Additional Liter Research Articles

#4261 RELATIONSHIP BETWEEN FLUID OVERLOAD AND AVERAGE PLASMA REFILL RATE IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Attaining the optimal balance between achieving adequate volume removal while preserving organ perfusion remains challenging in patients on maintenance hemodialysis (HD). Quantification of fluid status using bioimpedance spectroscopy (BIS) has become routine in many countries. Inadequate vascular space refill from the interstitial tissue (plasma refill rate, PRR) is the main contributing factor of hemodynamic instability during HD. We aimed to explore the association between fluid overload (FO) and plasma refill rate (PRR) in chronic HD patients. Method Pre-HD FO [l] was assessed once per subject by BIS (Body Composition Monitor; Fresenius Medical Care) in four urban HD dialysis clinics in the U.S. For each treatment within 30 days before and after the BIS measurement, we calculated the respective pre-HD FO by assuming that differences in pre-HD body weight were equivalent to differences in FO. We then used intradialytic hematocrit (measured with the Crit-Line® Monitor, Fresenius Medical Care) and ultrafiltration data to quantify the average PRR, normalized by body weight (Wang et al. Kidney360, 2023): To calculate the starting blood volume (BV), we first calculated the ending BV using the Nadler equation, followed by back-calculating the starting BV based on the cumulative change in relative BV. Plasma refill volume was calculated as the sum of the changes in blood volume and ultrafiltration volume; plasma refill volume was then divided by treatment time and estimated clinical dry weight to calculate the PRR [ml/kg/hr]. Results We analyzed 746 HD sessions from 79 patients (age 61 ± 15 years; 52 (66%) males; 41 (52%) black and 33 (42%) white). Across all HD sessions, PRR was positively associated with FO [slope estimate 0.92 (95% confidence interval 0.83 to 1.02) ml/kg/hr per 1 l of FO, P value < 0.0001] (Figure 1). This was also the case in subgroup analyses of fluid depleted (r = 0.94, P<0.001), normohydrated (r = 1.03, P<0.0001), and fluid overloaded subjects (r = 0.83, P<0.0001). Conclusion Across the entire fluid status spectrum, from fluid depletion to fluid overload, higher FO was associated with higher PRR on average (overall, an increase of 0.92 ml/kg/hr in PRR for each additional liter of FO). While patients with greater FO would be expected to better tolerate higher ultrafiltration rates, there is large inter-individual variability in PRR. Further investigation of the utility of PRR throughout HD may offer novel insights into fluid management and intradialytic symptom mitigation.

Prognostic factors for development of acute respiratory distress syndrome following traumatic injury: a systematic review and meta-analysis.

Our purpose was to summarise the prognostic associations between various clinical risk factors and development of acute respiratory distress syndrome (ARDS) following traumatic injury. We conducted this review in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and CHARMS (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies) guidelines. We searched six databases from inception through December 2020. We included English language studies describing the clinical risk factors associated with development of post-traumatic ARDS, as defined by either the American-European Consensus Conference or Berlin definition. We pooled adjusted odds ratios for prognostic factors using the random effects method. We assessed risk of bias using the QUIPS (Quality in Prognosis Studies) tool and certainty of findings using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. We included 39 studies involving 5 350 927 patients. We identified the amount of crystalloid resuscitation as a potentially modifiable prognostic factor associated with development of post-traumatic ARDS (adjusted OR 1.19, 95% CI 1.15-1.24 for each additional litre of crystalloid administered within the first 6 h after injury; high certainty). Non-modifiable prognostic factors with a moderate or high certainty of association with post-traumatic ARDS included increasing age, non-Hispanic White race, blunt mechanism of injury, presence of head injury, pulmonary contusion or rib fracture and increasing chest injury severity. We identified one important modifiable factor, the amount of crystalloid resuscitation within the first 24 h of injury, and several non-modifiable factors associated with development of post-traumatic ARDS. This information should support the judicious use of crystalloid resuscitation in trauma patients and may inform development of risk stratification tools.

Is the development of obesogenic food environments a self-reinforcing process? Evidence from soft drink consumption

BackgroundUnderstanding how the development of obesogenic food environments and the consumption of ultra-processed foods and beverages influence each other can help policymakers to identify effective ways to curb the current obesity epidemic. This paper was designed to investigate whether, and to what extent, the consumption of soft drinks and the prevalence of obesity are linked through feedback effects.MethodsAn ecological study design and a simultaneous equation model were used to investigate the existence of a vicious cycle between the consumption of soft drinks and the prevalence of obesity. The analysis was based on a longitudinal dataset covering per capita sales of soft drinks, the age-standardised prevalence rate of obesity and several demographic and socio-economic control variables in a sample of 98 countries worldwide for the period 2005–2019.ResultsUsing a Two-Stage Least Squares (2SLS) regression model with fixed effects, we documented a self-reinforcing process that links consumption and obesity. Changes in the spread of obesity were associated with changes in soft drink consumption: a one-unit increase in the age-adjusted prevalence rate of obesity increased consumption by about 2.39 l per person per year. Similarly, as the consumption of soft drinks rose, so did the prevalence of obesity: the age-adjusted rate of obesity increased by 0.07% for every additional litre consumed per capita. Computing the impact multipliers, we found that the outcome of a one-unit decrease in the average price of soft drinks was twofold: a) the prevalence of obesity increased by around 0.17%; and b) consumption increased by around 2.40 l per person, the sum of the increase directly caused by the price reduction (2 l) and the increase due to the interplay between consumption and obesity (0.4 l).ConclusionsThis study has identified a feedback loop between unhealthy habits (i.e. the consumption of soft drinks) and health outcomes (i.e. the prevalence of obesity). This interplay amplifies the impact of any exogenous changes in the determinants of consumption and obesity. These feedback effects should be considered and exploited in planning effective strategies to tackle the burden of obesity and the global epidemic of non-​communicable diseases.

Male sex, ostomy, infection, and intravenous fluids are associated with increased risk of postoperative ileus in elective colorectal surgery

BackgroundPostoperative ileus is a common and costly complication after elective colorectal surgery. Effects of intravenous fluid administration remain controversial, and the effect of ostomy construction has not been fully evaluated. Various restrictive intravenous fluid protocols may adversely affect renal function. We aimed to investigate the impact of intestinal reconstruction and intravenous fluid on ileus and renal function after colorectal resection under an enhanced recovery protocol. MethodsA retrospective study of a prospectively maintained institutional database for a tertiary academic medical center following National Surgical Quality Improvement Program standards was reviewed, analyzing elective colorectal resections performed under enhanced recovery protocol from 2015 to 2018. Postoperative ileus was defined as nasogastric decompression, nil per os >3 days postoperatively, or nasogastric tube insertion. Patients with and without ileus were compared. Intravenous fluid and different anastomoses and ostomies were investigated. Acute kidney injury was a secondary outcome, due to the potential of renal damage with restriction of intravenous fluid volume during and after surgery and controversy in current literature in this matter. ResultsPostoperative ileus occurred in 18.5% of patients (n = 464). Male sex (odds ratio 1.97, 95% confidence interval 1.12–3.52) and postoperative infection (odds ratio 2.13, 95% confidence interval 1.03–4.35) were associated with ileus. Compared to colorectal anastomosis, ileostomy/ileorectal anastomosis had the highest risk of ileus (odds ratio 4.9, 95% confidence interval 2.33–11.3), colostomy second highest (odds ratio 3.3, 95% confidence interval 1.35–8.39), while ileocolic anastomosis did not significantly differ (odds ratio 2.06, 95% confidence interval 0.69–5.85) on multivariate analysis. Each liter of intravenous fluid within the first 72 hours significantly correlated with postoperative ileus (odds ratio 1.41, 95% confidence interval 1.27–1.59). Rates of acute kidney injury did not differ (P = .18). ConclusionEach additional liter of intravenous fluid given in the first 72 hours increased the risk of postoperative ileus 1.4-fold. There is substantially higher risk of ileus with male sex, infection, ileostomy/ileorectal anastomosis, and colostomy. Judicious use of intravenous fluid, as described in our enhanced recovery protocol, is not detrimental for renal function in the setting of normal baseline.

Cerebral Blood Flow in Patients with Severe Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUNDTranscatheter aortic valve implantation (TAVI) is a minimally invasive, life‐saving treatment for patients with severe aortic valve stenosis that improves quality of life. We examined cardiac output and cerebral blood flow in patients undergoing TAVI to test the hypothesis that improved cardiac output after TAVI is associated with an increase in cerebral blood flow.DESIGNProspective cohort study.SETTINGEuropean high‐volume tertiary multidisciplinary cardiac care.PARTICIPANTSThirty‐one patients (78.3 ± 4.6 years; 61% female) with severe symptomatic aortic valve stenosis.MEASUREMENTSNoninvasive prospective assessment of cardiac output (L/min) by inert gas rebreathing and cerebral blood flow of the total gray matter (mL/100 g per min) using arterial spin labeling magnetic resonance imaging in resting state less than 24 hours before TAVI and at 3‐month follow‐up. Cerebral blood flow change was defined as the difference relative to baseline.RESULTSOn average, cardiac output in patients with severe aortic valve stenosis increased from 4.0 ± 1.1 to 5.4 ± 2.4 L/min after TAVI (P = .003). The increase in cerebral blood flow after TAVI strongly varied between patients (7% ± 24%; P = .41) and related to the increase in cardiac output, with an 8.2% (standard error = 2.3%; P = .003) increase in cerebral blood flow per every additional liter of cardiac output following the TAVI procedure.CONCLUSIONFollowing TAVI, there was an association of increase in cardiac output with increase in cerebral blood flow. These findings encourage future larger studies to determine the influence of TAVI on cerebral blood flow and cognitive function.

Effectiveness of China's plug-in electric vehicle subsidy

Abstract Subsidies for promoting plug-in electric vehicle (PEV) adoption are a key component of China's overall plan for reducing local air pollution and greenhouse gas emissions from the light-duty vehicle sector. In this paper, we explore the impact and cost-effectiveness of the Chinese PEV subsidy program. In particular, a vehicle choice model is estimated using a large random sample of individual level, model year 2017 Chinese new vehicle purchases. The choice model is then used to predict PEV market share under alternative policies. Simulation results suggest that the 2.5% PEV market share of Chinese new vehicle sales in 2017 resulted in China's new vehicle fleet fuel economy improving by roughly 2%, reducing total gasoline consumption by 6.66 billion liters. However, the current PEV subsidy in China is expensive, costing $1.90 per additional liter of gasoline saved. This is due to a large number of non-additional PEV buyers, particularly high income consumers, who would have purchased the PEV regardless of the subsidy. Eliminating the subsidy for high income consumers and increasing it for low income consumers could result in a substantially lower cost per additional PEV ($13,758 versus $24,506). This would allow for greater PEV adoption (3.11% versus 2.47% market share) for the same budget. In terms of the impact of the recently announced subsidy reduction, results suggest that the PEV market share in China would have declined by 21% had the subsidy been halved without any countervailing measures. Using the same reduced budget, had zero PEV subsidies been given to high-income consumers and higher subsidies been given to low-income consumers, the PEV market share would have declined by only 8%.

Variability in usual care fluid resuscitation and risk-adjusted outcomes for mechanically ventilated patients in shock

RationaleThere remains significant controversy regarding the optimal approach to fluid resuscitation for patients in shock. The magnitude of care variability in shock resuscitation, the confounding effects of disease severity and comorbidity, and the relative impact on sepsis survival are poorly understood.ObjectiveTo evaluate usual care variability and determine the differential effect of observed and predicted fluid resuscitation volumes on risk-adjusted hospital mortality for mechanically ventilated patients in shock.MethodsWe performed a retrospective outcome analysis of mechanically ventilated patients admitted to intensive care units using the 2013 Premier Hospital Database (Premier, Inc.). Observed and predicted hospital mortality were evaluated by observed and predicted day 1 fluid administration, using the difference in predicted and observed outcomes to adjust for disease severity between groups. Both predictive models were validated using a second large administrative database (Truven Health Analytics Inc.). Secondary outcomes included duration of mechanical ventilation, hospital and ICU length of stay, and cost.ResultsAmong 33,831 patients, observed hospital mortality was incrementally higher than predicted for each additional liter of day 1 fluid beginning at 7 L (40.9% vs. 37.2%, p = 0.008). Compared to patients that received expected (± 1.5 L predicted) day 1 fluid volumes, greater-than-expected fluid resuscitation was associated with increased risk-adjusted hospital mortality (52.3% vs. 45.0%, p < 0.0001) among all patients with shock and among a subgroup of shock patients with comorbid conditions predictive of lower fluid volume administration (47.1% vs. 41.5%, p < 0.0001). However, in patients with shock but without such conditions, both greater-than-expected (57.5% vs. 49.2%, p < 0.0001) and less-than-expected (52.1% vs. 49.2%, p = 0.037) day 1 fluid resuscitation were associated with increased risk-adjusted hospital mortality.ConclusionsHighly variable day 1 fluid resuscitation was associated with a non-uniform impact on risk-adjusted hospital mortality among distinct subgroups of mechanically ventilated patients with shock. These findings support closer evaluation of fluid resuscitation strategies that include broadly applied fluid volume targets in the early phase of shock resuscitation.

Cost analysis showed that feeding preterm infants with donor human milk was significantly more expensive than mother's milk or formula.

This study analysed the comparative cost of feeding donor human milk to preterm infants compared to mother's own milk and formula. A document and process analysis and a time measurement study were carried out at the milk bank of the Level 1 Perinatal Center of the University Hospital of Greifswald, Germany, from April to June 2017. The cost analysis data were provided by the University's financial department. The total cost per year was €92085.02 for 300 litres of donor human milk: 27% of this was material costs, 51% was personnel costs, and 22% was other overheads. The average cost per litre was €306.95, and staff time was 492minutes per litre. The total marginal cost for each additional litre of donor human milk, formula or unpasteurised mother´s milk was €82.88, €10.28 and €38.42, respectively. Pasteurising a litre of donor milk cost €3.51. Providing preterm infants with donor milk was much more expensive than using formula or mother's own milk, but the cost of pasteurisation was minimal.

Prediction of Poststorage Cardiac Function From Cardioplegic Effluent in an Ex Vivo Porcine Heart Model

Abstract The use of slaughterhouse-based hearts has advantages over hearts obtained from laboratory animals for preclinical testing. However, slaughterhouse hearts have greater variability in cardiac function; this has resulted in a dispute over their actual reproducibility. This study explores the feasibility of examining the cardioplegic effluent during hypothermic cardiac arrest for the presence of biomarkers to predict poststorage heart function of slaughterhouse hearts. This may enable proactive measures to optimize preservation strategies and improve the initial cardiac performance of slaughterhouse heart experiments. Slaughterhouse pig hearts (n = 9; 420 ± 30 g) were arrested and flushed with an additional liter cardioplegia after 1 h. Effluent samples were examined for ammonia, lactate, troponin, and inorganic phosphate. After 2 h, hearts were hemoreperfused in the ex vivo heart platform PhysioHeart™ to restore physiological cardiac functions and to identify correlations between biomarkers and cardiac output. There was a negative correlation between cardiac output of revived hearts and levels of ammonia (r = −0.865; p = 0.002) and lactate (r = −0.763; p = 0.01). No correlation was found between cardiac output and levels of phosphate (r = −0.553; p = 0.12) and troponin (r = −0.367; p = 0.331). The analysis approach to assess cardioplegic biomarkers was feasible and enabled the estimation of the effectiveness of organ protection and cardiac function before reperfusion. Ammonia is a predictor for cardiac dysfunction. Effluent analysis prior to heart revival can uncover poststorage cardiac dysfunction in isolated hearts and may prevent failed experiments while improving reproducibility and standardization.

Risk Factors for Early Infection in Pediatric Spinal Deformity Surgery: A Multivariate Analysis

Study DesignRetrospective case-control study. ObjectivesTo identify risk factors for early deep surgical site infections (SSIs; within three months of index procedure) following pediatric spinal deformity surgery. BackgroundDeep surgical site infections (SSIs) following pediatric spinal deformity surgery are a source of significant morbidity. We sought to identify independent risk factors for early infection following primary, definitive single-stage pediatric posterior spinal fusion and instrumentation (PSFI). MethodsA total of 616 consecutive patients (2001–2016) from an institutional prospectively maintained Pediatric Orthopaedic Spine database were identified that met inclusion criteria of definitive single-stage PSFI. Early deep SSI was defined as infection within three months of index procedure requiring surgical intervention. A multivariate analysis of demographics, comorbidities, and perioperative factors was performed and independent risk factors were identified. ResultsEleven patients (1.6%) developed an early deep SSI. Independent risk factors for SSI identified were nonidiopathic (neuromuscular, syndromic, and congenital) etiologies of scoliosis (adjusted odds ratio [aOR]: 8.384, 95% confidence interval [CI]: 1.784-39.386, p = .007) and amount of intraoperative crystalloids (aOR: 1.547 per additional liter of fluid, 95% CI: 1.057-2.263, p = .025). Mean crystalloid administered in the SSI group was 3.3 ± 1.2 L versus 2.4 ± 1.0 L in the noninfected group (p = .019). On univariate analysis, there was no significant difference in weight of patients between cohorts (p = .869) or surgery time (p = .089). There was also no significant difference in infection rates from redosing of antibiotics intraoperatively after 3 hours of surgery (p = .231). ConclusionsNonidiopathic scoliosis and amount of intraoperative crystalloids were independently associated with early postoperative SSI. Further investigation into intraoperative fluid management may identify modifiable risk factors for early postoperative SSI in primary pediatric spinal deformity posterior spinal fusion patients. Level of EvidenceLevel III, case-control study.

Fluid resuscitation during persistent postpartum haemorrhage and maternal outcome: A nationwide cohort study

ObjectiveTo determine the association between increasing volumes of crystalloids and colloids administered before transfusion of packed red blood cells in women with persistent postpartum haemorrhage and adverse maternal outcomes. Study designRetrospective cohort study in the Netherlands. Women with persistent postpartum haemorrhage and known clear fluids volume for resuscitation were included. Women who received ≤2 L of clear fluids were the reference group. We determined the effect of every additional litre of clear fluids on total blood loss, severe maternal morbidity and mortality. Results were adjusted for patient and bleeding characteristics. ResultsOf the 883 included women, 199 received ≤2 L of clear fluids. Median blood loss for the reference group was 2.9 L (interquartile range 2.2–3.4). Adjusted mean difference in blood loss compared with the reference group was 0.2 L (95% confidence interval −0.1 to 0.5) for women in the >2 to ≤3 L, 0.4 L (0.1–0.7) for the >3 to ≤4 L category, 0.6 L (0.5–0.7) for the >4 to ≤5 L category, and 1.9 L (1.5–2.3) for the >5 to ≤7 L category. Adjusted odds ratios for adverse maternal outcomes were 1.0 (0.7–1.6), 1.2 (0.8–1.9), 1.8 (1.1–3.1) and 4.4 (2.6–7.5) for women in the 2 to ≤3 L category, >3 to ≤4 L, >4 to ≤5 L, and >5 to ≤7 L volume categories respectively. Results were similar in strata of different severities of bleeding. ConclusionClear fluids volume >4 L was independently associated with adverse maternal outcome in women with persistent postpartum haemorrhage.

Factors associated with passive immunity transfer in dairy calves: combined effect of delivery time, amount and quality of the first colostrum meal

Despite the well-known importance of an adequate colostral immunoglobulin (Ig) transfer to calf health and survival, failed transfer of passive immunity (FTPI) remains a widespread problem in dairy farming. The aim of this study was to investigate the management factors associated with FTPI in newborn calves, evaluating particularly the combined effect of delivery time, amount and quality of the first colostrum meal. The study was conducted from March to August 2014 on 21 Italian dairy farms. Farmers were asked as first to answer a farm-level questionnaire on calf management. Blood sampling was then performed on overall 244 calves (1 to 5 days of age) born from Holstein cows, and a sample of the first colostrum meal of each calf was collected. Individual information on calves and the respective colostrum management were recorded. Serum and colostrum Ig concentrations were assessed by electrophoresis. A mixed effects multivariable logistic regression model was used to investigate the association of the variables obtained from both the management questionnaire and the individual calf data with FTPI (calf serum Ig concentration <10.0 g/l). A cumulative colostrum management score (CMS) that considered delivery time, amount and quality of the first colostrum meal was generated for 236 calves, with higher values indicating better colostrum management. Overall, 41.0% of the calves were found having FTPI, and within-farm percentage of FTPI was over 20.0% in 71.4% of the farms. The risk of having FTPI was higher both for Holstein purebred calves compared with Holstein-beef crossbreds and for females compared with males. Moreover, it increased by 13% with every hour of delay of the first colostrum meal provision since birth, whereas it decreased by 59% and 3%, respectively, with every additional liter of colostrum given and every additional gram of Ig per liter contained in the colostrum fed. Calf serum Ig concentration varied significantly according to the CMS, increasing by 1.53 g/l with every additional CMS point. In order to completely avoid FTPI, calves should receive at least 2.5 l of high-quality colostrum (Ig concentration >87.6 g/l) within 1.0 h from birth. Considerable improvements are still needed about colostrum management for newborn calves in dairy farms. The results of this study will help in developing farm-specific programs for reducing the occurrence of FTPI.

Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database.

The optimal strategy of fluid resuscitation in the early hours of severe sepsis and septic shock is controversial, with both an aggressive and conservative approach being recommended. We used the 2013 Premier Hospital Discharge database to analyse the administration of fluids on the first ICU day,in 23,513 patients with severe sepsis and septic shock,who were admitted to an ICU from the emergency department. Day1 fluid was grouped into categories 1L wide,starting with 1-1.99L up to ≥9L,to examine the effect of day1 fluids on patient mortality. We built binary response models for hospital mortality and the propensity for receiving more than 5L of fluids on day1, using patient age and acute conditions present on admission. Patients were grouped by the requirement for mechanical ventilation and the presence or absence of shock. We assessed trends in the difference between actual and expected mortality,in the low fluid range (1-5L day1 fluids) and the high fluid range (5 to ≥9L day1 fluids) categories,using weighted linear regression controlling for the effects of sample size and variation within the day1 fluid category. Day1 fluid administration averaged 4.4L being lowest in the group with no mechanical ventilation and no shock (3.6L) and highest (5.4L) in the group receiving mechanical ventilation and in shock. The administration of day1 fluids was remarkably consistent on the basis of hospital size, teaching status, rural/urban location, and region of the country. The hospital mortality in the entire cohort was 25.8%, with a mean ICU and hospital length of stay of 5.1 and 9.1days, respectively. In the entire cohort, low volume resuscitation (1-4.99L) was associated with a small but significant reduction in mortality,of -0.7% per litre (95% CI -1.0%, -0.4%; p=0.02). However, in patients receiving high volume resuscitation (5 to ≥9L),the mortality increased by 2.3% (95% CI 2.0, 2.5%; p=0.0003) for each additional litre above 5L. Total hospital cost increased by $999 for each litre of fluid above 5L (adjusted R 2=92.7%, p=0.005). The mean amount of fluid administered to patients with severe sepsis and septic shock in the USA during the first ICU day is less than that recommended by the Surviving Sepsis Campaign guidelines. The administration of more than 5L of fluid during the first ICU day is associated with a significantly increased risk of death and significantly higherhospital costs.

Beverage-Specific Alcohol Sales and Gender Difference in Suicide Rates in Russia

Background: In the Western world, males die from suicide three to four times more often than females. The reasons behind the gender gap in suicide mortality are hotly debated in the scientific literature. Russia retains one of the highest gender gap in suicide rates in the world. Some researchers have reported a close link between alcohol and suicide in Russia both in present and the past. Objective: The aim of the current study was to examine the aggregate-level relationship between the consumption of different alcoholic beverages and gender difference in suicide rates in Russia between 1970 and 2015. Method: The ARIMA (autoregressive integrated moving average) modeling technique was used to evaluate the relationship between changes in the consumption of different types of alcoholic beverages and gender difference in suicide mortality across the study period. Results: The results of ARIMA analysis indicate that vodka sales is closely linked with gender difference in suicide mortality in Russia: an additional liter of vodka sales per capita was estimated to increase in the difference between male and female suicide mortality rates by 10.3%. Conclusions: This piece of evidence provides support for the hypothesis that high level of vodka consumption in conjunction with binge drinking pattern may be a major reason for the high gender difference in suicide rates and its dramatic fluctuations in Russia during the last few decades.

Abstract 5581: A model incorporating spirometry to predict absolute risk of lung cancer: The UK Biobank prospective cohort study

Abstract Background Screening with computed tomography has been shown to reduce the rate of death from lung cancer, but at substantial cost in terms of morbidity associated with overdiagnosis. The performance of screening programs can be improved by restricting screening to those people who are at sufficiently high risk of lung cancer. We sought to develop a lung cancer risk prediction model incorporating a measure of lung function (forced expiratory volume in one second: FEV1) as well as other information that is routinely available to general practitioners. Methods We built the model using participants and data from the UK Biobank prospective cohort study, which recruited 500000 people aged 37 to 73 years between 2006-2010. Follow-up for cancer incidence and death was conducted via linkage to registries. Each participant was followed up for an average of 3 years and a maximum of 6 years. We investigated factors that are routinely available or can be easily ascertained by general practitioners: sex, variables related to smoking history and addiction to nicotine, personal medical history, and family history of lung cancer. We additionally investigated lung function, which was assessed via sprirometry as the forced expiratory volume in 1 second (FEV1, litres). Conditional on these predictors, we separately modeled the hazard of lung cancer and the hazard of death using flexible parametric survival models with age as the timescale, and combined the estimated hazards to predict the 2-year absolute risk of lung cancer. Internal validation of model discrimination was assessed by calculating the bootstrap optimism-corrected c-statistic. Results There were 738 incident lung cancer diagnoses and 3956 deaths from all causes among the UK Biobank population in the follow-up period. FEV1 at baseline was strongly and inversely associated with subsequent lung cancer risk: hazard ratios [95% confidence intervals] of 0.57 [0.43,0.77] per additional liter of FEV for never, 0.50 [0.40,0.63] for former, and 0.62 [0.48,0.80] for current smoking participants. Model discrimination was high (c-statistic 0.85) and the model is likely to discriminate well when applied to new data (bootstrap optimism-corrected c-statistic 0.83). Applying the current National Lung Screening Trial(NLST) inclusion criteria to the UK Biobank data yielded a specificity of 0.95 and sensitivity of 0.37. By applying a risk prediction model-based inclusion criteria where additional factors such as FEV1 were taken into account, we could improve the sensitivity to 0.47 for the same specificity. Conclusions Comprehensive risk prediction models based on standard risk factor information, along with FEV1, can clearly outperform currently used screening criteria in terms of specificity and sennsitivity in predicting future lung cancer diagnoses, and applying a model-based screening strategy has the potential to improve the performance of lung cancer screening programs. Citation Format: David C. Muller, Mattias Johansson, Paul Brennan. A model incorporating spirometry to predict absolute risk of lung cancer: The UK Biobank prospective cohort study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5581. doi:10.1158/1538-7445.AM2015-5581

Cooling cows efficiently with sprinklers: Physiological responses to water spray

Dairies in the United States commonly cool cattle with sprinklers mounted over the feed bunk that intermittently spray the cows’ backs. These systems use potable water—an increasingly scarce resource—but there is little experimental evidence about how much is needed to cool cows or about droplet size, which is thought to affect hair coat penetration. Our objectives were to determine how sprinkler flow rate and droplet size affect physiological measures of heat load in a hot, dry climate, and to evaluate cooling effectiveness against water use. The treatments were an unsprayed control and 6 soaker nozzles that delivered four 3-min spray applications of 0.4, 1.3, or ≥4.5 L/min (with 2 droplet sizes within each flow rate) and resulting in 30 to 47% of spray directly wetting each cow. Data were collected from high-producing lactating Holsteins (n=19) tested individually in ambient conditions (air temperature=31.2±3.8°C, mean ± standard deviation). Cows were restrained in headlocks for 1h and received 1 treatment/d for 3d each, with order of exposure balanced in a crossover design. When cows were not sprayed, physiological measures of heat load increased during the 1-h treatment. All measures responded rapidly to spray: skin temperature decreased during the first water application, and respiration rate and body temperature did so before the second. Droplet size had no effect on cooling, but flow rate affected several measures. At the end of 1h, 0.4 L/min resulted in lower respiration rate and skin temperature on directly sprayed body parts relative to the control but not baseline values, and body temperature increased to 0.2°C above baseline. When 1.3 or ≥4.5 L/min was applied, respiration rate was lower than the control and decreased relative to baseline, and body temperature stayed below baseline for at least 30min after treatment ended. The treatment that best balanced cooling effectiveness against water usage was 1.3 L/min: although ≥4.5 L/min reduced respiration rate relative to baseline by 4 more breaths/min than 1.3L/min did (−13 vs. −9 breaths/min, respectively), each additional liter of water decreased this measure by only ≤0.1 breaths/min (≤1% of the total reduction achieved using 1.3 L/min). We found similar water efficiency patterns for skin temperature and the amount of time that body temperature remained below baseline after treatment ended. Thus, when using this intermittent spray schedule in a hot, dry climate, applying at least 1.3 L/min improved cooling, but above this, additional physiological benefits were relatively minor.

Delayed volume resuscitation during initial management of ruptured abdominal aortic aneurysm

In acute traumatic bleeding, permissive arterial hypotension with delayed volume resuscitation is an established lifesaving concept as abridge to surgical control. This study investigated whether preoperatively administered volume also correlated inversely with survival after ruptured abdominal aortic aneurysm (rAAA). This retrospective study analyzed prospectively collected and validated data of a consecutive cohort of patients with rAAAs (January 2001 to December 2010). Generally, fluid resuscitation was guided clinically by the patient's blood pressure and consciousness. All intravenous fluids (crystalloids, colloids, and blood products) administered before aortic clamping or endovascular sealing were abstracted from paramedic and anesthesia documentation and normalized to speed of administration (liters per hour). Logistic regression modeling, adjusted for suspected confounding covariates, was used to investigate whether total volume was independently associated with risk of death within 30 days of rAAA repair. A total of 248 patients with rAAAs were analyzed, of whom 237 (96%) underwent open repair. A median of 0.91 L of total volume per hour (interquartile range, 0.54-1.50 L/h) had been administered preoperatively to these patients. The postoperative 30-day mortality rate was 15.3% (38 deaths). The preoperative rate of fluid infusion correlated with 30-day mortality after adjustment for confounding factors, and the association persisted robustly through sensitivity analyses: each additional liter per hour increased the odds of perioperative death by 1.57-fold (95% confidence interval, 1.06-2.33; P = .026). Aggressive volume resuscitation of patients with rAAAs before proximal aortic control predicted an increased perioperative risk of death, which was independent of systolic blood pressure. Therefore, volume resuscitation should be delayed until surgical control of bleeding is achieved.

Hyperfibrinolysis at admission is an uncommon but highly lethal event associated with shock and prehospital fluid administration

Hyperfibrinolysis (HF) has been reported to occur in a range of 2% to 34% of trauma patients. Using rapid thromboelastography (r-TEG), we hypothesized that HF is (1) rarely present at admission on patients with severe injury and (2) associated with crystalloid hemodilution. To further strengthen this hypothesis, we created an in vitro hemodilution model to improve our mechanistic understanding of the early HF. The trauma registry was queried for patients who were our highest-level trauma activations and admitted directly from the scene (October 2009-October 2010). HF was defined as more than 7.5% amplitude reduction 30 minutes after maximal amplitude (LY30). Using r-TEG, we then created an in vitro hemodilution model (0.9% NS) with and without tissue injury (addition of tissue factor and tissue plasminogen activator) to identify crystalloid volumes and injury needed to achieve specific LY30 values. Admission r-TEG values were captured on 1996 consecutive admissions. Only 41 patients (2%) had HF at admission r-TEG. The groups were similar in demographics. Compared with patients without HF, the HF group had more prehospital crystalloid (1.5 vs. 0.5 L), higher median Injury Severity Score (25 vs. 16), greater admission base deficit (20 vs. 2), and higher mortality (76% vs. 10%); all p < 0.001. Controlling for Injury Severity Score and base deficit on arrival, prehospital fluid was associated with a significant increase in likelihood of HF. In fact, each additional liter of crystalloid was associated with a 15% increased odds of HF. The in vitro model found that hemodilution to 15% of baseline and tissue factor + tissue plasminogen activator was required to achieve an LY30 of 50%. Although uncommon immediately after injury, HF is associated with prehospital crystalloid administration and shock at admission and is highly lethal. Our in vitro model confirms that tissue injury and significant crystalloid hemodilution result in severe and immediate HF.

Troponin T for the Detection of Dialysis-Induced Myocardial Stunning in Hemodialysis Patients

Circulating troponin T levels are frequently elevated in patients undergoing long-term dialysis. The pathophysiology underlying these elevations is controversial. In 70 prevalent hemodialysis (HD) patients, HD-induced myocardial stunning was assessed echocardiographically at baseline and after 12 months. Nineteen patients were not available for the follow-up analysis. The extent to which predialysis troponin T was associated with the occurrence of HD-induced myocardial stunning was assessed as the primary endpoint. The median troponin T level in this hemodialysis cohort was 0.06 ng/ml (interquartile range, 0.02-0.10). At baseline, 64% of patients experienced myocardial stunning. These patients showed significantly higher troponin T levels than patients without stunning (0.08 ng/ml [0.05-0.12] versus 0.02 ng/ml [0.01-0.05]). Troponin T levels were significantly correlated to measures of myocardial stunning severity (number of affected segments: r=0.42; change in ejection fraction from beginning of dialysis to end of dialysis: r=-0.45). In receiver-operating characteristic analyses, predialytic troponin T achieved an area under the curve of 0.82 for the detection of myocardial stunning. In multivariable analysis, only ultrafiltration volume (odds ratio, 4.38 for every additional liter) and troponin T (odds ratio, 9.33 for every additional 0.1 ng/ml) were independently associated with myocardial stunning. After 12 months, nine patients had newly developed myocardial stunning and showed a significant increase in troponin T over baseline (0.03 ng/ml at baseline versus 0.05 ng/ml at year 1). Troponin T levels in HD patients are associated with the presence and severity of HD-induced myocardial stunning.

Per capita alcohol consumption and suicide mortality in a panel of US states from 1950 to 2002.

introduction and aims: The relationship between per capita alcohol consumption and suicide rates has been found to vary in significance and magnitude across countries. This study utilises a panel of time-series measures from the US states to estimate the effects of changes in current and lagged alcohol sales on suicide mortality risk. Generalised least squares estimation utilised 53 years of data from 48 US states or state groups to estimate relationships between total and beverage-specific alcohol consumption measures and age-standardised suicide mortality rates in first-differenced semi-logged models. An additional litre of ethanol from total alcohol sales was estimated to increase suicide rates by 2.3% in models utilising a distributed lag specification while no effect was found in models including only current alcohol consumption. A similar result is found for men, while for women both current and distributed lag measures were found to be significantly related to suicide rates with an effect of approximately 3.2% per litre from current and 5.8% per litre from the lagged measure. Beverage-specific models indicate that spirits is most closely linked with suicide risk for women while beer and wine are for men. Unemployment rates are consistently positively related to suicide rates. DISCUSSION AND CONCLUSIONS" Results suggest that chronic effects, potentially related to alcohol abuse and dependence, are the main source of alcohol's impact on suicide rates in the USA for men and are responsible for about half of the effect for women.