Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study

Background The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. Methods and findings Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician–principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had—or were at risk of progression to—severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. Conclusions These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. Trial registration ClinicalTrials.gov NCT#: NCT04338360.

Geographic barriers to establishing a successful hospital referral system in rural Madagascar

BackgroundThe provision of emergency and hospital care has become an integral part of the global vision for universal health coverage. To strengthen secondary care systems, we need to accurately understand the time necessary for populations to reach a hospital. The goal of this study was to develop methods that accurately estimate referral and prehospital time for rural districts in low and middle-income countries. We used these estimates to assess how local geography can limit the impact of a strengthened referral programme in a rural district of Madagascar.MethodsWe developed a database containing: travel speed by foot and motorised vehicles in Ifanadiana district; a full mapping of all roads, footpaths and households; and remotely sensed data on terrain, land cover and climatic characteristics. We used this information to calibrate estimates of referral and prehospital time based on the shortest route algorithms and statistical models of local travel speed. We predict the impact on referral numbers of strategies aimed at reducing referral time for underserved populations via generalised linear mixed models.ResultsAbout 10% of the population lived less than 2 hours from the hospital, and more than half lived over 4 hours away, with variable access depending on climatic conditions. Only the four health centres located near the paved road had referral times to the hospital within 1 hour. Referral time remained the main barrier limiting the number of referrals despite health system strengthening efforts. The addition of two new referral centres is estimated to triple the population living within 2 hours from a centre with better emergency care capacity and nearly double the number of expected referrals.ConclusionThis study demonstrates how adapting geographic accessibility modelling methods to local scales can occur through improving the precision of travel time estimates and pairing them with data on health facility use.

Place of Death Among Assisted Living Residents as a Factor of Hospice Regulations

Our objective was to examine the likelihood of dying in RC/AL among a national cohort of fee-for-service Medicare beneficiaries who died in 2018 (N=31,414) as a factor regulations allowing hospice care. We estimated multivariable logistic regression models to examine the association between RC/AL as place of death and supportive hospice regulations, controlling for demographic characteristics, dual Medicare/Medicaid eligibility, years in AL, and hospital referral region (HRR) to control for hospice practice patterns. A majority of beneficiaries in our cohort died in RC/AL; more than half while receiving hospice services. In unadjusted models, the odds of remaining in RC/AL communities until death were significantly higher in the presence of regulations supportive of hospice care. This relationship was no longer significant once adjusting for covariates and an HRR fixed effect, suggesting important variation in end-of-life experiences for AL residents not explained by hospice regulations.

Facility Characteristics Associated With Intensity of Care of Nursing Home Residents With Advanced Dementia

Profound variations in care intensity of nursing home (NH) residents with advanced dementia exist for NHs within and across hospital referral regions (HRRs). Little is known about how these levels of influence relate. Nationwide 2016-2017 Minimum DataSet was used to categorize NHs and HRRs into 4 levels of care intensity based on hospital transfer and tube-feeding rates among residents with advanced dementia: low intensity NH in low intensity HRR; high intensity NH in low intensity HRR; low intensity NH in high intensity HRR; and high intensity NH in high intensity HRR. We used multinomial logistic regression to identify NH characteristics associated with belonging to each of 4-levels of intensity as compared to low intensity NH in low intensity HRRs (reference). We found high intensity NHs in high intensity HRRs were more likely to be in an urbanized area, not have an dementia unit, have an NP/PA on staff, have a higher proportion of residents who were male, age &lt;65, of Black race, and had pressure ulcers, and relatively fewer days on hospice. Whereas in low intensity HRRs, higher proportion of Black residents was the only characteristic associated with being a high intensity NH. These findings suggest potentially modifiable factors within high intensity HRRs that could be targeted to reduce burdensome care, including having a dementia unit, palliative care training for NP/PAs, or increased use of hospice care. This study underscores the critical need to better understand the role race plays in the intensity of care of NH residents with dementia.

Equitable access to cancer patient pathways in Norway – a national registry-based study

Background In 2015, cancer patient pathways (CPP) were implemented in Norway to reduce unnecessary non-medical delay in the diagnostic process and start of treatment. The main aim of this study was to investigate the equality in access to CPPs for patients with either lung, colorectal, breast or prostate cancer in Norway. Methods National population-based data on individual level from 2015 to 2017 were used to study two proportions; i) patients in CPPs without the cancer diagnosis, and ii) cancer patients included in CPPs. Logistic regression was applied to examine the associations between these proportions and place of residence (hospital referral area), age, education, income, comorbidity and travel time to hospital. Results Age and place of residence were the two most important factors for describing the variation in proportions. For the CPP patients, inconsistent differences were found for income and education, while for the cancer patients the probability of being included in a CPP increased with income. Conclusions The age effect can be related to both the increasing risk of cancer and increasing number of GP and hospital contacts with age. The non-systematic results for CPP patients according to income and education can be interpreted as equitable access, as opposed to the systematic differences found among cancer patients in different income groups. The inequalities between income groups among cancer patients and the inequalities based on the patients’ place of residence, for both CPP and cancer patients, are unwarranted and need to be addressed.

Increasing Use of Anticoagulants in Germany and Its Impact on Hospitalization for Tooth Extraction

Objectives This article aimed to compare nationwide time trends of oral anticoagulant prescriptions with the time trend of hospitalization for tooth extraction (TE) in Germany from 2006 through 2017. Patients and Methods We derived the annual number of hospital admissions for TE from the Nationwide Hospital Referral File of the Federal Bureau of Statistics and defined daily doses (DDD) of prescribed anticoagulants in outpatients from reports of the drug information system of the statutory health insurance. Results From 2005 to 2017, annual oral anticoagulation (OAC) treatment rates increased by 143.7%. In 2017, direct oral anticoagulants (DOACs) represented 57.1% of all OAC treatments. The number of cases hospitalized for TE increased by 28.0 only. From all the cases hospitalized for TE in Germany in 2006, 14.2% had a documented history of long-term use of OACs. This proportion increased to 19.6% in 2017. Age-standardized hospitalization rates for all TE cases with long-term use of OACs increased from 6.6 in 2006 to 10.5 cases per 100,000 person-years in 2014 and remained almost unchanged thereafter. Conclusion Our comparison showed that the large increase in OAC treatment rates in general from 2006 to 2017 had only a small impact on hospitalized TE cases with long-term use of OAC which flattens since 2014.

Hospital and Operator Variation in Cardiac Rehabilitation Referral and Participation After Percutaneous Coronary Intervention: Insights From Blue Cross Blue Shield of Michigan Cardiovascular Consortium

BACKGROUND: Despite its established benefit and strong endorsement in international guidelines, cardiac rehabilitation (CR) use remains low. Identifying determinants of CR referral and use may help develop targeted policies and quality improvement efforts. We evaluated the variation in CR referral and use across percutaneous coronary intervention (PCI) hospitals and operators. Methods: We performed a retrospective observational cohort study of all patients who underwent PCI at 48 nonfederal Michigan hospitals between January 1, 2012 and March 31, 2018 and who had their PCI clinical registry record linked to administrative claims data. The primary outcomes included in-hospital CR referral and CR participation, defined as at least one outpatient CR visit within 90 days of discharge. Bayesian hierarchical regression models were fit to evaluate the association between PCI hospital and operator with CR referral and use after adjusting for patient characteristics. Results: Among 54 217 patients who underwent PCI, 76.3% received an in-hospital referral for CR, and 27.1% attended CR within 90 days after discharge. There was significant hospital and operator level variation in in-hospital CR referral with median odds ratios of 3.88 (95% credible interval [CI], 3.06–5.42) and 1.64 (95% CI, 1.55–1.75), respectively, and in CR participation with median odds ratios of 1.83 (95% CI, 1.63–2.15) and 1.40 (95% CI, 1.35–1.47), respectively. In-hospital CR referral was significantly associated with an increased likelihood of CR participation (adjusted odds ratio, 1.75 [95% CI, 1.52–2.01]), and this association varied by treating PCI hospital (odds ratio range, 0.92–3.75) and operator (odds ratio range, 1.26–2.82). Conclusions: In-hospital CR referral and 90-day CR use after PCI varied significantly by hospital and operator. The association of in-hospital CR referral with downstream CR use also varied across hospitals and less so across operators suggesting that specific hospitals and operators may more effectively translate CR referrals into downstream use. Understanding the factors that explain this variation will be critical to developing strategies to improve CR participation overall.

The impact of pulse oximetry on diagnosis, management and outcomes of acute febrile illness in low-income and middle-income countries: a systematic review

BackgroundAcute fever is a common presenting symptom in low/middle-income countries (LMICs) and is strongly associated with sepsis. Hypoxaemia predicts disease severity in such patients but is poorly detected by clinical examination. Therefore, including pulse oximetry in the assessment of acutely febrile patients may improve clinical outcomes in LMIC settings.MethodsWe systematically reviewed studies of any design comparing one group where pulse oximetry was used and at least one group where it was not. The target population was patients of any age presenting with acute febrile illness or associated syndromes in LMICs. Studies were obtained from searching PubMed, EMBASE, CABI Global Health, Global Index Medicus, CINAHL, Cochrane CENTRAL, Web of Science and DARE. Further studies were identified through searches of non-governmental organisation websites, snowballing and input from a Technical Advisory Panel. Outcomes of interest were diagnosis, management and patient outcomes. Study quality was assessed using the Cochrane Risk of Bias 2 tool for Cluster Randomised Trials and Risk of Bias in Non-randomized Studies of Interventions tools, as appropriate.ResultsTen of 4898 studies were eligible for inclusion. Their small number and heterogeneity prevented formal meta-analysis. All studies were in children, eight only recruited patients with pneumonia, and nine were conducted in Africa or Australasia. Six were at serious risk of bias. There was moderately strong evidence for the utility of pulse oximetry in diagnosing pneumonia and identifying severe disease requiring hospital referral. Pulse oximetry used as part of a quality-assured facility-wide package of interventions may reduce pneumonia mortality, but studies assessing this endpoint were at serious risk of bias.ConclusionsVery few studies addressed this important question. In LMICs, pulse oximetry may assist clinicians in diagnosing and managing paediatric pneumonia, but for the greatest impact on patient outcomes should be implemented as part of a health systems approach. The evidence for these conclusions is not widely generalisable and is of poor quality.

Characteristics, hospital referrals and 60-day mortality of older patients living in nursing homes with COVID-19 assessed by a liaison geriatric team during the first wave: a research article

Background The infection by SARS-CoV-2 (COVID-19) has been especially serious in older patients. The aim of this study is to describe baseline and clinical characteristics, hospital referrals, 60-day mortality, factors associated with hospital referrals and mortality in older patients living in nursing homes (NH) with suspected COVID-19. Methods A retrospective observational study was performed during March and April 2020 of institutionalized patients assessed by a liaison geriatric hospital-based team. Were collected all older patients living in 31 nursing homes of a public hospital catchment area assessed by a liaison geriatric team due to the suspicion of COVID-19 during the first wave, when the hospital system was collapsed. Sociodemographic variables, comprehensive geriatric assessment, clinical characteristics, treatment received including care setting, and 60-days mortality were recorded from electronic medical records. A logistic regression analysis was performed to analyze the factors associated with mortality. Results 419 patients were included in the study (median age 89 years old, 71.6 % women, 63.7 % with moderate-severe dependence, and 43.8 % with advanced dementia). 31.1 % were referred to the emergency department in the first assessment, with a higher rate of hospital referral in those with better functional and mental status. COVID-19 atypical symptoms like functional decline, delirium, or eating disorders were frequent. 36.9% had died in the 60 days following the first call. According to multivariate logistic regression age (p 0.010), Barthel index <60 (p 0.002), presence of tachypnea (p 0.021), fever (p 0.006) and the use of ceftriaxone (p 0.004) were associated with mortality. No mortality differences were found between those referred to the hospital or cared at the nursing home. Conclusions and implications 31% of the nursing home patients assessed by a liaison geriatric hospital-based team for COVID-19 were referred to the hospital, being more frequently referred those with a better functional and cognitive situation. The 60-days mortality rate due to COVID-19 was 36.8% and was associated with older age, functional dependence, the presence of tachypnea and fever, and the use of ceftriaxone. Geriatric comprehensive assessment and coordination between NH and the hospital geriatric department teams were crucial.