Prehospital Systolic Blood Pressure Thresholds: A Community‐based Outcomes Study

Objectives Emergency medical services (EMS) personnel commonly use systolic blood pressure ( sBP ) to triage and treat acutely ill patients. The definition of prehospital hypotension and its associated outcomes are poorly defined. The authors sought to determine the discrimination of prehospital sBP thresholds for 30‐day mortality and to compare patient classification by best‐performing thresholds to traditional cutoffs. Methods In a community‐based cohort of adult, nontrauma, noncardiac arrest patients transported by EMS between 2002 and 2006, entries to state hospital discharge data and death certificates were linked. Prehospital sBP thresholds between 40 and 140 mm Hg in derivation ( n =  132,624) and validation ( n =  22,020) cohorts and their discrimination for 30‐day mortality, were examined. Cutoffs were evaluated using the 0/1 distance, Youden index, and adjusted Z‐statistics from multivariable logistic regression models. Results In the derivation cohort, 1,594 (1.2%) died within 24 hours, 7,404 (6%) were critically ill during hospitalization, and 6,888 (5%) died within 30 days. The area under the receiver operating characteristic (ROC) curve for sBP was 0.60 (95% confidence interval [CI] = 0.59, 0.61) for 30‐day mortality and 0.64 (95% CI = 0.62 0.66) for 24‐hour mortality. The 0/1 distance, Youden index, and adjusted Z‐statistics found best‐performing sBP thresholds between 110 and 120 mm Hg. When compared to an sBP ≤ 90 mm Hg, a cutoff of 110 mm Hg would identify 17% ( n =  137) more deaths at 30 days, while overtriaging four times as many survivors. Conclusions Prehospital sBP is a modest discriminator of clinical outcomes, yet no threshold avoids substantial misclassification of 30‐day mortality among noninjured patients. Resumen Los Umbrales de la Presión Arterial Sistólica Prehospitalaria: Un Estudio de Base Comunitaria Acerca de la Evolución de los Pacientes Objetivos El personal de los sistemas de emergencias médicas ( SEM ) usa frecuentemente la presión arterial sistólica ( PAS ) para clasificar y tratar a los pacientes agudos. Las definiciones de hipotensión prehospitalaria y sus resultados asociados están pobremente definidos. Se determinó la discriminación de los umbrales de PAS prehospitalaria para la mortalidad a los 30 días, y se comparó la clasificación del paciente por los mejores umbrales con los puntos de corte tradicionales. Metodología Estudio de cohorte de base comunitaria de pacientes adultos no traumatológicos ni con paradas cardiorrespiratorias transportados por los SEM entre 2002 y 2006, cuyas historias estaban vinculadas con los datos de alta hospitalaria y los certificados de mortalidad. Se examinaron los umbrales de PAS prehospitalaria entre 40 mm Hg y 140 mm Hg en las cohortes de derivación ( n =  132.624), y validación ( n =  22,020), y su discriminación para la mortalidad a los 30 días. Los puntos de corte se evaluaron usando la distancia 0/1, el índice de Youden y los estadísticos Z ajustados de los modelos de regresión logística multivariable. Resultados: En la cohorte de derivación, 1.594 (1,2%) fallecieron en las primeras 24 horas, 7.404 (6%) estuvieron críticamente enfermos durante el ingreso y 6.888 (5%) fallecieron en los 30 primeros días. El área bajo la curva de la ROC para PAS fue 0,60 ( IC 95% = 0,59–0,61) para la mortalidad a los 30 días y 0,64 ( IC 95% = 0,62–0,66) para la mortalidad a las 24 horas. La distancia 0/1, el índice de Youden y las estadísticas Z ajustadas hallaronque los mejores umbrales de PAS estaban entre 110 y 120 mm Hg. Cuando se comparó con una PAS ≤ 90 mm Hg, un punto de corte de 110 mm Hg identificaría un 17% ( n =  137) más de muertes a los 30 días, mientras que sobreclasificaría cuatro veces más a los supervivientes. Conclusiones La presión arterial sistólica es un discriminador modesto de resultados clínicos. No obstante, ningún umbral evita una mala clasificación de la mortalidad a los 30 días entre los pacientes no traumatológicos.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/1/acem12142-sup-0002-DataSupplementS2_FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/2/acem12142-sup-0007-DataSupplementS7_FigS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/3/acem12142-sup-0006-DataSupplementS6_FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/4/acem12142-sup-0009-DataSupplementS9_TableS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/5/acem12142-sup-0003-DataSupplementS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/6/acem12142-sup-0008-DataSupplementS8_TableS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/7/acem12142-sup-0004-DataSupplementS4_TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/8/acem12142-sup-0001-DataSupplementS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/9/acem12142.pd

SCAMP:standardised, concentrated, additional macronutrients, parenteral nutrition in very preterm infants: a phase IV randomised, controlled exploratory study of macronutrient intake, growth and other aspects of neonatal care

<p>Abstract</p> <p>Background</p> <p>Infants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake.</p> <p>Methods</p> <p>We propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational age</p> <p>Trial registration</p> <p>Current controlled trials: <a href="http://www.controlled-trials.com/ISRCTN76597892">ISRCTN76597892</a>; EudraCT Number: 2008-008899-14</p

Vaporized Nicotine Inhalation Increases Arterial Pressure in both Supine and 70o Head-up Positions

ABSTRACT Electronic cigarettes (e-cigs) are popular with smokers looking for a healthier alternative to tobacco cigarettes. E-cigs utilize a battery, activated on inhalation, to heat propylene glycol-suspended nicotine which is inhaled as vapor, and which does not include harmful poisons found in conventional cigarettes. Although the health claims of e-cigs continue to be debated, the effects of nicotine delivered as vapor on the cardiovascular system have not been studied. Because nicotine is a sympathomemetic agent, we tested the hypothesis that e-cigs would increase arterial pressure and protect against challenges associated with upright posture. Ten non-smoking subjects (5 male) participated in two experimental trials, separated by one week (randomized). Seated blood pressures were taken after a 10 min quiet rest period, and then subjects either inhaled (once every 30 s for 10 min) on an e-cig with a placebo cartridge (0 mg nicotine) or an active cartridge (18 mg nicotine). After an additional 10 min quiet seated rest, we measured blood pressure again, and then subjects provided a urine sample for analysis of cotinine (a nicotine biomarker). We recorded ECG and finger photoplethysmographic arterial pressure. Subjects breathed to a metronome set at 15 breaths/min for 5 min supine, 5 min head-up (70o), and 5 min supine (recovery). Cotinine readings failed to register the presence of nicotine in urine, but a majority of subjects experienced dizziness and nausea after the active, but not the placebo cartridge. Seated arterial pressures were similar after the placebo cartridge (p ≥ .05), but increased from 112 ± 3/62 ± 2 mmHg to 115 ± 3/67 ± 3 after the nicotine cartridge (p ≤. 05). Systolic and diastolic pressures were higher (all p ≤ .05) after the nicotine trial compared to placebo for supine (115 ± 3/69 ± 2 vs. 106 ± 4/62 ± 2 mmHg), tilt (105 ± 4/66 ± 3 vs. 93 ± 4/60 ± 3 mmHg), and recovery (117 ± 5/72 ± 2 vs. 106 ± 4/64 ± 3 mmHg). No subject experienced presyncope during tilt for either trial. We show, for the first time, that inhalation of vaporized nicotine increases arterial pressure in the seated, supine and head-up tilt positions - suggesting sympathomemetic properties. Although mild, acute increases in arterial pressure may seem harmless, it is possible that daily, continuous use of e-cigs could result in consistently elevated arterial pressure, resulting in higher afterload and chronic cardiac strain

Effectiveness and Safety of Adalimumab Biosimilar SB5 in IBD:Outcomes in Originator to SB5 Switch, Double Biosimilar Switch and Bio-Naieve SB5 Observational Cohorts

BACKGROUND AND AIMS: Multiple adalimumab [ADA] biosimilars are now approved for use in inflammatory bowel disease [IBD]; however, effectiveness and safety data remain scarce. We aimed to investigate long-term outcomes of the ADA biosimilar SB5 in IBD patients following a switch from the ADA originator [SB5-switch cohort] or after start of SB5 [SB5-start cohort]. METHODS: We performed an observational cohort study in a tertiary IBD referral centre. All IBD patients treated with Humira underwent an elective switch to SB5. We identified all these patients in a biological prescription database that prospectively registered all ADA start and stop dates including brand names. Data on IBD phenotype, C-reactive protein [CRP], drug persistence, ADA drug and antibody levels, and faecal calprotectin were collected. RESULTS: In total, 481 patients were treated with SB5, 256 in the SB5-switch cohort (median follow-up: 13.7 months [IQR 8.6–15.2]) and 225 in the SB5-start cohort [median follow-up: 8.3 months [4.2–12.8]). Of the SB5-switch cohort, 70.8% remained on SB5 beyond 1 year; 90/256 discontinued SB5, mainly due to adverse events [46/90] or secondary loss of response [37/90]. In the SB5-start cohort, 81/225 discontinued SB5, resulting in SB5-drug persistence of 60.3% beyond 1 year. No differences in clinical remission [p = 0.53], CRP [p = 0.80], faecal calprotectin [p = 0.40] and ADA trough levels [p = 0.55] were found between baseline, week 26 and week 52 following switch. Injection site pain was the most frequently reported adverse event. CONCLUSION: Switching from ADA originator to SB5 appeared effective and safe in this study with over 12 months of follow-up

A simple clinical predictive index for objective estimates of mortality in acute lung injury

Objective: We sought to develop a simple point score that would accurately capture the risk of hospital death for patients with acute lung injury (ALI). Design: This is a secondary analysis of data from two randomized trials. Baseline clinical variables collected within 24 hours of enrollment were modeled as predictors of hospital mortality using logistic regression and bootstrap resampling to arrive at a parsimonious model. We constructed a point score based on regression coefficients. Setting: Medical centers participating in the Acute Respiratory Distress Syndrome Clinical Trials Network (ARDSnet). Patients: Model development: 414 patients with nontraumatic ALI participating in the low tidal volume arm of the ARDSnet Acute Respiratory Management in ARDS study. Model validation: 459 patients participating in the ARDSnet Assessment of Low tidal Volume and elevated End-expiratory volume to Obviate Lung Injury study. Model Validation: 459 patients participating in the ARDSnet Assessment of Low tidal Volume and elevated End-expiratory volume to Obviate Lung Injury trial. Interventions: None. Measurements and Main Results: Variables comprising the prognostic model were hematocrit 2.5 L positive (1 point), and age (1 point for age 40-64 years, 2 points for age ≥65 years). Predicted mortality (95% confidence interval) for 0, 1, 2, 3, and 4+ point totals was 8% (5% to 14%), 17% (12% to 23%), 31% (26% to 37%), 51% (43% to 58%), and 70% (58% to 80%), respectively. There was an excellent agreement between predicted and observed mortality in the validation cohort. Observed mortality for 0, 1, 2, 3, and 4+ point totals in the validation cohort was 12%, 16%, 28%, 47%, and 67%, respectively. Compared with the Acute Physiology Assessment and Chronic Health Evaluation III score, areas under the receiver operating characteristic curve for the point score were greater in the development cohort (0.72 vs. 0.67, p = 0.09) and lower in the validation cohort (0.68 vs. 0.75, p = 0.03). Conclusions: Mortality in patients with ALI can be predicted using an index of four readily available clinical variables with good calibration. This index may help inform prognostic discussions, but validation in nonclinical trial populations is necessary before widespread use.Supported, in part, by F32 HL090220, N01 HR46055, NO1 HR46058 from the National Institutes of Health.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84157/1/Cooke - Simple ALI mortality model.pd

Interhemispheric antiphasing of neotropical precipitation during the past millennium

Uncertainty about the influence of anthropogenic radiative forcing on the position and strength of convective rainfall in the Intertropical Convergence Zone (ITCZ) inhibits our ability to project future tropical hydroclimate change in a warmer world. Paleoclimatic and modeling data inform on the timescales and mechanisms of ITCZ variability; yet a comprehensive, long-term perspective remains elusive. Here, we quantify the evolution of neotropical hydroclimate over the preindustrial past millennium (850 to 1850 CE) using a synthesis of 48 paleo-records, accounting for uncertainties in paleo-archive age models. We show that an interhemispheric pattern of precipitation antiphasing occurred on multicentury timescales in response to changes in natural radiative forcing. The conventionally defined “Little Ice Age” (1450 to 1850 CE) was marked by a clear shift toward wetter conditions in the southern neotropics and a less distinct and spatiotemporally complex transition toward drier conditions in the northern neotropics. This pattern of hydroclimatic change is consistent with results from climate model simulations indicating that a relative cooling of the Northern Hemisphere caused a southward shift in the thermal equator across the Atlantic basin and a southerly displacement of the ITCZ in the tropical Americas, with volcanic forcing as the principal driver. These findings are at odds with proxy-based reconstructions of ITCZ behavior in the western Pacific basin, where changes in ITCZ width and intensity, rather than mean position, appear to have driven hydroclimate transitions over the last millennium. This reinforces the idea that ITCZ responses to external forcing are region specific, complicating projections of the tropical precipitation response to global warming

Social Influence in Televised Election Debates: A Potential Distortion of Democracy

A recent innovation in televised election debates is a continuous response measure (commonly referred to as the “worm”) that allows viewers to track the response of a sample of undecided voters in real-time. A potential danger of presenting such data is that it may prevent people from making independent evaluations. We report an experiment with 150 participants in which we manipulated the worm and superimposed it on a live broadcast of a UK election debate. The majority of viewers were unaware that the worm had been manipulated, and yet we were able to influence their perception of who won the debate, their choice of preferred prime minister, and their voting intentions. We argue that there is an urgent need to reconsider the simultaneous broadcast of average response data with televised election debates

The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease

Background: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD. Methods: Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria. Results: 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80). Conclusion: Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.Department of Veterans Affairs, Health Services Research and Development (DHA), American Lung Association (CI- 51755-N) awarded to DHA, the American Thoracic Society Fellow Career Development AwardPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84155/1/Cooke - ICD9 validity in COPD.pd