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Importance: Although mindfulness-based interventions (MBIs) are evidence-based treatments for chronic pain and comorbid conditions, implementing them at scale poses many challenges, such as the need for dedicated space and trained instructors. Objective: To examine group and self-paced, scalable, telehealth MBIs, for veterans with chronic pain, compared to usual care. Design, Setting, and Participants: This was a randomized clinical trial of veterans with moderate to severe chronic pain, recruited from 3 Veterans Affairs facilities from November 2020 to May 2022. Follow-up was completed in August 2023. Interventions: Two 8-week telehealth MBIs (group and self-paced) were compared to usual care (control). The group MBI was done via videoconference with prerecorded mindfulness education and skill training videos by an experienced instructor, accompanied by facilitated discussions. The self-paced MBI was similar but completed asynchronously and supplemented by 3 individual facilitator calls. Main Outcomes and Measures: The primary outcome was pain-related function using the Brief Pain Inventory interference scale at 3 time points: 10 weeks, 6 months, and 1 year. Secondary outcomes included biopsychosocial outcomes: pain intensity, physical function, anxiety, fatigue, sleep disturbance, participation in social roles and activities, depression, patient ratings of improvement of pain, and posttraumatic stress disorder. Results: Among 811 veterans randomized (mean [SD] age, 54.6 [12.9] years; 387 [47.7%] women), 694 participants (85.6%) completed the trial. Averaged across all 3 time points, pain interference scores were significantly lower for both MBIs compared to usual care (group MBI vs control difference: -0.4 [95% CI, -0.7 to -0.2]; self-paced vs control difference: -0.7 [95% CI, -1.0 to -0.4]). Additionally, both MBI arms had significantly better scores on the following secondary outcomes: pain intensity, patient global impression of change, physical function, fatigue, sleep disturbance, social roles and activities, depression, and posttraumatic stress disorder. Both group and self-paced MBIs did not significantly differ from one another. The probability of 30% improvement from baseline compared to control was greater for group MBI at 10 weeks and 6 months, and for self-paced MBI, at all 3 time points. Conclusions and Relevance: In this randomized clinical trial, scalable telehealth MBIs improved pain-related function and biopsychosocial outcomes compared to usual care among veterans with chronic pain. Relatively low-resource telehealth-based MBIs could help accelerate and improve the implementation of nonpharmacological pain treatment in health care systems. Trial Registration: ClinicalTrials.gov Identifier: NCT04526158.
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BACKGROUND: Childhood maltreatment is associated with elevated adult weight. It is unclear whether this association extends to pregnancy, a critical window for the development of obesity. METHODS: We examined associations of childhood maltreatment histories with pre-pregnancy BMI and gestational weight gain among women who had participated for >20 years in a longitudinal cohort.At age 26-35 participants reported childhood maltreatment (physical, sexual, and emotional abuse; emotional neglect) and, 5 years later, about pre-pregnancy weight and gestational weight gain for previous pregnancies (n=656). Modified Poisson regression models were used to estimate associations of maltreatment history with pre-pregnancy BMI and gestational weight gain z-scores, adjusting for sociodemographics. We used Multivariate Imputation by Chained Equations to adjust outcome measures for misclassification using data from an internal validation study. RESULTS: Before misclassification adjustment, results indicated a higher risk of pre-pregnancy BMI ≥30 kg/m2 in women with certain types of maltreatment (e.g., emotional abuse RR=2.4; 95% CI: 1.5, 3.7) compared with women without that maltreatment type. After misclassification adjustment, estimates were attenuated but still modestly elevated (e.g., emotional abuse RR=1.7; 95% CI: 1.1, 2.7). Misclassification-adjusted estimates for maltreatment associations with gestational weight gain z-scores were close to the null and imprecise. CONCLUSIONS: Findings suggest an association of maltreatment with pre-pregnancy BMI ≥30 kg/m2 but not with high gestational weight gain. Results suggest a potential need for equitable interventions that can support all women, including those with maltreatment histories, as they enter pregnancy.
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BACKGROUND: Recruitment for clinical trials and large-scale studies is challenging, especially for patients with complex conditions like chronic pain. Email recruitment has the potential to increase efficiency, to reduce costs, and to improve access for underrepresented patient populations. The objective of this study was to examine the effectiveness, efficiency, and equitability of email versus postal mail recruitment for the Learning to Apply Mindfulness to Pain (LAMP) study, a three-site clinical trial of mindfulness-based interventions for chronic pain. METHODS: Patients with chronic pain diagnoses were recruited from three United States Department of Veterans Affairs (VA) facilities using the VA electronic health record (EHR). Recruitment materials were sent using either postal mail (n = 7986) or email (n = 19,333). Patients in the email recruitment group were also mailed introductory postcards before any emails. Mailing addresses and email addresses were obtained from the EHR. Effectiveness was measured by the response rate of patients who logged into the secure LAMP study website. Efficiency was measured by the number of days from when the recruitment materials were sent to when patients logged into the LAMP portal as well as the estimated costs of each recruitment approach. To assess equitability, we examined whether email recruitment was less effective for underrepresented populations, based on demographic information from the EHR. RESULTS: Effectiveness-unadjusted response rates were greater for email versus postal-mail recruitment (18.9% versus 6.3%), and adjusted response rates were over three times greater for email recruitment (RR = 3.5, 95% CI 3.1-3.8) based on a multivariable analysis controlling for age, gender, race, ethnicity, rurality, and site. Efficiency-email recruitment had a significantly lower mean response time (1 day versus 8 days) and a lower cost. Equity-email recruitment led to higher response rates for all subpopulations, including older, non-White, Hispanic, rural, and female Veterans. CONCLUSIONS: Email recruitment is an effective, efficient, and equitable way to recruit VA patients to large-scale, chronic pain clinical trials. TRIAL REGISTRATION: Clinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020.
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Dolor Crónico , Correo Electrónico , Selección de Paciente , Humanos , Dolor Crónico/terapia , Dolor Crónico/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Estados Unidos , Anciano , United States Department of Veterans Affairs , Registros Electrónicos de Salud , Servicios Postales , AdultoRESUMEN
PURPOSE: Self-collected testing for human papillomavirus (HPV) is poised to transform cervical cancer screening. Self-tests demonstrate similar accuracy to clinician-collected tests, but for the half a million women served by the Veterans Health Administration (VA) and their clinicians, self-collected cervical cancer screening would be a new practice. We examined VA patient and staff perspectives to inform future implementation. METHODS: Semi-structured telephone interviews were conducted between 2021 and 2022 with female veterans receiving VA care (n = 22) and VA women's health nurses, clinicians, and administrators (n = 27). Interviews were audio-recorded and transcribed. Interview questions addressed knowledge and interest, potential advantages or disadvantages, and any questions participants had about self-collected screening. Responses were analyzed using rapid qualitative methods. MAIN FINDINGS: Five overarching themes were identified. Both patients and staff indicated high interest and enthusiasm for self-collected HPV testing, tempered by questions about test accuracy and logistical considerations. Familiarity with self-testing for other conditions such as colon-cancer screening or COVID made self-collection seem like a simple, convenient option. However, self-testing was not viewed as a good fit for all patients, and concerns about lost opportunities or missed incidental lesions were raised. Patients and staff described challenges with pelvic examinations for patients with past sexual trauma, particularly in the male-dominated VA environment. Pelvic exams can leave patients feeling vulnerable and exposed; self-collected testing was seen as a mechanism for patient empowerment. PRINCIPAL CONCLUSIONS: Veteran patients and VA staff shared common perspectives about potential advantages and disadvantages of self-collected HPV testing. Self-collected HPV testing has the potential to improve trauma-informed preventive health care for veterans.
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BACKGROUND: Post-traumatic stress disorder (PTSD) and chronic pain are highly prevalent comorbid conditions. Veterans dually burdened by PTSD and chronic pain experience more severe outcomes compared to either disorder alone. Few studies have enrolled enough women Veterans to test gender differences in pain outcomes [catastrophizing, intensity, interference] by the severity of PTSD symptoms. AIM: Examine gender differences in the association between PTSD symptoms and pain outcomes among Veterans enrolled in a chronic pain clinical trial. METHODS: Participants were 421 men and 386 women Veterans with chronic pain who provided complete data on PTSD symptoms and pain outcomes. We used hierarchical linear regression models to examine gender differences in pain outcomes by PTSD symptoms. RESULTS: Adjusted multivariable models indicated that PTSD symptoms were associated with higher levels of pain catastrophizing (0.57, 95% CI [0.51, 0.63]), pain intensity (0.30, 95% CI [0.24, 0.37]), and pain interference (0.46, 95% CI [0.39, 0.52]). No evidence suggesting gender differences in this association were found in either the crude or adjusted models (all interaction p-values<0.05). CONCLUSION: These findings may reflect the underlying mutual maintenance of these conditions whereby the sensation of pain could trigger PTSD symptoms, particularly if the trauma and pain are associated with the same event. Clinical implications and opportunities testing relevant treatments that may benefit both chronic pain and PTSD are discussed.
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Dolor Crónico , Trastornos por Estrés Postraumático , Veteranos , Humanos , Trastornos por Estrés Postraumático/psicología , Trastornos por Estrés Postraumático/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Veteranos/psicología , Dolor Crónico/psicología , Índice de Severidad de la Enfermedad , Adulto , Anciano , Factores Sexuales , Catastrofización/psicología , Dimensión del Dolor , Caracteres SexualesRESUMEN
BACKGROUND: Prepregnancy body mass index (BMI) and gestational weight gain (GWG) are determinants of maternal and child health. However, many studies of these factors rely on error-prone self-reported measures. METHODS: Using data from Life-course Experiences And Pregnancy (LEAP), a US-based cohort, we assessed the validity of prepregnancy BMI and GWG recalled on average 8 years postpartum against medical record data treated as alloyed gold standard ("true") values. We calculated probabilities of being classified into a self-reported prepregnancy BMI or GWG category conditional on one's true category (analogous to sensitivities and specificities) and probabilities of truly being in each prepregnancy BMI or GWG category conditional on one's self-reported category (analogous to positive and negative predictive values). RESULTS: There was a tendency toward under-reporting prepregnancy BMI. Self-report misclassified 32% (95% confidence interval [CI] = 19%, 48%) of those in LEAP with truly overweight and 13% (5%, 27%) with obesity into a lower BMI category. Self-report correctly predicted the truth for 72% (55%, 84%) with self-reported overweight to 100% (90%, 100%) with self-reported obesity. For GWG, both under- and over-reporting were common; self-report misclassified 32% (15%, 55%) with truly low GWG as having moderate GWG and 50% (28%, 72%) with truly high GWG as moderate or low GWG. Self-report correctly predicted the truth for 45% (25%, 67%) with self-reported high GWG to 85% (76%, 91%) with self-reported moderate GWG. Misclassification of BMI and GWG varied across maternal characteristics. CONCLUSION: Findings can be used in quantitative bias analyses to estimate bias-adjusted associations with prepregnancy BMI and GWG.
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Índice de Masa Corporal , Ganancia de Peso Gestacional , Recuerdo Mental , Autoinforme , Humanos , Femenino , Embarazo , Adulto , Adulto Joven , Estudios de Cohortes , Estados UnidosRESUMEN
BACKGROUND: Life course factors may be associated with pre-pregnancy body mass index and gestational weight gain; however, collecting information on pre-pregnancy exposures and pregnancy health in the same cohort is challenging. OBJECTIVES: The Life-course Experiences And Pregnancy (LEAP) study aims to identify adolescent and young adult risk factors for pre-pregnancy weight and gestational weight gain (GWG). We built upon an existing cohort study to overcome challenges inherent to studying life course determinants of pregnancy health. POPULATION: Participants in an ongoing prospective cohort study of weight-related health who identified as women. DESIGN: Retrospective cohort study. METHODS: In 2019-2020, 1,252 women participating since adolescence in a cohort study of weight-related health were invited to complete an online reproductive history survey. Participants who reported a live birth were invited to release their prenatal, delivery, and postpartum medical records for validation of survey reports. Descriptive analyses were conducted to assess the characteristics of the overall cohort and the medical record validation subsample, and to describe adolescent and young adult characteristics of those with high (>80th percentile), moderate (20th-80th percentile), and low (<20th percentile) GWG z-score for gestational age and pre-pregnancy weight status. PRELIMINARY RESULTS: Nine hundred seventy-seven women (78%) completed the LEAP survey and 656 reported a live birth. Of these, 379 (58%) agreed to release medical records, and 250 records were abstracted (66% of the 379). Of the 977 survey respondents 769 (79%) reported attempting a pregnancy, and 656 (67%) reported at least one live birth. The validation subsample was similar to the overall cohort. Women with a high GWG had a higher adolescent BMI percentile and prevalence of unhealthy weight control behaviors than those with moderate or low GWG. CONCLUSIONS: LEAP offers a valuable resource for identifying life course factors that may influence the health of pregnant people and their offspring.
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Ganancia de Peso Gestacional , Adulto Joven , Adolescente , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Estudios de Cohortes , Estudios Prospectivos , Acontecimientos que Cambian la Vida , Salud Reproductiva , Nacimiento Vivo , Índice de Masa Corporal , Resultado del Embarazo/epidemiologíaRESUMEN
Background: Although studies have documented higher rates of chronic pain among women Veterans compared to men Veterans, there remains a lack of comprehensive information about potential contributors to these disparities. Materials and Methods: This study examined gender differences in chronic pain and its contributors among 419 men and 392 women Veterans, enrolled in a mindfulness trial for chronic pain. We conducted descriptive analyses summarizing distributions of baseline measures, obtained by survey and through the electronic health record. Comparisons between genders were conducted using chi-square tests for categorical variables and t-tests for continuous measures. Results: Compared to men, women Veterans were more likely to have chronic overlapping pain conditions and had higher levels of pain interference and intensity. Women had higher prevalence of psychiatric and sleep disorder diagnoses, greater levels of depression, anxiety, post-traumatic stress disorder, fatigue, sleep disturbance, stress and pain catastrophizing, and lower levels of pain self-efficacy and participation in social roles and activities. However, women were less likely to smoke or have a substance abuse disorder and used more nonpharmacological pain treatment modalities. Conclusion: Among Veterans seeking treatment for chronic pain, women differed from men in their type of pain, had greater pain intensity and interference, and had greater prevalence and higher levels of many known biopsychosocial contributors to pain. Results point to the need for pain treatment that addresses the comprehensive needs of women Veterans.Clinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020.
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OBJECTIVE: A growing body of literature suggests that the COVID-19 pandemic is a traumatic stressor capable of causing posttraumatic stress symptoms. People with a history of trauma, particularly those with posttraumatic stress disorder (PTSD), may be particularly vulnerable to the negative mental health impacts of the pandemic. However, qualitative research exploring potential differences in the lived experiences of and reactions to COVID-19 between people with and without PTSD is lacking. METHOD: Semistructured interviews were conducted with 31 women (n = 15 women with probable PTSD, n = 16 women without probable PTSD) recruited from an ongoing U.S.-based cohort study. Themes were identified using inductive thematic analysis. RESULTS: The majority of women with PTSD described their level of fear or perceived safety related to COVID-19 as a major factor influencing their mental health during the pandemic. In contrast, women without PTSD indicated that their level of distress was largely driven by pandemic-related restrictions on normal activities and family events. Many women with PTSD also described feeling anger or frustration toward people they perceived as not taking the COVID-19 pandemic seriously. Only one participant without PTSD expressed similar feelings. CONCLUSIONS: This study found notable differences in reactions to the COVID-19 pandemic between people with and without PTSD, with findings that are likely relevant to future disasters. These findings can inform the development of preparedness policies for future disasters, pandemics, or other collective traumas to prevent distress and improve mental health, particularly for vulnerable populations such as individuals with preexisting PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Angiosarcoma is a rare, almost universally fatal malignant neoplasm in kidney transplant recipients. No evidence-based guidelines are available for disseminated disease. Here, we report a case of a 66-year-old woman who developed disseminated angiosarcoma 4 months after living nonrelated kidney transplant. She underwent only 2 rounds of chemotherapy because of intolerable adverse effects. Her mycophenolic acid and tacrolimus were withdrawn and sirolimus use was started. In addition to its immunosuppressant effects, sirolimus has been shown to have antineoplastic properties. Remarkably, at almost 2 years post-transplant, the patient has had complete resolution of all gross metastatic disease with only immunosuppressant medication changes. This case highlights the interesting possibility that sirolimus is an effective adjunct treatment for disseminated angiosarcoma in kidney transplant recipients.
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Hemangiosarcoma , Trasplante de Riñón , Humanos , Femenino , Anciano , Sirolimus/efectos adversos , Trasplante de Riñón/efectos adversos , Hemangiosarcoma/tratamiento farmacológico , Inmunosupresores/efectos adversos , Tacrolimus/efectos adversos , Ácido Micofenólico/efectos adversos , Rechazo de InjertoRESUMEN
OBJECTIVES: To characterize the overall trend and differences by sex in opioid overdose death (OOD) and alcohol-related opioid overdose deaths (AOOD) in Minnesota between 2011 and 2020 in relation to drug overdose deaths. METHODS: Using Minnesota death certificate data from 2011 to 2020, we identified OOD and AOOD among Minnesota residents aged 15 and older who died of a drug overdose death. We calculated significant differences in the annual proportion of OOD and AOOD and sex differences using Pearson x2 tests. RESULTS: Approximately 59% of all drug overdose deaths are attributed to opioids, and 18% of those deaths are alcohol-related. Significant increases in the proportion of OOD were found between 2019 and 2020 and a significant decrease between 2017 and 2018 for women only. No significant changes were found in the overall proportion of AOOD. Men had higher on average proportions of OOD and alcohol-related OOD. CONCLUSIONS: Proportions of OOD in relation to overdose deaths increased between 2011 and 2020, with a precipitous increase between 2019 and 2020 while the proportion of AOOD remained relatively stable over the period. Alcohol remains a contributing factor in approximately 1 in 5 OODs in Minnesota. These results support the need for accessible, evidence-based prevention and treatment programs to prevent drug overdose.
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Sobredosis de Droga , Sobredosis de Opiáceos , Analgésicos Opioides , Etanol , Femenino , Humanos , Masculino , Minnesota/epidemiologíaRESUMEN
Childhood and adult adversities occur more frequently among women and persons of colour, possibly influencing racial/ethnic disparities in substance use behaviours. This study investigates how childhood and adult adversities cluster together by race/ethnicity and how these clusters predict binge drinking, tobacco, e-cigarette, and marijuana use. Latent class analysis (LCA) was used in a combined sample from the 2015 to 2018 Minnesota College Student Health Survey to identify clusters of childhood and adult adversities among Asian, Black, Latina, and White women aged 18-25. Each substance use outcome was regressed on each adversity cluster across each race/ethnicity group. Across all racial/ethnic groups and substance use outcomes, the high adversity cluster exhibited the greatest risk. Significant racial/ethnic disparities were observed across several substance use behaviours; these were attenuated among women with fewer adversities. The reduced substance use disparities found among those with lower adversities suggest that prevention of adversities may advance health equity.
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Sistemas Electrónicos de Liberación de Nicotina , Trastornos Relacionados con Sustancias , Adolescente , Adulto , Etnicidad , Femenino , Humanos , Análisis de Clases Latentes , Masculino , Grupos Raciales , Trastornos Relacionados con Sustancias/epidemiología , Adulto JovenRESUMEN
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic increased mothers' caregiving demands, potentially placing them at increased risk for reduced engagement in healthful behaviors and high psychological distress. PURPOSE: The purpose of this study was to describe perceived changes in moderate-vigorous physical activity (MVPA) and sedentary behaviors and the prevalence of different measures of psychological distress (depressive and anxiety symptoms, perceived stress, and positive and negative affect) among mothers. We also evaluated the associations of perceived change in MVPA and sedentary behaviors with measures of psychological distress. METHODS: We conducted a cross-sectional survey with 317 mothers living with children (0-20 years old) at home. Mothers self-reported perceived changes in MVPA and sedentary behaviors from before the pandemic to during COVID-19 stay-at-home orders and early reopening, and levels of depression and anxiety symptomatology, perceived stress, and positive and negative affect during the pandemic. RESULTS: Compared to pre-pandemic levels, 39% of mothers reported engaging less in MVPA, and 63% reported engaging in more sedentary activities. One-quarter and 31% of mothers reported moderate/severe depressive and anxiety symptoms, respectively, and 78% medium/high levels of perceived stress. Adjusted linear regression analyses revealed that reduced MVPA and increased sedentary behaviors were associated with high average scores of depressive and anxiety symptoms, perceived stress, negative affect, and low scores of positive affect. CONCLUSION: A large proportion of mothers reported being less physically active and more engaged in sedentary behaviors, which were associated with increases in psychological distress. Clinical and public health intervention efforts should consider how to improve mothers' physical and mental health as the country emerges from this crisis.
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INTRODUCTION: Per police data, the case fatality rate (CFR) of firearm assault in New Orleans (NO) over the last several years ranged between 27% and 35%, compared with 18%-22% in Philadelphia. The reasons for this disparity are unknown, and potentially reflect important system differences with broader implications for the reduction of firearm mortality. METHODS: A retrospective analysis of police and city-specific trauma databases between 2012 and 2017 was performed. Victims of firearm assaults within city limits were included. Univariate analysis was performed using chi-square for categorical and t-test for continuous variables. Bivariate analysis was conducted using logistic regression. RESULTS: Per police data, the CFR of firearm assault was 31% in NO and 20% in Philadelphia. However, per trauma registry data, the CFR of firearm assault was 14% in NO and 25% in Philadelphia. Patients in Philadelphia were older, had higher injury severity score, and lower blood pressure. Patients in NO had higher rates of head injury. 51% of patients in Philadelphia arrived via police compared to <1% in NO. There was no mortality difference between police and emergency medical service (EMS) transport. Longer EMS prehospital times were associated with increased mortality in NO but not Philadelphia. A much larger percentage of patients died on-scene in NO than Philadelphia. CONCLUSIONS: Our findings suggest that the major driver of increased mortality following firearm assault in NO compared with Philadelphia is death prior to the arrival of first responders. Interventions that shorten prehospital time will likely have the greatest impact on mortality in NO. This should include the consideration of police transport.
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Heridas por Arma de Fuego/mortalidad , Adulto , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Nueva Orleans/epidemiología , Philadelphia/epidemiología , Policia , Sistema de Registros , Estudios Retrospectivos , Factores de Tiempo , Transporte de Pacientes/estadística & datos numéricosRESUMEN
INTRODUCTION: Preventable deaths following trauma are high and unchanged over the last two decades. The objective of this study was to describe the location of death in patients with penetrating trauma, stratified by anatomic location of injury, in order to better tailor our approach to reducing preventable deaths from trauma. METHODS: This retrospective analysis of a prospectively maintained trauma registry included consecutive adult trauma activations with penetrating trauma at a level 1 trauma center between 07/2012 and 03/2018. Injuries were categorized as extremity, junctional, and torso. Head and neck injuries were excluded. Patients injured in >1 defined location were categorized as "multiple." Location of death was defined as on-scene, emergency department (ED), or hospital. Two-sided χ2 tests were used to compare groups. Multivariate analysis was performed using logistic regression. RESULTS: A total of 1024 patients were included with an overall case fatality rate (CFR) of 7.8%. The CFR following extremity injury (3.0%) was significantly lower than all other injury sites (P = .02).There were no significant differences in CFR for junctional (10.4%), torso (8.3%), or multiple injuries (9.6%). Forty percent of fatalities following junctional injury occurred on-scene and an additional 20% occurred in the ED. DISCUSSION: To our knowledge, this is the first study to describe location of death stratified by anatomic location of injury. There was no difference in the CFRs of junctional and torso injuries, and a large proportion of deaths occurred prior to reaching the hospital or in the trauma bay. These findings support reevaluating the classical algorithms and care pathways for patients with proximal penetrating trauma.
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Servicios Médicos de Urgencia/estadística & datos numéricos , Mortalidad Hospitalaria , Heridas Penetrantes/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Modelos Logísticos , Louisiana/epidemiología , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Centros Traumatológicos/estadística & datos numéricosRESUMEN
BACKGROUND: Ischemia/reperfusion injury (IRI) has been shown to cause endothelial glycocalyx (EG) damage.Whether the hypoxic/ischemic insult or the oxidative and inflammatory stress of reperfusion plays a greater part in glycocalyx damage is not known. Furthermore, the mechanisms by which IRI causes EG damage have not been fully elucidated. The aims of this study were to determine if hypoxia alone or hypoxia/reoxygenation (H/R) caused greater damage to the glycocalyx, and if this damage was mediated by reactive oxygen species (ROS) and Ca signaling. METHODS: Human umbilical vein endothelial cells were cultured to confluence and exposed to either normoxia (30 minutes), hypoxia (2% O2 for 30 minutes), or H/R (30 minutes hypoxia followed by 30 minutes normoxia). Some cells were pretreated with ROS scavengers TEMPOL, MitoTEMPOL, Febuxostat, or Apocynin, or with the Ca chelator BAPTA or Ca channel blockers 2-aminoethoxydiphenyl borate, A967079, Pyr3, or ML204. Intracellular ROS was quantified for all groups. Endothelial glycocalyx was measured using fluorescently tagged wheat germ agglutinin and imaged with fluorescence microscopy. RESULTS: Glycocalyx thickness was decreased in both hypoxia and H/R groups, with the decrease being greater in the H/R group. TEMPOL, MitoTEMPOL, BAPTA, and 2-aminoethoxydiphenyl borate prevented loss of glycocalyx in H/R. The ROS levels were likewise elevated compared with normoxia in both groups, but were increased in the H/R group compared with hypoxia alone. BAPTA did not prevent ROS production in either group. CONCLUSION: In our cellular model for shock, we demonstrate that although hypoxia alone is sufficient to produce glycocalyx loss, H/R causes a greater decrease in glycocalyx thickness. Under both conditions damage is dependent on ROS and Ca signaling. Notably, we found that ROS are generated upstream of Ca, but that ROS-mediated damage to the glycocalyx is dependent on Ca.
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Señalización del Calcio/fisiología , Endotelio/patología , Glicocálix/patología , Daño por Reperfusión/fisiopatología , Choque/fisiopatología , Calcio/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Hipoxia de la Célula/fisiología , Línea Celular , Quelantes/farmacología , Endotelio/citología , Depuradores de Radicales Libres/farmacología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/patología , Choque/patologíaAsunto(s)
Cobertura del Seguro , Seguro de Salud , Tiempo de Internación , Heridas y Lesiones/terapia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Increased prevalence of antibiotic resistance in skin and soft tissue infections is a concerning public health challenge currently facing medical science. A combinatory, broad spectrum biocidal antiseptic has been developed ("ASP") as a topically applied solution to potential resistant and polymicrobial infected wounds that may be encountered in this context. The ASP-105 designate was evaluated in vitro by determining the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), against different strains of methicillin-resistant Staphylococcus aureus (MRSA), resulting estimates of which approximated the positive control (bacitracin). To evaluate in vivo microbicide efficacy, we utilized a murine full thickness wound model to study bacterial infection and wound healing kinetics. Mice were experimentally wounded dorsally and infected with bioluminescent MRSA. The infected wound was splinted, dressed and treated topically with either ASP-105, vehicle (-control), or bacitracin. Bacterial burden and wound healing was monitored using an in vivo imaging system and evaluation of biofilm formation using scanning electron microscopy of wound dressing. Treatment with ASP-105 significantly reduced bacterial burdens in the first 3 days of infection and inhibited MRSA biofilm formation on the surgical dressing. Notably, treatment with ASP-105 resulted in a sterilizing effect of any detectable MRSA in nearly all (80%; 4/5) of treatment group. All mice receiving vehicle control developed highly MRSA-luminescent and purulent wound beds as a result of experimental infection. The ASP-105 therapy facilitated natural healing in the absence of MRSA infection. Results of this study suggests that that the novel "ASP" combinatory topical antiseptic can be used directly in wounds as a potent, broad-spectrum microbicide against drug resistant S. aureus without injury to the wound bed and impediment of natural restorative processes associated with wound healing. Further studies are warranted to test the effectiveness of this biocidal formulation against other recalcitrant bacterial and fungal pathogens in the context of serious wound infections, and to assess utility of use in both clinical and self-treat scenarios.