Comparative analysis of financial toxicity between SARS-CoV-2 infection and common comorbidities.

Financial toxicity is common in individuals with COVID-19 and Long COVID. However, the extent of financial toxicity experienced, in comparison to other common comorbidities, is uncertain. Contributing factors exacerbating financial challenges in Long COVID are also unclear. These knowledge gaps are addressed via a cross-sectional analysis utilizing data from the 2022 National Health Interview Survey (NHIS), a representative sample drawn from the United States. COVID-19 cases were identified through self-reported positive testing or physician diagnoses. Long COVID was defined as experiencing COVID-19-related symptoms for more than three months. Comorbidity was assessed based on self-reported diagnoses of ten doctor-diagnosed conditions (Yes/No). Financial toxicity was defined as having difficulty paying medical bills, cost-related medication nonadherence, delaying healthcare due to cost, and/or not obtained healthcare due to cost. A total of 27,492 NHIS 2022 respondents were included in our analysis, representing 253 million U.S. adults. In multivariable logistic regression models, adults with Long COVID (excluding respondents with COVID-19 but not Long COVID), showed increased financial toxicity compared to those with other comorbidities, such as epilepsy (OR [95% CI]: 1.69 [1.22, 2.33]), dementia (1.51 [1.01, 2.25]), cancer (1.43 [1.19, 1.71]) or respiratory/cardiovascular conditions (1.18 [1.00, 1.40]/1.23 [1.02, 1.47]). Long COVID-related financial toxicity was associated with female sex, age <65 years, lack of medical insurance, current paid employment, residence region, food insecurity, fatigue, mild to severe depression symptoms experienced during the survey completion, visits to hospital emergency rooms, presence of arthritis, cardiovascular or respiratory conditions, and social activity limitations. In conclusion, American adults with Long COVID, but not those who had prior COVID-19 infection without Long COVID, exhibited a higher prevalence of financial toxicity compared to individuals with common comorbidities. Vulnerable populations were at greater risk for financial toxicity. These findings emphasize the importance of evaluating strategies to reduce economic burden and increase awareness of the effect of Long COVID-related financial toxicity on patient's healthcare and health status.

Delirium Screening in Critically Ill Children: Secondary Analysis of the Multicenter PICU Up! Pilot Trial Dataset, 2019-2020.

OBJECTIVES: To determine the patient-level factors associated with performing daily delirium screening in PICUs with established delirium screening practices. DESIGN: A secondary analysis of 2019-2020 prospective data from the baseline phase of the PICU Up! pilot stepped-wedge multicenter trial (NCT03860168). SETTING: Six PICUs in the United States. PATIENTS: One thousand sixty-four patients who were admitted to a PICU for 3 or more days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1064 patients, 74% (95% CI, 71-76%) underwent delirium screening at least once during their PICU stay. On 57% of the 8965 eligible patient days, screening was conducted. The overall prevalence of delirium was 46% across all screened days, and 64% of screened patients experienced delirium at some point during their PICU stay. Factors associated with greater adjusted odds ratio (aOR) of increased daily delirium screening included PICU stay longer than 15 days compared with 1-3 days (aOR 3.36 [95% CI, 2.62-4.30]), invasive mechanical ventilation as opposed to room air (aOR 1.67 [95% CI, 1.32-2.12]), dexmedetomidine infusions (aOR 1.23 [95% CI, 1.04-1.44]) and propofol infusions (aOR 1.55 [95% CI, 1.08-2.23]). Conversely, decreased aOR of daily delirium screening was associated with female gender (aOR 0.78 [95% CI, 0.63-0.96]), and the administration of continuous infusions of opioids (aOR 0.75 [95% CI, 0.63-0.90]) or ketamine (aOR 0.48 [95% CI, 0.29-0.79]). Neither patient age, the presence of family or physical restraints, or benzodiazepine infusions were associated with daily delirium screening rates. CONCLUSIONS: In the 2019-2020 PICU UP! cohort, across six PICUs, delirium screening occurred on only 57% of days, despite the presence of established practices. Female gender, patients in the early stages of their PICU stay, and patients not receiving mechanical ventilation were associated with lower odds of daily delirium screening. Our results highlight the need for structured quality improvement processes to both standardize and increase the frequency of delirium screening.

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.

Bodily pain in survivors of acute respiratory distress syndrome: A 1-year longitudinal follow-up study.

PURPOSE: Acute respiratory distress syndrome (ARDS) survivors frequently experience bodily pain during recovery after the intensive care unit. Longitudinal course, risk factors and associations with physical and neuropsychological health is lacking. METHODS: We collected self-reported pain using the Short Form-36 Bodily Pain (SF-36 BP) scale, normalized for sex and age (range: 0-100; higher score = less pain), along with physical and mental health measures in a multi-center, prospective cohort of 826 ARDS survivors at 6- and 12-month follow-up. We examined baseline and ICU variables' associations with pain via separate unadjusted regression models. RESULTS: Pain prevalence (SF-36 BP ≤40) was 45% and 42% at 6 and 12 months, respectively. Among 706 patients with both 6- and 12-month data, 34% reported pain at both timepoints. Pre-ARDS employment was associated with less pain at 6-months (mean difference (standard error), 5.7 (0.9), p < 0.001) and 12-months (6.3 (0.9), p < 0.001); smoking history was associated with greater pain (-5.0 (0.9), p < 0.001, and - 5.4 (1.0), p < 0.001, respectively). In-ICU opioid use was associated with greater pain (-6.3 (2.7), p = 0.02, and - 7.3 (2.8), p = 0.01, respectively). At 6 months, 174 (22%) patients reported co-occurring pain, depression and anxiety, and 227 (33%) reported co-occurring pain and impaired physical function. CONCLUSION: Nearly half of ARDS survivors reported bodily pain at 6- and 12-month follow-up; one-third reported pain at both time points. Pre-ARDS unemployment, smoking history, and in-ICU opioid use may identify patients who report greater pain during recovery. Given its frequent co-occurrence, clinicians should manage both physical and neuropsychological issues when pain is reported.

COVID-19 survivorship: How otolaryngologist-head and neck surgeons can restore quality of life after critical illness.

Mortality from COVID-19 has obscured a subtler crisis - the swelling ranks of COVID-19 survivors. After critical illness, patients often suffer post-intensive care syndrome (PICS), which encompasses physical, cognitive, and/or mental health impairments that are often long-lasting barriers to resuming a meaningful life. Some deficits after COVID-19 critical illness will require otolaryngologic expertise for years after hospital discharge. There are roles for all subspecialties in preventing, diagnosing, or treating sequelae of COVID-19. Otolaryngologist leadership in multidisciplinary efforts ensures coordinated care. Timely tracheostomy, when indicated, may shorten the course of intensive care unit stay and thereby potentially reduce the impairments associated with PICS. Otolaryngologists can provide expertise in olfactory disorders; thrombotic sequelae of hearing loss and vertigo; and laryngotracheal injuries that impair speech, voice, swallowing, communication, and breathing. In the aftermath of severe COVID-19, otolaryngologists are poised to lead efforts in early identification and intervention for impairments affecting patients' quality of life.

Participant retention in trauma intensive care unit (ICU) follow-up studies: a post-hoc analysis of a previous scoping review.

BACKGROUND: The study aimed to synthesize participant retention-related data for longitudinal follow-up studies of survivors from trauma intensive care units (ICUs). METHODS: Within a published scoping review evaluating ICU patient outcomes after hospital discharge, two screeners independently searched for trauma ICU survivorship studies. RESULTS: There were 11 trauma ICU follow-up studies, all of which were cohort studies. Twelve months (range: 1-60 months) was the most frequent follow-up time point for assessment (63% of studies). Retention rates ranged from 54% to 94% across time points and could not be calculated for two studies (18%). Pooled retention rates at 3, 6, and 12 months were 75%, 81%, and 81%, respectively. Mean patient age (OR 0.85 per 1-year increase, 95% CI 0.73 to 0.99, p=0.036), percent of men (OR 1.07, 95% CI 1.04 to 1.10, p=0.002), and publication year (OR 0.89 per 1-year increase, 95% CI 0.82 to 0.95, p=0.007) were associated with retention rates. Early (3-month) versus later (6-month, 12-month) follow-up time point was not associated with retention rates. DISCUSSION: Pooled retention rates were >75%, at 3-month, 6-month, and 12-month time points, with wide variability across studies and time points. There was little consistency with reporting participant retention methodology and related data. More detailed reporting guidelines, with better author adherence, will help improve reporting of participant retention data. Utilization of existing research resources may help improve participant retention. LEVEL OF EVIDENCE: Level III: meta-analyses (post-hoc analyses) of a prior scoping review.

Antipsychotics for Treating Delirium in Hospitalized Adults: A Systematic Review.

Background: Delirium is common in hospitalized patients and is associated with worse outcomes. Antipsychotics are commonly used; however, the associated benefits and harms are unclear. Purpose: To conduct a systematic review evaluating the benefits and harms of antipsychotics to treat delirium in adults. Data Sources: PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception to July 2019 without language restrictions. Study Selection: Randomized controlled trials (RCTs) of antipsychotic versus placebo or another antipsychotic, and prospective observational studies reporting harms. Data Extraction: One reviewer extracted data and assessed strength of evidence (SOE) for critical outcomes, with confirmation by another reviewer. Risk of bias was assessed independently by 2 reviewers. Data Synthesis: Across 16 RCTs and 10 observational studies of hospitalized adults, there was no difference in sedation status (low and moderate SOE), delirium duration, hospital length of stay (moderate SOE), or mortality between haloperidol and second-generation antipsychotics versus placebo. There was no difference in delirium severity (moderate SOE) and cognitive functioning (low SOE) for haloperidol versus second-generation antipsychotics, with insufficient or no evidence for antipsychotics versus placebo. For direct comparisons of different second-generation antipsychotics, there was no difference in mortality and insufficient or no evidence for multiple other outcomes. There was little evidence demonstrating neurologic harms associated with short-term use of antipsychotics for treating delirium in adult inpatients, but potentially harmful cardiac effects tended to occur more frequently. Limitations: Heterogeneity was present in terms of dose and administration route of antipsychotics, outcomes, and measurement instruments. There was insufficient or no evidence regarding multiple clinically important outcomes. Conclusion: Current evidence does not support routine use of haloperidol or second-generation antipsychotics to treat delirium in adult inpatients. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).

Antipsychotics for Preventing Delirium in Hospitalized Adults: A Systematic Review.

Background: Delirium is an acute disorder marked by impairments in attention and cognition, caused by an underlying medical problem. Antipsychotics are used to prevent delirium, but their benefits and harms are unclear. Purpose: To conduct a systematic review evaluating the benefits and harms of antipsychotics for prevention of delirium in adults. Data Sources: PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception through July 2019, without restrictions based on study setting, language of publication, or length of follow-up. Study Selection: Randomized, controlled trials (RCTs) that compared an antipsychotic with placebo or another antipsychotic, and prospective observational studies with a comparison group. Data Extraction: One reviewer extracted data and graded the strength of the evidence, and a second reviewer confirmed the data. Two reviewers independently assessed the risk of bias. Data Synthesis: A total of 14 RCTs were included. There were no differences in delirium incidence or duration, hospital length of stay (high strength of evidence [SOE]), and mortality between haloperidol and placebo used for delirium prevention. Little to no evidence was found to determine the effect of haloperidol on cognitive function, delirium severity (insufficient SOE), inappropriate continuation, and sedation (insufficient SOE). There is limited evidence that second-generation antipsychotics may lower delirium incidence in the postoperative setting. There is little evidence that short-term use of antipsychotics was associated with neurologic harms. In some of the trials, potentially harmful cardiac effects occurred more frequently with antipsychotic use. Limitations: There was significant heterogeneity in antipsychotic dosing, route of antipsychotic administration, assessment of outcomes, and adverse events. There were insufficient or no data available to draw conclusions for many of the outcomes. Conclusion: Current evidence does not support routine use of haloperidol or second-generation antipsychotics for prevention of delirium. There is limited evidence that second-generation antipsychotics may lower the incidence of delirium in postoperative patients, but more research is needed. Future trials should use standardized outcome measures. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).

Screening for posttraumatic stress disorder in ARDS survivors: validation of the Impact of Event Scale-6 (IES-6).

BACKGROUND: Posttraumatic stress disorder (PTSD) symptoms are common in acute respiratory distress syndrome (ARDS) survivors. Brief screening instruments are needed for clinical and research purposes. We evaluated internal consistency, external construct, and criterion validity of the Impact of Event Scale-6 (IES-6; 6 items) compared to the original Impact of Event Scale-Revised (IES-R; 22 items) and to the Clinician Administered PTSD Scale (CAPS) reference standard evaluation in ARDS survivors. METHODS: This study is a secondary analysis from two independent multi-site, prospective studies of ARDS survivors. Measures of internal consistency, and external construct and criterion validity were evaluated. RESULTS: A total of 1001 ARDS survivors (51% female, 76% white, mean (SD) age 49 (14) years) were evaluated. The IES-6 demonstrated internal consistency over multiple time points up to 5 years after ARDS (Cronbach's alpha = 0.86 to 0.91) and high correlation with the IES-R (0.96; 95% confidence interval (CI): 0.94 to 0.97). The IES-6 demonstrated stronger correlations with related constructs (e.g., anxiety and depression; |r| = 0.32 to 0.52) and weaker correlations with unrelated constructs (e.g., physical function and healthcare utilization measures (|r| = 0.02 to 0.27). Criterion validity evaluation with the CAPS diagnosis of PTSD in a subsample of 60 participants yielded an area under receiver operating characteristic curve (95% CI) of 0.93 (0.86, 1.00), with an IES-6 cutoff score of 1.75 yielding 0.88 sensitivity and 0.85 specificity. CONCLUSIONS: The IES-6 is reliable and valid for screening for PTSD in ARDS survivors and may be useful in clinical and research settings.

Coordination of Pharyngeal and Laryngeal Swallowing Events During Single Liquid Swallows After Oral Endotracheal Intubation for Patients with Acute Respiratory Distress Syndrome.

To evaluate timing and duration differences in airway protection and esophageal opening after oral intubation and mechanical ventilation for acute respiratory distress syndrome (ARDS) survivors versus age-matched healthy volunteers. Orally intubated adult (≥ 18 years old) patients receiving mechanical ventilation for ARDS were evaluated for swallowing impairments via a videofluoroscopic swallow study (VFSS) during usual care. Exclusion criteria were tracheostomy, neurological impairment, and head and neck cancer. Previously recruited healthy volunteers (n = 56) served as age-matched controls. All subjects were evaluated using 5-ml thin liquid barium boluses. VFSS recordings were reviewed frame-by-frame for the onsets of 9 pharyngeal and laryngeal events during swallowing. Eleven patients met inclusion criteria, with a median (interquartile range [IQR]) intubation duration of 14 (9, 16) days, and VFSSs completed a median of 5 (4, 13) days post-extubation. After arrival of the bolus in the pharynx, ARDS patients achieved maximum laryngeal closure a median (IQR) of 184 (158, 351) ms later than age-matched, healthy volunteers (p < 0.001) and it took longer to achieve laryngeal closure with a median (IQR) difference of 151 (103, 217) ms (p < 0.001), although there was no significant difference in duration of laryngeal closure. Pharyngoesophageal segment opening was a median (IQR) of - 116 (- 183, 1) ms (p = 0.004) shorter than in age-matched, healthy controls. Evaluation of swallowing physiology after oral endotracheal intubation in ARDS patients demonstrates slowed pharyngeal and laryngeal swallowing timing, suggesting swallow-related muscle weakness. These findings may highlight specific areas for further evaluation and potential therapeutic intervention to reduce post-extubation aspiration.

Understanding patient outcomes after acute respiratory distress syndrome: identifying subtypes of physical, cognitive and mental health outcomes.

PURPOSE: With improving short-term mortality in acute respiratory distress syndrome (ARDS), understanding survivors' posthospitalisation outcomes is increasingly important. However, little is known regarding associations among physical, cognitive and mental health outcomes. Identification of outcome subtypes may advance understanding of post-ARDS morbidities. METHODS: We analysed baseline variables and 6-month health status for participants in the ARDS Network Long-Term Outcomes Study. After division into derivation and validation datasets, we used weighted network analysis to identify subtypes from predictors and outcomes in the derivation dataset. We then used recursive partitioning to develop a subtype classification rule and assessed adequacy of the classification rule using a kappa statistic with the validation dataset. RESULTS: Among 645 ARDS survivors, 430 were in the derivation and 215 in the validation datasets. Physical and mental health status, but not cognitive status, were closely associated. Four distinct subtypes were apparent (percentages in the derivation cohort): (1) mildly impaired physical and mental health (22% of patients), (2) moderately impaired physical and mental health (39%), (3) severely impaired physical health with moderately impaired mental health (15%) and (4) severely impaired physical and mental health (24%). The classification rule had high agreement (kappa=0.89 in validation dataset). Female Latino smokers had the poorest status, while male, non-Latino non-smokers had the best status. CONCLUSIONS: We identified four post-ARDS outcome subtypes that were predicted by sex, ethnicity, pre-ARDS smoking status and other baseline factors. These subtypes may help develop tailored rehabilitation strategies, including investigation of combined physical and mental health interventions, and distinct interventions to improve cognitive outcomes.

The intensive care delirium research agenda: a multinational, interprofessional perspective.

Delirium, a prevalent organ dysfunction in critically ill patients, is independently associated with increased morbidity. This last decade has witnessed an exponential growth in delirium research in hospitalized patients, including those critically ill, and this research has highlighted that delirium needs to be better understood mechanistically to help foster research that will ultimately lead to its prevention and treatment. In this invited, evidence-based paper, a multinational and interprofessional group of clinicians and researchers from within the fields of critical care medicine, psychiatry, pediatrics, anesthesiology, geriatrics, surgery, neurology, nursing, pharmacy, and the neurosciences sought to address five questions: (1) What is the current standard of care in managing ICU delirium? (2) What have been the major recent advances in delirium research and care? (3) What are the common delirium beliefs that have been challenged by recent trials? (4) What are the remaining areas of uncertainty in delirium research? (5) What are some of the top study areas/trials to be done in the next 10 years? Herein, we briefly review the epidemiology of delirium, the current best practices for management of critically ill patients at risk for delirium or experiencing delirium, identify recent advances in our understanding of delirium as well as gaps in knowledge, and discuss research opportunities and barriers to implementation, with the goal of promoting an integrated research agenda.

Versão brasileira da Escala de Estado Funcional em UTI: tradução e adaptação transcultural / Brazilian version of the Functional Status Score for the ICU: translation and cross-cultural adaptation

RESUMO Objetivo: Traduzir e adaptar culturalmente a Escala de Estado Funcional em UTI (FSS-ICU - Functional Status Score for the ICU) para o português do Brasil. Métodos: O presente estudo consistiu das seguintes fases: tradução (realizada por dois tradutores independentes), síntese da tradução inicial, tradução de volta ao inglês (realizada por dois tradutores independentes não familiarizados com a FSS-ICU original) e fase de teste, para avaliar a compreensão por parte da audiência alvo. Um comitê de especialistas supervisionou todas as fases e foi responsável pelos ajustes ao longo do processo e pela versão final da tradução. Resultados: A fase de testes incluiu dois fisioterapeutas experientes que avaliaram um total de 30 pacientes críticos (escore da FSS-ICU médio de 25 ± 6). Como os fisioterapeutas não relataram problemas com incertezas ou problemas de interpretação que afetassem seu desempenho, não foram feitos outros ajustes à versão em português brasileiro após a fase de teste. Obteve-se uma boa confiabilidade entre observadores para cada uma das cinco tarefas da FSS-ICU e entre os escores dos dois avaliadores (o coeficiente de correlação intraclasse variou de 0,88 a 0,91). Conclusão: A versão adaptada da FSS-ICU para o português brasileiro comprovou ser de fácil compreensão e aplicação clínica no ambiente da unidade de terapia intensiva.

ABSTRACT Objective: The aim of the present study was to translate and cross-culturally adapt the Functional Status Score for the intensive care unit (FSS-ICU) into Brazilian Portuguese. Methods: This study consisted of the following steps: translation (performed by two independent translators), synthesis of the initial translation, back-translation (by two independent translators who were unaware of the original FSS-ICU), and testing to evaluate the target audience's understanding. An Expert Committee supervised all steps and was responsible for the modifications made throughout the process and the final translated version. Results: The testing phase included two experienced physiotherapists who assessed a total of 30 critical care patients (mean FSS-ICU score = 25 ± 6). As the physiotherapists did not report any uncertainties or problems with interpretation affecting their performance, no additional adjustments were made to the Brazilian Portuguese version after the testing phase. Good interobserver reliability between the two assessors was obtained for each of the 5 FSS-ICU tasks and for the total FSS-ICU score (intraclass correlation coefficients ranged from 0.88 to 0.91). Conclusion: The adapted version of the FSS-ICU in Brazilian Portuguese was easy to understand and apply in an intensive care unit environment.

Predictors of 6-month health utility outcomes in survivors of acute respiratory distress syndrome.

BACKGROUND: With improving short-term mortality in acute respiratory distress syndrome (ARDS), understanding and improving quality of life (QOL) outcomes in ARDS survivors is a clinical and research priority. We sought to identify variables associated with QOL, as measured by the EQ-5D health utility score, after ARDS using contemporary data science methods. METHODS: Analysis of prospectively acquired baseline variables and 6-month EQ-5D health utility scores for adults with ARDS enrolled in the ARDS Network Long-Term Outcomes Study (ALTOS). Penalised regression identified predictors of health utility, with results validated using 10-fold cross-validation. RESULTS: Among 616 ARDS survivors, several predictors were associated with 6-month EQ-5D utility scores, including two lifestyle factors. Specifically, older age, female sex, Hispanic/Latino ethnicity, current smoking and higher body mass index were associated with lower EQ-5D utilities, while living at home without assistance at baseline and AIDS were associated with higher EQ-5D utilities in ARDS survivors. No acute illness variables were associated with EQ-5D utility. CONCLUSIONS: Acute illness variables do not appear to be associated with postdischarge QOL among ARDS survivors. Functional independence and lifestyle factors, such as obesity and tobacco smoking, were associated with worse QOL. Future analyses of postdischarge health utility among ARDS survivors should incorporate measures of demographics and functional independence at baseline. TRIAL REGISTRATION NUMBERS: NCT00719446 (ALTOS), NCT00434993 (ALTA), NCT00609180 (EDEN/OMEGA), and NCT00883948 (EDEN); Post-results.

Effects of neuromuscular electrical stimulation on cytokines in peripheral blood for healthy participants: a prospective, single-blinded Study.

INTRODUCTION: The effect of exercise on cytokines may improve muscle strength. Neuromuscular electrical stimulation (NMES) is a muscle-preserving therapy that benefits patients unable to participate in active exercise. How NMES alters cytokines is unclear. The aim of this study was to study the effects of 1 NMES session on cytokines associated with protein metabolism during exercise. METHODS: We evaluated the effects of NMES on IL-1, IL-6, IL-10 and TNF-α levels in peripheral blood. Participants received NMES to bilateral lower extremity muscles (quadriceps, tibialis anterior, gastrocnemius) for 30 min. Blood samples immediately pre- and post-NMES were drawn at 15-min intervals to 2-h follow-up, and the mean values of pre-NMES levels were compared to peak and trough post-NMES levels. For cytokines with significant changes, we conducted a repeated-measures linear regression analysis. We also measured post-NMES lactate and creatine kinase levels. RESULTS: We enrolled nine eligible participants. There was a significant increase in peak IL-6 from the mean pre-NMES value [0·65 (0·89) to 1·04 (0·89) pg ml-1 , P = 0·001] and a significant decrease in trough IL-1 [0·08 (0·07) to 0·02 (0·02) pg ml-1 , P = 0·041] and TNF-α [2·42 (0·54) to 2·16 (0·59) pg ml-1 , P = 0·021]. In repeated-measures regression analysis, we identified significantly higher mean IL-6 values throughout the full 120 min post-NMES period, and a significantly higher mean IL-1 value at 30 min post-NMES. There were no significant differences in peak IL-10, trough IL-6, lactate, or creatine kinase values. CONCLUSIONS: In nine healthy humans, 30 min of NMES was temporally associated with changes in cytokines similar to the effects of active exercise and may mediate NMES' observed effects on reducing muscle weakness.

Antipsychotic Medication for Prevention and Treatment of Delirium in Hospitalized Adults: A Systematic Review and Meta-Analysis.

OBJECTIVES: To evaluate the effectiveness of antipsychotic medications in preventing and treating delirium. DESIGN: Systematic review and meta-analysis. SETTING: PubMed, EMBASE, CINAHL, and ClinicalTrials.gov databases were searched from January 1, 1988, to November 26, 2013. PARTICIPANTS: Adult surgical and medical inpatients. INTERVENTION: Antipsychotic administration for delirium prevention or treatment in randomized controlled trials or cohort studies. MEASUREMENTS: Two authors independently reviewed all citations, extracted relevant data, and assessed studies for potential bias. Heterogeneity was considered as chi-square P < .1 or I(2) > 50%. Using a random-effects model (I(2) > 50%) or a fixed-effects model (I(2) < 50%), odds ratios (ORs) were calculated for dichotomous outcomes (delirium incidence and mortality), and mean or standardized mean difference for continuous outcomes (delirium duration, severity, hospital and intensive care unit (ICU) length of stay (LOS)). Sensitivity analyses included postoperative prevention studies only, exclusion of studies with high risk of bias, and typical versus atypical antipsychotics. RESULTS: Screening of 10,877 eligible records identified 19 studies. In seven studies comparing antipsychotics with placebo or no treatment for delirium prevention after surgery, there was no significant effect on delirium incidence (OR = 0.56, 95% confidence interval (CI) = 0.23-1.34, I(2) = 93%). Using data reported from all 19 studies, antipsychotic use was not associated with change in delirium duration, severity, or hospital or ICU LOS, with high heterogeneity among studies. No association with mortality was detected (OR = 0.90, 95% CI = 0.62-1.29, I(2) = 0%). CONCLUSION: Current evidence does not support the use of antipsychotics for prevention or treatment of delirium. Additional methodologically rigorous studies using standardized outcome measures are needed.

Long-Term Outcomes of Older Adults with and Without Delirium Immediately After Recovery from General Anesthesia for Surgery.

OBJECTIVE: Postoperative delirium, occurring days after surgery, is associated with both short- and long-term adverse events. Postanesthesia care unit (PACU) delirium, immediately after recovery from anesthesia, is associated with continued delirium in the succeeding days and adverse cognitive outcomes at discharge. Longer-term consequences are unclear. The objective was to evaluate 18-month outcomes of patients with versus without delirium in the PACU after surgery with general anesthesia. METHODS: In a prospective, observational, cohort study, 91 consecutive English-speaking patients, aged at least 70 years and capable of independently providing informed consent before surgery, were followed after admission for a surgical procedure in one teaching hospital. Patients completed cognitive testing before surgery. After recovery from general anesthesia, they were evaluated for a DSM-IV diagnosis of delirium. Participants or proxies were evaluated, at a median of 19 months after surgery (interquartile range: 18-20 months), for survival, cognitive and physical functioning, and healthcare utilization outcomes. RESULTS: All 91 patients or proxies (41 with delirium [45%]) were contacted at follow-up, with 7 deaths (8%) and 3 declining further participation (3%); 81 (96% of survivors) completed follow-up evaluations, demonstrating no significant cognitive or functional decline from baseline, with 75% of the cohort living independently in the community, and no differences in any outcomes between patients with versus without PACU delirium. CONCLUSION: In a small cohort of older patients evaluated 18 months after surgery, we could not detect an association of delirium diagnosed in the PACU with patient survival, cognitive/physical functioning, and healthcare utilization.

Outcomes of early delirium diagnosis after general anesthesia in the elderly.

BACKGROUND: Postoperative delirium in the elderly, measured days after surgery, is associated with significant negative clinical outcomes. In this study, we evaluated the prevalence and in-hospital outcomes of delirium diagnosed immediately after general anesthesia and surgery in elderly patients. METHODS: Consecutive English-speaking surgical candidates, aged 70 years or older, were prospectively enrolled during July to August 2010. After surgery, each participant was evaluated for a Diagnostic and Statistical Manual of Mental Disorders IV diagnosis of delirium in the postanesthesia care unit (PACU) and repeatedly thereafter while hospitalized. Delirium in the PACU was evaluated for an independent association with change in cognitive function from preoperative baseline testing and discharge disposition. RESULTS: Ninety-one (58% female) patients, 78% of whom were living independently before surgery, were found to have a prevalence of delirium in the PACU of 45% (41/91); 74% (14/19) of all delirium episodes detected during subsequent hospitalization started in the PACU. Early delirium was independently associated with impaired cognition (i.e., decreased category word fluency) relative to presurgery baseline testing (adjusted difference [95% confidence interval] for change in T-score: -6.02 [-10.58 to -1.45]; P = 0.01). Patients whose delirium had resolved by postoperative day 1 showed negative outcomes that were intermediate in severity between those who were never delirious during hospitalization and those whose delirium in the PACU persisted after transfer to hospital wards (adjusted probability [95% confidence interval] of discharge to institution: 3% [0%-10%], 26% [1%-51%], 39% [0%-81%] for the 3 groups, respectively). CONCLUSIONS: Delirium in the PACU is common, but not universal. It is associated with subsequent delirium on the ward, and potentially with a decline in cognitive function and increased institutionalization at hospital discharge.