Is faster better? An economic evaluation of rapid and ultra-rapid genomic testing in critically ill infants and children

PurposeTo evaluate whether the additional cost of providing increasingly faster genomic results in pediatric critical care is outweighed by reductions in health care costs and increases in personal utility.MethodsHospital costs and medical files from a cohort of 40 children were analyzed. The health economic impact of rapid and ultra-rapid genomic testing, with and without early initiation, relative to standard genomic testing was evaluated.ResultsShortening the time to results led to substantial economic and personal benefits. Early initiation of ultra-rapid genomic testing was the most cost-beneficial strategy, leading to a cost saving of AU$26,600 per child tested relative to standard genomic testing and a welfare gain of AU$12,000 per child tested. Implementation of early ultra-rapid testing of critically ill children is expected to lead to an annual cost saving of AU$7.3 million for the Australian health system and an aggregate welfare gain of AU$3.3 million, corresponding to a total net benefit of AU$10.6 million.ConclusionEarly initiation of ultra-rapid genomic testing can offer substantial economic and personal benefits. Future implementation of rapid genomic testing programs should focus not only on optimizing the laboratory workflow to achieve a fast turnaround time but also on changing clinical practice to expedite test initiation.     

Tracheostomy in special groups of critically ill patients: Who,when, and where?

Tracheostomy is one of the most common procedures undertaken in critically ill patients. It offers many theoretical advantages over translaryngeal intubation. Recent evidence in a heterogeneous group of critically ill patients, however, has not demonstrated a benefit for tracheostomy, in terms of mortality, length of stay in Intensive Care Unit (ICU), or incidence of ventilator-associated pneumonia. It may be a beneficial intervention in articular subsets of ICU patients. In this article, we will focus on the evidence for the timing of tracheostomy and its effect on various subgroups of patients in critical care.     

Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients—a multinational observational study by the European Confederation of Medical Mycology

ObjectivesCoronavirus disease 2019 (COVID-19) -associated pulmonary aspergillosis (CAPA) has emerged as a complication in critically ill COVID-19 patients. The objectives of this multinational study were to determine the prevalence of CAPA in patients with COVID-19 in intensive care units (ICU) and to investigate risk factors for CAPA as well as outcome.MethodsThe European Confederation of Medical Mycology (ECMM) conducted a multinational study including 20 centres from nine countries to assess epidemiology, risk factors and outcome of CAPA. CAPA was defined according to the 2020 ECMM/ISHAM consensus definitions.ResultsA total of 592 patients were included in this study, including 11 (1.9%) patients with histologically proven CAPA, 80 (13.5%) with probable CAPA, 18 (3%) with possible CAPA and 483 (81.6%) without CAPA. CAPA was diagnosed a median of 8 days (range 0–31 days) after ICU admission predominantly in older patients (adjusted hazard ratio (aHR) 1.04 per year; 95% CI 1.02–1.06) with any form of invasive respiratory support (HR 3.4; 95% CI 1.84–6.25) and receiving tocilizumab (HR 2.45; 95% CI 1.41–4.25). Median prevalence of CAPA per centre was 10.7% (range 1.7%–26.8%). CAPA was associated with significantly lower 90-day ICU survival rate (29% in patients with CAPA versus 57% in patients without CAPA; Mantel–Byar p < 0.001) and remained an independent negative prognostic variable after adjusting for other predictors of survival (HR 2.14; 95% CI 1.59–2.87, p ≤ 0.001).ConclusionPrevalence of CAPA varied between centres. CAPA was significantly more prevalent among older patients, patients receiving invasive ventilation and patients receiving tocilizumab, and was an independent strong predictor of ICU mortality.     

High target attainment for β-lactam antibiotics in intensive care unit patients when actual minimum inhibitory concentrations are applied

Patients in the intensive care unit (ICU) are at risk for suboptimal levels of β-lactam antibiotics, possibly leading to poor efficacy. Our aim was to investigate whether the actual minimum inhibitory concentration (MIC) compared to the more commonly used arbitrary epidemiological cut-off values (ECOFFs) would affect target attainment in ICU patients on empirical treatment with broad-spectrum β-lactam antibiotics and to identify risk factors for not reaching target. In a prospective, multicenter study, ICU patients ≥18 years old and treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Clinical and laboratory data were recorded. Serum trough antibiotic levels from three consecutive days were analyzed by liquid chromatography–mass spectrometry (LC-MS). The target was defined as the free trough concentration above the MIC (100% fT_>MIC). MIC_ECOFF was used as the target and, when available, the actual MIC (MIC_ACTUAL) was applied. The median age of the patients was 70 years old, 52% (58/111) were males, and the median estimated glomerular filtration rate (eGFR) was 48.0 mL/min/1.73 m². The rate of patients reaching 100% fT?>?MIC_ACTUAL was higher (89%, 31/35) compared to the same patients using MIC_ECOFF (60%, p?=?0.002). In total, 55% (61/111) reached 100% fT?>?MIC_ECOFF. Increased renal clearance was independently associated to not reaching 100% fT?>?MIC_ECOFF. On repeated sampling, >77% of patients had stable serum drug levels around the MIC_ECOFF. Serum concentrations of β-lactam antibiotics vary extensively between ICU patients. The rate of patients not reaching target was markedly lower for the actual MIC than when the arbitrary MIC based on the ECOFF was used, which is important to consider in future studies.     

Risk factors for hospital-acquired hypernatremia among critically ill medical patients in a setting utilizing a preventive free water protocol: Do we need to do more?

Context:

Hospital-acquired hypernatremia (HAH) is a frequent concern in critical care, which carries high mortality.

Aims:

To study the risk factors for HAH in settings that practice a preventive protocol.

Settings and Design:

Two tertiary-care hospitals. Prospective observational study design.

Materials and Methods:

Patients aged >18 years admitted for an acute medical illness with normal serum sodium and need for intensive care >48 h formed the study population. Details of the basic panel of investigations on admission, daily electrolytes and renal function test, sodium content of all intake, free water intake (oral, enteral and intravenous) and fluid balance every 24 h were recorded. Individuals with serum Na 140-142 meq/l received 500 ml of free water every 24 h, and those with 143-145 meq/l received 1000 ml free water every 24 h.

Statistical Analysis Used:

Risk factors associated with HAH was analysed by multiple logistic regression.

Results:

Among 670 study participants, 64 (9.5%) developed HAH. The median duration of hypernatremia was 3 days. A total 60 of 64 participants with HAH had features of renal concentrating defect during hypernatremia. Age >60 years (P = 0.02), acute kidney injury (AKI) on admission (P = 0.01), mechanical ventilation (P = 0.01), need for ionotropes (P = 0.03), worsening Sequential Organ Failure Assessment (SOFA) score after admission (P < 0.001), enteral tube feeds (P = 0.002), negative fluid balance (P = 0.02) and mannitol use (P < 0.001) were the risk factors for HAH. Mortality rate was 34.3% among hypernatremic patients.

Conclusions:

The study suggests that administration of free water to prevent HAH should be more meticulously complied with in patients who are elderly, present with AKI, suffer multi-organ dysfunction, require mechanical ventilation, receive enteral feeds and drugs like mannitol or ionotropes.     

How to improve our ability to predict adverse events in major surgery of SLE patients?

Monitoring organ damage in systemic lupus erythematosus (SLE) patients addresses the aspect of the disease which is irreversible, independently of its cause: SLE , drugs and/or co-morbidities. Damage accrual correlates with morbidity, mortality and impaired quality of life. Once damage has occurred further deterioration is to be suspected. Cardiovascular (CV) events are considered the first single cause of death in SLE-patients, partly attributable to accelerated atherosclerosis; thus, monitoring traditional and modifiable CV risks in SLE patients is recommended. Damage assessment could be useful in evaluating cardiovascular surgery risks in SLE patients. In this report the clinical course after an ascending aorta and aortic valve replacement in a 32 year-old caucasian woman is described. Perhaps, time has come for a worldwide challenge to create an updated score to quantify damage in SLE patients.     

A retrospective evaluation of critically ill patients infected with H1N1 influenza A virus in Bursa,Turkey, during the 2009–2010 pandemic

Background

H1N1 influenza A virus infections were first reported in April 2009 and spread rapidly, resulting in mortality worldwide. The aim of this study was to evaluate patients with H1N1 infection treated in the intensive care unit (ICU) in Bursa, Turkey.

Methods

Demographic characteristics, clinical features, and outcome relating to H1N1 infection were retrospectively analysed in patients treated in the ICU.

Results

Twenty-three cases of H1N1 infection were treated in the ICU. The mean age of patients was 37 years range: (17–82). Fifteen patients were female (65.2%). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 19 range: (5–39). The most common symptoms were dyspnea (73.9%), fever (69.6%), and cough (60.9%). Mechanical ventilation was required for all patients. Oseltamivir and antibiotics were administered to all patients. Six (26.1%) patients died. APACHE II scores were higher in the deceased 28.5 range: [16–39] vs. 14 range: [5–28] in survivors; p = 0.013).

Conclusion

When compared to the literature, the demographic, epidemiological, and clinical characteristics were similar in the cases we encountered. The mortality rate was high despite the use of appropriate treatment. We believe that the high mortality is related to higher APACHE II scores. The H1N1 virus should be considered in community acquired pneumonia, especially in younger patients presenting with severe pneumonia.     

Would you be surprised if this patient died?: Preliminary exploration of first and second year residents' approach to care decisions in critically ill patients

Background  

How physicians approach decision-making when caring for critically ill patients is poorly understood. This study aims to explore how residents think about prognosis and approach care decisions when caring for seriously ill, hospitalized patients.     

Use of FRAX®-based fracture risk assessments to identify patients who will benefit from osteoporosis therapy

Several pharmacological interventions, including selective estrogen receptor modulators (SERMs), bisphosphonates, denosumab, and strontium ranelate have demonstrated efficacy in reducing the incidence of osteoporotic fractures, the most severe consequence of postmenopausal osteoporosis. Until recently, bone mineral density (BMD) was the primary factor used to determine which postmenopausal women may require osteoporosis treatment. However, clinical guidelines now recommend the use of the Fracture Risk Assessment Tool (FRAX^®), a computer-based algorithm introduced by the World Health Organization, to help primary care physicians identify postmenopausal women who may be candidates for pharmacological osteoporosis therapy based on the level of fracture risk. Beyond its utility as a resource for determining whether or not to initiate osteoporosis treatment, clinical studies have begun to evaluate the correlation between FRAX^®-based 10-year fracture probability and efficacy of different osteoporosis treatments. Bazedoxifene, clodronate, and denosumab have shown greater fracture risk reduction at higher FRAX^®-based 10-year fracture probabilities, but the efficacy of raloxifene, alendronate, and strontium ranelate were relatively stable regardless of fracture probability. In summary, these data suggest that the relationship between FRAX^®-based fracture probability and efficacy of different osteoporosis treatments varies depending upon the agent in question.     

Population pharmacokinetics and pharmacodynamics of fosfomycin in non–critically ill patients with bacteremic urinary infection caused by multidrug-resistant Escherichia coli

ObjectivesTo describe the population pharmacokinetics of fosfomycin for patients with bacteraemic urinary tract infection (BUTI). The analysis identified optimal regimens on the basis of pharmacodynamic targets and assessed the adequacy of Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) susceptibility breakpoints for Escherichia coli.MethodsData of 16 patients with BUTI caused by multidrug-resistant E. coli (FOREST clinical trial) received intravenous fosfomycin (4 g every 6 hours) were analysed. A population pharmacokinetic analysis was performed, and Monte Carlo simulations were undertaken using 4 g every 6 hours and 8 g every 8 hours. The probability of pharmacodynamic target attainment was assessed using pharmacodynamic targets for E. coli for static effect, 1-log drop in bacterial burden and resistance suppression.ResultsSixty-four plasma samples were collected over a single dosing interval (day 2 or 3 after starting fosfomycin treatment). Fosfomycin concentrations were highly variable. Pharmacodynamic target attainment analysis showed mild improvement by increasing fosfomycin dosing (4 g every 6 hours vs. every 8 hours). These dosages showed success for decreasing 1-log bacterial burden in 89% to 96% (EUCAST breakpoints) and 33% to 54% (CLSI breakpoints) of patients, but they were unable to reach bacterial resistance suppression targets.ConclusionsFosfomycin concentrations are highly variable—a fact partially explained by renal impairment. The present work supports the use of 4 g every 6 hours as an effective regimen for the treatment of non–critically ill patients with BUTI caused by multidrug-resistant E. coli, as higher dosages might increase toxicity but may not significantly increase efficacy. The current information may suggest that fosfomycin susceptibility breakpoints need to be reappraised.     

Hysterosalpingography: a potential alternative to laparoscopy in the evaluation of tubal obstruction in infertile patients?

BackgroundEvaluation of the fallopian tubes are important for infertile patients. The two most important diagnostic procedures used to evaluate tubal patency are hysterosalpingography and laparoscopy.ObjectivesTo asses the hysterosalpingography and laparoscopy results of patients diagnosed with infertility and investigate the diagnostic value of hysterosalpingography in patients with tubal factor infertility.MethodsThe hysterosalpingography and laparoscopy results of 208 patients who presented to the Obstetrics and Gynecology Clinic at Dicle University, Faculty of Medicine between January 2014- January 2018 were retrospectively evaluated. Hysterosalpingography and laparoscopy results were compared with regard to the investigation of the presence of tubal obstruction and of the pelvic structures that could cause tubal obstruction. The specificity, sensitivity, positive, and negative predictive values of hysterosalpingography were computed.ResultsThe number of patients evaluated was 208. The ratio of primary infertile patients was 57.2% and 42.8% was secondary infertile. Hysterosalpingography was found to have a specificity of 64.6%, the sensitivity of 81.3%, the positive predictive value of 56.4%, and a negative predictive value of 86% in the determination of tubal obstruction.ConclusionPatients with suspected tubal infertility can primarily be examined using hysterosalpingography in consideration of the invasive nature and the higher complication rate of laparoscopy.     

Variation in genes of β-glucan recognition pathway and susceptibility to opportunistic infections in HIV-positive patients

Opportunistic infections are the main cause of morbidity and death among HIV-positive patients. Most of these infections are linked to the immunodeficiency due to low CD4+ counts. However, not all patients with low CD4+ counts are equally susceptible to infections, and we hypothesize that variability in genes of innate immunity may also play an important role. The dectin-1/CARD9 pathway is crucial for recognition of both fungal and bacterial pathogens. The aim of this study was to assess the possible association between the occurrence of opportunistic infections and single nucleotide polymorphisms in DECTIN-1 and CARD9 in a cohort of 187 HIV-infected patients. The incidence of oropharyngeal candidiasis and other opportunistic infections was not influenced by either the Y238X DECTIN-1 or the S12N CARD9 polymorphism. Surprisingly however, the prevalence of pneumonia was significantly higher in patients bearing the defective variant DECTIN-1 allele. These results suggest a role of dectin-1 in the host defense against respiratory bacterial infections, and future studies are warranted to confirm this association.     

Which memory processes are affected in patients with obstructive sleep apnea? An evaluation of 3 types of memory

STUDY OBJECTIVE: To investigate which memory processes are affected by obstructive sleep apnea (OSA). DESIGN: Three separate memory systems were investigated in patients with OSA and normal subjects. Verbal episodic memory was tested after forced encoding, in order to control the level of attention during item presentation; procedural memory was tested using a simplified version of a standard test with an interfering task; lastly, working memory was examined with validated paradigms based on a theoretical model. SETTING: Sleep laboratory and outpatient sleep clinic in a French tertiary-care university hospital. PARTICIPANTS: Ninety-five patients with OSA and 95 control subjects matched for age and level of education. Group 1 (54 patients, 54 controls) underwent an extensive battery of tasks evaluating verbal episodic, procedural, and working memory. Group 2 (16 patients, 16 controls) underwent procedural memory tests only, and group 3 (25 patients, 25 controls) working memory tests only. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Compared with matched controls, patients with OSA exhibited a retrieval deficit of episodic memory but intact maintenance, recognition, and forgetfulness; decreased overall performance in procedural memory, although pattern learning did occur; and impairment of specific working memory capabilities despite normal short-term memory. No consistent correlation was found between OSA severity and memory deficit. The long duration of the test session did not negatively impact the patients' performance. CONCLUSIONS: Memory impairment in OSA is mild and does not affect all memory processes but, rather, specific aspects, underscoring the need for extensive and specific memory testing in clinical and research settings.