Turnover of strain-level diversity modulates functional traits in the honeybee gut microbiome between nurses and foragers.

BACKGROUND: Strain-level diversity is widespread among bacterial species and can expand the functional potential of natural microbial communities. However, to what extent communities undergo consistent shifts in strain composition in response to environmental/host changes is less well understood. RESULTS: Here, we used shotgun metagenomics to compare the gut microbiota of two behavioral states of the Western honeybee (Apis mellifera), namely nurse and forager bees. While their gut microbiota is composed of the same bacterial species, we detect consistent changes in strain-level composition between nurses and foragers. Single nucleotide variant profiles of predominant bacterial species cluster by behavioral state. Moreover, we identify strain-specific gene content related to nutrient utilization, vitamin biosynthesis, and cell-cell interactions specifically associated with the two behavioral states. CONCLUSIONS: Our findings show that strain-level diversity in host-associated communities can undergo consistent changes in response to host behavioral changes modulating the functional potential of the community.

Derivation and Validation of a New Equation for Estimating Free Valproate Concentration in Critically Ill Adult Patients.

IMPORTANCE: Protein binding of valproate varies among ICU patients, altering the biologically active free valproate concentration (VPAC). Free VPAC is measured at few laboratories and is often discordant with total VPAC. Existing equations to predict free VPAC are either not validated or are inaccurate in ICU patients. OBJECTIVES: We designed this study to derive and validate a novel equation to predict free VPAC using data from ICU patients and to compare its performance to published equations. DESIGN: Retrospective cohort study. SETTING: Two academic medical centers. PARTICIPANTS: Patients older than 18 years old with concomitant free and total VPACs measured in the ICU were included in the derivation cohort if admitted from 2014 to 2018, and the validation cohort if admitted from 2019 to 2022. MAIN OUTCOMES AND MEASURES: Multivariable linear regression was used to derive an equation to predict free VPAC. Modified Bland-Altman plots and the rate of therapeutic concordance between the measured and predicted free VPAC were compared. RESULTS: Demographics, median free and total VPACs, and valproate free fractions were similar among 115 patients in the derivation cohort and 147 patients in the validation cohort. The Bland-Altman plots showed the new equation performed better (bias, 0.3 [95% limits of agreement, -13.6 to 14.2]) than the Nasreddine (-9.2 [-26.5 to 8.2]), Kodama (-9.7 [-30.0 to 10.7]), Conde Giner (-7.9 [-24.9 to 9.1]), and Parent (-9.9 [-30.7 to 11.0]) equations, and similar to Doré (-2.0 [-16.0 to 11.9]). The Doré and new equations had the highest therapeutic concordance rate (73%). CONCLUSIONS AND RELEVANCE: For patients at risk of altered protein binding such as ICU patients, existing equations to predict free VPAC are discordant with measured free VPAC. A new equation had low bias but was imprecise. External validation should be performed to improve its precision and generalizability. Until then, monitoring free valproate is recommended during critical illness.

International Analgesia and Sedation Weaning and Withdrawal Practices in Critically Ill Adults: The Adult Iatrogenic Withdrawal Study in the ICU.

OBJECTIVES: Iatrogenic withdrawal syndrome (IWS) associated with opioid and sedative use for medical purposes has a reported high prevalence and associated morbidity. This study aimed to determine the prevalence, utilization, and characteristics of opioid and sedative weaning and IWS policies/protocols in the adult ICU population. DESIGN: International, multicenter, observational, point prevalence study. SETTING: Adult ICUs. PATIENTS: All patients aged 18 years and older in the ICU on the date of data collection who received parenteral opioids or sedatives in the previous 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICUs selected 1 day for data collection between June 1 and September 30, 2021. Patient demographic data, opioid and sedative medication use, and weaning and IWS assessment data were collected for the previous 24 hours. The primary outcome was the proportion of patients weaned from opioids and sedatives using an institutional policy/protocol on the data collection day. There were 2,402 patients in 229 ICUs from 11 countries screened for opioid and sedative use; 1,506 (63%) patients received parenteral opioids, and/or sedatives in the previous 24 hours. There were 90 (39%) ICUs with a weaning policy/protocol which was used in 176 (12%) patients, and 23 (10%) ICUs with an IWS policy/protocol which was used in 9 (0.6%) patients. The weaning policy/protocol for 47 (52%) ICUs did not define when to initiate weaning, and the policy/protocol for 24 (27%) ICUs did not specify the degree of weaning. A weaning policy/protocol was used in 34% (176/521) and IWS policy/protocol in 9% (9/97) of patients admitted to an ICU with such a policy/protocol. Among 485 patients eligible for weaning policy/protocol utilization based on duration of opioid/sedative use initiation criterion within individual ICU policies/protocols 176 (36%) had it used, and among 54 patients on opioids and/or sedatives ≥ 72 hours, 9 (17%) had an IWS policy/protocol used by the data collection day. CONCLUSIONS: This international observational study found that a small proportion of ICUs use policies/protocols for opioid and sedative weaning or IWS, and even when these policies/protocols are in place, they are implemented in a small percentage of patients.

PFAS levels and exposure determinants in sensitive population groups.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants. The first exposure to PFAS occurs in utero, after birth it continues via breast milk, food intake, environment, and consumer products that contain these chemicals. Our aim was to identify determinants of PFAS concentrations in sensitive population subgroups- pregnant women and newborns. METHODS: Nine European birth cohorts provided exposure data on PFAS in pregnant women (INMA-Gipuzkoa, Sabadell, Valencia, ELFE and MoBa; total N = 5897) or newborns (3xG study, FLEHS 2, FLEHS 3 and PRENATAL; total N = 940). PFOS, PFOA, PFHxS and PFNA concentrations were measured in maternal or cord blood, depending on the cohort (FLEHS 2 measured only PFOS and PFOA). PFAS concentrations were analysed according to maternal characteristics (age, BMI, parity, previous breastfeeding, smoking, and food consumption during pregnancy) and parental educational level. The association between potential determinants and PFAS concentrations was evaluated using multiple linear regression models. RESULTS: We observed significant variations in PFAS concentrations among cohorts. Higher PFAS concentrations were associated with higher maternal age, primipara birth, and educational level, both for maternal blood and cord blood. Higher PFAS concentrations in maternal blood were associated with higher consumption of fish and seafood, meat, offal and eggs. In cord blood, higher PFHxS concentrations were associated with daily meat consumption and higher PFNA with offal consumption. Daily milk and dairy consumption were associated with lower concentrations of PFAS in both, pregnant women and newborns. CONCLUSION: High detection rates of the four most abundant PFAS demonstrate ubiquitous exposure of sensitive populations, which is of concern. This study identified several determinants of PFAS exposure in pregnant women and newborns, including dietary factors, and these findings can be used for proposing measures to reduce PFAS exposure, particularly from dietary sources.

PFAS levels and determinants of variability in exposure in European teenagers - Results from the HBM4EU aligned studies (2014-2021).

BACKGROUND: Perfluoroalkyl substances (PFAS) are man-made fluorinated chemicals, widely used in various types of consumer products, resulting in their omnipresence in human populations. The aim of this study was to describe current PFAS levels in European teenagers and to investigate the determinants of serum/plasma concentrations in this specific age group. METHODS: PFAS concentrations were determined in serum or plasma samples from 1957 teenagers (12-18 years) from 9 European countries as part of the HBM4EU aligned studies (2014-2021). Questionnaire data were post-harmonized by each study and quality checked centrally. Only PFAS with an overall quantification frequency of at least 60% (PFOS, PFOA, PFHxS and PFNA) were included in the analyses. Sociodemographic and lifestyle factors were analysed together with food consumption frequencies to identify determinants of PFAS exposure. The variables study, sex and the highest educational level of household were included as fixed factors in the multivariable linear regression models for all PFAS and each dietary variable was added to the fixed model one by one and for each PFAS separately. RESULTS: The European exposure values for PFAS were reported as geometric means with 95% confidence intervals (CI): PFOS [2.13 µg/L (1.63-2.78)], PFOA ([0.97 µg/L (0.75-1.26)]), PFNA [0.30 µg/L (0.19-0.45)] and PFHxS [0.41 µg/L (0.33-0.52)]. The estimated geometric mean exposure levels were significantly higher in the North and West versus the South and East of Europe. Boys had significantly higher concentrations of the four PFAS compared to girls and significantly higher PFASs concentrations were found in teenagers from households with a higher education level. Consumption of seafood and fish at least 2 times per week was significantly associated with 21% (95% CI: 12-31%) increase in PFOS concentrations and 20% (95% CI: 10-31%) increase in PFNA concentrations as compared to less frequent consumption of seafood and fish. The same trend was observed for PFOA and PFHxS but not statistically significant. Consumption of eggs at least 2 times per week was associated with 11% (95% CI: 2-22%) and 14% (95% CI: 2-27%) increase in PFOS and PFNA concentrations, respectively, as compared to less frequent consumption of eggs. Significantly higher PFOS concentrations were observed for participants consuming offal (14% (95% CI: 3-26%)), the same trend was observed for the other PFAS but not statistically significant. Local food consumption at least 2 times per week was associated with 40% (95% CI: 19-64%) increase in PFOS levels as compared to those consuming local food less frequently. CONCLUSION: This work provides information about current levels of PFAS in European teenagers and potential dietary sources of exposure to PFAS in European teenagers. These results can be of use for targeted monitoring of PFAS in food.

Opioid Prescribing Patterns Before, During, and After Critical Illness: An Observational Study.

OBJECTIVES: The association between opioid therapy during critical illness and persistent opioid use after discharge is understudied relative to ICU opioid exposure and modifiable risk factors. Our objectives were to compare persistent opioid use after discharge among patients with and without chronic opioid use prior to admission (OPTA) and identify risk factors associated with persistent use. DESIGN: Retrospective cohort study. SETTING: Medical, trauma/surgical, or neurologic ICU at an academic hospital. PARTICIPANTS: Adult patients surviving hospital admission. INTERVENTIONS: Opioid use during the ICU and post-ICU stays. MEASUREMENTS AND MAIN RESULTS: The primary outcome was persistent opioid use accounting for greater than 70% of days 4-6 months after discharge. Among 2,975 included patients, 257 (8.6%) were classified as OPTA, and 305 (10.2%) persistently filled opioid prescriptions, including 186/257 (72%) OPTA and 119/2,718 (4.4%) with no chronic opioid fills prior to admission. Among all patients, OPTA was strongly associated with persistent opioid use (odds ratio, 57.2 [95% CI, 41.4-80.0]). Multivariable logistic regression revealed that male sex, surgical procedure, and ICU opioid-free days were associated with reduced persistent opioid use for OPTA patients. Age and ICU opioid-free days were associated with reduced persistent opioid use for non-OPTA patients. Total ICU opioid dose and dose per day of ICU exposure were not associated with persistent use for either group. CONCLUSIONS: In this mixed cohort of ICU patients, 10.2% persistently filled opioid prescriptions 4-6 months after discharge. Although ICU opioid doses were not associated with persistent use, duration of ICU opioid administration is a modifiable risk factor that may reduce persistent opioid use after critical illness.

Prospective Validation of Sedation Scale Scores That Identify Light Sedation: A Pilot Study.

BACKGROUND: Intensive care unit (ICU) sedation guidelines recommend targeting a light sedation level, but light sedation has no accepted definition, and inconsistent levels have been proposed. OBJECTIVE: To determine Sedation-Agitation Scale and Richmond Agitation-Sedation Scale scores that best describe patients' ability to follow voice commands. METHODS: This prospective, observational pilot study enrolled a convenience sample of ICU patients receiving mechanical ventilation. Pairs of trained investigators evaluated scores on the Sedation-Agitation Scale and Richmond Agitation-Sedation Scale and ability to follow commands before and up to 2 hours after sedation lightening in a blind, independent, simultaneous fashion. Positive predictive values (PPVs) and likelihood ratios (LRs) of Sedation-Agitation Scale and Richmond Agitation-Sedation Scale scores associated with light sedation (ability to follow at least 3 commands) were calculated. RESULTS: Ninety-six assessments (50 before and 46 after lightening of sedation) were performed in medical ICU patients. Scores best associated with ability to follow at least 3 commands were Sedation-Agitation Scale score of 4 (PPV, 0.88; 95% CI, 0.70-0.98; LR, 14.0) and Richmond Agitation-Sedation Scale score of -1 (PPV, 0.81; 95% CI, 0.61-0.93; LR, 10.7), superior to previously recommended thresholds of Sedation-Agitation Scale score of 3 (PPV, 0.62; 95% CI, 0.48-0.75; LR, 3.1) and Richmond Agitation-Sedation Scale score of -3 (PPV, 0.52; 95% CI, 0.39-0.64; LR, 2.0). CONCLUSIONS: The level of sedation most associated with the ability to follow commands appears higher than previously recommended. Further study is needed regarding the effects of sedation level on ICU patients' ability to follow commands and assessment of delirium, pain, and patient preferences.

Evaluation of Free Valproate Concentration in Critically Ill Patients.

Protein binding of valproate is variable in ICU patients, and the total valproate concentration does not predict the free valproate concentration, even when correcting for albumin. We sought to quantify valproate free concentration among ICU patients, identify risk factors associated with an increasing free valproate concentration, and evaluate the association between free valproate concentration with potential adverse drug effect. DESIGN: Retrospective multicenter cohort study. SETTING: Two academic medical centers. PATIENTS: Patients greater than or equal to 18 years of age with concomitant free and total valproate concentrations collected in the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-hundred fifty-six patients were included in the study, with a median age of 56 years (42-70) and 65% of patients were male. The median total valproate concentration was 53 µg/mL (38-70 µg/mL), the free valproate concentration was 12 µg/mL (7-20 µg/mL), and the free fraction was 23.6% (17.0-33.9%). Therapeutic discordance between the free and total valproate concentration occurred in 70% of patients. On multivariable analysis, increased free valproate concentration was associated with higher total valproate concentration (per 5 µg/mL increase, increase 1.72 µg/mL, 95% CI, 1.48-1.96) and lower serum albumin (per 1 g/dL decrease, increase 4.60 µg/mL, 95% CI, 2.71-6.49). There was no association between free valproate concentration and adverse effects. CONCLUSIONS: The valproate total and free concentration was discordant in the majority of patients (70%). Increased valproate free concentration was associated with hypoalbuminemia and total valproate concentration. Clinical decisions based on total valproate concentration may be incorrect for many ICU patients. Prospective, controlled studies are needed to confirm these findings and their clinical relevance.

Design of Clinical Trials Evaluating Sedation in Critically Ill Adults Undergoing Mechanical Ventilation: Recommendations From Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) Recommendation III.

OBJECTIVES: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators. DESIGN: A 2-day in-person meeting was held in Washington, DC, on March 28-29, 2019, followed by a three-round, online modified Delphi consensus process. PARTICIPANTS: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process. MEASUREMENTS AND MAIN RESULTS: The final recommendations were iteratively refined based on the survey results, participants' reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization. CONCLUSIONS: These recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials.

Methadone bioavailability and dose conversion implications with intravenous and enteral administration: A scoping review.

PURPOSE: Despite its availability for more than 70 years, many details concerning methadone remain contentious, such as the dosing equivalents for intravenous and enteral administration. A scoping review was performed to evaluate whether existing literature on methadone bioavailability in human subjects support the current recommendation that an equivalent enteral dose is twice the intravenous dose. METHODS: A librarian-assisted search of the PubMed and EMBASE databases identified all English-language articles with the terms methadone and bioavailability and/or conversion in the title or abstract published from inception though December 2019. A manual search of references was also performed to identify any additional articles. Studies were included in a scoping review if they were published in English and evaluated methadone bioavailability in human subjects. RESULTS: Among 65 publications initially identified, 6 studies involving a total of 50 patients were included in the review. Bioavailability data for healthy volunteers and patients with opioid use disorder, metastatic cancer, chronic pain from malignant or nonmalignant disease were available for analysis. The pooled mean (95% confidence interval) bioavailability (F) was 85.4% (75.2%-95.6%), with heterogeneity (I2) of 0. In the 4 studies that provided individual patient-level data, F was >50% in 40 of 42 patient measurements (95.2%) and ≥75% in 33 of 42 patient measurements (78.6%). CONCLUSION: Available evidence suggests the bioavailability of methadone is generally more than 75%, there is limited evidence for the currently recommended 1:2 ratio (intravenous:enteral), and a more appropriate dosing ratio may be 1:1.3. This scoping review underscores the need for further research to establish an effective and safe ratio when converting between intravenous and enteral dosing formulations of methadone.

Identification and characterization of a new soybean promoter induced by Phakopsora pachyrhizi, the causal agent of Asian soybean rust.

BACKGROUND: Phakopsora pachyrhizi is a biotrophic fungal pathogen responsible for the Asian soybean rust disease causing important yield losses in tropical and subtropical soybean-producing countries. P. pachyrhizi triggers important transcriptional changes in soybean plants during infection, with several hundreds of genes being either up- or downregulated. RESULTS: Based on published transcriptomic data, we identified a predicted chitinase gene, referred to as GmCHIT1, that was upregulated in the first hours of infection. We first confirmed this early induction and showed that this gene was expressed as early as 8 h after P. pachyrhizi inoculation. To investigate the promoter of GmCHIT1, transgenic soybean plants expressing the green fluorescence protein (GFP) under the control of the GmCHIT1 promoter were generated. Following inoculation of these transgenic plants with P. pachyrhizi, GFP fluorescence was detected in a limited area located around appressoria, the fungal penetration structures. Fluorescence was also observed after mechanical wounding whereas no variation in fluorescence of pGmCHIT1:GFP transgenic plants was detected after a treatment with an ethylene precursor or a methyl jasmonate analogue. CONCLUSION: We identified a soybean chitinase promoter exhibiting an early induction by P. pachyrhizi located in the first infected soybean leaf cells. Our results on the induction of GmCHIT1 promoter by P. pachyrhizi contribute to the identification of a new pathogen inducible promoter in soybean and beyond to the development of a strategy for the Asian soybean rust disease control using biotechnological approaches.

Dexmedetomidine for Facilitating Mechanical Ventilation Extubation in Difficult-to-Wean ICU Patients: Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: Agitation and delirium are common in mechanically ventilated adult intensive care unit (ICU) patients and may contribute to delayed extubation times. Difficult-to-wean ICU patients have been associated with an increased risk of longer ICU length of stays and mortality. The purpose of this systematic review and meta-analysis is to evaluate the evidence of dexmedetomidine facilitating successful mechanical ventilation extubation in difficult-to-wean ICU patients and clinical outcomes. METHODS: A literature search was conducted using MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Global Health, Cochrane Central Register of Controlled Trials, Clinical Trial Registries, and the Health Technology Assessment Database from inception to December 5, 2019. Randomized controlled trials evaluating dexmedetomidine with the intended purpose to facilitate mechanical ventilation liberation in adult ICU patients (≥18 years) experiencing extubation failure were included. The primary outcome of time to extubation was evaluated using the weighted mean difference (WMD), with a random effects model. Secondary analyses included hospital and ICU length of stay, in-hospital mortality, hypotension, and bradycardia. RESULTS: A total of 6 trials (n = 306 patients) were included. Dexmedetomidine significantly reduced the time to extubation (WMD: -11.61 hours, 95% CI: -16.5 to -6.7, P = .005) and ICU length of stay (WMD: -3.04 days; 95% CI: -4.66 to -1.43). Hypotension risk was increased with dexmedetomidine (risk ratio [RR]: 1.62, 95% CI: 1.05-2.51), but there was no difference in bradycardia risk (RR: 3.98, 95% CI: 0.70-22.78). No differences were observed in mortality rates (RR: 1.30, 95% CI: 0.45-3.75) or hospital length of stay (WMD: -2.67 days; 95% CI: -7.73 to 2.39). CONCLUSIONS: Dexmedetomidine was associated with a significant reduction in the time to extubation and shorter ICU stay in difficult-to-wean ICU patients. Although hypotension risk was increased with dexmedetomidine, no differences in other clinical outcomes were observed.

Analgesia and sedation in patients with ARDS.

Acute Respiratory Distress Syndrome (ARDS) is one of the most demanding conditions in an Intensive Care Unit (ICU). Management of analgesia and sedation in ARDS is particularly challenging. An expert panel was convened to produce a "state-of-the-art" article to support clinicians in the optimal management of analgesia/sedation in mechanically ventilated adults with ARDS, including those with COVID-19. Current ICU analgesia/sedation guidelines promote analgesia first and minimization of sedation, wakefulness, delirium prevention and early rehabilitation to facilitate ventilator and ICU liberation. However, these strategies cannot always be applied to patients with ARDS who sometimes require deep sedation and/or paralysis. Patients with severe ARDS may be under-represented in analgesia/sedation studies and currently recommended strategies may not be feasible. With lightened sedation, distress-related symptoms (e.g., pain and discomfort, anxiety, dyspnea) and patient-ventilator asynchrony should be systematically assessed and managed through interprofessional collaboration, prioritizing analgesia and anxiolysis. Adaptation of ventilator settings (e.g., use of a pressure-set mode, spontaneous breathing, sensitive inspiratory trigger) should be systematically considered before additional medications are administered. Managing the mechanical ventilator is of paramount importance to avoid the unnecessary use of deep sedation and/or paralysis. Therefore, applying an "ABCDEF-R" bundle (R = Respiratory-drive-control) may be beneficial in ARDS patients. Further studies are needed, especially regarding the use and long-term effects of fast-offset drugs (e.g., remifentanil, volatile anesthetics) and the electrophysiological assessment of analgesia/sedation (e.g., electroencephalogram devices, heart-rate variability, and video pupillometry). This review is particularly relevant during the COVID-19 pandemic given drug shortages and limited ICU-bed capacity.

Heparin-induced thrombocytopenia with thrombosis in COVID-19 adult respiratory distress syndrome.

Early reports of coronavirus disease 2019 (COVID-19) clinical features describe a hypercoagulable state, and recent guidelines recommend prophylactic anticoagulation for patients with COVID-19 with low-molecular-weight heparin, but this would be contraindicated in the presence of heparin-induced thrombocytopenia (HIT). We address the key clinical question whether HIT is also present during COVID-19. We report 3 cases of thrombocytopenia with antiplatelet factor 4 antibodies among 16 intubated patients with COVID-19 with adult respiratory distress syndrome, a higher-than-expected incidence of 19%. Each patient had evidence of thrombosis (pulmonary embolism, upper extremity venous thromboses, and skin necrosis, respectively). The serotonin release assay confirmed HIT in 1 case, and 2 cases were negative. We believe this is the first reported case of HIT during the COVID-19 pandemic. Recognition that the thrombocytopenia represented HIT in the confirmed case was delayed. We recommend clinicians monitor platelet counts closely during heparin therapy, with a low threshold to evaluate for HIT.

An Analysis of Psychoactive Medications Initiated in the ICU but Continued Beyond Discharge: A Pilot Study of Stewardship.

BACKGROUND: Psychoactive medications (PM) are frequently administered in the intensive care unit (ICU) to provide comfort. Interventions focused on preventing their continuation after the acute phase of illness are needed. OBJECTIVE: To determine the frequency that patients with ICU-initiated PM are continued upon ICU and hospital discharge. METHODS: This single-center, prospective, observational study assessed consecutive adult ICU patients who received scheduled PM. Frequency of PM continued at ICU and hospital discharge was recorded. The patient's primary treatment team was contacted by the pharmacist within 72 hours of ICU discharge to establish rationale for continued use or to suggest discontinuation. RESULTS: Of the 60 patients included, 72% were continued on PM at ICU discharge and 30% at hospital discharge. The pharmacist contacted 40% of treatment teams after ICU discharge and intervention resulted in PM discontinued in 50% of patients. Post ICU discharge, the indication of 41% of patients' PM was unknown by the non-ICU care team or incorrect. Medical ICU patients or those transferred to an outside facility were more likely remain on PM at hospital discharge. CONCLUSION: PM are frequently continued during transitions of care and often without knowledge of the initial indication. Future studies should establish effective PM stewardship methods.

Patients With Persistent Low Back Pain and Nerve Root Involvement: To Operate, or Not to Operate, That Is the Question.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: The aims of this study were to evaluate the outcome of surgical and nonsurgical treatment for patients with lumbar herniated disc (LHD) or lumbar spinal stenosis (LSS) after 2 years and to identify predictors for nonsuccess. SUMMARY OF BACKGROUND DATA: Studies regarding the clinician's ability to identify patients with a poor prognosis are not in concurrence and further studies are warranted. METHODS: This study included 390 patients with LHD or LSS referred for surgical evaluation after unsuccessful conservative treatment. Nonsuccess was defined as a Roland-Morris Disability score above 4 (0-23) or a Numeric Rating Scale back and leg pain score above 20 (0-60). Uni- and multivariate logistic regression analyses were used to investigate potential predictive factors including sociodemographic characteristics, history findings, levels of pain and disability, and magnetic resonance imaging findings. RESULTS: Rates of nonsuccess at 2 years were approximately 30% in surgically treated patients with LHD, approximately about 60% in patients with LSS for disability, and 30% and 40%, respectively for pain. For the main outcome variable, disability, in the final multiple logistic regression model, nonsuccess after surgery was associated with male sex (odds ratio [OR] 2.04, 95% confidence interval [CI]: 1.02-4.11, P = 0.04), low level of education (OR 2.60, 95% CI: 1.28-5.29, P = 0.01), high pain intensity (OR 3.06, 95% CI: 1.51-6.21, P < 0.01), and widespread pain (OR 3.59, 95% CI: 1.36-9.46, P = 0.01). CONCLUSION: The results indicate that the prognosis for patients referred for surgery with persistent LHD or LSS and unsuccessful conservative treatment is substantially better when surgery is performed as opposed to not performed. The predictive value of the variables male sex, low level of education, high pain intensity, and widespread pain location found in our study are partly in accordance with results of previous studies. Thus, our results warrant further investigation until firm conclusions can be made. LEVEL OF EVIDENCE: 3.

Accuracy of Point-of-Care Blood Glucose Level Measurements in Critically Ill Patients with Sepsis Receiving High-Dose Intravenous Vitamin C.

STUDY OBJECTIVE: High-dose intravenous vitamin C is a potential treatment option for patients with sepsis and may interfere with point-of-care (POC) blood glucose (BG) testing. This study aimed to determine if vitamin C dosing used for sepsis affected POC BG level results. DESIGN: Prospective observational pilot study. SETTING: Intensive care unit in a large academic tertiary care medical center. PATIENTS: Five consecutive critically ill adults hospitalized between April 1 and June 1, 2017, who received two or more doses of intravenous vitamin C 1500 mg for the treatment of sepsis and had at least two paired POC BG levels and laboratory venous BG levels measured within 1 hour of each other during vitamin C therapy. MEASUREMENTS AND MAIN RESULTS: The performance of POC BG level measurement was compared with the reference method of laboratory BG level measurement. The concordance to minimum accuracy criteria for BG meters set forth by the International Organization for Standardization (ISO) 15197:2013, the measurement of agreement between POC BG level and laboratory BG level using the Bland-Altman method, and the clinical accuracy through Parkes error grid analysis were assessed. A total of 16 paired POC and laboratory BG level measurements from the five patients were included. The accuracy of POC BG with laboratory BG level measurements during vitamin C administration according to ISO 15197:2013 criteria was 81.3%, which did not meet the minimum accuracy criteria of 95%. The Bland-Altman analysis showed a mean difference between POC and laboratory BG levels of 8.9 mg/dl, and the Parkes error grid analysis showed that the differences between POC and laboratory BG level measurements would not have resulted in a change in clinical action. CONCLUSION: The accuracy and agreement of POC and laboratory BG level measurements in critically ill patients receiving vitamin C were consistent with previously published reports in critically ill patients not receiving vitamin C and did not demonstrate clinically significant interference due to vitamin C dosing for sepsis.