Acute hospital specialist palliative care: multidisciplinary team models and workforce in South West England.

OBJECTIVES: Acute hospital specialist palliative care teams (SPCTs) improve patient care and reduce length of stay. UK guidance recommends SPCTs provide face-to-face assessments 7 days a week and offer 24-hour telephone advice. Little published data exist on SPCT staffing models.This paper aims to explore team structure, funding and impact of COVID-19 on SPCTs across the South West (SW) of England (population of nearly six million). METHODS: Electronic survey to SPCT clinical leads in 15 SW acute hospitals. RESULTS: All 15 acute hospitals have an SPCT. There was variability in SPC clinical nurse specialist and consultant availability, 0.27-2.7 whole-time equivalent (WTE) and 0.1-1.5 WTE, respectively, per 250 beds. 13/15 (87%) provide out-of-hours (OOH) palliative care advice with 60% reliant on charity services. Few SW teams meet national guidance for SPC staffing to bed ratios. 8/15 teams reported greater integration with other services during the COVID-19 pandemic. CONCLUSION: There is significant variability in SPCT structure and staffing. The charity sector (independent hospices) often provides OOH acute hospital SPC advice. Further research is needed to consider the impact of different SPCT models on patient and family outcomes, and the sustainability and opportunities offered by integration of services and collaboration across care settings during COVID-19.

Can nebulised HepArin Reduce morTality and time to Extubation in patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT): Protocol and statistical analysis plan for an investigator-initiated international meta-trial of prospective randomised clinical studies.

There is significant interest in the potential for nebulised unfractionated heparin (UFH), as a novel therapy for patients with COVID-19 induced acute hypoxaemic respiratory failure requiring invasive ventilation. The scientific and biological rationale for nebulised heparin stems from the evidence for extensive activation of coagulation resulting in pulmonary microvascular thrombosis in COVID-19 pneumonia. Nebulised delivery of heparin to the lung may limit alveolar fibrin deposition and thereby limit progression of lung injury. Importantly, laboratory studies show that heparin can directly inactivate the SARS-CoV-2 virus, thereby prevent its entry into and infection of mammalian cells. UFH has additional anti-inflammatory and mucolytic properties that may be useful in this context. METHODS AND INTERVENTION: The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT) is a collaborative prospective individual patient data analysis of on-going randomised controlled clinical trials across several countries in five continents, examining the effects of inhaled heparin in patients with COVID-19 requiring invasive ventilation on various endpoints. Each constituent study will randomise patients with COVID-19 induced respiratory failure requiring invasive ventilation. Patients are randomised to receive nebulised heparin or standard care (open label studies) or placebo (blinded placebo-controlled studies) while under invasive ventilation. Each participating study collect a pre-defined minimum dataset. The primary outcome for the meta-trial is the number of ventilator-free days up to day 28 day, defined as days alive and free from invasive ventilation.

Inhaled nebulised unfractionated heparin for the treatment of hospitalised patients with COVID-19: A multicentre case series of 98 patients.

AIMS: To determine the safety and efficacy-potential of inhaled nebulised unfractionated heparin (UFH) in the treatment of hospitalised patients with COVID-19. METHODS: Retrospective, uncontrolled multicentre single-arm case series of hospitalised patients with laboratory-confirmed COVID-19, treated with inhaled nebulised UFH (5000 IU q8h, 10 000 IU q4h, or 25 000 IU q6h) for 6 ± 3 (mean ± standard deviation) days. Outcomes were activated partial thromboplastin time (APTT) before treatment (baseline) and highest-level during treatment (peak), and adverse events including bleeding. Exploratory efficacy outcomes were oxygenation, assessed by ratio of oxygen saturation to fraction of inspired oxygen (FiO2 ) and FiO2 , and the World Health Organisation modified ordinal clinical scale. RESULTS: There were 98 patients included. In patients on stable prophylactic or therapeutic systemic anticoagulant therapy but not receiving therapeutic UFH infusion, APTT levels increased from baseline of 34 ± 10 seconds to a peak of 38 ± 11 seconds (P < .0001). In 3 patients on therapeutic UFH infusion, APTT levels did not significantly increase from baseline of 72 ± 20 to a peak of 84 ± 28 seconds (P = .17). Two patients had serious adverse events: bleeding gastric ulcer requiring transfusion and thigh haematoma; both were on therapeutic anticoagulation. Minor bleeding occurred in 16 patients, 13 of whom were on therapeutic anticoagulation. The oxygen saturation/FiO2 ratio and the FiO2 worsened before and improved after commencement of inhaled UFH (change in slope, P < .001). CONCLUSION: Inhaled nebulised UFH in hospitalised patients with COVID-19 was safe. Although statistically significant, inhaled nebulised UFH did not produce a clinically relevant increase in APTT (peak values in the normal range). Urgent randomised evaluation of nebulised UFH in patients with COVID-19 is warranted and several studies are currently underway.

Ethical Principles in Personal Protective Equipment Inventory Management Decisions and Partnerships Across State Lines During the COVID-19 Pandemic.

The COVID-19 pandemic created unprecedented strain on the personal protective equipment (PPE) supply chain. Given the dearth of PPE and consequences for transmission, GetMePPE Chicago (GMPC) developed a PPE allocation framework and system, distributing 886 900 units to 274 institutions from March 2020 to July 2021 to address PPE needs. As the pandemic evolved, GMPC made difficult decisions about (1) building reserve inventory (to balance present and future, potentially higher clinical acuity, needs), (2) donating to other states/out-of-state organizations, and (3) receiving donations from other states. In this case study, we detail both GMPC's experience in making these decisions and the ethical frameworks that guided these decisions. We also reflect on lessons learned and suggest which values may have been in conflict (eg, maximizing benefits vs duty to mission, defined in the context of PPE allocation) in each circumstance, which values were prioritized, and when that prioritization would change. Such guidance can promote a values-based approach to key issues concerning distribution of PPE and other scarce medical resources in response to the COVID-19 pandemic and related future pandemics.

America's housing affordability crisis: Perpetuating disparities among people with disability.

America's housing affordability crisis has had various indirect costs on health and safety among people living with disability. The skyrocketing housing prices have exponentially increased with the onset of the COVID-19 pandemic leaving many people at risk for eviction after federal and local moratoriums providing protection during the pandemic expire. Americans with disabilities have been particularly affected by the affordability crisis and it is expected that this major public health problem will only grow as government-provided protections and supports wane. It is critical that both government and various housing organizations consider ways to support affordability, quality, and accessibility in this particularly hard-hit population.

Use of Electronic Medical Records to Estimate Changes in Pregnancy and Birth Rates During the COVID-19 Pandemic.

Importance: The influence of the COVID-19 pandemic on fertility rates has been suggested in the lay press and anticipated based on documented decreases in fertility and pregnancy rates during previous major societal and economic shifts. Anticipatory planning for birth rates is important for health care systems and government agencies to accurately estimate size of economy and model working and/or aging populations. Objective: To use projection modeling based on electronic health care records in a large US university medical center to estimate changes in pregnancy and birth rates prior to and after the COVID-19 pandemic societal lockdowns. Design, Setting, and Participants: This cohort study included all pregnancy episodes within a single US academic health care system retrospectively from 2017 and modeled prospectively to 2021. Data were analyzed September 2021. Exposures: Pre- and post-COVID-19 pandemic societal shutdown measures. Main Outcomes and Measures: The primary outcome was number of new pregnancy episodes initiated within the health care system and use of those episodes to project birth volumes. Interrupted time series analysis was used to assess the degree to which COVID-19 societal changes may have factored into pregnancy episode volume. Potential reasons for the changes in volumes were compared with historical pregnancy volumes, including delays in starting prenatal care, interruptions in reproductive endocrinology and infertility services, and preterm birth rates. Results: This cohort study documented a steadily increasing number of pregnancy episodes over the study period, from 4100 pregnancies in 2017 to 4620 in 2020 (28 284 total pregnancies; median maternal [interquartile range] age, 30 [27-34] years; 18 728 [66.2%] White women, 3794 [13.4%] Black women; 2177 [7.7%] Asian women). A 14% reduction in pregnancy episode initiation was observed after the societal shutdown of the COVID-19 pandemic (risk ratio, 0.86; 95% CI, 0.79-0.92; P < .001). This decrease appeared to be due to a decrease in conceptions that followed the March 15 mandated COVID-19 pandemic societal shutdown. Prospective modeling of pregnancies currently suggests that a birth volume surge can be anticipated in summer 2021. Conclusions and Relevance: This cohort study using electronic medical record surveillance found an initial decline in births associated with the COVID-19 pandemic societal changes and an anticipated increase in birth volume. Future studies can further explore how pregnancy episode volume changes can be monitored and birth rates projected in real-time during major societal events.

Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Mechanical ventilation in intensive care for 48 h or longer is associated with the acute respiratory distress syndrome (ARDS), which might be present at the time ventilatory support is instituted or develop afterwards, predominantly during the first 5 days. Survivors of prolonged mechanical ventilation and ARDS are at risk of considerably impaired physical function that can persist for years. An early pathogenic mechanism of lung injury in mechanically ventilated, critically ill patients is inflammation-induced pulmonary fibrin deposition, leading to thrombosis of the microvasculature and hyaline membrane formation in the air sacs. The main aim of this study was to determine if nebulised heparin, which targets fibrin deposition, would limit lung injury and thereby accelerate recovery of physical function in patients with or at risk of ARDS. METHODS: The Can Heparin Administration Reduce Lung Injury (CHARLI) study was an investigator-initiated, multicentre, double-blind, randomised phase 3 trial across nine hospitals in Australia. Adult intensive care patients on invasive ventilation, with impaired oxygenation defined by a PaO2/FiO2 ratio of less than 300, and with the expectation of invasive ventilation beyond the next calendar day were recruited. Key exclusion criteria were heparin allergy, pulmonary bleeding, and platelet count less than 50 X 109/L. Patients were randomly assigned 1:1, with stratification by site and using blocks of variable size and random seed, via a web-based system, to either unfractionated heparin sodium 25 000 IU in 5 mL or identical placebo (sodium chloride 0·9% 5 mL), administered using a vibrating mesh membrane nebuliser every 6 h to day 10 while invasively ventilated. Patients, clinicians, and investigators were masked to treatment allocation. The primary outcome was the Short Form 36 Health Survey Physical Function Score (out of 100) of survivors at day 60. Prespecified secondary outcomes, which are exploratory, included development of ARDS to day 5 among at-risk patients, deterioration of the Murray Lung Injury Score (MLIS) to day 5, mortality at day 60, residence of survivors at day 60, and serious adverse events. Analyses followed the intention-to-treat principle. There was no imputation of missing data. The trial is registered with the Australian and New Zealand Clinical Trials Register, number ACTRN12612000418875 . FINDINGS: Between Sept 4, 2012, and Aug 23, 2018, 256 patients were randomised. Final follow-up was on Feb 25, 2019. We excluded three patients who revoked consent and one ineligible participant who received no intervention. Of 252 patients included in data analysis, the mean age was 58 years (SD 15), 157 (62%) were men, and 118 (47%) had ARDS. 128 (51%) patients were assigned to the heparin group and 124 (49%) to the placebo group, all of whom received their assigned intervention. Survivors in the heparin group (n=97) had similar SF-36 Physical Function Scores at day 60 compared to the placebo group (n=94; mean 53·6 [SD 31·6] vs 48·7 [35·7]; difference 4·9 [95% CI -4·8 to 14·5]; p=0·32). Compared with the placebo group, the heparin group had fewer cases of ARDS develop to day 5 among the at-risk patients (nine [15%] of 62 patients vs 21 [30%] of 71 patients; hazard ratio 0·46 [95% CI 0·22 to 0·98]; p=0·0431), less deterioration of the MLIS to day 5 (difference -0·14 [-0·26 to -0·02]; p=0·0215), similar day 60 mortality (23 [18%] of 127 patients vs 18 [15%] of 123 patients; odds ratio [OR] 1·29 [95% CI 0·66 to 2·53]; p=0·46), and more day 60 survivors at home (86 [87%] of 99 patients vs 73 [73%] of 100 patients; OR 2·45 [1·18 to 5·08]; p=0·0165). A similar number of serious adverse events occurred in each group (seven [5%] of 128 patients in the heparin group vs three [2%] of 124 patients in the placebo group; OR 2·33 [0·59 to 9·24]; p=0·23), which were a transient increase in airway pressure during nebulisation (n=3 in the heparin group), major non-pulmonary bleeding (n=2 in each group), haemoptysis (n=1 in the heparin group), tracheotomy site bleeding (n=1 in the heparin group), and hypoxaemia during nebulisation (n=1 in the placebo group). INTERPRETATION: In patients with or at risk of ARDS, nebulised heparin did not improve self-reported performance of daily physical activities, but was well tolerated and exploratory outcomes suggest less progression of lung injury and earlier return home. Further research is justified to establish if nebulised heparin accelerates recovery in those who have or are at risk of ARDS. FUNDING: Rowe Family Foundation, TR and RB Ditchfield Medical Research Endowment Fund, Patricia Madigan Charitable Trust, and The J and R McGauran Trust Fund.

INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and statistical analysis plan for an investigator-initiated international metatrial of randomised studies.

AIMS: Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus' entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anticoagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. METHODS: The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) metatrial is a prospective individual patient data analysis of on-going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the metatrial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have additional outcomes. ANALYSIS: We use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn. TRIAL REGISTRATION, ETHICS AND DISSEMINATION: The metatrial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board. Results of this study will be shared with the World Health Organisation, published in scientific journals and presented at scientific meetings.

Patient and provider perspectives of a new prenatal care model introduced in response to the coronavirus disease 2019 pandemic.

BACKGROUND: Randomized controlled trials document the safety and efficacy of reduced frequency prenatal visit schedules and virtual visits, but real-world data are lacking. Our institution created a prenatal care delivery model incorporating these alternative approaches to continue safely providing prenatal care during the coronavirus disease 2019 pandemic. OBJECTIVE: To evaluate institutional-level adoption and patient and provider experiences with the coronavirus disease 2019 prenatal care model. STUDY DESIGN: We conducted a single-site evaluation of a coronavirus disease 2019 prenatal care model incorporating a reduced frequency visit schedule and virtual visits deployed at a suburban academic institution on March 20, 2020. We used electronic health record data to evaluate institution-level model adoption, defined as changes in overall visit frequency and proportion of virtual visits in the 3 months before and after implementation. To evaluate the patient and provider experience with the coronavirus disease 2019 model, we conducted an online survey of all pregnant patients (>20 weeks' gestation) and providers in May 2020. Of note, 3 domains of care experience were evaluated: (1) access, (2) quality and safety, and (3) satisfaction. Quantitative data were analyzed with basic descriptive statistics. Free-text responses coded by the 3 survey domains elucidated drivers of positive and negative care experiences. RESULTS: After the coronavirus disease 2019 model adoption, average weekly prenatal visit volume fell by 16.1%, from 898 to 761 weekly visits; the average weekly proportion of prenatal visits conducted virtually increased from 10.8% (97 of 898) to 43.3% (330 of 761); and the average visit no-show rate remained stable (preimplementation, 4.3%; postimplementation, 4.2%). Of those eligible, 74.8% of providers (77 of 103) and 15.0% of patients (253 of 1690) participated in the surveys. Patient respondents were largely white (180 of 253; 71.1%) and privately insured (199 of 253; 78.7%), reflecting the study site population. The rates of chronic conditions and pregnancy complications also differed from national prevalence. Provider respondents were predominantly white (44 of 66; 66.7%) and female (50 of 66; 75.8%). Most patients and almost all providers reported that virtual visits improved access to care (patients, 174 of 253 [68.8%]; providers, 74 of 77 [96.1%]). More than half of respondents (patients, 124 of 253 [53.3%]; providers, 41 of 77 [62.1%]) believed that virtual visits were safe. Nearly all believed that home blood pressure cuffs were important for virtual visits (patients, 213 of 231 [92.2%]; providers, 63 of 66 [95.5%]). Most reported satisfaction with the coronavirus disease 2019 model (patients, 196 of 253 [77.5%]; providers, 64 of 77 [83.1%]). In free-text responses, drivers of positive care experiences were similar for patients and providers and included perceived improved access to care through decreased barriers (eg, transportation, childcare), perceived high quality of virtual visits for low-risk patients and increased safety during the pandemic, and improved satisfaction through better patient counseling. Perceived drivers of negative care experience were also similar for patients and providers, but less common. These included concerns that unequal access to virtual visits could deepen existing maternity care inequities, concerns that the lack of home devices (eg, blood pressure cuffs) would affect care quality and safety, and dissatisfaction with poor patient-provider continuity and inadequate expectation setting for the virtual visit experience. CONCLUSION: Reduced visit schedules and virtual visits were rapidly integrated into real-world care, with positive experiences for many patients and providers. Future research is needed to understand the health outcomes and care experience associated with alternative approaches to prenatal care delivery across more diverse patient populations outside of the coronavirus disease 2019 pandemic to inform broader health policy decisions.

Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence.

Nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential, for COVID-19-induced acute respiratory distress syndrome (ARDS). COVID-19 ARDS displays the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. Patients infected with SARS-CoV-2 who manifest severe disease have high levels of inflammatory cytokines in plasma and bronchoalveolar lavage fluid and significant coagulopathy. There is a strong association between the extent of the coagulopathy and poor clinical outcomes.The anti-coagulant actions of nebulised UFH limit fibrin deposition and microvascular thrombosis. Trials in patients with acute lung injury and related conditions found inhaled UFH reduced pulmonary dead space, coagulation activation, microvascular thrombosis and clinical deterioration, resulting in increased time free of ventilatory support. In addition, UFH has anti-inflammatory, mucolytic and anti-viral properties and, specifically, has been shown to inactivate the SARS-CoV-2 virus and prevent its entry into mammalian cells, thereby inhibiting pulmonary infection by SARS-CoV-2. Furthermore, clinical studies have shown that inhaled UFH safely improves outcomes in other inflammatory respiratory diseases and also acts as an effective mucolytic in sputum-producing respiratory patients. UFH is widely available and inexpensive, which may make this treatment also accessible for low- and middle-income countries.These potentially important therapeutic properties of nebulised UFH underline the need for expedited large-scale clinical trials to test its potential to reduce mortality in COVID-19 patients.