;95% CI of 1.8-11.5). OR for hyperkalemia is 5.7 (P= 0.001, 95% CI of 2.09-15.5) and for hemodialysis is 3.7 (P= 0.02, 95% CI of 1.2-11.2). Their mortality rate is increased 2.9 times (P=0.026, 95% CI of 1.23-7.44). In group 2, the incidence of AKI is 7.5 times higher (P= <0.001, 95% CI of 3.3-17) and 3.5 times (P=0.001, 95% CI of 1.6-7.7) for stage 2 above AKI. OR for the initiation of hemodialysis and the mortality rate are not statistically significant after adjusted with variables. In group 3, no statistically significant data were found. Conclusions: Our findings suggest that the initiation of ACEI/ARB in COVID 19 patients have increased risk of AKI, hyperkalemia, necessity of dialysis and mortality rate.