Prevalence, characteristics, and publication of discontinued randomized trials.

IMPORTANCE The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. OBJECTIVES To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. DESIGN AND SETTING Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. MAIN OUTCOMES AND MEASURES Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. RESULTS After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% [95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001). CONCLUSIONS AND RELEVANCE In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.

The Initial Slope of the Variogram, Foundation of the Trabecular Bone Score, Is Not or Poorly Associated With Vertebral Strength

Trabecular bone score (TBS) rests on the textural analysis of DXA to reflect the decay in trabecular structure characterising osteoporosis. Yet, its discriminative power in fracture studies remains incomprehensible as prior biomechanical tests found no correlation with vertebral strength. To verify this result possibly due to an unrealistic set-up and to cover a wide range of loading scenarios, the data from three previous biomechanical studies using different experimental settings was used. They involved the compressive failure of 62 human lumbar vertebrae loaded 1) via intervertebral discs to mimic the in vivo situation (“full vertebra”), 2) via the classical endplate embedding (“vertebral body”) or 3) via a ball joint to induce anterior wedge failure (“vertebral section”). HR-pQCT scans acquired prior testing were used to simulate anterior-posterior DXA from which areal bone mineral density (aBMD) and the initial slope of the variogram (ISV), the early definition of TBS, were evaluated. Finally, the relation of aBMD and ISV with failure load (Fexp) and apparent failure stress (σexp) was assessed and their relative contribution to a multi-linear model was quantified via ANOVA. We found that, unlike aBMD, ISV did not significantly correlate with Fexp and σexp, except for the “vertebral body” case (r2 = 0.396, p = 0.028). Aside from the “vertebra section” set-up where it explained only 6.4% of σexp (p = 0.037), it brought no significant improvement to aBMD. These results indicate that ISV, a replica of TBS, is a poor surrogate for vertebral strength no matter the testing set-up, which supports the prior observations and raises a fortiori the question of the deterministic factors underlying the statistical relationship between TBS and vertebral fracture risk.

Healing of localized gingival recessions treated with coronally advanced flap alone or combined with either a resorbable collagen matrix or subepithelial connective tissue graft: A preclinical study.

OBJECTIVES To histologically evaluate the effectiveness of a porcine derived collagen matrix (CM) and a subepithelial connective tissue graft (CTG) for coverage of localized gingival recessions. MATERIALS AND METHODS Chronic single Miller Class I-like recessions were created at the buccal at the canines and at the third and fourth premolars in the upper and lower jaws of six beagle dogs. The defects were randomly treated with (1) coronally advanced flap surgery (CAF) + CM, (2) CAF + CTG, or (3) CAF alone. At 12 weeks, histometric measurements were made, e.g., between a reference point (N) - and the gingival margin (GM) - and the outer contour of the adjacent soft tissue (gingival thickness [GT]). RESULTS The postoperative healing was uneventful in all animals. No complications such as allergic reactions, abscesses or infections were noted throughout the entire study period. All three treatments resulted in coverage of localized gingival recessions. The histological analysis failed to identify any residues of CM or CTG. The histometric measurements revealed comparable outcomes for N-GM and GT values for all three groups (CAF + CM: 1.04 ± 0.69 mm/0.68 ± 0.33 mm; CAF + CTG: 1.15 ± 1.12 mm/0.76 ± 0.37 mm; CAF: 1.43���± 0.45 mm/0.79 ± 0.24 mm). CONCLUSIONS In the used defect model, the application of CTG or CM in conjunction with CAF did not have an advantage over the use of CAF alone. CLINICAL RELEVANCE The use of CAF alone is a valuable option for the treatment localized Miller Class I recessions.

Older Breast Cancer Survivors: Geriatric Assessment Domains Are Associated With Poor Tolerance of Treatment Adverse Effects and Predict Mortality Over 7 Years of Follow-Up

Purpose To evaluate geriatric assessment (GA) domains in relation to clinically important outcomes in older breast cancer survivors. Methods Six hundred sixty women diagnosed with primary breast cancer in four US geographic regions (Los Angeles, CA; Minnesota; North Carolina; and Rhode Island) were selected with disease stage I to IIIA, age ≥ 65 years at date of diagnosis, and permission from attending physician to contact. Data were collected over 7 years of follow-up from consenting patients' medical records, telephone interviews, physician questionnaires, and the National Death Index. Outcomes included self-reported treatment tolerance and all-cause mortality. Four GA domains were described by six individual measures, as follows: sociodemographic by adequate finances; clinical by Charlson comorbidity index (CCI) and body mass index; function by number of physical function limitations; and psychosocial by the five-item Mental Health Index (MHI5) and Medical Outcomes Study Social Support Survey (MOS-SSS). Associations were evaluated using t tests, χ2 tests, and regression analyses. Results In multivariable regression including age and stage, three measures from two domains (clinical and psychosocial) were associated with poor treatment tolerance; these were CCI ≥ 1 (odds ratio [OR] = 2.49; 95% CI, 1.18 to 5.25), MHI5 score less than 80 (OR = 2.36; 95% CI, 1.15 to 4.86), and MOS-SSS score less than 80 (OR = 3.32; 95% CI, 1.44 to 7.66). Four measures representing all four GA domains predicted mortality; these were inadequate finances (hazard ratio [HR] = 1.89; 95% CI, 1.24 to 2.88; CCI ≥ 1 (HR = 1.38; 95% CI, 1.01 to 1.88), functional limitation (HR = 1.40; 95% CI, 1.01 to 1.93), and MHI5 score less than 80 (HR = 1.34; 95% CI, 1.01 to 1.85). In addition, the proportion of women with these outcomes incrementally increased as the number of GA deficits increased. Conclusion This study provides longitudinal evidence that GA domains are associated with poor treatment tolerance and predict mortality at 7 years of follow-up, independent of age and stage of disease.

Older Breast Cancer Survivors: Factors Associated with Self-reported Symptoms of Persistent Lymphedema Over 7 years of Follow-up

Lymphedema of the arm is a common complication of breast cancer with symptoms that can persist over long periods of time. For older women (over 50% of breast cancer cases) it means living with the potential for long-term complications of persistent lymphedema in conjunction with the common diseases and disabilities of aging over survivorship. We identified women > or =65 years diagnosed with primary stage I-IIIA breast cancer. Data were collected over 7 years of follow-up from consenting patients' medical records and telephone interviews. Data collected included self-reported symptoms of persistent lymphedema, breast cancer characteristics, and selected sociodemographic and health-related characteristics. The overall prevalence of symptoms of persistent lymphedema was 36% over 7 years of follow-up. Having stage II or III (OR = 1.77, 95% CI: 1.07-2.93) breast cancer and having a BMI >30 (OR = 3.04, 95% CI: 1.69-5.45) were statistically significantly predictive of symptoms of persistent lymphedema. Women > or =80 years were less likely to report symptoms of persistent lymphedema when compared to younger women (OR = 0.44, 95% CI: 0.18-0.95). Women with symptoms of persistent lymphedema consistently reported worse general mental health and physical function. Symptoms of persistent lymphedema were common in this population of older breast cancer survivors and had a noticeable effect on both physical function and general mental health. Our findings provide evidence of the impact of symptoms of persistent lymphedema on the quality of survivorship of older women. Clinical and research efforts focused on risk factors for symptoms of persistent lymphedema in older breast cancer survivors may lead to preventative and therapeutic measures that help maintain their health and well-being over increasing periods of survivorship.

Prognosis of Atrial Fibrillation in Patients with Symptomatic Peripheral Arterial Disease: Data from the REduction of Atherothrombosis for Continued Health (REACH) Registry

BACKGROUND: Atrial fibrillation (AF) is a significant risk factor for cardiovascular (CV) mortality. This study aims to evaluate the prognostic implication of AF in patients with peripheral arterial disease (PAD). METHODS: The International Reduction of Atherothrombosis for Continued Health (REACH) Registry included 23,542 outpatients in Europe with established coronary artery disease, cerebrovascular disease (CVD), PAD and/or >/=3 risk factors. Of these, 3753 patients had symptomatic PAD. CV risk factors were determined at baseline. Study end point was a combination of cardiac death, non-fatal myocardial infarction (MI) and stroke (CV events) during 2 years of follow-up. Cox regression analysis adjusted for age, gender and other risk factors (i.e., congestive heart failure, coronary artery re-vascularisation, coronary artery bypass grafting (CABG), MI, hypertension, stroke, current smoking and diabetes) was used. RESULTS: Of 3753 PAD patients, 392 (10%) were known to have AF. Patients with AF were older and had a higher prevalence of CVD, diabetes and hypertension. Long-term CV mortality occurred in 5.6% of patients with AF and in 1.6% of those without AF (p<0.001). Multivariable analyses showed that AF was an independent predictor of late CV events (hazard ratio (HR): 1.5; 95% confidence interval (CI): 1.09-2.0). CONCLUSION: AF is common in European patients with symptomatic PAD and is independently associated with a worse 2-year CV outcome.

A 10-year retrospective analysis of radiographic bone-level changes of implants supporting single-unit crowns in periodontally compromised vs. periodontally healthy patients

AIM: To compare the 10-year peri-implant bone loss (BL) rate in periodontally compromised (PCP) and periodontally healthy patients (PHP) around two different implant systems supporting single-unit crowns. MATERIALS AND METHODS: In this retrospective, controlled study, the mean BL (mBL) rate around dental implants placed in four groups of 20 non-smokers was evaluated after a follow-up of 10 years. Two groups of patients treated for periodontitis (PCP) and two groups of PHP were created. For each category (PCP and PHP), two different types of implant had been selected. The mBL was calculated by subtracting the radiographic bone levels at the time of crown cementation from the bone levels at the 10-year follow-up. RESULTS: The mean age, mean full-mouth plaque and full-mouth bleeding scores and implant location were similar between the four groups. Implant survival rates ranged between 85% and 95%, without statistically significant differences (P>0.05) between groups. For both implant systems, PCP showed statistically significantly higher mBL rates and number of sites with BL> or =3 mm compared with PHP (P<0.0001). CONCLUSIONS: After 10 years, implants in PCP yielded lower survival rates and higher mean marginal BL rates compared with those of implants placed in PHP. These results were independent of the implant system used or the healing modality applied.

Periodontitis: a future risk of acute coronary syndrome? A follow-up study over 3 years

BACKGROUND: Periodontitis has been associated with cardiovascular disease. We assess if the recurrence of acute coronary syndrome (ACS) could be predicted by preceding medical and periodontal conditions. METHODS: A total of 165 consecutive subjects with ACS and 159 medically healthy, matched control subjects were examined and followed for 3 years. Periodontitis was defined by alveolar bone loss. Subgingival microbial samples were studied by the checkerboard DNA-DNA hybridization method. RESULTS: The recurrence of ACS was found in 66 of 165 (40.0%) subjects, and a first ACS event was found in seven of 159 (4.4%) subjects among baseline control subjects. Subjects who later had a second ACS event were older (P <0.001). Significantly higher serum levels of high-density lipoprotein (P <0.05), creatinine (P <0.01), and white blood cell (WBC) counts (P <0.001) were found in subjects with future ACS. Periodontitis was associated with a first event of ACS (crude odds ratio [OR]: 10.3:1; 95% confidence interval [CI]: 6.1 to 17.4; P <0.001) and the recurrence of ACS (crude OR: 3.6:1; 95% CI: 2.0 to 6.6; P <0.001). General linear modeling multivariate analysis, controlling for age and the prediction of a future ACS event, identified that WBC counts (F = 20.6; P <0.001), periodontitis (F = 17.6; P <0.001), and serum creatinine counts (F = 4.5; P <0.05) were explanatory of a future ACS event. CONCLUSIONS: The results of this study indicate that recurrent ACS events are predicted by serum WBC counts, serum creatinine levels, and a diagnosis of periodontitis. Significantly higher counts of putative pathogens are found in subjects with ACS, but these counts do not predict future ACS events.

Ten-year results of a three-arm prospective cohort study on implants in periodontally compromised patients. Part 1: implant loss and radiographic bone loss

OBJECTIVES: The aim of this study was to compare the long-term outcomes of implants placed in patients treated for periodontitis periodontally compromised patients (PCP) and in periodontally healthy patients (PHP) in relation to adhesion to supportive periodontal therapy (SPT). MATERIAL AND METHODS: One hundred and twelve partially edentulous patients were consecutively enrolled in private specialist practice and divided into three groups according to their initial periodontal condition: PHP, moderate PCP and severe PCP. Perio and implant treatment was carried out as needed. Solid screws (S), hollow screws (HS) and hollow cylinders (HC) were installed to support fixed prostheses, after successful completion of initial periodontal therapy (full-mouth plaque score <25% and full-mouth bleeding score <25%). At the end of treatment, patients were asked to follow an individualized SPT program. At 10 years, clinical measures and radiographic bone changes were recorded by two calibrated operators, blinded to the initial patient classification. RESULTS: Eleven patients were lost to follow-up. During the period of observation, 18 implants were removed because of biological complications. The implant survival rate was 96.6%, 92.8% and 90% for all implants and 98%, 94.2% and 90% for S-implants only, respectively, for PHP, moderate PCP and severe PCP. The mean bone loss was 0.75 (+/- 0.88) mm in PHP, 1.14 (+/- 1.11) mm in moderate PCP and 0.98 (+/- 1.22) mm in severe PCP, without any statistically significant difference. The percentage of sites, with bone loss > or =3 mm, was, respectively, 4.7% for PHP, 11.2% for moderate PCP and 15.1% for severe PCP, with a statistically significant difference between PHP and severe PCP (P<0.05). Lack of adhesion to SPT was correlated with a higher incidence of bone loss and implant loss. CONCLUSION: Patients with a history of periodontitis presented a lower survival rate and a statistically significantly higher number of sites with peri-implant bone loss. Furthermore, PCP, who did not completely adhere to the SPT, were found to present a higher implant failure rate. This underlines the value of the SPT in enhancing the long-term outcomes of implant therapy, particularly in subjects affected by periodontitis, in order to control reinfection and limit biological complications.

Prevalence of cam-type deformity on hip magnetic resonance imaging in young males: a cross-sectional study

Objective To determine the prevalence of cam-type deformities on hip magnetic resonance imaging (MRI) in young males. Methods This was a population-based cross-sectional study in young asymptomatic male individuals who underwent clinical examination and completed a self-report questionnaire. A random sample of participants was invited for MRI of the hip. We graded the maximal offset at the femoral head–neck junction on radial sequences using grades from 0 to 3, where 0 = normal, 1 = possible, 2 = definite, and 3 = severe deformity. The prespecified main analyses were based on definite cam-type deformity grades 2 or 3. We estimated the prevalence of the cam-type deformity adjusted for the sampling process overall and according to the extent of internal rotation. Then we determined the location of the deformity on radial MRI sequences. Results A total of 1,080 subjects were included in the study and 244 asymptomatic males with a mean age of 19.9 years attended MRI. Sixty-seven definite cam-type deformities were detected. The adjusted overall prevalence was 24% (95% confidence interval [95% CI] 19–30%). The prevalence increased with decreasing internal rotation (P < 0.001 for trend). Among those with a clinically decreased internal rotation of <30°, the estimated prevalence was 48% (95% CI 37–59%). Sixty-one of 67 cam-type deformities were located in an anterosuperior position. Conclusion Cam-type deformities can be found on MRI in every fourth young asymptomatic male individual and in every second male with decreased internal rotation. The majority of deformities are located in an anterosuperior position.

Long-term anticoagulation treatment for acute venous thromboembolism in patients with and without cancer. The SWIss Venous ThromboEmbolism Registry (SWIVTER) II

In patients with acute cancer-associated thrombosis, current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved. Among 1,247 patients with acute venous thromboembolism (VTE) enrolled in the prospective Swiss Venous Thromboembolism Registry (SWIVTER) II from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, 83 (26%) prior cancer surgery, and 63 (20%) recurrent VTE. Long-term anticoagulation treatment for >12 months was more often planned in patients with versus without cancer (47% vs. 19%; p<0.001), with recurrent cancer-associated versus first cancer-associated VTE (70% vs. 41%; p<0.001), and with metastatic versus non-metastatic cancer (59% vs. 31%; p<0.001). In patients with cancer, recurrent VTE (OR 3.46; 95%CI 1.83-6.53), metastatic disease (OR 3.04; 95%CI 1.86-4.97), and the absence of an acute infection (OR 3.55; 95%CI 1.65-7.65) were independently associated with the intention to maintain anticoagulation for >12 months. In conclusion, long-term anticoagulation treatment for more than 12 months was planned in less than half of the cancer patients with acute VTE. The low rates of long-term anticoagulation in cancer patients with a first episode of VTE and in patients with non-metastatic cancer require particular attention.

Clinical outcome and predictors for adverse events after transcatheter aortic valve implantation with the use of different devices and access routes

Background Transcatheter aortic valve implantation (TAVI) is a treatment option for high-risk patients with severe aortic stenosis. Previous reports focused on a single device or access site, whereas little is known of the combined use of different devices and access sites as selected by the heart team. The purpose of this study is to investigate clinical outcomes of TAVI using different devices and access sites. Methods A consecutive cohort of 200 patients underwent TAVI with the Medtronic CoreValve Revalving system (Medtronic Core Valve LLC, Irvine, CA; n = 130) or the Edwards SAPIEN valve (Edwards Lifesciences LLC, Irvine, CA; n = 70) implanted by either the transfemoral or transapical access route. Results Device success and procedure success were 99% and 95%, respectively, without differences between devices and access site. All-cause mortality was 7.5% at 30 days, with no differences between valve types or access sites. Using multivariable analysis, low body mass index (<20 kg/m2) (odds ratio [OR] 6.6, 95% CI 1.5-29.5) and previous stroke (OR 4.4, 95% CI 1.2-16.8) were independent risk factors for short-term mortality. The VARC-defined combined safety end point occurred in 18% of patients and was driven by major access site complications (8.0%), life-threatening bleeding (8.5%) or severe renal failure (4.5%). Transapical access emerged as independent predictor of adverse outcome for the Valve Academic Research Consortium–combined safety end point (OR 3.3, 95% CI 1.5-7.1). Conclusion A heart team–based selection of devices and access site among patients undergoing TAVI resulted in high device and procedural success. Low body mass index and history of previous stroke were independent predictors of mortality. Transapical access emerged as a risk factor for the Valve Academic Research Consortium–combined safety end point.

Virus infections and winter losses of honey bee colonies (Apis mellifera)

Apiculturists have recently been confronted with drastic and inexplicable winter losses of colonies, and virus infections may be involved. Here, we surveyed 337 Swiss honey bee colonies in the winter of 2005 and 2006 and categorized their health status as: 1. dead (= no or few live bees left); 2. weak (= dwindling, high mortality of adult bees); or 3. healthy (= normal overwintering colony). From each colony, pooled adult workers were analyzed for deformed wing virus (DWV), acute bee paralysis virus (ABPV), chronic bee paralysis virus (CBPV) and Kashmir bee virus (KBV). Neither KBV nor CBPV were found, but significantly higher ABPV and DWV infections were found in dead vs. weak vs. healthy colonies (except DWV in 2006 between weak and healthy). Moreover, ABPV and DWV loads were positively correlated with each other. This is the first report demonstrating statistically significant correlations between viruses associated with Varroa destructor and winter mortality.

Effect of Mutation and Genetic Background on Drug Resistance in Mycobacterium tuberculosis

Bacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (TB). Only a few studies have reported on the interactions between different bacterial factors. We studied drug-resistant Mycobacterium tuberculosis isolates from a nationwide study conducted from 2000 to 2008 in Switzerland. We determined quantitative drug resistance levels of first-line drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant genes. We determined recent transmission by molecular methods and collected clinical data. Overall, we analyzed 158 isolates that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which were multidrug resistant. Among 154 isoniazid-resistant strains, katG mutations were associated with high-level and inhA promoter mutations with low-level drug resistance. Only katG(S315T) (65.6% of all isoniazid-resistant strains) and inhA promoter -15C/T (22.7%) were found in molecular clusters. M. tuberculosis lineage 2 (includes Beijing genotype) was associated with any drug resistance (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6; P < 0.0001). Lineage 1 was associated with inhA promoter -15C/T mutations (OR, 6.4; 95% CI, 2.0 to 20.7; P = 0.002). We found that the genetic strain background influences the level of isoniazid resistance conveyed by particular mutations (interaction tests of drug resistance mutations across all lineages; P < 0.0001). In conclusion, M. tuberculosis drug resistance mutations were associated with various levels of drug resistance and transmission, and M. tuberculosis lineages were associated with particular drug resistance-conferring mutations and phenotypic drug resistance. Our study also supports a role for epistatic interactions between different drug resistance mutations and strain genetic backgrounds in M. tuberculosis drug resistance.

Epidemiology and predictors of spinal injury in adult major trauma patients: European cohort study

This is a European cohort study on predictors of spinal injury in adult (≥16 years) major trauma patients, using prospectively collected data of the Trauma Audit and Research Network from 1988 to 2009. Predictors for spinal fractures/dislocations or spinal cord injury were determined using univariate and multivariate logistic regression analysis. 250,584 patients were analysed. 24,000 patients (9.6%) sustained spinal fractures/dislocations alone and 4,489 (1.8%) sustained spinal cord injury with or without fractures/dislocations. Spinal injury patients had a median age of 44.5 years (IQR = 28.8-64.0) and Injury Severity Score of 9 (IQR = 4-17). 64.9% were male. 45% of patients suffered associated injuries to other body regions. Age <45 years (≥45 years OR 0.83-0.94), Glasgow Coma Score (GCS) 3-8 (OR 1.10, 95% CI 1.02-1.19), falls >2 m (OR 4.17, 95% CI 3.98-4.37), sports injuries (OR 2.79, 95% CI 2.41-3.23) and road traffic collisions (RTCs) (OR 1.91, 95% CI 1.83-2.00) were predictors for spinal fractures/dislocations. Age <45 years (≥45 years OR 0.78-0.90), male gender (female OR 0.78, 95% CI 0.72-0.85), GCS <15 (OR 1.36-1.93), associated chest injury (OR 1.10, 95% CI 1.01-1.20), sports injuries (OR 3.98, 95% CI 3.04-5.21), falls >2 m (OR 3.60, 95% CI 3.21-4.04), RTCs (OR 2.20, 95% CI 1.96-2.46) and shooting (OR 1.91, 95% CI 1.21-3.00) were predictors for spinal cord injury. Multilevel injury was found in 10.4% of fractures/dislocations and in 1.3% of cord injury patients. As spinal trauma occurred in >10% of major trauma patients, aggressive evaluation of the spine is warranted, especially, in males, patients <45 years, with a GCS <15, concomitant chest injury and/or dangerous injury mechanisms (falls >2 m, sports injuries, RTCs and shooting). Diagnostic imaging of the whole spine and a diligent search for associated injuries are substantial.