Tietze's Syndrome Post-COVID-19 Infection in an Adult Patient.

Tietze's syndrome is a rare inflammatory disorder characterized by chest well swelling and inflammation of the costal cartilages. We describe a gentleman with repeated presentations to the emergency department (ED) with left-sided chest and sternoclavicular pain on a background of recent asymptomatic coronavirus disease 2019 (COVID-19) infection. He had elevated inflammatory markers and MRI subsequently confirmed the diagnosis of Tietze's syndrome. Anti-inflammatory medications and colchicine eventually led to a complete resolution of symptoms. This case highlights how Tietze's syndrome -- a disorder that is potentially self-limiting, can cause great distress and should be a differential diagnosis of chest pain after excluding life-threatening etiologies related to COVID-19.

Estimation of a Minimum Allowable Structural Strength Based on Uncertainty in Material Test Data.

Three types of uncertainties exist in the estimation of the minimum fracture strength of a full-scale component or structure size. The first, to be called the "model selection uncertainty," is in selecting a statistical distribution that best fits the laboratory test data. The second, to be called the "laboratory-scale strength uncertainty," is in estimating model parameters of a specific distribution from which the minimum failure strength of a material at a certain confidence level is estimated using the laboratory test data. To extrapolate the laboratory-scale strength prediction to that of a full-scale component, a third uncertainty exists that can be called the "full-scale strength uncertainty." In this paper, we develop a three-step approach to estimating the minimum strength of a full-scale component using two metrics: One metric is based on six goodness-of-fit and parameter-estimation-method criteria, and the second metric is based on the uncertainty quantification of the so-called A-basis design allowable (99 % coverage at 95 % level of confidence) of the full-scale component. The three steps of our approach are: (1) Find the "best" model for the sample data from a list of five candidates, namely, normal, two-parameter Weibull, three-parameter Weibull, two-parameter lognormal, and three-parameter lognormal. (2) For each model, estimate (2a) the parameters of that model with uncertainty using the sample data, and (2b) the minimum strength at the laboratory scale at 95 % level of confidence. (3) Introduce the concept of "coverage" and estimate the fullscale allowable minimum strength of the component at 95 % level of confidence for two types of coverages commonly used in the aerospace industry, namely, 99 % (A-basis for critical parts) and 90 % (B-basis for less critical parts). This uncertainty-based approach is novel in all three steps: In step-1 we use a composite goodness-of-fit metric to rank and select the "best" distribution, in step-2 we introduce uncertainty quantification in estimating the parameters of each distribution, and in step-3 we introduce the concept of an uncertainty metric based on the estimates of the upper and lower tolerance limits of the so-called A-basis design allowable minimum strength. To illustrate the applicability of this uncertainty-based approach to a diverse group of data, we present results of our analysis for six sets of laboratory failure strength data from four engineering materials. A discussion of the significance and limitations of this approach and some concluding remarks are included.

Computed Tomography Urography: Comparison of Image Quality and Radiation Dose between Single- and Split-Bolus Techniques.

INTRODUCTION: In this study, we aimed to compare the split-bolus and single-bolus computerised tomography (CT) urography and determine if this offers a reduction in radiation dose without compromising image quality. MATERIALS AND METHODS: A retrospective evaluation was performed on 88 patients undergoing split-bolus CT urography and this was compared to a control group of 101 consecutive patients undergoing single-bolus CT urography. A radiation dose analysis was performed on each subject. Subjects with urinary bladder lesions, hydronephrosis, renal masses or cysts >3 cm in diameter were excluded. All images were classified according to image quality by 2 consultant radiologists. RESULTS: Opacification of  the renal parenchyma, pelvicalyceal system, proximal ureters and urinary bladder were comparable between the 2 techniques, whilst image quality of the middle and distal third of the ureters was better using the split-bolus technique. The mean dose length product (DLP) for the single-bolus technique was 1324.1 mGy-cm, whilst that of  the split-bolus technique was 885.7 mGy-cm. The mean effective dose reduction was calculated to be 31.1% between the 2 groups. CONCLUSION: The split-bolus technique gives a reduced radiation dose without compromising image quality. The associated reduction in images is beneficial for data storage and reporting efficiency. As such, our department will adopt the split-bolus technique for young, low-risk patients.

Healthy body, healthy mind: A mixed methods study of outcomes, barriers and supports for exercise by people who have chronic moderate-to-severe acquired brain injury.

BACKGROUND: Few people with chronic moderate-to-severe brain injury are following recommended physical activity guidelines. OBJECTIVE: Investigate effects of planned, systematic physical activity while cultivating social and emotional well-being of people with chronic moderate-to-severe brain injury. HYPOTHESIS: Moderate-to-intensive physical activity would be associated with improvements in impairment and activity limitation measures (endurance, mobility, gait speed) immediately post-intervention and six weeks later (study week 12). METHODS: The intervention was a single group pre-/post-intervention study with 14 people with chronic moderate-to-severe brain injury who live in brain injury group homes and exercised 60-90 min, 3 days per week for 6 weeks at a maximum heart rate of 50-80%. Pre-post measures (administered weeks 0, 6 and 12) were the 6 Minute Walk Test, High-level Mobility Assessment Tool and 10 Meter Walk Test. The qualitative component used a brief survey and semi-structured interview guide with participants, family members, and staff. RESULTS: Following program completion, post-intervention group changes were noted on all outcome measures and greater than minimal detectable change for people with brain injury. Three transitioned from low to high ambulatory status and maintained this change at 12 weeks. During interviews, participants agreed the program was stimulating. More than eighty percent liked working out in a group and felt better being active. CONCLUSIONS: Program impact included physical, cognitive and social/emotional aspects. Social aspects (group format, trainers) were highly motivating and supported by residents, family, and staff. Investments in transportation and recruiting and training interns to assist participants are critical to program sustainability and expansion.

Uncertainty in multi-scale fatigue life modeling and a new approach to estimating frequency of in-service inspection of aging components.

Uncertainty in modeling the fatigue life of a full-scale component using experimental data at microscopic (Level 1), specimen (Level 2), and full-size (Level 3) scales, is addressed by applying statistical theory of prediction intervals, and that of tolerance intervals based on the concept of coverage, p. Using a nonlinear least squares fit algorithm and the physical assumption that the one-sided Lower Tolerance Limit (LTL), at 95% confidence level, of the fatigue life, i.e., the minimum cycles-to-failure, minNf, of a full-scale component, cannot be negative as the lack or "Failure" of coverage (Fp), defined as 1 - p, approaches zero, we develop a new fatigue life model, where the minimum cycles-to-failure, minNf, at extremely low "Failure" of coverage, Fp, can be estimated. Since the concept of coverage is closely related to that of an inspection strategy, and if one assumes that the predominent cause of failure of a full-size component is due to the "Failure" of inspection or coverage, it is reasonable to equate the quantity, Fp, to a Failure Probability, FP, thereby leading to a new approach of estimating the frequency of in-service inspection of a full-size component. To illustrate this approach, we include a numerical example using the published data of the fatigue of an AISI 4340 steel (N.E. Dowling, Journal of Testing and Evaluation, ASTM, Vol. 1(4) (1973), 271-287) and a linear least squares fit to generate the necessary uncertainties for performing a dynamic risk analysis, where a graphical plot of an estimate of risk with uncertainty vs. a predicted most likely date of a high consequence failure event becomes available. In addition, a nonlinear least squares logistic function fit of the fatigue data yields a prediction of the statistical distribution of both the ultimate strength and the endurance limit.

Automating the Renal Cell Carcinoma Registry in Singapore: A Case Study on the Integration of the Research Electronic Data Capture System with the Enterprise Data Warehouse.

The renal cell carcinoma registry (RCCR) at the Singapore General Hospital was established in the 1980s. In 2012, the registry transited to a partially automated system using Research Electronic Data Capture (REDCap) and Oracle Business Intelligence Enterprise Edition (OBIEE), which is a platform for retrieval of electronic data from the Electronic Health Intelligence System (eHIntS). A committee was formed of experts from the department of urology and the health services research center, as well as an information technology (IT) team to evaluate the efficacy of the partially automated system. In the 5 years after the new system was implemented, 1,751 cases were recorded in the RCCR. The casefinding completeness increased by 1.9%, the data accuracy rate was 97%, and the efficiency increased by 12%. Strengths of the new system after partial automation were: (1) secure access to the registry via the hospital Web, (2) direct access to REDCap via the electronic medical records system, (3) automated and timely data extraction, and (4) visual presentation of data. On the other hand, we also encountered several challenges in the process of automating the registry, including limited IT support, limited expertise in matching data variables from RCCR and eHIntS, and limited availability and accessibility of eHIntS information for import into REDCap. In summary, despite these challenges, partial automation was achieved with the REDCap/OBIEE system, enhancing efficiency, data security, and data quality.

Idarucizumab for Reversal of Dabigatran-Associated Anticoagulation.

OBJECTIVE: To review clinical data on idarucizumab for the reversal of dabigatran-associated anticoagulation. DATA SOURCES: Articles for this review were identified via PubMed using the MeSH term dabigatran combined with the keyword idarucizumab Additional online searches via PubMed and Google Scholar were conducted for both prescribing and cost information. STUDY SELECTION AND DATA EXTRACTION: English-language clinical trials published between 1946 and May 2016 were included for review. Bibliographies of selected articles were also manually reviewed for relevant publications that focused on reversal strategies for dabigatran-associated anticoagulation. DATA SYNTHESIS: The safety and tolerability of idarucizumab has been evaluated in 3 phase I clinical trials. The use of idarucizumab for reversing dabigatran-associated anticoagulation is also being evaluated in the phase III RE-VERSE AD study. Interim results of the RE-VERSE AD study have been published. CONCLUSIONS: Idarucizumab rapidly neutralizes the anticoagulant effect of dabigatran in healthy volunteers, in patients with life-threatening bleeding, and in patients requiring urgent surgery that cannot be delayed. These observations are largely based on laboratory assessments rather than clinical outcomes. Idarucizumab is well tolerated, and it does not appear to induce procoagulant or immunogenic adverse effects.

Pilot study of intensive exercise on endurance, advanced mobility and gait speed in adults with chronic severe acquired brain injury.

BACKGROUND AND PURPOSE: Effects of high-intensity exercise on endurance, mobility and gait speed of adults with chronic moderate-to-severe acquired brain injury (ABI) were investigated. It was hypothesized that intensive exercise would be associated with improvements in impairment and activity limitation measures. PARTICIPANTS: Fourteen adults with chronic ABI in supported independent living who could stand with minimal or no assist and walk with or without ambulation device were studied. Eight presented with low ambulatory status. METHODS: This was a single group pre- and post-intervention study. Participants received a 6-week exercise intervention for 60-90 minutes, 3 days/week assisted by personal trainers under physical therapist supervision. Measures (6MWT, HiMAT and 10MWT) were collected at baseline, post-intervention and 6 weeks later. Repeated measures T-test and Wilcoxon Signed Ranks test were used. RESULTS: Post-intervention improvements were achieved on average on all three measures, greater than minimal detectable change (MDC) for this population. Three participants transitioned from low-to-high ambulatory status and maintained the change 6 weeks later. DISCUSSION AND CONCLUSION: People with chronic ABI can improve endurance, demonstrate the ability to do advanced gait and improve ambulatory status with 6 weeks of intensive exercise. Challenges to sustainability of exercise programmes for this population remain.

The effect of chronic liver disease on venous thromboembolism among medically managed patients in Singapore General Hospital.

BACKGROUND: Chronic liver disease (CLD) has been suggested to be associated with venous thromboembolism (VTE) in western populations. However, little is known about the risk effects of CLD on VTE among Asians. OBJECTIVE: To compute the prevalence of VTE among hospitalised Asian patients, and to evaluate the pattern and scale of risk effects of CLD on VTE occurrence. METHOD: Retrospective study of hospital discharge database from 2004 to 2011 to identify patients with VTE and CLD using International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Australian Modification (ICD-9-AM) codes. RESULTS: Of 199904 medically managed inpatients during the 8years, 1744 (0.9%) patients had VTE. Patients with CLD had significant higher prevalence of VTE (non-cirrhosis CLD 1.5%, cirrhosis 2.0%) than patients without CLD (0.8%, p<0.001). In the logistic regression analyses, non-cirrhosis CLD (odds ratio, OR 1.4, 95% CI 1.2-1.7, p<0.001) and cirrhosis (OR 1.5, 95% CI 1.2-2.0, p=0.002) were significant predictors of VTE after adjustment for age, gender, ethnicity, hospital long stayer, cancer, infectious disease, and other comorbid conditions such as diabetic mellitus, anaemia, and cardiovascular, cerebrovascular, renal and pulmonary diseases. CONCLUSION: CLD, particular liver cirrhosis, increases the risks of VTE in hospitalised Asian patients. As CLD patients are perceived to be at risks of bleeding due to the prolonged clotting times and thrombocytopenia, the results of this study brings attention to opposite end of the haemostatic pendulum in patients with chronic liver disease.

Wireless implantable chip with integrated nitinol-based pump for radio-controlled local drug delivery.

We demonstrate an active, implantable drug delivery device embedded with a microfluidic pump that is driven by a radio-controlled actuator for temporal drug delivery. The polyimide-packaged 10 × 10 × 2 mm(3) chip contains a micromachined pump chamber and check valves of Parylene C to force the release of the drug from a 76 µL reservoir by wirelessly activating the actuator using external radio-frequency (RF) electromagnetic fields. The rectangular-shaped spiral-coil actuator based on nitinol, a biocompatible shape-memory alloy, is developed to perform cantilever-like actuation for pumping operation. The nitinol-coil actuator itself forms a passive 185 MHz resonant circuit that serves as a self-heat source activated via RF power transfer to enable frequency-selective actuation and pumping. Experimental wireless operation of fabricated prototypes shows successful release of test agents from the devices placed in liquid and excited by radiating tuned RF fields with an output power of 1.1 W. These tests reveal a single release volume of 219 nL, suggesting a device's capacity of ~350 individual ejections of drug from its reservoir. The thermal behavior of the activated device is also reported in detail. This proof-of-concept prototype validates the effectiveness of wireless RF pumping for fully controlled, long-lasting drug delivery, a key step towards enabling patient-tailored, targeted local drug delivery through highly miniaturized implants.

Interprofessional education with a community fall prevention event.

Implementation of interprofessional education (IPE) among multiple professional degree programs has many challenges. Students from four health science programs: pharmacy; nursing; physician assistant studies and physical therapy participated in an interprofessional community fall prevention event. This paper briefly describes the development of this IPE opportunity and the assessment of changes on students' attitudes about IPE after participation in the event. Differing views on teamwork and professional roles are reported by professions. Positive attitudes towards interprofessional teamwork were observed after participation in the event. Based on these data, it appears that an interprofessional community service event offers a useful approach forward for incorporating IPE into the curricula of different health care programs.

Imaging findings and clinical features of abdominal vascular compression syndromes.

OBJECTIVE: This article describes the typical imaging findings and clinical features that are associated with four abdominal vascular compression syndromes. We explain the underlying pathophysiology that results in these clinical syndromes so that the patient subset who will benefit from treatment can be identified. CONCLUSION: The abdominal vascular compression syndromes discussed here are uncommon and are potentially easily missed on a cursory review of radiologic examinations, particularly in a nonspecific and vague clinical setting. Hence, knowledge of the typical imaging findings and associated clinical symptoms is essential so that the they can be carefully sought and excluded. However, because these findings may also exist in healthy individuals as anatomic variants, it is important to correlate radiologic findings with clinical symptoms to identify the subset of patients who will benefit from treatment.

Sofosbuvir: A Nucleotide NS5B Inhibitor for the Treatment of Chronic Hepatitis C Infection.

OBJECTIVE: To review the use of sofosbuvir for the treatment of chronic hepatitis C virus (HCV). DATA SOURCES: Review and nonreview articles were identified through MEDLINE (1996-April 2014), citations of articles, and meeting abstracts using keywords, including NS5B polymerase inhibitor, GS-7977, sofosbuvir, direct-acting antiviral (DAA), and others. STUDY SELECTION AND DATA EXTRACTION: Phase 1, 2, and 3 studies describing dose-ranging potential, pharmacokinetics, efficacy, safety, and tolerability of sofosbuvir were identified. DATA SYNTHESIS: Sofosbuvir is an NS5B polymerase inhibitor that was approved for use by the Food and Drug Administration in December 2013 for the treatment of chronic HCV in combination with pegylated interferon (peg-IFN) and ribavirin (RBV) for genotype 1. Additionally, it has been evaluated with other oral DAAs, such as simeprevir and others in the pipeline. It is not recommended as monotherapy because of lower sustained virological response (SVR) rates in clinical studies. Most of the treatment regimens are 12 weeks in duration; however, certain populations require a longer duration. Sofosbuvir has activity against all 6 genotypes, although most clinical trials evaluated genotypes 1 to 3. Sofosbuvir has a favorable safety and tolerability profile, making it a recommended first-line agent for chronic HCV infection. CONCLUSION: In clinical trials, 12 weeks of sofosbuvir with concomitant peg-IFN and RBV therapy in treatment-naïve and experienced HCV genotype 1 patients resulted in SVR rates of >90%. An all-oral regimen of sofosbuvir and RBV is highly effective for genotype 2 and 3 patients. Sofosbuvir was found to be tolerable with minimal adverse effects (AEs), and no treatment discontinuations occurred secondary to drug related AEs..

Comparison of a low, fixed dose and a high, weight-based dose of recombinant factor VIIa in the treatment of warfarin-associated intracranial hemorrhage.

BACKGROUND: Recombinant activated Factor VII (rFVIIa) can be used for rapid INR normalization in patients with warfarin-associated intracranial hemorrhage (WA-ICH); however, the optimal dose to normalize INR has not been established. METHODS: This is a retrospective review comparing two rFVIIa hospital protocols for WA-ICH [weight-based dose (80 mcg/kg) or fixed dose (2 mg)]. Primary endpoint was the percentage of patients with INR reversal (INR <1.3) at the next INR draw and the need for further doses of rFVIIa. Secondary endpoints included time to documented INR reversal and sustained INR normalization, morbidity, mortality, change in hematoma size, cost, and adverse drug reactions. RESULTS: Twenty-nine patients were included in each group. The weight-based group received a mean dose of 78.9 ± 21 mcg/kg versus 26.6 ± 8 mcg/kg in the fixed dose group. More patients in the fixed dose protocol achieved documented INR reversal than those in the weight-based group (92.6 vs 72.4 %, p = 0.19). The weight-based group achieved INR normalization in 229.5 [102, 331] minutes versus 165 [83, 447] minutes in the fixed dose group (p=0.02). Time to sustained INR normalization was similar in both groups. Four patients in the fixed dose group received an additional dose of 1 mg per hospital protocol. With the exception of medication acquisition cost savings of about $4,300 per patient who received fixed dose protocol, all other endpoints were similar between groups. CONCLUSIONS: A low, fixed dose of rFVIIa appears to be as effective as a high, weight-based dose in achieving INR normalization in patients with WA-ICH.

Introduction to drug pharmacokinetics in the critically ill patient.

Despite regular use of drugs for critically ill patients, overall data are limited regarding the impact of critical illness on pharmacokinetics (PK). Designing safe and effective drug regimens for patients with critical illness requires an understanding of PK. This article reviews general principles of PK, including absorption, distribution, metabolism, and elimination, and how critical illness can influence these parameters. In the area of drug absorption, we discuss the impact of vasopressor use, delayed gastric emptying and feeding tubes, and nutrient interactions. On the topic of drug distribution, we review fluid resuscitation, alterations in plasma protein binding, and tissue perfusion. With drug metabolism, we discuss hepatic enzyme activity, protein binding, and hepatic blood flow. Finally, we review drug elimination in the critically ill patient and discuss the impact of augmented renal clearance and acute kidney injury on drug therapies. In each section, we highlight select literature reviewing the PK impact of these conditions on a drug PK profile and, where appropriate, provide general suggestions for clinicians on how to modify drug regimens to manage PK challenges.

Clinical outcomes with ertapenem as a first-line treatment option of infections caused by extended-spectrum ß-lactamase producing gram-negative bacteria.

BACKGROUND: Infections caused by extended-spectrum ß-lactamase (ESBL)-producing gram-negative organisms are a growing concern in hospitalized patients. Traditionally, these infections can be effectively treated by the carbapenem class of drugs. In 2005, our institution initiated a protocol for use of ertapenem, a carbapenem, as the first-line treatment option for these infections. It is unknown whether ertapenem is associated with similar clinical response and microbiologic cure rates as those achieved with group 2 carbapenems (imipenem, meropenem, doripenem). OBJECTIVE: To describe clinical response and microbiologic cure rates associated with ertapenem as first-line treatment of infections caused by ESBL-producing organisms. METHODS: This case series included patients who received ertapenem for more than 48 hours to treat a documented infection with a positive culture for an ESBL-producing organism. Efficacy was determined by the clinical response and microbiologic cure rates achieved with ertapenem. RESULTS: Seventy-three patients received ertapenem for a mean (SD) of 10.7 (5.9) days. The most common (59%) infection site was urine. The most common causative organisms were ESBL-producing Klebsiella pneumoniae (47%) and Escherichia coli (48%). Clinical response was observed in 78% of patients. Microbiologic cure was achieved in 92% of the evaluable population (n = 50). There were no significant differences in clinical or microbiologic cure rates across important subgroups. CONCLUSIONS: Patients treated with ertapenem achieved favorable clinical response and microbiologic cure rates. Our data suggest that ertapenem can be used as an alternative to group 2 carbapenems for the treatment of infections caused by ESBL-producing gram-negative organisms.

Impact of quetiapine on resolution of individual delirium symptoms in critically ill patients with delirium: a post-hoc analysis of a double-blind, randomized, placebo-controlled study.

INTRODUCTION: We hypothesized that delirium symptoms may respond differently to antipsychotic therapy. The purpose of this paper was to retrospectively compare duration and time to first resolution of individual delirium symptoms from the database of a randomized, double-blind, placebo-controlled study comparing quetiapine (Q) or placebo (P), both with haloperidol rescue, for critically ill patients with delirium. METHODS: Data for 10 delirium symptoms from the eight-domain, intensive care delirium screening checklist (ICDSC) previously collected every 12 hours were extracted for 29 study patients. Data between the Q and P groups were compared using a cut-off P-value of ≤ 0.10 for this exploratory study. RESULTS: Baseline ICDSC scores (5 (4 to 7) (Q) vs 5 (4 to 6)) (median, interquartile range (IQR)) and % of patients with each ICDSC symptom were similar in the two groups (all P > 0.10). Among patients with the delirium symptom at baseline, use of Q may lead to a shorter time (days) to first resolution of symptom fluctuation (4 (Q) vs. 14, P = 0.004), inattention (3 vs. 8, P = .10) and disorientation (2 vs. 10, P = 0.10) but a longer time to first resolution of agitation (3 vs. 1, P = 0.04) and hyperactivity (5 vs. 1, P = 0.07). Among all patients, Q-treated patients tended to spend a smaller percent of time with inattention (47 (0 to 67) vs. 78 (43 to 100), P = 0.025), hallucinations (0 (0 to 17) vs. 28 (0 to 43), P = 0.10) and symptom fluctuation (47 (19 to 67) vs. 89 (33 to 00), P = 0.04] and there was a trend for Q-treated patients to spend a greater percent of time at an appropriate level of consciousness (26% (13 to 63%) vs. 14% (0 to 33%), P = 0.17]. CONCLUSIONS: Our exploratory analysis suggests that quetiapine may resolve several intensive care unit (ICU) delirium symptoms faster than the placebo. Individual symptom resolution appears to differ in association with the pharmacologic intervention (that is, P vs Q, both with as needed haloperidol). Future studies evaluating antipsychotics in ICU patients with delirium should measure duration and resolution of individual delirium symptoms and their relation to long-term outcomes.

Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study.

OBJECTIVE: To compare the efficacy and safety of scheduled quetiapine to placebo for the treatment of delirium in critically ill patients requiring as-needed haloperidol. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Three academic medical centers. PATIENTS: Thirty-six adult intensive care unit patients with delirium (Intensive Care Delirium Screening Checklist score > or = 4), tolerating enteral nutrition, and without a complicating neurologic condition. INTERVENTIONS: Patients were randomized to receive quetiapine 50 mg every 12 hrs or placebo. Quetiapine was increased every 24 hrs (50 to 100 to 150 to 200 mg every 12 hrs) if more than one dose of haloperidol was given in the previous 24 hrs. Study drug was continued until the intensive care unit team discontinued it because of delirium resolution, therapy > or = 10 days, or intensive care unit discharge. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were similar between the quetiapine (n = 18) and placebo (n = 18) groups. Quetiapine was associated with a shorter time to first resolution of delirium [1.0 (interquartile range [IQR], 0.5-3.0) vs. 4.5 days (IQR, 2.0-7.0; p =.001)], a reduced duration of delirium [36 (IQR, 12-87) vs. 120 hrs (IQR, 60-195; p =.006)], and less agitation (Sedation-Agitation Scale score > or = 5) [6 (IQR, 0-38) vs. 36 hrs (IQR, 11-66; p =.02)]. Whereas mortality (11% quetiapine vs. 17%) and intensive care unit length of stay (16 quetiapine vs. 16 days) were similar, subjects treated with quetiapine were more likely to be discharged home or to rehabilitation (89% quetiapine vs. 56%; p =.06). Subjects treated with quetiapine required fewer days of as-needed haloperidol [3 [(IQR, 2-4)] vs. 4 days (IQR, 3-8; p = .05)]. Whereas the incidence of QTc prolongation and extrapyramidal symptoms was similar between groups, more somnolence was observed with quetiapine (22% vs. 11%; p = .66). CONCLUSIONS: Quetiapine added to as-needed haloperidol results in faster delirium resolution, less agitation, and a greater rate of transfer to home or rehabilitation. Future studies should evaluate the effect of quetiapine on mortality, resource utilization, post-intensive care unit cognition, and dependency after discharge in a broader group of patients.

Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study.

INTRODUCTION: While propofol is associated with an infusion syndrome (PRIS) that may cause death, the incidence of PRIS is unknown. Determining the incidence of PRIS and the frequency of PRIS-related clinical manifestations are key steps prior to the completion of any controlled studies investigating PRIS. This prospective, multicenter study sought to determine the incidence of PRIS and PRIS-related clinical manifestations in a large cohort of critically ill adults prescribed propofol. METHODS: Critically ill adults from 11 academic medical centers administered an infusion of propofol for [>or=] 24 hours were monitored at baseline and then on a daily basis until propofol was discontinued for the presence of 11 different PRIS-associated clinical manifestations and risk factors derived from 83 published case reports of PRIS. RESULTS: Among 1017 patients [medical (35%), neurosurgical (25%)], PRIS (defined as metabolic acidosis plus cardiac dysfunction and [>or=] 1 of: rhabdomyolysis, hypertriglyceridemia or renal failure occurring after the start of propofol therapy) developed in 11 (1.1%) patients an average of 3 (1-6) [median (range)] days after the start of propofol. While most (91%) of the patients who developed PRIS were receiving a vasopressor (80% initiated after the start of propofol therapy), few received a propofol dose >83 mcg/kg/min (18%) or died (18%). Compared to the 1006 patients who did not develop PRIS, the APACHE II score (25 +/- 6 vs 20 +/- 7, P = 0.01) was greater in patients with PRIS but both the duration of propofol use (P = 0.43) and ICU length of stay (P = 0.82) were similar. CONCLUSIONS: Despite using a conservative definition for PRIS, and only considering new-onset PRIS clinical manifestations, the incidence of PRIS slightly exceeds 1%. Future controlled studies focusing on evaluating whether propofol manifests the derangements of critical illness more frequently than other sedatives will need to be large. These studies should also investigate the mechanism(s) and risk factors for PRIS.