EXPLORING THE ROLE OF CENTRAL VENOUS OXYGEN SATURATION IN THE EVALUATION AND MANAGEMENT OF SEVERE HYPOXEMIA IN MECHANICALLY VENTILATED PATIENTS.

ABSTRACT: Background: Although central venous oxygen saturation (ScvO 2 ) has been used as an endpoint for the treatment of circulatory shock, its role in guiding the evaluation and treatment of patients with severe hypoxemia remains to be assessed. The aim of this study was to assess the incidence of low ScvO 2 in a cohort of hypoxemic patients and the association of this finding with differences in clinical management and patient outcomes. Methods: Retrospective review of data from adult intensive care unit patients with hypoxemia who required invasive mechanical ventilation for over 24 h and had at least one ScvO 2 measured within 6 h of a PaO 2 /FiO 2 ratio <200. Results: Of 442 mechanically ventilated patients with severe hypoxemia, 249 (56%) had an ScvO 2 <70%. When compared with patients with ScvO 2 ≥70%, those with low ScvO 2 had worse systemic oxygenation and hemodynamic parameters and were more likely to receive red blood cell transfusions (31.7% vs. 18.1%, P = 0.001), epinephrine (27.3% vs. 16.6%, P = 0.007), and inodilators. Outcomes such as median intensive care unit length of stay (7.5 vs. 8.3 days, P = 0.337) and hospital mortality (39.8% vs. 35.7%, P = 0.389) were not different between groups. When stratified by the central venous-to-arterial CO 2 difference (∆PCO 2 ), patients with a low ScvO 2 and normal ∆PCO 2 had lower median PaO 2 and hemoglobin levels and received more red blood cell transfusions, whereas those with an increased ∆PCO 2 had a lower pulse pressure and cardiac index and were more likely to receive epinephrine and milrinone. Conclusion: Low ScvO 2 is frequently observed in mechanically ventilated patients with severe hypoxemia, and these patients receive different interventions. Clinicians often use therapies targeting systemic oxygen delivery to correct low ScvO 2 . Prospective research is needed to identify patients with severe hypoxemia that might benefit from interventions targeting systemic oxygen delivery.

Comparative costs for critically ill patients with limited English proficiency versus English proficiency.

OBJECTIVES: To conduct comparative cost analysis of hospital care for critically ill patients with Limited English Proficiency (LEP) versus patients with English proficiency (controls). PATIENTS AND METHODS: We conducted a historical cohort study using propensity matching at Mayo Clinic Rochester, a quaternary care academic center. We included hospitalized patients who had at least one admission to ICU during a 10-year period between 1/1/2008-12/31/2017. RESULTS: Due to substantial differences in baseline characteristics of the groups, propensity matching for the covariates age, sex, race, ethnicity, APACHE 3 score, and Charlson Comorbidity score was used, and we achieved the intended balance. The final cohort included 80,404 patients, 4,246 with LEP and 76,158 controls. Patients with LEP had higher costs during hospital admission to discharge, with a mean cost difference of $3861 (95% CI $822 to $6900, p = 0.013) and also higher costs during index ICU admission to hospital discharge, with a mean cost difference of $3166 (95% CI $231 to $6101, p = 0.035). A propensity matched cohort including only those that survived showed those with LEP had significantly greater mean costs for all outcomes. Sensitivity analysis revealed that international patients with LEP had significantly greater overall hospital costs of $9,240 than patients with LEP who resided in the US (95% CI $3341 to $15,140, p = 0.002). CONCLUSION: This is the first study to demonstrate significantly higher costs for patients with LEP experiencing a critical illness. The causes for this may be increased healthcare utilization secondary to communication deficiencies that impede timely decision making about care.

Coagulation Tests and Bleeding Classification After Cardiopulmonary Bypass: A Prospective Study.

OBJECTIVE: No recent prospective studies have analyzed the accuracy of standard coagulation tests and thromboelastography (TEG) to identify patients with excessive microvascular bleeding following cardiopulmonary bypass (CPB). The aim of this study was to assess the value of coagulation profile tests, as well as TEG, for the classification of microvascular bleeding after CPB. DESIGN: A prospective observational study. SETTING: At a single-center academic hospital. PARTICIPANTS: Patients ≥18 years of age undergoing elective cardiac surgery. INTERVENTIONS: Qualitative assessment of microvascular bleeding post-CPB (surgeon and anesthesiologist consensus) and the association with coagulation profile tests and TEG values. MEASUREMENTS AND MAIN RESULTS: A total of 816 patients were included in the study-358 (44%) bleeders and 458 (56%) nonbleeders. Accuracy, sensitivity, and specificity for the coagulation profile tests and TEG values ranged from 45% to 72%. The predictive utility was similar across tests, with prothrombin time (PT) (62% accuracy, 51% sensitivity, 70% specificity), international normalized ratio (INR) (62% accuracy, 48% sensitivity, 72% specificity), and platelet count (62% accuracy, 62% sensitivity, 61% specificity) displaying the highest performance. Secondary outcomes were worse in bleeders versus nonbleeders, including higher chest tube drainage, total blood loss, transfusion of red blood cells, reoperation rates (p < 0.001, respectively), readmission within 30 days (p = 0.007), and hospital mortality (p = 0.021). CONCLUSIONS: Standard coagulation tests and individual components of TEG in isolation agree poorly with the visual classification of microvascular bleeding after CPB. The PT-INR and platelet count performed best but had low accuracy. Further work is warranted to identify better testing strategies to guide perioperative transfusion decisions in cardiac surgical patients.

Clot Stiffness Measured By Seer Sonorheometry As a Marker Of Poor Prognosis In Hospitalized COVID-19 Patients.

A high risk of thrombotic complications has been observed among severely ill COVID-19 patients. Viscoelastic tests (VET) have shown a hypercoagulable profile in these patients, although so far there is no clear evidence on the use of these tools as predictors of risk in the clinical course of patients. In this study we aimed to evaluate the association between Quantra® sonorheometry VET parameters, standard coagulation tests and inflammatory markers in 69 patients with COVID-19 on hospital admission with disease severity and outcome. Inflammatory markers were elevated in a high percentage of patients, as were coagulation-related parameters such as fibrinogen and D-dimer levels. Quantra® sonorheometry analysis revealed increased clot stiffness (CS), especially due to increased fibrinogen contribution (FCS) in 63.7%. Analysis of clot stability to lysis (CSL) on the Quantra showed a value of 100%, suggesting hypofibrinolysis, in 32.4%. Age > 65 years, elevated values of fibrinogen, D-dimer, LDH, increased CS and CSL were significantly associated with worsening disease. The combination of elevated FCS and D-dimer values showed a particularly high prognostic value in distinguishing patients with severe symptomatology. In conclusion, FCS measured by Quantra® system and its combination with D-dimer could be established as a powerful tool to identify poor prognosis in COVID-19 patients on hospital admission.

A quantitative biophysical principle to explain the 3D cellular connectivity in curved epithelia.

Epithelial cell organization and the mechanical stability of tissues are closely related. In this context, it has been recently shown that packing optimization in bended or folded epithelia is achieved by an energy minimization mechanism that leads to a complex cellular shape: the "scutoid". Here, we focus on the relationship between this shape and the connectivity between cells. We use a combination of computational, experimental, and biophysical approaches to examine how energy drivers affect the three-dimensional (3D) packing of tubular epithelia. We propose an energy-based stochastic model that explains the 3D cellular connectivity. Then, we challenge it by experimentally reducing the cell adhesion. As a result, we observed an increment in the appearance of scutoids that correlated with a decrease in the energy barrier necessary to connect with new cells. We conclude that tubular epithelia satisfy a quantitative biophysical principle that links tissue geometry and energetics with the average cellular connectivity.

Detecting professional interpreter use among patients with limited English proficiency: Derivation and validation study.

Objectives: The objective of this derivation and validation study was to develop and validate a search strategy algorithm to detect patients who used professional interpreter services. Methods: We identified all adults who had at least one intensive care unit admission during their hospital stay across the Mayo Clinic Enterprise between 1 January 2015 and 30 June 2020. Three random subsets of 100 patients were extracted from 60,268 patients to develop the search strategy algorithm. Two physician reviewers conducted gold standard manual chart review and any discrepancies were resolved by a third reviewer. These results were compared with the search strategy algorithm each time it was refined. Sensitivity and specificity were calculated during each phase by comparing the search strategy results to the reference gold standard for both derivation cohorts and the final validation cohort. Results: The first search strategy resulted in a sensitivity of 100% and a specificity of 89%. The second revised search strategy achieved a sensitivity of 100% and a specificity of 87%. The final version of the search strategy was applied to the validation subset and sensitivity and specificity were 100% and 89%, respectively. Conclusion: We derived and validated a search strategy algorithm to assess interpreter use among hospitalized patients. Using a search strategy algorithm with high sensitivity and specificity can reduce the time required to abstract data from the electronic medical records compared with manual data abstraction.

Diseño y caracterización de un sistema de entrega de fármacos autoemulsificable (SEDDS) de estradiol por diagramas de fases pseudoternarios y pruebas fisicoquímicas

Introducción: el estradiol es una hormona esteroide sexual femenina usada ampliamente como terapia hormonal que presenta una baja biodisponibilidad, debido a su baja solubilidad acuosa y a su alta hidrofobicidad, perteneciendo a la clase II del sistema de clasificación de biofarmacéutica. Objetivos: diseñar y caracterizar un sistema de entrega de fármacos autoemulsificable (SEDDS) para el fármaco estradiol por pruebas fisicoquímicas con el fin de obtener la relación óptima que permitiera mejorar su solubilidad acuosa, velocidad de disolución y potencialmente su biodisponibilidad. Método: estudios de solubilidad en diferentes solventes, diagramas de fases pseudoternarios constituidos por aceites, tensioactivos, cotensioactivos y agua permitieron reconocer las diferentes regiones de formación de SEDDS e identificar los porcentajes de excipientes que conducen a la formación de soluciones isotrópicas; las formulaciones resultantes fueron caracterizadas en tiempo de autoemulsificación, robustez a la dilución, punto de nube y perfil de disolución en capsula dura. Resultados: las formulaciones que contenían Capmul MCM®, Kolliphor® RH40 y Transcutol®, tuvieron un tiempo de autoemulsificación de aproximadamente 1 min; fueron estables en tres distintos pH (1,2; 4,5 y 7,2), en diferentes volúmenes de dilución, exhibiendo una apariencia transparente, ligeramente azulada, sin precipitados, o separación de fases, puntos de nube mayores en comparación de las formulaciones que contenían Gelucire® 44/14. Conclusiones: las estrategias de caracterización empleadas en el desarrollo de esta investigación demostraron ser eficientes para la selección adecuada de excipientes y su proporción óptima para el diseño eficaz de un sistema de entrega de fármaco autoemulsificable (SEDDS).

SUMMARY Introduction: Estradiol is a female sex steroid hormone widely used as hormonal therapy that has low bioavailability, due to its low aqueous solubility and high hydro-phobicity, belonging to class II of the Biopharmaceutical Classification System. Aim: To design and characterize a self-emulsifying drug delivery system (SEDDS) for the drug estradiol by physicochemical tests to obtain the most optimal ratio that would improve its aqueous solubility, dissolution rate, and potentially its bioavailability. Method: Solubility studies in different solvents; pseudo ternary phase diagrams made up of oils, surfactants, co-surfactants, and water, allowed to recognize the different regions of SEDDS formation and identify the percentages of excipients that lead to the formation of isotropic solutions; The resulting formulations were characterized in autoemulsification time, robustness to dilution, cloud point and dissolution profile in a hard capsule. Results: The formulations containing Capmul MCM®, Kolliphor® RH40, and Transcutol®, had an autoemulsification time of approximately 1 minute; were stable at three different pHs (1.2, 4.5 and 7.2), at different dilution volumes, exhibiting a transparent, slightly bluish appearance, without precipitates, or phase separation, higher cloud points compared to the formulations containing Gelucire® 44/14. Conclusions: The characterization strategies used in the development of this research proved to be efficient for the adequate selection of excipients and their optimal ratio for the effective design of a self-emulsifying drug delivery system (SEDDS).

Introdução: o estradiol é um hormônio esteroide sexual feminino amplamente utilizado como terapia hormonal que apresenta baixa biodisponibilidade devido à sua baixa solubilidade aquosa e alta hidrofobicidade, pertencente à classe II do sistema de classificação biofarmacêutica. Objetivos: projetar e caracterizar um sistema de liberação de drogas autoemulsificante (SEDDS) para o fármaco estradiol por meio de testes físico-químicos a fim de obter a proporção ideal que melhore sua solubilidade aquosa, taxa de dissolução e potencialmente sua biodisponibilidade. Método: estudos de solubilidade em diferentes solventes, diagramas de fases pseudoternários compostos por óleos, tensoativos, cotensoativos e água permitiram reconhecer as diferentes regiões de formação de SEDDS e identificar as porcentagens de excipientes que levam à formação de soluções isotrópicas; as formulações resultantes foram caracterizadas quanto ao tempo de autoemulsificação, robustez à diluição, ponto de turvação e perfil de dissolução da cápsula dura. Resultados: as formulações contendo Capmul MCM®, Kolliphor® RH40 e Transcutol®, tiveram um tempo de autoemulsificação de aproximadamente 1 min; foram estáveis em três diferentes pH's (1,2; 4,5 e 7,2), em diferentes volumes de diluição, apresentando aspecto transparente, levemente azulado, sem precipitados ou separação de fases, pontos de turvação mais elevados em relação às formulações contendo Gelucire® 44/14. Conclusões: as estratégias de caracterização utilizadas no desenvolvimento desta pesquisa mostraram-se eficientes para a seleção adequada de excipientes e sua proporção ideal para o desenho eficaz de um sistema de liberação de fármacos autoemulsificante (SEDDS).

Reintubation Summation Calculation: A Predictive Score for Extubation Failure in Critically Ill Patients.

OBJECTIVE: To derive and validate a multivariate risk score for the prediction of respiratory failure after extubation. PATIENTS AND METHODS: We performed a retrospective cohort study of adult patients admitted to the intensive care unit from January 1, 2006, to December 31, 2015, who received mechanical ventilation for ≥48 h. Extubation failure was defined as the need for reintubation within 72 h after extubation. Multivariate logistic regression model coefficient estimates generated the Re-Intubation Summation Calculation (RISC) score. RESULTS: The 6,161 included patients were randomly divided into 2 sets: derivation (n = 3,080) and validation (n = 3,081). Predictors of extubation failure in the derivation set included body mass index <18.5 kg/m2 [odds ratio (OR), 1.91; 95% CI, 1.12-3.26; P = 0.02], threshold of Glasgow Coma Scale of at least 10 (OR, 1.68; 95% CI, 1.31-2.16; P < 0.001), mean airway pressure at 1 min of spontaneous breathing trial <10 cmH2O (OR, 2.11; 95% CI, 1.68-2.66; P < 0.001), fluid balance ≥1,500 mL 24 h preceding extubation (OR, 2.36; 95% CI, 1.87-2.96; P < 0.001), and total mechanical ventilation days ≥5 (OR, 3.94; 95% CI 3.04-5.11; P < 0.001). The C-index for the derivation and validation sets were 0.72 (95% CI, 0.70-0.75) and 0.72 (95% CI, 0.69-0.75). Multivariate logistic regression demonstrated that an increase of 1 in RISC score increased odds of extubation failure 1.6-fold (OR, 1.58; 95% CI, 1.47-1.69; P < 0.001). CONCLUSION: RISC predicts extubation failure in mechanically ventilated patients in the intensive care unit using several clinically relevant variables available in the electronic medical record but requires a larger validation cohort before widespread clinical implementation.

Electronic Medical Record-Based Pager Notification Reduces Excess Oxygen Exposure in Mechanically Ventilated Subjects.

BACKGROUND: Liberal oxygenation during mechanical ventilation is harmful in critically ill patients and in certain subsets of patients, including those with stroke, acute myocardial infarction, and cardiac arrest. Surveillance through electronic medical records improves safety of mechanical ventilation in the ICU. To date, this practice has not been used for oxygen titration ([Formula: see text]) in adults. We hypothesize that a surveillance system based on the electronic medical record to alert respiratory therapists to titrate [Formula: see text] is feasible, safe, and efficacious. METHODS: In this pilot study, mechanically ventilated subjects were randomized to respiratory therapist-driven [Formula: see text] titration after an electronic alert versus standard of care (ie, titration based on physician order). An automated surveillance system utilizing a hyperoxemia-detection algorithm generated an electronic alert to a respiratory therapist's pager. Hyperoxemia was defined as [Formula: see text] > 0.5 and [Formula: see text] > 95% for > 30 min. No other aspects of treatment were changed. We assessed feasibility, safety, and preliminary efficacy. Primary outcome was duration of hyperoxemia during mechanical ventilation. An unsafe outcome was identified as hypoxemia ([Formula: see text] < 88%) within 1 h after titration per alert. Feasibility was assessed by a survey of respiratory therapists. RESULTS: Of 226 randomized subjects, 31 were excluded (eg, programming errors of the electronic alerts, no consent, physician discretion). We included 195 subjects, of whom 86 were in the intervention arm. Alert accuracy was 78%, and respiratory therapists responded to 64% of the alerts. During mechanical ventilation, exposure to hyperoxemia significantly decreased in the intervention group (median 13.5 h [interquartile range 6.2-29.4] vs 18.8 h [interquartile range 9.6-37.4]). No episodes of significant hypoxemia were registered. Most respiratory therapists agreed that the alert was helpful in reducing excessive oxygen exposure. CONCLUSIONS: Use of an electronic surveillance system to titrate [Formula: see text] was safe and feasible and showed preliminary efficacy in reducing hyperoxemia. Our study serves to justify larger randomized controlled trials for [Formula: see text] titration.

Association of negative fluid balance during the de-escalation phase of sepsis management with mortality: A cohort study.

PURPOSE: We aimed to evaluate the impact of negative fluid balance during the fluid de-escalation phase of sepsis management. MATERIAL AND METHODS: This is a historical cohort study of adult intensive care units (ICU) patients with septic shock and severe sepsis in a quaternary medical center, from January 2007 through December 2009. We used regression modeling to assess the impact of negative volume balance on mortality after adjustments for age, comorbidities, and illness severity. RESULTS: Among 633 enrolled patients, 387 patients reached negative fluid balance who in comparison with others had a lower 90-day mortality rate (36% vs. 44%; P = .048), despite higher severity of illness. Each 1-L negative daily fluid balance was associated with reduced ICU, hospital, 90-day and 1-year mortality (hazard ratio [HR] 0.39 [95%CI, 0.28-0.57], 0.76 [95%CI, 0.63-0.94], 0.69 [95%CI, 0.59-0.81], 0.67 [0.58-0.78], respectively; P < .05). This protective effect of negative volume balance was maintained when cumulative ICU fluid balance was utilized. CONCLUSIONS: There is not only a significant association between outcomes of patients who were resuscitated for sepsis and achieving negative fluid balance, but also the amount of daily or cumulative negative fluid balance is associated with lower mortality of these patients. Prospective clinical trials are needed to validate this finding.

Implementation of a patient blood management program in hematopoietic stem cell transplantation (Editorial, p. 2763).

BACKGROUND: Recipients of hematopoietic stem cell transplantation (HSCT) are among the highest consumers of allogeneic red blood cell (RBC) and platelet (PLT) components. The impact of patient blood management (PBM) efforts on HSCT recipients is poorly understood. STUDY DESIGN AND METHODS: This observational study assessed changes in blood product use and patient-centered outcomes before and after implementing a multidisciplinary PBM program for patients undergoing HSCT at a large academic medical center. The pre-PBM cohort was treated from January 1 through September 31, 2013; the post-PBM cohort was treated from January 1 through September 31, 2015. RESULTS: We identified 708 patients; 284 of 352 (80.7%) in the pre-PBM group and 225 of 356 (63.2%) in the post-PBM group received allogeneic RBCs (p < 0.001). Median (interquartile range [IQR]) RBC volumes were higher before PBM than after PBM (3 [2-4] units vs. 2 [1-4] units; p = 0.004). A total of 259 of 284 pre-PBM patients (91.2%) and 57 of 225 (25.3%) post-PBM patients received RBC transfusions when hemoglobin levels were more than 7 g/dL (p < 0.001). The median (IQR) PLT transfusion quantities was 3 (2-5) units for pre-PBM patients and 2 (1-4) units for post-PBM patients (p < 0.001). For patients with PLT counts of more than 10 × 109 /L, a total of 1219 PLT units (73.4%) were transfused before PBM and 691 units (48.8%) were transfused after PBM (p < 0.001). Estimated transfusion expenditures were reduced by $617,152 (18.3%). We noted no differences in clinical outcomes or transfusion-related adverse events. CONCLUSION: Patient blood management implementation for HSCT recipients was associated with marked reductions in allogeneic RBC and PLT transfusions and decreased transfusion-related costs with no detrimental impact on clinical outcomes.

Author Correction: Scutoids are a geometrical solution to three-dimensional packing of epithelia.

The original version of this Article contained an error in ref. 39, which incorrectly cited 'Fristrom, D. & Fristrom, J. W. in The Development of Drosophila melanogaster (eds. Bate, M. & Martinez-Arias, A.) II, (Cold spring harbor laboratory press, 1993)'. The correct reference is 'Condic, M.L, Fristrom, D. & Fristrom, J.W. Apical cell shape changes during Drosophila imaginal leg disc elongation: a novel morphogenetic mechanism. Development 111: 23-33 (1991)'. Furthermore, the last sentence of the fourth paragraph of the introduction incorrectly omitted citation of work by Rupprecht et al. The correct citation is given below. These errors have now been corrected in both the PDF and HTML versions of the Article. Rupprecht, J.F., Ong, K.H., Yin, J., Huang, A., Dinh, H.H., Singh, A.P., Zhang, S., Yu, W. & Saunders, T.E. Geometric constraints alter cell arrangements within curved epithelial tissues. Mol. Biol. Cell 28, 3582-3594 (2017).

Scutoids are a geometrical solution to three-dimensional packing of epithelia.

As animals develop, tissue bending contributes to shape the organs into complex three-dimensional structures. However, the architecture and packing of curved epithelia remains largely unknown. Here we show by means of mathematical modelling that cells in bent epithelia can undergo intercalations along the apico-basal axis. This phenomenon forces cells to have different neighbours in their basal and apical surfaces. As a consequence, epithelial cells adopt a novel shape that we term "scutoid". The detailed analysis of diverse tissues confirms that generation of apico-basal intercalations between cells is a common feature during morphogenesis. Using biophysical arguments, we propose that scutoids make possible the minimization of the tissue energy and stabilize three-dimensional packing. Hence, we conclude that scutoids are one of nature's solutions to achieve epithelial bending. Our findings pave the way to understand the three-dimensional organization of epithelial organs.

Intranasal insulin reverts central pathology and cognitive impairment in diabetic mother offspring.

BACKGROUND: Adverse effects in diabetic mothers offspring (DMO) are a major concern of increasing incidence. Among these, chronic central complications in DMO remain poorly understood, and in extreme cases, diabetes can essentially function as a gestational brain insult. Nevertheless, therapeutic alternatives for DMO are limited. METHODS: Therefore, we have analyzed the central long-term complications in the offspring from CD1 diabetic mothers treated with streptozotozin, as well as the possible reversion of these alterations by insulin administration to neonates. Brain atrophy, neuronal morphology, tau phosphorylation, proliferation and neurogenesis were assessed in the short term (P7) and in the early adulthood (10 weeks) and cognitive function was also analyzed in the long-term. RESULTS: Central complications in DMO were still detected in the adulthood, including cortical and hippocampal thinning due to synaptic loss and neuronal simplification, increased tau hyperphosphorylation, and diminished cell proliferation and neurogenesis. Additionally, maternal diabetes increased the long-term susceptibility to spontaneous central bleeding, inflammation and cognition impairment in the offspring. On the other hand, intracerebroventricular insulin administration to neonates significantly reduced observed alterations. Moreover, non-invasive intranasal insulin reversed central atrophy and tau hyperphosphorylation, and rescued central proliferation and neurogenesis. Vascular damage, inflammation and cognitive alterations were also comparable to their counterparts born to nondiabetic mice, supporting the utility of this pathway to access the central nervous system. CONCLUSIONS: Our data underlie the long-term effects of central complications in DMO. Moreover, observed improvement after insulin treatment opens the door to therapeutic alternatives for children who are exposed to poorly controlled gestational diabetes, and who may benefit from more individualized treatments.

Impact of Telemedicine Monitoring of Community ICUs on Interhospital Transfers.

OBJECTIVES: To study the effects of tele-ICU monitoring on interhospital transfers from community-based ICUs to the quaternary care hospital at Mayo Clinic, Rochester, MN. DESIGN: This is a retrospective review of data on interhospital transfers comparing trends prior to tele-ICU implementation to those following implementation. SETTING: Tele-ICU programs are increasingly utilized to fill resource gaps in caring for critically ill patients. How such programs impact population and bed management within a healthcare system are not known. Mayo Clinic serves as quaternary referral care center for hospitals in the region within the Mayo Clinic Health System. In August 2013, we implemented tele-ICU monitoring at six Mayo Clinic Health System hospital ICUs. SUBJECTS: All adult ICU admissions during the study period (preimplementation phase: January 1, 2012, to December 31, 2012; and postimplementation phase: January 1, 2014, to December 31, 2014) in any of the six specified community ICUs were included in the study. MEASUREMENTS AND MAIN RESULTS: Interhospital transfers significantly increased post institution of tele-ICU (p = 0.040) and was attributed primarily to transfer from less specialized ICUs (p = 0.037) as compared with more resource-intensive ICUs (p = 0.88). However, for such patient transfers, there were no significant differences before and after severity of illness scores, ICU mortality, or inhospital mortality. CONCLUSION: In a regional healthcare system, implementation of a tele-ICU program is associated with an increase in interhospital transfers from less resourced ICUs to the referral center, a trend that is not readily explained by increased severity of illness.

Chile's national nutritional supplementation program for older people: lessons learned.

Demographic changes in developing countries have resulted in rapid increases in the size of the older population. As a result, health-care budgets face increasing costs associated with the declining health and function of older people. Some governments have responded to this situation by designing innovative programs aimed at older people. One such program, implemented by the government of Chile, distributes an instant food mix fortified with vitamins and minerals to all persons over 70 years old who are registered by the national health service. The national health service covers approximately 90% of the older population. The program specifically targets nutritional vulnerability and micronutrient deficiency, which are common among poor older people in Chile. We present here the findings of a one-year investigation into all aspects of Chile's program for the elderly. The research included in-depth interviews with policy makers and program implementers, focus group discussions with user groups, analysis of the micronutrient content of the nutritional supplement, and telephone interviews of a random sample of older people. The results demonstrate that there can be a considerable degree of self-targeting within national programs; programs need to be sufficiently flexible to permit periodic protocol change; user groups must be consulted both before and during program implementation; and the design of an effective program evaluation must be in place before program implementation. It is hoped that these results will be useful to policy makers and implementers planning programs aimed at improving the health and function of older people.

Enfermedad hemolítica feto-neonatal: nuestra experiencia en transfusiones intra-uterinas intraperitoneales / Feto-neonatal haemolytic disease: our experience intraperitoneal intra-uterine transfusions

Desde enero de 1985 a diciembre de 1992 se realizaron 250 transfusiones intra-útero bajo control ecográfico en 106 pacientes con enfermedad hemolítica feto-neonatal severa (grado III) que es aproximadamente la cuarta parte (23,7 por ciento) de la población sensibilizada. Detallamos técnicas y metodología utilizada. Se analizan los resultados obtenidos (nacidos vivos o nacidos muertos) según semanas de iniciación del tratamiento y presencia o no de ascitis. La proporción de nacidos vivos fue significativamente superior cuando iniciamos el tratamiento en la semana 25 o después. La proporción de nacidos vivos fue significativamente menor cuando existió ascitis al inicio del tratamiento

Enfermedad hemolítica feto-neonatal: nuestra experiencia en transfusiones intra-uterinas intraperitoneales / Feto-neonatal haemolytic disease: our experience intraperitoneal intra-uterine transfusions

Desde enero de 1985 a diciembre de 1992 se realizaron 250 transfusiones intra-útero bajo control ecográfico en 106 pacientes con enfermedad hemolítica feto-neonatal severa (grado III) que es aproximadamente la cuarta parte (23,7 por ciento) de la población sensibilizada. Detallamos técnicas y metodología utilizada. Se analizan los resultados obtenidos (nacidos vivos o nacidos muertos) según semanas de iniciación del tratamiento y presencia o no de ascitis. La proporción de nacidos vivos fue significativamente superior cuando iniciamos el tratamiento en la semana 25 o después. La proporción de nacidos vivos fue significativamente menor cuando existió ascitis al inicio del tratamiento