Clinical Characteristics and Outcomes Among Adults Hospitalized with Laboratory-Confirmed SARS-CoV-2 Infection During Periods of B.1.617.2 (Delta) and B.1.1.529 (Omicron) Variant Predominance - One Hospital, California, July 15-September 23, 2021, and December 21, 2021-January 27, 2022.

In mid-December 2021, the B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, surpassed the B.1.617.2 (Delta) variant as the predominant strain in California.§ Initial reports suggest that the Omicron variant is more transmissible and resistant to vaccine neutralization but causes less severe illness compared with previous variants (1-3). To describe characteristics of patients hospitalized with SARS-CoV-2 infection during periods of Delta and Omicron predominance, clinical characteristics and outcomes were retrospectively abstracted from the electronic health records (EHRs) of adults aged ≥18 years with positive reverse transcription-polymerase chain reaction (RT-PCR) SARS-CoV-2 test results admitted to one academic hospital in Los Angeles, California, during July 15-September 23, 2021 (Delta predominant period, 339 patients) and December 21, 2021-January 27, 2022 (Omicron predominant period, 737 patients). Compared with patients during the period of Delta predominance, a higher proportion of adults admitted during Omicron predominance had received the final dose in a primary COVID-19 vaccination series (were fully vaccinated) (39.6% versus 25.1%), and fewer received COVID-19-directed therapies. Although fewer required intensive care unit (ICU) admission and invasive mechanical ventilation (IMV), and fewer died while hospitalized during Omicron predominance, there were no significant differences in ICU admission or IMV when stratified by vaccination status. Fewer fully vaccinated Omicron-period patients died while hospitalized (3.4%), compared with Delta-period patients (10.6%). Among Omicron-period patients, vaccination was associated with lower likelihood of ICU admission, and among adults aged ≥65 years, lower likelihood of death while hospitalized. Likelihood of ICU admission and death were lowest among adults who had received a booster dose. Among the first 131 Omicron-period hospitalizations, 19.8% of patients were clinically assessed as admitted for non-COVID-19 conditions. Compared with adults considered likely to have been admitted because of COVID-19, these patients were younger (median age = 38 versus 67 years) and more likely to have received at least one dose of a COVID-19 vaccine (84.6% versus 61.0%). Although 20% of SARS-CoV-2-associated hospitalizations during the period of Omicron predominance might be driven by non-COVID-19 conditions, large numbers of hospitalizations place a strain on health systems. Vaccination, including a booster dose for those who are fully vaccinated, remains critical to minimizing risk for severe health outcomes among adults with SARS-CoV-2 infection.

Comparison of clinical characteristics and outcomes of critically ill adults with SARS-CoV-2 infection during Delta and Omicron variant predominance periods: a single-hospital retrospective cohort study.

INTRODUCTION: Initial reports suggest the B.1.1.529 (Omicron) variant of SARS-CoV-2 causes less severe disease compared with the B.1.617.2 (Delta) variant, though more widespread vaccination contributed to these findings. Little is known about clinical characteristics and outcomes of patients with SARS-CoV-2 infection requiring intensive care during periods of Delta and Omicron variant predominance. AIM: To examine and compare characteristics of critically ill adults with SARS-CoV-2 infection during periods of Delta and Omicron variant predominance. METHODS: We conducted a retrospective cohort study of critically ill adults with SARS-CoV-2 infection at one academic hospital in Los Angeles during Delta (15 July 2021-23 September 2021) and Omicron (21 December 2021-27 January 2022) predominance. Patient characteristics were compared between Delta-period and Omicron-period hospitalisations, overall and stratified by vaccination status. RESULTS: 79 adults required intensive care during the Delta predominance period and 116 during the Omicron predominance period. We found similar proportions of intensive care unit admissions occurring in fully vaccinated patients between the two periods, despite Los Angeles County data revealing an almost 60% increase in the proportion of SARS-CoV-2 hospitalisations occurring in fully vaccinated persons. There was no difference in the need for invasive mechanical ventilation (IMV). Among those who required IMV, the median duration of IMV was shorter overall (Delta=18 days; Omicron=8 days; p=0.006) and among unvaccinated persons (Delta=19 days; Omicron=8.5 days; p=0.018). Among unvaccinated persons, the median intensive care unit length of stay was shorter (Delta=12 days; Omicron=5 days; p=0.037) during Omicron predominance. There was no difference in the proportion of patients who died while hospitalised. CONCLUSIONS: In this single-hospital study, critically ill patients with SARS-CoV-2 infection experienced less severe respiratory disease during Omicron predominance, likely due to reduced variant-specific virulence. Vaccination likely reduced development of critical illness in adults with SARS-CoV-2 infection during Omicron predominance.

Tocilizumab treatment in critically ill patients with COVID-19: A retrospective observational study.

OBJECTIVE: Elevated levels of pro-inflammatory cytokines are observed in severe COVID-19 infections, and cytokine storm is associated with disease severity. Tocilizumab, an interleukin-6 receptor antagonist, is used to treat chimeric antigen receptor T cell-induced cytokine release syndrome and may attenuate the dysregulated immune response in COVID-19. We compared outcomes among tocilizumab-treated and non-tocilizumab-treated critically ill COVID-19 patients. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective observational study conducted at a tertiary referral center investigating all patients admitted to the intensive care unit for COVID-19 who had a disposition from the hospital because of death or hospital discharge between March 1 and May 18, 2020 (n = 96). The percentages of death and secondary infections were compared between patients treated with tocilizumab (n = 55) and those who were not (n = 41). MEASUREMENTS AND MAIN RESULTS: More tocilizumab-treated patients required mechanical ventilation (44/55, 80%) compared to non-treated patients (15/41, 37%; P < 0.001). Of 55 patients treated with tocilizumab, 32 (58%) were on mechanical ventilation at the time of administration, and 12 (22%) progressed to mechanical ventilation after treatment. Of patients treated with tocilizumab requiring mechanical ventilation, 30/44 (68%) were intubated within 1 day of administration. Fewer deaths were observed among tocilizumab-treated patients, both in the overall population (15% vs 37%; P = 0.02) and among the subgroup of patients requiring mechanical ventilation (14% vs 60%; P = 0.001). Secondary infections were not different between the 2 groups (tocilizumab: 31%, non-tocilizumab: 17%; P = 0.16) and were predominantly related to invasive devices, such as urinary and central venous catheters. CONCLUSIONS: Tocilizumab treatment was associated with fewer deaths compared to non-treatment despite predominantly being used in patients with more advanced respiratory disease.

The Enhanced Care Program: Impact of a Care Transition Program on 30-Day Hospital Readmissions for Patients Discharged From an Acute Care Facility to Skilled Nursing Facilities.

BACKGROUND: Increased acuity of skilled nursing facility (SNF) patients challenges the current system of care for these patients. OBJECTIVE: Evaluate the impact on 30-day readmissions of a program designed to enhance the care of patients discharged from an acute care facility to SNFs. DESIGN: An observational, retrospective cohort analysis of 30-day hospital readmissions for patients discharged to 8 SNFs between January 1, 2014, and June 30, 2015. SETTING: A collaboration between a large, acute care hospital in an urban setting, an interdisciplinary clinical team, 124 community physicians, and 8 SNFs. PATIENTS: All patients discharged from Cedars-Sinai Medical Center to 8 partner SNFs were eligible for participation. INTERVENTION: The Enhanced Care Program (ECP) involved the following 3 interventions in addition to standard care: (1) a team of nurse practitioners participating in the care of SNF patients; (2) a pharmacist-driven medication reconciliation at the time of transfer; and (3) educational in-services for SNF nursing staff. MEASUREMENT: Thirty-day readmission rate for ECP patients compared to patients not enrolled in ECP. RESULTS: The average unadjusted, 30-day readmission rate for ECP patients over the 18-month study period was 17.2% compared to 23.0% among patients not enrolled in ECP (P < 0.001). After adjustment for sociodemographic and clinical characteristics, ECP patients had 29% lower odds of being readmitted within 30 days (P < 0.001). These effects were robust to stratified analyses, analyses adjusted for clustering, and balancing of covariates using propensity weighting. CONCLUSIONS: A coordinated, interdisciplinary team caring for SNF patients can reduce 30-day hospital readmissions.

Scoring system and clinical application of COPD diagnostic questionnaires.

OBJECTIVES: In most primary care settings, spirometric screening of all patients at risk is not practical. In prior work, we developed questionnaires to help identify COPD in two risk groups: (1) persons with a positive smoking history but no history of obstructive lung disease (case finding), and (2) patients with prior evidence of obstructive lung disease (differential diagnosis). For these questionnaires, we now present a scoring system for use in primary care. METHODS: Scores for individual questions were based on the regression coefficients from logistic regression models using a spirometry-based diagnosis of obstruction as the reference outcome. Receiver operator characteristic analysis was used to determine performance characteristics for each questionnaire. Several simplified scoring systems were developed and tested. RESULTS: For both scenarios, we created a scoring system with two cut points intended to place subjects within one of three zones: persons with a high likelihood of having obstruction (high predictive value of a positive test result); persons with a low likelihood of obstruction (high predictive value of a negative test result); and an intermediate zone. Using these scoring systems, we achieved sensitivities of 54 to 82%, specificities of 58 to 88%, positive predictive values of 30 to 78%, and negative predictive values of 71 to 93%. CONCLUSIONS: These questionnaires can be used to help identify persons likely to have COPD among specific risk groups. The use of a simplified scoring system makes these tools beneficial in the primary care setting. Used in conjunction with spirometry, these tools can help improve the efficiency and accuracy of COPD diagnosis in primary care.

Questions for COPD diagnostic screening in a primary care setting.

OBJECTIVES: To test questions usable in an ambulatory clinic to identify persons likely to have chronic obstructive pulmonary disease (COPD). METHODS: Analyses were performed as part of a study to identify patients with likely COPD in the Glenfield UK primary care clinic. Patients age 40 and older were recruited based on one of the following criteria: (1) respiratory medications in previous 2 years; (2) history of smoking or (3) history of asthma with no current medications based on case notes. Consenting patients reported smoking history, symptoms, and personal and family history of respiratory conditions. Spirometry with reversibility was conducted to ATS standards. Analyses were performed on this database to test questions for identifying patients with COPD from a sample of patients with a positive smoking history. Multivariate logistic regression identified the question set that best discriminated COPD from other conditions using receiver operating characteristic curves. The usefulness of a simple scoring system was assessed. RESULTS: The study sample included 369 current and former smokers. Patients were diagnosed as: COPD=62 (16.8%); asthma=30 (8.1%); or no obstructive lung disease=277 (75.1%). The best questions for discriminating between persons with and without COPD included items on age, dyspnoea on exertion, and wheeze. This set of questions identified COPD patients with a sensitivity of 77.4--87.1% and specificity of 71.3--76.2%. CONCLUSIONS: A simple questionnaire can facilitate the diagnosis of COPD in a primary care setting.

The impact of chronic obstructive pulmonary disease on long-term disability costs.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) as a cause of disability with subsequent costs remains poorly recognized. The small, growing body of literature on COPD shows that it is one of the leading causes of missed work.greater than asthma or diabetes. However, much less is known about the impact of COPD on long-term disability (LTD). Because the health care burden for disabled, working-age patients will fall heavily on managed care organizations, better estimates of the economic and pharmacoeconomic costs of COPD are required. We seek to improve understanding of the burden of COPD on several national LTD programs. METHODS: We reviewed occupational health and disability literature and government statistics to determine how long-term, respiratory-related disability is addressed by disability pension programs in 8 developed countries (Canada, France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States). We then applied respiratory-specific disability definitions to country-specific population and pension information to estimate the potential burden of COPD on LTD insurance programs in each country. RESULTS: Comprehensive, relevant data to evaluate respiratory-related disability are lacking. Of the study countries, only the United States has explicit respiratory specific criteria for disability eligibility, which are based solely on spirometry. We estimate that the total burden of COPD in the study countries may range from 5 billion dollars to as high as 25 billion dollars per year if all persons who met U.S. eligibility criteria for respiratory-related disability were granted compensation. CONCLUSION: The potential burden of COPD on LTD programs may be large. The lack of standard criteria for respiratory-related disability may lead to underrecognition of COPD's true potential impact. Further work is needed to develop consistent and cost-effective ways to measure the impact of COPD and to assist in disability determination for COPD patients.

Interpreting COPD prevalence estimates: what is the true burden of disease?

STUDY OBJECTIVES: To summarize the available data on COPD prevalence and assess reasons for conflicting prevalence estimates in the published literature. DESIGN: We reviewed published studies that (1) estimated COPD prevalence for a population, and (2) clearly described the methods used to obtain the estimates. RESULTS: Thirty-two sources of COPD prevalence rates, representing 17 countries and eight World Health Organization-classified regions, were identified and reviewed. Prevalence estimates were based on spirometry (11 studies), respiratory symptoms (14 studies), patient-reported disease (10 studies), or expert opinion. Reported prevalence ranged from 0.23 to 18.3%. The lowest prevalence rates (0.2 to 2.5%) were based on expert opinion. Sixteen studies had measured rates that could reasonably be extrapolated to an entire region or country. All were for Europe or North America, and most fell between 4% and 10%. CONCLUSIONS: There is considerable variation in the reported prevalence of COPD. The overall prevalence in adults appears to lie between 4% and 10% in countries where it has been rigorously measured. Some of the variation attributed to differences in risk exposure or population characteristics may be influenced by the methods and definitions used to measure disease. Spirometry is least influenced by local diagnostic practice, but it is subject to variation based on the lung function parameters selected to define COPD.

Analysis of medication use patterns:apparent overuse of antibiotics and underuse of prescription drugs for asthma, depression, and CHF.

OBJECTIVE: To assess the appropriateness of prescription medication use based upon widely accepted treatment guidelines. METHODS: We analyzed administrative claims for the period October 1, 1998, through September 20, 1999, supplied by 3 California health plans to determine medication use patterns for outpatient prescriptions. We compared these patterns to those expected in the presence of adherence to treatment guidelines. RESULTS: During the study period, only 27.5% of antidepressant users received the recommended 6 months of continuous therapy, only 49.0% of diagnosed asthma patients received at least one inhaled corticosteroid prescription (compared to 67.1% who received at least one inhaled beta-agonist prescription), and only 54.5% of patients diagnosed with congestive heart failure (CHF) received an angiotensin-converting enzyme (ACE) inhibitor. Of patients who had a diagnosis of common cold or upper respiratory tract infection, 35.7% received antibiotics. CONCLUSION: There is a remarkable degree of apparent overuse and underuse of prescription medications despite the existence of clinical guidelines to support appropriate use in the conditions studied. Effective medications appear to be underused for patients with asthma, CHF, and depression. Antibiotics appear to be overused for the common cold and upper respiratory infections. More effective efforts must be made to address appropriate use of medications. Without these efforts, improved quality of care and decreased total health system costs are unlikely to be realized.

International Primary Care Respiratory Group (IPCRG) Guidelines: integrating diagnostic guidelines for managing chronic respiratory diseases in primary care.

This is the first of the IPCRG Guideline papers. The IPCRG took on the task of producing an integrated guideline for the management of chronic respiratory diseases in primary care. This included some original work aimed at developing questionnaires suitable for improving the diagnosis and recognition of respiratory diseases in the primary care setting. This paper provides the background evidence and rationale for the integrated diagnostic section of the IPCRG Guideline. It focuses on identifying the unique challenges in respiratory disease diagnosis in primary care, the use of epidemiology to build a co-ordinated diagnostic framework, and the development of tools to support guideline implementation.

Symptom-based questionnaire for differentiating COPD and asthma.

BACKGROUND: Many patients with obstructive lung disease (OLD) carry an inaccurate diagnostic label. Symptom-based questionnaires could identify persons likely to need spirometry. OBJECTIVES: We prospectively tested questions derived from a comprehensive literature review and an international Delphi panel to help identify chronic OLD (COPD) in persons with prior evidence of OLD. METHODS: Subjects were recruited via random mailing to primary-care practices in Aberdeen, Scotland, and Denver, Colorado. Persons aged 40 and older reporting any prior diagnosis of OLD or any respiratory medications in the past year were enrolled. Participants answered 54 questions covering demographics and symptoms and underwent spirometry with reversibility testing. A study diagnosis of COPD was defined by fixed airway obstruction as measured by post-bronchodilator FEV(1)/FVC <0.70. We examined ability of individual questions in a multivariate framework to discriminate between persons with and without the study diagnosis of COPD. RESULTS: 597 persons completed all investigations and proceeded to analysis. The list of 54 questions yielded 52 items for analyses, which was reduced to 19 items for entry into a multivariate regression model. Nine items had significant relationships with the study diagnosis of COPD, including increased age, pack-years, worsening cough, breathing-related disability or hospitalization, worsening dyspnea, phlegm quantity, cold going to the chest, and receipt of treatment for breathing. Individual items yielded odds ratios ranging from 0.33 to 20.7. This questionnaire demonstrated a sensitivity of 72.0 and a specificity of 82.7. CONCLUSIONS: A short, symptom-based questionnaire identifies persons more likely to have COPD among persons with prior evidence of OLD.

Symptom-based questionnaire for identifying COPD in smokers.

BACKGROUND: Symptom-based questionnaires may enhance chronic obstructive pulmonary disease (COPD) screening in primary care. OBJECTIVES: We prospectively tested questions to help identify COPD among smokers without prior history of lung disease. METHODS: Subjects were recruited via random mailing to primary care practices in Aberdeen, UK, and Denver, Colo., USA. Current and former smokers aged 40 or older with no prior respiratory diagnosis and no respiratory medications in the past year were enrolled. Participants answered questions covering demographics and symptoms and then underwent spirometry with reversibility testing. A study diagnosis of COPD was defined as fixed airway obstruction as measured by post-bronchodilator FEV(1)/FVC <0.70. We examined the ability of individual questions in a multivariate framework to correctly discriminate between persons with and without COPD. RESULTS: 818 subjects completed all investigations and proceeded to analysis. The list of 54 questions yielded 52 items for analysis, which was reduced to 17 items for entry into multivariate regression. Eight items had significant relationships with the study diagnosis of COPD, including age, pack-years, body mass index, weather-affected cough, phlegm without a cold, morning phlegm, wheeze frequency, and history of any allergies. Individual items yielded odds ratios ranging from 0.23 to 12. This questionnaire demonstrated a sensitivity of 80.4 and specificity of 72.0. CONCLUSIONS: A simple patient self-administered questionnaire can be used to identify patients with a high likelihood of having COPD, for whom spirometric testing is particularly important. Implementation of this questionnaire could enhance the efficiency and diagnostic accuracy of current screening efforts.

Development of a population-based screening questionnaire for COPD.

COPD is commonly under-diagnosed, in part because people at risk are unaware of the relevant risk factors and do not recognize related symptoms. Providing this information might permit earlier disease identification but the questions chosen should identify those with spirometrically defined airflow obstruction. Using a population-based data set, we have determined which questions identify persons most likely to have airflow obstruction. Potential questions were selected by review of COPD risk factors and clinical features. Validation was by retrospective analysis of the NHANES III data set, a population-based U.S. household survey that included spirometry. We examined the predictive ability of individual questions in a multi-variate framework to correctly discriminate between persons with and without spirometric airway obstruction (defined as FEV1/FVC < 0.70). We then tested the discriminatory ability of the questions in combination. The following items showed significant predictive ability: increased age, smoking status, pack-years, cough, wheeze, and prior diagnosis of asthma or COPD. The best performing combination was age, smoking status, pack-years smoked, wheeze, phlegm, body mass index, and prior diagnosis of obstructive lung disease. Using this combination in a population of current and former smokers aged 40 and over, we achieved a sensitivity of 85% and specificity of 45%, with a positive predictive value of 38% and a negative predictive value of 88%. Performance of this tool is comparable to other screening methods designed for use in a general population. Symptom-based questionnaires can be a viable method to identify persons likely to have COPD in the general population. Dissemination of such tools should raise awareness among at-risk persons and help identify COPD patients in the primary care setting.

Comparison of existing symptom-based questionnaires for identifying COPD in the general practice setting.

OBJECTIVE: Underdiagnosis of COPD is widespread, at least in part due to underuse of spirometry. Symptom-based questionnaires may be helpful as an adjunct to spirometry. The aim of this study was to determine which types of questions might aid in identifying COPD. METHODOLOGY: Questionnaires were identified by literature review and input from a multinational advisory board of primary care providers. Questions were placed into groups and evaluated with respect to their ability to perform in two scenarios: (i) to identify persons with COPD from a general population (Case-finding scenario); and (ii) to distinguish persons with COPD from those with asthma (Differential Diagnosis scenario). Questions were retrospectively validated using the Third National Health and Nutrition Examination Survey data. Potential predictive ability was examined in bivariate and multivariate frameworks. RESULTS: Four published question sets and six additional documents were included. There was agreement in the use of smoking and symptom-based questions, but important differences in the use of demographic, personal history and other information. Most question types had significant bivariate relationships with airway obstruction. In multivariate analysis, age, BMI, smoking status and pack-years, symptoms (cough, phlegm, dyspnoea, wheeze), and prior diagnosis consistent with asthma or COPD all showed significant ability to discriminate between persons with and without obstruction in a general population. CONCLUSION: Simple self-administered questionnaires can be used to identify persons for whom spirometric testing may be especially appropriate. Development of such questionnaires will require additional study, including prospective validation of items in an appropriate clinical setting and policy recommendations on the use of these tools.

Worldwide guidelines for chronic obstructive pulmonary disease: a comparison of diagnosis and treatment recommendations.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a leading cause of worldwide burden of disease, but is underdiagnosed and undertreated. We performed a systematic review of worldwide COPD clinical practice guidelines (CPG) to determine the degree of international consensus on major guideline recommendations. METHODS: The COPD CPG were identified from the medical literature and through contact with respiratory experts and organizations. An abstraction form was developed to collect information related to COPD diagnosis and management. RESULTS: Locally developed COPD CPG are based upon expert consensus, but do not explicitly rate the strength of the evidence for recommendations. The detail and clarity of the 41 CPG varied regarding the diagnosis and management of COPD. Key differences included the lung function parameters that define a diagnosis and severity assignment of COPD. The use of anticholinergics, alone or in combination, was listed as a consideration for first-line therapy for persistent COPD in all 41 CPG. There was consensus regarding reserving corticosteroids for selected patients. CONCLUSIONS: There is variation and ambiguity within COPD CPG regarding specific recommendations that can be applied by clinicians at a patient-specific level. The variation in CPG for COPD may contribute to the underdiagnosis and suboptimal treatment of COPD. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop report may help resolve some of the variation surrounding COPD diagnosis and treatment. However, local guideline implementation efforts must assist physicians in applying guideline recommendations to support patient-specific management.

Coordinated diagnostic approach for adult obstructive lung disease in primary care.

AIMS: To present an age-stratified approach to the diagnosis of obstructive lung disease based on asthma and COPD guidelines and epidemiology. METHODS: Asthma guidelines emphasize the role of the history and physical examination, with pulmonary function used primarily to confirm the diagnosis. COPD guidelines begin with symptoms and risk exposure, presenting spirometry as the primary diagnostic maneuver. Data from the National Health Interview Survey and the Third National Health and Nutrition Examination Survey illustrate relationships in prevalence of asthma and COPD in nationally representative samples. RESULTS: Asthma prevalence in adults declines with age from 5-10% at age 20-40 to 4-8% above age 60. COPD is uncommon in adults under age 40 but increases with age, surpassing asthma in older adults. CONCLUSIONS: These trends suggest that asthma screening is most useful in adults up to age 40, after which COPD screening and differential diagnosis are of comparable or greater utility.