Risk factors and outcomes of chronic opioid use following trauma.

BACKGROUND: The growing problem of opioid misuse has become a serious crisis in many countries. The role of trauma as a gateway to opioid use is currently not determined. The study was undertaken to assess whether traumatic injury might be associated with chronic opioid use and accompanying increased long-term mortality. METHODS: Injured patients and controls from Sweden were matched for age, sex and municipality. After linkage to Swedish health registers, opioid consumption was assessed before and after trauma. Among injured patients, logistic regression was used to investigate factors associated with chronic opioid use, assessed by at least one written and dispensed prescription in the second quarter after trauma. Cox regression was employed to study excess risk of mortality. In addition, causes of death for postinjury opioid users were explored. RESULTS: Some 13 309 injured patients and 70 621 controls were analysed. Exposure to trauma was independently associated with chronic opioid use (odds ratio 3·28, 95 per cent c.i. 3·02 to 3·55); this use was associated with age, low level of education, somatic co-morbidity, psychiatric co-morbidity, pretrauma opioid use and severe injury. The adjusted hazard ratio for death from any cause 6-18 months after trauma for chronic opioid users was 1·82 (95 per cent c.i. 1·34 to 2·48). Findings were similar in a subset of injured patients with no pretrauma opioid exposure. CONCLUSION: Traumatic injury was associated with chronic opioid use. These patients have an excess risk of death in the 6-18 months after trauma.

ANTECEDENTES: El uso indebido de opioides es un problema creciente que se ha convertido en una grave crisis en muchos países. No se ha analizado el papel de las lesiones traumáticas como puerta de entrada al uso de opioides. Se estableció la hipótesis de que una lesión traumática podría asociarse con el uso crónico de opioides y acompañarse de un aumento de la mortalidad a largo plazo. MÉTODOS: Se ajustaron por edad, sexo y municipio a los pacientes suecos con lesiones traumáticas y sus controles. Después de vincular varios registros de salud suecos, se evaluó el consumo de opioides antes y después de la lesión traumática. En los pacientes con lesiones traumáticas, se utilizó una regresión logística para definir los factores asociados con el uso crónico de opioides, definida como una receta prescrita y dispensada en el segundo trimestre después de la lesión traumática, y ​​una regresión de Cox para estudiar el exceso de riesgo de mortalidad. Además, se exploraron las causas de muerte de los usuarios de opioides postraumáticos. RESULTADOS: Se analizaron 13.309 pacientes con lesiones traumáticas y 70.621 controles. La exposición a una lesión traumática se asoció de forma independiente con el uso crónico de opioides, (razón de oportunidades, odds ratio, OR) OR 3,3 (i.c. del 95% 3,0-3,6), y dicho uso se asoció con la edad, el bajo nivel educativo, las comorbilidad físicas y psiquiátricas, el uso previo de opioides y la gravedad de las lesiones. El cociente de riesgos instantáneos, hazard ratio, HR ajustado de muerte por cualquier causa a los 6-18 meses de la lesión traumática para los consumidores crónicos de opioides fue de 1,8 (i.c. del 95% 1,3-2,5). En un subconjunto de pacientes con lesiones traumáticas sin exposición previa a los opioides, los hallazgos fueron similares. CONCLUSIÓN: La lesión traumática se asoció con el uso crónico de opioides. Estos pacientes presentan un exceso de riesgo de mortalidad entre los 6 y 8 meses después del trauma.

Validation of the Norwegian survival prediction model in trauma (NORMIT) in Swedish trauma populations.

BACKGROUND: Trauma survival prediction models can be used for quality assessment in trauma populations. The Norwegian survival prediction model in trauma (NORMIT) has been updated recently and validated internally (NORMIT 2). The aim of this observational study was to compare the accuracy of NORMIT 1 and 2 in two Swedish trauma populations. METHODS: Adult patients registered in the national trauma registry during 2014-2016 were eligible for inclusion. The study populations comprised the total national trauma (NT) population, and a subpopulation of patients admitted to a single level I trauma centre (TC). The primary outcome was 30-day mortality. Model validation included receiver operating characteristic (ROC) curve analysis and GiViTI calibration belts. The calibration was also assessed in subgroups of severely injured patients (New Injury Severity Score (NISS) over 15). RESULTS: A total of 26 504 patients were included. Some 18·7 per cent of patients in the NT population and 2·6 per cent in the TC subpopulation were excluded owing to missing data, leaving 21 554 and 3972 respectively for analysis. NORMIT 1 and 2 showed excellent ability to distinguish between survivors and non-survivors in both populations, but poor agreement between predicted and observed outcome in the NT population with overestimation of survival, including in the subgroup with NISS over 15. In the TC subpopulation, NORMIT 1 underestimated survival irrespective of injury severity, but NORMIT 2 showed good calibration both in the total subpopulation and the subgroup with NISS over 15. CONCLUSION: NORMIT 2 is well suited to predict survival in a Swedish trauma centre population, irrespective of injury severity. Both NORMIT 1 and 2 performed poorly in a more heterogeneous national population of injured patients.

ANTECEDENTES: Los modelos de predicción de supervivencia en los traumatismos pueden ser utilizados para la evaluación de la calidad en las poblaciones con traumatismos. Recientemente, el modelo noruego de predicción de supervivencia en traumatismos (NORMIT) se ha actualizado y validado internamente (NORMIT 2). El objetivo de este estudio observacional fue comparar la precisión de los modelos NORMIT 1 y 2 en dos poblaciones suecas con traumatismos. MÉTODOS: Pacientes adultos registrados en el registro nacional de traumatismos durante 2014-2016 fueron elegibles para el estudio. Las poblaciones de estudio eran: (1) la población total nacional de traumatismos (national trauma, NT) y (2) una subpoblación de pacientes ingresados en un único centro de trauma de nivel I (trauma centre, TC). El resultado primario fue la mortalidad a los 30 días. La validación del modelo incluyó curvas de características operativas del receptor y cinturones GiViTI de calibración. La calibración también se evaluó en subgrupos de pacientes con lesiones graves (New Injury Severity Score, NISS >15). RESULTADOS: Se incluyeron un total de 26.504 pacientes. La exclusión por falta de datos fue del 18,7% en la población NT (n = 21.554) y del 2,6% en la población TC (n = 3.972). Los modelos NORMIT 1 y 2 mostraron una habilidad excelente para distinguir entre supervivientes y no supervivientes en ambas poblaciones, pero con un grado de acuerdo pobre entre el resultado predicho y el observado en la población NT, con sobreestimación de la supervivencia incluido el subgrupo de NISS >15. En la subpoblación TC, NORMIT 1 subestimó la supervivencia independientemente de la gravedad de la lesión, pero NORMIT 2 mostró una buena calibración tanto en la subpoblación total, como en el subgrupo NISS >15. CONCLUSIÓN: El modelo NORMIT 2 es muy apropiado para predecir la supervivencia en la población de un centro de traumatismos sueco independientemente de la gravedad de la lesión. Los modelos tanto NORMIT 1 como NORMIT 2 funcionan mal en una población de traumatismos nacional más heterogenea.

Mitogenomics of 'Old World Acraea' butterflies reveals a highly divergent 'Bematistes'.

Afrotropical Acraeini butterflies provide a fascinating potential model system to contrast with the Neotropical Heliconiini, yet their phylogeny remains largely unexplored by molecular methods and their generic level nomenclature is still contentious. To test the potential of mitogenomes in a simultaneous analysis of the radiation, we sequenced the full mitochondrial genomes of 19 African species. Analyses show the potential of mitogenomic phylogeny reconstruction in this group. Inferred relationships are largely congruent with a previous multilocus study. We confirm a monophyletic Telchinia to include the Asiatic Pareba with a complicated paraphylum, traditional (sub)genus Acraea, toward the base. The results suggest that several proposed subgenera and some species groups within Telchinia are not monophyletic, while two other (sub)genera could possibly be combined. Telchinia was recovered without strong support as sister to the potentially interesting system of distasteful model butterflies known as Bematistes, a name that is suppressed in some treatments. Surprisingly, we find that this taxon has remarkably divergent mitogenomes and unexpected synapomorphic tRNA rearrangements. These gene order changes, combined with evidence for deviating dN/dS ratios and evidence for episodal diversifying selection, suggest that the ancestral Bematistes mitogenome has had a turbulent past. Our study adds genetic support for treating this clade as a distinct genus, while the alternative option, adopted by some authors, of Acraea being equivalent to Acraeini merely promotes redundancy. We pave the way for more detailed mitogenomic and multi-locus molecular analyses which can determine how many genera are needed (possibly at least six) to divide Acraeini into monophyletic groups that also facilitate communication about their biology.

Causes of excessive late death after trauma compared with a matched control cohort.

BACKGROUND: Studies on mortality following trauma have been restricted mainly to in-hospital or 30-day death. Mortality risk may be sustained several years after trauma, but the causes of late death have not been elucidated. The aim was to investigate mortality and analyse causes of late death after trauma. METHODS: All injured patients from a regional trauma registry with long-term follow-up were matched in a 1 : 5 ratio with uninjured controls by age, sex and municipality. By linkage to national registries, long-term mortality, causes of death and co-morbidity status were identified. Excess mortality was examined by calculating the all-cause mortality rate ratio (MRR). RESULTS: Among the trauma cohort of 7382 patients, 662 (9·0 per cent) died within 3 years after the index trauma; the 30-day mortality rate was 5·0 per cent. Compared with the control group (36 759 individuals), there was a sustained increase in mortality up to 3 years after trauma; the MRR was 2·88 (95 per cent c.i. 2·37 to 3·50) for days 31-365, 1·59 (1·24 to 2·04) for years 1-2 and 1·43 (1·06 to 1·92) for years 2-3. External causes, including new trauma, were far more common causes of late death in injured patients than in matched controls. CONCLUSION: Postinjury mortality is increased for several years after trauma. Excess mortality is largely attributed to recurrent trauma and other external causes of death.

Selection on male sex pheromone composition contributes to butterfly reproductive isolation.

Selection can facilitate diversification by inducing character displacement in mate choice traits that reduce the probability of maladaptive mating between lineages. Although reproductive character displacement (RCD) has been demonstrated in two-taxa case studies, the frequency of this process in nature is still debated. Moreover, studies have focused primarily on visual and acoustic traits, despite the fact that chemical communication is probably the most common means of species recognition. Here, we showed in a large, mostly sympatric, butterfly genus, a strong pattern of recurrent RCD for predicted male sex pheromone composition, but not for visual mate choice traits. Our results suggest that RCD is not anecdotal, and that selection for divergence in male sex pheromone composition contributed to reproductive isolation within the Bicyclus genus. We propose that selection may target olfactory mate choice traits as a more common sensory modality to ensure reproductive isolation among diverging lineages than previously envisaged.

Stereoisomeric analysis of 6,10,14-trimethylpentadecan-2-ol and the corresponding ketone in wing extracts from African Bicyclus butterfly species.

Gas chromatography (GC) and mass spectrometry (MS) were used to determine the stereoisomeric compositions of 6,10,14-trimethylpentadecan-2-ol and 6,10,14-trimethylpentadecan-2-one in wing extracts from 17 Bicyclus butterfly species from different regions of Africa. All samples were purified using solid phase extraction (SPE). Since some species contained both alcohol and ketone, these were separated and the ketone was reduced to the alcohol before analysis as either (R)-trans-chrysanthemoyl or (S)-2-acetoxypropionyl esters. A novel asymmetric synthesis was developed for a reference mixture of (2R/S,6S,10R)-6,10,14-trimethylpentadecan-2-ol with known composition of the eight stereoisomers. The mixture then was used as the (R)-trans-chrysanthemoyl esters to correlate each of the eight gas chromatographic peaks to a specific stereoisomer of the extracted wing compounds. Seven butterfly species showed (2R,6R,10R)-configuration of the alcohol, four species contained minute amounts of alcohol too small to determine the stereochemistry, nine species showed (6R,10R)-configuration of the ketone, and one species contained minute amounts of ketone too small to determine the stereochemistry. No other stereoisomers of alcohol or ketone could be detected in the extracts, and the quantities of the compounds in the wing extracts varied from 5 to 900 ng per sample for each species.

Heparin-binding protein (HBP): an early marker of respiratory failure after trauma?

BACKGROUND: Trauma and its complications contribute to morbidity and mortality in the general population. Trauma victims are susceptible to acute respiratory distress syndrome (ARDS) and sepsis. Polymorphonuclear leucocytes (PMNs) are activated after trauma and there is substantial evidence of their involvement in the development of ARDS. Activated PMNs release heparin-binding protein (HBP), a granule protein previously shown to be involved in acute inflammatory reactions. We hypothesised that there is an increase in plasma HBP content after trauma and that the increased levels are related to the severity of the trauma or later development of severe sepsis and organ failure (ARDS). METHODS AND MATERIAL: We investigated HBP in plasma samples within 36 h from trauma in 47 patients admitted to a level one trauma centre with a mean injury severity score (ISS) of 26 (21-34). ISS, admission sequential organ failure assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were recorded at admission. ARDS and presence of severe sepsis were determined daily during intensive care. RESULTS: We found no correlation between individual maximal plasma HBP levels at admission and ISS, admission SOFA or APACHE II. We found, however, a correlation between HBP levels and development of ARDS (P = 0.026, n = 47), but not to severe sepsis. CONCLUSION: HBP is a potential biomarker candidate for early detection of ARDS development after trauma. Further research is required to confirm a casual relationship between plasma HBP and the development of ARDS.

High incidence of post-injury pneumonia in intensive care-treated trauma patients.

INTRODUCTION: Trauma patients are susceptible to post-injury infections. We investigated the incidence, as well as risk factors for development of pneumonia in intensive care unit (ICU)-treated trauma patients. In addition, we report pathogens identified in patients that developed pneumonia. METHODS: The study cohort consisted of 322 trauma patients admitted to the ICU at a level-one trauma centre following initial resuscitation. Patients 15 years or older with an ICU stay of more than 24 h were included. We investigated pre-hospital and hospital parameters during the first 24 h after admission and their possible association with pneumonia within 10 days of ICU admission. RESULTS: Majority of the patients were male (78%) and the median age was 41 years. The overall degree of injury was high with a median Injury Severity Score (ISS) of 24. Overall 30-day mortality was 9%. Eighty-five (26%) patients developed pneumonia during their first 10 days in the ICU. Univariate logistic regression revealed that intubation in the field, shock, Glasgow Coma Scale (GCS) 3-8, major surgery within 24 h after admission, massive transfusion and ISS > 24 were all risk factors for subsequent development of pneumonia. In the multivariable model, only GCS 3-8 was identified as an independent risk factor. In 42 out of the 85 cases of pneumonia, the diagnosis was defined by significant growth of at least one pathogen where Enterobacteriaceae and Staphylococcus aureus were the most common. CONCLUSIONS: Pneumonia is a common complication among ICU-treated trauma patients. Reduced consciousness is an independent risk factor for development of pneumonia after severe injury.

Gut microcirculatory and mitochondrial effects of hyperdynamic endotoxaemic shock and norepinephrine treatment.

BACKGROUND: Microcirculatory and mitochondrial dysfunction are important factors in the development of septic shock. In this study, we investigated the effects of fluid resuscitated endotoxaemic shock and norepinephrine treatment on intestinal microcirculation and mitochondrial function in sheep. METHODS: Eight anaesthetized sheep received an i.v. infusion of endotoxin. After 24 h, mean arterial pressure (MAP) was restored to baseline levels with a norepinephrine infusion. Five sheep served as sham experiments. Central and regional haemodynamics were monitored, and ileal microcirculation was evaluated with laser Doppler and sidestream dark-field videomicroscopy techniques. Gut mucosal acidosis was assessed by air tonometry, and ileal wall biopsies were analysed for mitochondrial activity. RESULTS: After 24 h of endotoxaemia, the animals had developed hyperdynamic shock with systemic and mucosal acidosis. Although superior mesenteric artery (SMA) flow was higher than the baseline values, ileal microcirculatory perfusion and mitochondrial complex I activity decreased. After norepinephrine was started, SMA flow, ileal microcirculation, and mucosal acidosis remained unchanged. Although no statistically significant difference could be demonstrated, norepinephrine increased mitochondrial complex I activity in five of the six animals from which ileal biopsies were taken. CONCLUSIONS: Although fluid resuscitated endotoxaemic shock increased regional blood flow, microcirculatory and mitochondrial alterations were still present. Restoring MAP with norepinephrine did not affect ileal microcirculation or mucosal acidosis, indicating that perfusion pressure manipulation is of limited importance to the intestinal microcirculation in established endotoxaemic shock.

Early predictors of morbidity and mortality in trauma patients treated in the intensive care unit.

BACKGROUND: We investigated the incidence and severity of post-injury morbidity and mortality in intensive care unit (ICU)-treated trauma patients. We also identified risk factors in the early phase after injury that predicted the later development of complications. METHODS: A prospective observational cohort study design was used. One hundred and sixty-four adult patients admitted to the ICU for more than 24 h were included during a 21-month period. The incidence and severity of morbidity such as multiple organ failure (MOF), acute lung injury (ALI), severe sepsis and 30-day post-injury mortality were calculated and risk factors were analyzed with uni- and multivariable logistic regression analysis. RESULTS: The median age was 40 years, the injury severity score was 24, the new injury severity score was 29, the acute physiology and chronic health evaluation II score was 15, sequential organ failure assessment maximum was 7 and ICU length of stay was 3.1 days. The incidences of post-injury MOF were 40.2%, ALI 25.6%, severe sepsis 31.1% and 30-day mortality 10.4%. The independent risk factors differed to some extent between the outcome parameters. Age, severity of injury, significant head injury and massive transfusion were independent risk factors for several outcome parameters. Positive blood alcohol was only a predictor of MOF, whereas prolonged rescue time only predicted death. Unexpectedly, injury severity was not an independent risk factor for mortality. CONCLUSIONS: Although the incidence of morbidity was considerable, mortality was relatively low. Early post-injury risk factors that predicted later development of complications differed between morbidity and mortality.

Effect of preadmission beta-blockade on mortality in multiple trauma.

BACKGROUND: High levels of circulating catecholamines after multiple trauma have been associated with increased morbidity and mortality. Beta-adrenergic receptor antagonist (beta-blocker) therapy has emerged as a potential treatment option, but the effect of preinjury beta-blockade on trauma-induced mortality is unclear. The aim of this study was to assess whether preinjury beta-blocker therapy is associated with reduced mortality after multiple trauma. METHODS: Severely injured patients, aged at least 50 years, admitted to a level one trauma centre over a 10-year interval were linked to national and local registries of co-morbidities, prescription drug use and level of education. The association between preinjury beta-blocker use and 30-day mortality was explored using logistic regression analysis. RESULTS: Some 1376 patients were included; 338 (24·6 per cent) were receiving beta-blockers at the time of trauma. Beta-blocker users had an increased crude 30-day mortality rate compared with that for non-users: 32·8 versus 19·7 per cent respectively (P < 0·001). After adjustment for baseline imbalances and injury-related factors, there was no association between preinjury beta-blocker use and mortality (OR 1·09, 95 per cent c.i. 0·70 to 1·70). Separate analyses of individuals with or without severe head injury did not significantly change this association. There was no significant difference in the rate of shock between beta-blocker users and non-users. CONCLUSION: Pretrauma beta-blockade is not associated with 30-day mortality beyond the effects of age, co-morbidity and injury severity.

Early postpartum mitral valve thrombosis requiring extra corporeal membrane oxygenation before successful valve replacement.

Pregnancy is associated with an increased risk of thrombosis in women with mechanical prosthetic heart valves. We present the case of a 29-year-old woman who developed early postpartum mitral valve thrombus after an elective cesarean delivery. The patient had a mechanical mitral valve and was treated with warfarin in the second trimester, which was replaced with high-dose dalteparin during late pregnancy. Elective cesarean delivery was performed under general anesthesia at 37weeks of gestation. The patient was admitted to the intensive care unit for postoperative care and within 30min she developed dyspnea and hypoxia requiring mechanical ventilation. She deteriorated rapidly and developed pulmonary edema, worsening hypoxia and severe acidosis. Urgent extra corporeal membrane oxygenation was initiated. Transesophageal echocardiography revealed a mitral valve thrombus. The patient underwent a successful mitral valve replacement after three days on extra corporeal membrane oxygenation. This case highlights the importance of multidisciplinary care and frequent monitoring of anticoagulation during care of pregnant women with prosthetic heart valves.