Red flags presented in current low back pain guidelines: a review.

OBJECTIVE: The purpose of this study was to identify and descriptively compare the red flags endorsed in guidelines for the detection of serious pathology in patients presenting with low back pain to primary care. METHOD: We searched databases, the World Wide Web and contacted experts aiming to find the multidisciplinary clinical guideline in low back pain in primary care, and selected the most recent one per country. We extracted data on the number and type of red flags for identifying patients with higher likelihood of serious pathology. Furthermore, we extracted data on whether or not accuracy data (sensitivity/specificity, predictive values, etc.) were presented to support the endorsement of specific red flags. RESULTS: We found 21 discrete guidelines all published between 2000 and 2015. One guideline could not be retrieved and after selecting one guideline per country we included 16 guidelines in our analysis from 15 different countries and one for Europe as a whole. All guidelines focused on the management of patients with low back pain in a primary care or multidisciplinary care setting. Five guidelines presented red flags in general, i.e., not related to any specific disease. Overall, we found 46 discrete red flags related to the four main categories of serious pathology: malignancy, fracture, cauda equina syndrome and infection. The majority of guidelines presented two red flags for fracture ('major or significant trauma' and 'use of steroids or immunosuppressors') and two for malignancy ('history of cancer' and 'unintentional weight loss'). Most often pain at night or at rest was also considered as a red flag for various underlying pathologies. Eight guidelines based their choice of red flags on consensus or previous guidelines; five did not provide any reference to support the choice of red flags, three guidelines presented a reference in general, and data on diagnostic accuracy was rarely provided. CONCLUSION: A wide variety of red flags was presented in guidelines for low back pain, with a lack of consensus between guidelines for which red flags to endorse. Evidence for the accuracy of recommended red flags was lacking

A critical role for the chromatin remodeller CHD7 in anterior mesoderm during cardiovascular development

CHARGE syndrome is caused by spontaneous loss-of-function mutations to the ATP-dependant chromatin remodeller chromodomain-helicase-DNA-binding protein 7 (CHD7). It is characterised by a distinct pattern of congenital anomalies, including cardiovascular malformations. Disruption to the neural crest lineage has previously been emphasised in the aetiology of this developmental disorder. We present evidence for an additional requirement for CHD7 activity in the Mesp1-expressing anterior mesoderm during heart development. Conditional ablation of Chd7 in this lineage results in major structural cardiovascular defects akin to those seen in CHARGE patients, as well as a striking loss of cardiac innervation and embryonic lethality. Genome-wide transcriptional analysis identified aberrant expression of key components of the Class 3 Semaphorin and Slit-Robo signalling pathways in Chd7(fl/fl);Mesp1-Cre mutant hearts. CHD7 localises at the Sema3c promoter in vivo, with alteration of the local chromatin structure seen following Chd7 ablation, suggestive of direct transcriptional regulation. Furthermore, we uncover a novel role for CHD7 activity upstream of critical calcium handling genes, and demonstrate an associated functional defect in the ability of cardiomyocytes to undergo excitation-contraction coupling. This work therefore reveals the importance of CHD7 in the cardiogenic mesoderm for multiple processes during cardiovascular development

Neuromatch Academy: a 3-week, online summer school in computational neuroscience

Neuromatch Academy (https://academy.neuromatch.io; (van Viegen et al., 2021)) was designed as an online summer school to cover the basics of computational neuroscience in three weeks. The materials cover dominant and emerging computational neuroscience tools, how they complement one another, and specifically focus on how they can help us to better understand how the brain functions. An original component of the materials is its focus on modeling choices, i.e. how do we choose the right approach, how do we build models, and how can we evaluate models to determine if they provide real (meaningful) insight. This meta-modeling component of the instructional materials asks what questions can be answered by different techniques, and how to apply them meaningfully to get insight about brain function

Red flags presented in current low back pain guidelines: a review

textabstractObjective: The purpose of this study was to identify and descriptively compare the red flags endorsed in guidelines for the detection of serious pathology in patients presenting with low back pain to primary care. Method: We searched databases, the World Wide Web and contacted experts aiming to find the multidisciplinary clinical guideline in low back pain in primary care, and selected the most recent one per country. We extracted data on the number and type of red flags for identifying patients with higher likelihood of serious pathology. Furthermore, we extracted data on whether or not accuracy data (sensitivity/specificity, predictive values, etc.) were presented to support the endorsement of specific red flags. Results: We found 21 discrete guidelines all published between 2000 and 2015. One guideline could not be retrieved and after selecting one guideline per country we included 16 guidelines in our analysis from 15 different countries and one for Europe as a whole. All guidelines focused on the management of patients with low back pain in a primary care or multidisciplinary care setting. Five guidelines presented red flags in general, i.e., not related to any specific disease. Overall, we found 46 discrete red flags related to the four main categories of serious pathology: malignancy, fracture, cauda equina syndrome and infection. The majority of guidelines presented two red flags for fracture (‘major or significant trauma’ and ‘use of steroids or immunosuppressors’) and two for malignancy (‘history of cancer’ and ‘unintentional weight loss’). Most often pain at night or at rest was also considered as a red flag for various underlying pathologies. Eight guidelines based their choice of red flags on consensus or previous guidelines; five did not provide any reference to support the choice of red flags, three guidelines presented a reference in general, and data on diagnostic accuracy was rarely provided. Conclusion: A wide variety of red flags was presented in guidelines for low back pain, with a lack of consensus between guidelines for which red flags to endorse. Evidence for the accuracy of recommended red flags was lacking