Post-COVID-19 paediatric inflammatory multisystem syndrome: association of ethnicity, key worker and socioeconomic status with risk and severity.

OBJECTIVES: Patients from ethnic minority groups and key workers are over-represented among adults hospitalised or dying from COVID-19. In this population-based retrospective cohort, we describe the association of ethnicity, socioeconomic and family key worker status with incidence and severity of Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS). SETTING: Evelina London Children's Hospital (ELCH), the tertiary paediatric hospital for the South Thames Retrieval Service (STRS) region. PARTICIPANTS: 70 children with PIMS-TS admitted 14 February 2020-2 June 2020. OUTCOME MEASURES: Incidence and crude ORs are presented, comparing ethnicity and socioeconomic status of our cohort and the catchment population, using census data and Index of Multiple Deprivation (IMD). Regression is used to estimate the association of ethnicity and IMD with admission duration and requirement for intensive care, inotropes and ventilation. RESULTS: Incidence was significantly higher in children from black (25.0 cases per 100 000 population), Asian (6.4/100 000) and other (17.8/100 000) ethnic groups, compared with 1.6/100 000 in white ethnic groups (ORs 15.7, 4.0 and 11.2, respectively). Incidence was higher in the three most deprived quintiles compared with the least deprived quintile (eg, 8.1/100 000 in quintile 1 vs 1.6/100 000 in quintile 5, OR 5.2). Proportions of families with key workers (50%) exceeded catchment proportions. Admission length of stay was 38% longer in children from black ethnic groups than white (95% CI 4% to 82%; median 8 days vs 6 days). 9/10 children requiring ventilation were from black ethnic groups. CONCLUSIONS: Children in ethnic minority groups, living in more deprived areas and in key worker families are over-represented. Children in black ethnic groups had longer admissions; ethnicity may be associated with ventilation requirement.This project was registered with the ELCH audit and service evaluation team, ref. no 11186.

Improving severe sepsis outcomes: cost and time to first antibiotic dose.

This study was conducted to determine the effect of an empiric antimicrobial guide on clinical and economic outcomes related to severe sepsis. As all critical care nurses know, severe sepsis is often life-threatening. The study found that an empiric antimicrobial guide specific for severe sepsis was associated with a reduced length of stay, a significantly earlier time to first dose antibiotic, and significantly lower total and variable hospital costs.

When is critical care medicine cost-effective? A systematic review of the cost-effectiveness literature.

BACKGROUND: Receiving care in an intensive care unit can greatly influence patients' survival and quality of life. Such treatments can, however, be extremely resource intensive. Therefore, it is increasingly important to understand the costs and consequences associated with interventions aimed at reducing mortality and morbidity of critically ill patients. Cost-effectiveness analyses (CEAs) have become increasingly common to aid decisions about the allocation of scarce healthcare resources. OBJECTIVES: To identify published original CEAs presenting cost/quality-adjusted life year or cost/life-year ratios for treatments used in intensive care units, to summarize the results in an accessible format, and to identify areas in critical care medicine that merit further economic evaluation. METHODS: We conducted a systematic search of the English-language literature for original CEAs of critical care interventions published from 1993 through 2003. We collected data on the target population, therapy or program, study results, analytic methods employed, and the cost-effectiveness ratios presented. RESULTS: We identified 19 CEAs published through 2003 with 48 cost-effectiveness ratios pertaining to treatment of severe sepsis, acute respiratory failure, and general critical care interventions. These ratios ranged from cost saving to 958,423 US dollars/quality-adjusted life year and from 1,150 to 575,054 US dollars/life year gained. Many studies reported favorable cost-effectiveness profiles (i.e., below 50,000 US dollars/life year or quality-adjusted life year). CONCLUSIONS: Specific interventions such as activated protein C for patients with severe sepsis have been shown to provide good value for money. However, overall there is a paucity of CEA literature on the management of the critically ill, and further high-quality CEA is needed. In particular, research should focus on costly interventions such as 24-hr intensivist availability, early goal-directed therapy, and renal replacement therapy. Recent guidelines for the conduct of CEAs in critical care may increase the number and improve the quality of future CEAs.

Drotrecogin alfa (activated) in sepsis: initial experience with patient selection, cost, and clinical outcomes.

During a 1-year period, the authors examined clinical experience with drotrecogin alfa, activated for sepsis in a 24-bed medical-surgical intensive care unit. Drotrecogin alfa, activated was administered 46 times to 44 patients (3% of all intensive care unit admissions). Eighty-six percent of patients were on vasopressors; 95% were mechanically ventilated. Mean Acute Physiology and Chronic Health Evaluation II score was 22.0 at admission and 21.9 during the 24 hours before drug administration. The 28-day all-cause mortality was 36.4% and hospital mortality was 43.2%, trending higher (P = .10) than in the PROWESS study, which can be attributed to clinical use in patients who would not have met PROWESS study inclusion criteria. Failure to complete a 96-hour infusion of drotrecogin alfa, activated and transfer from another hospital or nursing home before treatment were associated with poor outcome. Total cost of hospital care, including mean drotrecogin alfa, activated drug cost of 7,312 US dollars, exceeded reimbursement by a mean of 18,227 US dollars.

[New approaches to intensive care for sepsis]. / Intensivmedizinische Aspekte bei Sepsis. Gibt es neue therapeutische Ansätze?

In Germany, the mortality from sepsis remains high, and up to 60,000 patients die from it each year. Thus, sepsis is the third most common cause of death. More deaths occur only from coronary heart disease and acute myocardial infarction. In the last 3-4 years, substantial progress in sepsis therapy has been made. Based on these achievements, there is hope of reducing sepsis mortality by 25% in the next few years. Implementing new medical evidence in this context into daily clinical intensive care remains a major hurdle. The early diagnosis of sepsis prior to the onset of clinical deterioration is of particular interest, because this would increase the possibility of early and specified treatment, which is in turn the major determining factor of mortality in septic patients.

Epidemiology and economic evaluation of severe sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost.

PURPOSE: Severe sepsis is a leading cause of death in critically ill patients. We evaluated cost and workload according to infection site, place and time of acquisition, and severity. MATERIAL AND METHOD: We used a prospective 3-year database from 6 intensive care units (ICUs) including 1698 patients. RESULTS: Of the 1698 patients, 713 (42%) had severe sepsis at admission and 339 during the ICU stay (211 had both). Mortality was twice as high in patients with than those without ICU-acquired infection, independent of the presence of severe sepsis at admission. The mean (SD; median) cost of severe sepsis was 22 800 (21 400 ; 15 800 ). Among patients with severe sepsis at admission, workload and cost were higher for pneumonia, peritonitis, and multiple-site infections and for hospital-acquired (17,400 [14,700; 17,400]) vs community-acquired infection (12,600 [12,100 ; 8900 ]). Intensive care unit-acquired severe sepsis was associated with greater than 3-fold increases in workload and costs. By multiple linear regression, older age, emergency surgery, septic shock, Acute Physiological and Chronic Health Evaluation II score, and hospital or ICU-acquired severe sepsis were independently associated with higher costs. CONCLUSIONS: The wide variations in cost and workload invite efforts to identify patient subgroups most likely to benefit from high-cost treatments and from prevention, particularly targeting severe nosocomial infections.

Scope and epidemiology of pediatric sepsis.

OBJECTIVE: To summarize the scope and epidemiology of pediatric sepsis. DESIGN: Review of published literature. RESULTS: Sepsis is a leading cause of death in infants and children, with >42,000 cases of severe sepsis annually in the United States and millions worldwide. Half of the children with severe sepsis in the United States are infants, and half of infants are low- or very low-birth-weight babies. Underlying disease occurs in 49% of U.S. children with severe sepsis. National hospital costs associated with severe sepsis in the United States were $2.3 billion in 1999. Relatively simple strategies to identify and treat children with sepsis in the developing world have shown remarkable success. These strategies have included empirical antibiotics in babies at high risk of sepsis and aggressive fluid resuscitation in Dengue hemorrhagic fever. CONCLUSIONS: Sepsis is a major health problem among children in both developing and industrialized countries. However, sepsis is both preventable and treatable. Improved prevention and treatment of sepsis could have a substantial effect on survival and quality of life of all children, both those who are otherwise healthy and those who are chronically ill. The variations in the epidemiology of pediatric sepsis underscore the need for a multidisciplinary approach and consistently applied definitions.

Practice variation in suspected neonatal sepsis: a costly problem in neonatal intensive care.

OBJECTIVE: The most common admission to intensive care nurseries is the infant with suspected neonatal sepsis. To determine the clinical practice of neonatologists with respect to this diagnosis, we examined a large neonatal database during a 2-year period of time. The goal of this study was to define whether there were optimal practice strategies that could identify a "benchmark" clinical approach for this diagnosis. DESIGN: The PROACT database of ParadigmHealth was examined for all term infants with an admitting ICD - 9 code for suspected neonatal sepsis between January 1, 2001 and December 31, 2002. Infants had to be asymptomatic by 24 hours of life with no significant respiratory signs and receiving oral feedings. All infants had negative blood cultures. Maternal risk factors were examined to determine if they influenced the duration of therapy. The impact of treatment upon subsequent length of stay was also evaluated. Several areas of the country were individually examined to see if possible regional variations existed with respect to treatment of suspected sepsis. RESULTS: There were no significant differences noted in the management when maternal risk factors for suspected sepsis were assessed. In general, neonates were treated for 3.3+/-1.8 to 3.5+/-2.1 days, regardless of the number of maternal risk factors present at birth (p=NS). Length of stay ranged from 4.2+/-2.1 to 4.4+/-1.9 days in these groups (p=NS). The duration of treatment ranged from 1 to 10 days, even though all infants were clinically well and feeding by 24 hours of life. A total of 170 infants (17.0%) were treated for 4 to 6 days and 116 (11.6%) neonates received antibiotics for 7 to 10 days, even with negative blood cultures. One region of the country appeared to treat infants for a longer period of time than the other four regions examined, increasing the mean length of stay by 1.8 days (p<0.05). CONCLUSIONS: Treatment of neonates with suspected sepsis appears to be influenced by considerations other than maternal risk factors or the infant's clinical condition beyond the first day of life. There appears to be a great deal of practice variation among neonatologists confronted by patients with suspected sepsis. Awareness of this unnecessary variation may be of great value in reducing the duration of antibiotic therapy in the NICU and shortening the length of stay.

[Sepsis, a complicated syndrome with major medical and social consequences]. / Sepsis, een gecompliceerd syndroom met belangrijke medische en maatschappelijke consequenties.

Severe sepsis is a life-threatening complication of infection. Due to associated organ-failure treatment in an Intensive Care Unit is usually indicated. Since sepsis is defined by the combination and progression of clinical events, correct definitions are essential to enable good comparison between study results and determination of suitable treatment. Severe sepsis is associated with a mortality of 20-60% and decreases the health-related quality of life in survivors. It is estimated that annually in the Netherlands 9000 patients are admitted to an Intensive Care Unit with severe sepsis. Direct medical costs of severe sepsis are estimated at [symbol: see text] 19,500 per patient. Costs correlate strongly with the length of stay. Annually Euro dollar 168,6 million is spent on severe sepsis, which represents 0.5% of all health-care costs and 1.7% of the annual hospital budget in the Netherlands.

The costs of septic syndromes in the intensive care unit and influence of hospital-acquired sepsis.

OBJECTIVE: To document the costs and outcomes of the various forms of the septic syndromes [systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock), particularly those associated with infection acquired in an intensive care unit (ICU). DESIGN: Prospective data collection for all septic patients admitted to a medical ICU during a 1-year period. Costs were computed from the viewpoint of the hospital. RESULTS: Mean total hospital costs were Euro 26,256, Euro 35,185, and Euro 27,083 for patients with sepsis, severe sepsis, and septic shock, respectively. Total costs varied slightly according to the site of infection and the severity of sepsis but were influenced mostly by its mode of acquisition: patients having sepsis associated with ICU-acquired infection incurred total costs about three times those of patients presenting with infection and sepsis on ICU admission (from Euro 39,908 in patients with ICU acquired sepsis to Euro 44,851 in patients with ICU-acquired septic shock). Stratifying patients by the presence of ICU-acquired infection also showed that a first episode of infection complicated by ICU-acquired sepsis incurred at least 2.5 times more costs than a single episode of sepsis. CONCLUSIONS: In this series the medical costs of sepsis were not markedly influenced by its severity but by its mode of acquisition. Due to wide variations in ICU costs cost-effectiveness analyses of treatments for sepsis should document the case-mix of patients and the contribution to this of nosocomial infections.

Resource utilization among patients with sepsis syndrome.

OBJECTIVE: To assess the resource utilization associated with sepsis syndrome in academic medical centers. DESIGN: Prospective cohort study. SETTING: Eight academic, tertiary-care centers. PATIENTS: Stratified random sample of 1,028 adult admissions with sepsis syndrome and all 248,761 other adult admissions between January 1993 and April 1994. The main outcome measures were length of stay (LOS) in total and after onset of sepsis syndrome (post-onset LOS) and total hospital charges. RESULTS: The mean LOS for patients with sepsis was 27.7 +/- 0.9 days (median, 20 days), with sepsis onset occurring after a mean of 8.1 +/- 0.4 days (median, 3 days). For all patients without sepsis, the LOS was 7.2 +/- 0.03 days (median, 4 days). In multiple linear regression models, the mean for patients with sepsis syndrome was 18.2 days, which was 11.0 days longer than the mean for all other patients (P < .0001), whereas the mean difference in total charges was $43,000 (both P < .0001). These differences were greater for patients with nosocomial as compared with community-acquired sepsis, although the groups were similar after adjusting for pre-onset LOS. Eight independent correlates of increased post-onset LOS and 12 correlates of total charges were identified. CONCLUSIONS: These data quantify the resource utilization associated with sepsis syndrome, and demonstrate that resource utilization is high in this group. Additional investigation is required to determine how much of the excess post-onset LOS and charges are attributable to sepsis syndrome rather than the underlying medical conditions.

Economic burden of illness imposed by severe sepsis in Austria.

INTRODUCTION: Sepsis is a life-threatening disease, requiring instant treatment in an intensive care unit (ICU). The aim of this study was to determine the direct and indirect costs occurring in Austria due to this disease. PATIENTS AND METHODS: Direct costs were calculated based on a retrospective chart analysis in four adult Austrian ICUs, evaluating 74 patient records from the years 2000/2001. Patients were identified to have suffered from severe sepsis using ACCP-definitions. Assessed resource use (medication, laboratory analysis, microbiology analysis, consumer-goods, diagnostic procedures, staff costs, and basic bed costs) was linked with related center specific costs to determine direct costs per patient. Indirect costs due to productivity losses were calculated using official statistical material. RESULTS: The mean length of ICU stay (LOS ICU) of a severely septic patient was 18.1 days. Overall ICU mortality was found to be 43.2% and showed no gender difference. The mean daily direct ICU costs of care for severely septic patients were [symbol: see text] 1,617 and the mean total direct ICU costs per septic patient were [symbol: see text] 28,582. In total costs, survivors were equally expensive as non-survivors ([symbol: see text] 28,699 vs. 28,463) although their length of study was considerably longer (21.9 vs. 13.2 days). Considering a range of patients with severe sepsis in Austria from 6,700 to 9,500 per year, total direct costs in Austria range from [symbol: see text] 192 million to [symbol: see text] 272 million. Indirect costs determined by productivity losses due to unfitness for work (temporary and permanent) and premature death amount to [symbol: see text] 484 million to [symbol: see text] 686 million in Austria per year (same incidence range). Total costs, i.e. burden of illness, combining direct costs with indirect costs, range from [symbol: see text] 676 million to [symbol: see text] 958 million. CONCLUSION: Patients with severe sepsis have a high mortality rate, spend prolonged periods of time in the ICU, and are expensive to treat. Indirect costs of severe sepsis due to productivity losses, particularly by premature death, are considerable.

Inference for the cost-effectiveness acceptability curve and cost-effectiveness ratio.

The aim of this article is to consider Bayesian and frequentist inference methods for measures of incremental cost effectiveness in data obtained via a clinical trial. The most useful measure is the cost-effectiveness (C/E) acceptability curve. Recent publications on Bayesian estimation have assumed a normal posterior distribution, which ignores uncertainty in estimated variances, and suggest unnecessarily complicated methods of computation. We present a simple Bayesian computation for the C/E acceptability curve and a simple frequentist analogue. Our approach takes account of errors in estimated variances, resulting in calculations that are based on distributions rather than normal distributions. If inference is required about the C/E ratio, we argue that the standard frequentist procedures give unreliable or misleading inferences, and present instead a Bayesian interval.

Intravenous therapy in critically ill adults: developing a clinically and cost-effective approach.

Intravenous therapies are the most common intervention for critically ill adults. Using a systematic approach as described by Droogan and Song (1996), a review of the literature was undertaken to determine whether the frequency of changing intravenous administration sets in critically ill adults with central venous catheters (CVCs) affected the incidence of CVC-related sepsis/systemic inflammatory response syndrome (SIRS)/bacteraemia. Two major randomized controlled trials were included in the review (Maki et al. 1987; Snydman et al. 1987), which conclude that increasing the change frequency of administration sets from 24 to 72 hours does not significantly increase the incidence of sepsis. This can therefore lead to considerable cost savings as well as ensuring clinically effective care. The review criteria excluded a plethora of related studies. However, these studies do corroborate the findings of Maki et al. and Snydman et al. They are summarized in the tables and are taken into account when making recommendations for clinical practice and future research. Clinical practice guidelines which are being implemented and evaluated locally are offered for the reader's consideration.

C-reactive protein levels in the extremely premature infant: case studies and literature review.

Sepsis continues to be a significant source of morbidity and mortality in the neonatal intensive unit. At the same time, we need to contain medical costs and prevent the rapid growth of resistant organisms by limiting unnecessary antibiotic use. Among laboratory indexes studied as indirect indicators of the presence and resolution of infection and inflammation, C-reactive protein (CRP) has gained more recent widespread use. CRP usually increases in a delayed manner with the onset of inflammation and decreases as inflammation resolves. We follow serial CRP values in our neonatal intensive care unit from the start of a sepsis evaluation until antibiotic therapy is withdrawn. We describe two extremely low birth weight patients who improved clinically with therapy and whose CRP levels normalized in the face of continued positive blood cultures. The implications for the use of CRP in deciding when to halt therapy in premature infants are discussed.

Costs, effects and C/E-ratios alongside a clinical trial.

A general approach is discussed to assess the uncertainty surrounding the cost effectiveness ratio (C/E-ratio) estimated on the basis of data from a randomised clinical trial. The approach includes the calculation of a 95% probability ellipse and introduces the concept of a so called C/E-acceptability curve. This last curve defines for each predefined C/E-ratio the probability that the C/E-ratio found in the study is acceptable. The approach is illustrated by estimates of costs per life saved and costs per patient discharged alive on the basis of data from a phase II trial addressing the value of anakinra in treating sepsis syndrome.