Opioid Administration Practice Patterns in Patients With Acute Respiratory Failure Who Undergo Invasive Mechanical Ventilation.

IMPORTANCE: The opioid crisis is impacting people across the country and deserves attention to be able to curb the rise in opioid-related deaths. OBJECTIVES: To evaluate practice patterns in opioid infusion administration and dosing for patients with acute respiratory failure receiving invasive mechanical ventilation. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Patients from 21 hospitals in Kaiser Permanente Northern California and 96 hospitals in Philips electronic ICU Research Institute. MAIN OUTCOMES AND MEASURES: We assessed whether patients received opioid infusion and the dose of said opioid infusion. RESULTS: We identified patients with a diagnosis of acute respiratory failure who were initiated on invasive mechanical ventilation. From each patient, we determined if opioid infusions were administered and, among those who received an opioid infusion, the median daily dose of fentanyl infusion. We used hierarchical regression models to quantify variation in opioid infusion use and the median daily dose of fentanyl equivalents across hospitals. We included 13,140 patients in the KPNC cohort and 52,033 patients in the eRI cohort. A total of 7,023 (53.4%) and 16,311 (31.1%) patients received an opioid infusion in the first 21 days of mechanical ventilation in the KPNC and eRI cohorts, respectively. After accounting for patient- and hospital-level fixed effects, the hospital that a patient was admitted to explained 7% (95% CI, 3-11%) and 39% (95% CI, 28-49%) of the variation in opioid infusion use in the KPNC and eRI cohorts, respectively. Among patients who received an opioid infusion, the median daily fentanyl equivalent dose was 692 µg (interquartile range [IQR], 129-1341 µg) in the KPNC cohort and 200 µg (IQR, 0-1050 µg) in the eRI cohort. Hospital explained 4% (95% CI, 1-7%) and 20% (95% CI, 15-26%) of the variation in median daily fentanyl equivalent dose in the KPNC and eRI cohorts, respectively. CONCLUSIONS AND RELEVANCE: In the context of efforts to limit healthcare-associated opioid exposure, our findings highlight the considerable opioid exposure that accompanies mechanical ventilation and suggest potential under and over-treatment with analgesia. Our results facilitate benchmarking of hospitals' analgesia practices against risk-adjusted averages and can be used to inform usual care control arms of analgesia and sedation clinical trials.

Intravenous Opioid Administration During Mechanical Ventilation and Use After Hospital Discharge.

Importance: Guidelines recommend an analgesia-first strategy for sedation during mechanical ventilation, but associations between opioids provided during mechanical ventilation and posthospitalization opioid-related outcomes are unclear. Objective: To evaluate associations between an intravenous opioid dose received during mechanical ventilation and postdischarge opioid-related outcomes in medical (nonsurgical) patients. Design, Setting, and Participants: This retrospective cohort study evaluated adults receiving mechanical ventilation lasting 24 hours or more for acute respiratory failure and surviving hospitalization. Participants from 21 Kaiser Permanente Northern California hospitals from January 1, 2012, to December 31, 2019, were included. Data were analyzed from October 1, 2020, to October 31, 2023. Exposures: Terciles of median daily intravenous fentanyl equivalents during mechanical ventilation. Main Outcomes and Measures: The primary outcome was the first filled opioid prescription in 1 year after discharge. Secondary outcomes included persistent opioid use and opioid-associated complications. Secondary analyses tested for interaction between opioid doses during mechanical ventilation, prior opioid use, and posthospitalization opioid use. Estimates were based on multivariable-adjusted time-to-event analyses, with death as a competing risk, and censored for hospice or palliative care referral, rehospitalization with receipt of opioid, or loss of Kaiser Permanente plan membership. Results: The study included 6746 patients across 21 hospitals (median age, 67 years [IQR, 57-76 years]; 53.0% male). Of the participants, 3114 (46.2%) filled an opioid prescription in the year prior to admission. The median daily fentanyl equivalent during mechanical ventilation was 200 µg (IQR, 40-1000 µg), with terciles of 0 to 67 µg, more than 67 to 700 µg, and more than 700 µg. Compared with patients who did not receive opioids during mechanical ventilation (n = 1013), a higher daily opioid dose was associated with opioid prescriptions in the year after discharge (n = 2942 outcomes; tercile 1: adjusted hazard ratio [AHR], 1.00 [95% CI, 0.85-1.17], tercile 2: AHR, 1.20 [95% CI, 1.03-1.40], and tercile 3: AHR, 1.25 [95% CI, 1.07-1.47]). Higher doses of opioids during mechanical ventilation were also associated with persistent opioid use after hospitalization (n = 1410 outcomes; tercile 3 vs no opioids: odds ratio, 1.44 [95% CI, 1.14-1.83]). No interaction was observed between opioid dose during mechanical ventilation, prior opioid use, and posthospitalization opioid use. Conclusions and Relevance: In this retrospective cohort study of patients receiving mechanical ventilation, opioids administered during mechanical ventilation were associated with opioid prescriptions following hospital discharge. Additional studies to evaluate risks and benefits of strategies using lower opioid doses are warranted.

Evaluation of an outreach programme for patients with COVID-19 in an integrated healthcare delivery system: a retrospective cohort study.

OBJECTIVES: In the first year of the COVID-19 pandemic, health systems implemented programmes to manage outpatients with COVID-19. The goal was to expedite patients' referral to acute care and prevent overcrowding of medical centres. We sought to evaluate the impact of such a programme, the COVID-19 Home Care Team (CHCT) programme. DESIGN: Retrospective cohort. SETTING: Kaiser Permanente Northern California. PARTICIPANTS: Adult members before COVID-19 vaccine availability (1 February 2020-31 January 2021) with positive SARS-CoV-2 tests. INTERVENTION: Virtual programme to track and treat patients with 'CHCT programme'. OUTCOMES: The outcomes were (1) COVID-19-related emergency department visit, (2) COVID-19-related hospitalisation and (3) inpatient mortality or 30-day hospice referral. MEASURES: We estimated the average effect comparing patients who were and were not treated by CHCT. We estimated propensity scores using an ensemble super learner (random forest, XGBoost, generalised additive model and multivariate adaptive regression splines) and augmented inverse probability weighting. RESULTS: There were 98 585 patients with COVID-19. The majority were followed by CHCT (n=80 067, 81.2%). Patients followed by CHCT were older (mean age 43.9 vs 41.6 years, p<0.001) and more comorbid with COmorbidity Point Score, V.2, score ≥65 (1.7% vs 1.1%, p<0.001). Unadjusted analyses showed more COVID-19-related emergency department visits (9.5% vs 8.5%, p<0.001) and hospitalisations (3.9% vs 3.2%, p<0.001) in patients followed by CHCT but lower inpatient death or 30-day hospice referral (0.3% vs 0.5%, p<0.001). After weighting, there were higher rates of COVID-19-related emergency department visits (estimated intervention effect -0.8%, 95% CI -1.4% to -0.3%) and hospitalisation (-0.5%, 95% CI -0.9% to -0.1%) but lower inpatient mortality or 30-day hospice referral (-0.5%, 95% CI -0.7% to -0.3%) in patients followed by CHCT. CONCLUSIONS: Despite CHCT following older patients with higher comorbidity burden, there appeared to be a protective effect. Patients followed by CHCT were more likely to present to acute care and less likely to die inpatient.

AP-2α/AP-2ß Transcription Factors Are Key Regulators of Epidermal Homeostasis.

AP-2 transcription factors regulate ectodermal development, but their roles in epidermal homeostasis in adult skin are unknown. We find that AP-2α is the predominant AP-2 family member in adult epidermis, followed by AP-2ß. Through inactivation of AP-2α, AP-2ß, or both in keratinocytes, we assessed the effects of a gradient of epidermal AP-2 activity on skin function. We find that (i) loss of AP-2ß in keratinocytes is compensated for by AP-2α, (ii) loss of AP-2α impairs terminal keratinocyte differentiation and hair morphogenesis, and (iii) the combined loss of AP-2α/AP-2ß results in more severe skin and hair abnormalities. Keratinocyte differentiation defects precede progressive neutrophilic skin inflammation. Inducible inactivation of AP-2α/AP-2ß in the adult phenocopies these manifestations. Transcriptomic analyses of epidermis lacking AP-2α or AP-2α/AP-2ß in keratinocytes demonstrate a terminal keratinocyte differentiation defect with upregulation of alarmin keratins and of several immune pathway regulators. Moreover, our analyses suggest a key role of reduced AP-2α-dependent gene expression of CXCL14 and the keratin 15 gene K15 as an early pathogenic event toward the manifestation of skin inflammation. Thus, AP-2α and AP-2ß are critical regulators of epidermal homeostasis in adult skin.

KCTD1/KCTD15 complexes control ectodermal and neural crest cell functions, and their impairment causes aplasia cutis.

Aplasia cutis congenita (ACC) is a congenital epidermal defect of the midline scalp and has been proposed to be due to a primary keratinocyte abnormality. Why it forms mainly at this anatomic site has remained a long-standing enigma. KCTD1 mutations cause ACC, ectodermal abnormalities, and kidney fibrosis, whereas KCTD15 mutations cause ACC and cardiac outflow tract abnormalities. Here, we found that KCTD1 and KCTD15 can form multimeric complexes and can compensate for each other's loss and that disease mutations are dominant negative, resulting in lack of KCTD1/KCTD15 function. We demonstrated that KCTD15 is critical for cardiac outflow tract development, whereas KCTD1 regulates distal nephron function. Combined inactivation of KCTD1/KCTD15 in keratinocytes resulted in abnormal skin appendages but not in ACC. Instead, KCTD1/KCTD15 inactivation in neural crest cells resulted in ACC linked to midline skull defects, demonstrating that ACC is not caused by a primary defect in keratinocytes but is a secondary consequence of impaired cranial neural crest cells, giving rise to midline cranial suture cells that express keratinocyte-promoting growth factors. Our findings explain the clinical observations in patients with KCTD1 versus KCTD15 mutations, establish KCTD1/KCTD15 complexes as critical regulators of ectodermal and neural crest cell functions, and define ACC as a neurocristopathy.

AP-2α/AP-2ß transcription factors are key regulators of epidermal homeostasis.

AP-2 transcription factors regulate ectodermal development but their roles for epidermal homeostasis in the adult skin are unknown. We find that AP-2α is the predominant AP-2 family member in adult epidermis, followed by AP-2ß. Through inactivation of AP-2α, AP-2ß, or both in keratinocytes we assessed the effects of a gradient of epidermal AP-2 activity on skin function. We find that (1) loss of AP-2ß in keratinocytes is compensated for by AP-2α, (2) loss of AP-2α impairs terminal keratinocyte differentiation and hair morphogenesis, and (3) the combined loss of AP-2α/AP-2ß results in more severe skin and hair abnormalities. Keratinocyte differentiation defects precede a progressive neutrophilic skin inflammation. Inducible inactivation of AP-2α/AP-2ß in the adult phenocopies these manifestations. Transcriptomic analyses of epidermis lacking AP-2α or AP-2α/AP-2ß in keratinocytes demonstrate a terminal keratinocyte differentiation defect with upregulation of alarmin keratins and of several immune pathway regulators. Moreover, our analyses suggest a key role of loss of AP-2α-dependent gene expression of CXCL14 and KRT15 as an early pathogenic event towards the manifestation of skin inflammation. Thus, AP-2α/AP-2ß are critical regulators of epidermal homeostasis in the adult skin.

Trends in Outpatient Visits and Hospital and Intensive Care Unit Admissions of Adults With COVID-19 in an Integrated US Health Care System, March 2020 to January 2022.

This cohort study of patients at a single integrated health system examines trends in COVID-19­related treatment location and mortality.

Characterization and Genome Sequence of Arthrobacter Phage Iter.

Arthrobacter phage Iter was isolated in North Georgia. Its genome is 43,963 bp with 70 open reading frames (ORFs) and a GC content of 67.4%. It shares 89.11% nucleotide identity with Arthrobacter phage Phives. Actinobacteriophages that share over 50% nucleotide identity are sorted into clusters, with Iter in cluster AZ.

A randomised controlled trial of non-invasive ventilation compared with extracorporeal carbon dioxide removal for acute hypercapnic exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Patients presenting with acute hypercapnic respiratory failure due to exacerbations of chronic obstructive pulmonary disease (AECOPD) are typically managed with non-invasive ventilation (NIV). The impact of low-flow extracorporeal carbon dioxide removal (ECCO2R) on outcome in these patients has not been explored in randomised trials. METHODS: Open-label randomised trial comparing NIV (NIV arm) with ECCO2R (ECCO2R arm) in patients with AECOPD at high risk of NIV failure (pH < 7.30 after ≥ 1 h of NIV). The primary endpoint was time to cessation of NIV. Secondary outcomes included device tolerance and complications, changes in arterial blood gases, hospital survival. RESULTS: Eighteen patients (median age 67.5, IQR (61.5-71) years; median GOLD stage 3 were enrolled (nine in each arm). Time to NIV discontinuation was shorter with ECCO2R (7:00 (6:18-8:30) vs 24:30 (18:15-49:45) h, p = 0.004). Arterial pH was higher with ECCO2R at 4 h post-randomisation (7.35 (7.31-7.37) vs 7.25 (7.21-7.26), p < 0.001). Partial pressure of arterial CO2 (PaCO2) was significantly lower with ECCO2R at 4 h (6.8 (6.2-7.15) vs 8.3 (7.74-9.3) kPa; p = 0.024). Dyspnoea and comfort both rapidly improved with commencement of ECCO2R. There were no severe or life-threatening complications in the study population. There were no episodes of major bleeding or red blood cell transfusion in either group. ICU and hospital length of stay were longer with ECCO2R, and there was no difference in 90-day mortality or functional outcomes at follow-up. INTERPRETATION: There is evidence of benefit associated with ECCO2R with time to improvement in respiratory acidosis, in respiratory physiology and an immediate improvement in patient comfort and dyspnoea with commencement of ECCO2R. In addition, there was minimal clinically significant adverse events associated with ECCO2R use in patients with AECOPD at risk of failing or not tolerating NIV. However, the ICU and hospital lengths of stay were longer in the ECCO2R for similar outcomes. Trial registration The trial is prospectively registered on ClinicalTrials.gov: NCT02086084. Registered on 13th March 2014, https://clinicaltrials.gov/ct2/show/NCT02086084?cond=ecco2r&draw=2&rank=8.

A survey on the practices and capabilities in the management of respiratory failure in South East England.

INTRODUCTION: The variability of acute respiratory distress syndrome management may affect the referral practice to severe respiratory failure centres. We described the management of acute respiratory distress syndrome in our catchment area. METHODS: An electronic survey was administered to 42 intensive care units in South-East England. RESULTS: Response rate was 71.4%. High-flow nasal oxygen and non-invasive ventilation were used 'often' in moderate-acute respiratory distress syndrome by 46.7% and 60%. During invasive ventilation, 90% preferred pressure control, targeting tidal volumes of 6-8 ml/kg (53.3%) or 4-6 ml/kg (46.7%). Positive end-expiratory pressure was selected by positive end-expiratory pressure/inspiratory fraction of oxygen tables (50%) or decremental positive end-expiratory pressure trials (20%). Neuro-muscular blockers were widely used, although routinely by only 3.3%. High-frequency oscillatory ventilation (10%) and inhaled nitric oxide (13.3%) were rarely used. None used oesophageal manometry. Recruitment manoeuvres were used 'often' by 26.7%. Equipment (90%) and protocols (80%) for prone position were common, with sessions mostly lasting 12-18 h. CONCLUSIONS: Although variable, practice well reflected the available evidence. Proning was widely practiced with good availability of educational resources and protocolised care.

Physiological Basis of Extracorporeal Membrane Oxygenation and Extracorporeal Carbon Dioxide Removal in Respiratory Failure.

Extracorporeal life support (ECLS) for severe respiratory failure has seen an exponential growth in recent years. Extracorporeal membrane oxygenation (ECMO) and extracorporeal CO2 removal (ECCO2R) represent two modalities that can provide full or partial support of the native lung function, when mechanical ventilation is either unable to achieve sufficient gas exchange to meet metabolic demands, or when its intensity is considered injurious. While the use of ECMO has defined indications in clinical practice, ECCO2R remains a promising technique, whose safety and efficacy are still being investigated. Understanding the physiological principles of gas exchange during respiratory ECLS and the interactions with native gas exchange and haemodynamics are essential for the safe applications of these techniques in clinical practice. In this review, we will present the physiological basis of gas exchange in ECMO and ECCO2R, and the implications of their interaction with native lung function. We will also discuss the rationale for their use in clinical practice, their current advances, and future directions.

Otitis media susceptibility and shifts in the head and neck microbiome due to SPINK5 variants.

BACKGROUND: Otitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility. METHODS: We performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues. RESULTS: A large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare A2ML1 variants, a common FUT2 variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within SPINK5 (LOD=4.09). Carriage of the SPINK5 missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the outer ear and oral cavity but not the nasopharynx. Eight additional novel SPINK5 variants were identified in 12 families and individuals with OM. A role for SPINK5 in OM susceptibility is further supported by lower RNA counts in variant carriers, strong SPINK5 localisation in outer ear skin, faint localisation to middle ear mucosa and eardrum and increased SPINK5 expression in human cholesteatoma. CONCLUSION: SPINK5 variants confer susceptibility to non-syndromic OM. These variants potentially contribute to middle ear pathology through breakdown of mucosal and epithelial barriers, immunodeficiency such as poor vaccination response, alteration of head and neck microbiota and facilitation of entry of opportunistic pathogens into the middle ear.

Multi-omic studies on missense PLG variants in families with otitis media.

Otitis media (OM), a very common disease in young children, can result in hearing loss. In order to potentially replicate previously reported associations between OM and PLG, exome and Sanger sequencing, RNA-sequencing of saliva and middle ear samples, 16S rRNA sequencing, molecular modeling, and statistical analyses including transmission disequilibrium tests (TDT) were performed in a multi-ethnic cohort of 718 families and simplex cases with OM. We identified four rare PLG variants c.112A > G (p.Lys38Glu), c.782G > A (p.Arg261His), c.1481C > T (p.Ala494Val) and c.2045 T > A (p.Ile682Asn), and one common variant c.1414G > A (p.Asp472Asn). However TDT analyses for these PLG variants did not demonstrate association with OM in 314 families. Additionally PLG expression is very low or absent in normal or diseased middle ear in mouse and human, and salivary expression and microbial α-diversity were non-significant in c.1414G > A (p.Asp472Asn) carriers. Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and c.2045 T > A (p.Ile682Asn) were predicted to affect protein structure. Exploration of other potential disease mechanisms will help elucidate how PLG contributes to OM susceptibility in humans. Our results underline the importance of following up findings from genome-wide association through replication studies, preferably using multi-omic datasets.

Prediction of readiness to decannulation from venovenous extracorporeal membrane oxygenation.

OBJECTIVE: The criteria and process for liberation from extracorporeal membrane oxygenation in patients with severe acute respiratory distress syndrome are not standardized. The predictive accuracy of the oxygen challenge test as a diagnostic test in determining weaning and decannulation from venovenous extracorporeal membrane oxygenation was tested. DESIGN: A single-centre, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure centre in a university hospital in the United Kingdom. PATIENTS: 253 adults with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Patients had median age: 43 years (interquartile range: 32-52) years, extracorporeal membrane oxygenation days: 9 (interquartile range: 6-14) and acute physiology and chronic health evaluation II score 17.5 (interquartile range: 15-20). Oxygen challenge test value (PaO2-OCT) with best prediction was 31 kPa (232 mmHg; sensitivity 0.74; specificity 0.70; area under curve 0.77 (confidence interval: 0.73-0.81)). PaO2-OCT did not perform well as a prospective test to identify readiness to decannulation. Only 24 patients (10%) were decannulated 48 hours after their first positive oxygen challenge test (true positive) and 73.4% patients were false positives (positive oxygen challenge test but not decannulated). True positives had higher tidal volume (541 ± 218 vs 368 mL ± 210; p < 0.05) and minute ventilation (9.34 ± 5.36 vs 6.33 L/min ± 4.43; p < 0.05). Blood flow (3.17 ± 0.23 vs 3.53 L/min ± 0.56; p < 0.05), sweep gas flow (1.42 ±1.83 vs 3.74 L/min ± 2.43; p < 0.05) and extracorporeal membrane oxygenation minute volume at time of first positive oxygen challenge test was lower in true positives (1.66 ± 2.26 vs 4.82 ± 3.43 L/min). This was a strong predictor for decannulation within 48 hours (area under curve: 0.88, confidence interval: 0.88-0.89). CONCLUSIONS: In severe acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation, the PaO2-OCT is a poor predictor of readiness to decannulate from extracorporeal membrane oxygenation. Additional factors involved in the control of respiratory drive and carbon dioxide clearance, particularly native lung dead space and total minute ventilation, should be assessed.

Harms and benefits of opioids for management of non-surgical acute and chronic low back pain: a systematic review.

BACKGROUND: Consequences of prescription opioid use involve harms, addiction, tolerance and death. Despite routine prescription, opioids are not recommended for initial intervention by any major multidisciplinary low back pain (LBP) guideline. OBJECTIVE: Our primary purpose was to improve overall understanding of the harms and benefits associated with oral opioid interventions prescribed for treatment of acute or chronic back pain. Our second goal was to evaluate pain intensity and to compare and contrast these data with the harms. Our last objective was to evaluate conflicts of interest among the study authors and the findings. DESIGN/DATA/ELIGIBILITY CRITERIA: Studies incorporating oral prescription opioid management of non-surgical LBP were evaluated. After systematic assessment, no studies that met inclusion included participants with specifically acute LBP. Therefore, extracted data reflects only populations with subacute and chronic LBP. Data on reported harms, severe harms, pain outcomes and withdrawal rates were extracted and meta-analyses were completed for opioid versus placebo trials and opioids versus non-opioid trials. RESULTS: Fourteen studies met inclusion/exclusion requirements. All trials involved short-term management with limited follow-up. A high percentage of harms were identified across most studies. Opioids were not shown to be superior to other medications, and only showed superiority to placebo comparators (at cost of additional harms). CONCLUSION: This review identified trends of higher harms rates and higher percentages of severe harms in opioid arms for the management of subacute and chronic LBP. The majority of trials that demonstrated benefits with opioids also had potential conflicts of interest. Lastly, non-opioid medications demonstrated statistically significant pain improvement compared with opioids. We feel that the results of the trial are supportive of current LBP guidelines and do not condone the initial use of opioids in management of subacute or chronic LBP. TRIAL REGISTRATION NUMBER: CRD42017070914.

Adequacy of nutrition support during extracorporeal membrane oxygenation.

BACKGROUND: The use of veno-venous extracorporeal membrane oxygenation (vv-ECMO) is increasing in adults with severe respiratory failure. Observational data suggest that there are significant challenges to providing adequate nutrition support for patients on vv-ECMO. We aimed to describe firstly the nutrition support practices in a large single-centre providing vv-ECMO to adults and secondly any association with clinical outcome. METHODS: We conducted a retrospective review of patients receiving vv-ECMO on the Intensive Care Unit (ICU) of a large London teaching hospital. Adult patients admitted to the ICU with severe respiratory failure between December 2010 and December 2015 were included. Daily energy and protein delivery were compared with estimated targets and reasons for feeding interruptions were collected from electronic medical records. Adequate feeding was defined as 80-110% of estimated targets. RESULTS: We analysed 203 eligible patients. Median duration of ICU stay was 21.0 (IQR, 15.0-33.0) days and vv-ECMO 10.0 (IQR, 7.0-16.0) days. Although median energy (89.8% (IQR, 80.5-96.0%)) and protein (84.7% (IQR, 74.0-96.7%)) delivery was adequate, underfeeding of either energy or protein occurred on nearly one third (28.3%) of nutrition support days. A higher admission severity of illness score was associated with inadequate protein delivery (p = 0.040). Patients with more severe organ dysfunction on the first day of vv-ECMO received inadequate energy (p = 0.026). The most common reasons for interrupted feeding were medical procedures (39.1%) followed by poor gastric motility (22.8%). CONCLUSION: Adequate energy and protein delivery during vv-ECMO is possible but underfeeding is still common, especially in those who are more severely ill or who have more severe organ dysfunction. Patients with inadequate energy or protein delivery did not differ in ICU and 6-month survival. Prospective studies investigating optimal feeding in this patient cohort are required.

FUT2 Variants Confer Susceptibility to Familial Otitis Media.

Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154∗) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p.Arg202∗) variant co-segregates with otitis media in a Filipino pedigree (LOD = 4.0). Additionally, a rare variant, c.412C>T (p.Arg138Cys), is associated with recurrent/chronic otitis media in European-American children (p = 1.2 × 10-5) and US trios (TDT p = 0.01). The c.461G>A (p.Trp154∗) variant was also over-transmitted in US trios (TDT p = 0.01) and was associated with shifts in middle ear microbiota composition (PERMANOVA p < 10-7) and increased biodiversity. When all missense and nonsense variants identified in multi-ethnic US trios with CADD > 20 were combined, FUT2 variants were over-transmitted in trios (TDT p = 0.001). Fut2 is transiently upregulated in mouse middle ear after inoculation with non-typeable Haemophilus influenzae. Four FUT2 variants-namely p.Ala104Val, p.Arg138Cys, p.Trp154∗, and p.Arg202∗-reduced A antigen in mutant-transfected COS-7 cells, while the nonsense variants also reduced FUT2 protein levels. Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells. Our families demonstrate marked intra-familial genetic heterogeneity, suggesting that multiple combinations of common and rare variants plus environmental factors influence the individual otitis media phenotype as a complex trait.

Veno-arterio-venous ECMO for septic cardiomyopathy: a single-centre experience.

INTRODUCTION: The role of extracorporeal support for patients with septic shock remains unclear. METHODS: We conducted a retrospective analysis of our single-centre experience with veno-arterio-venous extracorporeal membrane oxygenation (VAV ECMO) in adult patients with severe respiratory failure and septic cardiomyopathy. Clinical data was extracted from electronic medical records including a dedicated ECMO referral and follow-up database. RESULTS: Twelve patients were commenced on VAV ECMO for septic cardiomyopathy for a median of four days (IQR 3.0 to 5.3) between 01/2014 and 12/2017. Five patients (41.7%) had a cardiac arrest prior to initiation of ECMO support. At baseline, median left ventricular ejection fraction was 16.25% (IQR 13.13 to 17.5) and median PaO2/FiO2 ratio was 9 kPa (IQR 6.5 to 12.0) [67.50 mmHg (IQR 48.75 to 90.00)]. The survival rate to hospital discharge for VAV ECMO was 75% in this cohort. None of the surviving patients died within the follow-up period (median six month). CONCLUSION: VAV ECMO is a feasible rescue strategy for a small proportion of patients with combined respiratory and cardiac failure secondary to septic shock with septic cardiomyopathy. We provide a detailed report of our experience with this technique. Further research is required comparing the different extracorporeal strategies directly to conventional resuscitation and against each other.

Telemanagement of Heart Failure Patients Across the Post-Acute Care Continuum.

BACKGROUND: Heart failure (HF) is a chronic condition causing nearly 1 million hospital admissions annually in the United States with 25% of patients rehospitalized within 30 days. INTRODUCTION: The purpose of this study was to investigate whether telemanagement of HF patients throughout the post-acute continuum of care would reduce rehospitalization rates and improve patient self-care knowledge and satisfaction. MATERIALS AND METHODS: HF patients discharged to a skilled nursing facility (SNF) received telemanagement by HF clinicians with opportunity for continuation at home with assistance of home healthcare (HHC) nurses. Wireless sensors worn at SNF and home captured continuous health information visible to HF clinicians on secure cloud database. Point-of-care devices were available at SNF. Patients had scheduled and as-needed video visits with audio and auscultation capacity with HF clinician. HF education was provided by SNF and HHC nursing. Patients were compared with historical control group receiving standard care at same SNF. RESULTS: Patients receiving telemanagement had 29% lower rehospitalization rates (17% vs. 24%), despite higher predicted rehospitalization risk. Median age was 81. Seven of eight patients who were rehospitalized in the telemanagement group had advanced HF symptoms (New York Heart Association Class IV). Five patients in telemanagement group were receiving continuous inotrope infusions. Patients reported good satisfaction and self-care knowledge. DISCUSSION: Reduction of rehospitalization rates was clinically significant in population of advanced age and HF symptoms. Technology enhanced communication content and timeliness across the post-acute care continuum. CONCLUSION: Post-acute telemanagement may reduce rehospitalization rates even in high-risk, older HF populations.