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The objectives of this study were to determine the prevalence of smoking, identify the effects of deployment on smoking behavior and risk factors for smoking, and determine the short-term health outcomes associated with smoking in Australian Defence Force (ADF) personnel. Participants were randomly sampled from ADF members who deployed to the Solomon Islands between 2003 and 2005 and from a nondeployed comparison group. In total, 435 of 995 (44%) eligible individuals completed the study questionnaires. The prevalence of current smoking was highest in those who had completed less formal education and those who served in the Navy. Nearly two-thirds (63%) of current or former smokers smoked more while on overseas deployment. Current smokers were more likely to report current wheeze, shortness of breath, and persistent cough compared with nonsmokers. The ADF should continue to address cigarette smoking through its health promotion and health review programs and implement activities to reduce cigarette smoking on deployment. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess the impact that Academic Detailing (AD) had on General Practitioners' use of diagnostic imaging for shoulder complaints in general practice and their knowledge and confidence to manage shoulder pain.Methods: One-to-one Academic Detailing (AD) for management of shoulder pain was delivered to 87 General Practitioners (GPs) in metropolitan Adelaide, South Australia, together with locally developed clinical guidelines and a video/DVD on how to examine the shoulder. Three months after the initial AD a further small group or an individual follow up session was offered. A 10-item questionnaire to assess knowledge about the shoulders was administered before, immediately after, and 3 months after AD, together with questions to assess confidence to manage shoulder complaints. The number of requests for plain film (X-ray) and ultrasound (US) imaging of the shoulder was obtained for the intervention group as well as a random comparison group of 90 GP's from the same two Divisions. The change in the rate of requests was assessed using a log Poisson GEE with adjustment for clustering at the practice level. A linear mixed effects model was used to analyse changes in knowledge.Results: In an average week 54% of GPs reported seeing fewer than 6 patients with shoulder problems. Mean (SD) GP knowledge score before, immediately after and 3-months after AD, was 6.2/ 10 (1.5); 8.6/10 (0.96) and; 7.2/ 10 (1.5) respectively (p < 0.0001). Three months after AD, GPs reported feeling able to take a more meaningful history, more confident managing shoulder pain, and felt their management of shoulder pain had improved. Requests for ultrasound imaging were approximately 43.8% higher in the period 2 years before detailing compared to six months after detailing (p < 0.0001), but an upward trend toward baseline was observed in the period 6 months to I year after AD. There was no statistically significant change in the rate of requests from before to after AD for plain-radiographs (p = 0.11). No significant changes in the rate of requests over time were observed in the control groups.Conclusion: These results provide evidence that AD together with education materials and guidelines can improve GPs' knowledge and confidence to manage shoulder problems and reduce the use of imaging, at least in the short term. [ABSTRACT FROM AUTHOR]

BACKGROUND: A cluster randomised trial was conducted to determine the effectiveness of locally adapted practice guidelines and education about paediatric asthma management, delivered to general practitioners (GPs) in small group interactive workshops. METHODS: Twenty-nine practices were randomly allocated to one of three study arms. Australian asthma management guidelines were adapted to accommodate characteristics of the local area. GPs in the intervention arm (Group 1, n = 18 GPs) participated in a small group based education program and were provided with the adapted guidelines. One control arm (Group 2, n = 18 GPs) received only the adapted guidelines, while the other control arm (Group 3, n = 15 GPs) received an unrelated education intervention. GPs' knowledge, attitudes and management of paediatric asthma was assessed. RESULTS: Post intervention, intervention arm GPs were no more likely to provide a written asthma action plan, but were better able to assess the severity of asthma attack (Group 1vs Group 2 p = 0.05 and Group 1 vs Group 3 p = 0.01), better able to identify patients at high risk of severe attack (Group 1vs Group 3 p = 0.06), and tended to score higher on the asthma knowledge questionnaire (Group 1 vs Group 2 p = 0.06 and Group 1 vs Group 3 p = 0.2). Most intervention arm GPs felt more confident than control GPs to manage acute asthma attack and ongoing management of infrequent episodic asthma. CONCLUSION: Using interactive small group workshops to disseminate locally adapted guidelines was associated with improvement in GP's knowledge and confidence to manage asthma, but did not change GP's self-reported provision of written action plans. [ABSTRACT FROM AUTHOR]

Background: Whole blood (WB) resuscitation is increasingly used at trauma centers. Prior studies investigating outcomes in WB versus component-only (CO) resuscitation have been limited by small cohorts, low volumes of WB resuscitation, and unbalanced CO resuscitation. This study aimed to address these limitations using data from a high-volume Level I trauma center, which adopted a WB-first resuscitation paradigm in 2018. We hypothesized that the resuscitation method, WB or balanced CO, would have no impact on patient mortality., Methods: A single-center, retrospective cohort study of adults presenting as a trauma activation from July 2016 through July 2021 was performed. Receipt of three or more units of WB or packed red blood cells (RBC) within the first hour of resuscitation was required for inclusion. Patients were grouped into WB versus CO resuscitation and important clinical outcomes were compared. Mortality was evaluated with Kaplan-Meier analysis, log-rank testing, and multivariable Cox proportional hazards modeling., Results: There were 180 patients in the WB group and 170 patients in the CO group. Of the 180 WB patients, 110 (61%) received only WB during the first 24 hours. The WB group received a median of 5.0 units (interquartile range, 4.0-8.0) of WB and CO group received a median of 6.0 units (interquartile range, 4.0-11.8) of RBCs during the first 24 hours of resuscitation. In the CO group, median RBC/plasma and RBC/platelet ratios approximated 1:1:1. Groups were similar in clinicopathologic characteristics including age, Injury Severity Score, mechanism of injury, and requirement for hemorrhage control interventions (WB 55% vs. CO 59%, p = 0.60). Unadjusted survival was equivalent at 24 hours ( p = 0.52) and 30 days ( p = 0.70) between both groups on Kaplan-Meier analysis with log-rank testing. On multivariable Cox regression, WB resuscitation was not independently associated with improved survival after accounting for age, Injury Severity Score, mechanism of injury, and receipt of hemorrhage control procedure (hazard ratio, 0.85; 95% confidence interval, 0.61-1.19, p = 0.34)., Conclusion: Balanced CO resuscitation is associated with similar mortality outcomes to that of WB based resuscitation., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Current Brain Injury Guidelines (BIG) characterize patients with intracranial hemorrhage taking antiplatelet or anticoagulant agents as BIG 3 (the most severe category) regardless of trauma severity. This study assessed the risk of in-hospital mortality or need for neurosurgery in patients taking low-dose aspirin who otherwise would be classified as BIG 1., Methods: This was a retrospective study at an academic level 1 trauma center. Patients were included if they were admitted with traumatic intracerebral hemorrhage and were evaluated by the BIG criteria. Exclusion criteria included indeterminate BIG status or patients with missing primary outcomes documentation. Patients were categorized as BIG 1, BIG 2, BIG 3, or BIG 1 on aspirin (patients with BIG 1 features taking low-dose aspirin). The primary endpoint was a composite of neurosurgical intervention and all-cause in-hospital mortality. Key secondary endpoints include rate of intracranial hemorrhage progression, and intensive care unit- and hospital-free days., Results: A total of 1,520 patients met the inclusion criteria. Median initial Glasgow Coma Scale was 14 (interquartile range [IQR], 12-15), Injury Severity Scale score was 17 (IQR, 10-25), and Abbreviated Injury Scale subscore head and neck (AIS Head ) was 3 (IQR, 3-4). The rate of the primary outcome for BIG 1, BIG 1 on aspirin, BIG 2, and BIG 3 was 1%, 2.2%, 1%, and 27%, respectively; the difference between BIG 1 on aspirin and BIG 3 was significant ( p < 0.001)., Conclusion: Patients taking low-dose aspirin with otherwise BIG 1-grade injuries experienced mortality and required neurosurgery significantly less often than other patients categorized as BIG 3. Inclusion of low-dose aspirin in the BIG criteria should be reevaluated., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Bedside percutaneous dilatational tracheostomy (PDT) and percutaneous endoscopic gastrostomy (PEG) are common procedures performed in the intensive care unit (ICU). Venous thromboembolism (VTE) prophylaxis is frequently prescribed to ICU patients and it remains unclear whether pre-procedure discontinuation is necessary., Methods: This multi-center prospective observational study aimed to describe bleeding rates in patients undergoing bedside PEG or PDT who did or did not have VTE prophylaxis held. Decision to hold prophylaxis was made by the operating physician. The primary endpoint was the rate of peri-procedural bleeding complications. Secondary endpoints included quantification of held doses in the peri-procedural period, rate of venous thromboembolism, and characteristics associated with having prophylaxis held., Results: 91 patients were included over a 2-year period. Patients were on average aged 54 years, 40% female, mostly admitted to the trauma service (59%), and most commonly underwent bedside PDT (59%). Overall, 21% of patients had doses of pre-procedure prophylaxis held. Bleeding events occurred in 1 patient (1.4%) who had prophylaxis continued and in 1 patient (5.0%) who had prophylaxis held, a rate difference of 3.6% (95% CI-9.5%, 16.7%). One bleeding event was managed with bedside surgical repair and one with blood transfusion. There were 10 VTE events, all of whom had prophylaxis continued during the pre-procedure period but 3 had prophylaxis held after the procedure., Conclusions: Bleeding complications were rare and did not significantly differ depending on whether prophylaxis was held or not. Future research is required to confirm the lack of risk with continuing prophylaxis through bedside procedures., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Introduction: Patients with traumatic intracranial hemorrhage (tICH) often require intensive care unit (ICU) admission until bleeding stability is demonstrated through interval head computed tomography (HCT). The brain injury guidelines (BIG) suggest a minimum 24-h ICU admission for severe patients (BIG 3) regardless of repeat CT stability. We sought to evaluate the rate of tICH expansion after an initial stable interval scan was obtained., Methods: A single-center retrospective cohort study at a level 1 trauma center was performed. All adult patients with tICH evaluated using BIG criteria were included. The primary endpoint was incidence of tICH expansion after initial stability on interval HCT performed at approximately 6 h. Secondary endpoints included time to tICH stability, frequency of neurosurgical intervention, and time to surgical intervention., Results: A total of 1517 patients met inclusion criteria. Of the 1121 patients with repeat imaging, 288 (25.7%) experienced progression with 94.4% detected on the initial 6-h interval scan. Of all patients with initially stable repeat imaging (n = 833), progression occurred in 16 (1.9%) patients. Of these patients, 5 required neurosurgical intervention, 4 received increased monitoring, 2 transitioned to comfort measures and 5 had no change in management. The median time from initial scan to expansion in these patients was 42.2 h. Median time to surgical intervention after post-stability expansion was 102 h., Conclusion: Patients who demonstrate bleeding stability on first interval HCT after tICH rarely experience expansion. Consideration should be given to discharging patients from the ICU when initial interval HCT shows no progression., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Preinjury antiplatelet agent (APA) use in trauma patients can increase traumatic hemorrhage and worsen outcomes. Thromboelastography with platelet mapping (TEGPM) has characterized platelet function via arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition in nontrauma settings, but limited data exist in the acute trauma population., Methods: A prospective observational study of adult trauma patients with suspected preinjury APA use who received TEGPM testing from 2017 to 2020 was performed. Patients on anticoagulants were excluded. Patients were grouped according to preinjury APA regimen: 81 mg or 325 mg of aspirin daily, 81 mg of aspirin and 75 mg of clopidrogrel daily, 75 mg of clopidrogrel daily, or no antiplatelet. Ability of TEGPM to detect APA use was assessed using predictive statistics and area under receiver operating characteristic curves (AUROCs)., Results: A total of 824 patients were included with most patients taking 81 mg of aspirin (n = 558). Patients on no antiplatelet were younger and had higher baseline platelet counts, while patients on 75 mg of clopidrogrel were more likely to be admitted after ground level fall. All other baseline characteristics were balanced. Admission TEG values were similar between groups. Median AA inhibition was higher in patients on aspirin containing regimens (p < 0.0001). Median ADP inhibition was higher in patients on clopidogrel containing regimens and those taking 325 mg of aspirin (p < 0.0001). Arachidonic acid inhibition accurately detected preinjury APA use and aspirin use (AUROC, 0.89 and 0.84, respectively); however, ADP inhibition performed poorly (AUROC, 0.58). Neither AA nor ADP inhibition was able to discern specific APA regimens or rule out APA use entirely., Conclusion: High AA inhibition accurately detects preinjury APA use in trauma patients. High ADP inhibition after trauma is common, limiting its utility to accurately identify preinjury APA use. Further study is needed to identify assays that can reliably detect and further characterize preinjury APA use in trauma populations., Level of Evidence: Diagnostic test, level II., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: While atopic conditions are associated with increased risk of mental health problems, the evidence that a range of allergic conditions are associated with psychological distress in young people is less clear. Methods: We recruited a longitudinal birth cohort study of 620 children with a family history of allergic disease. At the 18-year follow up, atopic sensitization was determined by skin prick testing. Surveys were used to determine psychological distress (Kessler 6), quality of life (SF12), respiratory symptoms and management, presence of current eczema and hay fever. Regression models were used to identify predictors of psychological distress and quality of life, while controlling for potential confounders. Results: Prevalence of serious psychological distress was quite low ( n  = 22, 5.3%), and there were no associations between psychological distress and current atopic sensitization, symptoms of hay fever, eczema or asthma. Smoking status and lower level of maternal education were associated with lower physical quality of life (SF12 PCS subscale). Psychological distress total score, lower maternal education, smoking, female sex, and current eczema were associated with worse mental quality of life (SF12 MCS subscale). Conclusion: We found relatively low levels of psychological distress in this cohort of young adults, despite a high prevalence of allergic diseases. Positive social factors may serve to buffer psychological distress amongst the cohort accounting for the low prevalence of serious psychological distress observed.

Background: The ability of focused assessment with sonography for trauma (FAST) to detect clinically significant hemorrhage in hypotensive injured patients remains unclear. We sought to describe the sensitivity and specificity of FAST using findings at laparotomy as the confirmatory test., Methods: Patients from the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study that had a systolic blood pressure < 90mm Hg and underwent FAST were analysed. Results were compared with findings at laparotomy. A therapeutic laparotomy (T-LAP) was defined as an abdominal operation within 6 hours in which a definitive procedure was performed. The sensitivity and specificity of FAST were calculated., Results: The cohort included 317 patients that underwent FAST (108 positive, 209 negative). T-LAP was performed in 69% (n=75) of FAST(+) patients and 22% (n=48) of FAST(-) patients. FAST had a sensitivity of 62% and specificity of 83%., Conclusions: In our multicenter cohort, 22% of FAST(-) patients underwent T-LAP within 6 hours of admission. In hypotensive patients with a negative FAST, clinicians should still maintain a high index of suspicion for significant abdominal hemorrhage., Level of Evidence: Level IV., Competing Interests: Competing interests: JBH reported serving on the board for Tenaxis, the Regional Advisory Council for Trauma and the National Trauma Institute; providing expert testimony for the Department of Justice; grants funded by the Haemonetics Corporation and KCI USA and consultant fees from the Winkenwerder Company. No other disclosures were reported.

Introduction: Life-threatening bleeding can complicate warfarin therapy. Rapid anticoagulant reversal via replacement of vitamin-K dependent clotting factors is essential for hemostasis. We compare two methods of rapid factor replacement for warfarin reversal., Methods: A retrospective cohort study of warfarin-treated patients experiencing life-threatening bleeding who received a reversal protocol comprised of 4F PCC or 3F PCC and rFVIIa was performed. Demographic, clinical and anticoagulant reversal information, and all adverse events attributed to warfarin reversal were recorded., Results: 195 patients were included in final analysis. While baseline demographics were similar between groups, the 3F-PCC group had a longer ICU LOS and higher in-hospital mortality (p < .01, .01). Pre-reversal INR was similar between both groups, but post-reversal INR was significantly lower in the 3F-PCC group, 0.8 versus 1.3 (p < .01). Significantly more patients experienced thromboembolic complications in the 3F-PCC group than the 4F-PCC group (p < .01). Receipt of rFVIIa was significantly associated with thromboembolic complications., Discussion: A 4F PCC reversal strategy is efficacious in INR reversal and provides lower thromboembolic risk as compared to 3F PCC with rFVIIa., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Study Objective: The objective of this study is to evaluate the difference in response to ventricular rate control with intravenous (IV) metoprolol compared to IV diltiazem in patients taking chronic beta-blocker therapy who present to the emergency department (ED) in atrial fibrillation (AF) with rapid ventricular rate (RVR)., Methods: This was a single-center, retrospective study of adult patients taking chronic oral metoprolol. Chronic metoprolol therapy was defined as patients prescribed and taking oral metoprolol within 5days of study inclusion. Rate control was defined as either a decrease in ventricular rate<100bpm or <120bpm if the decrease was at least 20% from the presenting heart rate., Results: A total of 332 patients were included, with 16 patients in the IV diltiazem group and 316 patients in the IV metoprolol group. In the diltiazem arm, 68.8% of patients achieved successful rate control compared to 42.4% of patients in the metoprolol group (p=0.067). Treatment with IV metoprolol resulted in more hospital admissions (58% vs. 6.25% with diltiazem, p<0.001). Treatment with diltiazem was associated with a greater incidence of bradycardia compared to IV metoprolol (13% vs. 0%, p=0.002)., Conclusions: The use of IV diltiazem was associated with a higher rate of successful response to rate control compared to IV metoprolol in patients in AF with RVR on chronic beta-blocker therapy, however the difference between groups was not statistically significant., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We evaluated whether a chronic obstructive pulmonary disease (COPD) assessment test (CAT) with adjusted weights for the CAT items could better predict future respiratory-related hospitalizations than the original CAT. Two focus groups (respiratory nurses and physicians) generated two adjusted CAT algorithms. Two multivariate logistic regression models for infrequent (≤1/year) versus frequent (>1/year) future respiratory-related hospitalizations were defined: one with the adjusted CAT score that correlated best with future hospitalizations and one with the original CAT score. Patient characteristics related to future hospitalizations ( p ≤ 0.2) were also entered. Eighty-two COPD patients were included. The CAT algorithm derived from the nurse focus group was a borderline significant predictor of hospitalization risk (odds ratio (OR): 1.07; 95% confidence interval (CI): 1.00-1.14; p = 0.050) in a model that also included hospitalization frequency in the previous year (OR: 3.98; 95% CI: 1.30-12.16; p = 0.016) and anticholinergic risk score (OR: 3.08; 95% CI: 0.87-10.89; p = 0.081). Presence of ischemic heart disease and/or heart failure appeared 'protective' (OR: 0.17; 95% CI: 0.05-0.62; p = 0.007). The original CAT score was not significantly associated with hospitalization risk. In conclusion, as a predictor of respiratory-related hospitalizations, an adjusted CAT score was marginally significant (although the original CAT score was not). 'Previous respiratory-related hospitalizations' was the strongest factor in this equation.

Objectives: To provide a concise review of the medical management of coagulopathy related to hepatic insufficiency. This review will focus on prevention and management of bleeding episodes in patients with hepatic insufficiency. The treatment and prevention of thromboembolic complications will also be addressed., Data Sources: Electronic search of PubMed database using relevant search terms, including hepatic coagulopathy, hemorrhage, liver diseases, blood coagulation disorders, blood transfusion, disseminated intravascular coagulation, and liver failure. Subsequent searches were done on specific issues., Study Selection: Articles considered include original articles, review articles, guidelines, consensus statements, and conference proceedings., Data Extraction: A detailed review of scientific, peer-reviewed data was performed. Relevant publications were included and summarized., Data Synthesis: Available evidence is used to describe and summarize currently available tests of hemostasis, utilization of prohemostatic agents, transfusion strategies, use of prophylactic anticoagulation and treatment of thromboembolic events in patients with hepatic insufficiency., Conclusions: Dynamic changes to hemostasis occur in patients with hepatic insufficiency. Routine laboratory tests of hemostasis are unable to reflect these changes and should not be used exclusively to evaluate coagulopathy. Newer testing methods are available to provide data on the entire spectrum of clotting but are not validated in acute bleeding. Prohemostatic agents utilized to prevent bleeding should only be considered when the risk of bleeding outweighs the risk of thrombotic complications. Restrictive transfusion strategies may avoid exacerbation of acute bleeding. Prophylaxis against and treatment of thromboembolic events are necessary and should consider patient specific factors.

Background: Reversal of warfarin-induced coagulopathy after traumatic injury may be done exclusively with prothrombin complex concentrates (PCCs). No direct comparisons between different PCC regimens exist to guide clinical decision-making. Our institution has used 2 distinct PCC strategies for warfarin reversal; a 3-Factor PCC (Profilnine) combined with activated Factor VII (3F-PCC+rVIIa), and a 4-Factor PCC (Kcentra) given without additional factor supplementation., Methods: Retrospective review of all PCC administrations to trauma patients with acute bleeding who were taking warfarin before injury. Primary endpoints were international normalized ratio (INR) reduction, in-hospital mortality, and diagnosis of deep venous thrombosis (DVT)., Results: Eighty-seven patients were identified from 2011 to 2015. Fifty-three were treated with 3F-PCC+rVIIa and 34 with 4F-PCC. Patient demographics, injury severity, and presenting laboratory data were similar. The 3F-PCC+rVIIa produced a lower median (IQR) INR postreversal compared with 4F-PCC (.75 (.69, 1.00) vs 1.28 (1.13, 1.36), P<.001). Both regimens were able to obtain an INR lower than 1.5 immediately after administration (3F+rVIIA 93.9% vs 4F 97.1%, P =.51). In the 4F-PCC group, there was a significant decrease in the incidence of DVT (2.9% vs 22.6%), P < .01), and a nonsignificant reduction in mortality (2.9% vs 17.0%, P = .08)., Conclusions: Use of 4F-PCC for warfarin reversal after traumatic hemorrhage is associated with a less severe decrease in INR, a significant reduction in DVT rates and a trend toward reduced mortality when compared with similar patients treated with 3F-PCC+rVIIa., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Study Objective: The objective of the study is to evaluate the difference in ventricular rate control using an intravenous (IV) metoprolol regimen commonly used in clinical practice in patients receiving chronic β-blocker therapy compared to patients considered β-blocker naive admitted to the emergency department (ED) for atrial fibrillation (AF) with rapid ventricular rate., Methods: A single-center retrospective cohort study of adult ED patients who were admitted with a rapid ventricular rate of 120 beats per minute (bpm) or greater and treated with IV metoprolol was performed. Rate control was defined as either a decrease in ventricular rate to less than 100 bpm or a 20% decrease in heart rate to less than 120 bpm after metoprolol administration. Patient demographics, differences in length of stay, and adverse events were recorded., Results: A total of 398 patients were included in the study, with 79.4% (n=316) receiving chronic β-blocker therapy. Patients considered to be β-blocker naive were more likely to achieve successful rate control with IV metoprolol compared to patients on chronic β-blocker therapy (56.1% vs 42.4%; P=.03). β-Blocker-naive status was associated with a shorter length of stay in comparison to patients receiving chronic β-blocker therapy (1.79 vs 2.64 days; P<.01)., Conclusion: Intravenous metoprolol for the treatment of atrial fibrillation with rapid ventricular rate was associated with a higher treatment response in patients considered β-blocker naive compared to patients receiving chronic β-blocker therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: How patients are selected and subsequently invited to take part in research has important implications for gaining informed, voluntary consent., Objective: This article identifies and discusses common ethical issues that are faced by researchers when recruiting patients from primary care settings., Discussion: Recruiting primary care patients for research studies should be guided by the core ethical values of merit and integrity, respect, justice and beneficence. Issues of patient privacy and risk of coercion are major concerns when selecting and recruiting primary care patients, but the ethical issues will depend on the type of research and the potential risks to participants. The National Statement on Ethical Conduct in Human Research, and Australian privacy laws and principles, should be reviewed to ensure recruitment meets contemporary ethical standards prior to submitting a study protocol for ethical review.

Providing effective pain management to acutely intoxicated trauma patients represents a challenge of balancing appropriate pain management with the risk of potential respiratory depression from opioid administration. The objective of this study was to quantify the incidence of respiratory depression in trauma patients acutely intoxicated with ethanol who received opioids as compared with those who did not and identify potential risk factors for respiratory depression in this population. Retrospective medical record review was conducted for subjects identified via the trauma registry who were admitted as a trauma activation and had a detectable serum ethanol level upon admission. Risk factors and characteristics compared included demographics, Injury Severity Score, Glasgow Coma Score, serum ethanol level upon arrival, urine drug screen results, incidence of respiratory depression, and opioid and other sedative medication use. A total of 233 patients were included (78.5% male). Patients who received opioids were more likely to have a higher Injury Severity Score and initial pain score on admission as compared with those who did not receive opioids. Blood ethanol content was higher in patients who did not receive opioids (0.205 vs 0.237 mg/dL, P = .015). Patients who did not receive opioids were more likely to be intubated within 4 hours of admission (1.7% vs 12.1%, P = .02). Opioid administration was not associated with increased risk of respiratory depression (19.7% vs 22.4%, P = .606). Increased cumulative fentanyl dose was associated with increased risk of respiratory depression. Increased cumulative fentanyl dose, but not opioid administration alone, was found to be a risk factor for respiratory depression., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Bleeding events and life-threatening hemorrhage are the most feared complications of warfarin therapy. Prompt anticoagulant reversal aimed at replacement of vitamin K-dependent clotting factors is essential to promote hemostasis. A retrospective cohort study of warfarin-treated patients experiencing a life-threatening hemorrhage treated with an institution-specific warfarin reversal protocol (postimplementation group) and those who received the prior standard of care (preimplementation group) was performed. The reversal protocol included vitamin K, 3-factor prothrombin complex concentrate, and recombinant factor VIIa. Demographic and clinical information, anticoagulant reversal information, and all adverse events attributed to warfarin reversal were recorded. A total of 227 patients were included in final analysis, 109 in the preimplementation group and 118 in the postimplementation group. Baseline patient characteristics were similar in both groups, with the exception of higher average Sequential Organ Failure Assessment scores in the postimplementation group (P = .0005). The most common indication for anticoagulation reversal was intraparenchymal hemorrhage. Prereversal international normalized ratios (INRs) were similar in both groups. Attainment of INR normalization to less than 1.4 was higher, and rebound INR was lower in the postimplementation group (P < .0001; P = .0013). Thromboembolic complications were significantly higher in the postimplementation group (P = .003). Elevated baseline Sequential Organ Failure Assessment score and mechanical valve as an indication for anticoagulation were independently associated with thrombotic complications (P = .005). A warfarin reversal protocol consisting of 3-factor prothrombin complex concentrate, recombinant factor VIIa, and vitamin K more consistently normalized INR values to less than 1.4 as compared to the prior standard of care in a diverse patient population. This success came at the cost of a 2-fold increase in risk of thromboembolic complications., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Adrenergic β-antagonists, commonly known as β-blockers, are prescribed for many indications including hypertension, heart failure, arrhythmias, and migraines. Metoprolol is a moderately lipophilic β-blocker that in overdose causes direct myocardial depression leading to bradycardia, hypotension, and the potential for cardiovascular collapse. We describe the case of a 59-year-old man who intentionally ingested ~7.5 g of metoprolol tartrate. Initial treatment of bradycardia and hypotension included glucagon, atropine, dopamine, and norepinephrine. Despite these treatment modalities, the patient developed cardiac arrest. Intravenous lipid emulsion (ILE) and hyperinsulinemia/euglycemia (HIE) therapies were initiated during advanced cardiac life support and were immediately followed by return of spontaneous circulation. Further treatment included gastric lavage, activated charcoal, continued vasopressor therapy, and a repeat bolus of ILE. The patient was weaned off vasoactive infusions and was extubated within 24 hours. HIE therapy was continued for 36 hours after metoprolol ingestion. A urine β-blocker panel using mass spectrometry revealed a metoprolol concentration of 120 ng/ml and the absence of other β-blocking agents. To date, no clear treatment guidelines are available for β-blocker overdose, and the response to toxic concentrations is highly variable. In this case of a life-threatening single-agent metoprolol overdose, the patient was successfully treated with HIE and ILE therapy. Due to the increasing frequency with which ILE and HIE are being used for the treatment of β-blocker overdose, clinicians should be aware of their dosing strategies and indications., (© 2015 Pharmacotherapy Publications, Inc.)

Background: Medicinal leeches (Hirudo medicinalis) are indicated for salvage of tissue flaps, grafts, or replants when venous congestion threatens tissue viability. The purpose of this study was to evaluate the efficacy of prophylactic antimicrobial agents in patients who received medicinal leech therapy., Materials and Methods: A multicenter retrospective cohort study of all adult patients between January 1, 2010, and February 28, 2013, who received medicinal leech therapy was conducted., Results: Antimicrobial prophylaxis was documented in 54 (91.5%) of the included patients, ciprofloxacin, trimethoprim-sulfamethoxazole, piperacillin-tazobactam, and ceftriaxone in 33 (61.1%), 18 (33.3%), 2 (3.7%), and 2 (3.7%) patients, respectively. Surgical site infection (SSI) was found in seven (11.9%) patients, all of whom received antimicrobial prophylaxis. Aeromonas spp. was isolated in four infections, and all isolates were resistant to the chosen prophylactic agent. The SSI incidence was similar between antimicrobial prophylaxis agents., Conclusion: Trimethoprim-sulfamethoxazole and ciprofloxacin appear equally effective at preventing leech-associated infections., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: We explored experiences of depression diagnosis and treatment amongst multimorbid patients referred to a metropolitan multidisciplinary outpatient clinic to identify commonalities across this patient group., Methods: Patients with two or more chronic conditions and a diagnosis of depression participated in semi-structured interviews that were digitally recorded and transcribed. Thematic analysis was performed on the transcriptions., Results: Multimorbid patients attributed depressive symptoms to the loss of 'normal' roles and functionality and struggled to reconcile the depression diagnosis with their sense of identity. Beliefs about themselves and depression affected their receptivity to diagnosis and intervention strategies. These included prescribed interventions, such as psychotherapy or pharmacotherapy, and patient-developed strategies., Conclusions: Functional and social role losses present a clear context in which GPs should raise the subject of mood, with the situational attribution of depression suggesting that psychotherapy, which is rarely offered, should be prioritised in these circumstances.

Background: A robust research base is required in General Practice. The research output for General Practice is much less than those of other clinical disciplines. A major impediment to more research in this sector is difficulty with recruitment. Much of the research in this area focuses on barriers to effective recruitment and many projects have great difficulty with this process. This paper seeks to describe a systematic approach to recruitment for a randomized controlled trial that allowed the study team to recruit a substantial number of subjects from General Practice over a brief time period., Methods: A systematic approach to recruitment in this setting based on prior literature and the experience of the investigator team was incorporated into the design and implementation of the study. Five strategies were used to facilitate this process. These included designing the study to minimize the impact of the research on the day-to-day operations of the clinics, engagement of general practitioners in the research, making the research attractive to subjects, minimizing attrition and ensuring recruitment was a major focus of the management of the study. Outcomes of the recruitment process were measured as the proportion of practices that agreed to participate, the proportion of potentially eligible subjects who consented to take part in the trial and the attrition rate of subjects. Qualitative interviews with a subset of successfully recruited participants were done to determine why they chose to participate in the study; data were analyzed using thematic analysis., Results: Five out of the six general practices contacted agreed to take part in the study. Thirty-eight per cent of the 1663 subjects who received a letter of invitation contacted the university study personnel regarding their interest in the project. Recruitment of the required number of eligible participants (n = 256) was accomplished in seven months. Thematic analysis of interviews with 30 participants regarding key factors in their study participation identified a personalised letter of endorsement from their general practitioner, expectation of personal benefit and altruism as important factors in their decision to participate., Conclusion: Recruitment can be successfully achieved in General Practice through design of the research project to facilitate recruitment, minimize the impact on general practice operations and ensure special care in enrolling and maintaining subjects in the project.

Objective: To examine if there is an increased participation in physical or sporting activities following an Olympic or Paralympic games., Design: Overview of systematic reviews., Methods: We searched the Medline, Embase, Cochrane, DARE, SportDISCUS and Web of Knowledge databases. In addition, we searched for 'grey literature' in Google, Google scholar and on the International Olympic Committee websites. We restricted our search to those reviews published in English. We used the AMSTAR tool to assess the methodological quality of those systematic reviews included., Primary and Secondary Outcome Measures: The primary outcome was evidence for an increased participation in physical or sporting activities. Secondary outcomes included public perceptions of sport during and after an Olympic games, barriers to increased sports participation and any other non-sporting health benefits., Results: Our systematic search revealed 844 citations, of which only two matched our inclusion criteria. The quality of these two reviews was assessed by three independent reviewers as 'good' using the AMSTAR tool for quality appraisal. Both reviews reported little evidence of an increased uptake of sporting activity following an Olympic Games event. Other effects on health, for example, changes in hospital admissions, suicide rates and drug use, were cited although there was insufficient evidence to see an overall effect., Conclusion: There is a paucity of evidence to support the notion that hosting an Olympic games leads to an increased participation in physical or sporting activities for host countries. We also found little evidence to suggest other health benefits. We conclude that the true success of these and future games should be evaluated by high-quality, evidence-based studies that have been commissioned before, during and following the completion of the event. Only then can the true success and legacy of the games be established.

Dabigatran etexilate is a new oral anticoagulant used for the prevention of systemic thromboembolism in patients with atrial fibrillation. Acute bleeding episodes are known to occur with dabigatran etexilate therapy; however, only a few case reports in the literature describe such events. We describe a 70-year-old man treated with dabigatran etexilate for newly diagnosed, nonvalvular atrial fibrillation who developed a large hemopericardium that appeared to be temporally related to dabigatran etexilate administration. One month after starting the drug, an incidental finding of a small pericardial effusion was found on echocardiography. One month later, the patient came to his pulmonologist's office complaining of shortness of breath; a large pericardial effusion was found on a noncontrast computed tomographic scan, and the patient was admitted to the hospital. Laboratory monitoring of his coagulation status was limited due to the lack of assays available to directly monitor the therapeutic effects of dabigatran. The internal laboratory was able to perform a dilute thrombin time (DTT) test as part of a quality improvement project aiming to validate an assay for monitoring patients receiving dabigatran therapy. A DTT was therefore performed in conjunction with routine coagulation assays to evaluate the patient's coagulation status. After pericardiocentesis, the patient recovered without incident and was discharged without anticoagulant therapy. Although the Naranjo adverse reaction probability scale only indicated a possible relationship (score of 1) between the patient's development of hemopericardium and dabigatran etexilate therapy, investigation into the patient's clinical course, comorbidities, and laboratory results led us to conclude that dabigatran etexilate was responsible for the hemopericardium. To our knowledge, this report is the first to describe a case of potentially life-threatening pericardial bleeding that was temporally related to starting dabigatran etexilate therapy. Although we found that the DTT was a viable method of monitoring coagulation status in a patient receiving dabigatran etexilate therapy, the assay lacks approval by the United States Food and Drug Administration, which limits its clinical utility and widespread use at this time. Clinicians should be aware of the potential for life-threatening bleeding with use of this agent and the difficulty associated with monitoring and reversing this therapy in the setting of acute bleeding., (© 2012 Pharmacotherapy Publications, Inc.)

Context: Prophylactic antibiotics, paired with wound care and surgical intervention, is considered the standard of care for patients with open fracture. Guidelines from the Eastern Association for the Surgery of Trauma (EAST) recommend specific prophylactic antimicrobial therapy based on the type of open fracture., Aims: We quantified adherence to EAST guideline recommendations and documented the incidence of infection in patients with open fracture., Settings and Design: A retrospective, observational study of all patients with open fracture admitted to our facility from January 2004 to December 2008 was conducted., Materials and Methods: Patients were divided into compliant and noncompliant groups according to the EAST guideline recommendations. Compliance was defined as an appropriate spectrum of therapy for guideline suggested duration. We assessed for surgical and non-surgical site infections, and morbidity outcomes., Statistical Analysis: Nominal data were explored using summary measures. Continuous variables were compared using the Student t-test or the Mann-Whitney U-test. Dichotomous data were compared using χ(2) statistic or Fisher's exact test., Results: The final analysis included 214 patients. Prophylactic antibiotics were guideline compliant in 28.5% of patients, and ranged from 10.0% in type 3b fractures to 52.7% in type 1 fractures. The most common reason for non-compliance was the use of guideline recommended coverage that exceeded the suggested duration (71.2%). Patients who received non-compliant therapy required prolonged hospital lengths of stay (6 vs. 3 days, P = 0.0001). The overall incidence of infection was similar regardless of guideline compliance (17.0% vs. 11.5%, P = 0.313)., Conclusions: Prophylactic antibiotics for open fracture frequently exceeded guideline recommendations in duration and spectrum of coverage, especially in more severe fracture types. Non-compliance with EAST recommendations was associated with increased in-hospital morbidity.

To identify epigenetic-based biomarkers for diagnosis of ovarian cancer we performed MeDIP-Chip in A2780 and CaOV3 ovarian cancer cell lines. Validation by Sequenom massARRAY methylation analysis confirmed a panel of six gene promoters (ARMCX1, ICAM4, LOC134466, PEG3, PYCARD & SGNE1) where hypermethylation discriminated 27 serous ovarian cancer clinical samples versus 12 normal ovarian surface epithelial cells (OSE) (ROC of 0.98). Notably, CpG sites across the transcription start site of a potential long-intergenic non-coding RNA (lincRNA) gene (LOC134466), was shown to be hypermethylated in 81% of serous EOC and could differentiate tumours from OSE (p<0.05). We propose that this potential biomarker panel holds great promise as a diagnostic test for high-grade (Type II) serous ovarian cancer., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Altered DNA methylation patterns hold promise as cancer biomarkers. In this study we selected a panel of genes which are commonly methylated in a variety of cancers to evaluate their potential application as biomarkers for prognosis and diagnosis in high grade serous ovarian carcinoma (HGSOC); the most common and lethal subtype of ovarian cancer., Methods: The methylation patterns of 10 genes (BRCA1, EN1, DLEC1, HOXA9, RASSF1A, GATA4, GATA5, HSULF1, CDH1, SFN) were examined and compared in a cohort of 80 primary HGSOC and 12 benign ovarian surface epithelium (OSE) samples using methylation-specific headloop suppression PCR., Results: The genes were variably methylated in primary HGSOC, with HOXA9 methylation observed in 95% of cases. Most genes were rarely methylated in benign OSE, with the exception of SFN which was methylated in all HGSOC and benign OSE samples examined. Methylation of DLEC1 was associated with disease recurrence, independent of tumor stage and suboptimal surgical debulking (HR 3.5 (95% CI:1.10-11.07), p=0.033). A combination of the methylation status of HOXA9 and EN1 could discriminate HGSOC from benign OSE with a sensitivity of 98.8% and a specificity of 91.7%, which increased to 100% sensitivity with no loss of specificity when pre-operative CA125 levels were also incorporated., Conclusions: This study provides further evidence to support the feasibility of detecting altered DNA methylation patterns as a potential diagnostic and prognostic approach for HGSOC., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Primary care providers often struggle to identify depression, with patients with multiple chronic conditions presenting additional unique challenges. Whilst the diagnosis and treatment of depression has been explored in a range of contexts in the literature, there is a paucity of information on the impact of multimorbidity on general practitioners (GPs) attempting to diagnose and manage depression in primary care. Eight GPs with multiple referrals to a multidisciplinary clinic engaged in a semi-structured interview to discuss the impact of multimorbidity on the diagnosis and detection of depression. Interviews were transcribed and thematic analysis was used to identify key themes. Grounded theory was generated from data relating to the role of multimorbidity. Participants described multimorbidity as obscuring symptom causation, but also creating time to investigate causation and negotiate the depression diagnosis with the patient, and generating relationship through frequent presentations. Knowledge of the patient impacted on intervention recommendations, and trust facilitated patient receptivity. Treatment was affected by a range of variables, and included medical and social interventions. GP process for multimorbid patients is similar to that of patients with chronic illness. Further research is needed to know whether different processes or diagnostic categories are warranted where multiple chronic illnesses are present. Also, GPs recommend social interventions where medical interventions are perceived as inappropriate. Research into the efficacy of social interventions in multimorbid patients is needed.

A grounded theory study was undertaken to understand how general practitioners (GPs) experience the death of their patients. Eleven GPs participated in semistructured interviews. The participants explained their experience of a patient's death using the "death journey" metaphor. This journey, the Journey with the Dying, could be described from 5 different moments in the participants' encounters with people who are dying: private acknowledgement, communication of prognosis, continuity of care, the moment of death, and looking after the family. Emotional responses for each of the stages, and coping strategies in general, were outlined. GPs' narratives about professional identity, learning about dying and death, and death beliefs were also important in the Journey with the Dying. The experience of death described by the GPs in this study was different from that reported by medical doctors in other care settings. The 5 phases of the Journey with the Dying identified here show the different adjustments and appraisals that GPs undertake to comprehend and to be able to work in the presence of death.

This study sought to characterize the variability of the acute cortisol response following trauma and its relationship to posttraumatic stress disorder (PTSD). Forty eight participants were recruited within 24h of a traumatic accident requiring hospital admission. A saliva sample was collected at 08.00 h and 16.00 h 2 days, 1 month and 6 months after hospital admission, together with 24-h urine collection. Participants completed a dexamethasone suppression test (0.5mg DEX at 21.00 h) at each follow up, together with self-report questionnaires. The Clinician Administered PTSD Scale (CAPS) was administered at 1 and 6 months to identify PTSD. Prevalence of PTSD was 27% at 1 month and 21% at 6 months. PTSD symptoms at 6 months were negatively correlated with salivary cortisol at 08.00 h on day 2 (r=-0.36, p=0.04), but positively correlated with 16.00 h cortisols (r=0.41, p=0.03). A lower rise in cortisol at 08.00 h on day 2 was associated with an increase in risk of PTSD at both 1 month (OR=1.411 (1.017, 1.957)) and 6 months (OR=1.411 (1.066, 1.866)). At 1 month, 70% of participants with PTSD suppressed cortisol to more than 90% of pre-dex levels compared with 25% without PTSD (χ(2)=6.77, p=0.034). Urinary cortisol excretion was not different between groups at any time point. The findings support a hypothesis that sensitization of the HPA axis and enhanced suppression of cortisol following the dexamethasone suppression test are established early in the disease process., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Associations between 24-hour urinary 6-sulphatoxy melatonin excretion and symptoms of posttraumatic stress disorder were assessed 2 days, 1 month and 6 months after traumatic injury requiring hospitalisation., Methods: Forty-eight participants were recruited following an admission to hospital for an acute traumatic injury. They completed assessments 48h after the accident, 1 month and 6 months later. A 24-hour urine collection was initiated the morning before questionnaires were administered. PTSD symptoms and caseness was determined using the Impact of Event Scale (IES-R) and the Clinician Administered PTSD Scale respectively. Urinary 6-sulphatoxy melatonin was assayed by radioimmunoassay., Results: Mean age of participants was 34 years (SD=12.72) and 75% were males. Ten (27%) participants met the criteria for PTSD 1 month post trauma and 6 (21%) met the criteria for PTSD at 6 months. Four of the six (67%) participants with PTSD at 6 months were also positive for major depression. Significant negative correlations were found between 6-sulphatoxy melatonin excretion at day 2 and all subscales and total score of the IES-R at the six month assessment. Controlling for depression, every one unit decrease in 6-sulphatoxy melatonin excretion was associated with a 13% increase in PTSD risk at six months (OR=1.13, 95% CI 1.00-1.27). However, this association was lost when self-reported pain, gender and employment was added to the model (OR=1.11, 0.93-1.32)., Conclusion: This study provides preliminary data suggesting disrupted melatonin levels in the first 48h following trauma may place individuals at increased risk of PTSD., (Copyright © 2010 Elsevier B.V. All rights reserved.)

This paper integrates perspectives from analytical chemistry, environmental engineering, and industrial hygiene to better understand how workers may be exposed to perfluorinated carboxylic acids when handling them in the workplace in order to identify appropriate exposure controls. Due to the dramatic difference in physical properties of the protonated acid form and the anionic form, this family of chemicals provides unique industrial hygiene challenges. Workplace monitoring, experimental data, and modeling results were used to ascertain the most probable workplace exposure sources and transport mechanisms for perfluorooctanoic acid (PFOA) and its ammonium salt (APFO). PFOA is biopersistent and its measurement in the blood has been used to assess human exposure since it integrates exposure from all routes of entry. Monitoring suggests that inhalation of airborne material may be an important exposure route. Transport studies indicated that, under low pH conditions, PFOA, the undissociated (acid) species, actively partitions from water into air. In addition, solid-phase PFOA and APFO may also sublime into the air. Modeling studies determined that contributions from surface sublimation and loss from low pH aqueous solutions can be significant potential sources of workplace exposure. These findings suggest that keeping surfaces clean, preventing accumulation of material in unventilated areas, removing solids from waste trenches and sumps, and maintaining neutral pH in sumps can lower workplace exposures.

Objective: To improve health outcomes of children and adolescents with asthma using a multifaceted intervention for GPs., Methods: The design of the study was a cluster randomized controlled trial. GPs were randomized at a practice level in general practice clinics in Melbourne, Australia. Participants were children/adolescents aged 2-14 years with asthma and their caregivers identified from the medical records of participating clinics. Questionnaires were completed by 411 at baseline and 341 at follow-up. The intervention arm (n = 18 GPs) participated in a small group asthma education programme and was provided with locally adapted paediatric asthma guidelines. One control arm (n = 18 GPs) received only the adapted paediatric asthma guidelines, while the other control arm (n = 15 GPs) received an unrelated educational intervention. The outcome measures of the study were children/adolescents and caregivers completed questionnaires about asthma management and control, asthma knowledge and quality of life at recruitment and 6 months later. Ownership of a written asthma action plan (WAAP) was the primary outcome., Results: There was no evidence for changes in ownership of WAAPs between the three study arms. Adolescents in the intervention group reported an improvement in quality of life subscale score 'positive effects' (mean difference = 2.64, P = 0.01), but there was no evidence for an effect of the intervention on other study outcomes among the three study arms., Conclusions: The intervention was associated with some improvement in quality of life for adolescents. However, overall, the intervention did not translate into increased ownership of WAAPs, control of asthma or improved quality of life.

This work assessed the usefulness of a current air quality model (American Meteorological Society/Environmental Protection Agency Regulatory Model [AERMOD]) for predicting air concentrations and deposition of perfluorooctanoate (PFO) near a manufacturing facility. Air quality models play an important role in providing information for verifying permitting conditions and for exposure assessment purposes. It is important to ensure traditional modeling approaches are applicable to perfluorinated compounds, which are known to have unusual properties. Measured field data were compared with modeling predictions to show that AERMOD adequately located the maximum air concentration in the study area, provided representative or conservative air concentration estimates, and demonstrated bias and scatter not significantly different than that reported for other compounds. Surface soil/grass concentrations resulting from modeled deposition flux also showed acceptable bias and scatter compared with measured concentrations of PFO in soil/grass samples. Errors in predictions of air concentrations or deposition may be best explained by meteorological input uncertainty and conservatism in the PRIME algorithm used to account for building downwash. In general, AERMOD was found to be a useful screening tool for modeling the dispersion and deposition of PFO in air near a manufacturing facility.