Identification of major hemorrhage in trauma patients in the prehospital setting: diagnostic accuracy and impact on outcome.

Background: Hemorrhage is the most common cause of potentially preventable death after injury. Early identification of patients with major hemorrhage (MH) is important as treatments are time-critical. However, diagnosis can be difficult, even for expert clinicians. This study aimed to determine how accurate clinicians are at identifying patients with MH in the prehospital setting. A second aim was to analyze factors associated with missed and overdiagnosis of MH, and the impact on mortality. Methods: Retrospective evaluation of consecutive adult (≥16 years) patients injured in 2019-2020, assessed by expert trauma clinicians in a mature prehospital trauma system, and admitted to a major trauma center (MTC). Clinicians decided to activate the major hemorrhage protocol (MHPA) or not. This decision was compared with whether patients had MH in hospital, defined as the critical admission threshold (CAT+): administration of ≥3 U of red blood cells during any 60-minute period within 24 hours of injury. Multivariate logistical regression analyses were used to analyze factors associated with diagnostic accuracy and mortality. Results: Of the 947 patients included in this study, 138 (14.6%) had MH. MH was correctly diagnosed in 97 of 138 patients (sensitivity 70%) and correctly excluded in 764 of 809 patients (specificity 94%). Factors associated with missed diagnosis were penetrating mechanism (OR 2.4, 95% CI 1.2 to 4.7) and major abdominal injury (OR 4.0; 95% CI 1.7 to 8.7). Factors associated with overdiagnosis were hypotension (OR 0.99; 95% CI 0.98 to 0.99), polytrauma (OR 1.3, 95% CI 1.1 to 1.6), and diagnostic uncertainty (OR 3.7, 95% CI 1.8 to 7.3). When MH was missed in the prehospital setting, the risk of mortality increased threefold, despite being admitted to an MTC. Conclusion: Clinical assessment has only a moderate ability to identify MH in the prehospital setting. A missed diagnosis of MH increased the odds of mortality threefold. Understanding the limitations of clinical assessment and developing solutions to aid identification of MH are warranted. Level of evidence: Level III-Retrospective study with up to two negative criteria. Study type: Original research; diagnostic accuracy study.

Diagnostic accuracy of clinical examination to identify life- and limb-threatening injuries in trauma patients.

BACKGROUND: Timely and accurate identification of life- and limb-threatening injuries (LLTIs) is a fundamental objective of trauma care that directly informs triage and treatment decisions. However, the diagnostic accuracy of clinical examination to detect LLTIs is largely unknown, due to the risk of contamination from in-hospital diagnostics in existing studies. Our aim was to assess the diagnostic accuracy of initial clinical examination for detecting life- and limb-threatening injuries (LLTIs). Secondary aims were to identify factors associated with missed injury and overdiagnosis, and determine the impact of clinician uncertainty on diagnostic accuracy. METHODS: Retrospective diagnostic accuracy study of consecutive adult (≥ 16 years) patients examined at the scene of injury by experienced trauma clinicians, and admitted to a Major Trauma Center between 01/01/2019 and 31/12/2020. Diagnoses of LLTIs made on contemporaneous clinical records were compared to hospital coded diagnoses. Diagnostic performance measures were calculated overall, and based on clinician uncertainty. Multivariate logistic regression analyses identified factors affecting missed injury and overdiagnosis. RESULTS: Among 947 trauma patients, 821 were male (86.7%), median age was 31 years (range 16-89), 569 suffered blunt mechanisms (60.1%), and 522 (55.1%) sustained LLTIs. Overall, clinical examination had a moderate ability to detect LLTIs, which varied by body region: head (sensitivity 69.7%, positive predictive value (PPV) 59.1%), chest (sensitivity 58.7%, PPV 53.3%), abdomen (sensitivity 51.9%, PPV 30.7%), pelvis (sensitivity 23.5%, PPV 50.0%), and long bone fracture (sensitivity 69.9%, PPV 74.3%). Clinical examination poorly detected life-threatening thoracic (sensitivity 48.1%, PPV 13.0%) and abdominal (sensitivity 43.6%, PPV 20.0%) bleeding. Missed injury was more common in patients with polytrauma (OR 1.83, 95% CI 1.62-2.07) or shock (systolic blood pressure OR 0.993, 95% CI 0.988-0.998). Overdiagnosis was more common in shock (OR 0.991, 95% CI 0.986-0.995) or when clinicians were uncertain (OR 6.42, 95% CI 4.63-8.99). Uncertainty improved sensitivity but reduced PPV, impeding diagnostic precision. CONCLUSIONS: Clinical examination performed by experienced trauma clinicians has only a moderate ability to detect LLTIs. Clinicians must appreciate the limitations of clinical examination, and the impact of uncertainty, when making clinical decisions in trauma. This study provides impetus for diagnostic adjuncts and decision support systems in trauma.

Health Beliefs Associated With Metformin Use Among Insured Adults With Prediabetes.

OBJECTIVE: To use the framework of the Health Belief Model (HBM) to explore factors associated with metformin use among adults with prediabetes. RESEARCH DESIGN AND METHODS: We analyzed survey data from 200 metformin users and 1,277 nonmetformin users with prediabetes identified from a large, insured workforce. All subjects were offered the National Diabetes Prevention Program (DPP) at no out-of-pocket cost. We constructed bivariate and multivariate models to investigate how perceived threat, perceived benefits, self-efficacy, and cues to action impacted metformin use and how demographic, clinical, sociopsychological, and structural variables impacted the associations. RESULTS: Adults with prediabetes who used metformin were younger and more likely to be women and to have worse self-rated health and higher BMIs than those with prediabetes who did not use metformin. Those who used metformin were also more likely to be aware of their prediabetes and to have a personal history of gestational diabetes mellitus or a family history of diabetes. After consideration of perceived threat, perceived benefits, self-efficacy, and cues to action, the only independent predictors of metformin use were younger age, female sex, higher BMI, and cues to action, most specifically, a doctor offering metformin therapy. CONCLUSIONS: Demographic and clinical factors and cues to action impact the likelihood of metformin use for diabetes prevention. Perceived threat, perceived benefits, and self-efficacy were not independently associated with metformin use. These results highlight the importance of patient-centered primary care and shared decision-making in diabetes prevention. Clinicians should proactively offer metformin to patients with prediabetes to facilitate effective diabetes prevention.

Domains from the health belief model predict enrollment in the National Diabetes Prevention Program among insured adults with prediabetes.

AIMS: To examine enrollment in the National Diabetes Prevention Program (DPP) by insured adults with prediabetes according to domains of the Health Belief Model (HBM). METHODS: Between 2015 and 2019, University of Michigan employees, retirees, and dependents with prediabetes were offered the National DPP at no out-of-pocket cost. Individuals with prediabetes were identified and mailed letters encouraging them to enroll. We surveyed those who enrolled and a random sample of those who did not using the HBM as a framework to examine factors associated with enrollment. Analyses were performed using multivariable logistic regression models. RESULTS: Of 64,131 employees, retirees, and dependents, 8131 were identified with prediabetes and 776 (9.5%) enrolled in the National DPP. Of those surveyed, 532 of 776 National DPP enrollees and 945 of 2673 non-enrollees responded to the survey (adjusted response rates 74% and 43%, respectively). Among survey respondents, factors associated with National DPP enrollment included older age, female sex, higher BMI, prediabetes awareness, greater perceived benefits of health-protective action, and one or more cues to action. CONCLUSIONS: Optimizing National DPP enrollment among adults with prediabetes will require identifying individuals with prediabetes, increasing personal awareness of the diagnosis, increasing perceived benefits of enrollment, and providing strong cues to action.

Non-Targeted Analysis Using Gas Chromatography-Mass Spectrometry for Evaluation of Chemical Composition of E-Vapor Products.

The Premarket Tobacco Product Applications (PMTA) guidance issued by the Food and Drug Administration for electronic nicotine delivery systems (ENDSs) recommends that in addition to reporting harmful and potentially harmful constituents (HPHCs), manufacturers should evaluate these products for other chemicals that could form during use and over time. Although e-vapor product aerosols are considerably less complex than mainstream smoke from cigarettes and heated tobacco product (HTP) aerosols, there are challenges with performing a comprehensive chemical characterization. Some of these challenges include the complexity of the e-liquid chemical compositions, the variety of flavors used, and the aerosol collection efficiency of volatile and semi-volatile compounds generated from aerosols. In this study, a non-targeted analysis method was developed using gas chromatography-mass spectrometry (GC-MS) that allows evaluation of volatile and semi-volatile compounds in e-liquids and aerosols of e-vapor products. The method employed an automated data analysis workflow using Agilent MassHunter Unknowns Analysis software for mass spectral deconvolution, peak detection, and library searching and reporting. The automated process ensured data integrity and consistency of compound identification with >99% of known compounds being identified using an in-house custom mass spectral library. The custom library was created to aid in compound identifications and includes over 1,100 unique mass spectral entries, of which 600 have been confirmed from reference standard comparisons. The method validation included accuracy, precision, repeatability, limit of detection (LOD), and selectivity. The validation also demonstrated that this semi-quantitative method provides estimated concentrations with an accuracy ranging between 0.5- and 2.0-fold as compared to the actual values. The LOD threshold of 0.7 ppm was established based on instrument sensitivity and accuracy of the compounds identified. To demonstrate the application of this method, we share results from the comprehensive chemical profile of e-liquids and aerosols collected from a marketed e-vapor product. Applying the data processing workflow developed here, 46 compounds were detected in the e-liquid formulation and 55 compounds in the aerosol sample. More than 50% of compounds reported have been confirmed with reference standards. The profiling approach described in this publication is applicable to evaluating volatile and semi-volatile compounds in e-vapor products.

Use of metformin following a population-level intervention to encourage people with pre-diabetes to enroll in the National Diabetes Prevention Program.

INTRODUCTION: The National Diabetes Prevention Program (NDPP) and metformin are interventions to slow progression from pre-diabetes to type 2 diabetes. When coverage for the NDPP was offered by a public research university's health insurance plan, proactive strategies were used to combat historically low enrollment. Although not specifically targeted by these strategies, metformin use was higher than expected, leading to this evaluation. RESEARCH DESIGN AND METHODS: We used insurance enrollment, claims, pharmacy, and laboratory data for 64 131 adult employees, dependents, and retirees to identify individuals with pre-diabetes and invite them to enroll in the NDPP at no out-of-pocket cost. The characteristics of individuals with pre-diabetes who used metformin before and after their invitation were compared with NDPP enrollees. RESULTS: 8131 individuals with pre-diabetes were identified. Of these, 776 (9.5%) enrolled in a NDPP and 802 (9.9%) used metformin. Metformin users were younger, had higher body mass index, were more likely to have comorbidities, and had higher baseline hemoglobin A1c levels than non-users. Timing of metformin use varied with 107 (13%) discontinuing, 426 (53%) continuing, and 269 (34%) initiating metformin use after their NDPP invitation. Of NDPP enrollees, 13 (2%) discontinued, 56 (7%) continued, and 34 (4%) initiated metformin use when they enrolled. CONCLUSIONS: Despite no active encouragement, use of metformin was similar to the rate of enrollment in the NDPP. Metformin use was higher for individuals with higher likelihood of responding. With the proven cost-effectiveness of metformin, targeted strategies to increase metformin use in individuals with pre-diabetes who are likely to respond, but not willing to enroll in a lifestyle intervention, are needed.

The Effectiveness of a Proactive, Three-Level Strategy to Identify People With Prediabetes in a Large Workforce With Employer-Sponsored Health Insurance.

OBJECTIVE: Rates of diagnosis of prediabetes and uptake of the National Diabetes Prevention Program (NDPP) are low. We evaluated a proactive three-level strategy to identify individuals with prediabetes in a population with employer-sponsored health insurance. RESEARCH DESIGN AND METHODS: We studied 64,131 insured employees, dependents, and retirees ≥18 years of age without diagnosed diabetes, 19,397 (30%) of whom were estimated to have prediabetes. Individuals with prediabetes were identified by 1) searching claims diagnoses and previously performed HbA1c test results, 2) risk stratifying people 40-64 years of age without diabetes, prediabetes, or documented normal HbA1c to identify individuals at higher risk and encourage them to be tested, and 3) using a media campaign to encourage employees not otherwise targeted to self-screen and, if at higher risk, to be tested. RESULTS: Using claims and laboratory data, 11% of the population was identified as having prediabetes. Of those 40-64 years of age, 25% were identified as being at higher risk, and 27% of them were tested or diagnosed within 1 year. Of employees exposed to the media campaign, 14% were tested or diagnosed within 1 year. Individuals with prediabetes were older, heavier, and more likely to have hypertension and dyslipidemia. Testing and diagnosis were associated with receiving medical care and provider outreach. A total of 8,129 individuals, or 42% of those with prediabetes, were identified. CONCLUSIONS: Analysis of existing health insurance data facilitated the identification of individuals with prediabetes. Better identification of people with prediabetes is a first step in increasing uptake of the NDPP.

A latitudinal gradient in thermal transgenerational plasticity and a test of theory.

Transgenerational plasticity (TGP) occurs when phenotypes are shaped by the environment in both the current and preceding generations. Transgenerational responses to rainfall, CO2 and temperature suggest that TGP may play an important role in how species cope with climate change. However, little is known about how TGP will evolve as climate change continues. Here, we provide a quantitative test of the hypothesis that the predictability of the environment influences the magnitude of the transgenerational response. To do so, we take advantage of the latitudinal decrease in the predictability of temperatures in near shore waters along the US East Coast. Using sheepshead minnows (Cyprinodon variegatus) from South Carolina, Maryland, and Connecticut, we found the first evidence for a latitudinal gradient in thermal TGP. Moreover, the degree of TGP in these populations depends linearly on the decorrelation time for temperature, providing support for the hypothesis that thermal predictability drives the evolution of these traits.

Clinical Courses of HeartMate II Left Ventricular Assist Device Thrombosis.

We observed different temporal patterns of HeartMate II left ventricular assist device (LVAD) thrombosis regarding clinical manifestations and lactate dehydrogenase (LDH) trends. We propose nomenclature for classification of LVAD thrombosis and compare patient characteristics and outcomes in each pattern of LVAD thrombosis. We reviewed electronic medical records of 362 consecutive HeartMate II devices implanted at Cleveland Clinic from October 2008 to July 2014. We categorized clinical courses of confirmed device thrombosis based on clinical manifestations and LDH patterns. Patients' characteristics, clinical variables, and outcomes were collected for comparison. From a total of 19 confirmed device thromboses, we categorized the patterns of thrombosis into three distinctive types; abrupt thrombosis (Type 1), subacute thrombosis (Type 2), and asymptomatic hemolysis (Type 3). Abrupt thrombosis (Type 1) tended to be the most morbid clinical course with acute-onset thrombosis at 56.5 (interquartile range: 44-71) days, all New York Heart Association functional class III or IV at presentation. Death and need for surgical intervention were not different in each pattern. Asymptomatic hemolysis had unique comorbidities of preexisting cardiac thrombi and preoperative bacteremia. Confirmed LVAD thrombosis has different patterns of clinical presentation and each pattern of thrombosis has unique characteristics and clinical manifestations.

Dynamic prediction of left ventricular assist device pump thrombosis based on lactate dehydrogenase trends.

AIMS: The risk of HeartMate II (HMII) left ventricular assist device (LVAD) thrombosis has been reported, and serum lactate dehydrogenase (LDH), a biomarker of haemolysis, increases secondary to LVAD thrombosis. This study evaluated longitudinal measurements of LDH post-LVAD implantation, hypothesizing that LDH trends could timely predict future LVAD thrombosis. METHODS AND RESULTS: From October 2004 to October 2014, 350 HMIIs were implanted in 323 patients at Cleveland Clinic. Of these, patients on 339 HMIIs had at least one post-implant LDH value (7996 total measurements). A two-step joint model combining longitudinal biomarker data and pump thrombosis events was generated to assess the effect of changing LDH on thrombosis risk. Device-specific LDH trends were first smoothed using multivariate boosted trees, and then used as a time-varying covariate function in a multiphase hazard model to analyse time to thrombosis. Pre-implant variables associated with time-varying LDH values post-implant using boostmtree were also investigated. Standardized variable importance for each variable was estimated as the difference between model-based prediction error of LDH when the variable was randomly permuted and prediction error without permuting the values. The larger this difference, the more important a variable is for predicting the trajectory of post-implant LDH. Thirty-five HMIIs (10%) had either confirmed (18) or suspected (17) thrombosis, with 15 (43%) occurring within 3 months of implant. LDH was associated with thrombosis occurring both early and late after implant (P < 0.0001 for both hazard phases). The model demonstrated increased probability of HMII thrombosis as LDH trended upward, with steep changes in LDH trajectory paralleling trajectories in probability of pump thrombosis. The most important baseline variables predictive of the longitudinal pattern of LDH were higher bilirubin, higher pre-implant LDH, and older age. The effect of some pre-implant variables such as sodium on the post-implant LDH longitudinal pattern differed across time. CONCLUSIONS: Longitudinal trends in surveillance LDH for patients on HMII support are useful for dynamic prediction of pump thrombosis, both early after implant and late. Incorporating upward and downward trends in LDH that dynamically update a model of LVAD thrombosis risk provides a useful tool for clinical management and decisions.

Elevated CO2 alters behavior, growth, and lipid composition of Pacific cod larvae.

High-latitude seas, which support a number of commercially important fisheries, are predicted to be most immediately impacted by ongoing ocean acidification (OA). Elevated CO2 levels have been shown to induce a range of impacts on the physiology and behavior of marine fish larvae. However, these responses have yet to be characterized for most fishery species, including Pacific cod (Gadus macrocephalus). Based on laboratory experiments, we present a multi-faceted analysis of the sensitivity of Pacific cod larvae to elevated CO2. Fish behavior in a horizontal light gradient was used to evaluate the sensitivity of behavioral phototaxis in 4-5 week old cod larvae. Fish at elevated CO2 levels (∼1500 and 2250 µatm) exhibited a stronger phototaxis (moved more quickly to regions of higher light levels) than fish at ambient CO2 levels (∼600 µatm). In an independent experiment, we examined the effects of elevated CO2 levels on growth of larval Pacific cod over the first 5 weeks of life under two different feeding treatments. Fish exposed to elevated CO2 levels (∼1700 µatm) were smaller and had lower lipid levels at 2 weeks of age than fish at low (ambient) CO2 levels (∼500 µatm). However, by 5 weeks of age, this effect had reversed: fish reared at elevated CO2 levels were slightly (but not significantly) larger and had higher total lipid levels and storage lipids than fish reared at low CO2. Fatty acid composition differed significantly between fish reared at high and low CO2 levels (p < 0.01) after 2 weeks of feeding, but this effect diminished by week 5. Effects of CO2 on FA composition of the larvae differed between the two diets, an effect possibly related more to dietary equilibrium and differential lipid class storage than a fundamental effect of CO2 on fatty acid metabolism. These experiments point to a stage-specific sensitivity of Pacific cod to the effects of OA. Further understanding of these effects will be required to predict the impacts on production of Pacific cod fisheries.

Bottlenose dolphins modify behavior to reduce metabolic effect of tag attachment.

Attaching bio-telemetry or -logging devices ('tags') to marine animals for research and monitoring adds drag to streamlined bodies, thus affecting posture, swimming gaits and energy balance. These costs have never been measured in free-swimming cetaceans. To examine the effect of drag from a tag on metabolic rate, cost of transport and swimming behavior, four captive male dolphins (Tursiops truncatus) were trained to swim a set course, either non-tagged (n=7) or fitted with a tag (DTAG2; n=12), and surface exclusively in a flow-through respirometer in which oxygen consumption VO2 and carbon dioxide production (VO2; ml kg(-1) min(-1)) rates were measured and respiratory exchange ratio (VO2/resting VO2) was calculated. Tags did not significantly affect individual mass-specific oxygen consumption, physical activity ratios (exercise /resting ), total or net cost of transport (COT; J m(-1) kg(-1)) or locomotor costs during swimming or two-minute recovery phases. However, individuals swam significantly slower when tagged (by ~11%; mean ± s.d., 3.31±0.35 m s(-1)) than when non-tagged (3.73±0.41 m s(-1)). A combined theoretical and computational fluid dynamics model estimating drag forces and power exertion during swimming suggests that drag loading and energy consumption are reduced at lower swimming speeds. Bottlenose dolphins in the specific swimming task in this experiment slowed to the point where the tag yielded no increases in drag or power, while showing no difference in metabolic parameters when instrumented with a DTAG2. These results, and our observations, suggest that animals modify their behavior to maintain metabolic output and energy expenditure when faced with tag-induced drag.

Real-time reporting of baleen whale passive acoustic detections from ocean gliders.

In the past decade, much progress has been made in real-time passive acoustic monitoring of marine mammal occurrence and distribution from autonomous platforms (e.g., gliders, floats, buoys), but current systems focus primarily on a single call type produced by a single species, often from a single location. A hardware and software system was developed to detect, classify, and report 14 call types produced by 4 species of baleen whales in real time from ocean gliders. During a 3-week deployment in the central Gulf of Maine in late November and early December 2012, two gliders reported over 25,000 acoustic detections attributed to fin, humpback, sei, and right whales. The overall false detection rate for individual calls was 14%, and for right, humpback, and fin whales, false predictions of occurrence during 15-min reporting periods were 5% or less. Transmitted pitch tracks--compact representations of sounds--allowed unambiguous identification of both humpback and fin whale song. Of the ten cases when whales were sighted during aerial or shipboard surveys and a glider was within 20 km of the sighting location, nine were accompanied by real-time acoustic detections of the same species by the glider within ±12 h of the sighting time.

Functional responses and scaling in predator-prey interactions of marine fishes: contemporary issues and emerging concepts.

Predator-prey interactions are a primary structuring force vital to the resilience of marine communities and sustainability of the world's oceans. Human influences on marine ecosystems mediate changes in species interactions. This generality is evinced by the cascading effects of overharvesting top predators on the structure and function of marine ecosystems. It follows that ecological forecasting, ecosystem management, and marine spatial planning require a better understanding of food web relationships. Characterising and scaling predator-prey interactions for use in tactical and strategic tools (i.e. multi-species management and ecosystem models) are paramount in this effort. Here, we explore what issues are involved and must be considered to advance the use of predator-prey theory in the context of marine fisheries science. We address pertinent contemporary ecological issues including (1) the approaches and complexities of evaluating predator responses in marine systems; (2) the 'scaling up' of predator-prey interactions to the population, community, and ecosystem level; (3) the role of predator-prey theory in contemporary fisheries and ecosystem modelling approaches; and (4) directions for the future. Our intent is to point out needed research directions that will improve our understanding of predator-prey interactions in the context of the sustainable marine fisheries and ecosystem management.

Common humpback whale (Megaptera novaeangliae) sound types for passive acoustic monitoring.

Humpback whales (Megaptera novaeangliae) are one of several baleen whale species in the Northwest Atlantic that coexist with vessel traffic and anthropogenic noise. Passive acoustic monitoring strategies can be used in conservation management, but the first step toward understanding the acoustic behavior of a species is a good description of its acoustic repertoire. Digital acoustic tags (DTAGs) were placed on humpback whales in the Stellwagen Bank National Marine Sanctuary to record and describe the non-song sounds being produced in conjunction with foraging activities. Peak frequencies of sounds were generally less than 1 kHz, but ranged as high as 6 kHz, and sounds were generally less than 1 s in duration. Cluster analysis distilled the dataset into eight groups of sounds with similar acoustic properties. The two most stereotyped and distinctive types ("wops" and "grunts") were also identified aurally as candidates for use in passive acoustic monitoring. This identification of two of the most common sound types will be useful for moving forward conservation efforts on this Northwest Atlantic feeding ground.

Excess longitudinal decline in lung function in grain farmers.

Workers in intensive agricultural operations are exposed to dust and endotoxin that are associated with respiratory effects. The authors investigated the longitudinal changes in lung function in male grain farmers. In this study, male grain farmers (n = 263) and male nonfarming control subjects (n = 261) studies initially in 1990/91 were followed-up in 1994/95 and 2003/04. After controlling for potential confounders, grain farmers had an excess annual decline of 9.2 ml/year (95% confidence interval [CI]: 2.7, 15.8, p = .006) in forced vital capacity (FVC) in comparison to control. Long-term exposure to grain dust and other substances in lifetime grain farmers results in progressive loss in lung function.

Effects of MMP-9 inhibition by doxycycline on proteome of lungs in high tidal volume mechanical ventilation-induced acute lung injury.

BACKGROUND: Although mechanical ventilation (MV) is a major supportive therapy for patients with acute respiratory distress syndrome, it may result in side effects including lung injury. In this study we hypothesize that MMP-9 inhibition by doxycycline might reduce MV-related lung damage. Using a proteomic approach we identified the pulmonary proteins altered in high volume ventilation-induced lung injury (VILI). Forty Wistar rats were randomized to an orally pretreated with doxycycline group (n = 20) or to a placebo group (n = 20) each of which was followed by instrumentation prior to either low or high tidal volume mechanical ventilation. Afterwards, animals were euthanized and lungs were harvested for subsequent analyses. RESULTS: Mechanical function and gas exchange parameters improved following treatment with doxycycline in the high volume ventilated group as compared to the placebo group. Nine pulmonary proteins have shown significant changes between the two biochemically analysed (high volume ventilated) groups. Treatment with doxycycline resulted in a decrease of pulmonary MMP-9 activity as well as in an increase in the levels of soluble receptor for advanced glycation endproduct, apoliporotein A-I, peroxiredoxin II, four molecular forms of albumin and two unnamed proteins. Using the pharmacoproteomic approach we have shown that treatment with doxycycline leads to an increase in levels of several proteins, which could potentially be part of a defense mechanism. CONCLUSION: Administration of doxycycline might be a significant supportive therapeutic strategy in prevention of VILI.

Lung function and farm size predict healthy worker effect in swine farmers.

BACKGROUND: Swine farmers are exposed to a number of airborne contaminants associated with respiratory ill health. OBJECTIVES: To examine the factors associated with healthy worker effect in the swine industry from a longitudinal follow-up of farmers at 4 years and 13 years. DESIGN: A prospective study of swine farmers and nonexposed rural residents was conducted using similar questionnaires and same spirometer at each time point. RESULTS: In the original observations in 1990/1991, we studied 302 swine farmers and 261 nonfarming control subjects. Four years later in 1994/1995, 217 swine farmers and 171 nonfarming control subjects of the original group participated again. In 2003/2004, 163 swine farmers and 118 control subjects were retested. Of the 163 swine farmers, 52 remained active swine farmers and 111 were no longer swine farming, thus providing the opportunity to evaluate work continuity in the industry. Among farmers studied in 2003/2004, mean values for percentage of predicted FEV(1)/FVC ratio and forced expiratory flow between 25% and 75% of FVC were lower in those who had quit swine farming compared to those still swine farming and nonfarming control subjects. The herd size in the barn at baseline in 1990/1991 and at interim follow-up in 1994/1995 was a significant predictor of quitting swine farming. In addition, percentage of predicted FEV(1)/FVC at the interim observation was a significant predictor of quitting swine farming. CONCLUSIONS: There is a significant healthy worker effect among swine farmers. The continuation of work in the facilities may be predicted by herd size and interim lung function.