Longitudinal associations between incident lumbar spine MRI findings and chronic low back pain or radicular symptoms: retrospective analysis of data from the longitudinal assessment of imaging and disability of the back (LAIDBACK)

BACKGROUND: There are few longitudinal cohort studies examining associations between incident MRI findings and incident spine-related symptom outcomes. Prior studies do not discriminate between the two distinct outcomes of low back pain (LBP) and radicular symptoms. To address this gap in the literature, we conducted a secondary analysis of existing data from the Longitudinal Assessment of Imaging and Disability of the Back (LAIDBACK). The purpose of this study was to examine the association of incident lumbar MRI findings with two specific spine-related symptom outcomes: 1) incident chronic bothersome LBP, and 2) incident radicular symptoms such as pain, weakness, or sensation alterations in the lower extremity. METHODS: The original LAIDBACK study followed 123 participants without current LBP or sciatica, administering standardized MRI assessments of the lumbar spine at baseline and at 3-year follow-up, and collecting information on participant-reported spine-related symptoms and signs every 4 months for 3 years. These analyses examined bivariable and multivariable associations between incident MRI findings and symptom outcomes (LBP and radicular symptoms) using logistic regression. RESULTS: Three-year cumulative incidence of new MRI findings ranged between 2 and 8%, depending on the finding. Incident annular fissures were associated with incident chronic LBP, after adjustment for prior back pain and depression (adjusted odds ratio [OR] 6.6; 95% confidence interval [CI] 1.2-36.9). All participants with incident disc extrusions (OR 5.4) and nerve root impingement (OR 4.1) reported incident radicular symptoms, although associations were not statistically significant. No other incident MRI findings showed large magnitude associations with symptoms. CONCLUSIONS: Even when applying more specific definitions for spine-related symptom outcomes, few MRI findings showed large magnitude associations with symptom outcomes. Although incident annular fissures, disc extrusions, and nerve root impingement were associated with incident symptom outcomes, the 3-year incidence of these MRI findings was extremely low, and did not explain the vast majority of incident symptom cases

Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine

Patient-Centered Outcomes Measurement: Does It Require Information From Patients?

Purpose: Since collecting outcome measure data from patients can be expensive, time-consuming, and subject to memory and nonresponse bias, we sought to learn whether outcomes important to patients can be obtained from data in the electronic health record (EHR) or health insurance claims. Methods: We previously identified 21 outcomes rated important by patients who had advanced imaging tests for back or abdominal pain. Telephone surveys about experiencing those outcomes 1 year after their test from 321 people consenting to use of their medical record and claims data were compared with audits of the participants’ EHR progress notes over the time period between the imaging test and survey completion. We also compared survey data with algorithmically extracted data from claims files for outcomes for which data might be available from that source. Results: Of the 16 outcomes for which patients’ survey responses were considered to be the best information source, only 2 outcomes for back pain and 3 for abdominal pain had kappa scores above a very modest level of ≥ 0.2 for chart audit of EHR data and none for algorithmically obtained EHR/claims data. Of the other 5 outcomes for which claims data were considered to be the best information source, only 2 outcomes from patient surveys and 3 outcomes from chart audits had kappa scores ≥ 0.2. Conclusions: For the types of outcomes studied here, medical record or claims data do not provide an adequate source of information except for a few outcomes where patient reports may be less accurate

What is the role of imaging in acute low back pain?

In patients with non specific acute low back pain, without the red flags, a conservative approach is preferable, with assessment in 4–6 weeks. The natural history of low back pain is favorable with improvement over time, thus reassurance to such patients is very important. However, a plain radiograph or more advanced imaging techniques like MRI/CT may be ordered in back pain associated with radiculopathy or spinal stenosis and back pain associated with progressive neurologic deficits. There is limited role of imaging in non specific acute low back pain without the red flags, as the findings correlate poorly with symptoms

Returning genome sequences to research participants:Policy and practice

Despite advances in genomic science stimulating an explosion of literature around returning health-related findings, the possibility of returning entire genome sequences to individual research participants has not been widely considered. Through direct involvement in large-scale translational genomics studies, we have identified a number of logistical challenges that would need to be overcome prior to returning individual genome sequence data, including verifying that the data belong to the requestor and providing appropriate informatics support. In addition, we identify a number of ethico-legal issues that require careful consideration, including returning data to family members, mitigating against unintended consequences, and ensuring appropriate governance. Finally, recognising that there is an opportunity cost to addressing these issues, we make some specific pragmatic suggestions for studies that are considering whether to share individual genomic datasets with individual study participants. If data are shared, research should be undertaken into the personal, familial and societal impact of receiving individual genome sequence data

The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.

BACKGROUND: Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. DISCUSSION: Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. SUMMARY: Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care

Fin development in a cartilaginous fish and the origin of vertebrate limbs

Recent fossil finds and experimental analysis of chick and mouse embryos highlighted the lateral fin fold theory, which suggests that two pairs of limbs in tetrapods evolved by subdivision of an elongated single fin1. Here we examine fin development in embryos of the primitive cartilaginous fish, Scyliorhinus canicula (dogfish) using scanning electron microscopy and investigate expression of genes known to be involved in limb positioning, identity and patterning in higher vertebrates. Although we did not detect lateral fin folds in dogfish embryos, Engrailed-1 expression suggests that the body is compartmentalized dorso-ventrally. Furthermore, specification of limb identity occurs through the Tbx4 and Tbx5 genes, as in higher vertebrates. In contrast, unlike higher vertebrates, we did not detect Shh transcripts in dogfish fin-buds, although dHand (a gene involved in establishing Shh) is expressed. In S. canicula, the main fin axis seems to lie parallel to the body axis. 'Freeing' fins from the body axis and establishing a separate 'limb' axis has been proposed to be a crucial step in evolution of tetrapod limbs2, 3. We suggest that Shh plays a critical role in this process

Endoskeletal structure in Cheirolepis (Osteichthyes, Actinopterygii), An early ray-finned fish

As the sister lineage of all other actinopterygians, the Middle to Late Devonian (Eifelian–Frasnian) Cheirolepis occupies a pivotal position in vertebrate phylogeny. Although the dermal skeleton of this taxon has been exhaustively described, very little of its endoskeleton is known, leaving questions of neurocranial and fin evolution in early ray‐finned fishes unresolved. The model for early actinopterygian anatomy has instead been based largely on the Late Devonian (Frasnian) Mimipiscis, preserved in stunning detail from the Gogo Formation of Australia. Here, we present re‐examinations of existing museum specimens through the use of high‐resolution laboratory‐ and synchrotron‐based computed tomography scanning, revealing new details of the neuro‐cranium, hyomandibula and pectoral fin endoskeleton for the Eifelian Cheirolepis trailli. These new data highlight traits considered uncharacteristic of early actinopterygians, including an uninvested dorsal aorta and imperforate propterygium, and corroborate the early divergence of Cheirolepis within actinopterygian phylogeny. These traits represent conspicuous differences between the endoskeletal structure of Cheirolepis and Mimipiscis. Additionally, we describe new aspects of the parasphenoid, vomer and scales, most notably that the scales display peg‐and‐socket articulation and a distinct neck. Collectively, these new data help clarify primitive conditions within ray‐finned fishes, which in turn have important implications for understanding features likely present in the last common ancestor of living osteichthyans