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Background: There is limited high-quality research examining conservative treatments for back-related leg pain (BRLP). This feasibility study was done in preparation for a full-scale trial comparing a whole-person supported self-management intervention to medical care for chronic BRLP., Methods: Participants were randomized to 12 weeks of individualized supported self-management delivered by physical therapists and chiropractors or medical care consisting of guideline-based pharmacologic care. Supported self-management was based on a behavioral model that used a whole person approach to enhance participants capabilities, opportunities, and motivations to engage in self-care. It combined BRLP education with psychosocial strategies (e.g., relaxed breathing, progressive muscle relaxation, guided imagery, communication skills) and physical modalities such as exercise and spinal manipulation therapy. Providers were trained to address participants' individualized needs and use behavior change and motivational communication techniques to develop a therapeutic alliance to facilitate self-management. Feasibility was assessed using pre-specified targets for recruitment and enrollment, intervention delivery, and data collection over the six-month study period. In addition, areas for potential refinement and optimization of processes and protocols for the full-scale trial were assessed., Results: We met or exceeded nearly all feasibility targets. Forty-two participants were enrolled over a six-month period in 2022 and very few individuals declined participation due to preferences for one treatment. All but one participant received treatment and 95% of participants attended the minimum number of visits (self-management = 6, medical care = 2). At 12 weeks, 95% of participants in the self-management group reported engaging in self-management practices learned in the program and 77% of medical care participants reported taking medications as prescribed. Satisfaction with the self-management intervention was high with 85% of participants reporting satisfaction with the program overall. Self-management intervention providers delivered all required activities at 72% of visits. Providers also noted some challenges navigating the shared decision-making process and deciding what self-management tools to prioritize. Over the six-month study period, completion rates were 91% for monthly surveys and 86% for weekly surveys., Conclusion: We were able to demonstrate that a full-scale randomized trial comparing a whole-person supported self-management intervention to medical care for chronic BRLP is feasible and identified important areas for optimization., Competing Interests: Declarations. Ethics approval and consent to participate: The research reported in this report has been performed in accordance with the Declaration of Helsinki. Ethical approval for the study was provided by the Institutional Review Board at the University of Minnesota (STUDY00013265). All participants provided consent to participate. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Importance: Although mindfulness-based interventions (MBIs) are evidence-based treatments for chronic pain and comorbid conditions, implementing them at scale poses many challenges, such as the need for dedicated space and trained instructors., Objective: To examine group and self-paced, scalable, telehealth MBIs, for veterans with chronic pain, compared to usual care., Design, Setting, and Participants: This was a randomized clinical trial of veterans with moderate to severe chronic pain, recruited from 3 Veterans Affairs facilities from November 2020 to May 2022. Follow-up was completed in August 2023., Interventions: Two 8-week telehealth MBIs (group and self-paced) were compared to usual care (control). The group MBI was done via videoconference with prerecorded mindfulness education and skill training videos by an experienced instructor, accompanied by facilitated discussions. The self-paced MBI was similar but completed asynchronously and supplemented by 3 individual facilitator calls., Main Outcomes and Measures: The primary outcome was pain-related function using the Brief Pain Inventory interference scale at 3 time points: 10 weeks, 6 months, and 1 year. Secondary outcomes included biopsychosocial outcomes: pain intensity, physical function, anxiety, fatigue, sleep disturbance, participation in social roles and activities, depression, patient ratings of improvement of pain, and posttraumatic stress disorder., Results: Among 811 veterans randomized (mean [SD] age, 54.6 [12.9] years; 387 [47.7%] women), 694 participants (85.6%) completed the trial. Averaged across all 3 time points, pain interference scores were significantly lower for both MBIs compared to usual care (group MBI vs control difference: -0.4 [95% CI, -0.7 to -0.2]; self-paced vs control difference: -0.7 [95% CI, -1.0 to -0.4]). Additionally, both MBI arms had significantly better scores on the following secondary outcomes: pain intensity, patient global impression of change, physical function, fatigue, sleep disturbance, social roles and activities, depression, and posttraumatic stress disorder. Both group and self-paced MBIs did not significantly differ from one another. The probability of 30% improvement from baseline compared to control was greater for group MBI at 10 weeks and 6 months, and for self-paced MBI, at all 3 time points., Conclusions and Relevance: In this randomized clinical trial, scalable telehealth MBIs improved pain-related function and biopsychosocial outcomes compared to usual care among veterans with chronic pain. Relatively low-resource telehealth-based MBIs could help accelerate and improve the implementation of nonpharmacological pain treatment in health care systems., Trial Registration: ClinicalTrials.gov Identifier: NCT04526158.

Meta-analysis is commonly used to combine results from multiple clinical trials, but traditional meta-analysis methods do not refer explicitly to a population of individuals to whom the results apply and it is not clear how to use their results to assess a treatment's effect for a population of interest. We describe recently-introduced causally interpretable meta-analysis methods and apply their treatment effect estimators to two individual-participant data sets. These estimators transport estimated treatment effects from studies in the meta-analysis to a specified target population using the individuals' potentially effect-modifying covariates. We consider different regression and weighting methods within this approach and compare the results to traditional aggregated-data meta-analysis methods. In our applications, certain versions of the causally interpretable methods performed somewhat better than the traditional methods, but the latter generally did well. The causally interpretable methods offer the most promise when covariates modify treatment effects and our results suggest that traditional methods work well when there is little effect heterogeneity. The causally interpretable approach gives meta-analysis an appealing theoretical framework by relating an estimator directly to a specific population and lays a solid foundation for future developments., (© 2023 John Wiley & Sons, Ltd.)

Background: Chronic low back pain (cLBP) is widespread, costly, and burdensome to patients and health systems. Little is known about non-pharmacological treatments for the secondary prevention of cLBP. There is some evidence that treatments addressing psychosocial factors in higher risk patients are more effective than usual care. However, most clinical trials on acute and subacute LBP have evaluated interventions irrespective of prognosis., Methods: We have designed a phase 3 randomized trial with a 2 × 2 factorial design. The study is also a Hybrid type 1 trial with focus on intervention effectiveness while simultaneously considering plausible implementation strategies. Adults (n = 1000) with acute/subacute LBP at moderate to high risk of chronicity based on the STarT Back screening tool will be randomized in to 1 of 4 interventions lasting up to 8 weeks: supported self-management (SSM), spinal manipulation therapy (SMT), both SSM and SMT, or medical care. The primary objective is to assess intervention effectiveness; the secondary objective is to assess barriers and facilitators impacting future implementation. Primary effectiveness outcome measures are: (1) average pain intensity over 12 months post-randomization (pain, numerical rating scale); (2) average low back disability over 12 months post-randomization (Roland-Morris Disability Questionnaire); (3) prevention of cLBP that is impactful at 10-12 months follow-up (LBP impact from the PROMIS-29 Profile v2.0). Secondary outcomes include: recovery, PROMIS-29 Profile v2.0 measures to assess pain interference, physical function, anxiety, depression, fatigue, sleep disturbance, and ability to participate in social roles and activities. Other patient-reported measures include LBP frequency, medication use, healthcare utilization, productivity loss, STarT Back screening tool status, patient satisfaction, prevention of chronicity, adverse events, and dissemination measures. Objective measures include the Quebec Task Force Classification, Timed Up & Go Test, the Sit to Stand Test, and the Sock Test assessed by clinicians blinded to the patients' intervention assignment., Discussion: By targeting those subjects at higher risk this trial aims to fill an important gap in the scientific literature regarding the effectiveness of promising non-pharmacological treatments compared to medical care for the management of patients with an acute episode of LBP and the prevention of progression to a severe chronic back problem., Trial Registration: ClinicalTrials.gov Identifier: NCT03581123., (© 2023. The Author(s).)

Background: Low back pain (LBP) is influenced by interrelated biological, psychological, and social factors, however current back pain management is largely dominated by one-size fits all unimodal treatments. Team based models with multiple provider types from complementary professional disciplines is one way of integrating therapies to address patients' needs more comprehensively., Methods: This parallel group randomized clinical trial conducted from May 2007 to August 2010 aimed to evaluate the relative clinical effectiveness of 12 weeks of monodisciplinary chiropractic care (CC), versus multidisciplinary integrative care (IC), for adults with sub-acute and chronic LBP. The primary outcome was pain intensity and secondary outcomes were disability, improvement, medication use, quality of life, satisfaction, frequency of symptoms, missed work or reduced activities days, fear avoidance beliefs, self-efficacy, pain coping strategies and kinesiophobia measured at baseline and 4, 12, 26 and 52 weeks. Linear mixed models were used to analyze outcomes., Results: 201 participants were enrolled. The largest reductions in pain intensity occurred at the end of treatment and were 43% for CC and 47% for IC. The primary analysis found IC to be significantly superior to CC over the 1-year period (P = 0.02). The long-term profile for pain intensity which included data from weeks 4 through 52, showed a significant advantage of 0.5 for IC over CC (95% CI 0.1 to 0.9; P = 0.02; 0 to 10 scale). The short-term profile (weeks 4 to 12) favored IC by 0.4, but was not statistically significant (95% CI - 0.02 to 0.9; P = 0.06). There was also a significant advantage over the long term for IC in some secondary measures (disability, improvement, satisfaction and low back symptom frequency), but not for others (medication use, quality of life, leg symptom frequency, fear avoidance beliefs, self-efficacy, active pain coping, and kinesiophobia). Importantly, no serious adverse events resulted from either of the interventions., Conclusions: Participants in the IC group tended to have better outcomes than the CC group, however the magnitude of the group differences was relatively small. Given the resources required to successfully implement multidisciplinary integrative care teams, they may not be worthwhile, compared to monodisciplinary approaches like chiropractic care, for treating LBP. Trial registration NCT00567333., (© 2022. The Author(s).)

Objectives: CaringBridge (CB) is an online health community for people undergoing challenging health journeys. Loving Kindness Meditation (LKM) is a systemized mind-body approach developed to increase loving acceptance and has previously been reported to increase resilience in the face of adversity. Materials and Methods: Results of a randomized controlled trial of immediate compared with deferred 21-day LKM intervention in an online community are reported. The deferred group received LKM intervention after a waiting period of 3 weeks. Inclusion criteria were >18 years old, ability to understand English, willingness to participate in a mind-body practice, and use of CB for a cancer journey. Change in perceived stress, self-compassion, social connectedness and assurance, and compassionate love scales from baseline to 21 days was assessed. Results: Of the 979 participants included in the study, 649 (66%) provided 3-week follow-up data and 330 (49%) self-reported engaging in the LKM practice 5 or more days/week. Participants in the immediate LKM group reported medium effect size improvement in stress (0.4), self-compassion (0.5), and social connectedness (0.4) compared with the deferred LKM group. Changes in perceived stress and self-compassion were larger in magnitude and increased with more frequent engagement in LKM. Conclusions: The immediate LKM group showed improvements in stress, self-compassion, and social connectedness compared with the deferred control group. Differential study retention rates by treatment arm and self-reported engagement in LKM subject the results to selection bias. Future research of similar interventions within online health communities might pay greater attention to promoting intervention adherence and engaging a more diverse economic and racial/ethnic population. ClinicalTrials.gov (NCT05002842).

The mechanisms underlying chemical respiratory sensitization are incompletely understood. One of the major cell types involved in this pathology are dendritic cells. In this study, the mechanisms of the NRF2-Keap1 pathway were studied using a bone marrow-derived dendritic cell model exposed to two respiratory sensitizers: ammonium hexachloroplatinate (HCP) and ammonium tetrachloroplatinate (ATCP). Expression levels for two Nrf2-regulated genes, hmox1 and srxn1 , were analyzed by real time-quantitative polymerase chain reaction. A flow cytometry-based method was also developed to measure intracellular Nrf2 accumulation in dendritic cells following exposure. Exposure to HCP and ATCP increased both hmox1 and srxn1 gene expression, and was associated with accumulation of Nrf2 protein in cells. Overall, these results show that the respiratory sensitizers, in addition to skin sensitizers, can also induced markers associated with NRF2-Keap1 pathway activation in dendritic cells. This study contributes to a better understanding of the adverse outcome of respiratory sensitization., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Back and neck pain are associated with disability and loss of independence in older adults. Whether long-term management using commonly recommended treatments is superior to shorter-term treatment is unknown. This randomized clinical trial compared short-term treatment (12 weeks) versus long-term management (36 weeks) of back- and neck-related disability in older adults using spinal manipulative therapy (SMT) combined with supervised rehabilitative exercises (SRE)., Methods: Eligible participants were ages ≥65 years with back and neck disability for ≥12 weeks. Coprimary outcomes were changes in Oswestry Disability Index (ODI) and Neck Disability Index (NDI) scores after 36 weeks. An intent-to-treat approach used linear mixed-model analysis to detect between-group differences. Secondary analyses included other self-reported outcomes, adverse events, and objective functional measures., Results: A total of 182 participants were randomized. The short-term and long-term groups demonstrated significant improvements in back disability (ODI score -3.9 [95% confidence interval (95% CI) -5.8, -2.0] versus ODI score -6.3 [95% CI -8.2, -4.4]) and neck disability (NDI score -7.3 [95% CI -9.1, -5.5] versus NDI score -9.0 [95% CI -10.8, -7.2]) after 36 weeks, with no difference between groups (back ODI score 2.4 [95% CI -0.3, 5.1]; neck NDI score 1.7 [95% CI 0.8, 4.2]). The long-term management group experienced greater improvement in neck pain at week 36, in self-efficacy at weeks 36 and 52, and in functional ability, and balance., Conclusion: For older adults with chronic back and neck disability, extending management with SMT and SRE from 12 to 36 weeks did not result in any additional important reduction in disability., (© 2018, American College of Rheumatology.)

Background: Low back pain (LBP) is a common disabling condition in older adults which often limits physical function and diminishes quality of life. Two clinical trials in older adults have shown spinal manipulative therapy (SMT) results in similar or small improvements relative to medical care; however, the effectiveness of adding SMT or rehabilitative exercise to home exercise is unclear., Methods: We conducted a randomized clinical trial assessing the comparative effectiveness of adding SMT or supervised rehabilitative exercise to home exercise in adults 65 or older with sub-acute or chronic LBP. Treatments were provided over 12-weeks and self-report outcomes were collected at 4, 12, 26, and 52 weeks. The primary outcome was pain severity. Secondary outcomes included back disability, health status, medication use, satisfaction with care, and global improvement. Linear mixed models were used to analyze outcomes. The primary analysis included longitudinal outcomes in the short (week 4-12) and long-term (week 4-52). An omnibus test assessing differences across all groups over the year was used to control for multiplicity. Secondary analyses included outcomes at each time point and responder analyses. This study was funded by the US Department of Health and Human Services, Health Resources and Services Administration., Results: 241 participants were randomized and 230 (95%) provided complete primary outcome data. The primary analysis showed group differences in pain over the one-year were small and not statistically significant. Pain severity was reduced by 30 to 40% after treatment in all 3 groups with the largest difference (eight percentage points) favoring SMT and home exercise over home exercise alone. Group differences at other time points ranged from 0 to 6 percentage points with no consistent pattern favoring one treatment. One-year post-treatment pain reductions diminished in all three groups. Secondary self-report outcomes followed a similar pattern with no important group differences, except satisfaction with care, where the two combination groups were consistently superior to home exercise alone., Conclusions: Adding spinal manipulation or supervised rehabilitative exercise to home exercise alone does not appear to improve pain or disability in the short- or long-term for older adults with chronic low back pain, but did enhance satisfaction with care., Trial Registration: NCT00269321., Competing Interests: Ethical approval for the study was provided by the Institutional Review Boards at Northwestern Health Sciences University and the Minneapolis Medical Research Foundation. All participants provided written informed consent to participate.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objectives: CaringBridge (CB) is a web-based social network where people share information, enlist support, and access resources following a difficult diagnosis; it can also be used to disseminate supportive self-care tools, such as a gratitude practice, for its users. Gratitude practices are shown to reduce stress and fear, improve sleep, and increase positive emotions and overall well-being. The purpose of this article was to report the findings of a brief gratitude intervention delivered to CB users. Design, setting/location, subjects: This is a nonrandomized, prospective, pre- and post-evaluation study in an online community. Inclusion criteria were adults 18 years or older, English literate, willingness to participate in a mind-body practice, and active users of CB: patient, caregiver, or visitor to a site., Interventions: Participants were engaged in a daily, 21-day brief gratitude practice and were given weekly automated reminders to do their practice., Outcome Measures: Outcomes included perceived stress, gratitude, social connectedness, and social assurance scales. Paired t tests were used to assess changes in outcomes; multivariate regression models were used to assess the relationship between the frequency of gratitude practice and change in outcomes., Results: Follow-up data were collected from 882/1598 participants, and nearly 70% self-reported engaging in the gratitude practice five or more days/week. Participants reported statistically significant improvement in all outcomes with small standardized effect sizes for gratitude (0.39), social connectedness (0.24), and social assurance (0.10). Changes in perceived stress (-0.73) were larger in magnitude and increased with more frequent practice., Conclusions: Among this online community, there was a high level of engagement with a brief gratitude practice, and improvements in stress, gratitude, and social support were observed. This design did not control for changes in outcomes that may be due to time trends, placebo or contextual effects, regression to the mean, or selection bias.

Background: Spinal pain is a common and disabling condition with considerable socioeconomic burden. Spine pain management in the United States has gathered increased scrutiny amidst concerns of overutilization of costly and potentially harmful interventions and diagnostic tests. Conservative interventions such as spinal manipulation, exercise and self-management may provide value for the care of spinal pain, but little is known regarding the cost-effectiveness of these interventions in the U.S. Our primary objective for this project is to estimate the incremental cost-effectiveness of spinal manipulation, exercise therapy, and self-management for spinal pain using an individual patient data meta-analysis approach., Methods/design: We will estimate the incremental cost-effectiveness of spinal manipulation, exercise therapy, and self-management using cost and clinical outcome data collected in eight randomized clinical trials performed in the U.S. Cost-effectiveness will be assessed from both societal and healthcare perspectives using QALYs, pain intensity, and disability as effectiveness measures. The eight randomized clinical trials used similar methods and included different combinations of spinal manipulation, exercise therapy, or self-management for spinal pain. They also collected similar clinical outcome, healthcare utilization, and work productivity data. A two-stage approach to individual patient data meta-analysis will be conducted., Discussion: This project capitalizes on a unique opportunity to combine clinical and economic data collected in a several clinical trials that used similar methods. The findings will provide important information on the value of spinal manipulation, exercise therapy, and self-management for spinal pain management in the U.S., Competing Interests: Ethical approval for the proposed study was provided by the Institutional Review Board at the University of Minnesota, Minneapolis, MN, USA. (#1508E77089).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background Context: The optimal number of visits for the care of cervicogenic headache (CGH) with spinal manipulative therapy (SMT) is unknown., Purpose: The present study aimed to identify the dose-response relationship between visits for SMT and chronic CGH outcomes and to evaluate the efficacy of SMT by comparison with a light-massage control., Study Design/setting: This is a two-site, open-label randomized controlled trial., Patient Sample: Participants were 256 adults with chronic CGH., Outcome Measures: The primary outcome was days with CGH in the previous 4 weeks evaluated at the 12- and 24-week primary end points. Secondary outcomes included CGH days at remaining end points, pain intensity, disability, perceived improvement, medication use, and patient satisfaction., Methods: Participants were randomized to four dose levels of chiropractic SMT: 0, 6, 12, or 18 sessions. They were treated three times per week for 6 weeks and received a focused light-massage control at sessions when SMT was not assigned. Linear dose effects and comparisons with the no-manipulation control group were evaluated at 6, 12, 24, 39, and 52 weeks. The present study was funded by the National Center for Complementary and Integrative Health (R01AT006330) and is registered at ClinicalTrials.gov (NCT01530321). The authors declare no conflicts of interest., Results: A linear dose-response was observed for all follow-ups, a reduction of approximately 1 CGH day/4 weeks per additional 6 SMT visits (p<.05); a maximal effective dose could not be determined. Cervicogenic headache days/4 weeks were reduced from about 16 to 8 for the highest and most effective dose of 18 SMT visits. Mean differences in CGH days/4 weeks between 18 SMT visits and control were -3.3 (p=.004) and -2.9 (p=.017) at the primary end points, and were similar in magnitude at the remaining end points (p<.05). Differences between other SMT doses and control were smaller in magnitude (p>.05). Cervicogenic headache intensity showed no important improvement nor differed by dose. Other secondary outcomes were generally supportive of the primary outcome., Conclusions: There was a linear dose-response relationship between SMT visits and days with CGH. For the highest and most effective dose of 18 SMT visits, CGH days were reduced by half and about 3 more days per month than for the light-massage control., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Low back pain (LBP) is common in adolescence, but there is a paucity of high-quality research to inform care. We conducted a multicenter randomized trial comparing 12 weeks of spinal manipulative therapy (SMT) combined with exercise therapy (ET) to ET alone. Participants were 185 adolescents aged 12 to 18 years with chronic LBP. The primary outcome was LBP severity at 12, 26, and 52 weeks. Secondary outcomes included disability, quality of life, medication use, patient- and caregiver-rated improvement, and satisfaction. Outcomes were analyzed using longitudinal linear mixed effect models. An omnibus test assessing differences in individual outcomes over the entire year controlled for multiplicity. Of the 185 enrolled patients, 179 (97%) provided data at 12 weeks and 174 (94%) at 26 and 52 weeks. Adding SMT to ET resulted in a larger reduction in LBP severity over the course of 1 year (P = 0.007). The group difference in LBP severity (0-10 scale) was small at the end of treatment (mean difference = 0.5; P = 0.08) but was larger at weeks 26 (mean difference = 1.1; P = 0.001) and 52 (mean difference = 0.8; P = 0.009). At 26 weeks, SMT with ET performed better than ET alone for disability (P = 0.04) and improvement (P = 0.02). The SMT with ET group reported significantly greater satisfaction with care at all time points (P ≤ 0.02). There were no serious treatment-related adverse events. For adolescents with chronic LBP, spinal manipulation combined with exercise was more effective than exercise alone over a 1-year period, with the largest differences occurring at 6 months. These findings warrant replication and evaluation of cost effectiveness.

Background: Clinical practice guidelines (CPGs) have the ability to increase efficiency and standardize care. A CPG based on forced vital capacity (FVC) for rib fractures was developed as a tool for triage of these patients. The objectives of this study were to assess the efficacy and compliance of physicians with this rib fracture CPG., Methods: Patients >18 that were discharged from an urban level 2 trauma center emergency department (ED) between the dates of January 1, 2014, to December 31, 2016, were eligible for the study. Demographics, mechanism, outcomes and FVC were abstracted by review of the electronic medical record. Compliance with the CPG was examined, and comparisons were made between patients successfully discharged and patients who returned., Results: 455 patients met were identified during the study period. 233 were eligible after exclusions. 64% of the cohort was male with median age of 53 years. Falls were the most common mechanism (59.6%). The median number of rib fractures was 2 and median FVC 2500 mL. 28 (12.0%) of the 233 returned to the ED after discharge. The groups were well matched with no significant differences. The most common reason for return was pain (95%). Adjusted analysis showed that increasing age (adjusted OR (AOR) 0.968) and FVC (AOR 0.999) were independent predictors. Adherence with the CPG was good for hemothorax/pneumothorax and bilateral fractures (96%), but lagged with the number of fractures (74%)., Conclusions: This study confirms that the rib fracture CPG is safe and an FVC of 1500 mL is a safe criterion for discharging patients with rib fractures. Interestingly, it appears that older age is protective. More work needs to be done on effective pain control to decrease return to ED visits using this CPG., Level of Evidence: IV., Type of Study: Therapeutic., Competing Interests: Competing interests: None declared.

Background: Following blunt splenic injury, there is conflicting evidence regarding the natural history and appropriate management of patients with vascular injuries of the spleen such as pseudoaneurysms or blushes. The purpose of this study was to describe the current management and outcomes of patients with pseudoaneurysm or blush., Methods: Data were collected on adult (aged ≥18 years) patients with blunt splenic injury and a splenic vascular injury from 17 trauma centers. Demographic, physiologic, radiographic, and injury characteristics were gathered. Management and outcomes were collected. Univariate and multivariable analyses were used to determine factors associated with splenectomy., Results: Two hundred patients with a vascular abnormality on computed tomography scan were enrolled. Of those, 14.5% were managed with early splenectomy. Of the remaining patients, 59% underwent angiography and embolization (ANGIO), and 26.5% were observed. Of those who underwent ANGIO, 5.9% had a repeat ANGIO, and 6.8% had splenectomy. Of those observed, 9.4% had a delayed ANGIO, and 7.6% underwent splenectomy. There were no statistically significant differences between those observed and those who underwent ANGIO. There were 111 computed tomography scans with splenic vascular injuries available for review by an expert trauma radiologist. The concordance between the original classification of the type of vascular abnormality and the expert radiologist's interpretation was 56.3%. Based on expert review, the presence of an actively bleeding vascular injury was associated with a 40.9% risk of splenectomy. This was significantly higher than those with a nonbleeding vascular injury., Conclusions: In this series, the vast majority of patients are managed with ANGIO and usually embolization, whereas splenectomy remains a rare event. However, patients with a bleeding vascular injury of the spleen are at high risk of nonoperative failure, no matter the strategy used for management. This group may warrant closer observation or an alternative management strategy., Level of Evidence: Prognostic study, level III.

Study Design Cross-sectional. Background Although low back pain (LBP) occurs commonly in adolescence, little is known about the relationship between objectively measured physical activity and chronic LBP. Objectives To assess the relationship between an objective physical activity measure (accelerometer) and standard clinical measures (pain intensity, disability, and quality of life) in a sample of adolescents with recurrent or chronic LBP. Methods The study included a subsample of 143 adolescents, 12 to 18 years of age, from a randomized clinical trial. Pearson correlations (r) and bivariate linear regression were used to assess the relationship between baseline measures of sedentary, light, and moderate-to-vigorous physical activity using accelerometers and clinical measures of LBP (pain intensity, disability, and quality of life). Results Participants spent an average of 610.5 minutes in sedentary activity, 97.6 minutes in light physical activity, and 35.6 minutes in moderate-to-vigorous physical activity per day. Physical activity was very weakly associated with clinical measures of LBP (r<0.13). None of the assessed correlations were statistically significant, and bivariate regression models showed that physical activity measures explained very little of the variability for clinical measures of LBP (R 2 <0.02). Conclusion We found no important relationship between objectively measured physical activity and self-reported LBP intensity, disability, or quality of life in adolescents with recurrent or chronic LBP. The parent randomized clinical trial was registered at ClinicalTrials.gov (NCT01096628). J Orthop Sports Phys Ther 2017;47(10):769-774. Epub 12 Sep 2017. doi:10.2519/jospt.2017.7345.

Background Context: Chronic neck pain is a prevalent and disabling condition among older adults. Despite the large burden of neck pain, little is known regarding the cost-effectiveness of commonly used treatments., Purpose: This study aimed to estimate the cost-effectiveness of home exercise and advice (HEA), spinal manipulative therapy (SMT) plus HEA, and supervised rehabilitative exercise (SRE) plus HEA., Study Design/setting: Cost-effectiveness analysis conducted alongside a randomized clinical trial (RCT) was performed., Patient Sample: A total of 241 older adults (≥65 years) with chronic mechanical neck pain comprised the patient sample., Outcome Measures: The outcome measures were direct and indirect costs, neck pain, neck disability, SF-6D-derived quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) over a 1-year time horizon., Methods: This work was supported by grants from the National Center for Complementary and Integrative Health (#F32AT007507), National Institute of Arthritis and Musculoskeletal and Skin Diseases (#P60AR062799), and Health Resources and Services Administration (#R18HP01425). The RCT is registered at ClinicalTrials.gov (#NCT00269308). A societal perspective was adopted for the primary analysis. A healthcare perspective was adopted as a sensitivity analysis. Cost-effectivenesswas a secondary aim of the RCT which was not powered for differences in costs or QALYs. Differences in costs and clinical outcomes were estimated using generalized estimating equations and linear mixed models, respectively. Cost-effectiveness acceptability curves were calculated to assess the uncertainty surrounding cost-effectiveness estimates., Results: Total costs for SMT+HEA were 5% lower than HEA (mean difference: -$111; 95% confidence interval [CI] -$1,354 to $899) and 47% lower than SRE+HEA (mean difference: -$1,932; 95% CI -$2,796 to -$1,097). SMT+HEA also resulted in a greater reduction of neck pain over the year relative to HEA (0.57; 95% CI 0.23 to 0.92) and SRE+HEA (0.41; 95% CI 0.05 to 0.76). Differences in disability and QALYs favored SMT+HEA. The probability that adding SMT to HEA is cost-effective at willingness to pay thresholds of $50,000 to $200,000 per QALY gained ranges from 0.75 to 0.81. If adopting a health-care perspective, costs for SMT+HEA were 66% higher than HEA (mean difference: $515; 95% CI $225 to $1,094), resulting in an ICER of $55,975 per QALY gained., Conclusion: On average, SMT+HEA resulted in better clinical outcomes and lower total societal costs relative to SRE+HEA and HEA alone, with a 0.75 to 0.81 probability of cost-effectiveness for willingness to pay thresholds of $50,000 to $200,000 per QALY., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Cervicogenic headache is a prevalent and costly pain condition commonly treated by chiropractors. There is evidence to support the effectiveness for spinal manipulation, but the dose of treatment required to achieve maximal relief remains unknown. The purpose of this paper is to describe the methodology for a randomized controlled trial evaluating the dose-response of spinal manipulation for chronic cervicogenic headache in an adult population., Methods/design: This is a mixed-methods, two-site, prospective, parallel groups, observer-blind, randomized controlled trial conducted at university-affiliated research clinics in the Portland, OR and Minneapolis, MN areas. The primary outcome is patient reported headache frequency. Other outcomes include self-reported headache intensity, disability, quality of life, improvement, neck pain intensity and frequency, satisfaction, medication use, outside care, cervical motion, pain pressure thresholds, health care utilization, health care costs, and lost productivity. Qualitative interviews are also conducted to evaluate patients' expectations of treatment., Discussion: With growing concerns regarding the costs and side effects of commonly used conventional treatments, greater numbers of headache sufferers are seeking other approaches to care. This is the first full-scale randomized controlled trial assessing the dose-response of spinal manipulation therapy on outcomes for cervicogenic headache. The results of this study will provide important evidence for the management of cervicogenic headache in adults., Trial Registration: ClinicalTrials.gov (Identifier: NCT01530321).

This is the protocol for a review and there is no abstract. The objectives are as follows: To quantify and compare the short- and long-term effects of manual treatment and spinal rehabilitative exercise for cervicogenic headache, classified according to the International Headache Society's (IHS) diagnostic criteria, with an active or placebo/sham comparison or wait-list control., Competing Interests: DECLARATIONS OF INTEREST Four authors are researchers with chiropractic training, one is a physical therapy researcher, one is a statistician and two are medical doctors with a research background. All members may have a potential special professional interest in the effectiveness of these interventions. Mitchell Haas: none known. Gert Bronfort: none known. Roni Evans: none known. Brent Leininger: none known. John Schmitt: none known. Morris Levin: none known. ML has received small honoraria for consulting with Depomed and Allergan who produce medications for migraine headache and related conditions. These companies did not fund this review. Kristine Westrom: none known. Charlie Goldsmith: none known. Review authors who have been authors of clinical trials that may be included in the review will not be involved in decisions regarding the inclusion or ’Risk of bias’ assessment of such trials to minimize potential personal conflicts of interest.

Objective: The purpose of this study was to determine whether use of chiropractic manipulative treatment (CMT) was associated with lower healthcare costs among multiply-comorbid Medicare beneficiaries with an episode of chronic low back pain (cLBP)., Methods: We conducted an observational, retrospective study of 2006 to 2012 Medicare fee-for-service reimbursements for 72326 multiply-comorbid patients aged 66 and older with cLBP episodes and 1 of 4 treatment exposures: chiropractic manipulative treatment (CMT) alone, CMT followed or preceded by conventional medical care, or conventional medical care alone. We used propensity score weighting to address selection bias., Results: After propensity score weighting, total and per-episode day Part A, Part B, and Part D Medicare reimbursements during the cLBP treatment episode were lowest for patients who used CMT alone; these patients had higher rates of healthcare use for low back pain but lower rates of back surgery in the year following the treatment episode. Expenditures were greatest for patients receiving medical care alone; order was irrelevant when both CMT and medical treatment were provided. Patients who used only CMT had the lowest annual growth rates in almost all Medicare expenditure categories. While patients who used only CMT had the lowest Part A and Part B expenditures per episode day, we found no indication of lower psychiatric or pain medication expenditures associated with CMT., Conclusions: This study found that older multiply-comorbid patients who used only CMT during their cLBP episodes had lower overall costs of care, shorter episodes, and lower cost of care per episode day than patients in the other treatment groups. Further, costs of care for the episode and per episode day were lower for patients who used a combination of CMT and conventional medical care than for patients who did not use any CMT. These findings support initial CMT use in the treatment of, and possibly broader chiropractic management of, older multiply-comorbid cLBP patients., (Copyright © 2016 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.)

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the short- and long-term effects of manual treatment and spinal rehabilitative exercise for the prevention of tension-type headache in adults., Competing Interests: DECLARATIONS OF INTEREST Four authors are researchers with chiropractic training, one is a physical therapy researcher, one is a statistician and two are medical doctors with research backgrounds. All members may have a potential special professional interest in the effectiveness of these interventions. Gert Bronfort declares no financial conflicts of interest. Roni Evans declares no financial conflicts of interest. Mitchell Haas declares no financial conflicts of interest. Charlie Goldsmith declares no financial conflicts of interest. Brent Leininger declares no financial conflicts of interest. Morris Levin declares no financial conflicts of interest. ML has received small honoraria for consulting with Depomed and Allergan who produce medications for migraine headache and related conditions. These companies did not fund this review. John Schmitt declares no financial conflicts of interest. Kristine Westrom declares no financial conflicts of interest. Review authors who have been authors of clinical trials that may be included in the review will not be involved in decisions regarding the inclusion or ‘Risk of bias’ assessment of such trials, to minimize potential personal conflicts of interest.

Objective: Patients who use complementary and integrative health services like chiropractic manipulative treatment (CMT) often have different characteristics than do patients who do not, and these differences can confound attempts to compare outcomes across treatment groups, particularly in observational studies when selection bias may occur. The purposes of this study were to provide an overview on how propensity scoring methods can be used to address selection bias by balancing treatment groups on key variables and to use Medicare data to compare different methods for doing so., Methods: We described 2 propensity score methods (matching and weighting). Then we used Medicare data from 2006 to 2012 on older, multiply comorbid patients who had a chronic low back pain episode to demonstrate the impact of applying methods on the balance of demographics of patients between 2 treatment groups (those who received only CMT and those who received no CMT during their episodes)., Results: Before application of propensity score methods, patients who used only CMT had different characteristics from those who did not. Propensity score matching diminished observed differences across the treatment groups at the expense of reduced sample size. However, propensity score weighting achieved balance in patient characteristics between the groups and allowed us to keep the entire sample., Conclusions: Although propensity score matching and weighting have similar effects in terms of balancing covariates, weighting has the advantage of maintaining sample size, preserving external validity, and generalizing more naturally to comparisons of 3 or more treatment groups. Researchers should carefully consider which propensity score method to use, as using different methods can generate different results., (Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.)

Deficiency in the methyl donors vitamin B12 and folate during pregnancy and postnatal life impairs proper brain development. We studied the consequences of this combined deficiency on cerebellum plasticity in offspring from rat mothers subjected to deficient diet during gestation and lactation and in rat neuroprogenitor cells expressing cerebellum markers. The major proteomic change in cerebellum of 21-d-old deprived females was a 2.2-fold lower expression of synapsins, which was confirmed in neuroprogenitors cultivated in the deficient condition. A pathway analysis suggested that these proteomic changes were related to estrogen receptor α (ER-α)/Src tyrosine kinase. The influence of impaired ER-α pathway was confirmed by abnormal negative geotaxis test at d 19-20 and decreased phsophorylation of synapsins in deprived females treated by ER-α antagonist 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP). This effect was consistent with 2-fold decreased expression and methylation of ER-α and subsequent decreased ER-α/PPAR-γ coactivator 1 α (PGC-1α) interaction in deficiency condition. The impaired ER-α pathway led to decreased expression of synapsins through 2-fold decreased EGR-1/Zif-268 transcription factor and to 1.7-fold reduced Src-dependent phosphorylation of synapsins. The treatment of neuroprogenitors with either MPP or PP1 (4-(4'-phenoxyanilino)-6,7-dimethoxyquinazoline, 6,7-dimethoxy-N-(4-phenoxyphenyl)-4-quinazolinamine, SKI-1, Src-l1) Src inhibitor produced similar effects. In conclusion, the deficiency during pregnancy and lactation impairs the expression of synapsins through a deregulation of ER-α pathway., (© FASEB.)

Background: Low back pain is among the most common and costly chronic health care conditions. Recent research has highlighted the common occurrence of non-specific low back pain in adolescents, with prevalence estimates similar to adults. While multiple clinical trials have examined the effectiveness of commonly used therapies for the management of low back pain in adults, few trials have addressed the condition in adolescents. The purpose of this paper is to describe the methodology of a randomized clinical trial examining the effectiveness of exercise with and without spinal manipulative therapy for chronic or recurrent low back pain in adolescents., Methods/design: This study is a randomized controlled trial comparing twelve weeks of exercise therapy combined with spinal manipulation to exercise therapy alone. Beginning in March 2010, a total of 184 participants, ages 12 to 18, with chronic or recurrent low back pain are enrolled across two sites. The primary outcome is self-reported low back pain intensity. Other outcomes include disability, quality of life, improvement, satisfaction, activity level, low back strength, endurance, and motion. Qualitative interviews are conducted to evaluate participants' perceptions of treatment., Discussion: This is the first randomized clinical trial assessing the effectiveness of combining spinal manipulative therapy with exercise for adolescents with low back pain. The results of this study will provide important evidence on the role of these conservative treatments for the management of low back pain in adolescents., Trial Registration: (ClinicalTrials.gov NCT01096628).

In this systematic review, we present a comprehensive and up-to-date systematic review of the literature as it relates to the efficacy and effectiveness of spinal manipulation or mobilization in the management of cervical, thoracic, and lumbar-related extremity pain. There is moderate quality evidence that spinal manipulation is effective for the treatment of acute lumbar radiculopathy. The quality of evidence for chronic lumbar spine-related extremity symptoms and cervical spine-related extremity symptoms of any duration is low or very low. At present, no evidence exists for the treatment of thoracic radiculopathy. Future high-quality studies should address these conditions., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The purpose of this report is to provide a succinct but comprehensive summary of the scientific evidence regarding the effectiveness of manual treatment for the management of a variety of musculoskeletal and non-musculoskeletal conditions., Methods: The conclusions are based on the results of systematic reviews of randomized clinical trials (RCTs), widely accepted and primarily UK and United States evidence-based clinical guidelines, plus the results of all RCTs not yet included in the first three categories. The strength/quality of the evidence regarding effectiveness was based on an adapted version of the grading system developed by the US Preventive Services Task Force and a study risk of bias assessment tool for the recent RCTs., Results: By September 2009, 26 categories of conditions were located containing RCT evidence for the use of manual therapy: 13 musculoskeletal conditions, four types of chronic headache and nine non-musculoskeletal conditions. We identified 49 recent relevant systematic reviews and 16 evidence-based clinical guidelines plus an additional 46 RCTs not yet included in systematic reviews and guidelines.Additionally, brief references are made to other effective non-pharmacological, non-invasive physical treatments., Conclusions: Spinal manipulation/mobilization is effective in adults for: acute, subacute, and chronic low back pain; migraine and cervicogenic headache; cervicogenic dizziness; manipulation/mobilization is effective for several extremity joint conditions; and thoracic manipulation/mobilization is effective for acute/subacute neck pain. The evidence is inconclusive for cervical manipulation/mobilization alone for neck pain of any duration, and for manipulation/mobilization for mid back pain, sciatica, tension-type headache, coccydynia, temporomandibular joint disorders, fibromyalgia, premenstrual syndrome, and pneumonia in older adults. Spinal manipulation is not effective for asthma and dysmenorrhea when compared to sham manipulation, or for Stage 1 hypertension when added to an antihypertensive diet. In children, the evidence is inconclusive regarding the effectiveness for otitis media and enuresis, and it is not effective for infantile colic and asthma when compared to sham manipulation.Massage is effective in adults for chronic low back pain and chronic neck pain. The evidence is inconclusive for knee osteoarthritis, fibromyalgia, myofascial pain syndrome, migraine headache, and premenstrual syndrome. In children, the evidence is inconclusive for asthma and infantile colic.

Background: Intussusception is a rare cause of bowel obstruction in adults, typically associated with malignancy, granuloma formation, a foreign body or an anatomic defect., Case: A 21-year-old, primiparous woman presented at 33 5/7 weeks' gestation with vague abdominal symptoms consistent with acute viral gastroenteritis. She did not improve with conservative measures. A presumptive diagnosis of severe preeclampsia was made based on elevated blood pressure, abnormal liver function tests and epigastric pain. Labor was induced 34 5/7 weeks' gestation. The patient did not improve after an uncomplicated vaginal delivery. Abdominal radiographs and computed tomography were consistent with intussusception. Surgical findings were consistent with the radiologic findings. The patient underwent a right hemicolectomy with stapled anastomosis. No pathologic or anatomically anomalous lead point was identified intraoperatively or on final pathology., Conclusion: Intussusception is a rare finding in the peripartum period, often presenting with vague abdominal symptoms and mistaken for benign obstetric and nonobstetric diseases. This case is only the second one of adult perinatal intussusception without an anatomic or pathologic lead point.

The efficacy of fungicides in controlling cottonball disease of cranberry was tested during 1996 to 1998 at three locations in Wisconsin. For some fungicides, the efficacy of four applications, two each during shoot elongation and bloom, was compared with two applications during bloom only. Spraying twice during bloom was as effective in controlling secondary infection as spraying twice during shoot elongation plus twice during bloom. Azoxystrobin, cyprodinil, and propiconazole were equally effective. None of the treatments affected yield, fruit retention, or berry weight compared with the controls. Sensitivity of M. oxycocci, the cottonball pathogen, to fenbuconazole and propiconazole was tested in vitro by comparing the distributions of ED 50 values of populations collected from three sites that differed in previous exposure to fungicides. Median ED 50 values for fenbuconazole were significantly greater at sites where sterol demethylation inhibitor fungicides had been used compared with a site where fungicides had never been used, but median ED 50 values for propiconazole did not differ among sites. There was no correlation between the sensitivities to fenbuconazole and propiconazole. The data will form the basis of recommendations aimed at delaying the onset of fungicide resistance and will provide a baseline for monitoring resistance to fenbuconazole and propiconazole in populations of M. oxycocci in the future.

The Minnesota Multiphasic Personality Inventory (MMPI) was administered to 73 patients with traumatic brain injury to objectively evaluate emotional status. Profile analysis indicated that many patients were suffering from emotional disturbance. Higher distress levels were evident among those with minor head injury relative to severe head injury. Observed MMPI profiles for these two head injury groups were consistent with previous research and expectations related to the typical consequences of the post-concussion syndrome. The potential value of the MMPI with the head injury population as well as the need for cautious interpretation and integration of impressions derived from other sources is discussed.

Among the drug-metabolizing enzymes present in the rat brain, one form of UDP-glucuronyltransferase catalyzes the formation of the polar metabolite 1-naphthyl-beta-D-glucuronide from 1-naphthol. We measured the activity of this isoform in different brain regions and showed its heterogeneous distribution. Conjugation activities were found to be the highest in the olfactory bulbs (25.4 nmol/h/mg protein) and lowest in the cerebellum (4.5 nmol/h/mg protein). As the blood-brain barrier prevents the passage of hydrosoluble molecules, we studied in vivo the characteristics of the efflux of labeled 1-naphthyl-beta-D-glucuronide injected into the lateral ventricle and the cortex tissue, using tritiated water and labeled inulin as reference compounds. The results reported here indicate that intracerebrally formed glucuronide is cleared from brain tissue by both diffusion and a saturable efflux process.

Several families of brain parenchyma and microvessel endothelial cell enzymes can metabolize substrates of exogenous origin. This xenobiotic metabolism includes functionalization and conjugation reactions and results in detoxication, but also possibly in the formation of pharmacologically active or neurotoxic products. The brain is partially protected from chemical insults by the physical barrier formed by the cerebral microvasculature of endothelial cells, which prevents the influx of hydrophilic molecules. These cells provide also, as a result of their drug-metabolizing enzyme activities, a metabolic barrier against penetrating lipophilic substances. The involvement of these enzymatic activities in neurotoxic events, probably responsible for neuronal dysfunctioning and/or death, neurodegenerative diseases and normal aging, is discussed.

We studied 33 consecutive patients with tuberculous pulmonary cavities complicated by fungus balls to evaluate their treatment. Nineteen had surgical resection for massive or recurrent bleeding or possibility of tumor. One patient died of postpneumonectomy empyema (30-day surgical mortality, 5 percent). Fourteen had no surgery. No patient died of hemoptysis. Respiratory failure contributed most often to death. Hepatic complications and other problems of alcoholism were also prominent. Good results can be obtained by resection in these severely ill patients if care is taken to preserve functioning pulmonary tissue and to avoid complications of alcoholic hepatic disease. Within these constraints, tuberculous cavities complicated by mycetomas should be resected for massive or recurrent hemoptysis.