Effect of Ward-Based High-Flow Nasal Cannula (HFNC) Oxygen Therapy on Critical Care Utilization During the COVID-19 Pandemic: A Retrospective Cohort Analysis.

BACKGROUND: Hospitals expanded critical care capacity during the COVID-19 pandemic by treating COVID-19 patients with high-flow nasal cannula oxygen therapy (HFNC) in non-traditional settings, including general internal medicine (GIM) wards. The impact of this practice on intensive care unit (ICU) capacity is unknown. OBJECTIVE: To describe how our hospital operationalized the use of HFNC on GIM wards, assess its impact on ICU capacity, and examine the characteristics and outcomes of treated patients. DESIGN: Retrospective cohort study of all patients treated with HFNC on GIM wards at a Canadian tertiary care hospital. PARTICIPANTS: All patients admitted with COVID-19 and treated with HFNC on GIM wards from December 28, 2020, to June 13, 2021, were included. MAIN MEASURES: We combined administrative data on critical care occupancy daily with chart-abstracted data for included patients to establish the total number of patients receiving ICU-level care at our hospital per day. We also collected data on demographics, medical comorbidities, illness severity, COVID-19 treatments, HFNC care processes, and patient outcomes. KEY RESULTS: We treated 124 patients with HFNC on the GIM wards (median age 66 years; 48% female). Patients were treated with HFNC for a median of 5 days (IQR 3 to 8); collectively, they received HFNC for a total of 740 hospital days, 71% of which were on GIM wards. At peak ICU capacity strain (144%), delivering HFNC on GIM wards added 20% to overall ICU capacity by managing up to 14 patients per day. Patients required a median maximal fraction of inspired oxygen of 80% (IQR 60 to 95). There were 18 deaths (15%) and 85 patients (69%) required critical care admission; of those, 40 (47%) required mechanical ventilation. CONCLUSIONS: With appropriate training and resources, treatment of COVID-19 patients with HFNC on GIM wards appears to be a feasible strategy to increase critical care capacity.

Frequency of Screening for Weaning From Mechanical Ventilation: Two Contemporaneous Proof-of-Principle Randomized Controlled Trials.

OBJECTIVES: It is unknown whether more frequent screening of invasively ventilated patients, identifies patients earlier for a spontaneous breathing trial, and shortens the duration of ventilation. We assessed the feasibility of conducting a large trial to evaluate screening frequency in critically ill adults in the North American context. DESIGN: We conducted two contemporaneous, multicenter, pilot, randomized controlled trials (the LibeRation from MEchanicaL VEntilAtion and ScrEening Frequency [RELEASE] and Screening Elderly PatieNts For InclusiOn in a Weaning [SENIOR] trials) to address concerns regarding the potential for higher enrollment, fewer adverse events, and better outcomes in younger patients. SETTING: Ten and 11 ICUs in Canada, respectively. PATIENTS: Parallel trials of younger (RELEASE < 65 yr) and older (SENIOR ≥ 65 yr) critically ill adults invasively ventilated for at least 24 hours. INTERVENTIONS: Each trial compared once daily screening to "at least twice daily" screening led by respiratory therapists. MEASUREMENTS AND MAIN RESULTS: In both trials, we evaluated recruitment (aim: 1-2 patients/month/ICU) and consent rates, reasons for trial exclusion, protocol adherence (target: ≥ 80%), crossovers (aim: ≤ 10%), and the effect of the alternative screening frequencies on adverse events and clinical outcomes. We included 155 patients (53 patients [23 once daily, 30 at least twice daily] in RELEASE and 102 patients [54 once daily, 48 at least twice daily] in SENIOR). Between trials, we found similar recruitment rates (1.32 and 1.26 patients/month/ICU) and reasons for trial exclusion, high consent and protocol adherence rates (> 92%), infrequent crossovers, and few adverse events. Although underpowered, at least twice daily screening was associated with a nonsignificantly faster time to successful extubation and more successful extubations but significantly increased use of noninvasive ventilation in both trials combined. CONCLUSIONS: Similar recruitment and consent rates, few adverse events, and comparable outcomes in younger and older patients support conduct of a single large trial in North American ICUs assessing the net clinical benefits associated with more frequent screening.

Is there still room to explore cyclodextrin glycosyltransferase-producers in Brazilian biodiversity?

In the present work, different Brazilian biomes aiming to identify and select cyclodextrin glycosyltransferase-producer bacteria are explored. This enzyme is responsible for converting starch to cyclodextrin, which are interesting molecules to carry other substances of economic interest applied by textile, pharmaceutical, food, and other industries. Based on the enzymatic index, 12 bacteria were selected and evaluated, considering their capacity to produce the enzyme in culture media containing different starch sources. It was observed that the highest yields were presented by the bacteria when grown in cornstarch. These bacteria were also characterized by sequencing of the 16S rRNA region and were classified as Bacillus, Paenibacillus, Gracilibacillus and Solibacillus.

Patient and Organizational Factors Associated With Delays in Antimicrobial Therapy for Septic Shock.

OBJECTIVES: To identify clinical and organizational factors associated with delays in antimicrobial therapy for septic shock. DESIGN: In a retrospective cohort of critically ill patients with septic shock. SETTING: Twenty-four ICUs. PATIENTS: A total of 6,720 patients with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Higher Acute Physiology Score (+24 min per 5 Acute Physiology Score points; p < 0.0001); older age (+16 min per 10 yr; p < 0.0001); presence of comorbidities (+35 min; p < 0.0001); hospital length of stay before hypotension: less than 3 days (+50 min; p < 0.0001), between 3 and 7 days (+121 min; p < 0.0001), and longer than 7 days (+130 min; p < 0.0001); and a diagnosis of pneumonia (+45 min; p < 0.01) were associated with longer times to antimicrobial therapy. Two variables were associated with shorter times to antimicrobial therapy: community-acquired infections (-53 min; p < 0.001) and higher temperature (-15 min per 1°C; p < 0.0001). After adjusting for confounders, admissions to academic hospitals (+52 min; p< 0.05), and transfers from medical wards (medical vs surgical ward admission; +39 min; p < 0.05) had longer times to antimicrobial therapy. Admissions from the emergency department (emergency department vs surgical ward admission, -47 min; p< 0.001) had shorter times to antimicrobial therapy. CONCLUSIONS: We identified clinical and organizational factors that can serve as evidence-based targets for future quality-improvement initiatives on antimicrobial timing. The observation that academic hospitals are more likely to delay antimicrobials should be further explored in future trials.

The Postcardiac Arrest Consult Team: Impact on Hospital Care Processes for Out-of-Hospital Cardiac Arrest Patients.

OBJECTIVE: To evaluate whether a Post-Arrest Consult Team improved care and outcomes for patients with out-of-hospital cardiac arrest. DESIGN: Prospective cohort study of Post-Arrest Consult Team implementation at two hospitals, with concurrent controls from 27 others. SETTING: Twenty-nine hospitals within the Strategies for Post-Arrest Care Network of Southern Ontario, Canada. PATIENTS: We included comatose adult nontraumatic out-of-hospital cardiac arrest patients surviving more than or equal to 6 hours after emergency department arrival who had no contraindications to targeted temperature management. INTERVENTION: The Post-Arrest Consult Team was an advisory consult service to improve 1) targeted temperature management, 2) assessment for percutaneous coronary intervention, 3) electrophysiology assessment, and 4) appropriately delayed neuroprognostication. MEASUREMENTS AND MAIN RESULTS: We used generalized linear mixed models to explore the association between Post-Arrest Consult Team implementation and performance of targeted processes. We included 1,006 patients. The Post-Arrest Consult Team was associated with a significant reduction over time in rates of withdrawal of life-sustaining therapy within 72 hours of emergency department arrival on the basis of predictions of poor neurologic prognosis (ratio of odds ratios, 0.13; 95% CI, 0.02-0.98). Post-Arrest Consult Team was not associated with improved successful targeted temperature management (ratio of odds ratios, 0.91; 95% CI, 0.31-2.65), undergoing angiography (ratio of odds ratios, 1.91; 95% CI, 0.17-21.04), receiving electrophysiology consultation (ratio of odds ratios, 0.93; 95% CI, 0.11-8.16), or functional survival (ratio of odds ratios, 0.75; 95% CI, 0.19-2.94). CONCLUSIONS: Implementation of a Post-Arrest Consult Team reduced premature withdrawal of life-sustaining therapy but did not improve rates of successful targeted temperature management, coronary angiography, formal electrophysiology assessments, or functional survival for comatose patients after out-of-hospital cardiac arrest.

Communication and Culture in the Surgical Intensive Care Unit: Boundary Production and the Improvement of Patient Care.

This ethnography explores communication around critically ill surgical patients in three surgical intensive care units (ICUs) in Canada. A boundary framework is used to articulate how surgeons', intensivists', and nurses' communication practices shape and are shaped by their respective disciplinary perspectives and experiences. Through 50 hours of observations and 43 interviews, these health care providers are found to engage in seven communication behaviors that either mitigate or magnify three contested symbolic boundaries: expertise, patient ownership, and decisional authority. Where these boundaries are successfully mitigated, experiences of collaborative, high-quality patient care are produced; by contrast, boundary magnification produces conflict and perceptions of unsafe patient care. Findings reveal that high quality and safe patient care are produced through complex social and cultural interactions among surgeons, intensivists, and nurses that are also expressions of knowledge and power. This enhances our understanding of why current quality improvement efforts targeting communication may be ineffective.

"It's Parallel Universes": An Analysis of Communication Between Surgeons and Intensivists.

OBJECTIVES: The intensivist-led model of ICU care requires surgical consultants and the ICU team to collaborate in the care of ICU patients and to communicate effectively across teams. We sought to characterize communication between intensivists and surgeons and to assess enablers and barriers of effective communication. DESIGN: Qualitative interview study. An inductive data analysis approach was taken. SETTING: Seven intensivist-led ICUs in four academic hospitals. SUBJECTS: Surgeons (attendings and residents), intensivists (attendings and residents), and ICU nurses participating in the care of surgical patients in the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Communication enablers and barriers existed at two distinct levels: 1) organizational and 2) cultural. At an organizational level, participants identified that formally sanctioned communication structures and processes often acted as barriers to communication. Participants had developed informal strategies to improve communication. At a cultural level, surgical and ICU participants often expressed conflicting perspectives regarding patient ownership, scope of practice, and clinical expertise. CONCLUSIONS: Major barriers to optimal communication between surgical and ICU teams exist in the intensivist-led ICU environment. Many are related to the structures and processes meant to facilitate communication across teams and others to how some aspects of care in the ICU are conceptualized. Multiple actionable opportunities exist to improve communication in the intensivist-led ICU.

Patient safety, resident well-being and continuity of care with different resident duty schedules in the intensive care unit: a randomized trial.

BACKGROUND: Shorter resident duty periods are increasingly mandated to improve patient safety and physician well-being. However, increases in continuity-related errors may counteract the purported benefits of reducing fatigue. We evaluated the effects of 3 resident schedules in the intensive care unit (ICU) on patient safety, resident well-being and continuity of care. METHODS: Residents in 2 university-affiliated ICUs were randomly assigned (in 2-month rotation-blocks from January to June 2009) to in-house overnight schedules of 24, 16 or 12 hours. The primary patient outcome was adverse events. The primary resident outcome was sleepiness, measured by the 7-point Stanford Sleepiness Scale. Secondary outcomes were patient deaths, preventable adverse events, and residents' physical symptoms and burnout. Continuity of care and perceptions of ICU staff were also assessed. RESULTS: We evaluated 47 (96%) of 49 residents, all 971 admissions, 5894 patient-days and 452 staff surveys. We found no effect of schedule (24-, 16- or 12-h shifts) on adverse events (81.3, 76.3 and 78.2 events per 1000 patient-days, respectively; p = 0.7) or on residents' sleepiness in the daytime (mean rating 2.33, 2.61 and 2.30, respectively; p = 0.3) or at night (mean rating 3.06, 2.73 and 2.42, respectively; p = 0.2). Seven of 8 preventable adverse events occurred with the 12-hour schedule (p = 0.1). Mortality rates were similar for the 3 schedules. Residents' somatic symptoms were more severe and more frequent with the 24-hour schedule (p = 0.04); however, burnout was similar across the groups. ICU staff rated residents' knowledge and decision-making worst with the 16-hour schedule. INTERPRETATION: Our findings do not support the purported advantages of shorter duty schedules. They also highlight the trade-offs between residents' symptoms and multiple secondary measures of patient safety. Further delineation of this emerging signal is required before widespread system change. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT00679809.

Predictive score for estimating cancer after venous thromboembolism: a cohort study.

BACKGROUND: Venous thromboembolism (VTE) has been associated with a higher risk of developing malignancy and mortality, and patients with VTE may therefore benefit from increased surveillance. We aimed to construct a clinical predictive score that could classify patients with VTE according to their risk for developing these outcomes. METHODS: Observational cohort study using an existing clinical registry in a tertiary academic teaching hospital in Buenos Aires, Argentina. 1264 adult patients greater than 17 years of age presented new VTE between June 2006 and December 2011 and were included in the registry. We excluded patients with previous or incident cancer, those who died during the first month, and those with less than one year of follow up (< 5%). 540 patients were included. Primary outcome was new cancer diagnosis during one year of follow-up, secondary composite outcome was any new cancer diagnosis or death. The score was developed using a multivariable logistic regression model to predict cancer or death. RESULTS: During follow-up, one-quarter (26.4%) of patients developed cancer (9.2%) or died (23.7%). Patients with the primary outcome had more comorbidities, were more likely to have previous thromboembolism and less likely to have recent surgery. The final score developed for predicting cancer alone included previous episode of VTE, recent surgery and comorbidity (Charlson comorbidity score), [AUC of 0.75 (95% CI 0.66-0.84) and 0.79 (95% CI 0.63-0.95) in the derivation and validation cohorts, respectively]. The version of this score developed to predict cancer or death included age, albumin level, comorbidity, previous episode of VTE, and recent surgery [AUC = 0.72 (95% CI 0.66-0.78) and 0.71 (95% CI 0.63-0.79) in the derivation and validation cohorts, respectively]. CONCLUSIONS: A simple clinical predictive score accurately estimates patients' risk of developing cancer or death following newly diagnosed VTE. This tool could be used to help reassure low risk patients, or to identify high-risk patients that might benefit from closer surveillance and additional investigations. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01372514.

3D Filaments Based on Polyhydroxy Butyrate-Micronized Bacterial Cellulose for Tissue Engineering Applications.

In this work, scaffolds based on poly(hydroxybutyrate) (PHB) and micronized bacterial cellulose (BC) were produced through 3D printing. Filaments for the printing were obtained by varying the percentage of micronized BC (0.25, 0.50, 1.00, and 2.00%) inserted in relation to the PHB matrix. Despite the varying concentrations of BC, the biocomposite filaments predominantly contained PHB functional groups, as Fourier transform infrared spectroscopy (FTIR) demonstrated. Thermogravimetric analyses (i.e., TG and DTG) of the filaments showed that the peak temperature (Tpeak) of PHB degradation decreased as the concentration of BC increased, with the lowest being 248 °C, referring to the biocomposite filament PHB/2.0% BC, which has the highest concentration of BC. Although there was a variation in the thermal behavior of the filaments, it was not significant enough to make printing impossible, considering that the PHB melting temperature was 170 °C. Biological assays indicated the non-cytotoxicity of scaffolds and the provision of cell anchorage sites. The results obtained in this research open up new paths for the application of this innovation in tissue engineering.

Effects of increasing compliance with minimal sedation on duration of mechanical ventilation: a quality improvement intervention.

INTRODUCTION: In the past two decades, healthcare adopted industrial strategies for process measurement and control. In the industry model, care is taken to avoid minimal deviations from a standard. In healthcare there is scarce data to support that a similar strategy can lead to better outcomes. Briefly, when compliance is high, further attempts to improve uptake of a process are seldom made. Our intensive care unit (ICU) improved the compliance with minimizing sedation from a high baseline of 80.4% (95% CI: 66.9 to 90.2) to 96.2% (95% CI: 95.2 to 97.0) 12 months after a quality improvement initiative. We sought to measure whether this minute improvement in compliance led to a reduction in duration of mechanical ventilation. METHODS: We collected data on compliance with the process during 12 months. A trained data collector abstracted data from charts every other day. Our database contains data for length of mechanical ventilation, mortality, type of admission, and acute physiology and chronic health evaluation (APACHE) II scores for the 12 months before and after the process improvement. RESULTS: We included 1556 patients. There was an immediate effect of the intervention (regression coefficient = -0.129, P value < 0.001) and the secular trend was a determinant of length of mechanical ventilation (regression coefficient = 0.010, P value = 0.004). The trend post-intervention was not significant (regression coefficient = 0.004, P value = 0.380). CONCLUSIONS: In a system already working at high levels of compliance, outcomes can still be improved. Our intervention was successful in reducing the length of mechanical ventilation. ICUs should have a process of quality assurance in place to provide constant monitoring of key quality of care processes and correct deviations from the proposed standard.

A Kunitz proteinase inhibitor from corms of Xanthosoma blandum with bactericidal activity.

Bacterial infections directly affect the world's population, and this situation has been aggravated by indiscriminate use of antimicrobial agents, which can generate resistant microorganisms. In this report, an initial screening of proteins with antibacterial activity from corms of 15 species of the Xanthosoma genus was conducted. Since Xanthosoma blandum corms showed enhanced activity toward bacteria, a novel protein with bactericidal activity was isolated from this particular species. Edman degradation was used for protein N-termini determination; the primary structure showed similarities with Kunitz inhibitors, and this protein was named Xb-KTI. This protein was further challenged against serine proteinases from different sources, showing clear inhibitory activities. Otherwise, no hemolytic activity was observed for Xb-KTI. The results demonstrate the biotechnological potential of Xb-KTI, the first proteinase inhibitor with antimicrobial activity described in the Xanthosoma genus.

Reducing redundant creatine kinase testing in cardiac injury.

BACKGROUND: Creatine kinase (CK) testing in the setting of suspected cardiac injury is commonly performed yet rarely provides clinical value beyond troponin testing. We sought to evaluate and reduce CK testing coupled with troponin testing by 50% or greater. METHODS: We performed root cause analysis to study prevailing processes and patterns of CK testing. We developed new institutional guidelines, removed CK from high-volume paper and electronic order bundles and conducted academic detailing for departments with highest ordering frequency. We evaluated consecutive patients at Sunnybrook Health Sciences Centre between 1 January 2018 and 31 March 2020 who had either a CK or troponin level measured. We prespecified successful implementation as a reduction of 50% in total CK orders and a decrease in the ratio of CK-to-troponin tests to one-third or less. We retained additional data beyond our study period to assess for sustained reductions in testing. RESULTS: Total CK tests decreased over the study period from 3963 to 2111 per month, amounting to a 46.7% reduction (95% CI 33.2 to 60.2; p<0.001) equalling 61 fewer tests per hospital day. Troponin testing did not significantly change during the intervention. Ratio of CK-to-troponin tests decreased from 0.91 to 0.49 (p<0.001). The reduction coincided with changes to order-sets, was observed across all clinical units and was sustained during additional months beyond the study period. These reductions in testing resulted in a projected annual cost savings of C$28 446. CONCLUSIONS: We demonstrate that a low-cost and feasible quality improvement initiative may lead to significant reduction in unnecessary CK testing and substantial savings in healthcare costs for patients with suspected cardiac injury.

Short-term effects of maximal dynamic exercise on flow-mediated dilation in professional female soccer players.

BACKGROUND: Endothelial function assessment may provide important insights into the cardiovascular function and long-term effects of exercise training. Many studies have investigated the possible negative effects on cardiovascular function due to extreme athletic performance, leading to undesirable effects. The purposes of this study were to investigate the acute effects of maximal intensity exercise on endothelium-dependent vasodilation, and to understand the patterns of flow-mediated dilation (FMD) change following maximal exercise in elite female athletes with a high-volume training history. METHODS: Twenty-six elite female soccer players (mean age, 22±4 years; BMI, 21±2 kg/m2; VO2max, 41±4 mL/kg/min) were evaluated. Brachial artery FMD was determined using high-resolution ultrasound at rest, and after 15 and 60 min of maximal cardiopulmonary exercise (CPX) testing on a treadmill. Flow velocity was measured at baseline and during reactive hyperemia at the same periods. RESULTS: Rest FMD was 12.4±5.5%. Peak diameter in response to reactive hyperemia was augmented after 15 min of CPX (3.5±0.4 vs. 3.6±0.4 mm, P<0.05), returning to resting values after 60 min. However, %FMD did not change among time periods. There were two characteristic patterns of FMD response following CPX. Compared to FMD at rest, half of the subjects responded with an increased FMD following maximum exercise (10.5±6.1 vs. 17.8±7.5%, P<0.05). The other subjects demonstrated a reduced FMD response following maximum exercise (14.2±4.3 vs. 10.9±3.2%, P<0.01). CONCLUSIONS: These results indicate that elite female soccer players presented robust brachial artery FMD at rest, with a heterogeneous FMD response to acute exercise with a 50% FMD improvement rate.

An international perspective on the frequency, perception of utility, and quality of interprofessional rounds practices in intensive care units.

PURPOSE: To describe international variation in interprofessional rounds in intensive care units (ICUs). MATERIALS AND METHODS: Survey of ICU clinicians on their practices and perceptions of rounds using societal mailing lists and social media. RESULTS: Out of 2402 respondents, 1752 (72.8%) use rounds. Teams are mostly composed of intensivists, nurses and medical trainees. The majority of rounds (57.5%) last >2 h, and North Americans report the highest rates of rounds allowing family attendance (92.4%). Shorter rounds (1-2 h, OR 0.67, 0.52-0.86, p < 0.01; <1 h, OR 0.72, 0.53-0.97, p = 0.03), and strategies such as designating a person for writing (OR 0.73, 0.57-0.95, p = 0.01), and designating a person to assist other patients (OR 0.75, 0.57-0.98, p = 0.04) are associated with a lower perception of negative outcomes. Using daily goals during rounds is associated with a higher perception of positive outcomes (OR 1.85, 1.17-2.90, p < 0.01). CONCLUSIONS: Three-quarters of respondents perform rounds, and models of rounds are heterogeneous, creating challenges for future studies on improving rounds. Respondents reporting better outcomes also experience shorter rounds, and adopt strategies such as discussion of daily goals, and designation individuals for writing or assisting other patients during rounds.

Comparison of 2 Triage Scoring Guidelines for Allocation of Mechanical Ventilators.

Importance: In the current setting of the coronavirus disease 2019 pandemic, there is concern for the possible need for triage criteria for ventilator allocation; to our knowledge, the implications of using specific criteria have never been assessed. Objective: To determine which and how many admissions to intensive care units are identified as having the lowest priority for ventilator allocation using 2 distinct sets of proposed triage criteria. Design, Setting, and Participants: This retrospective cohort study conducted in spring 2020 used data collected from US hospitals and reported in the Philips eICU Collaborative Research Database. Adult admissions (N = 40 439) to 291 intensive care units from 2014 to 2015 who received mechanical ventilation and were not elective surgery patients were included. Exposures: New York State triage criteria and original triage criteria proposed by White and Lo. Main Outcomes and Measures: Sequential Organ Failure Assessment (SOFA) scores were calculated for admissions. The proportion of patients who met initial criteria for the lowest level of priority for mechanical ventilation using each set of criteria and their characteristics and outcomes were assessed. Agreement was compared between the 2 sets of triage criteria, recognizing differences in stated criteria aims. Results: Among 40 439 intensive care unit admissions of patients who received mechanical ventilation, the mean (SD) age was 62.6 (16.6) years, 54.9% were male, and the mean (SD) SOFA score was 4.5 (3.7). Using the New York State triage criteria, 8.9% (95% CI, 8.7%-9.2%) were in the lowest priority category; these lowest priority admissions had a mean (SD) age of 62.9 (16.6) years, used a median (interquartile range) of 57.3 (20.1-133.5) ventilator hours each, and had a hospital survival rate of 38.6% (95% CI, 37.0%-40.2%). Using the White and Lo triage criteria, 4.3% (95% CI, 4.1%-4.5%) were in the lowest priority category; these admissions had a mean (SD) age of 68.6 (13.2) years, used a median (interquartile range) of 61.7 (24.3-142.8) ventilator hours each, and had a hospital survival rate of 56.2% (95% CI, 53.8%-58.7%). Only 655 admissions (1.6%) were in the lowest priority category for both guidelines, with the κ statistic for agreement equal to 0.20 (95% CI, 0.18-0.21). Conclusions and Relevance: Use of 2 initially proposed ventilator triage guidelines identified approximately 1 in every 10 to 25 admissions as having the lowest priority for ventilator allocation, with little agreement. Clinical assessment of different potential criteria for triage decisions in critically ill populations is important to ensure valid and equitable allocation of resources.

Amphotericin B in poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) nanoparticles against paracoccidioidomycosis.

OBJECTIVES: The present study reports on the preparation and testing of a desoxycholate amphotericin B (D-AMB) sustained delivery system based on poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) polymeric blends (Nano-D-AMB) aimed at reducing the number of AMB administrations required to treat mycosis. METHODS: BALB/c mice were infected with the yeast Paracoccidioides brasiliensis intravenously to mimic the chronic form of paracoccidioidomycosis. At 30 days post-infection, the animals were treated with Nano-D-AMB [6 mg/kg of encapsulated D-AMB, intraperitoneally (ip), interval of 72 h] or D-AMB (2 mg/kg, ip, interval of 24 h). Drug efficacy was investigated by the fungal burden recovery from tissues. Toxicity was assessed by renal and hepatic biochemical parameters, physical appearance of the animals and haematological investigation. The control groups used were non-infected and the infected mice mock treated with PBS. RESULTS: Nano-D-AMB presented results comparable to free D-AMB, with a marked antifungal efficacy. The Nano-D-AMB-treated group presented lower loss of body weight and absence of stress sign (piloerection and hypotrichosis) observed after D-AMB treatment. No renal [blood urea nitrogen (BUN), creatinine] or hepatic (pyruvic and oxalacetic glutamic transaminases) biochemical abnormalities were found. The micronucleus assay showed no significant differences in both the micronucleus frequency and percentage of polychromatic erythrocytes for Nano-D-AMB, indicating the absence of genotoxicity and cytotoxic effects. CONCLUSIONS: The D-AMB-coated PLGA-DMSA nanoparticle showed antifungal efficacy, fewer undesirable effects and a favourable extended dosing interval. Nano-D-AMB comprises an AMB formulation able to lessen the number of drug administrations. Further studies would elucidate whether Nano-D-AMB would be useful to treat systemic fungal infections such as paracoccidioidomycosis, candidiasis, aspergillosis and cryptococcosis.

Predicting Future Health Transitions Among Newly Admitted Nursing Home Residents With Heart Failure.

OBJECTIVES: To understand how a heart failure diagnosis and admission health instability predict health transitions and outcomes among newly admitted nursing home residents. DESIGN: Retrospective cohort study of linked administrative data, including the Continuing Care Report System MDS 2.0 for nursing homes, the Discharge Abstract Database for hospitalized patients, and National Ambulatory Care Reporting System to track emergency department visits. SETTING AND PARTICIPANTS: Older adults, aged 65 years and above, admitted to nursing homes in Ontario, Alberta, and British Columbia, Canada, from 2010 to 2016. MEASURES: Mortality and hospitalization were plotted over 1 year. Multistate Markov models were used to estimate adjusted odds ratios (ORs) for transitions to different states of health in stability, hospitalization, and death, stratified by heart failure diagnosis and by interRAI Changes in Health and End-stage disease Signs and Symptoms (CHESS) score, at 90 days following admission to a nursing home. RESULTS: The final sample included 143,067 residents. Adverse events were most common in the first 90 days. A diagnosis of heart failure predicted worsening health instability, hospitalizations, and mortality. The effect of heart failure on hospitalizations and death was strongest for low baseline health instability (CHESS = 0; OR 1.63, 95% confidence interval (CI) 1.58-1.68, and OR 1.71, 95% CI 1.57-1.86, respectively), versus moderate instability (CHESS = 1-2; OR 1.36, 95% CI 1.32-1.39, and OR 1.48, 95% CI 1.41-1.55), versus high instability (CHESS = 3; OR 1.12, 95% CI 1.03-1.23, and OR 1.21, 95% CI 1.11-1.32). The magnitude of the impact of a heart failure diagnosis was greatest for lower baseline health instability. Residents with the highest degree of health instability were also most likely to die in hospital. CONCLUSIONS AND IMPLICATIONS: A diagnosis of heart failure and health instability provide complementary information to predict transfers, deaths, and adverse outcomes. Clearly identifying these at-risk patients may be useful in targeting interventions in nursing homes.