Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection.

Importance: Understanding the effect of serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on susceptibility to infection is important for identifying at-risk populations and could have implications for vaccine deployment. Objective: The study purpose was to evaluate evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among patients with positive vs negative test results for antibodies in an observational descriptive cohort study of clinical laboratory and linked claims data. Design, Setting, and Participants: The study created cohorts from a deidentified data set composed of commercial laboratory tests, medical and pharmacy claims, electronic health records, and hospital chargemaster data. Patients were categorized as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test in the database. Main Outcomes and Measures: Primary end points were post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, including recorded signs and symptoms or prior evidence of coronavirus 2019 (COVID) diagnoses or positive NAAT results and recorded comorbidities. Results: The cohort included 3 257 478 unique patients with an index antibody test; 56% were female with a median (SD) age of 48 (20) years. Of these, 2 876 773 (88.3%) had a negative index antibody result, and 378 606 (11.6%) had a positive index antibody result. Patients with a negative antibody test result were older than those with a positive result (mean age 48 vs 44 years). Of index-positive patients, 18.4% converted to seronegative over the follow-up period. During the follow-up periods, the ratio (95% CI) of positive NAAT results among individuals who had a positive antibody test at index vs those with a negative antibody test at index was 2.85 (95% CI, 2.73-2.97) at 0 to 30 days, 0.67 (95% CI, 0.6-0.74) at 31 to 60 days, 0.29 (95% CI, 0.24-0.35) at 61 to 90 days, and 0.10 (95% CI, 0.05-0.19) at more than 90 days. Conclusions and Relevance: In this cohort study, patients with positive antibody test results were initially more likely to have positive NAAT results, consistent with prolonged RNA shedding, but became markedly less likely to have positive NAAT results over time, suggesting that seropositivity is associated with protection from infection. The duration of protection is unknown, and protection may wane over time.

Real-world data suggest antibody positivity to SARS-CoV-2 is associated with a decreased risk of future infection.

Importance There is limited evidence regarding whether the presence of serum antibodies to SARS-CoV-2 is associated with a decreased risk of future infection. Understanding susceptibility to infection and the role of immune memory is important for identifying at-risk populations and could have implications for vaccine deployment. Objective The purpose of this study was to evaluate subsequent evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among individuals who are antibody-positive compared with those who are antibody-negative, using real-world data. Design This was an observational descriptive cohort study. Participants The study utilized a national sample to create cohorts from a de-identified dataset composed of commercial laboratory test results, open and closed medical and pharmacy claims, electronic health records, hospital billing (chargemaster) data, and payer enrollment files from the United States. Patients were indexed as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test recorded in the database. Patients with more than 1 antibody test on the index date where results were discordant were excluded. Main Outcomes/Measures Primary endpoints were index antibody test results and post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, as measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, such as recorded signs and symptoms or prior evidence of COVID-19 (diagnoses or NAAT+) and recorded comorbidities. Results We included 3,257,478 unique patients with an index antibody test. Of these, 2,876,773 (88.3%) had a negative index antibody result, 378,606 (11.6%) had a positive index antibody result, and 2,099 (0.1%) had an inconclusive index antibody result. Patients with a negative antibody test were somewhat older at index than those with a positive result (mean of 48 versus 44 years). A fraction (18.4%) of individuals who were initially seropositive converted to seronegative over the follow up period. During the follow-up periods, the ratio (CI) of positive NAAT results among individuals who had a positive antibody test at index versus those with a negative antibody test at index was 2.85 (2.73 - 2.97) at 0-30 days, 0.67 (0.6 - 0.74) at 31-60 days, 0.29 (0.24 - 0.35) at 61-90 days), and 0.10 (0.05 - 0.19) at >90 days. Conclusions Patients who display positive antibody tests are initially more likely to have a positive NAAT, consistent with prolonged RNA shedding, but over time become markedly less likely to have a positive NAAT. This result suggests seropositivity using commercially available assays is associated with protection from infection. The duration of protection is unknown and may wane over time; this parameter will need to be addressed in a study with extended duration of follow up.

The clinical and economic burden of pneumonia in patients enrolled in Medicare receiving dialysis: a retrospective, observational cohort study.

BACKGROUND: End-stage renal disease (ESRD) patients receiving dialysis are at particular risk for infection. We assessed the clinical and economic burden of pneumonia in a population of Medicare-enrolled ESRD patients with respect to incidence and case fatality rates, rates of all-cause and cardiovascular hospitalization, and costs. METHODS: Patients received dialysis between 01 January 2009 and 31 December 2011 and were enrolled in Medicare Parts A and B. Pneumonia episodes were identified from institutional and supplier claims. Patients were considered at-risk from first date of Medicare coverage and were censored upon transplant, withdrawal from dialysis, recovery of renal function, loss of Medicare benefits, or death. Linear mixed-effects models were used to assess hospitalization rates and costs over the 3 months prior to and 12 months following pneumonia episodes. RESULTS: The pneumonia incidence rate for the study period was 21.4 events/100 patient-years; the majority of episodes (90.1%) required inpatient treatment. The 30-day case fatality rate was 10.7%. Compared to month -3 prior to event, rates of all-cause and cardiovascular hospitalization were higher in the month of the pneumonia episode (IRR, 4.61 and 4.30). All-cause admission rates remained elevated through month 12; cardiovascular admission rates remained elevated through month 6. Mean per-patient per-month costs were $10,976 higher in the month of index episode compared to month -3, largely driven by increased inpatient costs, and remained elevated through end of 12-month follow-up. CONCLUSION: Pneumonia episodes are frequent among ESRD patients and result in hospitalizations and greater overall costs to Medicare over the following year.

Clinical and economic burden of bloodstream infections in critical care patients with central venous catheters.

PURPOSE: Bloodstream infections (BSIs) complicate the management of intensive care unit (ICU) patients. We assessed the clinical and economic impact of BSI among patients of a managed care provider group who had a central venous catheter (CVC) placed in the ICU. METHODS: We considered hospitalizations occurring between January 1, 2011, and September 30, 2014, that involved an ICU stay during which a CVC was placed. Comparisons were made between episodes where the patient did vs did not develop BSI after CVC insertion. Length of stay, costs of index hospitalization, and total costs over the 180 days after discharge were compared using linear mixed models. Inhospital mortality and 30-day readmission rates were compared using negative binomial regression models. RESULTS: Development of BSI was associated with longer hospital stay (+7 days), more than 3-fold increase in risk of inhospital death, and an additional $129 000 in costs for the index hospitalization. No statistically significant differences in 30-day readmission rates or costs of care over the 180-day period after discharge from the index admission were observed. CONCLUSION: Bloodstream infections after CVC placement in ICU patients are associated with significant increases in costs of care and risk of death during the index hospitalization but no differences in readmissions or costs after discharge.

Diabetes disease management in Medicare Advantage reduces hospitalizations and costs.

OBJECTIVE: To evaluate the effectiveness of a telephonic diabetes disease management intervention in a Medicare Advantage population with comorbid diabetes and coronary artery disease (CAD). STUDY DESIGN: Prospective unequal randomization design of 526 members from a Medicare Advantage segment of one region of a large national health plan from May 2005 through April 2007. METHODS: High-risk and high-cost patients with diabetes and CAD who were enrolled in telephonic diabetes disease management were compared with a randomly selected comparison group receiving usual care. Wilcoxon signed-rank tests were used to compare the groups on all-cause hospital admissions, diabetes-related hospital admissions, all-cause and diabetes-related emergency department (ED) visits, and all-cause medical costs. Changes in self-reported clinical outcomes also were measured in the intervention group. RESULTS: Patients receiving telephonic diabetes disease management had significantly decreased all-cause hospital admissions and diabetes-related hospital admissions (P <.05). The intervention group had decreased all-cause and diabetes-related ED visits, although the difference was not statistically significant. The comparison group had increased ED utilization. The intervention group decreased their all-cause total medical costs by $984.87 per member per year (PMPY) compared with a $4547.06 PMPY increase in the comparison group (P <.05). All clinical measures significantly improved (P <.05) in the intervention group. CONCLUSIONS: A disease management program for high-risk patients with diabetes and CAD was effective in reducing hospital inpatient admission and total costs in a Medicare Advantage population.

Characteristics associated with pediatric inpatient death.

OBJECTIVE: The primary objective of this study was to obtain a broad understanding of inpatient deaths across academic children's hospitals. METHODS: A nonconcurrent cohort study of children hospitalized in 37 academic children's hospitals in 2005 was performed. The primary outcome was death. Patient characteristics including age, gender, race, diagnostic grouping, and insurance status and epidemiological measures including standardized mortality rate and standardized mortality ratios (SMRs) were used. RESULTS: A total of 427 615 patients were discharged during the study period, of whom 4529 (1.1%) died. Neonates had the highest mortality rate (4.03%; odds ratio: 8.66; P < .001), followed by patients >18 years of age (1.4%; odds ratio: 2.86; P < .001). The SMRs ranged from 0.46 (all patient-refined, diagnosis-related group 663, other anemias and disorders of blood) to 30.0 (all patient-refined, diagnosis-related group 383, cellulitis and other bacterial skin infections). When deaths were compared according to institution, there was considerable variability in both the number of children who died and the SMRs at those institutions. CONCLUSIONS: Patient characteristics, such as age, severity, and diagnosis, were all substantive factors associated with the death of children. Opportunities to improve the environment of care by reducing variability within and between hospitals may improve mortality rates for hospitalized children.

Outcomes and milestone achievement differences for very low-birth-weight multiples compared with singleton infants.

We examined if very low-birth-weight (VLBW) infants of multiple gestation pregnancies experience more complications and take longer to achieve clinical milestones compared with similar singletons. We performed a retrospective analysis of all infants less than 1500 g at birth in a large neonatal database. Singletons were compared with twins and higher-order multiples for demographic, morbidities, and process milestones including feeding, respiratory, thermoregulation, and length of stay. Multivariable regression analyses were performed to control for potential confounding variables. A total of 5507 infants were included: 3792 singletons, 1391 twins, and 324 higher-order multiples. There were no differences in Apgar scores, small for gestational age status, and incidence of necrotizing enterocolitis, severe retinopathy of prematurity, severe intraventricular hemorrhage, sepsis, bronchopulmonary dysplasia, or the need for surgery. Multiples had higher rates of apnea and patent ductus arteriosus than singletons. VLBW multiples achieved milestones at similar rates in most areas compared with singletons except for the achievement of full oral feedings. Length of stay, after controlling for confounding variables, did not differ between the groups. Compared with singletons, VLBW multiples had similar morbidity and achieved most feeding and thermoregulation milestones at similar rates.

Blood transfusions in children: a multi-institutional analysis of practices and complications.

BACKGROUND: Blood product transfusions are a valuable health-care resource. Guidelines for transfusion exist, but variability in their application, particularly in children, remains. The risk factors that threaten transfusion safety are well established, but because their occurrence in children is rare, single-institution studies have limited utility in determining the rates of occurrence. An epidemiologic approach that investigates blood transfusions in hospitalized children may help improve our understanding of transfused blood products in this vulnerable population. STUDY DESIGN AND METHODS: This was a nonconcurrent cohort study of pediatric patients not more than 18 years of age hospitalized from 2001 to 2003 at 35 academic children's hospitals that are members of the Pediatric Health Information System (PHIS). RESULTS: A total of 51,720 (4.8%) pediatric patients received blood product transfusions during the study period. Red blood cells (n = 44,632) and platelets (n = 14,274) were the two most frequently transfused products. The rate of transfusions was highest among children with neutropenia, agranulocytosis, and sickle cell crisis. Asian and American Indian patients had important differences in the rate of blood transfusions and their complications. Resource use in terms of length of stay and costs were higher in patients who received transfusion. Of those patients who received transfusions, 492 (0.95%) experienced a complication from the administered blood product. This accounted for a rate of complications of 10.7 per 1,000 units transfused. CONCLUSIONS: The administration of blood products to children is a common practice in academic children's hospitals. Complications associated with these transfused products are rare.

Pediatric patient safety events during hospitalization: approaches to accounting for institution-level effects.

OBJECTIVE: To determine the rates, patient, and institutional characteristics associated with the occurrence of patient safety indicators (PSIs) in hospitalized children and the degree of statistical difference derived from using three approaches of controlling for institution level effects. DATA SOURCE: Pediatric Health Information System Dataset consisting of all pediatric discharges (<21 years of age) from 34 academic, freestanding children's hospitals for calendar year 2003. METHODS: The rates of PSIs were computed for all discharges. The patient and institutional characteristics associated with these PSIs were calculated. The analyses sequentially applied three increasingly conservative methods to control for the institution-level effects robust standard error estimation, a fixed effects model, and a random effects model. The degree of difference from a "base state," which excluded institution-level variables, and between the models was calculated. The effects of these analyses on the interpretation of the PSIs are presented. PRINCIPAL FINDINGS: PSIs are relatively infrequent events in hospitalized children ranging from 0 per 10,000 (postoperative hip fracture) to 87 per 10,000 (postoperative respiratory failure). Significant variables associated PSIs included age (neonates), race (Caucasians), payor status (public insurance), severity of illness (extreme), and hospital size (>300 beds), which all had higher rates of PSIs than their reference groups in the bivariable logistic regression results. The three different approaches of adjusting for institution-level effects demonstrated that there were similarities in both the clinical and statistical significance across each of the models. CONCLUSIONS: Institution-level effects can be appropriately controlled for by using a variety of methods in the analyses of administrative data. Whenever possible, resource-conservative methods should be used in the analyses especially if clinical implications are minimal.

Leadership and management training of pediatric intensivists: how do we gain our skills?

BACKGROUND: Intensivists manage a diverse team of health care professionals. For decades, business literature has recognized the value of leadership and management skills, yet this is relatively unexplored in critical care. OBJECTIVE: Investigate the status of intensivists' preparation for the clinical leadership and management roles that they will assume after medical training. DESIGN: Authoritative business leadership literature was reviewed to identify attributes of successful leadership and management relevant to critical care. A survey was designed to assess the process by which intensivists learn these attributes and to assess their perceived level of preparedness (20 items). Each survey item received a preparedness score structured as a Likert scale (1=not prepared, 5=very prepared), representing the averaged response to each item. In addition, an inadequate preparedness percentage was created representing the percentage of respondents answering "not at all prepared" and "hardly prepared" on the Likert-scaled items. SETTING: Pediatric Critical Care Medicine Board Review Course, Washington, DC, 2004. SUBJECTS: Physician course participants (n=259). INTERVENTION: Survey administration. MEASUREMENTS AND MAIN RESULTS: The response rate was 61% (n = 159). The majority of respondents (69%) had completed fellowship training (median, 1 yr posttraining). Modeling the behavior of other physicians was the dominant technique for leadership and management skill acquisition (86%). The respondents were taught these skills by a variety of sources (attendings, 92%; other fellows, 42%; nurses, 37%; teachers, 20%; residents, 14%). Most (82%) thought that leadership and management training was important or very important, yet only 47% had received any formal training (40% fellowship, 36% residency, 21% medical school, 16% masters, 30% other). Overall, respondents felt only "somewhat prepared" for the 20 leadership and management items surveyed (mean+/- sd of preparedness score, 2.8+/- 0.2). Respondents were least prepared to manage conflict within a team, manage conflict with other groups, and manage stress effectively (preparedness scores of 2.5, 2.4, and 2.6 and inadequate preparedness percentages of 19.5%, 15.7%, and 18.9%, respectively). Respondents were most prepared to "set high standards" (preparedness score=3.3). Of the respondents feeling at least somewhat prepared, only 33% credited medical training as preparing them. CONCLUSIONS: Although leadership and management training was perceived as important to this sample of pediatric generally young intensivists, most feel inadequately prepared for critical aspects of these responsibilities, most notably, stress and conflict management. These findings provide an opportunity for specific curriculum development in leadership and management for those believing these skills should be further refined.

Hospital-reported medical errors in premature neonates.

OBJECTIVE: To determine the national rate of hospital-reported medical errors in premature neonates and describe the patient and organizational characteristics associated with their occurrence. DESIGN: Nonconcurrent, cohort study. SETTING: The Healthcare Cost and Utilization Project (HCUP) contains discharge data collected at community hospitals sited in >20 states. PATIENTS: All neonatal discharges from the 1997 edition of HCUP were included in these analyses. The definition of prematurity included any hospitalized neonate with a birth weight <2500 g, which corresponds to approximately 37 wks gestation. Medical error was defined as an International Classification of Diseases-9 discharge diagnosis of 996-999 in any of the diagnosis fields associated with the discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The national rate of hospital-reported medical errors in premature neonates is 1.2 per 100 discharges. There was a significant linear increase in the rate of medical errors based on birth weight (Cochran-Armitage test for trend, p <.001). After we controlled for case mix and organizational characteristics using a logistic regression model, medical errors continued to be associated with birth weight, gender, insurance status, and hospital characteristics. CONCLUSIONS: The rate of hospital-reported medical errors in premature neonates is lower than that reported in both the adult and pediatric populations. Specific patient and organizational characteristics are associated with an increased risk of medical errors. These characteristics may help to identify opportunities to improve patient safety efforts in this vulnerable population.