Early physical rehabilitation dosage in the IntensiveCare Unit predicts hospital outcomes after criticalCOVID-19.

Objective: to examine the relationship between physical rehabilitation parameters including a novel approach to quantifying dosage with hospital outcomes for patients with critical COVID-19. Design: Retrospective practice analysis from March 5, 2020, to April 15, 2021. Setting: Intensive care units (ICU) at four medical institutions. Patients: n = 3,780 adults with ICU admission and diagnosis of COVID-19. Interventions: We measured the physical rehabilitation treatment delivered in ICU and patient outcomes: 1) mortality; 2) discharge disposition; and 3) physical function at hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) "6-Clicks" (6-24, 24=greater functional independence). Physical rehabilitation dosage was defined as the average mobility level scores in the first three sessions (a surrogate measure of intensity) multiplied by the rehabilitation frequency (PT + OT frequency in hospital). Measurements and Main Results: The cohort was a mean 64 ± 16 years old, 41% female, mean BMI of 32 ± 9 kg/m2 and 46% (n=1739) required mechanical ventilation. For 2191 patients with complete data, rehabilitation dosage and AM-PAC at discharge were moderately, positively associated (Spearman's rho [r] = 0.484, p < 0.001). Multivariate linear regression (model adjusted R2= 0.68, p <0.001) demonstrates mechanical ventilation (ß = -0.86, p = 0.001), average mobility score in first three sessions (ß = 2.6, p <0.001) and physical rehabilitation dosage (ß = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS. Conclusions: Greater physical rehabilitation exposure early in the ICU is associated with physical function at hospital discharge.

Separation of gold from irradiated actinide material utilizing a 2- thenoyltrifluoroacetone extraction resin.

Post-detonation nuclear forensics capabilities depend on the ability to rapidly isolate radionuclides to improve measurement quality. In this work an extraction chromatography resin was developed utilizing thenoyltrifluoroacetone and 1-octanol supported on Eichrom prefilter resin. The resin was tested in nitric and hydrochloric acid matrices. In nitric acid the resin was able to extract zirconium, while in hydrochloric acid matrices it was possible to extract iron and gallium. In all acid conditions tested, gold was retained but can be eluted from the column with 10 % thiourea.

MyoVision-US: an Artificial Intelligence-Powered Software for Automated Analysis of Skeletal Muscle Ultrasonography.

Introduction/Aims: Muscle ultrasound has high utility in clinical practice and research; however, the main challenges are the training and time required for manual analysis to achieve objective quantification of morphometry. This study aimed to develop and validate a software tool powered by artificial intelligence (AI) by measuring its consistency and predictability of expert manual analysis quantifying lower limb muscle ultrasound images across healthy, acute, and chronic illness subjects. Methods: Quadriceps complex (QC [rectus femoris and vastus intermedius]) and tibialis anterior (TA) muscle ultrasound images of healthy, intensive care unit, and/or lung cancer subjects were captured with portable devices. Automated analyses of muscle morphometry were performed using a custom-built deep-learning model (MyoVision-US), while manual analyses were performed by experts. Consistency between manual and automated analyses was determined using intraclass correlation coefficients (ICC), while predictability of MyoVision -US was calculated using adjusted linear regression (adj.R 2 ). Results: Manual analysis took approximately 24 hours to analyze all 180 images, while MyoVision - US took 247 seconds, saving roughly 99.8%. Consistency between the manual and automated analyses by ICC was good to excellent for all QC (ICC:0.85-0.99) and TA (ICC:0.93-0.99) measurements, even for critically ill (ICC:0.91-0.98) and lung cancer (ICC:0.85-0.99) images. The predictability of MyoVision-US was moderate to strong for QC (adj.R 2 :0.56-0.94) and TA parameters (adj.R 2 :0.81-0.97). Discussion: The application of AI automating lower limb muscle ultrasound analyses showed excellent consistency and strong predictability compared with human analysis. Future work needs to explore AI-powered models for the evaluation of other skeletal muscle groups.

Assessing Gas-Phase Ion Reactivity of 50 Elements with NO and the Direct Application for 239Pu in Complex Matrices Using ICP-MS/MS.

Understanding the reactivity of metal cations with various reaction gases in inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) is important to determine the best gas to use for a given analyte/interference pair. In this study, nitric oxide (NO) was investigated as the reaction gas following previous experimental designs. The reactions with 50 elements were investigated to examine periodic trends in reactivity, validate theoretical modeling of reaction enthalpies as a method to screen reactant gases, and provide a baseline data set for potential in-line gas separation methods. ICP-MS/MS studies involving actinides are typically limited to Th, U, and Pu, with analyses of Np and Am rarely reported in the literature. To date, only two previous methods have investigated the use of NO in ICP-MS/MS analyses. To showcase the utility of NO, a method was developed to measure 239Pu in the presence of environmental matrix constituent and other actinides, like what could be expected from postdetonation debris, with no chemical separation prior to analysis. 239Pu+ was reacted to form 239Pu16O+, eliminating interferences derived from the sample matrix by measuring the 239Pu+ intensity at m/z = 255 (239Pu16O+). To validate NO for 238U1H+ interference removal in environmental matrices, standard reference materials were diluted to 1 mg/g of solution and spiked to 0.05 pg/g of 239Pu and 1 µg/g 238U (Pu/U = 5 × 10-8). Measured 239Pu concentrations were within 6% of the spiked value. These results demonstrate that reliable 239Pu measurements can be made at levels relevant to nuclear forensics without the need for extensive chemical matrix separation prior to analysis.

The importance of ion kinetic energy for interference removal in ICP-MS/MS.

The effect of ion kinetic energy on gas phase ion reactivity with ICP-MS/MS was investigated in order to explore tuning strategies for interference removal. The collision/reaction gases CO2, N2O and O2 were used to observe the ion product distribution for 48 elements using an Agilent tandem ICP-MS (ICP-MS/MS) as a function of reaction gas flow rate (pressure) and ion kinetic energy. The kinetic energy of the incident ion was varied by adjusting the octopole bias (Voct). The three gases all form oxides (MO+) as the primary product with differing reaction enthalpies that result in distinct differences in the ion energies required for reaction with product ion distributions that vary with Voct. Consequently, by varying the ion kinetic energy (i.e., Voct), differences in interference reactivity can be used to achieve maximum separation. Three practical application examples were reported to demonstrate how the ion kinetic energy can be varied to achieve the ideal ion product distribution for interference resolution: CO2 for the removal of 238U in Pu analyses, CO2 for the removal of 40Ar16O vs. 56Fe, and O2 for the removal of Sm in Eu analyses, analogous to Pu/Am. The results demonstrate how the starting ion energy defined by Voct is an important factor to fully leverage the utility of any given reaction gas to remove interferences in the mass spectrum using ICP-MS/MS.

Construct and criterion validity of muscle ultrasonography for assessment of skeletal muscle in patients recovering from COVID-19.

Background: The purpose was to investigate the content, construct, and criterion validity of muscle ultrasound in a mixed cohort of participants recovering from mild and critical COVID-19. Methods: A secondary analysis of a prospective cross-sectional study was conducted on data obtained from a battery of muscle and physical function assessments including a muscle biopsy and muscle ultrasonography (US). Rectus femoris (RF) muscle thickness (mT), quadricep complex (QC) mT, RF muscle cross-sectional area (CSA) using 2D freeform trace and estimated from Feret's diameter, and RF echo intensity (EI) were assessed with US. Muscle fiber CSA, fiber type, protein content in muscle fibers, extracellular matrix content (ECM; wheat-germ agglutin), and percent area of collagen in ECM (picrosirius red) were examined from vastus lateralis muscle biopsies. Spearman rho correlations (r) were performed to assess validity of ultrasound parameters. Results: Thirty-three individuals participated including 11 patients surviving critical COVID-19, 15 individuals recovering from mild-COVID, and 7 controls. There were several significant correlations between RF mT, QC mT, RF CSA, and RF EI with age, comorbid burden, body-mass index, and measures of muscle strength, muscle power, and physical function (range r = 0.35-0.83). RF Feret's CSA correlated to CSA of type II muscle fibers (r = 0.41, p = 0.022) and the average size of all muscle fibers (r = 0.39, p = 0.031). RF EI was correlated with collagen in muscle ECM (r = 0.53, p = 0.003) and protein content in muscle tissue (r = -0.52, p = 0.012). Conclusion: Muscle size and quality measured using US has moderate content and construct validity, and to lesser extent, fair to moderate criterion validity in a mixed cohort of individuals recovering from COVID. Muscle ultrasound quality (EI) appears to be sensitive at detecting muscle dysfunction as it is associated with strength, power, physical function, and collagen distribution in a mixed group of individuals recovering from COVID-19.

Development and psychometric properties of the Person-centered Palliative Care Nursing Instrument (PPCNI) in the Philippines.

Background: Over the years, a few tools and instruments have been developed to assist in the assessment within a palliative care setting. However, many of these tools and instruments do not reflect a person-centered palliative care model. Objective: This study aims to develop a Person-centered Palliative Care Nursing Instrument (PPCNI) in the Philippines. Methods: An exhaustive search of the literature was conducted to develop a pool of items for the instrument. The validity of the instrument was evaluated using the content validity index (CVI), while the factor structure was assessed using exploratory factor analysis (EFA) using maximum likelihood estimation with Promax rotation. Also, the internal reliability was evaluated using Cronbach's alpha. Results: EFA yielded three factors: 1) Caring as maintaining person's dignity (13 items), 2) caring as empowerment of person's autonomy (14 items), and 3) caring as understanding person's momentary concerns (10 items). Whereas the internal consistency reliability of these subscales appeared excellent (i.e., 0.95, 0.96, and 0.93, respectively), the Cronbach's alpha for the overall scale was 0.98. The item-total correlation coefficients were >0.30 for all items, ranging from 0.310 to 0.726. Conclusion: Findings support a three-factor, 37-item PPCNI that can be used in clinical practice to ensure that nurses provide palliative care based on patient needs and preferences.

Nutrition in the intensive care unit and early recovery influence functional outcomes for survivors of critical illness: A prospective cohort study.

BACKGROUND: Patients who are critically ill may receive suboptimal nutrition that leads to weight loss and increased risk of functional deficits. METHODS: Our overarching hypothesis is that nutrition in the intensive care unit (ICU) and the early recovery phase associates with functional outcomes at short-term follow-up. We enrolled adult patients who attended the University of Kentucky ICU recovery clinic (ICU-RC) from November 2021 to June 2022. Patients participated in muscle and functional assessments. Nutrition intake and status during the ICU stay were analyzed. The Subjective Global Assessment and a nutrition questionnaire were used to identify changes in intake, ongoing gastrointestinal symptoms, and patient's access to food at the ICU-RC appointment. RESULTS: Forty-one patients enrolled with a median hospital length of stay (LOS) of 23 days. Patients with 0 days of nil per os (NPO) status throughout hospitalization had a shorter LOS (P = 0.05), were able to complete the five times sit-to-stand test (P = 0.02), and were less likely to experience ICU-acquired weakness (P = 0.04) at short-term follow-up compared with patients with ≥1 day of NPO status. Twenty (48%) patients reported changes in nutrition intake in early recovery compared with before hospitalization. Eight (20%) patients reported symptoms leading to decreased intake and four (10%) reported access to food as a barrier to intake. CONCLUSION: Barriers to nutrition exist during critical illness and persist after discharge, with almost half of patients reporting a change in intake. Inpatient nutrition intake is associated with functional outcomes and warrants further exploration.

The Reviewer Academy of the Society of Critical Care Medicine: Key Principles and Strategic Plan.

The Society of Critical Care Medicine (SCCM) Reviewer Academy seeks to train and establish a community of trusted, reliable, and skilled peer reviewers with diverse backgrounds and interests to promote high-quality reviews for each of the SCCM journals. Goals of the Academy include building accessible resources to highlight qualities of excellent manuscript reviews; educating and mentoring a diverse group of healthcare professionals; and establishing and upholding standards for insightful and informative reviews. This manuscript will map the mission of the Reviewer Academy with a succinct summary of the importance of peer review, process of reviewing a manuscript, and the expected ethical standards of reviewers. We will equip readers to target concise, thoughtful feedback as peer reviewers, advance their understanding of the editorial process and inspire readers to integrate medical journalism into diverse professional careers.

Critical illness myopathy and trajectory of recovery in acute kidney injury requiring continuous renal replacement therapy: a prospective observational trial protocol.

INTRODUCTION: Acute kidney injury requiring renal replacement therapy (AKI-RRT) is common in the intensive care unit (ICU) and is associated with significant morbidity and mortality. Continuous RRT (CRRT) non-selectively removes large amounts of amino acids from plasma, lowering serum amino acid concentrations and potentially depleting total-body amino acid stores. Therefore, the morbidity and mortality associated with AKI-RRT may be partly mediated through accelerated skeletal muscle atrophy and resulting muscle weakness. However, the impact of AKI-RRT on skeletal muscle mass and function during and following critical illness remains unknown. We hypothesise that patients with AKI-RRT have higher degrees of acute muscle loss than patients without AKI-RRT and that AKI-RRT survivors are less likely to recover muscle mass and function when compared with other ICU survivors. METHODS AND ANALYSIS: This protocol describes a prospective, multicentre, observational trial assessing skeletal muscle size, quality and function in ICU patients with AKI-RRT. We will perform musculoskeletal ultrasound to longitudinally evaluate rectus femoris size and quality at baseline (within 48 hours of CRRT initiation), day 3, day 7 or at ICU discharge, at hospital discharge, and 1-3 months postdischarge. Additional skeletal muscle and physical function tests will be performed at hospital discharge and postdischarge follow-up. We will analyse the effect of AKI-RRT by comparing the findings in enrolled subjects to historical controls of critically ill patients without AKI-RRT using multivariable modelling. ETHICS AND DISSEMINATION: We anticipate our study will reveal that AKI-RRT is associated with greater degrees of muscle loss and dysfunction along with impaired postdischarge recovery of physical function. These findings could impact the in-hospital and postdischarge treatment plan for these patients to include focused attention on muscle strength and function. We intend to disseminate findings to participants, healthcare professionals, the public and other relevant groups via conference presentation and publication without any publication restrictions. TRIAL REGISTRATION NUMBER: NCT05287204.

Post-intensive care syndrome and pulmonary fibrosis in patients surviving ARDS-pneumonia of COVID-19 and non-COVID-19 etiologies.

The purpose was to examine patient-centered outcomes and the occurrence of lung fibrotic changes on Chest computed tomography (CT) imaging following pneumonia-related acute respiratory distress syndrome (ARDS). We sought to investigate outpatient clinic chest CT imaging in survivors of COVID19-related ARDS and non-COVID-related ARDS, to determine group differences and explore relationships between lung fibrotic changes and functional outcomes. A retrospective practice analysis of electronic health records at an ICU Recovery Clinic in a tertiary academic medical center was performed in adult patients surviving ARDS due to COVID-19 and non-COVID etiologies. Ninety-four patients with mean age 53 ± 13 and 51% male were included (n = 64 COVID-19 and n = 30 non-COVID groups). There were no differences for age, sex, hospital length of stay, ICU length of stay, mechanical ventilation duration, or sequential organ failure assessment (SOFA) scores between the two groups. Fibrotic changes visualized on CT imaging occurred in a higher proportion of COVID-19 survivors (70%) compared to the non-COVID group (43%, p < 0.001). Across both groups, patients with fibrotic changes (n = 58) were older, had a lower BMI, longer hospital and ICU LOS, lower mean RASS scores, longer total duration of supplemental oxygen. While not statistically different, patients with fibrotic changes did have reduced respiratory function, worse performance on the six-minute walk test, and had high occurrences of anxiety, depression, emotional distress, and mild cognitive impairment regardless of initial presenting diagnosis. Patients surviving pneumonia-ARDS are at high risk of impairments in physical, emotional, and cognitive health related to Post-Intensive Care Syndrome. Of clinical importance, pulmonary fibrotic changes on chest CT occurred in a higher proportion in COVID-ARDS group; however, no functional differences were measured in spirometry or physical assessments at ICU follow-up. Whether COVID infection imparts a unique recovery is not evident from these data but suggest that long-term follow up is necessary for all survivors of ARDS.

Assessment of Symptom, Disability, and Financial Trajectories in Patients Hospitalized for COVID-19 at 6 Months.

Importance: Individuals who survived COVID-19 often report persistent symptoms, disabilities, and financial consequences. However, national longitudinal estimates of symptom burden remain limited. Objective: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19-related hospitalization. Design, Setting, and Participants: A national US multicenter prospective cohort study with 1-, 3-, and 6-month postdischarge visits was conducted at 44 sites participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network's Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. Participants included hospitalized English- or Spanish-speaking adults without severe prehospitalization disabilities or cognitive impairment. Participants were enrolled between August 24, 2020, and July 20, 2021, with follow-up occurring through March 30, 2022. Exposure: Hospitalization for COVID-19 as identified with a positive SARS-CoV-2 molecular test. Main Outcomes and Measures: New or worsened cardiopulmonary symptoms, financial problems, functional impairments, perceived return to baseline health, and quality of life. Logistic regression was used to identify factors associated with new cardiopulmonary symptoms or financial problems at 6 months. Results: A total of 825 adults (444 [54.0%] were male, and 379 [46.0%] were female) met eligibility criteria and completed at least 1 follow-up survey. Median age was 56 (IQR, 43-66) years; 253 (30.7%) participants were Hispanic, 145 (17.6%) were non-Hispanic Black, and 360 (43.6%) were non-Hispanic White. Symptoms, disabilities, and financial problems remained highly prevalent among hospitalization survivors at month 6. Rates increased between months 1 and 6 for cardiopulmonary symptoms (from 67.3% to 75.4%; P = .001) and fatigue (from 40.7% to 50.8%; P < .001). Decreases were noted over the same interval for prevalent financial problems (from 66.1% to 56.4%; P < .001) and functional limitations (from 55.3% to 47.3%; P = .004). Participants not reporting problems at month 1 often reported new symptoms (60.0%), financial problems (23.7%), disabilities (23.8%), or fatigue (41.4%) at month 6. Conclusions and Relevance: The findings of this cohort study of people discharged after COVID-19 hospitalization suggest that recovery in symptoms, functional status, and fatigue was limited at 6 months, and some participants reported new problems 6 months after hospital discharge.

Transcranial ultrasonography to detect intracranial pathology: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Transcranial ultrasonography (TCU) can be a useful diagnostic tool in evaluating intracranial pathology in patients with limited or delayed access to routine neuroimaging in critical care or austere settings. We reviewed available literature investigating the diagnostic utility of TCU for detecting pediatric and adult patient's intracranial pathology in patients with intact skulls and reported diagnostic accuracy measures. METHODS: We performed a systematic review of PubMed® , Cochrane Library, Embase® , Scopus® , Web of Science™, and Cumulative Index to Nursing and Allied Health Literature databases to identify articles evaluating ultrasound-based detection of intracranial pathology in comparison to routine imaging using broad Medical Subject Heading sets. Two independent reviewers reviewed the retrieved articles for bias using the Quality Assessment of Diagnostic Accuracy Studies tools and extracted measures of diagnostic accuracy and ultrasound parameters. Data were pooled using meta-analysis implementing a random-effects approach to examine the sensitivity, specificity, and accuracy of ultrasound-based diagnosis. RESULTS: A total of 44 studies out of the 3432 articles screened met the eligibility criteria, totaling 2426 patients (Mean age: 60.1 ± 14.52 years). We found tumors, intracranial hemorrhage (ICH), and neurodegenerative diseases in the eligible studies. Sensitivity, specificity, and accuracy of TCU and their 95% confidence intervals were 0.80 (0.72, 0.89), 0.71 (0.59, 0.82), and 0.76 (0.71, 0.82) for neurodegenerative diseases; 0.88 (0.74, 1.02), 0.81 (0.50, 1.12), and 0.94 (0.92, 0.96) for ICH; and 0.97 (0.92, 1.03), 0.99 (0.96, 1.01), and 0.99 (0.97, 1.01) for intracranial masses. No studies reported ultrasound presets. CONCLUSIONS: TCU has a reasonable sensitivity and specificity for detecting intracranial pathology involving ICH and tumors with clinical applications in remote locations or where standard imaging is unavailable. Future studies should investigate ultrasound parameters to enhance diagnostic accuracy in diagnosing intracranial pathology.

Methodological and Clinimetric Evaluation of Inspiratory Respiratory Muscle Ultrasound in the Critical Care Setting: A Systematic Review and Meta-Analysis.

OBJECTIVE: Significant variations exist in the use of respiratory muscle ultrasound in intensive care with no society-level consensus on the optimal methodology. This systematic review aims to evaluate, synthesize, and compare the clinimetric properties of different image acquisition and analysis methodologies. DATA SOURCES: Systematic search of five databases up to November 24, 2021. STUDY SELECTION: Studies were included if they enrolled at least 50 adult ICU patients, reported respiratory muscle (diaphragm or intercostal) ultrasound measuring either echotexture, muscle thickness, thickening fraction, or excursion, and evaluated at least one clinimetric property. Two independent reviewers assessed titles, abstracts, and full text against eligibility. DATA EXTRACTION: Study demographics, ultrasound methodologies, and clinimetric data. DATA SYNTHESIS: Sixty studies, including 5,025 patients, were included with 39 studies contributing to meta-analyses. Most commonly measured was diaphragm thickness (DT) or diaphragm thickening fraction (DTF) using a linear transducer in B-mode, or diaphragm excursion (DE) using a curvilinear transducer in M-mode. There are significant variations in imaging methodology and acquisition across all studies. Inter- and intrarater measurement reliabilities were generally excellent, with the highest reliability reported for DT (ICC, 0.98; 95% CI, 0.94-0.99). Pooled data demonstrated acceptable to excellent accuracy for DT, DTF, and DE to predicting weaning outcome after 48 to 72 hours postextubation (DTF AUC, 0.79; 95% CI, 0.73-0.85). DT imaging was responsive to change over time. Only three eligible studies were available for intercostal muscles. Intercostal thickening fraction was shown to have excellent accuracy of predicting weaning outcome after 48-hour postextubation (AUC, 0.84; 95% CI, 0.78-0.91). CONCLUSIONS: Diaphragm muscle ultrasound is reliable, valid, and responsive in ICU patients, but significant variation exists in the imaging acquisition and analysis methodologies. Future work should focus on developing standardized protocols for ultrasound imaging and consider further research into the role of intercostal muscle imaging.

Early posthospitalization recovery after extracorporeal membrane oxygenation in survivors of COVID-19.

OBJECTIVE: We sought to determine the influence of venovenous extracorporeal membrane oxygenation (ECMO) on outcomes of mechanically ventilated patients with COVID-19 during the first 120 days after hospital discharge. METHODS: Five academic centers conducted a retrospective analysis of mechanically ventilated patients with COVID-19 admitted during March through May 2020. Survivors had access to a multidisciplinary postintensive care recovery clinic. Physical, psychological, and cognitive deficits were measured using validated instruments and compared based on ECMO status. RESULTS: Two hundred sixty two mechanically ventilated patients were compared with 46 patients cannulated for venovenous ECMO. Patients receiving ECMO were younger and traveled farther but there was no significant difference in gender, race, or body mass index. ECMO patients were mechanically ventilated for longer durations (median, 26 days [interquartile range, 19.5-41 days] vs 13 days [interquartile range, 7-20 days]) and were more likely to receive inhaled pulmonary vasodilators, neuromuscular blockade, investigational COVID-19 therapies, blood transfusions, and inotropes. Patients receiving ECMO experienced greater bleeding and clotting events (P < .01). However, survival at discharge was similar (69.6% vs 70.6%). Of the 217 survivors, 65.0% had documented follow-up within 120 days. Overall, 95.5% were residing at home, 25.7% had returned to work or usual activity, and 23.1% were still using supplemental oxygen; these rates did not differ significantly based on ECMO status. Rates of physical, psychological, and cognitive deficits were similar. CONCLUSIONS: Our data suggest that COVID-19 survivors experience significant physical, psychological, and cognitive deficits following intensive care unit admission. Despite a more complex critical illness course, longer average duration of mechanical ventilation, and longer average length of stay, patients treated with venovenous ECMO had similar survival at discharge and outcomes within 120 days of discharge.

Effect of collaborative dementia care on potentially inappropriate medication use: Outcomes from the Care Ecosystem randomized clinical trial.

INTRODUCTION: Potentially inappropriate medications (PIMs) cause adverse events and death. We evaluate the Care Ecosystem (CE) collaborative dementia care program on medication use among community-dwelling persons living with dementia (PLWD). METHODS: Secondary analysis of a randomized clinical trial (RCT) comparing CE to usual care (UC) on changes in PIMs, over 12 months between March 2015 and May 2020. Secondary outcomes included change in number of medications, clinically relevant PIMs, and anti-dementia medications. RESULTS: Of 804 PLWD, N = 490 had complete medication data. The CE resulted in significantly fewer PIMs compared to UC (-0.35; 95% CI, -0.49 to -0.20; P < 0.0001). Number needed to prevent an increase in 1 PIM was 3. Total medications, PIMs for dementia or cognitive impairment, CNS-active PIMs, anticholinergics, benzodiazepines, and opioids were also fewer. Anti-dementia medication regimens were modified more frequently. CONCLUSION: The CE medication review intervention embedded in collaborative dementia care optimized medication use among PLWD. HIGHLIGHTS: Compared to usual care (UC), the Care Ecosystem (CE) medication review intervention prevented increases in potentially inappropriate medications (PIMs). Use of anticholinergics, benzodiazepines, and opioids were significantly reduced, with a trend for antipsychotics. Anti-dementia medications were adjusted more frequently. The CE medication review intervention embedded in collaborative dementia care optimized medication use.

Intensive Care Unit-Acquired Weakness in Patients With Acute Kidney Injury: A Contemporary Review.

Acute kidney injury (AKI) and intensive care unit-acquired weakness (ICU-AW) are 2 frequent complications of critical illness that, until recently, have been considered unrelated processes. The adverse impact of AKI on ICU mortality is clear, but its relationship with muscle weakness-a major source of ICU morbidity-has not been fully elucidated. Furthermore, improving ICU survival rates have refocused the field of intensive care toward improving long-term functional outcomes of ICU survivors. We begin our review with the epidemiology of AKI in the ICU and of ICU-AW, highlighting emerging data suggesting that AKI and AKI treated with kidney replacement therapy (AKI-KRT) may independently contribute to the development of ICU-AW. We then delve into human and animal data exploring the pathophysiologic mechanisms linking AKI and acute KRT to muscle wasting, including altered amino acid and protein metabolism, inflammatory signaling, and deleterious removal of micronutrients by KRT. We next discuss the currently available interventions that may mitigate the risk of ICU-AW in patients with AKI and AKI-KRT. We conclude that additional studies are needed to better characterize the epidemiologic and pathophysiologic relationship between AKI, AKI-KRT, and ICU-AW and to prospectively test interventions to improve the long-term functional status and quality of life of AKI survivors.

Relationship of Age And Mobility Levels During Physical Rehabilitation With Clinical Outcomes in Critical Illness.

Objective: To determine whether age, mobility level, and change in mobility level across the first 3 physical rehabilitation sessions associate with clinical outcomes of patients who are critically ill. Design: Retrospective, observational cohort study. Setting: Medical Intensive Care Unit (MICU). Participants: Hospitalized adults (n = 132) who received 3 or more, consecutive rehabilitation sessions in the MICU. Interventions: Not applicable. Measurements and Main Results: Sample included 132 patients with 60 (45%) classified as younger (18-59 years) and 72 (55%) as older (60+ years). The most common diagnosis was sepsis/septicemia (32.6%). Older relative to younger patients had a significantly slower rate of improvement in ICU Mobility Scale (IMS) scores across rehabilitation sessions (mean slope coefficient 0.3 vs 0.6 points, P<.001), were less likely to be discharged to home (30.6% vs 55.0%, P=.005), and were more likely to die within 12 months (41.7% vs 25.0%, P=.046). Covariate-adjusted models indicated greater early improvement in IMS scores were associated with discharge home (P=.005). Longer time to first rehabilitation session, lower initial IMS scores, and slower improvement in IMS scores were associated with increased ICU days (all P<.03). Conclusion: Older age and not achieving the mobility milestone of sitting at edge of bed or limited progression of mobility across sessions is associated with poor patient outcomes. Our findings suggest that age and mobility level contribute to outcome prognostication, and can aide in clinical phenotyping and rehabilitative service allocation.

Monitoring PD-L1 Expression on Circulating Tumor-Associated Cells in Recurrent Metastatic Non-Small-Cell Lung Carcinoma Predicts Response to Immunotherapy With Radiation Therapy.

PURPOSE: Current diagnostic methods to determine programmed death 1 (PD-1) receptor and its ligand (PD-L1)/PD-1 immunotherapy (immune checkpoint inhibitor [ICI]) efficacy in recurrent or metastatic non-small-cell lung carcinoma (rmNSCLC) are imprecise. Although previously shown that patients with high tumor PD-L1 (≥ 50%) demonstrate clinical benefit in the form of disease reduction and improved survival, patients with low PD-L1 (< 50%) sometimes benefit from treatment. Since the PD-L1/PD-1 pathway is dynamic, monitoring PD-L1 levels during treatment may be more accurate than a static baseline tumor biopsy; however, rebiopsying the primary or metastatic disease is rarely feasible. Liquid biopsies that measure the upregulation of PD-L1 on tumor-associated cells (TACs), ie, cancer-associated macrophage-like cells and circulating tumor cells, have been performed, but their predictive value for ICI therapy efficacy is unknown. MATERIALS AND METHODS: We initiated a single-blind prospective study to evaluate TAC PD-L1 expression changes in rmNSCLC from blood samples before (T0) and after (T1) treatment with ICI (ICI, n = 41) or without ICI (no ICI, n = 41). Anonymized blood was filtered to isolate TACs, which were then quantified for high/low PD-L1 expression. Progression-free survival (PFS) or overall survival (OS) hazard ratios (HRs) were evaluated at 18 and 24 months by censored univariate analysis. RESULTS: Increased TAC PD-L1 expression between T0 and T1 in patients who were not treated with ICI had no relationship with PFS or OS. However, increased TAC PD-L1 expression between T0 and T1 in patients treated with ICI had significantly better PFS (HR, 3.49; 95% CI, 1.5 to 8.3; P = .0091) and OS (HR, 3.058; 95% CI, 1.2 to 7.9; P = .0410). CONCLUSION: Blood-based monitoring of dynamic changes in PD-L1 in TACs appears to identify patients with rmNSCLC who may benefit from ICI.