Scripps Mercy Hospital

The oral administration of finasteride, a 4-aza-steroid inhibitor of 5 alpha-reductase, decreases serum dihydrotestosterone levels, but has little effect on serum testosterone. The current study was designed to assess the effect of finasteride on dihydrotestosterone levels in the prostates of men with benign prostatic hyperplasia. In a double blind, placebo-controlled study, 69 men with symptomatic prostatic hyperplasia were treated with placebo or 1, 5, 10, 50, or 100 mg/day finasteride for 7 days before transurethral resection of the prostate. In the placebo group the mean concentration of prostatic dihydrotestosterone was 10.3 +/- 0.6 nmol/kg (+/- SE), and the mean concentration of testosterone was 0.7 +/- 0.1 nmol/kg. After 7 days of treatment with all doses of finasteride, prostatic dihydrotestosterone declined to 15% or less of control levels, and the testosterone concentration increased in a reciprocal fashion. Compared to the placebo group, there was no significant difference in the mean prostatic dihydrotestosterone level achieved in any of the finasteride-treated groups. However, prostatic dihydrotestosterone levels were lower in the groups receiving higher doses of the drug. In two additional patients, finasteride treatment for 2 days also caused a decrease in prostatic dihydrotestosterone levels. No significant adverse experiences occurred during the study. We conclude that finasteride causes profound decrease in prostatic dihydrotestosterone.

Statins inhibit HMG-CoA reductase, a key enzyme in cholesterol synthesis, and are widely used to treat hypercholesterolemia. These drugs can lead to a number of side effects in muscle, including muscle fiber breakdown; however, the mechanisms of muscle injury by statins are poorly understood. We report that lovastatin induced the expression of atrogin-1, a key gene involved in skeletal muscle atrophy, in humans with statin myopathy, in zebrafish embryos, and in vitro in murine skeletal muscle cells. In cultured mouse myotubes, atrogin-1 induction following lovastatin treatment was accompanied by distinct morphological changes, largely absent in atrogin-1 null cells. In zebrafish embryos, lovastatin promoted muscle fiber damage, an effect that was closely mimicked by knockdown of zebrafish HMG-CoA reductase. Moreover, atrogin-1 knockdown in zebrafish embryos prevented lovastatin-induced muscle injury. Finally, overexpression of PGC-1alpha, a transcriptional coactivator that induces mitochondrial biogenesis and protects against the development of muscle atrophy, dramatically prevented lovastatin-induced muscle damage and abrogated atrogin-1 induction both in fish and in cultured mouse myotubes. Collectively, our human, animal, and in vitro findings shed light on the molecular mechanism of statin-induced myopathy and suggest that atrogin-1 may be a critical mediator of the muscle damage induced by statins.

This is a recommended evaluation and management algorithm from the Western Trauma Association (WTA) Algorithms Committee focused on the management of pharmacologic prophylaxis for venous thromboembolism (VTE) prevention in trauma patients. Because there are few related published prospective, randomized clinical trials that have generated class I data on this topic in the trauma population, these recommendations are based primarily on published prospective and retrospective cohort studies, and expert opinion of the WTA members. The final algorithm is the result of an iterative process including an initial internal review and revision by the WTA Algorithm Committee members, and then final revisions based on input during and after presentation of the algorithm to the full WTA membership. Goals The algorithm (Fig. 1) and accompanying comments represent a safe and sensible approach to reducing VTE in trauma patients. The aim for this approach was to provide updated guidelines that apply to most patients, most of the time. We recognize that there will be multiple factors that may warrant or require deviation from any single recommended algorithm and that no algorithm can completely replace expert bedside clinical judgment. We encourage institutions and clinicians to use this algorithm as a general framework in the approach to trauma patients and to customize and adapt it to better suit the specifics of that program or location.Figure 1: The WTA algorithm for VTE prophylaxis after trauma. Circled letters correspond to sections in the associated article. Algorithm circle-bubbles represent patient criteria; algorithm square-bubbles represent expert recommendations. CrCl, creatinine clearance; Hb, hemoglobin; LMWH, enoxaparin; q8h, every 8 hours; q12h, every 12 hours; UFH, unfractionated heparin.Burden of Disease Venous thromboembolism, including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a potentially preventable complication after trauma. The focus of this algorithm is on optimizing the delivery of pharmacologic prophylaxis to prevent VTE and minimize any associated complications. For those trauma patients diagnosed with a DVT or PE, including distal upper extremity or calf thrombosis, specific treatments are addressed in other guidelines and will not be covered in this algorithm.1,2 Without pharmacologic prophylaxis, a 1994 study determined that the DVT rate was 58% in severely injured trauma patients who undergo serial impedance plethysmography with lower extremity contrast venography.3 In a landmark, 1996 New England Journal of Medicine publication 30 mg of subcutaneous enoxaparin twice daily performed better than 5,000 U of subcutaneous heparin twice daily at reducing DVT in moderate to severely injured trauma patients (31% vs. 44%, p = 0.04).4 The risk of major bleeding was low regardless of therapy, and importantly, the first dose of pharmacologic prophylaxis was initiated within 36 hours of the injury and continued through all surgical procedures except spinal fixation when a single preoperative dose was held.4 This study established that early, uninterrupted enoxaparin was superior to heparin at reducing VTE after trauma. In the last decade, a number of reviews and societal recommendations focused on improving the guidelines to reduce the rate of VTE and related complications after trauma.1,2,5–11 Despite this progress, debate persists regarding optimal dosing and timing of enoxaparin, including when to initiate, hold, and resume it before and after surgery or epidural placement. Trauma patients frequently receive a delayed, suboptimal dose of enoxaparin, which is then held for any potential surgical procedure despite substantial evidence that encourages early, uninterrupted pharmacologic prophylaxis. An updated algorithm on the appropriate management of VTE prophylaxis is therefore indicated. ALGORITHM The following lettered sections correspond to the letters identifying specific sections of the algorithm shown in Figure 1. In each section, we provide a brief summary of the important aspects and options that should be considered at that point in the evaluation and management process. A This algorithm is designed for adult trauma patients 18 years and older. Importantly, although younger children have a significantly lower VTE risk, older children and adolescents have a VTE risk that approaches their adult counterparts.12 Guidance for VTE prophylaxis in children can be found in the joint practice management guideline from the Pediatric Trauma Society and the Eastern Association for the Surgery of Trauma, which recommends, “pharmacologic prophylaxis be considered for children older than 15 years old and in younger postpubertal children with Injury Severity Score (ISS) greater than 25.”11 B Assessment of VTE risk will assist in determining which patients require pharmacologic prophylaxis. In general, an ISS of 10 or more suggests that pharmacologic prophylaxis should be initiated as soon as possible, whereas patients with an ISS of less than 10 are at lower VTE risk and may not require pharmacologic prophylaxis.13–15 Because ISS is not calculated in real time, the Greenfield Risk Assessment Profile or the Trauma Embolic Scoring System can assist with calculating VTE risk.13–15 Patients with spine or pelvic fractures, repair of venous injury, a history of VTE, or inherited clotting disorders have increased VTE risk and should be considered for pharmacologic prophylaxis.2,13,14 Among trauma patients with minor injuries, independent predictors of increased VTE risk are increased age, obesity, and lower extremity fractures; any combination of these three characteristics should encourage initiation of pharmacologic prophylaxis.13 C Patients with minor trauma may not require pharmacologic prophylaxis. Given the related pain with injection, potential for hematoma at the injection site, cost for the medication, and nursing costs for administration, avoiding pharmacologic prophylaxis may be indicated for select low-risk patients after minor trauma. The Trauma Embolic Scoring System can be used to assess VTE risk, as patients with a low score require no pharmacologic prophylaxis because of their low VTE rate.13 Ambulatory patients with minor injuries and short hospital stays may not require pharmacologic prophylaxis. Trauma patients capable of ambulation but confined to bed because of intoxication, restraints, or other reasons should receive pharmacologic prophylaxis. In general, trauma patients who require hospital admission for more than 24 hours require pharmacologic prophylaxis, whereas those hospitalized for less than 24 hours do not. For the patients who do not receive pharmacologic prophylaxis, mechanical prophylaxis and/or aspirin are low cost and low morbidity options, although their benefit is uncertain given the low VTE rate.13–16 D Appropriate delays in pharmacologic prophylaxis may occur for those patients with an active bleed, coagulopathy, hemodynamic instability, solid organ injury, traumatic brain injury (TBI), or spinal trauma. Quantifying the risk and benefit of initiating pharmacologic prophylaxis for each patient is a challenge that is best determined by the trauma team at bedside. Detailing every indication where a delay may be indicated is outside the scope of these guidelines; several are described below. However, it is important to note that the guidance in both the literature and clinical practice supports very short delays to the initiation of pharmacologic prophylaxis, even among these cohorts. Active Bleeding, Coagulopathy, or Hemodynamic Instability Control of active bleeding is necessary before starting pharmacologic prophylaxis. In the presence of hemodynamic instability, a hemoglobin drop of greater than 2 g/dL in under 12 hours or ongoing blood transfusion is an appropriate indication to delay the initiation of pharmacologic prophylaxis.2,4 Systemic coagulopathy was previously proposed as a reason to delay pharmacologic prophylaxis with one study holding pharmacologic prophylaxis for an elevated prothrombin time of more than 3 seconds above control or a platelet count of less than 50,000 per cubic millimeter.4 More recent studies indicate that prothrombin time and platelet count are not as reliable at predicting systemic coagulopathy as viscoelastic hemostatic assays, which may demonstrate hypocoagulability and hypercoagulability after trauma.2,17–19 The hypocoagulability due to trauma largely resolves within 24 hours, after which hypercoagulability becomes prevalent. In this setting, pharmacologic prophylaxis may be considered after the initial resuscitation is complete.17,20 Deferring the initiation of pharmacologic prophylaxis during trauma-induced coagulopathy is associated with an increased VTE rate such that the initiation of pharmacologic prophylaxis is encouraged if the hypocoagulable state is expected to resolve and there are no signs of ongoing bleeding.17 Solid Organ Injury Delays occur in the initiation of pharmacologic prophylaxis for patients with solid organ injury. Several studies indicate that patients with solid organ injury who received early pharmacologic prophylaxis had lower DVT and PE rates without increased risk of failure of nonoperative management, bleeding complications, or mortality; these risks did not increase when pharmacologic prophylaxis was started within 24 hours compared with within 48 hours.20–23 Early pharmacologic prophylaxis within 12 to 24 hours appeared to be safe across moderate American Association for the Surgery of Trauma injury grade and type of solid organ injury (liver, spleen, and/or kidney), without an increased risk of bleeding that necessitated intervention or blood transfusion.21 Although those with grade IV and V injuries should be approached with caution, pharmacologic prophylaxis may be initiated within 24 hours for most patients with solid organ injury.21–23 Traumatic Brain Injury Concern for progression of TBI is a common reason for the delay in initiation of pharmacologic prophylaxis. This delay is dependent on the type of TBI; those with “cerebral contusion, localized petechial hemorrhages, or diffuse axonal damage” may safely receive pharmacologic prophylaxis without delay.4 When pharmacologic prophylaxis is appropriately delayed, the follow-up computed tomography (CT) after TBI diagnosis is an important indicator for when to initiate pharmacologic prophylaxis.24 For patients with TBI progression on the follow-up CT, exposure to pharmacologic prophylaxis is a predictor for further progression, and it should be held until a follow-up CT demonstrates no progression.24 In contrast, if the follow-up CT demonstrates no TBI progression, then pharmacologic prophylaxis should be initiated.24 Importantly, progression of TBI occurs in about 10% of patients with a stable follow-up CT, regardless of whether pharmacologic prophylaxis is provided or not.24 Those trauma centers that provide pharmacologic prophylaxis within 24 hours after TBI have significantly lower rates of VTE with no difference in rates of late neurosurgical intervention.23,25–30 Even in the setting of combat related penetrating TBI, initiating pharmacologic prophylaxis 24 hours after injury for those patients with a stable CT was safe, with similar progression rates regardless of pharmacologic prophylaxis.29 The majority of TBI patients with a stable CT may be initiated on enoxaparin within 24 hours, and nearly all TBI patients should receive pharmacologic prophylaxis within 72 hours of the time of injury.23,28,31 Spinal Trauma In the absence of pharmacologic prophylaxis, patients who undergo spine surgery or those with spine trauma, fracture, or cord injury have a of and delays than 72 hours to a substantial increase in the VTE prophylaxis be initiated as soon as after spine surgery or any spine that provide pharmacologic prophylaxis or after fixation are considered When a was that pharmacologic prophylaxis or the of spine the VTE rate and the rate of spinal hematoma was pharmacologic prophylaxis initiated within 48 hours of fixation of traumatic spine did not increase the risk of progression of injury, or complications including spinal prophylaxis for moderate to VTE risk patients is encouraged regardless of pharmacologic prophylaxis. For patients who are not started on pharmacologic prophylaxis, mechanical prophylaxis with and when possible, should be the DVT if no pharmacologic prophylaxis is initiated and therefore is recommended for patients with a to pharmacologic In contrast, the of in patients who received pharmacologic prophylaxis did not to a in the DVT although the study had a low DVT rate and of the trauma mechanical prophylaxis with pharmacologic prophylaxis is therefore encouraged for moderate to VTE risk patients in because those who received the combination had a lower of do not to reduce the VTE rate in the presence of pharmacologic but may provide a benefit to those trauma patients who be started on pharmacologic is an important for VTE as early to a in A is safe in trauma patients and may reduce patient the rate of of spinal is associated with an increased DVT rate and should be to early venous should be considered in patients at VTE risk who be started or on pharmacologic prophylaxis. Although debate with venous is not indicated or for all trauma after trauma not the risk of PE or PE, and to In trauma patients at low VTE risk, the cost and low of that the practice may be institutions for in low-risk trauma patients to both and which may and the related complications such as venous venous or pain with For trauma patients at VTE risk, is associated with a PE The Greenfield Risk Assessment Profile can which trauma patients may benefit from may be in VTE risk patients who be started or on pharmacologic prophylaxis. the of DVT should not be a that all trauma patients have rates of and those centers with that do not will have DVT rates because of a lower for a venous prophylaxis be initiated as soon as and for most trauma patients may be initiated within 24 When VTE risk trauma patients who receive enoxaparin within 24 hours of admission are compared with those who receive mechanical prophylaxis, minor and major bleeding do not in appropriate delays may occur in the initiation of pharmacologic prophylaxis because of active coagulopathy, hemodynamic instability, solid organ injury, TBI, or spinal trauma. In most pharmacologic prophylaxis may be started in less than 24 hours, and in every pharmacologic prophylaxis may be started in less than 72 prophylaxis is held because of surgery despite the evidence that it may be initiated before most surgical Trauma patients who require an are in that their first may occur within of or the pharmacologic prophylaxis is or for which to an increased VTE dosing of pharmacologic prophylaxis is not to trauma. In other patient at risk for VTE, the use of preoperative pharmacologic prophylaxis the DVT rate without the complication for in should be initiated and continued Patients who surgery who received low heparin hours before surgery had a lower rate of DVT without or bleeding This benefit was not when low heparin was provided 12 hours or more We that the common and process of pharmacologic prophylaxis for 12 to 24 hours before surgical procedures is and will result in an increased VTE risk without an accompanying in the risk of bleeding to pharmacologic prophylaxis, the specific and initial dose should be determined for each is the recommended for most trauma patients with considered the of The for pharmacologic prophylaxis is the low heparin enoxaparin because of increased and more and compared with unfractionated less with which may reduce bleeding complications compared with unfractionated a lower of and not have the associated with heparin When the initial mg of enoxaparin twice daily should be considered the for most trauma patients, as 30 mg twice daily frequently in pharmacologic patients 18 to years with of more than and a creatinine of more than should be started on mg of enoxaparin twice as this dose is safe and the VTE Patients who are older than less than or who have a creatinine of 30 to should to receive initial dosing at 30 mg of enoxaparin twice The initial enoxaparin dose for trauma patients with a may be based on twice twice or 30 mg for to patients, mg for to patients, and mg for patients greater than Patients who are initiated on of enoxaparin based should be by because of the in creatinine after trauma that to in the enoxaparin Although enoxaparin is to heparin for pharmacologic prophylaxis, institutions to dose unfractionated heparin at 5,000 U three daily based in on a randomized that that this be and compared with 30 mg of enoxaparin twice This practice should be as the was because of an DVT rate of for unfractionated heparin for enoxaparin, and a 10% for the The difference in the VTE rate was which enoxaparin without vs. enoxaparin, p = In the study was not to a difference in the rate of PE or both of which the complication rate and More 30 mg of enoxaparin twice daily was established as superior to U of unfractionated heparin three daily at the prevention of VTE and for Quantifying the risk and benefit of the type and initial dose of pharmacologic prophylaxis for each patient is a challenge best determined by the trauma team at bedside. mg of enoxaparin twice daily is the recommended initial pharmacologic prophylaxis for most trauma patients. Detailing every indication where an or dose may be indicated is outside the scope of these guidelines; several are described below. In the presence of or a creatinine of subcutaneous unfractionated heparin at U every 8 hours may be Because enoxaparin is by the to patients with failure may to increased bleeding complications and should be not and for use in patients. lower enoxaparin in the setting of a creatinine of may be in the but is necessary before this can be In most other enoxaparin is to unfractionated as enoxaparin to lower VTE rates without increased bleeding Brain and Trauma For TBI patients, enoxaparin is associated with less VTE and than unfractionated heparin with no difference in the progression of brain regardless if the dose was in less than 24 hours after 24 to 48 hours, or after 48 those patients with spine trauma should receive early Patients with brain and spine trauma should be initiated on 30 mg of enoxaparin twice daily and considered for dose by Patients patients require specific dose recommendations for pharmacologic prophylaxis after trauma because of the as as the increase in and that occur the of require enoxaparin with more unfractionated heparin enoxaparin the and both are considered safe to use in during an admission for trauma, patients should receive 30 mg of enoxaparin twice daily by a of to or a of to For patients who more than initiating mg of enoxaparin twice daily is recommended with similar and prophylaxis with or aspirin should not be a for pharmacologic prophylaxis for most trauma patients because of the of related clinical The use of or aspirin may be considered in the setting of injuries, but if the patient injection with enoxaparin or unfractionated are for pharmacologic prophylaxis after 10 mg of and mg of twice both which are trials that or to enoxaparin demonstrate that have to better VTE rates with similar to bleeding In contrast, other that enoxaparin a lower VTE and a lower bleeding Because retrospective have the use of for pharmacologic prophylaxis after trauma, randomized trials are necessary before a for trauma The use of low dose aspirin may be considered for pharmacologic prophylaxis in trauma patients with injuries who For those trauma patients started on a for pharmacologic prophylaxis, aspirin may replace the after with similar prevention of I trauma patients require dose after initiating Because of the in and enoxaparin by is In one of trauma patients of mg or and of mg or enoxaparin by or to lower the VTE rate without bleeding complications in moderate to severely injured patients, trauma patients who require injuries, and surgical Although debate on the appropriate for suggests to for or to for should be considered for those patients who receive Although not for pharmacologic prophylaxis, with platelet may assist with platelet A randomized that used as an to enoxaparin did not lower rates of VTE with the enoxaparin In contrast, with platelet may if a hypercoagulability is due to platelet which encourages the of aspirin to the pharmacologic prophylaxis aspirin is the initial recommended dose is mg daily with the of the dose to mg daily on with platelet The uninterrupted dosing of pharmacologic prophylaxis should be the for most trauma patients their hospital Although the and benefit of uninterrupted pharmacologic prophylaxis established more than of trauma patients A is the number of and DVT risk such that patients who to have DVT risk compared with those with no For TBI patients who are started on pharmacologic prophylaxis, dosing an increase in the VTE The following are common reasons for pharmacologic procedure patient was from the for bleeding epidural and When holding pharmacologic prophylaxis, the rate of bleeding with pharmacologic prophylaxis is no than without VTE are compared with bleeding complications, the pharmacologic should focus on pharmacologic prophylaxis without The appropriate for holding or pharmacologic prophylaxis spinal epidural or and these are below. Although VTE is not indicated for all trauma may be in those at VTE venous should be performed for evidence of DVT such as or For those trauma patients with injuries and in pharmacologic prophylaxis, venous may be a DVT or PE is then is necessary per and if it is then an should be considered as in Surgery in holding pharmacologic prophylaxis because of surgery is with few for brain or spine Given the delays and of that may occur during trauma patient holding pharmacologic prophylaxis can of pharmacologic prophylaxis. pharmacologic prophylaxis is safe for trauma and to a lower VTE The preoperative of pharmacologic prophylaxis is encouraged for surgical patients in other who have a VTE risk and to a lower DVT rate without the complication The lower VTE rate is if pharmacologic prophylaxis is provided more than 12 hours reduce morbidity and in trauma patients injuries and are a of pain Patients who require an epidural have in pharmacologic such that epidural is associated with an increased VTE whereas previously this was not the a enoxaparin dose and epidural by a to before enoxaparin is at 10 and 10 the dose may be held for 10 epidural to for the necessary without prophylaxis. 10 the enoxaparin dosing may one dose is of enoxaparin are for pharmacologic prophylaxis, a for enoxaparin before epidural by a to before at of enoxaparin should be for any enoxaparin enoxaparin are encouraged with to the VTE rate associated with epidural For unfractionated a to is recommended before epidural by a before unfractionated heparin is which for uninterrupted platelet should be considered for those trauma patients who receive pharmacologic prophylaxis because of the risk of is recommended for patients who are considered risk for every 3 from to or until pharmacologic prophylaxis is Trauma patients who are to enoxaparin may be considered low risk for and may not require platelet as the rate of clinical was with heparin compared with with The clinical diagnosis of may be by that thrombosis, and the heparin be with such as the which can for trauma patients for because of the of these and the with dosing and their may be considered in the setting of DVT or PE when there is a to appropriate The use of is among trauma centers although their is without a in PE is not In a randomized of VTE risk trauma patients who to receive pharmacologic prophylaxis during the first 72 hours of a did not lower the of PE or which established the of of early of an in this The of an not regardless of whether a DVT is or guidelines provide recommendations and most studies have among patients diagnosed with an DVT or PE who receive an should be considered to reduce the rate of PE without the Trauma patients with TBI, or spine injuries, and those who undergo major surgery are at VTE risk and should be considered for pharmacologic prophylaxis. prophylaxis after for VTE risk trauma patients is by evidence that demonstrates the practice is safe, and and may be considered for patients with TBI, or spine injuries, and those who undergo major The VTE risk occurs during the first 3 after injury with until the VTE rate to that of the general Venous for of trauma at a cost of pharmacologic prophylaxis with enoxaparin is associated with a low rate of bleeding complications, and is in patients at VTE The of pharmacologic prophylaxis following or pelvic surgery for or was associated with a in VTE Because the optimal dose and of enoxaparin after trauma are not more than 30 mg twice daily should be and the of pharmacologic prophylaxis may be considered for to after the of For those who undergo major pharmacologic prophylaxis may be to from the of may be initiated for pharmacologic prophylaxis for VTE risk trauma patients, as it shown to be as as enoxaparin with less bleeding complications and better and is not by the of may be considered for pharmacologic prophylaxis after This algorithm was designed to provide and guidance at reducing the VTE rate after trauma. Although there are multiple factors that will to from the most trauma patients should be initiated on early and of enoxaparin that should be by For most trauma patients, pharmacologic prophylaxis should uninterrupted the hospital and at after preventable and delays to the initiation and of pharmacologic prophylaxis should be a focus of all trauma and it associated with rates of VTE

An association between hypoxemia and poor outcomes from traumatic brain injury (TBI) is well documented. However, it is unclear whether hyperoxygenation is beneficial. This registry-based analysis explores the relationship between early hypoxemia and hyperoxemia on outcome from moderate-to-severe TBI. TBI patients (Abbreviated Injury Scale score 3+) were identified from the San Diego County trauma registry. Patients were stratified by arrival partial oxygen pressure (Po(2)) value. Trauma and injury severity score (TRISS) was then used to calculate predicted survival for each patient, with the mean observed-predicted survival differential determined for each arrival Po(2) stratification. Logistic regression was used to quantify the relationship between hypoxemia, hyperoxemia, and outcome from TBI after adjusting for multiple variables including intubation and ventilation status. A total of 3420 patients were included in the analysis. TRISS calculations revealed worse outcomes than predicted for both hypoxemia and extreme hyperoxemia. Logistic regression revealed an optimal Po(2) range (110-487 mm Hg), with an independent association observed between decreased survival and both hypoxemia (OR 0.54; 95% CI 0.42, 0.69; p < 0.001) and extreme hyperoxemia (OR 0.50; 95% CI 0.36, 0.71; p < 0.001). The association between hypoxemia and extreme hyperoxemia and worse outcomes was also present with use of "good outcomes" as the outcome variable (discharge to home, rehabilitation, jail, or psychiatric facility, or leaving against medical advice). We conclude that both hypoxemia and extreme hyperoxemia are associated with increased mortality and a decrease in good outcomes among TBI patients.

Lipid-lowering drugs produce myopathic side effects in up to 7% of treated patients, with severe rhabdomyolysis occurring in as many as 0.5%. Underlying metabolic muscle diseases have not been evaluated extensively. In a cross-sectional study of 136 patients with drug-induced myopathies, we report a higher prevalence of underlying metabolic muscle diseases than expected in the general population. Control groups included 116 patients on therapy with no myopathic symptoms, 100 asymptomatic individuals from the general population never exposed to statins, and 106 patients with non-statin-induced myopathies. Of 110 patients who underwent mutation testing, 10% were heterozygous or homozygous for mutations causing three metabolic myopathies, compared to 3% testing positive among asymptomatic patients on therapy (P = 0.04). The actual number of mutant alleles found in the test group patients was increased fourfold over the control group (P < 0.0001) due to an increased presence of mutation homozygotes. The number of carriers for carnitine palmitoyltransferase II deficiency and for McArdle disease was increased 13- and 20-fold, respectively, over expected general population frequencies. Homozygotes for myoadenylate deaminase deficiency were increased 3.25-fold with no increase in carrier status. In 52% of muscle biopsies from patients, significant biochemical abnormalities were found in mitochondrial or fatty acid metabolism, with 31% having multiple defects. Variable persistent symptoms occurred in 68% of patients despite cessation of therapy. The effect of statins on energy metabolism combined with a genetic susceptibility to triggering of muscle symptoms may account for myopathic outcomes in certain high-risk groups.

Although statins are remarkably effective, they are still underprescribed because of concerns about muscle toxicity. We review the aspects of statin myopathy that are important to the primary care physician and provide a guide for evaluating patients on statins who present with muscle complaints. We outline the differential diagnosis, the risks and benefits of statin therapy in patients with possible toxicity, and the subsequent treatment options.

BACKGROUND: Peripheral neuropathy can significantly impact the quality of life for those who are affected, as therapies from the current treatment algorithm often fail to deliver adequate symptom relief. There has, however, been an increasing body of evidence for the use of cannabinoids in the treatment of chronic, noncancer pain. The efficacy of a topically delivered cannabidiol (CBD) oil in the management of neuropathic pain was examined in this four-week, randomized and placebocontrolled trial. METHODS: In total, 29 patients with symptomatic peripheral neuropathy were recruited and enrolled. 15 patients were randomized to the CBD group with the treatment product containing 250 mg CBD/3 fl. oz, and 14 patients were randomized to the placebo group. After four weeks, the placebo group was allowed to crossover into the treatment group. The Neuropathic Pain Scale (NPS) was administered biweekly to assess the mean change from baseline to the end of the treatment period. RESULTS: The study population included 62.1% males and 37.9% females with a mean age of 68 years. There was a statistically significant reduction in intense pain, sharp pain, cold and itchy sensations in the CBD group when compared to the placebo group. No adverse events were reported in this study. CONCLUSION: Our findings demonstrate that the transdermal application of CBD oil can achieve significant improvement in pain and other disturbing sensations in patients with peripheral neuropathy. The treatment product was well tolerated and may provide a more effective alternative compared to other current therapies in the treatment of peripheral neuropathy.

Each family member’s own health may be affected by whether his or her needs are met and by the actions of the health care team.This poem is based on a true experience that I had with an elderly woman when I was working as a nurse manager/clinical nurse specialist. The woman experienced unnecessary distress after her husband’s death because she lacked information about the cause of death and had misinterpreted events. She carried this burden for a whole year before getting clarification. The vignette illuminates a common problem in the intensive care unit (ICU). Patients’ family members are personally affected by the experience with critical care. Each family member’s own health and well-being may be affected by whether his or her needs are met and by the actions of the health care team.1–7In the terms of the grand theorist, Sister Calista Roy, critical illness causes a disruption in life.8 The disruption requires a period of adjustment called the compensatory process that results in adaptation to the event. Adaptation can be positive or negative, complete or incomplete, depending on what happens during the adjustment period. The process repeats itself, and as a patient’s condition changes, the patient’s family must adapt to these changes. For the widow represented in “Anniversary,” her husband’s caregivers did not provide her with the information that would have decreased her distress. The lack of a timely debriefing to clarify misconceptions led, in this case, to a maladaptation to bereavement. The impetus for writing this article came from work on a project to synthesize the family support literature to create a guideline for family support in the patient-centered ICU9 for the American College of Critical Care Medicine and the Society of Critical Care Medicine. That guideline includes a section titled “Family Coping” that briefly summarizes how patients’ families adapt to critical illness. The summary concludes with recommendations to provide patients’ families with timely, accurate, and consistent information in an attempt to optimize the families’ experience.In this article on family adaptation to critical illness, I review the results of descriptive studies related to needs of patients’ families, studies on the relationship between meeting family needs and adverse psychological outcomes, and studies intended to help define nursing interventions to meet the needs of patients’ families.1–3,10–13 The level of current evidence guiding practice is defined according to the GRADE (grading of recommendations, assessment, development, and evaluation) system.14 The GRADE system has 4 levels of evidence: high, unlikely further research would change findings; moderate, some likelihood further research may change findings; low, very likely further research may change findings; and very low, evidence is not strong enough to truly estimate effect of intervention at this time.In a qualitative study by Titler et al,15 patients’ family members reported that the ICU experience was an overriding threat characterized by vulnerability, intense emotion, fear, and anxiety. In addition, the experience caused a disruption and changed intrafamily relationships, resulting in role strain. Titler et al concluded that nurses should test interventions that are geared toward conveying information between a patient’s nurse and the patient’s family.Several studies have focused on the need for information and communication. In another qualitative study, Nelson et al16 found that families of patients who required long-term mechanical ventilation and tracheostomy valued receiving information on the illness and treatment, what would happen in the future, treatment burden, potential complications, what to expect after hospitalization, and alternatives to treatment. The results of 3 surveys17–19 of bereaved relatives of ICU patients suggest a relationship between perceived effectiveness of communication, proximity to the patient, and satisfaction with care. In a multidisciplinary study by Cuthbertson et al18 on family needs, the largest volume of complaints offered by patients’ families were related to restricted access and poor communication. Satisfaction of patients’ families was inversely proportional to the number of attending physicians involved in the case. Satisfaction also decreased as the number of nurses who cared for a patient increased. Cuthbertson et al concluded that consistency in communication was a key to the satisfaction of patients’ families.In a survey by Abbott et al,19 48% of respondents reported family conflict during the ICU experience and indicated that this conflict was caused by ineffective or inappropriate communication by the health care team. Family members frequently reported the need to know more information but never reported that too much information was given. That study setting had an open visiting policy, and the survey respondents commented on how much they appreciated the unrestricted access. In another survey,17 17% of respondents thought that they had received unclear information or not enough information. These studies indicate that the needs of patients’ families for information and proximity are commonly left unmet.The importance of information and proximity are further supported by the group of studies in which the Critical Care Family Needs Inventory (CCFNI)20 was used.The CCFNI has 5 categories of needs: support, comfort, information, proximity to the patient, and assurance.20 In an analysis of 18 studies in which the CCFNI was used, Leske21 found the tool valid and reliable in its complete form. Although all needs on the CCFNI may not be important,22 informational needs are the most important23–27 and are often unmet.28 Recently, a group of physicians in France used the CCFNI in a multi-center study29 and found that the satisfaction of patients’ families decreased when conflicting information was received by the families and when not enough time was spent giving information, further reinforcing the importance of information and communication.Additional studies with the CCFNI focused on the difference between needs that patients’ family members thought were important and the health care providers’ assessment of the members’ needs. Researchers found that nurses and physicians assume what a family needs on the basis of the care providers’ own values, which may not accurately reflect the actual needs of a patient’s family.30 Nurses repeatedly have been found to underestimate the importance of a family’s needs, such as the need for information or the need to be close to the patient.24,31,32 These studies collectively suggest that nurses should ask a patient’s family members about the members’ needs rather than basing interventions on presumptions about those needs. One study33 showed that empathy has a significant relationship with the ability to anticipate needs of patients’ families and that nurses with more experience actually predicted family needs less accurately than did less experienced nurses. As these results indicate, nurses should proactively ask patients’ family members about the members’ needs.Burr34 conducted a study to validate the CCFNI by interviewing patients’ family members and comparing the members’ stated needs with the needs indicated by scores on the CCFNI. Most items on the CCFNI were also disclosed during the interviews. However, family members in this Australian study reported 2 additional needs: to provide support and to protect the patient. Protecting the patient was further defined through interviews as “maintaining the vigil” or “watch[ing] over the patient” in the event that something might happen.34(p164) These 2 additional needs suggest that nurses should allow family presence as a way of helping patients’ family members meet the need to provide support and safety.The Institute of Medicine35 further supports the concept of allowing family presence in an effort to improve safety and recommends that health care delivery systems become patient-centered in an effort to improve patient safety. According to the institute’s patient-centered model, the patient-family dyad should be kept informed and actively involved in medical decision making and self-management. Involvement of patients’ families is especially important in the ICU because patients are too ill to advocate for themselves.For a patient-centered care model to be operationalized in the ICU, patients’ family members and surrogate decision makers must become active partners in decision making and care.9,36,37 Patients’ family members often have first-hand insight into patients’ preferences and can make important contributions to care decisions. Research studies have not measured the effect of family presence on patients’ safety. However, family members of patients may play a role in reducing medical errors by alerting staff to issues such as new changes in level of consciousness, previous response to medications, and medications taken at home.38,39 The findings from Burr’s study34 suggest that family members want to be involved in safeguarding the patient. Logically, then, meeting the need of a patient’s family members to participate, support, and protect the patient would help family members to cope with the situation. Proximity through liberal visitation will permit the safekeeping role desired by some family members.The following real-life example occurred while I was interviewing a family in the ICU. The interview was conducted after the family members had completed the CCFNI survey. The example describes the family’s need to protect the patient while showing how difficult it is for family members to adequately express their concerns without help from the nurse (J. E. Davidson, D. Agan, J. Murphy, P. Guiterrez, unpublished data, 2007). When asked, “Is there anything else I can do for you that would make this a better experience given what you’ve been through?” the son of an ICU patient reported an issue after being prompted by his sister. The sister was seething with anger. She demanded that he speak up. The son (brother) looked down and offered, in a measured serious voice, (paraphrased) “She has a bloody bandage on her neck. It has been there for 2 days. It is hard to look at. We only want her cared for.” It appeared by the intensity of their responses that they had both been ruminating about this bandage for 2 days and that it was causing them a great deal of stress. Until then, though, they did not bring it up to the nurse. Upon inspection of the patient, it was found that it was not blood at all, but povidone-iodine on gauze covering an old central catheter insertion site. The patient’s nurse, upon hearing this, asked why the family had not asked about it before. According to Weick’s organizational sensemaking theory,40,41 the family members’ misconception had gone unchecked because they were afraid to ask about it, and reflective activity to sort through the cues in their environment had not been encouraged. These descriptions suggest that nurses, through probing questions designed to ferret out issues, concerns, misconceptions, and distortions, can prevent such events. Patients’ families need to make sense of ambiguous situations, but they may not be able to do so without help.Canadian researchers4–6,13 have focused on the incidence of anxiety in family members of critically ill patients in relationship to whether the families’ needs were met or not met according to the CCFNI. Anxiety was higher in women and was significantly influenced by family needs.13 The research was replicated with others in a multicenter design,5 and again a significant relationship was found between situational anxiety and family needs. Kloos42 also found high levels of anxiety in family members of ICU patients.Recently, the psychological impact of critical illness on a patient’s family member, particularly risk of anxiety, depression, and posttraumatic stress disorder (PTSD), has gained attention in the literature.2,3,11,12 The largest study to date was a multicenter French longitudinal study.3 At 90 days after discharge or death of the patient, 33% of family members of ICU patients had moderate to high risk for PTSD. The risk increased to 80% for those family members involved in end-of-life decision making. The risk was also significantly higher in women and when not enough time was given for communication, information was incomplete, or information was not easy to understand. Pochard et al12 also found that 73.4% and 35.3% of family members had symptoms of anxiety and depression, respectively. Because of the differences between France and the United States in culture, visiting hours, and decision-making models (paternalistic vs shared), it is not known whether these findings can be generalized to the United States.In contrast to the extensive studies on the needs of patients’ families, relatively few studies have involved an attempt to change outcomes in patients’ family members. I used MEDLINE, CINAHL, Proquest (Dissertations and Abstracts), and Psyc-INFO databases and the terms family and intensive care or critical care to search the literature. All the studies I found that had significant findings are reported here. The results are synthesized in the TableT1 and scored according to the GRADE system.14Researchers in 2 studies7,43 found significantly improved satisfaction among patients’ families when an effort was made to improve communication. In the study by Chien et al,43 family members given an individualized program of information by a trained nurse whose role it was to provide education to patients’ families had lower anxiety and better satisfaction than did a comparison group. In the study by Medland and Ferrans,7 the need for patients’ family members to be called at home about changes in the patients’ condition was identified from previous research in which the CCFNI was used. A 3-pronged strategy was then implemented: the ICU nurse met with each patient’s family within 24 hours of the patient’s admission, gave the family a pamphlet, and an ICU nurse called the family daily to provide an update. Satisfaction and perception of information needs met were significantly higher in the experimental group. These findings support the ideas that information should be tailored to the situation and that a preformatted pamphlet may not exclusively meet the needs of all family members.A randomized controlled trial10 of mothers and their children in a pediatric ICU indicated that a multimodal educational program to help mothers participate meaningfully at the bedside reduced PTSD symptoms at 1-year follow-up, with a trend toward reduction at earlier testing points. In that study,10 in-person instruction, a video, and written materials were given to the parents. Maternal self-reports of stress were reduced and maternal participation in care increased once the child was out of the ICU. Depression was reduced at 1 and 6 months but not at 3 months and 1 year after discharge.Another randomized controlled trial1 that involved bereaved family members in French adult ICUs showed that improving communication by using case conferencing plus an information leaflet decreased the risk of PTSD depression scores as well as combined anxiety and depression. Results of this cluster of studies1,7,10,43 further suggest that individualized, multimodal, in-person techniques to improve meeting the needs of patients’ families may have a greater effect on psychological well-being of the family members than would a single intervention or a nonindividualized format. Thus, if the ICU has developed brochures for patients’ family members, the brochure alone may not be enough to help family members cope with the situation. Family members need in-person assistance, communication, clarification, and guidance with information tailored to their individual needs.In summary, family members of ICU patients may witness a life-threatening crisis. The crisis disrupts normal life and role function.8 Patients’ family members may not be able to act to meet the members’ own needs independently at this time without assistance to sort through environmental cues and to clarify distortions and misinterpretations.40 The response to the crisis may result in dissatisfaction, anxiety, depression, and PTSD.1–6,10,13,42 Nurses can assist in the compensatory process leading to adaptation through a structured approach to providing family support. Supportive actions to promote attainment of the needs of patients’ families may include reflective inquiry (looking back to clarify what has happened) and family inclusion in care.10,41Family members of ICU patients have a variety of needs (eg, proximity, information, support, assurance, and comfort) that must be fulfilled in order to support the patients through active involvement and protect the patients through maintaining a vigil.20,34,44 Needs are often left unmet.15,17,18 Fulfillment of families’ needs may decrease adverse psychological outcomes, but studies to date geared toward this effort have had mixed results.24,42,45,46 Larger studies1,10 with multiple methods of intervention, at least one of which involves personal individualized interaction with a patient’s family, can improve the family’s outcomes.1,10 Therefore, individualized instruction with proactive assessment of a family’s needs may help fulfill the family’s needs and maximize the adaptation of patients’ family members to critical illness.Caution is required, however, because the current level of the evidence to guide practice is very low. Although randomized controlled trials have been conducted, each trial addressed different interventions and outcomes in different settings and populations, so generalization of findings to all of critical care is not possible. Further research is indicated to validate the findings of the initial work done in this area and to test the effect of other supportive strategies on the outcomes of patients’ families.

BACKGROUND: Existing radiographic classification schemes (eg, Tönnis criteria) for DDH quantify the severity of disease based on the position of the ossific nucleus relative to Hilgenreiner's and Perkin's lines. By definition, this method requires the presence of an ossification centre, which can be delayed in appearance and eccentric in location within the femoral head. A new radiographic classification system has been developed by the International Hip Dysplasia Institute (IHDI), which uses the mid-point of the proximal femoral metaphysis as a reference landmark, and can therefore be applied to children of all ages. The purpose of this study was to compare the reliability of this new method with that of Tönnis, as the first step in establishing its validity and clinical utility. METHODS: Twenty standardized anteroposterior pelvic radiographs of children with untreated DDH were selected purposefully to capture the spectrum of age (range, 3 to 32 mo) at presentation and disease severity. Each of the hips was classified separately by the IHDI and Tönnis methods by 6 experienced pediatric orthopaedists from the United States, Canada, Mexico, United Kingdom, and by 2 orthopaedic senior residents. The inter-rater reliability was tested using the Intra Class Correlation coefficient (ICC) to measure concordance between raters. RESULTS: All 40 hips were classifiable by the IHDI method by all raters. Ten of the 40 hips could not be classified by the Tönnis method because of the absence of the ossific nucleus on one or both sides. The ICC (95% confidence interval) for the IHDI method for all raters was 0.90 (0.83-0.95) and 0.95 (0.91-0.98) for the right and left hips, respectively. The corresponding ICCs for the Tönnis method were 0.63 (0.46-0.80) and 0.60 (0.43-0.78), respectively. There was no significant difference between the ICCs of the 6 experts and 2 trainees. CONCLUSIONS: The IHDI method of classification has excellent inter-rater reliability, both among experts and novices, and is more widely applicable than the Tönnis method as it can be applied even when the ossification centre is absent. LEVEL OF EVIDENCE: Level II (diagnostic).

INTRODUCTION: Since their release in 2017, standing electric motorized scooters (eScooters) have risen in popularity as an alternative mode of transportation. We sought to examine the incidence of injury, injury patterns, prevalence of helmet and drug and alcohol use in eScooter trauma. METHODS: This was a multi-institutional retrospective case series of patients admitted for injuries related to operation of an eScooter following the widespread release of these devices in September 2017 (September 1, 2017 to October 31, 2018). Demographics, drug and alcohol use, helmet use, admission vitals, injuries, procedures, hospital and intensive care unit length of stay (LOS), death, and disposition were analyzed. RESULTS: 103 patients were admitted during the study period, and monthly admissions increased significantly over time. Patients were young men (mean age 37.1 years; 65% male), 98% were not wearing a helmet. Median LOS was 1 day (IQR 1-3). 79% of patients were tested for alcohol and 48% had a blood alcohol level >80 mg/dL. 60% of patients had a urine toxicology screen, of which 52% were positive. Extremity fractures were the most frequent injury (42%), followed by facial fractures (26%) and intracranial hemorrhage (18%). Median Injury Severity Score was 5.5 (IQR 5-9). One-third of patients (n=34) required an operative intervention, the majority of which were open fixations of extremity and facial fractures. No patients died during the study. The majority of patients were discharged home (86%). CONCLUSION: eScooter-related trauma has significantly increased over time. Alcohol and illicit substance use among these patients was common, and helmet use was extremely rare. Significant injuries including intracranial hemorrhage and fractures requiring operative intervention were present in over half (51%) of patients. Interventions aimed at increasing helmet use and discouraging eScooter operation while intoxicated are necessary to reduce the burden of eScooter-related trauma. LEVEL OF EVIDENCE: Level IV.

Criminologists tend to focus their attention on the dynamics of offending, paying limited theoretical and empirical attention to the well-established relation between offending and victimization. However, a number of criminological theories predict similarities in the correlates and etiology of victimization and offending, suggesting substantial overlap across offender and victim populations. Empirical research confirms this overlap across offender and victim populations, at least among those involved in non-lethal incidents. This research explores whether similarities between offender and victim populations extend to homicide, using criminal justice, health care, and U.S. Census data linked to homicide offenders and victims in Bernalillo County, New Mexico, between 1996 and 2001. Findings indicate substantial overlap in the social contexts and risk behaviors of homicide offenders and victims. However, results also side with more recent suggestions that although many victims overlap with offender populations, there is also a group of victims that appears to be distinguishable from offender groups. These findings have important implications for both theory and intervention.

BACKGROUND AND PURPOSE: Therapeutic hypothermia is a potent neuroprotectant approved for cerebral protection after neonatal hypoxia-ischemia and cardiac arrest. Therapeutic hypothermia for acute ischemic stroke is safe and feasible in pilot trials. We designed a study protocol to provide safer, faster therapeutic hypothermia in stroke patients. METHODS: Safety procedures and 4°C saline infusions for faster cooling were added to the ICTuS trial (Intravascular Cooling in the Treatment of Stroke) protocol. A femoral venous intravascular cooling catheter after intravenous recombinant tissue-type plasminogen activator in eligible patients provided 24 hours cooling followed by a 12-hour rewarm. Serial safety assessments and imaging were performed. The primary end point was 3-month modified Rankin score 0,1. RESULTS: Of the intended 1600 subjects, 120 were enrolled before the study was stopped. Randomly, 63 were to receive hypothermia plus antishivering treatment and 57 normothermia. Compared with previous studies, cooling rates were improved with a cold saline bolus, without fluid overload. The intention-to-treat primary outcome of 90-day modified Rankin Score 0,1 occurred in 33% hypothermia and 38% normothermia subjects, odds ratio (95% confidence interval) of 0.81 (0.36-1.85). Serious adverse events occurred equally. Mortality was 15.9% hypothermia and 8.8% normothermia subjects, odds ratio (95% confidence interval) of 1.95 (0.56-7.79). Pneumonia occurred in 19% hypothermia versus 10.5% in normothermia subjects, odds ratio (95% confidence interval) of 1.99 (0.63-6.98). CONCLUSIONS: Intravascular therapeutic hypothermia was confirmed to be safe and feasible in recombinant tissue-type plasminogen activator-treated acute ischemic stroke patients. Protocol changes designed to reduce pneumonia risk appeared to fail, although the sample is small. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01123161.

BACKGROUND: Although spiral computed tomographic scanning (SCT) is frequently used for spinal imaging in injured patients, many trauma centers continue to rely on plain film radiography (PFR). The purpose of this study was to determine the effects of a trauma center's transition from PFR to SCT for initial spine evaluation in trauma patients by comparing diagnostic sensitivity, time required for radiographic imaging, costs, charges, and radiation exposure. METHODS: Registry-based review of all trauma patients evaluated for spinal trauma during two three-month intervals, one before (1999, "X-ray Group"), and one after (2002, "CT Group") adopting SCT as the initial spinal imaging method. Demographic data, mechanism of injury, Injury Severity Score (ISS), the presence and location of spine fractures, and the results of all spine imaging were recorded. The dates and diagnostic sensitivity for spine fractures, time for initial imaging, costs, and charges were compared between groups. Radiation exposure associated with both SCT and PFR of the spine was measured. RESULTS: There were 254 patients in the X-ray Group and 319 in the CT Group, with similar demographic data, ISS, mechanism of injury, and incidence of spine fractures. Sensitivity in the detection of spine fractures was 70% (14 out of 20) in the X-ray Group compared with 100% (34 out of 34) for the CT Group (p < 0.001). Mean time in the radiology department during initial evaluation decreased significantly in the CT Group compared with the X-ray Group (1.0 hours vs. 1.9 hours; p < 0.001). SCT of the spine was associated with higher mean overall spinal imaging charges than PFR (4,386 dollars vs. 513 dollars, p < 0.001), but a similar mean overall spinal imaging cost per patient (172 dollars vs. 164 dollars). Radiation exposure was higher with SCT versus PFR for cervical spine imaging (26 mSv vs. 4 mSv) but SCT involved lower levels of exposure than PFR for thoracolumbar imaging (13 mSv vs. 26 mSv). CONCLUSIONS: SCT is a more rapid and sensitive modality for evaluating the spine compared with PFR and is obtained at a similar cost. The advantages of SCT suggest that this readily available diagnostic modality may replace PFR as the standard of care for the initial evaluation of the spine in trauma patients.

BACKGROUND: The evaluation of patients with head, neck, and torso trauma frequently includes high-definition spiral computed tomography (SCT) scanning, which can reveal non-injury-related lesions. These incidental findings vary in their importance, from trivial lesions to findings that may have a greater impact on the health of the trauma patient than the injuries that led to the SCT. We evaluated the incidence and clinical importance of incidental findings found on SCT, and the effectiveness of a trauma practice guideline calling for appropriate management and follow-up. METHODS: The trauma registry was accessed to identify patients evaluated at an urban Level I trauma center from January to November, 2002. Trauma registry data, inpatient chart records, and the digital record of the filmless radiology archives were reviewed. Demographic data, including age, sex, type and mechanism of injury, and outcome, were recorded. All CT studies were reviewed for incidental findings. Mucus retention cysts, sinusitis (except mastoiditis), degenerative joint disease, evidence of previous operation, and age-related cerebral atrophy were excluded. Incidental findings were divided into three categories based on clinical importance. Category 1 required attention before discharge. Category 2 required follow-up with primary doctor within 1 or 2 weeks, and Category 3 required no specific follow-up. Categories 1 and 2 were considered clinically significant findings. RESULTS: Complete data were available for 991 patients (677 men, 314 women). Eight hundred and forty-eight (85.6%) patients received at least one CT scan. A total of 289 incidental findings were discovered. Thirty-one patients (3.1%) had 36 Category 1 findings. There were 108 Category 2 and 145 Category 3 findings. When comparing those patients with at least one incidental finding, the incidence of incidental findings was higher in women than in men (34.1% versus 27.6%; p < 0.05). Older patients also had a higher incidence of all categories of findings (over 40 versus 40 and younger: 46.1% versus 19.9%; p < 0.001). SCT yielded 90 (62.5%) of the clinically significant incidental findings in the abdomen/pelvis, 29 (20.1%) in the chest, and 25 (17.4%) in the head and neck. The charts of only 15 (48.4%) of the patients with Category 1 findings adequately documented the management of the incidental finding. CONCLUSIONS: SCT for the evaluation of trauma patients reveals a significant number of incidental findings. These lesions are common in the abdomen and pelvis and show an increased incidence in women and among older patients. Although many require early follow-up and specialty physician referral, there was insufficient documentation of the management of these injuries. Incidental findings in the injured remain a significant challenge for trauma centers. An organized approach is required for successful follow-up and management.

OBJECTIVE: Numerous studies have demonstrated increased load of de novo copy number variants or single nucleotide variants in individuals with neurodevelopmental disorders, including epileptic encephalopathies, intellectual disability, and autism. METHODS: We searched for de novo mutations in a family quartet with a sporadic case of epileptic encephalopathy with no known etiology to determine the underlying cause using high-coverage whole exome sequencing (WES) and lower-coverage whole genome sequencing. Mutations in additional patients were identified by WES. The effect of mutations on protein function was assessed in a heterologous expression system. RESULTS: We identified a de novo missense mutation in KCNB1 that encodes the KV 2.1 voltage-gated potassium channel. Functional studies demonstrated a deleterious effect of the mutation on KV 2.1 function leading to a loss of ion selectivity and gain of a depolarizing inward cation conductance. Subsequently, we identified 2 additional patients with epileptic encephalopathy and de novo KCNB1 missense mutations that cause a similar pattern of KV 2.1 dysfunction. INTERPRETATION: Our genetic and functional evidence demonstrate that KCNB1 mutation can result in early onset epileptic encephalopathy. This expands the locus heterogeneity associated with epileptic encephalopathies and suggests that clinical WES may be useful for diagnosis of epileptic encephalopathies of unknown etiology.

OBJECTIVE: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. BACKGROUND: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. METHODS: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. RESULTS: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P <0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients ( P <0.0001). CONCLUSIONS: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients.

From the Scripps Mercy, (S.R.S.), San Diego, CA. Submitted: September 9, 2018, Accepted: September 9, 2018, Published online: September 13, 2018. Address for correspondence: Steven R. Shackford, MD, 818 I Avenue Coronado, CA 92118; email: [email protected], [email protected]. This was presented as the Paint the Ceiling Lecture at the 2018 Annual Meeting of the Western Trauma Association held in Whistler, British Columbia. It represents my own work, has not previously been published, and was completed without any support from government agencies, pharmaceutical companies, or NGOs.

BACKGROUND: Venous thromboembolism (VTE) in trauma can occur in patients at low risk. Conventional coagulation tests do not predict VTE. Studies investigating thromboelastography (TEG) for VTE risk are conflicting and have not included routine surveillance to detect deep vein thrombosis (DVT). We undertook a prospective study of TEG to evaluate its utility in predicting VTE. METHODS: We conducted a prospective cohort study on all adult trauma patients admitted to our Level I trauma center from 2013 to 2015. TEG was performed immediately on arrival to the trauma bay. Hypercoagulable TEG was defined as reaction time (R) below, angle (α) above, or maximum amplitude (MA) above reference ranges. All patients received mechanical and/or pharmacologic prophylaxis and were followed up for DVT with our ultrasound surveillance protocol. The primary outcome was lower-extremity DVT. After bivariate analysis of variables related to DVT, those with p values of 0.100 or less were included for multivariate logistic regression. RESULTS: A total of 983 patients were evaluated with TEG on admission; of these, 684 (69.6%) received at least one surveillance ultrasound during the index admission. Lower-extremity DVT was diagnosed in 99 (14.5%) patients. Hypercoagulability based on admission TEG occurred in 582 (85.1%) patients. The lower-extremity DVT rate was higher in patients with hypercoagulable TEG than in those without hypercoagulable TEG (15.6% vs. 8%; p = 0.039). Multivariate analysis showed hypercoagulable TEG remained associated with DVT after adjustment for relevant covariates available at admission, with an odds ratio of 2.41 (95% confidence interval, 1.11-5.24; p = 0.026). CONCLUSION: Most trauma patients were hypercoagulable at admission and remained at risk of developing DVT. The rate of DVT doubled in patients with hypercoagulable TEG indices despite prophylaxis. Beyond its current clinical roles, TEG is useful for assessing DVT risk, particularly in patients otherwise perceived to be at low risk. LEVEL OF EVIDENCE: Prognostic study, level II.

Abstract Background. Invasive aspergillosis may occur in the setting of severe influenza infections due to viral-induced respiratory epithelium disruption and impaired immune effects, but data are limited. Methods. A retrospective study was conducted among severe influenza cases requiring medical intensive care unit (ICU) admission at an academic center during the 2015–2016 season. Data collected included respiratory cultures, medical conditions and immunosuppressants, laboratory and radiographic data, and outcomes. A systematic literature review of published cases in the English language of aspergillosis complicating influenza was conducted. Results. Six (75%) of 8 ICU influenza cases had Aspergillus isolated; 5 were classified as invasive disease. No ICU patient testing negative for influenza infection developed aspergillosis during the study period. Among cases with invasive aspergillosis, influenza infection was type A (H1N1) (n = 2) and influenza B (n = 3). Published and current cases yielded n = 57 (European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria: 37% proven, 25% probable, and 39% possible cases). An increasing number of cases were reported since 2010. Sixty-five percent of cases lacked classic underlying conditions at admission for aspergillosis, 86% had lymphopenia, and 46% died. Conclusions. Aspergillosis may occur in the setting of severe influenza infections even among immunocompetent hosts. Risks may include influenza A (H1N1) or B infections and viral-induced lymphopenia, although further studies are needed. Prompt diagnosis and antifungal therapy are recommended given high mortality rates.

Placental mesenchymal dysplasia (PMD) is a rare condition of placentomegaly and abnormal chorionic villi often clinically mistakenly as partial hydatidiform mole. However, it is clinicopathologically distinct with high incidence of intrauterine growth restriction (IUGR) and fetal death. This study presents 11 new PMD cases and provides a meta-analysis of the associated IUGR and fetal death rates. The cases were identified between 1971 and 2005, mostly from consultation files. To our knowledge, 71 PMD cases have previously been reported; 15 of these were associated with Beckwith-Wiedemann syndrome (BWS). With the addition of our new results, among all cases without BWS, 50% had IUGR and 43% had intrauterine fetal demise (IUFD) or neonatal death. Females represented 82% of cases. Thus, PMD is associated with high IUGR and IUFD/neonatal death rates and disproportionally affects females. The pathogenesis is yet unknown. The current understanding and hypotheses involving PMD are discussed.