Genome-wide association study reveals novel genetic loci: a new polygenic risk score for mitral valve prolapse.

AIMS: Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder. METHODS AND RESULTS: We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors. CONCLUSION: We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-ß signalling molecules and spectrin ß. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention.

Uptake of Plasmodium falciparum Gametocytes During Mosquito Bloodmeal by Direct and Membrane Feeding.

Plasmodium falciparum remains one of the leading causes of child mortality, and nearly half of the world's population is at risk of contracting malaria. While pathogenesis results from replication of asexual forms in human red blood cells, it is the sexually differentiated forms, gametocytes, which are responsible for the spread of the disease. For transmission to succeed, both mature male and female gametocytes must be taken up by a female Anopheles mosquito during its blood meal for subsequent differentiation into gametes and mating inside the mosquito gut. Observed circulating numbers of gametocytes in the human host are often surprisingly low. A pre-fertilization behavior, such as skin sequestration, has been hypothesized to explain the efficiency of human-to-mosquito transmission but has not been sufficiently tested due to a lack of appropriate tools. In this study, we describe the optimization of a qPCR tool that enables the relative quantification of gametocytes within very small input samples. Such a tool allows for the quantification of gametocytes in different compartments of the host and the vector that could potentially unravel mechanisms that enable highly efficient malaria transmission. We demonstrate the use of our gametocyte quantification method in mosquito blood meals from both direct skin feeding on Plasmodium gametocyte carriers and standard membrane feeding assay. Relative gametocyte abundance was not different between mosquitoes fed through a membrane or directly on the skin suggesting that there is no systematic enrichment of gametocytes picked up in the skin.

Empowered Holistic Nursing Education as the Philosophical Framework for an RN-BS Program: A Six-Year Impact Evaluation Study.

The educational structure of many nursing programs is largely monocultural, with a traditional pedagogy. Empowered holistic nursing education (EHNE) creates a learning environment with more cultural responsiveness and support for diverse classrooms. The aim of this study was to determine what impact the theory had on diversification. With EHNE the philosophical framework of a new RN-to-BSN program, student demographic data were collected, along with exit survey questions. A statistically significant increase was found in the diversification of the six cohorts. The EHNE shows potential as a programmatic framework for increasing diversification of the nursing profession.

Assessing Attitudes of Nursing Pedagogy: An Instrument Based on the Midrange Theory of Empowered Holistic Nursing Education.

BACKGROUND AND PURPOSE: The Empowered Holistic Nursing Education (EHNE) midrange theory provides a structure for a pedagogy for nursing, bringing the core values of nursing into the classroom. There are five principles of EHNE: Self-Care, Interconnectedness, Prior Knowledge, Contextual Teaching-Learning, and Meet Them Where They Are. METHODS: The Thurstone method was used in the development of this scale, resulting in two subscales representing unique phenomena, each with 11 relational items that represent the spectrum of attitudes for the phenomenon. RESULTS: With a CVI score of 0.92 (n = 23) for subscale 1 and 0.89 (n = 23) for subscale 2, the scale was found to have high inter-rater reliability with an agreement of K = 0.814 (99% confidence interval). Analysis revealed a significant, positive association between the two subscales (r = .96 and sig/2 tailed = .003). CONCLUSIONS: This instrument development study as a whole allows for further testing of the midrange theory and advancement to implementation and intervention research.

Postdischarge Mortality after Geriatric Low-Level Falls: A Five-Year Analysis.

Geriatric trauma patients with low-level falls often have multiple comorbidities and limited physiologic reserve. Our aim was to investigate postdischarge mortality in this population. We hypothesized that five-year mortality would be higher relative to other blunt mechanisms. The registry of our Level 1 trauma center was queried for patients evaluated between July 2008 and December 2012. Adult patients identified were matched with mortality data from 2008 to 2013 from the National Death Index. Low-level falls were identified by E Codes; other types of blunt trauma were based on registry classification. Patients with multiple admissions were excluded. Univariate analysis was performed using Fisher's exact and Wilcoxon tests. Kaplan-Meier curves were plotted to compare postdischarge mortality. Seven thousand nine hundred sixteen patients were evaluated, 35.1 per cent were females. Patients aged less than 65 years and penetrating trauma were excluded, yielding 1997 patients-63.7 per cent with low-level falls versus 36.3 per cent with other blunt traumas. Geriatric patients sustaining low-level falls were older, more likely female, had a higher inpatient mortality, and were less likely to return home at discharge. Injury severity score, hospital length of stay, and intensive care unit length of stay were similar. Survival analysis demonstrated increased postdischarge mortality in the low-level fall group with 25 per cent mortality at 120 days. Geriatric patients with other blunt trauma had a significantly lower postdischarge mortality. Geriatric patients injured in low-level falls have a higher inhospital mortality, are more likely to be functionally dependent on discharge, and have a high postdischarge mortality. Opportunities likely exist for injury prevention, consideration of palliative care, and postdischarge rehabilitation.

Is the Face an Air Bag for the Brain and Torso?-The Potential Protective Effects of Severe Midface Fractures.

We investigated the patterns of injury associated with major midface trauma. Our hypothesis is that midface injuries are associated with a decrease in certain traumatic brain injuries as well as major torso injuries. The registry of our Level I trauma center was queried for all adult patients treated over 25 years from 1989 to 2013. Patients with midface fractures were identified based on the ICD-9 code. Associated injuries were defined based both on individual ICD-9 codes as well as the Barell Injury Matrix. Injury etiology was defined based on e-codes. Univariate analysis was performed using chi-squared test, Fisher's exact test, and Wilcoxon test. A total of 29,152 patients were identified. Excluding pediatric patients, those with exclusively penetrating trauma, and patients with incomplete data, 20,971 patients were included for subsequent analysis. Midface fractures were identified in 752 patients. Patients with Le Fort fractures were more likely to be male, have a higher Injury Severity Score, a lower arrival Glasgow Coma Scale, and more likely to require intensive care unit admission and mechanical ventilation, with a longer hospital length of stay. Patients with midface fractures had significantly fewer subdural hematomas, subarachnoid hemorrhages, spine fractures, and were less likely to have associated abdominal and pelvic injuries. Patients with midface fractures were more likely to require facial reconstruction procedures and craniotomy. Patients presenting with midface fractures after blunt trauma have a distinctly different pattern of injuries. One potential mechanism for this is a deceleration effect, where midface impact and resulting fractures dissipate some of the energy.

The Utility of Additional Imaging in Trauma Consults with Mild to Moderate Injury.

Limiting CT imaging in the ED has gained interest recently. After initial trauma workup for consultations in the ED, additional CT imaging is frequently ordered. We assessed the benefits of this additional imaging. Our hypothesis was that additional imaging in lower acuity trauma consults results in the diagnosis of new significant injuries with a change in treatment plan and increased Injury Severity Score (ISS). The registry at our Level I trauma center was queried from November 2015 to November 2016 for trauma consults initially evaluated by ED physicians. Patients with mild to moderate injuries were included. Injury findings before and after additional imaging were determined by chart review and pre- and postimaging ISS were calculated. Blinded trauma surgeons assessed the findings for clinical significance and changes in treatment. Four hundred and twenty-one patients were evaluated, 41 were excluded. One hundred and forty patients (37%) underwent additional CT imaging. Forty-seven patients (34%) had additional injuries found, with 16 (12%) increasing their ISS (mean 0.54, SD 1.66). Ninety-three per cent of cases resulted in at least one physician finding the new injuries clinically significant; however, agreement was low (κ = 0.095). For 70 per cent, at least one physician felt the findings warranted a change in treatment plan (κ = 0.405). Additional imaging in ED trauma consults resulted in the identification of new injuries in 1/3 of our patient sample. This suggests that current efforts to limit the use of CT imaging in trauma patients may result in significant injuries going undiscovered and undertreated. Further research is needed to determine the risk of attempts to limit imaging.

The Critical Research Evaluation Tool (CRET): A Teaching and Learning Tool to Evaluate Research for Cultural Competence.

The aim of this study was to present the Critical Research Evaluation Tool (CRET) which teaches evaluation of the researchers' worldview, applicability to multicultural populations, and ethics surrounding potential harms to communities. To provide best cultural care nurses' need to understand how historical/social/political experiences impact health and also influence research. The Student using the CRET reported receiving a strong foundation in research fundamentals, gaining a better understanding of critical frameworks in research, and learning more about themselves and reflecting on their own privileges and biases. The CRET provides nursing students and nursing faculty with a tool for examining diversity and ultimately decreasing health disparity.

Parathyroid hormone as a marker for hypoperfusion in trauma: A prospective observational study.

BACKGROUND: Hyperparathyroidism is common in critical illness. Intact parathyroid hormone has a half-life of 3 minutes to 5 minutes due to rapid clearance by the liver, kidneys, and bone. In hemorrhagic shock, decreased clearance may occur, thus making parathyroid hormone a potential early marker for hypoperfusion. We hypothesized that early hyperparathyroidism predicts mortality and transfusion in trauma patients. METHODS: A prospective observational study was performed at a Level I trauma center in consecutive adult patients receiving the highest level of trauma team activation. Parathyroid hormone and lactic acid were added to the standard laboratory panel drawn in the trauma bay on arrival, before the administration of any blood products. The primary outcomes assessed were transfusion in 24 hours and mortality. RESULTS: Forty-six patients were included. Median age was 47 years, 82.6% were men, 15.2% suffered penetrating trauma, and 21.7% died. Patients who were transfused in the first 24 hours (n = 17) had higher parathyroid hormone (182.0 pg/mL vs. 73.5 pg/mL, p < 0.001) and lactic acid (4.6 pg/mL vs. 2.3 pg/mL, p = 0.001). Patients who did not survive to discharge (n = 10) also had higher parathyroid hormone (180.3 pg/mL vs. 79.3 pg/mL, p < 0.001) and lactic acid (5.5 mmol/L vs. 2.5 mmol/L, p = 0.001). For predicting transfusion in the first 24 hours, parathyroid hormone has an area under the receiver operating characteristic curve of 0.876 compared with 0.793 for lactic acid and 0.734 for systolic blood pressure. Parathyroid hormone has an area under the receiver operating characteristic curve of 0.875 for predicting mortality compared with 0.835 for lactic acid and 0.732 for systolic blood pressure. CONCLUSION: Hyperparathyroidism on hospital arrival in trauma patients predicts mortality and transfusion in the first 24 hours. Further research should investigate the value of parathyroid hormone as an endpoint for resuscitation. LEVEL OF EVIDENCE: Prognostic, level II.

Survival from Traumatic Injury Does Not End at Hospital Discharge: Hospital-Acquired Infections Increase Post-Discharge Mortality.

BACKGROUND: Hospital-acquired infections (HAI) in trauma patients increase inpatient morbidity and mortality. However, their impact on long-term mortality is not well understood. PATIENTS AND METHODS: A retrospective trauma registry analysis of all patients admitted to an academic level I trauma center between July 1, 2008 and December 31, 2012 was performed. Patients included survived to discharge and were 18 years of age or older. Age, gender, Injury Severity Score (ISS), ventilator use, history of chronic obstructive pulmonary disease (COPD), and HAI were reviewed. Name, social security number, and date of birth were used to extract National Death Index data from 2008-2013 for an outcome of mortality after discharge, time to death, and cause of death. Unadjusted logistic regression was performed. Multiple logistic regression was used to adjust for patient and injury characteristics and to determine odds of mortality in the post-discharge period. RESULTS: A total of 8,275 patients met inclusion criteria; 65.4% were male and the median age was 47. The mean ISS was 11 ± 8.9. Nine hundred seventeen patients (11.1%) died after discharge; 4.8% of patients had hospital-acquired pneumonia (HAP) and 4.2% had a urinary tract infection (UTI). The unadjusted odds ratio (OR) of mortality after discharge in patients who had pneumonia and UTI were 1.77 (1.35, 2.31, p < 0.001) and 2.44 (1.87, 3.17, p < 0.001), respectively. After adjusting for patient age, gender, ISS, ventilator use, and history of COPD (pneumonia patients only), the odds for mortality after discharge remained significant for pneumonia (OR = 1.57 (1.09, 2.23), p = 0.013) but not for UTI (OR = 1.25 (0.93, 1.68), p = 0.147). The top causes of death after discharge in patients with HAP were COPD (11.4%) and falls (7.1%). CONCLUSIONS: Trauma patients with HAP have higher mortality after hospital discharge. Prevention strategies for HAP including pulmonary toilet, early mobility, pain control, and early extubation must be a priority. Unfortunately, patients who develop pneumonia may have a decreased reserve, or ability to recover from their traumatic injuries and HAI. Further characterization of HAP and its subsequent treatment strategies are needed.

Contact Isolation Precautions in Trauma Patients: An Analysis of Infectious Complications.

BACKGROUND: Victims of traumatic injuries represent a population at risk for a wide variety of complications. Contact isolation (CI) is a set of restrictions designed to help prevent the transmission of medically significant organisms in the healthcare setting. A growing body of literature demonstrates that CI can have significant implications for the individual isolated patient. Our goal was to characterize the use of contact isolation at our Level I trauma center and investigate the association of CI with infectious complications. PATIENTS AND METHODS: An existing trauma database containing data on patients admitted at our Level I trauma center between January 1, 2011 and December 31, 2012, along with their contact isolation status, was queried. Demographics, injuries, and the presence of infections were collected. Diagnosis of pneumonia or UTI was based on clinical documentation in the patient's medical record. A chart review was performed to ascertain the reason for CI including specific organisms. Because of differences in patient demographics between the CI and non-CI groups, linear regression was performed to adjust for the effects of different variables. RESULTS: A total of 4,423 patients were admitted over this period. Of these, 4,318 (97.6%) had complete records and were included in the subsequent analysis. The CI was in place in 249 (5.8%) patients; 4,069 (94.2%) were not isolated. The number who had CI initiated for MRSA nasal colonization was 173 (69.5%). Twenty-two (8.9%) had no reason for CI documented. Pneumonia occurred in 190 (4.4%), 54 (21.7) in the CI group versus 136 (3.3%) in the non-CI group. Urinary tract infection (UTI) was diagnosed in 166 (3.8%), 48 (19.3%) in the CI group versus 118 (2.9%) in the non-CI group. Using logistic regression and excluding patients placed on contact isolation for the development of a new resistant nosocomial infection, CI, Injury Severity Score, gender, length of stay, and mechanical ventilation were identified as common covariates for pneumonia (PNA) and UTI. Chronic obstructive pulmonary disease COPD was specifically identified for PNA. Spinal cord injury, vertebral column injury and pelvic-urogenital injury were also significant for UTI. CONCLUSIONS: The development of pneumonia and UTI in patients with trauma was significantly associated with the use of CI. Because the majority of these patients had CI precautions in place for asymptomatic colonization, the CI provided them no direct benefit. Because the use of CI is associated with multiple negative outcomes, its use in the trauma population needs to be carefully re-evaluated.

Alternatives to Indwelling Catheters Cause Unintended Complications.

To reduce the risk of catheter-associated urinary tract infection (CAUTI), limiting use of indwelling catheters is encouraged with alternative collection methods and early removal. Adverse effects associated with such practices have not been described. We also determined if CAUTI preventative measures increase the risk of catheter-related complications. We hypothesized that there are complications associated with early removal of indwelling catheters. We described complications associated with indwelling catheterization and intermittent catheterization, and compared complication rates before and after policy updates changed catheterization practices. We performed retrospective cohort analysis of trauma patients admitted between August 1, 2009, and December 31, 2013 who required indwelling catheter. Associations between catheter days and adverse outcomes such as infection, bladder overdistention injury, recatheterization, urinary retention, and patients discharged with indwelling catheter were evaluated. The incidence of CAUTI and the total number of catheter days pre and post policy change were similar. The incidence rate of urinary retention and associated complications has increased since the policy changed. Practices intended to reduce the CAUTI rate are associated with unintended complications, such as urinary retention. Patient safety and quality improvement programs should monitor all complications associated with urinary catheterization practices, not just those that represent financial penalties.

Vital Signs Strongly Predict Massive Transfusion Need in Geriatric Trauma Patients.

Early recognition of massive transfusion (MT) requirement in geriatric trauma patients presents a challenge, as older patients present with vital signs outside of traditional thresholds for hypotension and tachycardia. Although many systems exist to predict MT need in trauma patients, none have specifically evaluated the geriatric population. We sought to evaluate the predictive value of presenting vital signs in geriatric trauma patients for prediction of MT. We retrospectively reviewed geriatric trauma patients presenting to our Level I trauma center from 2010 to 2013 requiring full trauma team activation. The area under the receiver operating characteristic curve was calculated to assess discrimination of arrival vital signs for MT prediction. Ideal cutoffs with high sensitivity and specificity were identified. A total of 194 patients with complete data were analyzed. Of these, 16 patients received MT. There was no difference between the MT and non-MT groups in sex, age, or mechanism. Systolic blood pressure, pulse pressure, diastolic blood pressure, and shock index all were strongly predictive of MT need. Interestingly, we found that heart rate does not predict MT. MT in geriatric trauma patients can be reliably and simply predicted by arrival vital signs. Heart rate may not reflect serious hemorrhage in this population.

Black Feminism: An Integrated Review of Literature.

This study presents a systematic literature review exploring the uses and potential benefits of Black Feminism in nursing research. Black Feminism may benefit knowledge development for nursing in a variety of ways, such as illuminating the multifaceted factors of Black women's identities in helping scholars move away from generalization of experiences, to improve understanding of health disparities, and making such changes by broadening the social consciousness of the nurse researchers, who are predominantly White. Discrimination in health disparities may be deconstructed if the focus is placed on asking different research questions and offering different interventions with the social structures that contributes to such actions. When Black Feminism guides the research method (including research questions and analysis), the accuracy of representing the experiences of Black women is increased. In this research, Black Feminism highlights experience, coping mechanisms, spiritual values, a tradition of strength, and a holistic view of identity.

Provider Bias Impacts Tidal Volume Selection and Ventilator Days in Trauma Patients.

BACKGROUND: The ARDSnet (Acute Respiratory Distress Syndrome Clinical Network) study demonstrated that low tidal volume (Vt) reduces mortality from ARDS. It is unknown whether low Vt is beneficial in at-risk trauma patients. We hypothesized that Vt selection would be low in accordance with ARDSnet criteria and that subsequent outcomes would be improved. STUDY DESIGN: A 1-year retrospective observational study was conducted on all trauma patients aged 15 years and older and on mechanical ventilation for 48 hours or longer, excluding those with cardiopulmonary disease. Using maximum Vt, we identified low and high Vt groups (≤8 mL/predicted body weight (PBW) and >8 mL/PBW). Data collected included demographic characteristics, lengths of stay, ventilator and ICU days, ARDS, and other complications. RESULTS: A total of 364 patients were identified and organized into low Vt (n = 181) and high Vt (n = 183) groups. There was no difference between groups in age, Injury Severity Score, Glasgow Coma Scale, or mechanism of injury. The rate of ARDS was the same in each group. Patients with a high Vt had lower PBW (63.1 ± 8.8 vs 71.7 ± 6.9; p < 0.001), higher BMI(29.7 ± 6.9 kg/m(2) vs 26.6 ± 6.5 kg/m(2); p < 0.001), and were more likely to be female. Height was inversely correlated with Vt (r(2) = -0.579; p < 0.001). The high Vt group experienced longer ICU stays (9.9 ± 8.8 days vs 8.1 ± 7.9 days; p = 0.045) and more ventilator days (8.55 ± 10.5 days vs 6.14 ± 7.4 days; p = 0.015). CONCLUSIONS: Trauma patients receiving high Vt were shorter, had higher BMI, and were more likely to be female. The consequences included longer ICU stays and more ventilator days. Formal calculation of PBW and subsequent Vt is advocated.

Organ donation as an outcome of traumatic cardiopulmonary arrest: A cost evaluation.

BACKGROUND: Survival after traumatic cardiopulmonary arrest (TCPA) is rare and requires significant resource expenditure. Organ donation as an outcome of TCPA resuscitation has not yet been included in a cost analysis. The aims of this study were to identify variables associated with survival and organ donation after TCPA, and to estimate the cost of achieving these outcomes. We hypothesized that the inclusion of organ donation as a potential outcome would make TCPA resuscitation more cost-effective. METHODS: Adult patients who required resuscitation for TCPA at a level I trauma center were retrospectively reviewed over 36 months. Data were obtained from medical records, hospital accounting records, and the local organ procurement agency. Outcomes included survival to discharge, neurologic function, and organ donor eligibility. An individual-level state-transition cost-effectiveness model was used to evaluate the cost of TCPA resuscitation with and without organ donation included as an outcome. Incremental cost-effectiveness ratio was calculated to determine additional cost per life saved when organ donation is included. RESULTS: Over the study period, 8,932 subjects were evaluated. Traumatic cardiopulmonary arrest occurred in 237 patients (3%). The mortality rate was 97%. Variables associated with survival included emergency department disposition to the operating room (p < 0.01) and reactive pupils (p < 0.001). Of seven survivors, four were discharged neurologically intact. Of the patients with TCPA, 5% were eligible for organ donation with a procurement rate of 2%. Organ donor eligibility was associated with arrest after arrival to the emergency department (p < 0.01) and transfusion of fresh frozen plasma (p = 0.01). The cost of TCPA resuscitation per survivor was $1.8 million; cost per survivor or life saved by donation was $538,000. The incremental cost-effectiveness ratio was $76,816 per additional life saved including donation as an outcome. CONCLUSION: The decision to pursue resuscitation should continue to be based on the presence of signs of life, especially pupil reactivity and duration of arrest. If the primary objective is survival, organ procurement will be maximized without conflict of interest. Early fresh frozen plasma transfusion may increase successful organ donation. The financial burden of TCPA resuscitation can be mitigated by expanding end points to include organ donation. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III; cost analysis, level V.