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Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: The ProHOSP randomized controlled trial
Abstract
Context: In previous smaller trials, a procalcitonin (PCT) algorithm reduced antibiotic use in patients with lower respiratory tract infections (LRTIs). Objective: To examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes. Design, Setting, and Patients: A multicenter, noninferiority, randomized controlled trial in emergency departments of 6 tertiary care hospitals in Switzerland with an open intervention of 1359 patients with mostly severe LRTIs randomized between October 2006 and March 2008. Intervention: Patients were randomized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics (PCT group) or according to standard guidelines (control group). Serum PCT was measured locally in each hospital and instructions were Web-based. Main Outcome Measures: Noninferiority of the composite adverse outcomes of death, intensive care unit admission, disease-specific complications, or recurrent infection requiring antibiotic treatment within 30 days, with a predefined noninferiority boundary of 7.5%; and antibiotic exposure and adverse effects from antibiotics. Results: The rate of overall adverse outcomes was similar in the PCT and control groups (15.4% [n=103] vs 18.9% [n=130]; difference, -3.5%; 95% CI, -7.6% to 0.4%). The mean duration of antibiotics exposure in the PCT vs control groups was lower in all patients (5.7 vs 8.7 days; relative change, -34.8%; 95% CI, -40.3% to -28.7%) and in the subgroups of patients with community-acquired pneumonia (n=925, 7.2 vs 10.7 days; -32.4%; 95% CI, -37.6% to -26.9%), exacerbation of chronic obstructive pulmonary disease (n=228, 2.5 vs 5.1 days; -50.4%; 95% CI, -64.0% to -34.0%), and acute bronchitis (n=151, 1.0 vs 2.8 days; -65.0%; 95% CI, -84.7% to -37.5%). Antibiotic-associated adverse effects were less frequent in the PCT group (19.8% [n=133] vs 28.1% [n=193]; difference, -8.2%; 95% CI, -12.7% to -3.7%). Conclusion: In patients with LRTIs, a strategy of PCT guidance compared with standard guidelines resulted in similar rates of adverse outcomes, as well as lower rates of antibiotic exposure and antibiotic-associated adverse effects. Trial Registration: isrctn.org Identifier: ISRCTN95122877
... In the ProHOSP study, PCT was measured in patients with suspected LRTI to determine whether to administer antibiotics [19]. The PCT-guided algorithm recommended starting antibiotics in those with PCT levels > 0.25 µg/L measured within 1 hour of admission. ...
... The above-mentioned ProHOSP study also evaluated the effect of PCT-guided antibiotic management on antibiotic discontinuation in patients with LRTI [19]. PCT was measured on days 3, 5, and 7 of antibiotic treatment. ...
... Different results may be obtained in real-world clinical practice than in clinical trials. A study in Switzerland thus applied the ProHOSP study algorithm to actual clinical practice [19,71], in which there were more patients with renal disease, cancer, or immunosuppression. Pneumonia severity and CAP rates were higher among real-world patients than in the ProHOSP cohort. ...
Biomarkers are playing an increasingly important role in antimicrobial stewardship. Their applications have included use in algorithms that evaluate suspected bacterial infections or provide guidance on when to start or stop antibiotic therapy, or when therapy should be repeated over a short period (6–12 h). Diseases in which biomarkers are used as complementary tools to determine the initiation of antibiotics include sepsis, lower respiratory tract infection (LRTI), COVID-19, acute heart failure, infectious endocarditis, acute coronary syndrome, and acute pancreatitis. In addition, cut-off values of biomarkers have been used to inform the decision to discontinue antibiotics for diseases such as sepsis, LRTI, and febrile neutropenia. The biomarkers used in antimicrobial stewardship include procalcitonin (PCT), C-reactive protein (CRP), presepsin, and interleukin (IL)-1β/IL-8. The cut-off values vary depending on the disease and study, with a range of 0.25–1.0 ng/mL for PCT and 8–50 mg/L for CRP. Biomarkers can complement clinical diagnosis, but further studies of microbiological biomarkers are needed to ensure appropriate antibiotic selection.
... The study by Philipp Schuetz et al [17] was a multicenter, non-inferiority, randomized controlled trial which included 1381 patients with a primary diagnosis of LRTI at ED. In the PCT group (n = 687), the administration of antibiotics was based on a PCT algorithm, while in standard group (n = 694) administration of antibiotics was given according to standard guidelines. ...
... Mortality was reported by a total of 15 studies, 4 of which were on CAP [8,10,12,13], 3 on LRTIs [11,17,18], 3 on VAP [7,19,21], 1 on aspiration pneumonia [22], 1 on HAP [23] and 3 on COPD exacerbation [8,9,24]. Most of the studies had wide confidence intervals. ...
... Antibiotic Prescription: 9 studies reported this outcome, four of the studies included patients with CAP [11,12,13,16], three included patients with LRTI [17,18,10] and two included patients with COPD [9,10]. This outcome was measured at different time-points ranging from antibiotic prescription on admission-initial consultation up to 30-day follow-up. ...
Objectives: Biomarker-based clinical practice is currently gaining ground and increasingly affects decision making. A variety of biomarkers have been studied through the years and some of them have already an established role in modern medicine, such as procalcitonin (PCT) which has been proposed to reduce antibiotic exposure. We purposed to systematically review all biomarkers examined for guiding the clinical practice in patients with pneumonia.
Methods: A systematic review on PubMed was performed on April 2023 by two independent researchers using the PRISMA guidelines. Randomized trials which enrolled patients with pneumonia and compared biomarker-guided strategies to standard of care were included.
Results: 1242 studies were recorded, from whom 16 were eligible for this study. 14 studies investigated PCT as a biomarker. From these, 8 studies reported on community acquired pneumonia (CAP), 2 on ventilator associated pneumonia (VAP), 1 on aspiration pneumonia, 1 on hospital acquired pneumonia (HAP) and 2 on exacerbation of chronic obstructive pulmonary disease (ECOPD). There was 1 study, referred to VAP, that investigated interleukin-1β (IL-1β) and interleukin-8 (IL-8) and 1 study that reported the role of C-reactive protein (CRP) in ECOPD. In a total of 4751 patients in 15 studies, the biomarker-based approach did not lead to increased mortality [OR: 0.998 (95%CI: 0.74-1.34, p value: 0.991). I2:19%]. Among different types of pneumonia and time-points of assessment, biomarker-guided practice appeared to improve antibiotic-related outcomes, such as rate of antibiotic prescription, duration of antibiotic therapy and rate of antibiotic exposure, while 5 studies reported a possible decrease in antibiotic-related adverse effects. Biomarker-guided practice did not seem to lead in an increase in other adverse outcomes such as need for hospitalization and duration of hospitalization. However, the included studies have high risk of bias mainly due to improper blinding of participants/personnel and outcome assessors.
Conclusion: Biomarker-guided clinical practice improves provided healthcare, in terms of reduced antibiotic consumption with no inferiority to mortality, relapses and exacerbations in patients with different types of pneumonia. Thus, such approaches should be further evaluated to achieve personalized medicine.
... Procalcitonin (PCT) is a host inflammatory biomarker which is usually elevated in bacterial and/or severe infections [19]. While PCT can be used to safely guide antibiotic use, its impact on their prescription remains controversial mainly due to variable physician adherence to PCT guidance [13,20,21]. If none of these tools in isolation is sufficient to optimize antibiotic prescription, a combined approach could improve diagnostic performance, ensure patients' safety, and maximize clinicians' adherence to guidance. ...
... Patients with features of pneumonia on LUS PCT will be measured in all patients with LUS features of pneumonia to identify those in whom it is safe to withhold antibiotics (lower probability of bacterial or severe CAP in those with a low PCT value) [19,20]. To ensure safety, a 28-day mortality risk will be calculated at the bed-side using the DS-CRB-65, and antibiotics will be prescribed if the score is ≥3 in patients with contradictory results (positive LUS and PCT <0.25 μg/L) [31]. ...
... Patients' selection will be stratified according to age, sex, nationality, and level of education. To ensure that they are representative of the population with LRTI in EDs, we will focus on a population aged 59 years and over (median age of 73 years, based on the ProHOSP randomized controlled trial) [20]. Half of the patients will be part of the control group (managed as usual), and half will be part of the intervention group (managed with the PLUS intervention) to highlight the differences in perception between usual care and a management with new diagnostic tools. ...
Background
Lower respiratory tract infections (LRTIs) are among the most frequent infections and a significant contributor to inappropriate antibiotic prescription. Currently, no single diagnostic tool can reliably identify bacterial pneumonia. We thus evaluate a multimodal approach based on a clinical score, lung ultrasound (LUS), and the inflammatory biomarker, procalcitonin (PCT) to guide prescription of antibiotics. LUS outperforms chest X-ray in the identification of pneumonia, while PCT is known to be elevated in bacterial and/or severe infections. We propose a trial to test their synergistic potential in reducing antibiotic prescription while preserving patient safety in emergency departments (ED).
Methods
The PLUS-IS-LESS study is a pragmatic, stepped-wedge cluster-randomized, clinical trial conducted in 10 Swiss EDs. It assesses the PLUS algorithm, which combines a clinical prediction score, LUS, PCT, and a clinical severity score to guide antibiotics among adults with LRTIs, compared with usual care. The co-primary endpoints are the proportion of patients prescribed antibiotics and the proportion of patients with clinical failure by day 28. Secondary endpoints include measurement of change in quality of life, length of hospital stay, antibiotic-related side effects, barriers and facilitators to the implementation of the algorithm, cost-effectiveness of the intervention, and identification of patterns of pneumonia in LUS using machine learning.
Discussion
The PLUS algorithm aims to optimize prescription of antibiotics through improved diagnostic performance and maximization of physician adherence, while ensuring safety. It is based on previously validated tests and does therefore not expose participants to unforeseeable risks. Cluster randomization prevents cross-contamination between study groups, as physicians are not exposed to the intervention during or before the control period. The stepped-wedge implementation of the intervention allows effect calculation from both between- and within-cluster comparisons, which enhances statistical power and allows smaller sample size than a parallel cluster design. Moreover, it enables the training of all centers for the intervention, simplifying implementation if the results prove successful.
The PLUS algorithm has the potential to improve the identification of LRTIs that would benefit from antibiotics. When scaled, the expected reduction in the proportion of antibiotics prescribed has the potential to not only decrease side effects and costs but also mitigate antibiotic resistance.
Trial registration
This study was registered on July 19, 2022, on the ClinicalTrials.gov registry using reference number: NCT05463406.
Trial status
Recruitment started on December 5, 2022, and will be completed on November 3, 2024. Current protocol version is version 3.0, dated April 3, 2023.
... The procalcitonin test is cleared by the Food and Drug Administration (FDA) for use in several clinical scenarios, including as a guide to decisionmaking about initiating and discontinuing antibiotics for patients with lower respiratory tract infections (LRTIs) [3]. Several randomized controlled trials and a large meta-analysis have demonstrated lower rates of antibiotic exposure with procalcitonin-guided treatment of LRTIs [4][5][6][7]. However, realworld studies on whether procalcitonin testing helps decrease antibiotic duration have reached conflicting results [8][9][10][11]. ...
... The failure to see a meaningful difference in antibiotic exposure with procalcitonin monitoring may also reflect poor implementation of the test. Our data indicate that procalcitonin was not typically being ordered in a serial fashion (eg, every 1-2 days), which is in contrast to its use in clinical trials [5][6][7][8]. Furthermore, in the patients who did have documentation of low or declining procalcitonin values, only 1 out of every 2 patients had antibiotics discontinued. ...
Background
Randomized controlled trials have shown that procalcitonin-guided algorithms can reduce antibiotic duration for lower respiratory tract infections (LRTIs). The goal of this study was to compare antibiotic duration for LRTIs with and without procalcitonin testing in real-life practice.
Methods
This retrospective cohort study included all acute care hospital admissions for presumed LRTIs between 1/2018 and 12/2021 at 81 Veterans Affairs facilities with on-site procalcitonin testing. The exposure was procalcitonin testing; the primary outcome was antibiotic duration. We used 1:1 nearest-neighbor propensity score matching to estimate the difference in outcome between procalcitonin-tested and nontested patients.
Results
A total of 35 610 patients with LRTIs were included (6015 [16.9%] with procalcitonin testing; 29 595 [83.1%] without testing). In tested patients, the median number of procalcitonin levels checked (interquartile range) was 2 (1–3). The mean antibiotic duration was 10.0 days in the procalcitonin group compared with 8.3 days in nontested patients (unadjusted difference, 1.7 days; P < .0001). After propensity score matching with 3903 pairs, antibiotic duration remained greater in the procalcitonin group (9.6 days vs 9.2 days; P < .0001). In a subgroup analysis of 2241 tested patients with a procalcitonin value at the standard threshold for antibiotic discontinuation, antibiotic duration was shorter in tested vs nontested patients, with a mean difference of 0.1 days (P < .01).
Conclusions
In this retrospective propensity-matched cohort of patients with presumed LRTIs across a geographically diverse group of hospitals, patients who underwent procalcitonin testing did not have a meaningful reduction in antibiotic duration compared with those who were not tested. Poor implementation of procalcitonin testing may have undermined its effectiveness.
... 12,25 The increased mortality seen in individuals with PCT values more than 0.25 ng/ml corroborates other authors' findings, establishing a correlation between elevated PCT values and severe illness or death. 26,27 Greater PCT is likely to represent bacterial superinfection and resultant deterioration in many situations. The prospect of improving antimicrobial stewardship by using a higher PCT threshold or other criteria is also conceivable in severe COVID-19 patients, where PCT levels can be possibly elevated independent of bacterial infection. ...
Procalcitonin (PCT), a key hormone regulating calcium homeostasis, has previously shown the potential to differentiate between bacterial and viral infections. However, when we move further into the field of COVID-19 pandemic, an unprecedented question was raised: Can PCT levels increase without bacterial co-infection in SARS-CoV-2 infection? This review systematically searched PubMed, Scopus, and Google Scholar for articles on procalcitonin (PCT) in the context of COVID-19 published from 2019 to 2023. Inclusion criteria focused on relevant articles, excluding non-English publications. Increasing PCT levels were observed in COVID-19 patients, especially in severe cases, often interpreted as evidence of bacterial co-infection. However, the role of PCT in the immune response to SARS-CoV-2 remains unclear. The proposed mechanisms suggest that SARS-CoV-2 can stimulate the production of PCT even in the absence of bacterial co-infection by modulating the interferon (IFN) pathway and reducing the regulation of monocyte function. Furthermore, PCT has implications in antibiotic management, with guidelines recommended to avoid antibiotics in patients with low serum PCT levels. Increased PCT values show associations with the severity of disease, including increased mortality, which further underlines the need for a detailed understanding of the dynamics of the PCT in COVID-19. This review emphasizes the evolving significance of PCT in COVID-19, with elevated PCT levels emerging as a valuable prognostic indicator, aiding in disease severity assessment and management. However, the intricate dynamics of PCT in COVID-19 demand further investigation, particularly in distinguishing viral infection from bacterial co-infection.
... Between patients in the subgroup with CAP, antibiotics exposure was lower in the PCT-guided group without significant differences in adverse outcomes (925 patients, 7.2 vs. 10.7 days; À32.4%; 95% CI: À37.6 to À26.9%). 13 A recent meta-analysis compiled 12 studies gathering 2,408 patients with confirmed CAP. Kamat et al found in this meta-analysis a sensibility of 55% (95% CI: 0.37-0.71) ...
Community acquired pneumonia (CAP) is a prevalent infectious disease often requiring hospitalization, although its diagnosis remains challenging as there is no gold standard test. In severe CAP, clinical and radiologic criteria have poor sensitivity and specificity, and microbiologic documentation is usually delayed and obtained in less than half of sCAP patients. Biomarkers could be an alternative for diagnosis, treatment monitoring and establish resolution. Beyond the existing evidence about biomarkers as an adjunct diagnostic tool, most evidence comes from studies including CAP patients in primary care or emergency departments, and not only sCAP patients. Ideally, biomarkers used in combination with signs, symptoms, and radiological findings can improve clinical judgment to confirm or rule out CAP diagnosis, and may be valuable adjunctive tools for risk stratification, differentiate viral pneumonia and monitoring the course of CAP. While no single biomarker has emerged as an ideal one, CRP and PCT have gathered the most evidence. Overall, biomarkers offer valuable information and can enhance clinical decision-making in the management of CAP, but further research and validation are needed to establish their optimal use and clinical utility.
... All patients were treated according to published community-acquired pneumonia guidelines [18]. Stewardship of antibiotic treatment duration by procalcitonin was encouraged by the study protocol according to Schuetz and colleagues [19]. Baseline data included medical history items, relevant comorbidities, clinical items of pneumonia, and all variables required for the calculation of the pneumonia severity index (PSI) [20]. ...
Background
Several trials and meta-analyses found a benefit of adjunct corticosteroids for community-acquired pneumonia with respect to short-term outcome, but there is uncertainty about longer-term health effects. Herein, we evaluated clinical outcomes at long term in patients participating in the STEP trial (Corticosteroid Treatment for Community-Acquired Pneumonia).
Methods
This predefined secondary analysis investigated 180-day outcomes in 785 adult patients hospitalized with community-acquired pneumonia included in STEP, a randomised, placebo-controlled, double-blind trial. The primary endpoint was time to death from any cause at 180 days verified by telephone interview. Additional secondary endpoints included pneumonia-related death, readmission, recurrent pneumonia, secondary infections, new hypertension, and new insulin dependence.
Results
From the originally included 785 patients, 727 were available for intention-to-treat analysis at day 180. There was no difference between groups with respect to time to death from any cause (HR for corticosteroid use 1.15, 95% CI 0.68 to 1.95, p = 0.601). Compared to placebo, corticosteroid-treated patients had significantly higher risks for recurrent pneumonia (OR 2.57, 95% CI 1.29 to 5.12, p = 0.007), secondary infections (OR 1.94, 95% CI 1.25 to 3.03, p = 0.003) and new insulin dependence (OR 8.73, 95% CI 1.10 to 69.62, p = 0.041). There was no difference regarding pneumonia-related death, readmission and new hypertension.
Conclusions
In patients with community-acquired pneumonia, corticosteroid use was associated with an increased risk for recurrent pneumonia, secondary infections and new insulin dependence at 180 days. Currently, it is uncertain whether these long-term adverse effects outweigh the short-term effects of corticosteroids in moderate CAP.
Trial registration
This trial was registered with ClinicalTrials. gov, number NCT00973154 before the recruitment of the first patient. First posted: September 9, 2009. Last update posted: April 21, 2015.
... Mixed clinical data exists on the impact these tests have on antibiotic use for ARI; however, use of influenza NAAT and rapid streptococcal testing is recommended by the Infectious Diseases Society of America (IDSA) in patients with concern for pneumonia or pharyngitis, respectively [13][14][15]. Biomarkers, such as procalcitonin and C-reactive protein (CRP), have also been of interest in the management of ARI, though their role in therapy remains uncertain at this time [16][17][18]. While the diagnostic testing methods mentioned can be advantageous in providing objective information to use in antibiotic prescribing pathways, they are also costly and can leave the door open for misinterpretation if not used correctly. ...
Purpose of Review
Inappropriate and unnecessary antibiotic prescriptions are common in the outpatient setting and as patients transition from inpatient to outpatient care. This review is designed to discuss effective strategies aimed to improve appropriate antibiotic use during transitions of care and in the outpatient setting for high-priority syndrome areas including acute respiratory infections (ARI), urinary tract infections (UTI), skin and soft tissue infections (SSTI), and bone and joint infections (BJI).
Recent Findings
Unlike inpatient stewardship programs, outpatient stewardship practices are currently not standardized across many healthcare systems. Since starting an outpatient ASP can be overwhelming, many programs opt to start by focusing on a smaller subset of high-priority locations or syndromes where antibiotics may be inappropriately prescribed. Numerous studies have identified effective antimicrobial stewardship strategies that can be incorporated on transitions of care and in the outpatient setting; however, a multimodal approach combining several stewardship strategies is often cited as the most effective approach. Available syndrome-specific interventions include opportunities at time of diagnosis, order entry, and post-prescription which may be tailored to meet individual program needs.
Summary
Outpatient ASP interventions targeted at diagnostic stewardship, adjustments to duration of therapy, optimization of agent selection, and avoidance of intravenous therapy remain high-priority target areas to prevent inappropriate antibiotic use.
Latar Belakang: Sepsis adalah masalah kesehatan global, yang ditandai adanya disfungsi organ disebabkan oleh disregulasi respon inang dalam menanggapi infeksi mikroba. Insidensi dan mortalitas pasien sepsis yang dirawat di ICU masih cukup tinggi. Diagnosis dinisangat diperlukan untuk pengobatan yang efektif dan menghindari penggunaan antibiotikyang tidak perlu. Procalcitonin adalah biomarker yang menunjukkan nilai diagnostik yang lebih baik daripada penanda proinflamasi lainnya dalam mengidentifikasi pasien dengan sepsis dan dapat digunakan dalam diagnosis infeksi bakteri. Tujuan dari penelitian ini adalah untuk menentukan sensitivitas dan spesifisitas prokalsitonin sebagai biomarker pada pasien sepsis.Metode: Desain penelitian ini adalah retrospektif dengan menggunakan data rekam medis pada pasien yang dirawat di ICU RSUP Dr. Sardjito Yogyakarta periode Januari – Desember 2018. Uji diagnostik dilakukan pada pasien sespsis dan non-sepsis yang mengalami disfungsi organ sesuai dengan kriteria skor SOFA. Cutoff point procalsitonin ditentukan menggunakan analisis receiver operating characteristic (ROC). Analisis data dilakukan untuk mengetahui sensitivitas, spesisifitas, nilai duga positif, nilai duga negatif procalcitonin pada pasien sepsis.Hasil: Pada uji diagnostik procalcitonin pada pasien sepsis dengan cut-off point 3,27 ng/ml, didapatkan hasil sensitivitas 89,0%, spesifisitas 90%, nilai duga positif 90,1% dan nilai duga negatif 88,9%. Pada analisa ROC procalcitonin terhadap sepsis, didapatkan AUC 0,941 (AUC > 0,9).Kesimpulan: Procalcitonin juga memiliki nilai diagnostik yang baik sebagai biomarker pada pasien sepsis yang dirawat di ICU RSUP Dr. Sardjito. Procalcitonin memiliki kemampuan diskriminasi sangat kuat untuk pasien sepsis.
Latar Belakang: Sepsis adalah masalah kesehatan global, yang ditandai adanya disfungsi organ disebabkan oleh disregulasi respon inang dalam menanggapi infeksi mikroba. Insidensi dan mortalitas pasien sepsis yang dirawat di ICU masih cukup tinggi. Diagnosis dinisangat diperlukan untuk pengobatan yang efektif dan menghindari penggunaan antibiotikyang tidak perlu. Procalcitonin adalah biomarker yang menunjukkan nilai diagnostik yang lebih baik daripada penanda proinflamasi lainnya dalam mengidentifikasi pasien dengan sepsis dan dapat digunakan dalam diagnosis infeksi bakteri. Tujuan dari penelitian ini adalah untuk menentukan sensitivitas dan spesifisitas prokalsitonin sebagai biomarker pada pasien sepsis.Metode: Desain penelitian ini adalah retrospektif dengan menggunakan data rekam medis pada pasien yang dirawat di ICU RSUP Dr. Sardjito Yogyakarta periode Januari – Desember 2018. Uji diagnostik dilakukan pada pasien sespsis dan non-sepsis yang mengalami disfungsi organ sesuai dengan kriteria skor SOFA. Cutoff point procalsitonin ditentukan menggunakan analisis receiver operating characteristic (ROC). Analisis data dilakukan untuk mengetahui sensitivitas, spesisifitas, nilai duga positif, nilai duga negatif procalcitonin pada pasien sepsis.Hasil: Pada uji diagnostik procalcitonin pada pasien sepsis dengan cut-off point 3,27 ng/ml, didapatkan hasil sensitivitas 89,0%, spesifisitas 90%, nilai duga positif 90,1% dan nilai duga negatif 88,9%. Pada analisa ROC procalcitonin terhadap sepsis, didapatkan AUC 0,941 (AUC > 0,9).Kesimpulan: Procalcitonin juga memiliki nilai diagnostik yang baik sebagai biomarker pada pasien sepsis yang dirawat di ICU RSUP Dr. Sardjito. Procalcitonin memiliki kemampuan diskriminasi sangat kuat untuk pasien sepsis.
The current review on glucocorticoids (GCs), inflammation and bone is focused on three aspects: (1) the mutual effects between GCs, inflammation and bone in inflammatory rheumatic diseases, (2) current views on fracture risk assessment in patients using GCs and (3) non-pharmacological and pharmacological treatment to prevent fractures in GC-using patients with inflammatory rheumatic diseases. The use of GCs results in increased risk for fractures due to both direct and indirect negative effects of GCs on bone mass, and on bone and muscle strength. However, also the underlying inflammatory rheumatic disease is associated with the increased bone loss and fracture risk due to the chronic inflammation itself, and due to disability/immobility caused by active disease or joint destruction. The rapid and strong anti-inflammatory effect of GCs in patients with rheumatoid arthritis seems to balance the negative effects of GCs on bone in the early, active phase of the disease. Recently, an update of the American College of Rheumatology guidelines for prevention and treatment of GC-induced osteoporosis was published with renewed recommendations. To prevent fractures, general measures, including treatment of the underlying inflammatory disease adequately (even with GCs when indicated), a healthy lifestyle, including adequate calcium and vitamin D supplementation, and regular weight bearing exercises are important. In rheumatic patients with high fracture risk using GCs, especially when the cumulative dose is high and/or the underlying inflammatory disease is active, treatment with anti-osteoporotic drugs, usually an oral bisphosphonate, is indicated.
APACHE II has been used worldwide for measuring ICU performance. The patient cohort from which APACHE II was derived was calibrated and validated two decades ago. Due to substantial advancement in critical care, a new cohort was studied recently and APACHE IV was derived for benchmarking ICU performance. The objective of the study is to compare APACHE II with APACHE IV outcome prediction in the same cohort of critically ill population.
Although there are many studies on arterial catheter-related infection (ACRI), there are scarce data on such infection according to the catheter access site. Which particular arterial catheter site is associated with a higher risk of infection remains controversial. The guidelines of the Centers for Disease Control and Prevention make no recommendation about which site or sites minimize the risk of catheter-related infection. In previous studies, we have found a higher incidence of ACRI in arterial femoral than in radial access sites. In the present study, we increased the number of arterial catheters in order to increase the probability of finding significant differences in the incidence of ACRI between other arterial accesses. The objective of this study was to analyze the incidence of ACRI according to different access sites.
A recent mandate emphasizes severity of liver disease to determine priorities in allocating organs for liver transplantation and necessitates a disease severity index based on generalizable, verifiable, and easily obtained variables. The aim of the study was to examine the generalizability of a model previously created to estimate survival of patients undergoing the transjugular intrahepatic portosystemic shunt (TIPS) procedure in patient groups with a broader range of disease severity and etiology. The Model for End-Stage Liver Disease (MELD) consists of serum bilirubin and creatinine levels, International Normalized Ratio (INR) for prothrombin time, and etiology of liver disease. The model's validity was tested in 4 independent data sets, including (1) patients hospitalized for hepatic decompensation (referred to as "hospitalized" patients), (2) ambulatory patients with noncholestatic cirrhosis, (3) patients with primary biliary cirrhosis (PBC), and (4) unselected patients from the 1980s with cirrhosis (referred to as "historical" patients). In these patients, the model's ability to classify patients according to their risk of death was examined using the concordance (c)-statistic. The MELD scale performed well in predicting death within 3 months with a c-statistic of (1) 0.87 for hospitalized patients, (2) 0.80 for noncholestatic ambulatory patients, (3) 0.87 for PBC patients, and (4) 0.78 for historical cirrhotic patients. Individual complications of portal hypertension had minimal impact on the model's prediction (range of improvement in c-statistic: <.01 for spontaneous bacterial peritonitis and variceal hemorrhage to ascites: 0.01-0.03). The MELD scale is a reliable measure of mortality risk in patients with end-stage liver disease and suitable for use as a disease severity index to determine organ allocation priorities.
Background
Cardiac arrest with widespread cerebral ischemia frequently leads to severe neurologic impairment. We studied whether mild systemic hypothermia increases the rate of neurologic recovery after resuscitation from cardiac arrest due to ventricular fibrillation.
Methods
In this multicenter trial with blinded assessment of the outcome, patients who had been resuscitated after cardiac arrest due to ventricular fibrillation were randomly assigned to undergo therapeutic hypothermia (target temperature, 32°C to 34°C, measured in the bladder) over a period of 24 hours or to receive standard treatment with normothermia. The primary end point was a favorable neurologic outcome within six months after cardiac arrest; secondary end points were mortality within six months and the rate of complications within seven days.
Results
Seventy-five of the 136 patients in the hypothermia group for whom data were available (55 percent) had a favorable neurologic outcome (cerebral-performance category, 1 [good recovery] or 2 [moderate disability]), as compared with 54 of 137 (39 percent) in the normothermia group (risk ratio, 1.40; 95 percent confidence interval, 1.08 to 1.81). Mortality at six months was 41 percent in the hypothermia group (56 of 137 patients died), as compared with 55 percent in the normothermia group (76 of 138 patients; risk ratio, 0.74; 95 percent confidence interval, 0.58 to 0.95). The complication rate did not differ significantly between the two groups.
Conclusions
In patients who have been successfully resuscitated after cardiac arrest due to ventricular fibrillation, therapeutic mild hypothermia increased the rate of a favorable neurologic outcome and reduced mortality.
In patients mechanically ventilated for severe respiratory failure, respiratory system mechanics are non-linear, i.e., volume-dependent. We present a new computer-based multipoint method for simultaneously determining volume-dependent dynamic compliance and resistance. Our method is based on continuously determined tracheal pressure (Ptrach). Tidal volume is subdivided into six volume slices of equal size. One compliance value (intrinsic PEEP considered) and one resistance value are determined for each volume slice by applying of the least-squares-fit (LSF) analysis based on the linear RC-model; we therefore call this the SLICE method. The method gives the course of dynamic compliance and resistance within the tidal volume. The method was evaluated using physical models of the respiratory system with linear and non-linear passive mechanical properties. The relative error of the method is smaller than ±5%. The method needs no special ventilatory pattern. Using data from 14 patients mechanically ventilated for adult respiratory distress syndrome (ARDS) we found a very good correspondence between the measured end-inspiratory airway pressure (Paw,Ie) and the end-inspiratory alveolar pressure (Palv,Ie) calculated from the dynamic compliance values determined with the SLICE method (Palv,Ie = 1.02 * Paw,Ie + 0.097; r2 = 0.977). The SLICE method allows continuous monitoring of non-linear pulmonary mechanics on a breath-by-breath basis at the bedside.
Direct hemoperfusion therapy with polymyxin-B immobilized fibers (PMX-DHP) has been widely applied as the therapeutic method for the patients with septic shock in Japan since 1994. Optimal usage of PMX-DHP for the patients with septic shock remains a matter of debate, mainly because of a lack of adequately designed clinical trials.
Conclusion Intoxications in elderly patients differ from those in younger patients with respect to the types of drugs ingested, course and mortality. The most frequent reasons for suicide in old patients are loneliness, severe diseases or depressive disorders.