Inadequate Delivery Research Articles

Abstract 11328: Risk Analytics and Clinical Decision Support System Role in Identifying Elevated Serum Lactate Level for Pediatric Cardiac Patients

Introduction: Pediatric patients with congenital heart defect are predisposed for low cardiac output syndrome (LCOS). Serum lactate is a well-defined marker of LCOS. To improve the quality and safety of care, new tools that are less invasive, more sensitive and specific are needed. Hypothesis: We hypothesize that analytics algorithms can compute risk indices that are associated with elevated lactate. Methods: Quality improvement project in tertiary pediatric cardiac intensive care unit. Data used were collected retrospectively throughout 6/2019-8/2020. The risk analytics algorithm uses a model of patient physiology with vitals and lab data to compute probability density curves for various physiologic variables in real-time. These densities are used to calculate the Hyperlactatemia Index (HLA) and Inadequate Delivery of Oxygen Index (IDO2) [Etiometry Inc., Boston, MA]. HLA and IDO2 represent the integrated probabilities that the current lactate is greater than 4 mmol/L and that the current SvO2 is less than 40% respectively. The minimum data required to calculate HLA and IDO2 is heart rate every 60 seconds, oxygen saturation via pulse oximetry, blood pressures every ten minutes, and at least one lactate lab per day (HLA only). The reported lactates were categorized in four groups. We subdivided the preceding three hours period before the lactate into 30 minutes windows. Subsequently, we calculated the mean IDO2 and HLA and compared the positive predictive value (PPV) of lactate > 4 for both. Results: We included 484 patients in our analysis, 20% of which were neonates. The median patient age was 7.7 months (IQR:2,46). IDO2 and HLA trended higher when lactate levels were elevated, especially in the 30 minutes immediately preceding the lactate check. When the individual probability > 50%, lactate was > 4 in 44% ( + 10%) for HLA and 3% for IDO2. Conclusions: HLA shows a strong association with lactate and is superior to IDO2 across all time points. Performance of the indices was better in the 30min prior to the elevated lactate. Future studies validating this new tool prospectively are critical before its usage in the clinical setting.

Poor cancer care in Zimbabwe

Zimbabwe is facing a critical situation with respect to cancer care as a consequence of the country's inadequate health-care delivery system, with the chances of survival of patients with cancer being very low in the country owing to the failure of the health sector. Justice Mudavanhu (Ministry of Health and Child Care, Harare, Zimbabwe) has expressed concerns regarding the management of cancer care in Zimbabwe.

Use of a Risk Analytic Algorithm to Inform Weaning From Vasoactive Medication in Patients Following Pediatric Cardiac Surgery.

Advanced clinical decision support tools, such as real-time risk analytic algorithms, show promise in assisting clinicians in making more efficient and precise decisions. These algorithms, which calculate the likelihood of a given underlying physiology or future event, have predominantly been used to identify the risk of impending clinical decompensation. There may be broader clinical applications of these models. Using the inadequate delivery of oxygen index, a U.S. Food and Drug Administration-approved risk analytic algorithm predicting the likelihood of low cardiac output state, the primary objective was to evaluate the association of inadequate delivery of oxygen index with success or failure of weaning vasoactive support in postoperative cardiac surgery patients. Multicenter retrospective cohort study. Three pediatric cardiac ICUs at tertiary academic children's hospitals. Infants and children greater than 2 kg and less than 12 years following cardiac surgery, who required vasoactive infusions for greater than 6 hours in the postoperative period. None. Postoperative patients were identified who successfully weaned off initial vasoactive infusions (n = 2,645) versus those who failed vasoactive wean (required reinitiation of vasoactive, required mechanical circulatory support, renal replacement therapy, suffered cardiac arrest, or died) (n = 516). Inadequate delivery of oxygen index for final 6 hours of vasoactive wean was captured. Inadequate delivery of oxygen index was significantly elevated in patients with failed versus successful weans (inadequate delivery of oxygen index 11.6 [sd 19.0] vs 6.4 [sd 12.6]; p < 0.001). Mean 6-hour inadequate delivery of oxygen index greater than 50 had strongest association with failed vasoactive wean (adjusted odds ratio, 4.0; 95% CI, 2.5-6.6). In patients who failed wean, reinitiation of vasoactive support was associated with concomitant fall in inadequate delivery of oxygen index (11.1 [sd 18] vs 8.9 [sd 16]; p = 0.007). During the de-escalation phase of postoperative cardiac ICU management, elevation of the real-time risk analytic model, inadequate delivery of oxygen index, was associated with failure to wean off vasoactive infusions. Future studies should prospectively evaluate utility of risk analytic models as clinical decision support tools in de-escalation practices in critically ill patients.

Fluid Restriction Contributes to Poor Nutritional Adequacy in Patients With Congenital Heart Disease Receiving Renal Replacement Therapy

Critically ill patients receiving renal replacement therapy (RRT) in the pediatric cardiac intensive care unit (CICU) are at high risk for inadequate nutrition delivery. The objective of this study is to evaluate barriers to adequate energy and protein delivery in critically ill patients with congenital heart disease receiving RRT. This is a single-center retrospective cohort study of patients receiving RRT in the CICU from 2011 to 2019. Energy and protein adequacy was recorded over the first 7days of RRT. Adequacy was defined as delivery of >80% of the energy and protein targets during this time period. Patients who achieved adequacy were compared to those who did not. Multivariable logistic regression models were constructed to determine factors independently associated with energy and protein adequacy while receiving RRT. Sixty patients were included for analysis. Fifty-five patients (92%) achieved energy adequacy and 37 patients (62%) achieved protein adequacy. A higher weight-for-age z-score (WAZ) on admission to the CICU was the only independent predictor of inadequate energy intake (odds ratio 0.07, 95% confidence interval 0.01-0.58, P=.014); median WAZ was -1.17 versus +1.24 for those with adequate versus inadequate energy intake, respectively. Fluid restriction to <80% of maintenance fluid at the time of RRT initiation was more likely in patients with higher WAZ. Fluid restriction was the only independent predictor of inadequate protein intake (odds ratio 0.13, 95% confidence interval 0.02-0.7, P=.018); 5% versus 30% were fluid restricted in those with adequate versus inadequate protein intake, respectively. Azotemia was not associated with inadequate protein intake. Initiation of RRT did not allow for liberalization of fluid intake over the time period evaluated. Protein delivery was inadequate in 38% of children undergoing RRT in the CICU. Fluid restriction was associated with inadequate protein intake and higher WAZ was associated with inadequate energy intake.

Predictive Value of Maternal Anemia in Cases of Fetal Growth Restriction

Anemia can be defined as a state of inadequate O2 delivery to tissues due to reduction of the O2 carrying capacity of blood practically, anemia is diagnosed when there is reduction in the hemoglobin concentration or haematocrit level below normal values. Iron deficiency anemia is a major public health problem among women of reproductive age in most of developing countries approximately 50% of pregnant women and 35% of non pregnant women are anemic. These nutritional disorders, has profound negative effects on pregnancy outcome, health of mothers and babies. The objective of this study: Is to evaluate the maternal anemia during pregnancy as a risk factor for fetal growth restriction. The study was done this study conducted on 120 pregnant women. Pregnant women with inclusion criteria: Singleton pregnancy, Gestational age more than 28 week and Hb level less than 10mg/dl. We exclude multiple pregnancy, Gestational age less than 28 week, Hb level more than 10 mg/dl and other medical disorder with pregnancy. The results of this study reveal the following: There was significant difference between group 1, 2, 3, 4 as regard to Hb level, (PCV), (MCV), (MCH), (MCHC), (Ht) and (CBC). The restriction of fatal growth was significant lower in sever anemic patient rather than mild or moderate anemic patient In conclusions: The result of this study shows that there was restriction of fatal growth was significantly high in sever anemic group than mild or moderate group also, incidence of low birth weight and risk of fatal morbidity or mortality was significantly high in sever anemic group than mild or moderate group.

Comparative evaluation of the immune responses of seven chicken ecotypes to vaccination against Newcastle disease

Newcastle disease (ND) is a highly contagious viral disease of poultry with high mortality. The local velogenic viral pool of the ND strains influences its severity and occurrence. ND vaccination is the most feasible approach to control the disease. However, some ND-vaccinated groups within chicken populations are susceptible to velogenic ND infection developing outbreaks with marked pathological lesions and shedding of the virus. Vaccine strain-related factors as well as inadequate vaccine application and delivery methods during vaccination might explain the suboptimum ND vaccine efficacy. In this study, however, we propose that host factors may contribute to the suboptimal vaccine efficacy in vaccinated chickens. We, therefore, compared the immune response of five Ethiopian chicken ecotypes to ND immunization in the presence of two reference breeds (Fayoumi and Bovans). All chickens received initial immunization at age of 21 days with HB1 ND vaccine followed by two-times LaSota booster immunization at age 50 and 120 days. Subsequently, serum was collected fortnightly post-vaccination at age 35, 65, and 135 days for immune response analysis using the hemagglutination inhibition (HI) test. HIantibody was significantly higher at days 135 &gt; 65 &gt; 35 in each ecotype following the third, second, and first vaccination, respectively. The different chicken ecotypes had significant differences in HI antibody response to the ND vaccination. Accordingly, the HI titer was significantly higher in Jarso &gt; Cheffe &gt; Fayoumi &gt; Arsi &gt; Bovans &gt; Tepi &gt; Horro suggesting antibody titer and ND vaccine efficacy of the ND vaccine depends on host factors. Moreover, some chicken groups within each ecotype had low HI titer. Chicken ecotypes with weak immune responses may not completely clear the virus from their body; thus, they can serve as a reservoir host by maintaining the ND virus. We conclude that herd immunity level and blanket vaccination program based on the results of a single host genetic group can be misleading during developing and recommending a new vaccine. Hence, understanding the host determinant factors in the immune response during vaccination can lead to improved efficacy and protection against ND in chicken populations.

Keratin-Based Nanoparticles with Tumor-Targeting and Cascade Catalytic Capabilities for the Combinational Oxidation Phototherapy of Breast Cancer.

Photodynamic therapy (PDT) holds tantalizing prospects of a prominent cancer treatment strategy. However, its efficacy remains limited by virtue of the hypoxic tumor microenvironment and the inadequate tumor-targeted delivery of photosensitizers, and these can be further exacerbated by the lack of development of a well-controlled nitric oxide (NO) release system at the target site. Inspired by Chinese medicine, we propose a revealing new keratin application. Keratin has garnered attention as an NO generator; however, its oncological use has rarely been investigated. We hypothesized that the incorporation of a phenylboronic acid (PBA) targeting ligand/methylene blue (MB) photosensitizer with a keratin NO donor would facilitate precise tumor delivery, enhancing PDT. Herein, we demonstrated that MB@keratin/PBA/d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) nanoparticles (MB@KPTNPs) specifically targeted breast cancer cells and effectively suppressed their growth. Through MB-mediated biometabolism, the endocytic MB@KPTNPs produced a sufficient amount of intracellular NO that reduced the glutathione level while boosting the efficiency of PDT. A therapeutic combination of NO/PDT was therefore achieved, resulting in significant inhibition of both in vivo tumor growth and lung metastasis. These findings underscore the importance of utilizing keratin-based nanoparticles that simultaneously combine targeting of the tumor and self-generating NO with a cascading catalytic ability as a novel oxidation therapeutic strategy for enhancing PDT.

Nanomedicine Applications in Treatment of Primary Central Nervous System Lymphoma: Current State of the Art.

Primary central nervous system lymphoma (PCNSL) is a rare but highly aggressive subtype of extra nodal non-Hodgkin lymphoma (NHL), which is confined in the central nervous system (CNS). Despite recent advancements in treatment options, the overall prognosis of PCNSL remains poor. Among many unfavorable factors affecting efficacy, inadequate drug delivery into the CNS is still the thorniest challenge. Blood-brain barrier (BBB) constitutes a significant impediment, restricting entry of most therapeutics to the brain. Nanotechnology has offered great promise for brain diseases, as various nano-based drug delivery systems (NDDSs) have been developed for delivery of theranostic agents in to the CNS. These drug delivery systems possess significant advantages, including good feasibility, reliable safety profile, excellent BBB penetration and potent antitumor effects. As for treatment of PCNSL, numerous well-developed BBB-crossing nano-based strategies can be applied with proper modifications and improvements. Some exquisitely designed NDDSs specific for PCNSL have shown great potential. In this review, we provide a summary on current status of diagnosis and treatment of PCNSL, followed by an overview of BBB-crossing strategies applied in management of PCNSL, both novel and wellestablished. Finally, challenges and future perspectives in this field are also discussed.

Tailoring nutrition therapy amid the COVID-19 pandemic: Does it work?

BackgroundThe COVID-19 pandemic has been a challenge for nutrition monitoring and delivery. This study evaluates clinical and nutritional characteristics of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and investigates the relationship between nutrition delivery and clinical outcomes.MethodsProspective observational study of adults admitted for >24 hrs to a tertiary-care hospital during a period of 2months. Data was collected on disease severity, energy, protein delivery and adequacy, use of mechanical ventilation (MV), hospital length of stay (LOS). Multivariate logistic regression models were used to determine the associations with mortality as the primary outcome.Results1083 patients: 69% male (n = 747), 31% females (n = 336), mean age 58.2 ± 12.8 with 26.6 ± 4.32 BMI were analysed. 1021 patients survived and 62 deaths occurred, with 183 and 900 patients in the ICU and ward, respectively. Inadequate calorie and protein delivery had significantly higher mortality than those with adequate provision (p < 0.001) among the ICU patients. In bivariate logistic regression analysis, inadequacy of energy and protein, disease severity, comorbidities ≥3, NRS score ≥3 and prone ventilation correlates with mortality (p < 0.001). In multivariate logistic regression analysis of the ICU patients, energy inadequacy (OR:3.6, 95%CI:1.25–10.2) and prone ventilation (OR:11.0, 95%CI:3.8–31.9) were significantly (p < 0.05) associated with mortality after adjusting for disease severity, comorbidities and MV days.ConclusionMost patients infected with SARS-CoV-2 are at nutrition risk that can impact outcome. Our data suggest that addressing nutritional adequacy can be one of the measures to reduce hospital LOS, and mortality among nutritionally risk patients.

A Value Framework for Transforming Behavioral Health

Summary The behavioral health system in the United States is failing at a time when we need it the most. Rates of mental health and substance use disorders are rising in the wake of Covid-19, and increased suicide and drug overdose deaths can be expected to follow. Effective behavioral health treatments exist, but access is limited by multiple barriers, including inadequate care delivery, workforce shortages, lack of outcome measurement, and payment methodologies that disincentivize value. To overcome these limitations and meet the growing demand, a comprehensive overhaul of the current system is required. The author adopts the Porter-Lee value agenda and applies it to behavioral health, building on current pockets of innovation to deliver an effective and efficient system at a national scale. Changes in policy needed to expedite these advances also are defined.

Effects of water stably-enriched with oxygen as a novel method of tissue oxygenation on mitochondrial function, and as adjuvant therapy for type 2 diabetes in a randomized placebo-controlled trial.

Diabetes mellitus is associated with inadequate delivery of oxygen to tissues. Cellular hypoxia is associated with mitochondrial dysfunction which increases oxidative stress and hyperglycaemia. Hyperbaric oxygenation therapy, which was shown to improve insulin sensitivity, is impractical for regular use. We evaluated the effects of water which is stably-enriched with oxygen (ELO water) to increase arterial blood oxygen levels, on mitochondrial function in the presence of normal- or high-glucose environments, and as glucose-lowering therapy in humans. We compared arterial blood oxygen levels in Sprague-Dawley rats after 7 days of ad libitum ELO or tap water consumption. Mitochondrial stress testing, and flow cytometry analysis of mitochondrial mass and membrane potential, were performed on human HepG2 cells cultured in four Dulbecco's Modified Eagle Medium media, made with ELO water or regular (control) water, at normal (5.5 mM) or high (25 mM) glucose concentrations. We also randomized 150 adults with type 2 diabetes (mean age 53 years, glycated haemoglobin HbA1c 8.9% [74 mmol/mol], average duration of diabetes 12 years) to drink 1.5 litres daily of bottled ELO water or drinking water. ELO water raised arterial oxygen tension pO2 significantly (335 ± 26 vs. 188 ± 18 mmHg, p = 0.006) compared with tap water. In cells cultured in control water, mitochondrial mass and membrane potential were both significantly lower at 25 mM glucose compared with 5.5 mM glucose; in contrast, mitochondrial mass and membrane potential did not differ significantly at normal or high glucose concentrations in cells cultured in ELO water. The high-glucose environment induced a greater mitochondrial proton leak in cells cultured in ELO water compared to cells cultured in control medium at similar glucose concentration. In type 2 diabetic adults, HbA1c decreased significantly (p = 0.002) by 0.3 ± 0.7% (4 ± 8 mmol/mol), with ELO water after 12 weeks of treatment but was unchanged with placebo. ELO water raises arterial blood oxygen levels, appears to have a protective effect on hyperglycaemia-induced reduction in mitochondrial mass and mitochondrial dysfunction, and may be effective adjuvant therapy for type 2 diabetes.

Hemorrhagic shock and hemostatic resuscitation in canine trauma.

Hemorrhage is a significant cause of death among military working dogs and in civilian canine trauma. While research specifically aimed at canine trauma is limited, many principles from human trauma resuscitation apply. Trauma with significant hemorrhage results in shock and inadequate oxygen delivery to tissues. This leads to aberrations in cellular metabolism, including anaerobic metabolism, decreased energy production, acidosis, cell swelling, and eventual cell death. Considering blood and endothelium as a single organ system, blood failure is a syndrome of endotheliopathy, coagulopathy, and platelet dysfunction. In severe cases following injury, blood failure develops and is induced by inadequate oxygen delivery in the presence of hemorrhage, tissue injury, and acute stress from trauma. Severe hemorrhagic shock is best treated with hemostatic resuscitation, wherein blood products are used to restore effective circulating volume and increase oxygen delivery to tissues without exacerbating blood failure. The principles of hemostatic resuscitation have been demonstrated in severely injured people and the authors propose an algorithm for applying this to canine patients. The use of plasma and whole blood to resuscitate severely injured canines while minimizing the use of crystalloids and colloids could prove instrumental in improving both mortality and morbidity. More work is needed to understand the canine patient that would benefit from hemostatic resuscitation, as well as to determine the optimal resuscitation strategy for these patients.

Abstract 1369: Predicting clinical pharmacokinetics and toxicity of current and emerging oncology therapeutics by normothermic perfusion of isolated human-sized organs

Abstract Novel cancer therapeutics have less than a 12% probability of translating from bench to bedside. Unwarranted toxicity and inadequate therapeutic delivery due to uptake by clearance organs, not predicted by current preclinical methods, have contributed towards this high rate of attrition. In the present work, we propose normothermic machine perfusion of human or human-sized organs as a more predictive, closer-to-human model to investigate drug pharmacokinetics and toxicity. Over the past decade, developments in the field of organ preservation for transplantation have enabled prolonged (&amp;gt;12 hours) normothermic machine perfusion (NMP) of isolated porcine or human organs ex vivo, maintaining quasi-physiological haemodynamic, synthetic and metabolic function using a packed red cell perfusate with physiological oxygenation and nutrient levels at normal body temperature. This preserves physiological processes such as metabolism and drug elimination, and enables easy access to tissue, blood and excreted biological fluids, with NMP livers producing bile and NMP kidneys producing urine. We hypothesise that this will provide a physiologically relevant platform to investigate drug pharmacokinetics and toxicity. We selected a widely used small-molecule chemotherapeutic (Irinotecan hydrochloride 2mg/ml, Medac, UK) which has seen decades of clinical use and benefits from extensive clinical pharmacokinetic data. The small-molecule drug was infused into isolated porcine and human livers and kidneys, with quantification of concentration time profiles of the prodrug and its main metabolites in plasma, bile and urine over 16-24 hours of NMP. In addition to irinotecan (CPT11), three of its metabolites (APC, SN38G, SN38) were successfully detected and quantified, demonstrating peak plasma concentrations (Cmax ~ 10,000 ng/mL, 1000 ng/mL, 100 ng/g, 30 ng/g), plasma decay rates and percentages of injected dose in bile (%ID ~20%, 8%, 25%, 1%) and urine (%ID ~20%, 0.06%, 0.5%,0.1%) that are comparable to clinical data. Drug-tissue toxicity could also be adequately replicated in the NMP model. In conclusion, we have demonstrated that human-sized isolated, normothermically perfused livers and kidneys accurately represent the clinically observed pharmacokinetic and toxicity profiles of an established small-molecule therapeutic. Further model validation is ongoing for biologics and other nanomedicines which are susceptible to clearance by the mononuclear phagocytic system or are hepato- or nephrotoxic. If this proves successful, normothermic machine perfusion of isolated porcine and human organs could greatly aid the early screening of candidate therapeutics and significantly enhance the pace and success rate with which they are translated into patients. Citation Format: Tamsyn Clark, Luca Bau, Fungai Dengu, Daniel Voyce, Robert Carlisle, Peter Friend, Constantin Coussios. Predicting clinical pharmacokinetics and toxicity of current and emerging oncology therapeutics by normothermic perfusion of isolated human-sized organs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1369.

Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation.

BackgroundThe clinical use of therapeutic peptides has been limited because of their inefficient delivery approaches and, therefore, inadequate delivery to target sites. Buccal administration of therapeutic peptides offers patients a potential alternative to the current invasive routes of administration.PurposeThe aim of the study was to fabricate hydrophobic ion-pairing (HIP)-nanocomplexes (C1 and C2) utilizing anionic bile salts and cationic peptides, and to assess their permeability across TR146 buccal cell layers and porcine buccal tissue.MethodsC1 and C2-nanocomplexes were fabricated using the HIP approach. In addition, their physiochemical and morphological attributes, in vitro and ex vivo permeability properties, and qualitative and quantitative cellular uptake were evaluated and compared. The localization of C1 and C2-nanocomplexes in porcine buccal tissue was determined using confocal laser scanning microscopy.ResultsThe C1-nanocomplex was the superior nanocarrier and significantly enhanced the transport of insulin across TR146 cell layers and porcine buccal tissue, exhibiting a 3.00- and 51.76-fold increase in permeability coefficient, respectively, when compared with insulin solution (p < 0.01). C1-nanocomplex was more efficient than C2-nanocomplex at facilitating insulin permeability, with a 2.18- and 27.64-fold increase across TR146 cell layers and porcine buccal tissue, respectively. The C1-nanocomplex demonstrated immense uptake and localization of insulin in TR146 cells and porcine buccal tissue, as evidenced by a highly intense fluorescence in TR146 cells, and a great shift of fluorescence intensity towards the inner region of buccal tissue over time. The increase in fluorescence intensity was observed in the order of C1 > C2 > insulin solution.ConclusionIn this study, we highlighted the efficacy of potential nanocarriers in addressing the daunting issues associated with the invasive administration of insulin and indicated a promising strategy for the buccal administration and delivery of this life-saving peptide hormone.

Hearing healthcare gaps in LMICS: snapshot from a semi-urban community in Nigeria.

Low and middle-income countries (LMICs) have high prevalence of hearing loss which are mainly due to preventable causes. While urban communities in LMICs are likely to have functional hearing healthcare delivery infrastructure, rural and semi-urban communities may have different reality. This study aimed to provide: (i) a snapshot of the burden of ear diseases and (ii) a description of available hearing healthcare resources in a semi-urban Nigerian community. A cross-sectional study of households selected by multistage random sampling technique. Seventy-four participants: 39 males and 35 females with mean age of 34 years ± 5.24 were recruited and answered a structured questionnaire. In addition, the availability of hearing healthcare services in 15 health centers within the community were determined. All participants reported recent occurrence of ear complaints or gave similar history in a household member. Common complaints were ear discharge, ear pain and hearing loss. Medical intervention was sought from patent medicine stores, hospitals and traditional healers. None of the assessed hospitals within the study site was manned by an ENT surgeon or ENT trained nurse. Despite the heavy burden of ear complaints there is inadequate hearing healthcare delivery in a typical LMIC community. This highlights the need for urgent improvement of hearing healthcare.

Association Between Nutrition Delivery, Modified Nutrition Risk In Critically III Score, and 28-Day Mortality.

Nutrition delivery, is a key component in the management of critical illness. Traditional scoring systems are inadequate in the intensive care unit (ICU), as patients are sedated. Our study examines the associations between calorie and protein adequacy, 28-day mortality, and modified Nutrition Risk in Critically Ill (mNUTRIC) score and identify at-risk ICU patients who may benefit more from nutrition intervention. Prospective observational study of adults admitted for >24h to the ICU of a tertiary care hospital during a period of 7 months. Data were collected on nutrition delivery, mNUTRIC score, use of mechanical ventilation, and ICU/hospital length of stay (LOS). Multivariate logistic regression analysis was done with 28-day mortality as the primary outcome. Two hundred forty-eight patients were recruited for the study with 60% male, 40% female, mean age 60.8 ± 14.7, and body mass index of 24.2 ± 4.8. Patients with inadequate calorie and protein delivery had significantly higher 28-day mortality than those with adequate provision (P=.032 and P =. 017). In bivariate logistic regression analysis, mNUTRIC score (odds ratio [OR], 1.802; 95% CI, 1.042-3.117; P = .035) and adequacy of energy (OR, 1.92) and protein (OR, 2.49) correlate with 28-day mortality. The Kaplan-Meier survival curve showed a survival benefit in the ≥80% energy and protein group among the total patients and was also significantly associated with lower hospital and ICU LOS, even after matching (log-rank test, P < 0.001). Adequacy of energy and protein to ≥80% may shorten ICU/hospital LOS and reduce 28-day mortality among both high and low nutrition risk patients.

A study protocol to evaluate the implementation and effectiveness of the Clinical Nurse Leader Care Model in improving quality and safety outcomes.

AimsPatients are harmed or die every year because of unsafe, inappropriate or inadequate healthcare delivery. Registered Nurses are a recognized patient safety strategy. However, variability in research findings indicate the relationship is not as simple as “more nurses=better outcomes.” Hence, currently there exists no evidence‐based frontline nursing care model. One emerging model is the Clinical Nurse Leader care model.DesignThis Hybrid Type II Implementation‐Effectiveness study will evaluate the effect of the care model on standardized quality and safety outcomes and identify implementation characteristics that are sufficient and necessary to achieve outcomes.MethodsThis study leverages a natural experiment in 66 clinical care units in nine hospitals across five states in the United States that have implemented the Clinical Nurse Leader care model.ResultsFindings will elucidate Registered Nurse's mechanisms of action as organized into frontline models of care and link actions to improved care quality and safety.

Skin Viability and Microvascular Function Under Localised Applications of Heat and Pressure

Soft tissue pressure injuries are localised injuries to surface and deep tissue, caused by sustained compression of skin and muscle between a bony area of the body, and for example, a hospital mattress or medical device. Prolonged cell deformation is known to reduce the structural integrity of the cell cytoskeleton, leading to cascade of cell death, inflammation, oedema and oxidative stress, factors that are likely exacerbated by inadequate blood flow and oxygen delivery. Numerous secondary factors are thought to accelerate this cascade, including systemic hypoxia and changes in tissue temperature. By examining the responses of various skin viability markers, both during and after the application of temperature and pressure stimuli, the present study aims to expand understanding of the secondary factors affecting pressure ulcer onset and progression. In the present study, a custom skin deformation device, with an area of 33cm2, was used to apply a combination of pressures (6, 20 and 40mmHg) and temperatures (23, 33, 38°C) at the sacrum of four healthy volunteers (data collection ongoing). A laser doppler flowmetry probe, embedded into the skin deformation device, was used to measure baseline skin blood flow, skin blood flow under pressure, and reactive hyperaemia (RH) on pressure release. All measurements were calculated as a percentage of heat-induced maximal cutaneous vascular conductance (%CVCmax). Changes in stratum corneum and epidermal hydration were calculated using the difference in tissue electrical capacitance (corneometry) measurements before and after skin deformation. The results indicated a significant difference in loaded skin blood flow between the pressures of 6-20mmHg (p=0.045), and 6-40mmHg (p=0.018), decreasing from 30.5 ± 9.1 %CVCmax to 21.8 ± 9.0 %CVCmax and 17.5 ± 6.7 %CVCmax respectively. Furthermore, there was a significant increase (p=0.030) from 16.9 ± 8.2 %CVCmax to 29.8 ± 5.4 %CVCmax in loaded skin blood flow, between the temperatures of 28-38°C. Finally, blood flow saw a significant (p=0.005) increase on pressure release, from a loaded average of 19.7 ± 8.2 %CVCmax to an unloaded average of 29.0 ± 12.0 %CVCmax, however there was no significant effect of pressure level or temperature on reactive hyperemia. Changes in stratum corneum hydration between 28-33°C (p=0.044), and 28-38°C (p=0.019), increased from 20.8 ± 11.3% to 38.8 ± 12.7% and 48.5 ± 15.5% respectively. Differing pressures and temperatures had no significant effect on epidermal hydration. Initial indications from the present study suggest low local tissue temperature reduces tissue blood flow under pressure, thereby potentially reducing oxygen transport to, and metabolites away from, areas of loaded tissue. However, increased local temperature results in greater moisture accumulation on the surface layer of the cutaneous tissues, potentially resulting in a lower structural integrity. On balance, a neutral skin temperature may be best to balance the harmful effects pressure on tissue viability, but further investigation is required to fully understand the influence of temperature on each aspect of the pressure injury cascade, including cell cytoskeleton integrity, inflammation, and oedema, as well as blood flow dynamics, oxygen delivery, cell metabolism and oxidative stress.

Mass Disasters and Burnout in Nephrology Personnel: From Earthquakes and Hurricanes to COVID-19 Pandemic.

Mass disasters result in extensive health problems and make health care delivery problematic, as has been the case during the COVID-19 pandemic. Although COVID-19 was initially considered a pulmonary problem, it soon became clear that various other organs were involved. Thus, many care providers, including kidney health personnel, were overwhelmed or developed burnout. This review aims to describe the spectrum of burnout in mass disasters and suggests solutions specifically for nephrology personnel by extending previous experience to the COVID-19 pandemic. Burnout (a psychologic response to work-related stress) is already a frequent part of routine nephrology practice and, not surprisingly, is even more common during mass disasters due to increased workload and specific conditions, in addition to individual factors. Avoiding burnout is essential to prevent psychologic and somatic health problems in personnel as well as malpractice, understaffing, and inadequate health care delivery, all of which increase the health care burden of disasters. Burnout may be prevented by predisaster organizational measures, which include developing an overarching plan and optimizing health care infrastructure, and ad hoc disaster-specific measures that encompass both organizational and individual measures. Organizational measures include increasing safety, decreasing workload and fear of malpractice, optimizing medical staffing and material supplies, motivating personnel, providing mental health support, and enabling flexibility in working circumstances. Individual measures include training on coping with stress and problematic conditions, minimizing the stigma of emotional distress, and maintaining physical health. If these measures fall short, asking for external help is mandatory to avoid an inefficient disaster health care response. Minimizing burnout by applying these measures will improve health care provision, thus saving as many lives as possible.

Integrating Microfluidic Models with Hemoglobin‐Based Oxygen Carriers for Investigating Oxygen‐Mediated Endothelial Function

Inadequate oxygen delivery to tissue, or hypoxia, is caused by extensive abnormalities in the structure and function of the vascular network. Hypoxia also has a significant role in vascular diseases such as stroke, pregnancy disorders, and cancer. Despite its prevalence, there is no established method for alleviating hypoxia and its deleterious effects to vascular function. Existing experimental models are incapable of enabling cellular and intercellular microcirculatory measurements while also controlling the local oxygen environment, impeding our ability to mechanistically study these effects. Hemoglobin-based oxygen carriers (HBOCs) are a promising class of red blood cell substitute which have been well characterized for transfusion medicine applications, yet little has been done to study the effects of HBOC administration on vascular function at the cellular level. In this work, we put forth a novel integration of microfluidic vascular models with HBOCs to investigate the effects of oxygen transport in microcirculation in vitro. We hypothesize that alleviating hypoxia with HBOCs restores normal blood vessel structure and function. We fabricated fully-lumenized microvessels in vitro which mimic post-capillary venules. We assessed vessel stability by immunofluorescence staining, and permeability under environmentally-controlled normoxic and hypoxic conditions. We then synthesized polymerized hemoglobin (PolyHb), an HBOC with favorable molecular weight and oxygen-carrying properties to alleviate hypoxia while minimizing extravasation and subsequent toxicity. We validated that PolyHb may be synthesized under varying conditions to selectively control the HBOC size and oxygen affinity, demonstrating that these properties can be modified to enable favorable oxygen transport and may be varied based on the desired application. As compared to previous generation HBOCs, PolyHb can attain molecular weights which will enable intravascular circulation to minimize toxicity, making PolyHb an ideal candidate for microfluidic investigation into the physiological effects of rescuing hypoxia. In future work, we will perfuse PolyHb through the engineered microvessels at constant flow and physiological shear stress levels to assess the ability of PolyHb to relieve induced hypoxia under imposed circumferential and longitudinally oriented hypoxia gradients.