Prognostic factors for whiplash associated disorders

Disability and chronic pain secondary to low- speed vehicle collisions has been a known condition since the nineteenth century. Today, whiplash-associated disorders (WAD) are the most common personal injuries reported to insurance companies after motor vehicle accidents (MVAs). The prognosis has great variations, spanning from discomfort for a few days to lifelong disability and severe reduction in quality of life. A few well-accepted prognostic factors exist, including high level of pain immediately after the accident, post- traumatic stress and anxiety, and previous history of pain conditions. However, there is no accepted universal pathomechanism and there is a need for additional surveys regarding common characteristics of individuals with poor recovery potential after a whiplash injury. The overall objective of this thesis was to investigate possible risk factors for non- recovery after whiplash trauma. Specifically, we aimed to identify potential associations between non-recovery and involvement of insurance companies, genetic markers, cervical radiological degeneration, and sagittal align- ment. Additionally, we aimed to investigate the effect of an educational video-intervention on the recovery rate. The participants in this thesis are derived from four cohorts. The first cohort comprised individuals aged 18–65 years seeking care at an emergency department (Studies I and III). The second cohort comprised individuals aged 18– 65 years reporting neck pain to insurance companies after an MVA (Studies I and II). The third and fourth cohorts consisted of individuals aged 16–65 years, also recruited from an emergency department after whiplash trauma (Studies IV , V , VI, and VII). In all seven studies of this thesis, inclusion was made by the study team. Information in baseline questionnaires were filled in with regard to demographics and physical and mental health. The patients were followed up with regard to a patient-reported outcome measure (PROM), defined as reported non- recovery or recovery. Secondary outcome measures were level of pain and distress and the Whiplash Disability Questionnaire (WDQ). For Study V, we performed a randomization to either the intervention with the educational video or to a standard information sheet. In the studies included in this thesis, financial compensation from insurance companies, facet joint degeneration, sagittal alignment variables (low thoracic inlet angle (TIA) and Neck Tilt), high level of pain and distress were associated with non-recovery. Further, expectation of poor recovery was a risk factor. No prognostic or therapeutic value was demonstrated for genetic markers (represented by COMT gene haplotypes), the educational video, disc degeneration, or cervical sagittal curvature. This thesis contributes to the general knowledge on those groups of individuals that are at risk of poor prognosis after whiplash trauma. It raises a few new questions regarding prognostic factors. The findings of radiologic profiles being associated with non-recovery must be re-examined in the future, tentatively emphasizing the association between facet joint degeneration and continuous pain

Clinical and echocardiographic predictors of mortality in acute pulmonary embolism

Purpose: The aim of this study was to evaluate the utility of adding quantitative assessments of cardiac function from echocardiography to clinical factors in predicting the outcome of patients with acute pulmonary embolism (PE). Methods: Patients with a diagnosis of acute PE, based on a positive ventilation perfusion scan or computed tomography (CT) chest angiogram, were identified using the Duke University Hospital Database. Of these, 69 had echocardiograms within 24–48 h of the diagnosis that were suitable for offline analysis. Clinical features that were analyzed included age, gender, body mass index, vital signs and comorbidities. Echocardiographic parameters that were analyzed included left ventricular (LV) ejection fraction (EF), regional, free wall and global RV speckle-tracking strain, RV fraction area change (RVFAC), Tricuspid Annular Plane Systolic Excursion (TAPSE), pulmonary artery acceleration time (PAAT) and RV myocardial performance (Tei) index. Univariable and multivariable regression statistical analysis models were used. Results: Out of 69 patients with acute PE, the median age was 55 and 48 % were female. The median body mass 2 index (BMI) was 27 kg/m . Twenty-nine percent of the cohort had a history of cancer, with a significant increase in cancer prevalence in non-survivors (57 % vs 29 %, p = 0.02). Clinical parameters including heart rate, respiratory rate, troponin T level, active malignancy, hypertension and COPD were higher among non-survivors when compared to survivors (p ≤ 0.05). Using univariable analysis, NYHA class III symptoms, hypoxemia on presentation, tachycardia, tachypnea, elevation in Troponin T, absence of hypertension, active malignancy and chronic obstructive pulmonary disease (COPD) were increased in non-survivors compared to survivors (p ≤ 0.05). In multivariable models, RV Tei Index, global and free (lateral) wall RVLS were found to be negatively associated with survival probability after adjusting for age, gender and systolic blood pressure (p ≤ 0.05). Conclusion: The addition of echocardiographic assessment of RV function to clinical parameters improved the prediction of outcomes for patients with acute PE. Larger studies are needed to validate these findings

COMT genotype and non-recovery after a whiplash injury in a Northern European population

Background: The COMT (Catechol-O-Methyl Transferase) gene may influence a person's vulnerability to develop long-term pain and some COMT single nucleotide polymorphisms (SNPs) may associate with patterns of acute or chronic pain. Many patients with whiplash-associated disorders (WADs) suffer from long-term pain and other related symptoms, but it is less known if genetic factors play a role in the recovery process. The primary aim of this study was to evaluate whether self-reported non-recovery, including pain, was related to COMT genotype in patients with WAD. The secondary aim was to investigate whether or not background factors, including mental health, were related to genotype and non-recovery. Methods: A total of 133 patients with neck pain after a whiplash trauma were included. Background factors were collected and blood samples were taken during the acute phase after the accident. DNA was isolated from blood and used to genotype the SNPs rs6269, rs4633, rs4818 and rs4680 in the COMT gene; additionally haplotypes were estimated and haplogenotypes inferred. The patients were followed up after 12 months and asked to rate their recovery including pain, mental health and quality of life. Results: The overall reported non-recovery rate at 12 months was 44% with no significant differences in distribution of the COMT haplotypes. High levels of self-reported pain (OR 7.2) and anxiety (OR 4.4) after the accident were associated with non-recovery, but not related to the haplotypes. None of the other background factors were related to the haplotypes or non-recovery. Conclusion: No association between self-reported non-recovery or pain levels and COMT haplotypes in patients with acute whiplash injuries could be detected. Independent replications are necessary to discard the hypothesis that COMT haplotypes do not influence non-recovery or pain levels in patients with acute whiplash injuries. High levels of initial pain and anxiety were associated with non-recovery, thereby confirming previously published reports

Bacteria: back pain, leg pain and Modic sign-a surgical multicentre comparative study

Purpose To compare bacterial findings in pain-generating degenerated discs in adults operated on for lumbar disc herniation (LDH), and mostly also suffering from low back pain (LBP), with findings in adolescent patients with non-degenerated non-pain-generating discs operated on for scoliosis, and to evaluate associations with Modic signs on magnetic resonance imaging (MRI). Cutibacterium acnes (Propionibacterium acnes) has been found in painful degenerated discs, why it has been suggested treating patients with LDH/LBP with antibiotics. As multidrug-resistant bacteria are a worldwide concern, new indications for using antibiotics should be based on solid scientific evidence. Methods Between 2015 and 2017, 40 adults with LDH/LBP (median age 43, IQR 33-49) and 20 control patients with scoliosis (median age 17, IQR 15-20) underwent surgery at seven Swedish hospitals. Samples were cultured from skin, surgical wound, discs and vertebrae. Genetic relatedness of C. acnes isolates was investigated using single-nucleotide polymorphism analysis. DNA samples collected from discs/vertebrae were analysed using 16S rRNA-based PCR sequencing. MRI findings were assessed for Modic changes. Results No bacterial growth was found in 6/40 (15%) LDH patients, compared with 3/20 (15%) scoliosis patients. Most positive samples in both groups were isolated from the skin and then from subcutis or deep within the wound. Of the four disc and vertebral samples from each of the 60 patients, 235/240 (98%) were DNA negative by bacterial PCR. A single species, C. acnes, was found exclusively in the disc/vertebra from one patient in each group. In the LDH group, 29/40 (72%) patients had at least one sample with growth of C. acnes, compared to 14/20 (70%) in the scoliosis group. Bacterial findings and Modic changes were not associated. Conclusions Cutibacterium acnes found in discs and vertebrae during surgery for disc herniation in adults with degenerated discs may be caused by contamination, as findings in this group were similar to findings in a control group of young patients with scoliosis and non-degenerated discs. Furthermore, such findings were almost always combined with bacterial findings on the skin and/or in the wound. There was no association between preoperative Modic changes and bacterial findings. Antibiotic treatment of lumbar disc herniation with sciatica and/or low back pain, without signs of clinical discitis/spondylitis, should be seriously questioned.Funding Agencies|FORSS, a Swedish regional research foundation</p