Online vs in-person delivery of preclinical coursework: A retrospective cohort study evaluating National Board of Chiropractic Examiners performance.

OBJECTIVE: To evaluate the association between basic science curriculum delivery method with other academic and demographic factors on National Board of Chiropractic Examiners (NBCE) part I pass rates. METHODS: This was a retrospective cohort study of students from 3 campuses of 1 chiropractic institution who matriculated in 2018 or 2020. COVID-19 regulations required online delivery of a basic science curriculum for students in the 2020 cohorts, whereas students in the 2018 cohorts experienced a traditional classroom delivery. A general linear model estimated odds ratios for passing NBCE part I, comparing individual online cohorts with the combined classroom cohort while adjusting for academic and demographic variables. RESULTS: A total of 968 students were included, 55% from the classroom cohort. The spring 2020 cohort had the fewest students with bachelors' degrees (59%) and more students with high in-program grade point averages (GPA; 61%) along with the lowest estimated odds ratio [0.80 (95% CI: 0.73-0.87)] for passing vs the classroom cohort. The fall 2020 cohort had significantly higher odds [1.06 (95% CI: 1.00-1.03)] of passing vs the classroom cohort. Additional predictors included main campus matriculation, white ethnicity, bachelors' degree, no alternative admission status, and in-program GPA. Students with high in-program GPA (vs low) had a 36% increased odds of passing. CONCLUSION: Compared to the classroom cohort, the spring 2020 cohort had the lowest odds while the fall 2020 cohort had the highest odds of passing part I. In-program GPA had the highest association with passing. These results provide information on how curriculum delivery impacts board exam performance.

Dosing of lumbar spinal manipulative therapy and its association with escalated spine care: A cohort study of insurance claims.

OBJECTIVE: The objective of this study was to evaluate the relationship between three distinct spinal manipulative therapy dose groups and escalated spine care by analyzing insurance claims from a cohort of patients with low back pain. METHODS: We compared three distinct spinal manipulative therapy dose groups (low = 1 SMT visits, moderate = 2-12 SMT visits, high = 13+ SMT visits), to a control group (no spinal manipulative therapy) regarding the outcome of escalated spine care. Escalated spine care procedures include imaging studies, injection procedures, emergency department visits, surgery, and opioid medication use. Propensity score matching was performed to address treatment selection bias. Modified Poisson regression modeling was used to estimate the relative risk of spine care escalation among three spinal manipulative therapy doses, adjusting for age, sex, retrospective risk score and claim count. RESULTS: 83,025 claims were categorized into 11,114 unique low back pain episodes; 8,137 claims had 0 spinal manipulative therapy visits, with the remaining episodes classified as low dose (n = 404), moderate dose (n = 1,763) or high dose (n = 810). After propensity score matching, 5,348 episodes remained; 2,454 had 0 spinal manipulative therapy visits with the remaining episodes classified as low dose (n = 404), moderate dose (n = 1,761), or high dose (n = 729). The estimated relative risk (vs no spinal manipulative therapy) for any escalated spine care was 0.45 (95% confidence interval 0.38, 0.55, p <0.001), 0.58 (95% confidence interval 0.53, 0.63, p <0.001), and 1.03 (95% confidence interval 0.95, 1.13, p = 0.461) for low, moderate, and high dose spinal manipulative therapy groups, respectively. CONCLUSIONS: For claims associated with initial episodes of low back pain, low and moderate dose spinal manipulative therapy groups were associated with a 55% and 42% reduction, respectively, in the relative risk of any escalated spine care.

Predictors of Pain Management Strategies in Adults with Low-Back Pain: A Secondary Analysis of Amazon Mechanical Turk Survey Data.

Objective: To evaluate the associations between baseline demographics, health conditions, pain management strategies, and health-related quality-of-life (HRQoL) measures with pain management strategies at 3-month follow-up in respondents reporting current low-back pain (LBP). Study design: Cohort study of survey data collected from adults with LBP sampled from Amazon Mechanical Turk crowdsourcing panel. Methods: Demographics, health conditions, and the Patient-Reported Outcomes Measurement Information System (PROMIS)-10 were included in the baseline survey. Respondents reporting LBP completed a more comprehensive survey inquiring about pain management strategies and several HRQoL measures. Bivariate then multivariate logistic regression estimated odds ratios (ORs) with 95% confidence intervals (CIs) for the association between baseline characteristics and pain management utilization at 3-month follow-up. Model fit statistics were evaluated to assess the predictive value. Results: The final cohort included 717 respondents with completed surveys. The most prevalent pain management strategy at follow-up was other care (n = 474), followed by no care (n = 94), conservative care only (n = 76), medical care only (n = 51), and medical and conservative care combined (n = 22). The conservative care only group had higher (better) mental and physical health PROMIS-10 scores as opposed to the medical care only and combination care groups, which had lower (worse) physical health scores. In multivariate models, estimated ORs (95% CIs) for the association between baseline and follow-up pain management ranged from 4.6 (2.7-7.8) for conservative care only to 16.8 (6.9-40.7) for medical care only. Additional significant baseline predictors included age, income, education, workman's compensation claim, Oswestry Disability Index score, and Global Chronic Pain Scale grade. Conclusions: This study provides important information regarding the association between patient characteristics, HRQoL measures, and LBP-related pain management utilization.

Nonoperative Management of Lateral Epicondyle Tendinopathy: An Umbrella Review.

Objective: The primary objective of this review was to summarize systematic reviews and meta-analyses reporting on nonoperative management of lateral epicondyle tendinopathy. Methods: An umbrella review of all published systematic reviews and meta-analyses was performed. Three databases were searched using the key words "tennis elbow," "lateral epicondylitis," "non-operative," and "non-surgical modalities." The search was limited to English-language systematic reviews and meta-analyses between the years of 2000 and 2022. Results: There were 114 systematic reviews/meta-analyses, of which 35 met our inclusion criteria. These articles reviewed the following nonoperative management strategies: ultrasound, shockwave therapy, injection procedures, low-level laser therapy, joint mobilizations, exercise therapy, and electrophysical modalities. Exercise therapy was beneficial in decreasing pain regardless of dosage or type. Conflicting results were seen with ultrasound, laser, and shockwave therapy. Corticosteroid injections provided the most short-term pain relief, and platelet-rich plasma and autologous blood injections were most effective in the long term. Conclusion: A variety of nonoperative interventions were found to be effective for short- and long-term pain relief as well as functional improvement, with most interventions indicating mixed results. Due to variations in study populations and study quality, results should be interpreted with caution.

Guideline-concordant utilization of magnetic resonance imaging in adults receiving chiropractic manipulative therapy vs other care for radicular low back pain: a retrospective cohort study.

BACKGROUND: Lumbar magnetic resonance imaging (LMRI) is often performed early in the course of care, which can be discordant with guidelines for non-serious low back pain. Our primary hypothesis was that adults receiving chiropractic spinal manipulative therapy (CSMT) for incident radicular low back pain (rLBP) would have reduced odds of early LMRI over 6-weeks' follow-up compared to those receiving other care (a range of medical care, excluding CSMT). As a secondary hypothesis, CSMT recipients were also expected to have reduced odds of LMRI over 6-months' and 1-years' follow-up. METHODS: A national 84-million-patient health records database including large academic healthcare organizations (TriNetX) was queried for adults age 20-70 with rLBP newly-diagnosed between January 31, 2012 and January 31, 2022. Receipt or non-receipt of CSMT determined cohort allocation. Patients with prior lumbar imaging and serious pathology within 90 days of diagnosis were excluded. Propensity score matching controlled for variables associated with LMRI utilization (e.g., demographics). Odds ratios (ORs) of LMRI over 6-weeks', 6-months', and 1-years' follow-up after rLBP diagnosis were calculated. RESULTS: After matching, there were 12,353 patients per cohort (mean age 50 years, 56% female), with a small but statistically significant reduction in odds of early LMRI in the CSMT compared to other care cohort over 6-weeks' follow-up (9%, 10%, OR [95% CI] 0.88 [0.81-0.96] P = 0.0046). There was a small but statistically significant increase in odds of LMRI among patients in the CSMT relative to the other care cohort over 6-months' (12%, 11%, OR [95% CI] 1.10 [1.02-1.19], P < 0.0174) and 1-years' follow-up (14%, 12%, OR [95% CI] 1.21 [1.13-1.31], P < 0.0001). CONCLUSIONS: These results suggest that patients receiving CSMT for newly-diagnosed rLBP are less likely to receive early LMRI than patients receiving other care. However, CSMT recipients have a small increase in odds of LMRI over the long-term. Both cohorts in this study had a relatively low rate of early LMRI, possibly because the data were derived from academic healthcare organizations. The relationship of these findings to other patient care outcomes and cost should be explored in a future randomized controlled trial. REGISTRATION: Open Science Framework ( https://osf.io/t9myp ).

Risk of Treatment Escalation in Recipients vs Nonrecipients of Spinal Manipulation for Musculoskeletal Cervical Spine Disorders: An Analysis of Insurance Claims.

OBJECTIVE: The purpose of this study was to evaluate the relationship between treatment escalation and spinal manipulation in a retrospective cohort of people diagnosed with musculoskeletal disorders of the cervical spine. METHODS: We used retrospective analysis of insurance claims data (2012-2018) from a single Fortune 500 company. After isolating the first episode of care, we categorized 58 147 claims into 7951 unique patient episodes. Treatment escalation included claims where imaging, injection, emergency room, or surgery was present. Modified Poisson regression was used to determine the relative risk of treatment escalation comparing recipients vs nonrecipients of spinal manipulation, adjusted for age, sex, episode duration, and risk scores. RESULTS: The sample was 55% women, with a mean age of 44 years (range, 18-103). Treatment escalation was present in 42% of episodes overall: 2448 (46%) associated with other care and 876 (26%) associated with spinal manipulation. The estimated risk of any treatment escalation was 2.38 times higher in those who received other care than in those who received spinal manipulation (95% confidence interval, 2.22-2.55, P = .001). CONCLUSION: Among episodes of care associated with neck pain diagnoses, those associated with other care had twice the risk of any treatment escalation compared with those associated with spinal manipulation. In the United States, over 90% of spinal manipulation is provided by doctors of chiropractic; therefore, these findings are relevant and should be considered in addressing solutions for neck pain. Additional research investigating the factors influencing treatment escalation is necessary to moderate the use of high-cost and guideline-incongruent procedures in people with neck pain.

Three Patterns of Spinal Manipulative Therapy for Back Pain and Their Association With Imaging Studies, Injection Procedures, and Surgery: A Cohort Study of Insurance Claims.

OBJECTIVE: The purpose of this study was to evaluate the relationship between procedures and care patterns in back pain episodes by analyzing health insurance claims. METHODS: We performed a retrospective cohort study of insurance claims data from a single Fortune 500 company. The 3 care patterns we analyzed were initial spinal manipulative therapy, delayed spinal manipulative therapy, and no spinal manipulative therapy. The 3 procedures analyzed were imaging studies, injection procedures, and back surgery. We considered "escalated care" to be any claims with diagnostic imaging, injection procedures, or back surgery. Modified-Poisson regression modeling was used to determine relative risk of escalated care. RESULTS: There were 83 025 claims that were categorized into 10 372 unique patient first episodes. Spinal manipulative therapy was present in 2943 episodes (28%). Initial spinal manipulation was present in 2519 episodes (24%), delayed spinal manipulation was present in 424 episodes (4%), and 7429 (72%) had no evidence of spinal manipulative therapy. The estimated relative risk, adjusted for age, sex, and risk score, for care escalation (eg, imaging, injections, or surgery) was 0.70 (95% confidence interval 0.65-0.75, P < .001) for initial spinal manipulation and 1.22 (95% confidence interval 1.10-1.35, P < .001) for delayed spinal manipulation with no spinal manipulation used as the reference group. CONCLUSION: For claims associated with initial episodes of back pain, initial spinal manipulative therapy was associated with an approximately 30% decrease in the risk of imaging studies, injection procedures, or back surgery compared with no spinal manipulative therapy. The risk of imaging studies, injection procedures, or back surgery in episodes in the delayed spinal manipulative therapy group was higher than those without spinal manipulative therapy.

Allele-Selective Knockdown of MYH7 Using Antisense Oligonucleotides.

Hundreds of dominant-negative myosin mutations have been identified that lead to hypertrophic cardiomyopathy, and the biomechanical link between mutation and disease is heterogeneous across this patient population. To increase the therapeutic feasibility of treating this diverse genetic population, we investigated the ability of locked nucleic acid (LNA)-modified antisense oligonucleotides (ASOs) to selectively knock down mutant myosin transcripts by targeting single-nucleotide polymorphisms (SNPs) that were found to be common in the myosin heavy chain 7 (MYH7) gene. We identified three SNPs in MYH7 and designed ASO libraries to selectively target either the reference or alternate MYH7 sequence. We identified ASOs that selectively knocked down either the reference or alternate allele at all three SNP regions. We also show allele-selective knockdown in a mouse model that was humanized on one allele. These results suggest that SNP-targeting ASOs are a promising therapeutic modality for treating cardiac pathology.

Exploration of pathomechanisms triggered by a single-nucleotide polymorphism in titin's I-band: the cardiomyopathy-linked mutation T2580I.

Missense single-nucleotide polymorphisms (mSNPs) in titin are emerging as a main causative factor of heart failure. However, distinguishing between benign and disease-causing mSNPs is a substantial challenge. Here, we research the question of whether a single mSNP in a generic domain of titin can affect heart function as a whole and, if so, how. For this, we studied the mSNP T2850I, seemingly linked to arrhythmogenic right ventricular cardiomyopathy (ARVC). We used structural biology, computational simulations and transgenic muscle in vivo methods to track the effect of the mutation from the molecular to the organismal level. The data show that the T2850I exchange is compatible with the domain three-dimensional fold, but that it strongly destabilizes it. Further, it induces a change in the conformational dynamics of the titin chain that alters its reactivity, causing the formation of aberrant interactions in the sarcomere. Echocardiography of knock-in mice indicated a mild diastolic dysfunction arising from increased myocardial stiffness. In conclusion, our data provide evidence that single mSNPs in titin's I-band can alter overall muscle behaviour. Our suggested mechanisms of disease are the development of non-native sarcomeric interactions and titin instability leading to a reduced I-band compliance. However, understanding the T2850I-induced ARVC pathology mechanistically remains a complex problem and will require a deeper understanding of the sarcomeric context of the titin region affected.

Single molecule force spectroscopy on titin implicates immunoglobulin domain stability as a cardiac disease mechanism.

Titin plays crucial roles in sarcomere organization and cardiac elasticity by acting as an intrasarcomeric molecular spring. A mutation in the tenth Ig-like domain of titin's spring region is associated with arrhythmogenic cardiomyopathy, a disease characterized by ventricular arrhythmias leading to cardiac arrest and sudden death. Titin is the first sarcomeric protein linked to arrhythmogenic cardiomyopathy. To characterize the disease mechanism, we have used atomic force microscopy to directly measure the effects that the disease-linked point mutation (T16I) has on the mechanical and kinetic stability of Ig10 at the single molecule level. The mutation decreases the force needed to unfold Ig10 and increases its rate of unfolding 4-fold. We also found that T16I Ig10 is more prone to degradation, presumably due to compromised local protein structure. Overall, the disease-linked mutation weakens the structural integrity of titin's Ig10 domain and suggests an Ig domain disease mechanism.

Titin-based tension in the cardiac sarcomere: molecular origin and physiological adaptations.

The passive stiffness of cardiac muscle plays a critical role in ventricular filling during diastole and is determined by the extracellular matrix and the sarcomeric protein titin. Titin spans from the Z-disk to the M-band of the sarcomere and also contains a large extensible region that acts as a molecular spring and develops passive force during sarcomere stretch. This extensible segment is titin's I-band region, and its force-generating mechanical properties determine titin-based passive tension. The properties of titin's I-band region can be modulated by isoform splicing and post-translational modification and are intimately linked to diastolic function. This review discusses the physical origin of titin-based passive tension, the mechanisms that alter titin stiffness, and titin's role in stress-sensing signaling pathways.

The effects of PKCalpha phosphorylation on the extensibility of titin's PEVK element.

Post-translational modifications, along with isoform splicing, of titin determine the passive tension development of stretched sarcomeres. It was recently shown that PKCalpha phosphorylates two highly-conserved residues (S26 and S170) of the PEVK region in cardiac titin, resulting in passive tension increase. To determine how each phosphorylated residue affects myocardial stiffness, we generated three recombinant mutant PEVK fragments (S26A, S170A and S170A/S26A), each flanked by Ig domains. Single-molecule force spectroscopy shows that PKCalpha decreases the PEVK persistence length (from 0.99 to 0.68 nm); the majority of this decrease is attributable to phosphorylation of S26. Before PKCalpha, all three mutant PEVK fragments showed at least 40% decrease in persistence length compared to wildtype. Furthermore, Ig domain unfolding force measurements indicate that PEVK's flanking Ig domains are relatively unstable compared to other titin Ig domains. We conclude that phosphorylation of S26 is the primary mechanism through which PKCalpha modulates cardiac stiffness.