Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses.

HIV-1-infected cells that persist despite antiretroviral therapy (ART) are frequently considered "transcriptionally silent," but active viral gene expression may occur in some cells, challenging the concept of viral latency. Applying an assay for profiling the transcriptional activity and the chromosomal locations of individual proviruses, we describe a global genomic and epigenetic map of transcriptionally active and silent proviral species and evaluate their longitudinal evolution in persons receiving suppressive ART. Using genome-wide epigenetic reference data, we show that proviral transcriptional activity is associated with activating epigenetic chromatin features in linear proximity of integration sites and in their inter- and intrachromosomal contact regions. Transcriptionally active proviruses were actively selected against during prolonged ART; however, this pattern was violated by large clones of virally infected cells that may outcompete negative selection forces through elevated intrinsic proliferative activity. Our results suggest that transcriptionally active proviruses are dynamically evolving under selection pressure by host factors.

Nurse and Social Worker Palliative Telecare Team and Quality of Life in Patients With COPD, Heart Failure, or Interstitial Lung Disease: The ADAPT Randomized Clinical Trial.

Importance: Many patients with chronic obstructive pulmonary disease (COPD), heart failure (HF), and interstitial lung disease (ILD) endure poor quality of life despite conventional therapy. Palliative care approaches may benefit this population prior to end of life. Objective: Determine the effect of a nurse and social worker palliative telecare team on quality of life in outpatients with COPD, HF, or ILD compared with usual care. Design, Setting, and Participants: Single-blind, 2-group, multisite randomized clinical trial with accrual between October 27, 2016, and April 2, 2020, in 2 Veterans Administration health care systems (Colorado and Washington), and including community-based outpatient clinics. Outpatients with COPD, HF, or ILD at high risk of hospitalization or death who reported poor quality of life participated. Intervention: The intervention involved 6 phone calls with a nurse to help with symptom management and 6 phone calls with a social worker to provide psychosocial care. The nurse and social worker met weekly with a study primary care and palliative care physician and as needed, a pulmonologist, and cardiologist. Usual care included an educational handout developed for the study that outlined self-care for COPD, ILD, or HF. Patients in both groups received care at the discretion of their clinicians, which could include care from nurses and social workers, and specialists in cardiology, pulmonology, palliative care, and mental health. Main Outcomes and Measures: The primary outcome was difference in change in quality of life from baseline to 6 months between the intervention and usual care groups (FACT-G score range, 0-100, with higher scores indicating better quality of life, clinically meaningful change ≥4 points). Secondary quality-of-life outcomes at 6 months included disease-specific health status (Clinical COPD Questionnaire; Kansas City Cardiomyopathy Questionnaire-12), depression (Patient Health Questionnaire-8) and anxiety (Generalized Anxiety Disorder-7) symptoms. Results: Among 306 randomized patients (mean [SD] age, 68.9 [7.7] years; 276 male [90.2%], 30 female [9.8%]; 245 White [80.1%]), 177 (57.8%) had COPD, 67 (21.9%) HF, 49 (16%) both COPD and HF, and 13 (4.2%) ILD. Baseline FACT-G scores were similar (intervention, 52.9; usual care, 52.7). FACT-G completion was 76% (intervention, 117 of 154; usual care, 116 of 152) at 6 months for both groups. Mean (SD) length of intervention was 115.1 (33.4) days and included a mean of 10.4 (3.3) intervention calls per patient. In the intervention group, 112 of 154 (73%) patients received the intervention as randomized. At 6 months, mean FACT-G score improved 6.0 points in the intervention group and 1.4 points in the usual care group (difference, 4.6 points [95% CI, 1.8-7.4]; P = .001; standardized mean difference, 0.41). The intervention also improved COPD health status (standardized mean difference, 0.44; P = .04), HF health status (standardized mean difference, 0.41; P = .01), depression (standardized mean difference, -0.50; P < .001), and anxiety (standardized mean difference, -0.51; P < .001) at 6 months. Conclusions and Relevance: For adults with COPD, HF, or ILD who were at high risk of death and had poor quality of life, a nurse and social worker palliative telecare team produced clinically meaningful improvements in quality of life at 6 months compared with usual care. Trial Registration: ClinicalTrials.gov Identifier: NCT02713347.

Impact of mail-based continuous positive airway pressure initiation on treatment usage and effectiveness.

PURPOSE: In-person visits with a trained therapist have been standard care for patients initiating continuous positive airway pressure (CPAP). These visits provide an opportunity for hands-on training and an in-person assessment of mask fit. However, to improve access, many health systems are shifting to remote CPAP initiation with equipment mailed to patients. While there are potential benefits of a mailed approach, relative patient outcomes are unclear. Specifically, many have concerns that a lack of in-person training may contribute to reduced CPAP adherence. To inform this knowledge gap, we aimed to compare treatment usage after in-person or mailed CPAP initiation. METHODS: Our medical center shifted from in-person to mailed CPAP dispensation in March 2020 during the COVID-19 pandemic. We assembled a cohort of patients with newly diagnosed obstructive sleep apnea (OSA) who initiated CPAP in the months before (n = 433) and after (n = 186) this shift. We compared 90-day adherence between groups. RESULTS: Mean nightly PAP usage was modest in both groups (in-person 145.2, mailed 140.6 min/night). We did not detect between-group differences in either unadjusted or adjusted analyses (adjusted difference - 0.2 min/night, 95% - 27.0 to + 26.5). CONCLUSIONS: Mail-based systems of CPAP initiation may be able to improve access without reducing CPAP usage. Future work should consider the impact of mailed CPAP on patient-reported outcomes and the impact of different remote setup strategies.

A Possible Sterilizing Cure of HIV-1 Infection Without Stem Cell Transplantation.

BACKGROUND: A sterilizing cure of HIV-1 infection has been reported in 2 persons living with HIV-1 who underwent allogeneic hematopoietic stem cell transplantations from donors who were homozygous for the CCR5Δ32 gene polymorphism. However, this has been considered elusive during natural infection. OBJECTIVE: To evaluate persistent HIV-1 reservoir cells in an elite controller with undetectable HIV-1 viremia for more than 8 years in the absence of antiretroviral therapy. DESIGN: Detailed investigation of virologic and immunologic characteristics. SETTING: Tertiary care centers in Buenos Aires, Argentina, and Boston, Massachusetts. PATIENT: A patient with HIV-1 infection and durable drug-free suppression of HIV-1 replication. MEASUREMENTS: Analysis of genome-intact and replication-competent HIV-1 using near-full-length individual proviral sequencing and viral outgrowth assays, respectively; analysis of HIV-1 plasma RNA by ultrasensitive HIV-1 viral load testing. RESULTS: No genome-intact HIV-1 proviruses were detected in analysis of a total of 1.188 billion peripheral blood mononuclear cells and 503 million mononuclear cells from placental tissues. Seven defective proviruses, some of them derived from clonally expanded cells, were detected. A viral outgrowth assay failed to retrieve replication-competent HIV-1 from 150 million resting CD4+ T cells. No HIV-1 RNA was detected in 4.5 mL of plasma. LIMITATIONS: Absence of evidence for intact HIV-1 proviruses in large numbers of cells is not evidence of absence of intact HIV-1 proviruses. A sterilizing cure of HIV-1 can never be empirically proved. CONCLUSION: Genome-intact and replication-competent HIV-1 were not detected in an elite controller despite analysis of massive numbers of cells from blood and tissues, suggesting that this patient may have naturally achieved a sterilizing cure of HIV-1 infection. These observations raise the possibility that a sterilizing cure may be an extremely rare but possible outcome of HIV-1 infection. PRIMARY FUNDING SOURCE: National Institutes of Health and Bill & Melinda Gates Foundation.

Ferroportin 3 is a dual-targeted mitochondrial/chloroplast iron exporter necessary for iron homeostasis in Arabidopsis.

Mitochondria and chloroplasts are organelles with high iron demand that are particularly susceptible to iron-induced oxidative stress. Despite the necessity of strict iron regulation in these organelles, much remains unknown about mitochondrial and chloroplast iron transport in plants. Here, we propose that Arabidopsis ferroportin 3 (FPN3) is an iron exporter that is dual-targeted to mitochondria and chloroplasts. FPN3 is expressed in shoots, regardless of iron conditions, but its transcripts accumulate under iron deficiency in roots. fpn3 mutants cannot grow as well as the wild type under iron-deficient conditions and their shoot iron levels are lower compared with the wild type. Analyses of iron homeostasis gene expression in fpn3 mutants and inductively coupled plasma mass spectrometry (ICP-MS) measurements show that iron levels in the mitochondria and chloroplasts are increased relative to the wild type, consistent with the proposed role of FPN3 as a mitochondrial/plastid iron exporter. In iron-deficient fpn3 mutants, abnormal mitochondrial ultrastructure was observed, whereas chloroplast ultrastructure was not affected, implying that FPN3 plays a critical role in the mitochondria. Overall, our study suggests that FPN3 is essential for optimal iron homeostasis.

The Effect of Mindfulness-based Programs on Cognitive Function in Adults: A Systematic Review and Meta-analysis.

Mindfulness-based programs (MBPs) are increasingly utilized to improve mental health. Interest in the putative effects of MBPs on cognitive function is also growing. This is the first meta-analysis of objective cognitive outcomes across multiple domains from randomized MBP studies of adults. Seven databases were systematically searched to January 2020. Fifty-six unique studies (n = 2,931) were included, of which 45 (n = 2,238) were synthesized using robust variance estimation meta-analysis. Meta-regression and subgroup analyses evaluated moderators. Pooling data across cognitive domains, the summary effect size for all studies favored MBPs over comparators and was small in magnitude (g = 0.15; [0.05, 0.24]). Across subgroup analyses of individual cognitive domains/subdomains, MBPs outperformed comparators for executive function (g = 0.15; [0.02, 0.27]) and working memory outcomes (g = 0.23; [0.11, 0.36]) only. Subgroup analyses identified significant effects for studies of non-clinical samples, as well as for adults aged over 60. Across all studies, MBPs outperformed inactive, but not active comparators. Limitations include the primarily unclear within-study risk of bias (only a minority of studies were considered low risk), and that statistical constraints rendered some p-values unreliable. Together, results partially corroborate the hypothesized link between mindfulness practices and cognitive performance. This review was registered with PROSPERO [CRD42018100904].

Participant Characteristics and Attendance Patterns for a Multispecialty Veterans Affairs ECHO Program 2012-2018.

Introduction: The Veteran Integrated Service Network (VISN) 20 Veterans Affairs-Extension for Community Healthcare Outcomes (VA-ECHO) program connects specialty and primary care providers (PCPs) across large geographic areas, utilizing video-teleconferencing with the intention of increasing access to care among underserved and isolated populations. No previously published work describes participation patterns of a multispecialty ECHO program. We describe the development of VISN 20 VA-ECHO program to inform the design and evaluation of ECHO programs. Methods: The participant cohort included VA-affiliated licensed health care professionals, including trainees, who attended at least one VISN 20 VA-ECHO session between April 2012 and December 2018. Participant characteristics reported include gender, clinical location, clinical specialty, discipline, and rurality. Results: Over the 6-year time frame, VISN 20 VA-ECHO offered 945 sessions in 14 clinical specialties and recorded 17,893 hours of attendance. The cohort included 1,346 participants, 74.3% of whom were female, 85.2% employed in medical centers, and 40.7% affiliated with primary care. Most participants (62.3%) attended one specialty exclusively; among all participants, 40% attended five or more sessions. Discussion: Although VA-ECHO was implemented to develop single specialty expertise among PCPs, our participant cohort represented a more diverse audience from a range of disciplines and specialties. Our experience may be valuable to other teams implementing ECHO programs. Conclusions: Through adaptability and strategies that actively promoted inclusion of a diverse audience, VISN 20 VA-ECHO expanded to include multiple clinical specialties and successfully engaged an audience across a large geographic area and beyond PCPs.

Practical implementation of noninvasive ventilation in Amyotrophic Lateral Sclerosis: lessons learned from a clinical case series.

PURPOSE: Noninvasive ventilation (NIV) may improve survival and quality of life in Amyotrophic Lateral Sclerosis (ALS) patients. There is a surprising paucity of practical guidelines for office-based implementation and management of NIV outside of tertiary ALS centers. We saw the need for a clinical protocol to allow feasible and consistent NIV management in this patient population. METHODS: We created a clinical protocol for office-based initiation of NIV implemented on consecutive ALS patients referred from our regional ALS multidisciplinary clinic. The protocol provided initial empiric settings using a bilevel device in volume-assured pressure support mode. A respiratory therapist (RT) initiated NIV in an office setting and made adjustments according to patient tolerance and therapy targets outlined in the protocol. Later setting changes were performed at patient or provider request. We evaluated patient adherence and efficacy via device download at 30 days and 1 year. RESULTS: We present data from a case series of the first 14 consecutive patients initiated on NIV over a 20-month period. Our protocol underwent iterative modification based on clinical experience and patient feedback. Early challenges included the significant time and resource burden required to coordinate device downloads and patient follow-up. Early 30-day NIV adherence was variable (median 20 out of 30 days), while 1-year NIV adherence was excellent (median 27.5 out of 30 days). CONCLUSIONS: Our RT-driven clinical NIV protocol was feasible but labor intensive. Achieving real-world adherence of NIV in our ALS patients required iterative protocol adjustment, significant RT provider time, and tele-based follow-up.

Unpacking the lunchbox: biopedagogies, mothering and social class.

This study investigates how mothers respond to school surveillance of their children's packed lunches. In a context where increasing attention is focused on healthy eating, we adopt a biopedagogical approach to illustrate different positions and strategies which mothers occupy in relation to feeding their children in the school setting. We use photo-elicitation interviews and focus groups to trace both the discursive and practical significance of these biopedagogies. We find that the subjective experiences of feeding children at school are infused with classed notions of mothering in public. Our analysis highlights two broad positions. Firstly, there were those with strong distinctions between home-food and school-food, which was associated more clearly with middle class families. Secondly, there were those with more fluid boundaries between home-food and school-food. This was more commonly encapsulated by working class mothers who were seen to place more emphasis on their children as autonomous decision-makers. Overall the findings document localised and classed practices of resisting the school's normalising gaze.

Maternal pre-gravid obesity and early childhood respiratory hospitalization: a population-based case-control study.

Inflammation in utero is linked to childhood respiratory and infectious complications. Obesity is an increasingly common chronic inflammatory state, yet little is known about its role in childhood respiratory illness. We sought to examine the association between maternal pre-gravid BMI and early childhood respiratory hospitalization. We conducted a population-based case-control study using the Washington State Comprehensive Hospital Abstract Reporting System and linked birth certificate data. Cases were children age 0-5 years, born in Washington state, with a respiratory hospitalization between 2003 and 2008. We identified 15,318 cases, frequency matching each case to two controls by birth year (total 31,060 controls). We used logistic regression to estimate the risk (approximated by odds ratios) of early childhood respiratory hospitalization according to maternal pre-gravid body mass index (BMI) category (underweight, normal, overweight, obese), after adjustment for maternal and infant characteristics. An elevated maternal pre-gravid BMI was associated with increased risk of childhood respiratory hospitalization, with an adjusted odds ratio OR [95 % CI] = 1.08 [1.03-1.14] for overweight mothers (BMI 25-29.9 kg/m(2)), and OR = 1.29 [1.22-1.36] for obese mothers (BMI ≥ 30 kg/m(2)). An elevated maternal pre-gravid BMI was associated with higher risk of early childhood respiratory hospitalization. Childhood respiratory illness may be an important complication of excess maternal weight that should be shared with expectant mothers.

Utilizing the RE-AIM framework for a multispecialty Veterans Affairs Extension for Community Healthcare Outcomes (VA-ECHO) program 2018-2022.

VA-ECHO (Veterans Affairs -Extension for Community Healthcare Outcomes) provides live, synchronous, continuing education accredited, case-based learning. Sessions deliver up-to-date, evidence-based, practice-relevant, Veteran-focused learning to healthcare team members. The primary goal of VA-ECHO is to increase Veterans' access to high quality care by improving knowledge and skills among VA care providers. Utilizing the RE-AIM framework, descriptive statistics for 23 VA-ECHO programs regarding program effectiveness, adoption, implementation, and maintenance during a five-year period (2018-2022) are reported. VA-ECHO offered 1,462 sessions and 157,238 contact hours, engaging 17,642 participants from 837 VA-based sites (20% rural-based sites). Effectiveness includes information on number and diversity of programs, as well as reported impact on participants' practice. Adoption includes descriptive statistics, including comparison of growth and change compared to prior years. Implementation describes change in the program over time, including the number of specialties offered, and types of continuing education offered. Maintenance includes a narrative regarding sustainability. The discussion focuses on implementation and maintenance strategies the program has used to address participant and VA needs within the RE-AIM framework, including adjustments to the program, iterative qualitative improvement, sustainment strategies, and opportunities for future evaluation.

Rest-Activity Rhythm Fragmentation and Weaker Circadian Strength Are Associated With Cognitive Impairment in Survivors of Acute Respiratory Failure.

Background: Survivors of acute respiratory failure (ARF) experience long-term cognitive impairment and circadian rhythm disturbance after hospital discharge. Although prior studies in aging and neurodegenerative diseases indicate actigraphy-estimated rest-activity circadian rhythm disturbances are risk factors for cognitive impairment, it is unclear if this applies to ARF survivors. This study explored the relationships of actigraphy-estimated rest-activity circadian rhythms with cognitive functioning in ARF survivors at 3 months after discharge. Methods: 13 ARF survivors (mean age 51 years and 69% males) completed actigraphy and sleep diaries for 9 days, followed by at-home neuropsychological assessment. Principal component factor analysis created global cognition and circadian rhythm variables, and these first components were used to examine the global relationships between circadian rhythm and cognitive measure scores. Results: Global circadian function was associated with global cognition function in ARF survivors (r = .70, p = .024) after adjusting for age, education, and premorbid cognition. Also, greater fragmented rest-activity circadian rhythm (estimated by intradaily variability, r = .85, p = .002), and weaker circadian strength (estimated by amplitude, r = .66, p = .039; relative strength, r = .70, p = .024; 24-h lag serial autocorrelation, r = .67, p = .035), were associated with global cognition and individual cognitive tests. Conclusions: These results suggest circadian rhythm disturbance is associated with poorer global cognition in ARF survivors. Future prospective research with larger samples is needed to confirm these results and increase understanding of the relationship between disrupted circadian rhythms and cognitive impairment among ARF survivors.

Improving adherence to PAP therapy: A brief PAP coaching intervention for health care providers.

Objectives: To evaluate a training program for non-specialist health care providers in a brief coaching intervention to improve positive airway pressure (PAP) usage in Veterans with sleep apnea. Methods: We conducted a national webinar training designed for non-specialist providers to implement a brief telephone coaching intervention to improve PAP adherence. The curriculum was crafted by experts in sleep medicine and behavioral sleep medicine based on principles of PAP desensitization. Providers who participated in this training were asked to complete evaluations at 30 days and 1 year. Results: Provider surveys indicated that most respondents had incorporated the intervention into their clinical practice and felt comfortable counseling patients about sleep apnea and adherence to PAP. Provider feedback suggested that future training programs should include refresher trainings, more training on PAP equipment specifics, and facilitated collaboration with local sleep medicine staff. Conclusions: This pilot training program demonstrated that a webinar format was a feasible method to increase training in PAP adherence among non-specialist health care providers. Innovation: Non-specialists can be trained as PAP coaches in webinar format, improving patients' access to effective strategies and support to be successful with PAP therapy.

A Retrospective Pilot Study of Imagery Rehearsal Therapy Enhanced with Narrative Therapy Principles for the Treatment of Nightmares in US Military Veterans.

Introduction Chronic nightmares are a common and disabling feature of posttraumatic stress disorder (PTSD) for which broadly effective treatments are still lacking. While imagery rehearsal therapy (IRT) demonstrates benefits for patients with idiopathic nightmares and some patients with PTSD-related nightmares, research indicates it may be less beneficial for veterans. Narrative therapy (NT) is a form of psychotherapy which is client-centered and value-focused and has demonstrated benefits for PTSD patients. The application of NT principles to IRT may provide a valuable therapeutic approach for treatment in veterans. Objective To perform a retrospective chart review of veteran clients participating in a novel, brief intervention developed by the first author consisting of IRT enhanced with NT principles (N-IRT) for the treatment of nightmares. The primary outcomes were nightmare frequency and intensity, and the secondary outcome was the impact of the intervention on nightmare distress and coping, subjective sleep quality, and overall PTSD symptoms. Materials and Methods We conducted retrospective chart reviews for eight veterans referred to the first author for the treatment of nightmares, who completed N-IRT, including baseline and end-of-treatment measures. The protocol involved a single 60-minute NT-enhanced rescripting session and assigned homework to rehearse the revised dream script, and a follow-up evaluation 4 weeks later. The subjects completed a sleep and nightmare interview developed by the first author and the PTSD Checklist at baseline and after the intervention at the follow-up evaluation. Paired t -tests were conducted to test for pre-to-post differences. Results In the statistical analysis, we observed a statistically significant and clinically meaningful reduction in the frequency ( p = 0.04) and intensity of nightmares ( p = 0.001) from pretreatment to the 1-month follow-up. Measures of nightmare-associated emotional distress, the ability to cope with nightmares, sleep duration and sleep efficiency, as well as overall PTSD symptoms also demonstrated significant improvements. Conclusion These pilot data provide compelling preliminary evidence that a single-session IRT intervention modified with NT (N-IRT) is effective in reducing nightmare frequency and intensity, reducing nightmare distress, improving the act of coping with nightmares, and improving sleep quality and overall PTSD symptoms in veterans. Further investigation of this method with gold-standard clinical trial designs and larger sample sizes is indicated to confirm effectiveness and to better understand the possible mechanisms of treatment effect.

Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy.

HIV-1 establishes a life-long reservoir of virally infected cells which cannot be eliminated by antiretroviral therapy (ART). Here, we demonstrate a markedly altered viral reservoir profile of long-term ART-treated individuals, characterized by large clones of intact proviruses preferentially integrated in heterochromatin locations, most prominently in centromeric satellite/micro-satellite DNA. Longitudinal evaluations suggested that this specific reservoir configuration results from selection processes that promote the persistence of intact proviruses in repressive chromatin positions, while proviruses in permissive chromosomal locations are more likely to be eliminated. A bias toward chromosomal integration sites in heterochromatin locations was also observed for intact proviruses in study participants who maintained viral control after discontinuation of antiretroviral therapy. Together, these results raise the possibility that antiviral selection mechanisms during long-term ART may induce an HIV-1 reservoir structure with features of deep latency and, possibly, more limited abilities to drive rebound viremia upon treatment interruptions.

Lymph node dendritic cells harbor inducible replication-competent HIV despite years of suppressive ART.

Although gut and lymph node (LN) memory CD4 T cells represent major HIV and simian immunodeficiency virus (SIV) tissue reservoirs, the study of the role of dendritic cells (DCs) in HIV persistence has long been limited to the blood due to difficulties to access lymphoid tissue samples. In this study, we show that LN migratory and resident DC subpopulations harbor distinct phenotypic and transcriptomic profiles. Interestingly, both LN DC subpopulations contain HIV intact provirus and inducible replication-competent HIV despite the expression of the antiviral restriction factor SAMHD1. Notably, LN DC subpopulations isolated from HIV-infected individuals treated for up to 14 years are transcriptionally silent but harbor replication-competent virus that can be induced upon TLR7/8 stimulation. Taken together, these results uncover a potential important contribution of LN DCs to HIV infection in the presence of ART.

Racial Disparity in Oxygen Saturation Measurements by Pulse Oximetry: Evidence and Implications.

The pulse oximeter is a ubiquitous clinical tool used to estimate blood oxygen concentrations. However, decreased accuracy of pulse oximetry in patients with dark skin tones has been demonstrated since as early as 1985. Most commonly, pulse oximeters may overestimate the true oxygen saturation in individuals with dark skin tones, leading to higher rates of occult hypoxemia (i.e., clinically unrecognized low blood oxygen saturation). Overestimation of oxygen saturation in patients with dark skin tones has serious clinical implications, as these patients may receive insufficiently rigorous medical care when pulse oximeter measurements suggest that their oxygen saturation is higher than the true value. Recent studies have linked pulse oximeter inaccuracy to worse clinical outcomes, suggesting that pulse oximeter inaccuracy contributes to known racial health disparities. The magnitude of device inaccuracy varies by pulse oximeter manufacturer, sensor type, and arterial oxygen saturation. The underlying reasons for decreased pulse oximeter accuracy for individuals with dark skin tones may be related to failure to control for increased absorption of red light by melanin during device development and insufficient inclusion of individuals with dark skin tones during device calibration. Inadequate regulatory standards for device approval may also play a role in decreased accuracy. Awareness of potential pulse oximeter limitations is an important step for providers and may encourage the consideration of additional clinical information for management decisions. Ultimately, stricter regulatory requirements for oximeter approval and increased manufacturer transparency regarding device performance are required to mitigate this racial bias.

Red blood cell transfusion and outcomes in patients with acute lung injury, sepsis and shock.

INTRODUCTION: In this study, we sought to determine the association between red blood cell (RBC) transfusion and outcomes in patients with acute lung injury (ALI), sepsis and shock. METHODS: We performed a secondary analysis of new-onset ALI patients enrolled in the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial (2000 to 2005) who had a documented ALI risk factor of sepsis or pneumonia and met shock criteria (mean arterial pressure (MAP) < 60 mmHg or vasopressor use) within 24 hours of randomization. Using multivariable logistic regression, we examined the association between RBC transfusion and 28-day mortality after adjustment for age, sex, race, randomization arm and Acute Physiology and Chronic Health Evaluation III score. Secondary end points included 90-day mortality and ventilator-free days (VFDs). Finally, we examined these end points among the subset of subjects meeting prespecified transfusion criteria defined by five simultaneous indicators: hemoglobin < 10.2 g/dL, central or mixed venous oxygen saturation < 70%, central venous pressure ≥ 8 mmHg, MAP ≥ 65 mmHg, and vasopressor use. RESULTS: We identified 285 subjects with ALI, sepsis, shock and transfusion data. Of these, 85 also met the above prespecified transfusion criteria. Fifty-three (19%) of the two hundred eighty-five subjects with shock and twenty (24%) of the subset meeting the transfusion criteria received RBC transfusion within twenty-four hours of randomization. We found no independent association between RBC transfusion and 28-day mortality (odds ratio = 1.49, 95% CI (95% confidence interval) = 0.77 to 2.90; P = 0.23) or VFDs (mean difference = -0.35, 95% CI = -4.03 to 3.32; P = 0.85). Likewise, 90-day mortality and VFDs did not differ by transfusion status. Among the subset of patients meeting the transfusion criteria, we found no independent association between transfusion and mortality or VFDs. CONCLUSIONS: In patients with new-onset ALI, sepsis and shock, we found no independent association between RBC transfusion and mortality or VFDs. The physiological criteria did not identify patients more likely to be transfused or to benefit from transfusion.