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BackgroundPatients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.Patients and methodsPatients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients).ResultsA total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality.ConclusionsClinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies.Clinical trial identifierNCT04354701.

Despite the apparent ease with which sheets of paper are crumpled and tossed away, crumpling dynamics are often considered a paradigm of complexity. This arises from the infinite number of configurations that disordered, crumpled sheets can take. Here we experimentally show that key aspects of axially confined crumpled Mylar sheets have a very simple description; evolution of damage in crumpling dynamics can largely be described by a single global quantity—the total length of creases. We follow the evolution of the damage network in repetitively crumpled elastoplastic sheets, and show that the dynamics are deterministic, depending only on the instantaneous state of the crease network and not on the crumpling history. We also show that this global quantity captures the crumpling dynamics of a sheet crumpled for the first time. This leads to a remarkable reduction in complexity, allowing a description of a highly disordered system by a single state parameter.

STUDY DESIGN: Prospective, multicenter, cohort study. OBJECTIVE: To examine which clinical and sociodemographic baseline variables can predict a favorable outcome in subjects with neck pain treated by chiropractors. SUMMARY OF BACKGROUND DATA: Relatively little is known on predictors of neck pain, particularly for those subjects undergoing chiropractic care. No previous study has examined predictors of outcome for subjects with neck pain by modeling the trajectories of subjects in a longitudinal design. METHODS: All new, consecutive patients, between 18 and 65 years of age with neck pain of any duration, who had not undergone chiropractic or manual therapy in the prior 3 months, were recruited. Questionnaires were administered at the first 3 visits, and at 3 and 12 months. In all, 29 putative prognostic baseline variables were evaluated. Multivariate multilevel longitudinal regression analyses were conducted using neck pain, neck disability, and perceived recovery as outcomes. RESULTS: In total, 529 patients fulfilled the inclusion criteria. The response rate at 12-months was 92%. In the multivariate analyses, 14 (48%) of the prognostic variables examined were retained in at least one of the models. Shorter duration of neck pain at the first visit was the only variable retained in all 3 final regression models. The following were predictive of a favorable outcome for any 2 of the 3 outcome measures examined: intermittent neck pain, those not on sick-leave or receiving workers compensation at baseline, a higher level of education, less tiredness, higher expectations that the treatment would be beneficial, lack of morning pain, and worse perceived general health. CONCLUSION: On the basis of the patient's history, the clinician can identify a number of determinants, which are predictive of a favorable outcome. Shorter duration of neck pain at the first visit was the only variable consistently found to be predictive of a favorable outcome for all 3 outcome measures examined. [ABSTRACT FROM AUTHOR]

STUDY DESIGN.: Systematic review of interventions. OBJECTIVE.: To assess the effects of spinal manipulative therapy (SMT) for acute low back pain. SUMMARY OF BACKGROUND DATA.: SMT is one of many therapies for the treatment of low back pain, which is a worldwide, extensively practiced intervention. METHODS.: An experienced librarian searched for randomized controlled trials (RCTs) in multiple databases up to March 13, 2011. RCTs that examined manipulation or mobilization in adults with acute low back pain (<6-week duration) were included. The primary outcomes were pain, functional status and perceived recovery. Secondary outcomes were return-to-work and quality of life. Two authors independently conducted the study selection, risk of bias assessment and data extraction. GRADE (grading of recommendations assessment, development, and evaluation) was used to assess the quality of the evidence. The effects were examined for SMT versus (1) inert interventions, (2) sham SMT, (3) other interventions, and (4) SMT as adjunct therapy. RESULTS.: We identified 20 RCTs (total participants = 2674), 12 (60%) of which were not included in the previous review. In total, 6 trials (30% of all included studies) had a low risk of bias. In general, for the outcomes of pain and functional status, there is low- to very low-quality evidence suggesting no difference in effect for SMT when compared with inert interventions, sham SMT or as adjunct therapy. There was varying quality of evidence (from very low to moderate) suggesting no difference in effect for SMT when compared with other interventions. Data were particularly sparse for recovery, return-to-work, quality of life, and costs of care. No serious complications were observed with SMT. CONCLUSION.: SMT is no more effective for acute low back pain than inert interventions, sham SMT or as adjunct therapy. SMT also seems to be no better than other recommended therapies. Our evaluation is limited by the few numbers of studies; therefore, future research is likely to have an important impact on these estimates. Future RCTs should examine specific subgroups and include an economic evaluation. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: Systematic review of interventions. OBJECTIVE: To assess the effects of spinal manipulative therapy (SMT) for chronic low-back pain. SUMMARY OF BACKGROUND DATA: SMT is one of the many therapies for the treatment of low-back pain, which is a worldwide, extensively practiced intervention. METHODS: Search methods. An experienced librarian searched for randomized controlled trials (RCTs) in multiple databases up to June 2009. Selection criteria. RCTs that examined manipulation or mobilization in adults with chronic low-back pain were included. The primary outcomes were pain, functional status, and perceived recovery. Secondary outcomes were return-to-work and quality of life. Data collection and analysis. Two authors independently conducted the study selection, risk of bias assessment, and data extraction. GRADE was used to assess the quality of the evidence. RESULTS: We included 26 RCTs (total participants = 6070), 9 of which had a low risk of bias. Approximately two-thirds of the included studies (N = 18) were not evaluated in the previous review. There is a high-quality evidence that SMT has a small, significant, but not clinically relevant, short-term effect on pain relief (mean difference -4.16, 95% confidence interval -6.97 to -1.36) and functional status (standardized mean difference -0.22, 95% confidence interval -0.36 to -0.07) in comparison with other interventions. There is varying quality of evidence that SMT has a significant short-term effect on pain relief and functional status when added to another intervention. There is a very low-quality evidence that SMT is not more effective than inert interventions or sham SMT for short-term pain relief or functional status. Data were particularly sparse for recovery, return-to-work, quality of life, and costs of care. No serious complications were observed with SMT. CONCLUSIONS: High-quality evidence suggests that there is no clinically relevant difference between SMT and other interventions for reducing pain and improving function in patients with chronic low-back pain. Determining cost-effectiveness of care has high priority. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: A prospective cohort study on chiropractic patients with neck pain. OBJECTIVE: To examine the association between self-reported benign adverse events after chiropractic care for neck pain and the outcome measures namely, perceived recovery, neck pain, and neck disability. SUMMARY OF BACKGROUND DATA: Only 1 study has examined the association between adverse events and outcome in subjects with neck pain treated by chiropractors, which concluded that those receiving cervical spinal manipulation were more likely to report an adverse event compared to cervical mobilization, and those reporting an adverse event were less likely to have improved outcomes at all follow-up measurements. METHODS: This was a prospective, multicenter, observational cohort study conducted in the private clinics of chiropractors throughout The Netherlands. All new, consecutive patients, between 18 and 65 years of age with neck pain of any duration, who had not undergone chiropractic or manual therapy in the prior 3 months, were eligible for recruitment. Self-reported questionnaires were administered at the first 3 visits and at 3 months. Multivariate multilevel logistic and linear regression analyses were used to evaluate the association between adverse events and recovery, neck pain, and neck disability. Outcomes were measured at the fourth visit and at 3 months. RESULTS: In total, 529 patients were recruited who fulfilled the inclusion criteria. The response rate at 3 months was 90%. At the fourth visit, subjects who reported a benign adverse event or 'intense' adverse event after any of the first 3 visits were less likely to be recovered, and had slightly worse levels of neck pain. However, the differences in neck pain were too small to be clinically meaningful. Intense adverse events, on the other hand, were not only associated with more neck disability but also clinically relevant differences. At 3 months, adverse events were not associated with better or worse outcomes for any of the three outcome measures examined. CONCLUSION: Self-reported benign adverse events after chiropractic care for neck pain are associated with worse short-term outcomes. Intense adverse events are associated with more neck disability and clinically relevant differences at the short-term only. However, there is no association between adverse events and worse outcomes at 3 months. [ABSTRACT FROM AUTHOR]

Background: To describe the societal costs during one year of follow-up among older adults seeking chiropractic care due to a new episode of low back pain (LBP), and to determine what factors predict high societal costs in this population., Methods: Prospective cohort study, within chiropractic private practices (n = 38) in the Netherlands. 223 people ≥ 55 years of age with a new episode of LBP seeking chiropractic care participated. The primary outcome was total societal costs. High societal costs were defined as patients with costs in the top 20th percentile. The final prediction models were obtained using forward selection. Results were presented for the total population and stratified for retirement status. The model's prognostic accuracy (Hosmer-Lemeshow X 2 , Nagelkerke's R 2 ) and discriminative ability [area under the receiver operating curve (AUC)] were assessed, and the models were internally validated using bootstrapping., Results: The mean total annual societal cost per patient was €5297 [95% confidence interval (CI): 4191-6403]. The biggest cost driver was presenteeism (65% of total costs), and costs were higher among non-retired participants (€7759; 95% CI 6047-9470) than retired participants (€1892; 95% CI 1088-2695). In the total population, younger age [odds ratio (OR): 0.87 for each additional year; 95% CI 0.80-0.95], being male instead of female (OR 2.96; 95% CI 1.19-7.44), less alcohol intake (OR 0.49; 95% CI 0.20-1.19), working instead of retirement (OR 9.37; 95% CI 1.83-48.04), and more disability at baseline (OR 1.08; 95% CI 1.00-1.16) were found to be predictive of high societal costs. Working was found to be the strongest predictor for high societal costs. After internal validation, the model's fit was good, it's explained variance was moderate (28%) and their AUCs could be interpreted as moderate (0.85). For non-pensioners, the same predictive factors were identified as for the entire population. The costs for the retired participants showed too little variation to be able to predict high costs., Conclusions: This study estimated the mean total annual societal cost of older adults seeking chiropractic care due to a new episode of LBP at €5297 (95% CI 4191-6403).These costs were mainly due to high levels of presenteeism, and extensively differed based upon work status., (© 2024. The Author(s).)

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an increasingly recognized disorder that occurs due to somatic mutations of a ubiquitin-activating enzyme encoded by ubiquitin-like modifier activating enzyme 1 gene, UBA1. Clinical findings associated with VEXAS syndrome include recurrent fevers, polychondritis, periorbital edema, pleural effusions, myocarditis and/or pericarditis, hepatosplenomegaly, myelodysplastic syndrome, cytopenias, inflammatory arthritis, neutrophilic dermatosis, and deep venous thrombosis. Novel renal manifestations like interstitial nephritis are infrequent, and to our knowledge, acute renal failure due to C3 glomerulonephritis (C3GN) has not yet been reported. Overwhelming systemic inflammation can result in morbid end-organ damage and death. While there is no formal guideline or established protocol for its management, treatment of VEXAS syndrome with tocilizumab, an interleukin-6 (IL-6)-directed therapy, has been described in the literature. Here, we report a case of a 71-year-old male patient presenting with C3GN as an initial manifestation of VEXAS syndrome and explore the rationale for our approach to treatment with IL-6 blockade. Our patient was initially treated with two inpatient doses of tocilizumab with successful transition to siltuximab in the outpatient setting. He continues to benefit from ongoing siltuximab treatment for more than one year to date without any safety issues or relapse of VEXAS syndrome., (© 2024. The Author(s).)

Introduction: The therapeutic landscape in relapsed/refractory multiple myeloma (RRMM) has changed rapidly, with twenty-two drug approvals since 2012. We characterized population-level trends in RRMM therapy selection, survival and cost outcomes associated with RRMM treatment over time., Materials and Methods: Our cohort included adults diagnosed with multiple myeloma (MM) in the SEER-Medicare database from 2007-2017 who received at least one antimyeloma agent. MM-directed therapies and lines of therapy were identified. Changes in 2LT regimens over time were described. Trends in overall survival from 2LT initiation over time were analyzed using a Cox proportional hazards model adjusting for factors associated with survival in MM. Trends in mean inflation-adjusted cost per 12 months of 2LT were analyzed using JoinPoint analysis., Results: A total of 9,822 patients met eligibility criteria, of whom 5,866 (59.7%) received 2LT. By 2018, 46% of 2LT regimens contained at least one agent approved in 2012 or later. Year of 2LT initiation was associated with improved overall survival (HR 0.78 per 5 years, 95% CI 0.74-0.84) after adjustment. Costs associated with 2LT increased over the study period, and the rate of cost increase increased significantly after 2012 (0.89%/year vs. 9.9%/year, P < .001), with higher total costs for regimens containing newer novel agents (mean $224,193 vs. $189,381, P < .001) CONCLUSION: Overall survival after initiation of 2LT has improved, however this has been accompanied by significant increases in costs of RRMM treatment, particularly for patients receiving newer novel agents. These findings provide useful context for existing and future drug approvals in RRMM., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The smallest worthwhile effect (SWE) is the smallest beneficial effect of an intervention that justifies the costs, risks, and inconveniences. The objective is to establish the SWE of spinal manipulative therapy (SMT) for the treatment of low back pain (LBP), and to gain insight into how different attributes of the treatment are traded among each other when choosing SMT. Part 1. A mixed-methods study will be conducted to establish and prioritize a list of attributes influencing choices for those who consider SMT for the treatment of LBP. Individual interviews and consensus groups with chiropractors, manual therapists, and osteopaths and their patients will be conducted. Interviews and consensus groups will be voice-recorded and transcribed verbatim. Part 2. A Discrete Choice Experiment (DCE) will be conducted among people with LBP who have limited to no experience with SMT. Participants will be recruited through an online independent panel company. The survey will consist of several choice sets with attributes and their levels established from Part 1. The DCE will be preceded by a short survey to understand the clinical aspects (i.e. presentation, history and previous treatment for LBP) as well as socio-demographic characteristics of the participants., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Three authors (LDLR, ADZ and SMR) are chiropractors who work in clinical practice, but have no direct financial interests linked with this survey., (© 2024 The Authors. Published by Elsevier B.V.)

In chronic musculoskeletal conditions, the prognosis tends to be more informative than the diagnosis for the future course of the disease. Many studies have identified clusters of patients who seemingly share similar pain trajectories. In a dataset of low back pain (LBP) patients, pain trajectories have been identified, and distinct trajectory types have been defined, making it possible to create pattern recognition software that can classify patients into respective pain trajectories reflecting their condition. It has been suggested that the classification of pain trajectories may create clinically meaningful subgroups of patients in an otherwise heterogeneous population of patients with LBP. A software tool was created that combined the ability to recognise the pain trajectory of patients with a system that could create subgroups of patients based on their characteristics. This tool is primarily meant for researchers to analyse trends in large heterogeneous datasets without large losses of data. Prospective analysis of pain trajectories is not directly helpful for clinicians. However, the tool might aid in the identification of patient characteristics which have predictive capabilities of the most likely trajectory a patient might experience in the future. This will help clinicians to tailor their advice and treatment for a specific patient., (© 2024. The Author(s).)

Objective: To assess the effectiveness of exercise for acute non-specific low back pain (LBP) vs our main comparisons: (1) sham treatment and (2) no treatment at short term (main follow-up time)., Data Sources and Study Selection: A comprehensive search up till November 2021 was conducted in numerous databases for randomized controlled trials on the effectiveness of exercise in adults with acute LBP (<6 weeks). Studies examining LBP with a specific etiology were excluded. The primary outcomes were back pain, back-specific functional status, and recovery., Data Extraction: Two review authors independently conducted the study selection, risk of bias assessment, and data extraction. GRADE was used to assess the certainty of the evidence., Data Synthesis: We identified 23 randomized controlled trials (2674 participants). There is very low-certainty evidence that exercise therapy compared with sham/placebo treatment has no clinically relevant effect on pain (mean difference [MD] -0.80, 95% confidence interval [CI] -5.79 to 4.19; 1 study, 299 participants) and on functional status (MD 2.00, 95% CI -2.20 to 6.20; 1 study, 299 participants) in the short term. There is very low-quality evidence which suggests no difference in effect on pain and functional status for exercise vs no treatment (2 studies; n=157, not pooled due to heterogeneity) at short-term follow-up. Similar results were found for the other follow-up moments. The certainty of the evidence was downgraded because many randomized controlled trials had a high risk of bias, were small in size, and/or there was substantial heterogeneity., Conclusion: Exercise therapy compared with sham/placebo and no treatment may have no clinically relevant effect on pain or functional status in the short term in people with acute non-specific LBP, but the evidence is very uncertain. Owing to insufficient reporting of adverse events, we were unable to reach any conclusions on the safety or harms related to exercise therapy., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study investigates the association between circulating microRNA (miRNA) expression and cardiovascular adverse events (CVAE) in multiple myeloma (MM) patients treated with a carfilzomib (CFZ)-based regimen. A cohort of 60 MM patients from the Prospective Observation of Cardiac Safety with Proteasome Inhibitor (PROTECT) study was analyzed. Among these, 31 patients (51.6%) developed CVAE post-CFZ treatment. The Taqman OpenArray Human microRNA panels were used for miRNA profiling. We identified 13 differentially expressed miRNAs at baseline, with higher expressions of miR-125a-5p, miR-15a-5p, miR-18a-3p, and miR-152-3p and lower expression of miR-140-3p in patients who later developed CVAE compared to those free of CVAE, adjusting for age, gender, race, and higher B-type natriuretic peptide levels. We also identified three miRNAs, including miR-150-5p, that were differentially expressed in patients with and without CVAE post-treatment. Additionally, five miRNAs responded differently to CFZ treatment in CVAE vs. non-CVAE patients, including significantly elevated post-treatment expression of miR-140-3p and lower expressions of miR-598, miR-152, miR-21, and miR-323a in CVAE patients. Pathway enrichment analysis highlighted the involvement of these miRNAs in cardiovascular diseases and vascular processes. These findings suggest that specific miRNAs could serve as predictive biomarkers for CVAE and provide insights into the underlying mechanisms of CFZ-CVAE. Further investigation is warranted before these findings can be applied in clinical settings.

Background: Research waste is defined as research outcomes with no or minimal societal benefits. It is a widespread problem in the healthcare field. Four primary sources of research waste have been defined: (1) irrelevant or low priority research questions, (2) poor design or methodology, (3) lack of publication, and (4) biased or inadequate reporting. This commentary, which was developed by a multidisciplinary group of researchers with spinal manipulative therapy (SMT) research expertise, discusses waste in SMT research and provides suggestions to improve future research., Main Text: This commentary examines common sources of waste in SMT research, focusing on design and methodological issues, by drawing on prior research and examples from clinical and mechanistic SMT studies. Clinical research is dominated by small studies and studies with a high risk of bias. This problem is compounded by systematic reviews that pool heterogenous data from varying populations, settings, and application of SMT. Research focusing on the mechanisms of SMT often fails to address the clinical relevance of mechanisms, relies on very short follow-up periods, and has inadequate control for contextual factors., Conclusions: This call to action is directed to researchers in the field of SMT. It is critical that the SMT research community act to improve the way research is designed, conducted, and disseminated. We present specific key action points and resources, which should enhance the quality and usefulness of future SMT research., (© 2024. The Author(s).)

Background: The Global Patient Safety Action Plan, an initiative of the World Health Organization (WHO), draws attention to patient safety as being an issue of utmost importance in healthcare. In response, the World Federation of Chiropractic (WFC) has established a Global Patient Safety Task Force to advance a patient safety culture across all facets of the chiropractic profession. This commentary aims to introduce principles and call upon the chiropractic profession to actively engage with the Global Patient Safety Action Plan beginning immediately and over the coming decade., Main Text: This commentary addresses why the chiropractic profession should pay attention to the WHO Global Patient Safety Action Plan, and what actions the chiropractic profession should take to advance these objectives. Each strategic objective identified by WHO serves as a focal point for reflection and action. Objective 1 emphasizes the need to view each clinical interaction as a chance to improve patient safety through learning. Objective 2 urges the implementation of frameworks that dismantle systemic obstacles, minimizing human errors and strengthening patient safety procedures. Objective 3 supports the optimization of clinical process safety. Objective 4 recognizes the need for patient and family engagement. Objective 5 describes the need for integrated patient safety competencies in training programs. Objective 6 explains the need for foundational data infrastructure, ecosystem, and culture. Objective 7 emphasizes that patient safety is optimized when healthcare professionals cultivate synergy and partnerships., Conclusions: The WFC Global Patient Safety Task Force provides a structured framework for aligning essential considerations for patient safety in chiropractic care with WHO strategic objectives. Embracing the prescribed action steps offers a roadmap for the chiropractic profession to nurture an inclusive and dedicated culture, placing patient safety at its core. This commentary advocates for a concerted effort within the chiropractic community to commit to and implement these principles for the collective advancement of patient safety., (© 2024. The Author(s).)

As a treatment for relapsed or refractory multiple myeloma (MM), carfilzomib has been associated with a significant risk of cardiovascular adverse events (CVAE). The goals of our study were to evaluate the metabolomic profile of MM patients to identify those at high risk prior to carfilzomib treatment and to explore the mechanisms of carfilzomib-CVAE to inform potential strategies to protect patients from this cardiotoxicity. Global metabolomic profiling was performed on the baseline and post-baseline plasma samples of 60 MM patients treated with carfilzomib-based therapy, including 31 who experienced CVAE, in a prospective cohort study. Baseline metabolites and post-baseline/baseline metabolite ratios that differ between the CVAE and no-CVAE patients were identified using unadjusted and adjusted methods. A baseline metabolomic risk score was created to stratify patients. We observed a lower abundance of tauroursodeoxycholic acid (T-UDCA) in CVAE patients at baseline (odds ratio [OR] = 0.47, 95% confidence interval [CI] = 0.21-0.94, p = 0.044) compared with the no-CVAE patients. A metabolite risk score was able to stratify patients into three risk groups. The area under the receiver-operating curve of the model with clinical predictors and metabolite risk score was 0.93. Glycochenodeoxycholic acid (OR = 0.56, 95% CI = 0.31-0.87, p = 0.023) was significantly lower in post-baseline/baseline ratios of CVAE patients compared with no-CVAE patients. Following metabolomic analysis, we created a baseline metabolite risk score that can stratify MM patients into different risk groups. The result also provided intriguing clues about the mechanism of carfilzomib-CVAE and potential cardioprotective strategies., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Little is known about lived experience of synchronous telehealth in patients with musculoskeletal (MSK) disorders., Objective: We conducted a rapid systematic review to answer: (1) what are the lived experiences and/or perspectives of people with MSK disorders receiving non-pharmacological interventions delivered through synchronous telehealth; and (2) what clinical implications can be inferred from qualitative studies focusing on lived experiences for how telehealth is delivered in the management of MSK disorders?, Data Sources: A comprehensive search of MEDLINE, CINAHL, PsycINFO, ProQuest, and Google Scholar from June 2010 to July 2023. Eligible qualitative and mixed methods studies capturing lived experiences of adults with MSK disorders receiving non-pharmacological interventions via synchronous telehealth were included., Study Methods: Systematic rapid review conducted according to WHO guidelines. Titles and abstracts screened by reviewers independently, eligible studies critically appraised, and data was extracted. Themes summarized using the Consolidated Framework for Implementation Research (CFIR). GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) used to assess confidence in synthesis findings., Results: We identified 9782 references, screened 8029, and critically appraised 22, and included 17 studies. There is evidence to suggest that the experience of telehealth prior to and during the pandemic was shaped by (1) patient perception of telehealth, (2) existing relationships with practitioners, (3) availability and accessibility of telehealth technologies, and (4) perceptions about the importance of the role of the physical exam in assessing and treating MSK disorders., Conclusion: The five identified implications could be used to inform future research, policy, and strategy development., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Introduction: Geriatric assessment (GA)-guided supportive care programs have been successful in improving treatment outcomes for older adults with solid-organ cancers. This study aimed to evaluate the feasibility of a GA-guided supportive care program among older adults treated for multiple myeloma (MM)., Materials and Methods: The study utilized an existing registry of adults with plasma cell disorders at the University of North Carolina. Patients with MM, aged 60 or older, and having a GA-identified deficit in one or more problem area were offered referrals to supportive care resources during routine visits. Problem areas included physical function deficits, polypharmacy, and anxiety or depression. Patients with physical function deficits were offered referral to physical therapy (PT), those with polypharmacy to an Oncology Clinical Pharmacist Practitioner (CPP), and those with mental health symptoms to the Comprehensive Cancer Support Program (CCSP)., Results: Of the 58 individuals identified as having at least one deficit on the GA, PT was the most commonly identified relevant resource (79%), followed by CPP visits (57%). Among individuals that were offered referral(s) to at least one new supportive care resource, the acceptance rate was 50%. Referral acceptance rates were highest among those recommended for a CPP visit (55% of those approached) and lowest for CCSP (0%)., Discussion: The study examined the feasibility and acceptability of a referral program for supportive care resources among older adults with MM who have deficits on GA. The most commonly identified deficit was physical functioning, followed by polypharmacy and mental health. The study found that physical interventions and referrals to CPPs were the most accepted interventions. However, the low proportion of patients who accepted physical therapy referrals indicates the need for tailored and more personalized approaches. Further research is needed to explore the feasibility and impact of supportive care referral programs for older adults with MM., Competing Interests: Declaration of Competing Interest The authors have no conflicts to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Fractures are ubiquitous and can lead to the catastrophic material failure of materials. Although fracturing in a two-dimensional plane is well understood, all fractures are extended in and propagate through three-dimensional space. Moreover, their behaviour is complex. Here we show that the forward propagation of a fracture front occurs through an initial rupture, nucleated at some localized position, followed by a very rapid transverse expansion at velocities as high as the Rayleigh-wave speed. We study fracturing in a circular geometry that achieves an uninterrupted extended fracture front and use a fluid to control the loading conditions that determine the amplitude of the forward jump. We find that this amplitude correlates with the transverse velocity. Dynamic rupture simulations capture the observations for only a high transverse velocity. These results highlight the importance of transverse dynamics in the forward propagation of an extended fracture., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

In clinical practice medications are often interchanged in treatment protocols when a patient negatively reacts to their first line of therapy. Although switching between medications is common, clinicians often lack structured guidance when choosing the initial dose and frequency of a new medication, given the former with respect to risk of adverse events. In this paper we propose to establish this dose toxo-equivalence relationship using published clinical trial results with one or both drugs of interest via a Bayesian meta-analysis model that accounts for both within- and between-study variances. With the posterior parameter samples from this model, we compute median and 95% credible intervals for equivalent dose pairs of the two drugs that are predicted to produce equal rates of an adverse outcome, relying solely on study-level information. Via extensive simulations, we show that this approach approximates well the true dose toxo-equivalence relationship, considering different study designs, levels of between-study variance, and the inclusion/exclusion of nonconfounder/nonmodifier subject-level covariates in addition to study-level covariates. We compare the performance of this study-level meta-analysis estimate to the equivalent individual patient data meta-analysis model and find comparable bias and minimal efficiency loss in the study-level coefficients used in the dose toxo-equivalence relationship. Finally, we present the findings of our dose toxo-equivalence model applied to two chemotherapy drugs, based on data from 169 published clinical trials.

Background: Low back pain (LBP) is the leading cause of disability globally. It generates considerable direct costs (healthcare) and indirect costs (lost productivity). The many available treatments for LBP include exercise therapy, which is practised extensively worldwide., Objectives: To evaluate the benefits and harms of exercise therapy for acute non-specific low back pain in adults compared to sham/placebo treatment or no treatment at short-term, intermediate-term, and long-term follow-up., Search Methods: This is an update of a Cochrane Review first published in 2005. We conducted an updated search for randomised controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, four other databases, and two trial registers. We screened the reference lists of all included studies and relevant systematic reviews published since 2004., Selection Criteria: We included RCTs that examined the effects of exercise therapy on non-specific LBP lasting six weeks or less in adults. Major outcomes for this review were pain, functional status, and perceived recovery. Minor outcomes were return to work, health-related quality of life, and adverse events. Our main comparisons were exercise therapy versus sham/placebo treatment and exercise therapy versus no treatment., Data Collection and Analysis: We used standard Cochrane methods. We evaluated outcomes at short-term follow-up (time point within three months and closest to six weeks after randomisation; main follow-up), intermediate-term follow-up (between nine months and closest to six months), and long-term follow-up (after nine months and closest to 12 months); and we used GRADE to assess the certainty of the evidence for each outcome., Main Results: We included 23 studies (13 from the previous review, 10 new studies) that involved 2674 participants and provided data for 2637 participants. Three small studies are awaiting classification, and four eligible studies are ongoing. Included studies were conducted in Europe (N = 9), the Asia-Pacific region (N = 9), and North America (N = 5); and most took place in a primary care setting (N = 12), secondary care setting (N = 6), or both (N = 1). In most studies, the population was middle-aged and included men and women. We judged 10 studies (43%) at low risk of bias with regard to sequence generation and allocation concealment. Blinding is not feasible in exercise therapy, introducing performance and detection bias. There is very low-certainty evidence that exercise therapy compared with sham/placebo treatment has no clinically relevant effect on pain scores in the short term (mean difference (MD) -0.80, 95% confidence interval (CI) -5.79 to 4.19; 1 study, 299 participants). The absolute difference was 1% less pain (95% CI 4% more to 6% less), and the relative difference was 4% less pain (95% CI 20% more to 28% less). The mean pain score was 20.1 (standard deviation (SD) 21) for the intervention group and 20.9 (SD 23) for the control group. There is very low-certainty evidence that exercise therapy compared with sham/placebo treatment has no clinically relevant effect on functional status scores in the short term (MD 2.00, 95% CI -2.20 to 6.20; 1 study, 299 participants). The absolute difference was 2% worse functional status (95% CI 2% better to 6% worse), and the relative difference was 15% worse (95% CI 17% better to 47% worse). The mean functional status score was 15.3 (SD 19) for the intervention group and 13.3 (SD 18) for the control group. We downgraded the certainty of the evidence for pain and functional status by one level for risk of bias and by two levels for imprecision (only one study with fewer than 400 participants). There is very low-certainty evidence that exercise therapy compared with no treatment has no clinically relevant effect on pain or functional status in the short term (2 studies, 157 participants). We downgraded the certainty of the evidence by two levels for imprecision and by one level for inconsistency. One study associated exercise with small benefits and the other found no differences. The first study was conducted in an occupational healthcare centre, where participants received one exercise therapy session. The other study was conducted in secondary and tertiary care settings, where participants received treatment three times per week for six weeks. We did not pool data from these studies owing to considerable clinical heterogeneity. In two studies, there were no reported adverse events. One study reported adverse events unrelated to exercise therapy. The remaining studies did not report whether any adverse events had occurred. Owing to insufficient reporting of adverse events, we were unable to reach any conclusions on the safety or harms related to exercise therapy., Authors' Conclusions: Exercise therapy compared to sham/placebo treatment may have no clinically relevant effect on pain or functional status in the short term in people with acute non-specific LBP, but the evidence is very uncertain. Exercise therapy compared to no treatment may have no clinically relevant effect on pain or functional status in the short term in people with acute non-specific LBP, but the evidence is very uncertain. We downgraded the certainty of the evidence to very low for inconsistency, risk of bias concerns, and imprecision (few participants)., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

The statistics of noise emitted by ultrathin crumpled sheets is measured while they exhibit logarithmic relaxations under load. We find that the logarithmic relaxation advanced via a series of discrete, audible, micromechanical events that are log-Poisson distributed (i.e., the process becomes a Poisson process when time stamps are replaced by their logarithms). The analysis places constraints on the possible mechanisms underlying the glasslike slow relaxation and memory retention in these systems.

Background: Proteasome inhibitor Carfilzomib (CFZ) is effective in treating patients with refractory or relapsed multiple myeloma (MM) but has been associated with cardiovascular adverse events (CVAE) such as hypertension, cardiomyopathy, and heart failure. This study aimed to investigate the contribution of germline genetic variants in protein-coding genes in CFZ-CVAE among MM patients using whole-exome sequencing (WES) analysis., Methods: Exome-wide single-variant association analysis, gene-based analysis, and rare variant analyses were performed on 603,920 variants in 247 patients with MM who have been treated with CFZ and enrolled in the Oncology Research Information Exchange Network (ORIEN) at the Moffitt Cancer Center. Separate analyses were performed in European Americans and African Americans followed by a trans-ethnic meta-analysis., Results: The most significant variant in the exome-wide single variant analysis was a missense variant rs7148 in the thymosin beta-10/TraB Domain Containing 2A ( TMSB10/TRABD2A ) locus. The effect allele of rs7148 was associated with a higher risk of CVAE [odds ratio (OR) = 9.3 with a 95% confidence interval of 3.9-22.3, p  = 5.42*10 -7 ]. MM patients with rs7148 AG or AA genotype had a higher risk of CVAE (50%) than those with GG genotype (10%). rs7148 is an expression quantitative trait locus (eQTL) for TRABD2A and TMSB10 . The gene-based analysis also showed TRABD2A as the most significant gene associated with CFZ-CVAE ( p  = 1.06*10 -6 )., Conclusions: We identified a missense SNP rs7148 in the TMSB10/TRABD2A as associated with CFZ-CVAE in MM patients. More investigation is needed to understand the underlying mechanisms of these associations., Competing Interests: MGF: research funding from Medtronic; Advisory board/consulting fees: Abbott, AstraZeneca, Myovant, Takeda, and Zoll. RCB: research funding from Janssen, Karyopharm, BMS, and Abbvie; Advisory board member for Janssen, Karyopharm, BMS, Shattuck labs, GSK, Pfizer, and Abbvie. RFC: Employed at AbbVie and stock shareholder. SMR: Advisory board member for Janssen, Sanofi, Roche Diagnostics, and EUSA pharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Tantawy, Yang, Algubelli, DeAvila, Rubinstein, Cornell, Fradley, Siegel, Hampton, Silva, Lenihan, Shain, Baz and Gong.)

Water transfer in wood plays a major role during the life time of timber structures but the physics of the various processes involved, such as wetting and imbibition, is not fully understood. Here we show that the angle of contact of a water drop placed in contact with an air dry wood surface is initially larger than 90°, then the drop slowly spreads over the surface, while the apparent (macroscopic) contact angle decreases down to a few tens of degrees. We show that similar results are obtained with a model material, i.e. hydrogel, as soon as a perturbation is induced onto the line of contact. We demonstrate that for the gel the initial large apparent contact angle results from a strong deformation of the gel in a thin softened region below the line of contact resulting from the fast diffusion of water and swelling of this region. This phenomenon ensures a real (local) contact angle close to zero. The spreading then results from the progressive diffusion of water at farther distance and successive perturbations of the line of contact when the drop enters in contact with small liquid droplets dispersed along the surface (residues of the chemical reaction during gel preparation). It is suggested that a similar effect occurs for the water drop over a wood surface and explains the large initial contact angle and slow spreading: the line of contact is initially pinned thanks to a wood surface deformation resulting from the wood surface swelling due to water absorption, thus leading to a large contact angle; it will then unpin when the local conditions have changed as a result of water diffusion at further distance, allowing for a small displacement up to the next pinning point and so on.

The roughness of a fracture surface records a crack's complex path through a material and can affect the resultant frictional or fluid transport properties of the broken medium. For brittle fractures, some of the most prominent surface features are long, step-like discontinuities called step lines. In heterogeneous materials, the mean crack surface roughness created by these step lines is well captured by a simple, one-dimensional ballistic annihilation model, which assumes the creation of these steps is a random processes with a single probability that depends on the heterogeneity of the material, and that their destruction occurs via pairwise interactions. Here, through an exhaustive study of experimentally generated crack surfaces in brittle hydrogels, we examine step interactions and show that interaction outcomes depend on the geometry of the incoming steps. The rules that govern step interactions can be categorized into three unique classes and are fully described, providing a complete framework for predicting fracture roughness.

Background: Understanding care seeking behaviour is vital to enabling access to care. In the context of low back pain (LBP), chiropractors offer services to patients of all ages. Currently, geriatric sub-populations tend to be under-investigated, despite the disproportionate effects of LBP on older adults. In the Netherlands, the chiropractic profession is relatively unknown and therefore, generally speaking, is not considered as the first choice for conservative musculoskeletal primary health care. The aim of this paper was to explore the experiences of older adults with LBP, seeking chiropracic care for the first time, in order to identify perceived barriers and facilitators in this process., Methods: Stage 1: Participants 56 years of age and older with chronic LBP who either sought or did not seek chiropractic care were interviewed to provide detailed information on the factors that promoted or impeded care-seeking behaviour. A purposive sampling strategy was used to recruit participants through a network of researchers, chiropractors and other healthcare professionals offering musculoskeletal health care services. Individuals with underlying pathology, previous surgery for LBP, or insufficient mastery of the Dutch language were excluded. Data were collected until saturation was reached and thematically analysed. Stage 2: To further explore the themes, a focus group interview was conducted with a provider stakeholder group consisting of:two physiotherapists, a nurse practitioner, a geriatrician, and a chiropractor. All interviews were conducted online, voice recorded, and transcribed verbatim., Results: We interviewed 11 older adults with low back pain. During this process four themes emerged that captured their perception and experiences in either seeking or dismissing chiropractic care for their LBP; these being 'generic', 'financial', 'expectation', and 'the image of the chiropractor'. The focus group members largely confirmed the identified themes, highlighting a lack of awarenes and accessibility as key barriers to care. On the other hand, whe chiropractior as an alternative care provider, with a focus on manual interventions, was seen as a facilitator., Conclusions: The lack of knowledge about chiropractic care was found to be the most important barrier to seeking care. The most important facilitator was insufficient resolution of their symptoms following previous care, making patients look further for a solution for their problem. These barriers and facilitators seem not to differ greatly from barriers and facilitators found among younger patients with neck pain. Age and health condition may therefore be weak determinants of care. This new information may help us optimize accessibility for older adults to the chiropractor., Competing Interests: Four authors (LDLR, ADZ, CM and SMR) are chiropractors who work in clinical practice, but have no direct financial interests linked with this survey. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 De la Ruelle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Geometric imperfections are understood to play an essential part in the buckling of a thin shell, but how multiple defects interact to control the onset of failure remains unclear. Here, we examine the failure of real cylindrical shells by experimentally poking soda cans with a large imparted dimple. By high-speed imaging of the can's surface, the initiation of buckling from axial loading is directly observed, revealing that larger dimples tend to set the initial buckling location. However, the influence of the shell's background geometric imperfections can still occasionally dominate, causing initiation to occur far from the dimple. In this situation, probing at the dimple leads to an over-prediction of the axial capacity. Using finite-element simulations, we understand our experimental results as a competition between the large dimple and the shell's inherent defect structure. In our simulations, we empirically observe a deformation-based criterion that connects the ideal poking location to the initiation site. This article is part of the theme issue 'Probing and dynamics of shock sensitive shells'.

Recent research into the buckling load of thin shells has focused on local poking of the shell. In this approach, the shell is poked under load to extract its stability landscape , and a ridge tracking method is performed to estimate the buckling load of the shell. It is the current understanding that the stability landscape measures the local stability of the shell and, as a result, that the accuracy of ridge tracking greatly relies on the location of poking. Currently, there is no method that can predict where poking should be performed on an experimental system. Here, we examine the global response of thin shells to poking through the energy landscape. We present an experimental method for measuring the energy landscape of thin shells and demonstrate its application on a thin plate strip. We show that by analysing the dynamics of the shell in the energy landscape we can experimentally measure the buckling mode of the system, which gives the correct point of poking for accurate ridge tracking, and identify two kinds of buckling points. Finally, we propose how this approach can be applied to more complex systems such as thin cylinders. This article is part of the theme issue 'Probing and dynamics of shock sensitive shells'.

Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines., Methods: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV)., Findings: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44)., Interpretation: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer., Funding: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH)., Competing Interests: TKC reports grants, personal fees and non-financial support from Merck, BMS, Exelixis, Astra Zeneca, Eli Lilly, Eisai, Novartis, GSK, Pfizer, EMD Serono; stocks in Pionyr, Tempest, outside the submitted work; In addition, TKC reports patent: pending International Patent Application No. PCT/US2018/12209, entitled “PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response,” filed January 3, 2018, claiming priority to U.S. Provisional Patent Application No. 62/445,094, filed January 11, 2017; pending International Patent Application No. PCT/US2018/058430, entitled “Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy,” filed October 31, 2018, claiming priority to U.S. Provisional Patent Application No. 62/581,175, filed November 3, 2017; TKC sits on National Comprehensive Cancer Network kidney panel. CL reports grants from Genentech/ImCore. ZB reports non-financial support from Bristol Myers Squibb, grants from Genentech/ImCore, personal fees from UpToDate, outside the submitted work. ALS reports non-financial support from Astellas and Pfizer outside the submitted work. GdLL reports personal fees from Boehringer Ingelheim, Pfizer, AstraZeneca; grants from AstraZeneca, Merck Sharp & Dohme, EMD Serono, AstraZeneca, Blueprint Medicines, Tesaro, Bavarian Nordic, Novartis, G1 Therapeutics, Adaptimmune, BMS, GSK, Abbvie, Rgenix, Pfizer, Roche, Genentech, Eli Lilly, Janssen; personal fees from Boehringer Ingelheim, Pfizer, E.R. Squibb Sons, LLC, Janssen; all outside the submitted work. CH reports grants from Merck, Bayer, Genentech, AstraZeneca, Bausch Health; Consulting fees from Tempus, Genzyme, EMD Sorono, payment or honoraria from OncLive/MJH Life Sciences, support for attending meetings and/or travel from Merck, participation on a data safety monitoring or advisory board of Henry Ford Cancer Institute, Hoosier Cancer Research Network; Leadership or fiduciary role in Wayne County Medical Society of Southeast Michigan; Stock or stock options in Johnson and Johnson, all outside the submitted work. EAG reports Consulting fees from Alexion Inc, Picnic Health, AbbVie, CTI Biopharma, Genentech Inc., Novartis, Celgene/Bristol Myers-Squibb, Takeda oncology, Taiho Oncology and Research Funding from Genentech Inc, Astex Pharmaceuticals, and BluePrint Medicines, outside the submitted work. SH reports grants/research supports from ASCO TAPUR, Astellas; honoraria or consultation fees from Sanofi, Aveo Oncology, outside the submitted work. SB reports Consulting fees from BMS, Exelexis, Eisai, Pfizer, Myovant, SeaGen; Payment or honoraria from Exelexis, Eisai, BMS; Participation on a Data Safety Monitoring Board or Advisory Board from SeaGen, Pfizer, Myovant; Stock or stock options in Natera; outside the submitted work. MJ reports grants from AstraZeneca, Pfizer; Eisai, personal fees from Seagen, Sanofi, outside the submitted work. NTNG reports personal fees from Novocure, outside the submitted work. RRM reports Advisory board/consultant—Aveo, AstraZeneca, Bayer, Bristol Myers Squib, Calithera, Caris, Dendreon, Exelixis, Janssen, Merck, Myovant, Novartis, Pfizer, Sanofi, Sorrento therapeutics, Pfizer, Tempus, Vividion, unrelated to this work. SMR reports advisory for Roche, Janssen, Sanofi, and EUSA Pharma, unrelated to this work. PV reports institutional research funding from Sanofi; stocks or stock options in Novavax, Biontech. HAZ acknowledges support from Georgia NCORP. CRF reports grants from Merck Foundation, grants from NCCN/Pfizer, grants from National Cancer Institute, other from National Cancer Institute, other from Patient-Centered Outcomes Research Institute, outside the submitted work. SM reports support from National Cancer Institute, and Intl Assoc. for the Study of Lung Cancer during the conduct of the study; and personal fees from National Geographic outside the submitted work. DF reports Grants or contracts from Merck, Viracor, Astellas; Support for attending meetings and/or travel from Viracor; outside the submitted work. JLW reports grants from NIH during the conduct of the study; personal fees from Roche, Westat, Flatiron Health, Melax Tech, IBM Watson Health, ownership of HemOnc.org LLC, grants from AACR; outside the submitted work. TMW-D reports grants from BMS, Merck & Co, GSK/Tesaro, Janssen; personal fees from Exicure, Shattuck Labs, SITC, Merck & Co, Caris Life Sciences, outside the submitted work. C-YH, SRKS, CJ, LBW, UW, TEO'C, OAP, EJK, HS, RN, TKN, RQ, MP, BHM, SADP, KR, BF, DYR, MKA, HS, DRR, YS, and SB have nothing to disclose. The content is solely the responsibility of the authors and does not necessarily represent the US Food and Drug Administration official views or policies., (© 2023 The Author(s).)

Purpose: Residents of communities facing social vulnerability (eg, poverty) have limited access to clinical trials, leaving them susceptible to experiencing poor health outcomes. We examined the association between North Carolina county-level social vulnerability and available multiple myeloma (MM) trials., Methods: Using a novel data linkage between ClinicalTrials.gov, the 2019 American Community Survey, and the Centers for Disease Control and Prevention's Social Vulnerability Index, we investigated at the county level (1) availability of MM trial sites and (2) the relationship between Social Vulnerability Index and MM trial site availability using logistic regression., Results: Between 2002 and 2021, 229 trials were registered across 462 nonunique trial sites in 34 counties. Nearly 50% of trial sites were in academic medical centers, 80% (n = 372) of all trials were industry-sponsored, 60% (n = 274) were early-phase, and 50% (n = 232) were for patients with relapsed or refractory MM. Counties with low as opposed to high poverty rates had six times greater odds of having ≥ 1 MM trial sites (odds ratio [OR], 5.60; 95% CI, 1.85 to 19.64; P = .004). Counties with the lowest percentage of Black Indigenous Persons of Color and non-native English speakers had 77% lower odds (OR, 0.23; 95% CI, 0.07 to 0.69; P = .011) of having ≥ 1 trial sites. The effect remained significant after accounting for the presence of five academic medical centers (n = 95; OR, 0.18; 95% CI, 0.05 to 0.6; P = .008) and adjustment for metropolitan, suburban, or rural status (OR, 0.25; 95% CI, 0.07 to 0.81; P = .025)., Conclusion: Counties with the lowest poverty rates had more MM trial sites, whereas those with the lowest percentage of Black Indigenous Persons of Color populations had fewer MM trial sites. Multilevel efforts are needed to improve the availability and access to trials for socially vulnerable populations.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common therapeutic complication affecting cancer patients' quality-of-life. We evaluated clinical characteristics, demographics, and lifestyle factors in association with CIPN following taxane treatment., Methods: Data were extracted from the electronic health record of 3387 patients diagnosed with a primary cancer and receiving taxane (i.e., paclitaxel or docetaxel) at Vanderbilt University Medical Center. Neuropathy was assessed via a validated computer algorithm. Univariate and multivariate regression models were applied to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) of CIPN-associated factors., Results: Female sex (OR = 1.28, 95% CI = 1.01-1.62), high body-mass index (BMI) (OR = 1.31, 95% CI = 1.06-1.61 for overweight, and OR = 1.49, 95% CI = 1.21-1.83 for obesity), diabetes (OR = 1.66, 95% CI = 1.34-2.06), high mean taxane dose (OR = 1.05, 95% CI = 1.03-1.08 per 10 mg/m 2 ), and more treatment cycles (1.12, 95% CI = 1.10-1.14) were positively associated with CIPN. Concurrent chemotherapy (OR = 0.74, 95% CI = 0.58-0.94) and concurrent radiotherapy (OR = 0.77, 95% CI = 0.59-1.00) were inversely associated with CIPN. Obesity and diabetes both had a stronger association with docetaxel CIPN compared to paclitaxel, although interaction was only significant for diabetes and taxane ( p = 0.019). Increased BMI was associated with CIPN only among non-diabetic patients (OR:1.34 for overweight and 1.68 for obesity), while diabetes increased CIPN risk across all BMI strata (ORs were 2.65, 2.41, and 2.15 for normal weight, overweight, and obese, respectively) compared to normal-weight non-diabetic patients ( p for interaction = 0.039)., Conclusions: Female sex, obesity, and diabetes are significantly associated with taxine-induced CIPN. Further research is needed to identify clinical and pharmacologic strategies to prevent and mitigate CIPN in at-risk patient populations.

SYNOPSIS: This position statement, stemming from the International IFOMPT (International Federation of Orthopaedic Manipulative Physical Therapists) Cervical Framework, was developed based upon the best contemporary evidence and expert opinion to assist clinicians during their clinical reasoning process when considering presentations involving the head and neck. Developed through rigorous consensus methods, the International IFOMPT Cervical Framework guides assessment of the cervical spine region for potential vascular pathologies of the neck in advance of planned interventions. Within the cervical spine, events and presentations of vascular pathologies of the neck are rare but are an important consideration as part of patient examination. Vascular pathologies may be recognizable if the appropriate questions are asked during the patient history-taking process, if interpretation of elicited data enables recognition of this potential, and if the physical examination can be adapted to explore any potential vasculogenic hypothesis. J Orthop Sports Phys Ther 2023;53(1):7-22. Epub: 14 September 2022. doi:10.2519/jospt.2022.11147 .