Higher Risk Of Hospitalization Research Articles

Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in female Syrian hamsters and retains partial susceptibility to treatment

The SARS-CoV-2 main protease (3CLpro) is one of the promising therapeutic targets for the treatment of COVID-19. Nirmatrelvir is the first 3CLpro inhibitor authorized for treatment of COVID-19 patients at high risk of hospitalization. We recently reported on the in vitro selection of SARS-CoV-2 3CLpro resistant virus (L50F-E166A-L167F; 3CLprores) that is cross-resistant with nirmatrelvir and other 3CLpro inhibitors. Here, we demonstrate that the 3CLprores virus replicates efficiently in the lungs of intranasally infected female Syrian hamsters and causes lung pathology comparable to that caused by the WT virus. Moreover, hamsters infected with 3CLprores virus transmit the virus efficiently to co-housed non-infected contact hamsters. Importantly, at a dose of 200 mg/kg (BID) of nirmatrelvir, the compound was still able to reduce the lung infectious virus titers of 3CLprores-infected hamsters by 1.4 log10 with a modest improvement in the lung histopathology as compared to the vehicle control. Fortunately, resistance to Nirmatrelvir does not readily develop in clinical setting. Yet, as we demonstrate, in case drug-resistant viruses emerge, they may spread easily which may thus impact therapeutic options. Therefore, the use of 3CLpro inhibitors in combination with other drugs may be considered, especially in immunodeficient patients, to avoid the development of drug-resistant viruses.

Summary of the National Advisory Committee on Immunization (NACI) Statement-Recommendations on Fractional Influenza Vaccine Dosing in the Event of a Shortage: Pandemic preparedness.

At the commencement of a pandemic, it is important to consider the impact of respiratory infections on the health system and the possibility of vaccine shortages due to increased demand. In the event of an influenza vaccine shortage, a strategy for administration of fractional influenza vaccine doses might be considered. This article reviews the available evidence for efficacy, effectiveness, immunogenicity and safety of fractional influenza vaccine dosing, and summarizes the National Advisory Committee on Immunization (NACI) recommendations on fractional dosing strategies by public health programs in Canada. Two rapid literature reviews were undertaken to evaluate the efficacy, effectiveness, immunogenicity and safety of fractional influenza vaccine dosing via the intramuscular or intradermal route. The NACI evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings, and apply an ethics, equity, feasibility and acceptability lens to develop recommendations. There was limited evidence for the effectiveness of fractional influenza vaccine dosing. Fractional dosing studies were primarily conducted in healthy individuals, mainly young children and infants, with no underlying chronic conditions. There was fair evidence for immunogenicity and safety. Feasibility issues were identified with intradermal use in particular. NACI recommended that, in the event of a significant population-level shortage of influenza vaccine, a full-dose influenza vaccine should continue to be used, and existing vaccine supply should be prioritized for those considered to be at high risk or capable of transmitting to those at high risk of influenza-related complications or hospitalizations. NACI recommended against the use of fractional doses of influenza vaccine in any population.

Potential predictors of severe course and outcome of community-acquired pneumonia

Severe pneumonia is a condition with a high risk of death and mandatory hospitalization in the intensive care unit. The incidence of severe pneumonia has increased dramatically during the pandemic of new coronavirus infection. Timely diagnosis and early initiation of adequate treatment of severe pneumonia are crucial for improving survival of critically ill patients.The aim of this review was to analyze published scientific research on molecular markers that allow to objectively assess the severity of pneumonia and to determine treatment tactics based on the predicted outcome upon admission to the hospital. A systematic search was conducted in the electronic databases PubMed, Medline, Web of Science for the period 2019 - 2022.Conclusion. The review focuses on the prognostic role of a number of markers of immune response, vascular transformation, as well as angiotensin II and angiotensin converting enzyme-2. Further prospective studies of potential predictors of severe pneumonia will enable using marker molecules in a comprehensive clinical and laboratory diagnosis for early prediction of the hospitalized patient’s condition and expected outcome.

Hospital admission decisions for older Veterans with community-onset pneumonia: An analysis of 118 U.S. Veterans Affairs Medical Centers.

Age is important for prognosis in community-onset pneumonia, but how it influences admission decisions in the emergency department (ED) is not well characterized. Using clinical data from the electronic health record in a national cohort, we examined pneumonia hospitalization patterns, variation, and relationships with mortality among older versus younger Veterans. In a retrospective cohort of patients ≥ 18 years presenting to EDs with a diagnosis of pneumonia at 118 VA Medical Centers January 1, 2006, to December 31, 2016, we compared observed, predicted, and residual hospitalization risk for Veterans < 70, 70-79, and ≥ 80 years of age using generalized estimating equations and machine learning models with 71 patient factors. We examined facility variation in residual hospitalization across facilities and explored whether facility differences in hospitalization risk correlated with differences in 30-day mortality. Among 297,498 encounters, 165,003 (55%) were for Veterans < 70 years, 61,076 (21%) 70-80, and 71,419 (24%) ≥ 80. Hospitalization rates were 52%, 67%, and 76%, respectively. After other patient factors were adjusting for, age 70-79 had an odds ratio (OR) of 1.39 (95% confidence interval [CI] 1.34-1.44) and ≥ 80 had an OR of 2.1 (95% CI 2.0-2.2) compared to age < 70. There was substantial variation in hospitalization across facilities among Veterans < 70 (<35% hospitalization at the lowest decile of facilities vs. > 66% at the highest decile) that was similar but with higher risk for patients 70-79 years (54% vs. 82%) and ≥ 80 years (59% vs. 85%) and remained after accounting for patient factors, with no consistently positive or negative associations with facility-level 30-day mortality. Older Veterans with community-onset pneumonia experience high risk of hospitalization, with widespread facility variation that has no clear relationship to short-term mortality.

Your Outpatient has Coronavirus Disease 2019: What Are the Treatment Options in the Current Severe Acute Respiratory Syndrome Coronavirus 2 Variant Climate?

Mutations accumulated by novel Severe Acute Respiratory Syndrome Coronavirus 2 Omicron sublineages contribute to evasion of previously effective monoclonal antibodies for treatment or prevention of Coronavirus Disease 2019 (COVID-19). Other authorized or approved antiviral drugs such as nirmatrelvir/ritonavir, remdesivir, and molnupiravir are, however, predicted to maintain activity against these sublineages and are key tools to reduce severe COVID-19 outcomes in vulnerable populations. A stepwise approach may be taken to target the appropriate antiviral drug to the appropriate patient, beginning with identifying whether a patient is at high risk for hospitalization or other complications of COVID-19. Among higher risk individuals, patient profile (including factors such as age, organ function, and comedications) and antiviral drug access inform suitable antiviral drug selection. When applied in targeted fashion, these therapies serve as a complement to vital ongoing nonpharmaceutical interventions and vaccination strategies that reduce morbidity and maximize protection against COVID-19.

Mass spectrometry and machine learning in the identification of COVID-19 biomarkers

Identifying specific diagnostic and prognostic biological markers of COVID-19 can improve disease surveillance and therapeutic opportunities. Mass spectrometry combined with machine and deep learning techniques has been used to identify pathways that could be targeted therapeutically. Moreover, circulating biomarkers have been identified to detect individuals infected with SARS-CoV-2 and at high risk of hospitalization. In this review, we have surveyed studies that have combined mass spectrometry-based omics techniques (proteomics, lipdomics, and metabolomics) and machine learning/deep learning to understand COVID-19 pathogenesis. After a literature search, we show 42 studies that applied reproducible, accurate, and sensitive mass spectrometry-based analytical techniques and machine/deep learning methods for COVID-19 biomarker discovery and validation. We also demonstrate that multiomics data results in classification models with higher performance. Furthermore, we focus on the combination of MALDI-TOF Mass Spectrometry and machine learning as a diagnostic and prognostic tool already present in the clinics. Finally, we reiterate that despite advances in this field, more optimization in the analytical and computational parts, such as sample preparation, data acquisition, and data analysis, will improve biomarkers that can be used to obtain more accurate diagnostic and prognostic tools.

Tobacco use in Crohn's disease patients and association with disease outcomes in the United States Medicaid population, 2010-2019.

To identify demographic factors associated with tobacco use in Crohn's disease (CD) patients in the US Medicaid population and examine how tobacco use affects disease outcomes. We included Medicaid-eligible patients who had ≥1 ICD code for CD, and 1 year of eligibility before and after the initial encounter. We used ICD codes to identify tobacco use with respect to the time of diagnosis and used logistic regression to identify the association between age, sex, and race with tobacco use at any point before diagnosis and after diagnosis, and determine the association of tobacco use before and after diagnosis on disease outcomes. We identified 98 176 eligible patients; 74.5% had no documented use of tobacco and 25.5% used tobacco at some point; 21.1% had used tobacco before their CD diagnosis and 11.8% had used tobacco after diagnosis. The population that used tobacco had a higher proportion of women, those who were White, non-Hispanic, and those in their middle ages (21-60) than the group that did not use tobacco. Tobacco use before diagnosis resulted in higher risk of hospitalization and surgery (OR: 1.85 and 1.36, respectively). Within the CD Medicaid population, tobacco use is more common in women than men, which differs from the general population, which is possibly a result of using diagnostic codes rather than survey data. Smoking cessation efforts should especially be directed at younger people who are at risk for CD, due to increased risk for more adverse outcomes among those who use tobacco before diagnosis.

Evaluation of the association of birth order and group childcare attendance with Kawasaki disease using data from a nationwide longitudinal survey.

Kawasaki disease (KD) is a form of pediatric systemic vasculitis. Although the etiology remains unclear, infections have been identified as possible triggers. Children with a later birth order and those who attend childcare are at a higher risk of infections due to exposure to pathogens from their older siblings and other childcare attendees. However, longitudinal studies exploring these associations are limited. Thus, we aimed to elucidate the relationship between birth order, group childcare attendance, and KD, using a nationwide longitudinal survey in Japan. In total, 36,885 children born in Japan in 2010 were included. The survey used questionnaires to identify hospitalized cases of KD. We evaluated the relationship between birth order classification, group childcare attendance, and KD prevalence every year, from 6 to 66 months of age. For each outcome, odds ratios (ORs), and 95% confidence intervals (CIs) were estimated after adjusting for child factors, parental factors, and region of residence. Children with higher birth orders were more likely to be hospitalized with KD at 6-18 months of age (second child OR: 1.77, 95% CI: 1.25-2.51; third child OR: 1.70, 95% CI: 1.08-2.65). This trend was stronger for children who did not attend group childcare (second child OR: 2.51, 95% CI: 1.57-4.01; third child OR: 2.41, 95% CI: 1.30-4.43). An increased risk of KD hospitalization owing to the birth order was not observed in any age group for children in the childcare group. Children with higher birth orders were at high risk for hospitalization due to KD at 6-18 months of age. The effect of birth order was more prominent among the children who did not attend group childcare.

Indicators of integrated care for patients with chronic cardiovascular disease in ambulatory care.

Patients with cardiovascular disease (CVD) have an increased need for medical care and a high risk of hospitalization. It is necessary to improve the integration between healthcare, long-term care and social care for these individuals, as poor integration limits the full potential of care. This study aims to identify effective indicators of CVD management, including variables that promote the horizontal and vertical integration of planned interventions. Patients with chronic CVD managed by a general practitioner (GP) or a primary care cardiologist will be enrolled in the study. The study will use the World Health Organization Quality of Life Questionnaire (WHOQOL)-BREF, the Health Behavior Inventory (HBI) questionnaire, the Camberwell Assessment of Need (CAN) Short Appraisal Schedule, the Hospital Anxiety and Depression Scale-Modified Version (HADS-M), a Self-Description Questionnaire, and the authors' self-prepared questionnaire to collect data. The main results will allow for the identification of the variables that influence the effectiveness of healthcare (understood as the synergy of high quality of life, intensification of health behaviors and high satisfaction of needs) for patients with CVD. In addition, an examination of the relationships between quality of life and health behaviors, assessment of needs (health and social), level of religiosity and spirituality, expectations, and variables affecting anxiety and depressive symptoms will allow for the identification of indicators that favor the integration of care both horizontally and vertically. The results of this study will support the development of systems aimed at identifying CVD patients at risk for lower effectiveness of care in integrated care. In addition, the results may help to develop clinical information and decision support systems aimed at designing personalized care models for patients with CVD. They may also help to develop coordinated care plans and patient education programs, and obtain data useful for implementing system changes.

Upper airway dimensions and the skeletal parameters in orthodontic patients who developed moderate-severe COVID-19 symptoms during the pandemic.

Large airway dimensions are associated with a rapid decline in the lung function and a higher risk of hospitalization. Therefore, the airway dimensions of healthy subjects who tested positive for coronavirus disease 2019 (COVID-19) may be associated with the severity of COVID-19 symptoms. The objectives of this study were to measure the upper airway dimensions and the craniofacial skeletal parameters in patients who tested positive for COVID-19, to compare the upper airway dimensions and the craniofacial skeletal parameters between patients who developed no/mild symptoms and those with moderate-severe COVID-19 symptoms, and to assess any association of the skeletal relationships (anteroposterior (AP) and vertical) and the upper airway dimensions with the severity of COVID-19 symptoms in adult subjects. A total of 204 orthodontic patients who tested positive for COVID-19 were evaluated. Of these, only 137 met the inclusion criteria. The sample was further subdivided into 2 groups based on the severity of symptoms: cases (moderate-severe symptoms; n = 56); and controls (asymptomatic/ mild symptoms; n = 81). The upper airway dimensions and the skeletal parameters were measured on lateral cephalograms. The nonparametric Mann-Whitney U test was used to detect differences between the cases and the controls. Binary logistic regression analysis was used to evaluate the association between the studied variables and the severity of symptoms. The cases had a reduced lower face height (LFH) and a reduced perpendicular distance from the hyoid bone to the line connecting the anteroinferior limit of the 3rd cervical vertebra (C3) and the retrognathion point (RGN) (HH1) as compared to the controls. Regression analysis revealed a significant association of LFH (p = 0.013), the vertical airway length (VAL) (p = 0.002) and HH1 (p = 0.021) with the severity of COVID-19 symptoms. The types of malocclusion were similar in the cases and the controls. Patients with reduced LFH and VAL, and a superiorly positioned hyoid bone in relation to the mandible developed more severe COVID-19 symptoms.

&lt;p&gt;The Winter Strategy &amp;ndash; a&amp;nbsp;Multifaceted Integrated&amp;nbsp;Care Intervention to&amp;nbsp;Support People with Chronic&amp;nbsp;and Complex Care Needs&amp;nbsp;during the Australian&amp;nbsp;Winter Period&lt;/p&gt;

Introduction: Health care demands increase over the winter period, especially for people with chronic diseases. Hospital avoidance programs have potential to address seasonal surges. Methods: An integrated care intervention was provided to patients at high risk of hospitalisation during the 2017 and 2018 winters in Northern New South Wales, Australia. Patients received increased support including general practice sick day action plans, automated admission notifications to the general practitioner, and care coordination services. Outcomes were provider and patient experience and preventable hospitalisation rates. Results: The program enrolled 1244 participating patients from 37 general practices with at least 12 months follow-up. It was associated with marked improvements in provider and patient experience. However, when compared to a propensity score matched control group there was no difference in hospital utilisation or emergency presentation rates. Discussion and Conclusion: An integrated care strategy to address chronic care needs of patients in winter was well received by practitioners and patients, but did not translate to changes in hospital utilisation or emergency presentation rates. Areas for improvement include: strengthening inter-professional engagement between hospital, specialists and primary care providers, more tailored support services for patients with complex health needs, and a more expansive set of process measures beyond hospital and emergency utilisation to assess impact.

How Important is Spirometry for Identifying Patients with COPD Appropriate for Palliative Care?

Providing palliative care to patients with chronic obstructive pulmonary disease (COPD) is a priority. Spirometry demonstrating airflow limitation is a diagnostic test for COPD and a common inclusion criterion for palliative care research. However, requiring spirometry with airflow limitation may exclude appropriate patients unable to complete spirometry, or patients with preserved-ratio impaired spirometry and symptoms or imaging consistent with COPD. To determine differences in quality of life (QOL) and symptoms between patients with COPD identified based on International Classification of Diseases (ICD) codes and spirometry with airflow limitation compared to ICD codes only. Patients with COPD enrolled in a palliative care trial were included. Patients were at high risk of hospitalization and death and reported poor QOL. Baseline measures of QOL (Functional Assessment of Cancer Therapy-General (FACT-G), the Clinical COPD Questionnaire, and Quality of Life at the End of Life), and symptoms (Patient Health Questionnaire-8, Generalized Anxiety Disorder-7, fatigue, Insomnia Severity Index) were compared. Two hundred eight patients with COPD were predominantly male, White, and average age was 68.4. Between patients with ICD codes and spirometry with airflow limitation compared to patients with ICD codes only, there were no significant differences in FACT-G (59.0 vs. 55.0, P=0.33), other measures of QOL, or symptoms between groups. These results imply that spirometry may not need to be a requirement for inclusion into palliative care research or clinical care for patients with poor quality of life and at high risk for adverse outcomes.

A real-world data analysis of Clinical Global Impression-Severity (CGI-S) as a transdiagnostic predictor of psychiatric hospitalisation

IntroductionPreventing psychiatric admissions holds benefits for patients as well as healthcare systems. The Clinical Global Impression-Severity (CGI-S) scale is a 7-point measurement of symptom severity, independent of diagnosis, which has shown capability of predicting risk of hospitalisation in schizophrenia. Due to its routine use in clinical practice and ease of administration, it may have potential as a transdiagnostic predictor of hospitalisation.ObjectivesTo investigate whether early trajectories of CGI-S scores predict risk of hospitalisation over a 6 month-follow-up period.MethodsA retrospective cohort study was conducted, analysing Electronic Health Record (EHR) data from the NeuroBlu Database (Patel et al. BMJ Open 2022;12:e057227). Patients were included if they had a psychiatric diagnosis and at least 5 recorded CGI-S scores within a 2-month period, defined as the ‘index’ period. The relationship between early CGI-S trajectories and risk of hospitalisation was investigated using Cox regression. The analysis was adjusted for age, gender, race, number of years in education, and psychiatric diagnosis. Early CGI-S trajectories were estimated as clinical severity (defined as the mean CGI-S score during the index period) and clinical instability (defined as a generalised Root Mean Squared Subsequent Differences of all CGI-S scores recorded during the index period). The primary outcome was time to psychiatric hospitalisation up to 6 months following the index period. Patients who had been hospitalised before or within the index period were excluded.ResultsA total of 36,914 patients were included (mean [SD] age: 29.7 [17.5] years; 57.3% female). Clinical instability (hazard ratio: 1.09, 95% CI 1.07-1.10, p&lt;0.001) and severity (hazard ratio: 1.11, 95% CI 1.09-1.12, p&lt;0.001) independently predicted risk of hospitalisation. These associations were consistent across all psychiatric diagnoses. Patients in the top 50% of severity and/or instability were at a 45% increased risk of hospitalisation compared to those in the bottom 50% (Figure 1).Image:ConclusionsEarly CGI-S trajectories reflecting clinical severity and instability independently predict risk of hospitalisation across diagnoses. This risk was compounded when instability and severity were present together. These results have translation potential in predicting individuals who are at high risk of hospitalisation and could benefit from preventative strategies to mitigate this risk.Disclosure of InterestE. Palmer Employee of: Holmusk, M. Taquet Consultant of: Holmusk, K. Griffiths Employee of: Holmusk, S. Ker Employee of: Holmusk, C. Liman Employee of: Holmusk, S. N. Wee Employee of: Holmusk, S. Kollins Employee of: Holmusk, R. Patel Grant / Research support from: National Institute of Health Research (NIHR301690); Medical Research Council (MR/S003118/1); Academy of Medical Sciences (SGL015/1020); Janssen, Employee of: Holmusk

Associations and relative risks of pulmonary hypertension and lung diseases in individuals with methamphetamine use disorder

ObjectiveMethamphetamine causes considerable short- and long-term adverse health effects. Our aim was to assess the effects of methamphetamine use on pulmonary hypertension and lung diseases at the population level. MethodsThis population-based retrospective study used data from the Taiwan National Health Insurance Research Database between 2000 and 2018 that included 18,118 individuals with methamphetamine use disorder (MUD) and 90,590 matched participants of the same age and sex without substance use disorder as the non-exposed group. A conditional logistic regression model was used to estimate associations of methamphetamine use with pulmonary hypertension and lung diseases such as lung abscess, empyema, pneumonia, emphysema, pleurisy, pneumothorax, or pulmonary hemorrhage. Incidence rate ratios (IRRs) of pulmonary hypertension and hospitalization due to lung diseases were determined between the methamphetamine group and non-methamphetamine group using negative binomial regression models. ResultsDuring an 8-year observation period, 32 (0.2%) individuals with MUD and 66 (0.1%) non-methamphetamine participants suffered from pulmonary hypertension, and 2652 (14.6%) individuals with MUD and 6157 (6.8%) non-methamphetamine participants suffered from lung diseases. After adjusting for demographic characteristics and comorbidities, individuals with MUD were 1.78 times (95% confidence interval (CI) = 1.07–2.95) more likely to have pulmonary hypertension and 1.98 times (95% CI = 1.88–2.08) more likely to have a lung disease, especially emphysema, lung abscess, and pneumonia in descending order. Furthermore, compared to the non-methamphetamine group, the methamphetamine group was associated with higher risks of hospitalization caused by pulmonary hypertension and lung diseases. The respective IRRs were 2.79 and 1.67. Individuals with polysubstance use disorder were associated with higher risks of empyema, lung abscess, and pneumonia compared to individuals with MUD alone, with respective adjusted odds ratios of 2.96, 2.21, and 1.67. However, pulmonary hypertension and emphysema did not differ significantly between MUD individuals with or without polysubstance use disorder. ConclusionsIndividuals with MUD were associated with higher risks of pulmonary hypertension and lung diseases. Clinicians need to ensure that a methamphetamine exposure history is obtained as part of the workup for these pulmonary diseases and provide timely management for this contributing factor.

Estimating COVID-19 vaccine uptake and its drivers among migrants, homeless and precariously housed people in France

BackgroundMigrants, people experiencing homelessness (PEH), or precariously housed (PH) are at high risk for COVID-19 infection, hospitalization, and death from COVID-19. However, while data on COVID-19 vaccine uptake in these populations are available in the USA, Canada, and Denmark, we are lacking, to the best of our knowledge, data from France.MethodsIn late 2021, we carried out a cross-sectional survey to determine COVID-19 vaccine coverage in PEH/PH residing in Ile-de-France and Marseille, France, and to explore its drivers. Participants aged over 18 years were interviewed face-to-face where they slept the previous night, in their preferred language, and then stratified for analysis into three housing groups (Streets, Accommodated, and Precariously Housed). Standardized vaccination rates were computed and compared to the French population. Multilevel univariate and multivariable logistic regression models were built.ResultsWe find that 76.2% (95% confidence interval [CI] 74.3–78.1) of the 3690 participants received at least one COVID-19 vaccine dose while 91.1% of the French population did so. Vaccine uptake varies by stratum, with the highest uptake (85.6%; reference) in PH, followed by Accommodated (75.4%; adjusted odds-ratio = 0.79; 95% CI 0.51–1.09 vs. PH) and lowest in Streets (42.0%; AOR = 0.38; 95%CI 0.25–0.57 vs. PH). Use for vaccine certificate, age, socioeconomic factors, and vaccine hesitancy is associated with vaccination coverage.ConclusionsIn France, PEH/PH, and especially the most excluded, are less likely than the general population to receive COVID-19 vaccines. While vaccine mandate has proved an effective strategy, targeted outreach, on-site vaccinations, and sensitization activities are strategies enhancing vaccine uptake that can easily be replicated in future campaigns and other settings.

Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: A retrospective cohort study

To compare the effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab with no treatment in preventing hospital admission or death in higher-risk patients infected with SARS-CoV-2 in the community. Retrospective cohort study of non-hospitalized adult patients with COVID-19 using the Secure Anonymised Information Linkage (SAIL) Databank. A real-world cohort study was conducted within the SAIL Databank (a secure trusted research environment containing anonymised, individual, population-scale electronic health record (EHR) data) for the population of Wales, UK. Adult patients with COVID-19 in the community, at higher risk of hospitalization and death, testing positive for SARS-CoV-2 between 16th December 2021 and 22nd April 2022. Molnupiravir, nirmatrelvir-ritonavir, and sotrovimab given in the community by local health boards and the National Antiviral Service in Wales. All-cause admission to hospital or death within 28 days of a positive test for SARS-CoV-2. Cox proportional hazard model with treatment status (treated/untreated) as a time-dependent covariate and adjusted for age, sex, number of comorbidities, Welsh Index of Multiple Deprivation, and vaccination status. Secondary subgroup analyses were by treatment type, number of comorbidities, and before and on or after 20th February 2022, when omicron BA.1 and omicron BA.2 were the dominant subvariants in Wales. Between 16th December 2021 and 22nd April 2022, 7013 higher-risk patients were eligible for inclusion in the study. Of these, 2040 received treatment with molnupiravir (359, 17.6%), nirmatrelvir-ritonavir (602, 29.5%), or sotrovimab (1079, 52.9%). Patients in the treatment group were younger (mean age 53 vs 57 years), had fewer comorbidities, and a higher proportion had received four or more doses of the COVID-19 vaccine (36.3% vs 17.6%). Within 28 days of a positive test, 628 (9.0%) patients were admitted to hospital or died (84 treated and 544 untreated). The primary analysis indicated a lower risk of hospitalization or death at any point within 28 days in treated participants compared to those not receiving treatment. The adjusted hazard rate was 35% (95% CI: 18-49%) lower in treated than untreated participants. There was no indication of the superiority of one treatment over another and no evidence of a reduction in risk of hospitalization or death within 28 days for patients with no or only one comorbidity. In patients treated with sotrovimab, the event rates before and on or after 20th February 2022 were similar (5.0% vs 4.9%) with no significant difference in the hazard ratios for sotrovimab between the time periods. In higher-risk adult patients in the community with COVID-19, those who received treatment with molnupiravir, nirmatrelvir-ritonavir, or sotrovimab were at lower risk of hospitalization or death than those not receiving treatment.

Intensive care management for high-risk veterans in a patient-centered medical home – do some veterans benefit more than others?

BackgroundPrimary care intensive management programs utilize interdisciplinary care teams to comprehensively meet the complex care needs of patients at high risk for hospitalization. The mixed evidence on the effectiveness of these programs focuses on average treatment effects that may mask heterogeneous treatment effects (HTEs) among subgroups of patients. We test for HTEs by patients’ demographic, economic, and social characteristics. MethodsRetrospective analysis of a VA randomized quality improvement trial. 3995 primary care patients at high risk for hospitalization were randomized to primary care intensive management (n = 1761) or usual primary care (n = 1731). We estimated HTEs on ED and hospital utilization one year after randomization using model-based recursive partitioning and a pre-versus post-with control group framework. Splitting variables included administratively collected demographic characteristics, travel distance, copay exemption, risk score for future hospitalizations, history of hospital discharge against medical advice, homelessness, and multiple residence ZIP codes. ResultsThere were no average or heterogeneous treatment effects of intensive management one year after enrollment. The recursive partitioning algorithm identified variation in effects by risk score, homelessness, and whether the patient had multiple residences in a year. Within each distinct subgroup, the effect of intensive management was not statistically significant. ConclusionsPrimary care intensive management did not affect acute care use of high-risk patients on average or differentially for patients defined by various demographic, economic, and social characteristics. ImplicationsReducing acute care use for high-risk patients is complex, and more work is required to identify patients positioned to benefit from intensive management programs.

Corticosteroids and Outcomes in Solid Organ Transplant Recipients Infected With Severe Acute Respiratory Syndrome Coronavirus 2

ObjectiveTo examine outcomes in organ transplant and nontransplant patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the initial 22 months of the pandemic. Patients and MethodsWe used Optum electronic health records to compare outcomes between an adult transplant group and a propensity-matched nontransplant group that tested positive for SARS-CoV-2 from February 1, 2020, to December 15, 2021. Baseline characteristics, hospitalization, intensive care unit admission, mechanical ventilation, renal replacement therapy, inpatient, and 90-day mortality were compared between the transplant and nontransplant groups and among specific transplant recipients. Cox proportional analysis was used to examine hospitalization and mortality by organ transplant, medical therapy, sex, and the period of the pandemic. ResultsWe identified 876,959 patients with SARS-CoV-2 infection, of whom 3548 were organ transplant recipients. The transplant recipients had a higher risk of hospitalization (30.6% vs 25%, respectively; P<.001), greater use of mechanical ventilation (7.8% vs 5.6%, respectively; P<.001), and increased inpatient mortality (6.7% vs 4.7%, respectively; P<.001) compared with the nontransplant patients. The initiation of mechanical ventilation was significantly more frequent in the transplant group. After adjustment for baseline characteristics and comorbidities, the transplant group had a higher risk of hospitalization (odds ratio, 1.38; 95% confidence interval, 1.19-1.59), without a difference in mortality. In the transplant group, lung transplant recipients had the highest inpatient mortality (11.6%). ConclusionAmong patients with SARS-CoV-2 infection, the transplant recipients were at a higher risk of hospitalization and inpatient mortality; however, mortality was mainly driven by advanced age and comorbidities rather than by transplant status or immunosuppressive medications. Lung transplant recipients had the greatest inpatient and 90-day mortality.

Evaluating a Care Management Program for Dual-Eligible Beneficiaries: Evidence from Rhode Island.

As health systems attempt to contain utilization and costs, care management programs are proliferating. However, there are mixed findings on their impact. In 2018, Rhode Island initiated a care management program for dually eligible Medicare and Medicaid beneficiaries at high risk of hospitalization or institutionalization. The objective of this study is to evaluate the association between health care utilization and costs and care management for dual-eligible participants (n = 169). The authors employed an interrupted time series analysis of administrative claims data using the Rhode Island All Payer Claims Database, which includes data from all major payers in the state, for 11 quarters (January 1, 2017 until September 1, 2019). On average, participants were younger (46.2% were 19-64 years of age vs. 41.9% of non-participants), female (71% vs. 62.6% of non-participants), and had a higher comorbidity burden (more commonly had anemia, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease, depression, diabetes, heart failure, hyperlipidemia, hypertension, ischemic heart disease, and stroke). Participation was associated with significantly fewer hospital admissions (118 fewer admissions per 1000 admissions per quarter; 95% confidence interval [CI] -11 to -22), and a reduction in Medicaid ($1841 less spent per quarter, 95% CI -2407 to -1275) and total ($2570 less spent per quarter; 95% CI -$4645 to -$495) costs. Participation was not significantly associated with a change in Emergency Department (ED) visits, preventable ED visits, Skilled Nursing Facility stays, or Medicare costs. These results suggest that targeted care management programs may provide dual-eligible beneficiaries with needed services while diverting inefficient health care utilization.

Using Digital Health Technology to Prevent and Treat Diabetes.

Using Digital Health Technology to Prevent and Treat Diabetes.