Search

Collin N Smith,1 John D Kraemer,2 Andrea C Johnson,1 Darren Mays1 1Department of Oncology, Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, DC, USA; 2Department of Health Systems Administration, School of Nursing and Health Studies, Georgetown University, Washington, DC, USA Abstract: Tobacco industry marketing is a primary factor influencing cigarette smoking behavior and the cigarette pack has become an important marketing vehicle for tobacco companies. Standardized “plain” cigarette packaging is advocated as a public health policy to prevent and reduce morbidity and mortality caused by smoking by reducing youth smoking initiation and promoting cessation among smokers. Plain packaging was implemented in Australia in December 2012, and several other countries are considering doing so, but each faces foreseeable legal resistance from opponents to such measures. Tobacco companies have challenged these public health policies, citing international trade agreements and intellectual property laws. Decision-making in these court cases will hinge in part on whether the evidence indicates the public health benefits of plain packaging outweigh any potential harm to tobacco manufacturers’ interests. We reviewed the available evidence in support of plain packaging, finding evidence from observational, experimental, and population-based studies. Results indicate that plain packaging can reduce positive perceptions of smoking and dissuade tobacco use. Governments deciding to implement plain cigarette packaging measures can rely on this evidence to help make a strong case that plain packaging plays an important role in the context of comprehensive smoking prevention efforts. Keywords: cigarette smoking, tobacco, plain packaging, regulation, policy

Americans with disabilities represent the largest historically underserved and marginalized health disparity population in the United States. This perspective piece will raise the awareness of physical therapist faculty and clinicians on gaps in health care provider knowledge about disability and provide actionable strategies, frameworks, and resources available to improve disability competence to make changes in clinical education and practice. In this perspective piece, 3 contributions are made. First, health disparities experienced by Americans with disabilities as a result of health care providers' biased assumptions about disability and lack of disability competence are described through an in-depth illustration of lived experiences of people with disabilities. Second, a discussion of disability competence in physical therapist education is provided. Finally, critical and evidence-based insights and actionable frameworks and resources to address disability competence training gaps and to promote anti-ableist practice are provided., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Tiagabine has been associated with reports of status epilepticus as well as encephalopathy, even when used within therapeutic doses. Vagus nerve stimulation (VNS) has been used successfully to reduce seizure frequency in the outpatient setting as well as in the acute setting of status epilepticus. It is also theorized to reduce cortical synchronization. We present a case of a patient on adjunctive tiagabine therapy who developed sudden onset encephalopathy and rhythmic delta activity soon after vagus nerve stimulation was turned off in preparation for magnetic resonance imaging. The bilateral rhythmic delta activity significantly reduced in burden after VNS was turned back on and encephalopathy also gradually improved to baseline. We hypothesize that vagus nerve stimulation successfully interrupted diffuse hypersynchrony, in the form of bilateral rhythmic delta activity, caused by tiagabine. To our knowledge, this is the first report of such a phenomenon., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Low temperatures pose a dramatic challenge to plant viability. Chilling and freezing disrupt cellular processes, forcing metabolic adaptations reflected in alterations to membrane compositions. Understanding the mechanisms of plant cold tolerance is increasingly important due to anticipated increases in the frequency, severity, and duration of cold events. This review synthesizes current knowledge on the adaptive changes of membrane glycerolipids, sphingolipids, and phytosterols in response to cold stress. We delve into key mechanisms of low temperature membrane remodeling, including acyl editing and headgroup exchange, lipase activity, and phytosterol abundance changes, focusing on their impact at the subcellular level. Furthermore, we tabulate and analyze current gycerolipidomic data from cold treatments of Arabidopsis, maize, and sorghum. This analysis highlights congruencies of lipid abundance changes in response to varying degrees of cold stress. Ultimately, this review aids in rationalizing observed lipid fluctuations and pinpoints key gaps in our current capacity to fully understand how plants orchestrate these membrane responses to cold stress., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Robust and sensitive clinical measures are needed for more accurate and earlier detection of Alzheimer's disease (AD), for staging preclinical AD, and for gauging the efficacy of treatments. Mild impairment on episodic memory tests is thought to indicate a cognitive risk of developing AD and mild cognitive impairment (MCI), considered to be a transitional stage between normal aging and AD. Novel tests of semantic memory, such as memory for news events, are also impaired early on but have received little clinical attention even though they may provide a novel way to assess cognitive risk for AD. We examined memory for news events in older adults with normal cognition (NC, N = 34), amnestic MCI (aMCI, N = 27), or non-aMCI (N = 10) using the Retrograde Memory News Events Test (RM-NET). We asked if news event memory was sensitive to 1) aMCI and also non-aMCI, which has rarely been examined, 2) genetic risk for dementia (positive family history of any type of dementia, presence of an APOE-4 allele, or polygenic risk for AD), and 3) subjective memory functioning judgments about the past. We found that both MCI subgroups exhibited impaired RM-NET Lifespan accuracy scores together with temporally-limited retrograde amnesia. For the aMCI group amnesia extended back 45 years prior to testing, but not beyond that time frame. The extent of retrograde amnesia could not be reliably estimated in the small non-aMCI group. The effect sizes of having MCI on the RM-NET were medium for the non-aMCI group and large for the aMCI group, whereas the effect sizes of participant characteristics on RM-NET accuracy scores were small. For the combined MCI group (N = 37), news event memory was significantly related to positive family history of dementia but was not related to the more specific genetic markers of AD risk. For the NC group, news event memory was not related to any measure of genetic risk. Objective measures of past memory from the RM-NET were not related to subjective memory judgements about the present or the recent past in either group. By contrast, when individuals subjectively compared their present versus past memory abilities, there was a significant association between this judgment and objective measures of the past from the RM-NET (direct association for the NC group and inverse for the MCI group). The RM-NET holds significant promise for early identification of those with cognitive and genetic risk factors for AD and non-AD dementias., Competing Interests: Declaration of competing interest None., (Published by Elsevier Ltd.)

Cotton is an important agricultural crop to many regions across the globe but is sensitive to low-temperature exposure. The activity of the enzyme SENSITIVE TO FREEZING 2 (SFR2) improves cold tolerance of plants and produces trigalactosylsyldiacylglycerol (TGDG), but its role in cold sensitive plants, such as cotton remains unknown. Recently, it was reported that cotton SFR2 produced very little TGDG under normal and cold conditions. Here, we investigate cotton SFR2 activation and TGDG production. Using multiple approaches in the native system and transformation into Arabidopsis thaliana , as well as heterologous yeast expression, we provide evidence that cotton SFR2 activates differently than previously found among other plant species. We conclude with the hypothesis that SFR2 in cotton is not activated in a similar manner regarding acidification or freezing like Arabidopsis and that other regions of SFR2 protein are critical for activation of the enzyme than previously reported.

Background: Diminished postoperative knee extension strength may occur after anterior cruciate ligament reconstruction (ACLR) with quadriceps tendon (QT) autograft. Factors influencing the restoration of knee extensor strength after ACLR with QT autograft remain undefined., Purpose: To identify factors that influence knee extensor strength after ACLR with QT autograft., Study Design: Case-control study; Level of evidence, 3., Methods: The authors performed a retrospective review of patients who underwent primary ACLR with QT autograft at a single institution between 2010 and 2021. Patients were included if they completed electromechanical dynamometer testing at least 6 months after surgery. Exclusion criteria consisted of revision ACLR, <6 months of follow-up, concomitant procedure (osteotomy, cartilage restoration), and concomitant ligamentous injury requiring surgery. Knee extension limb symmetry index (LSI) was obtained by comparing the peak torque of the operated and nonoperated extremities. Univariable and multivariable analyses were performed to identify factors associated with knee extension LSI in the patient, injury, rehabilitation, and preoperative patient-reported outcomes score domains., Results: A total of 107 patients (58 male; mean age, 22.8 years) were included. Mean knee extension LSI of the overall cohort was 0.82 ± 0.18 at 7.5 ± 2.0 months; 35 patients (33%) had a value of ≥0.90. Multivariable analysis demonstrated significant negative associations between knee extension LSI and female sex (-0.12; P < .001), increased age at the time of surgery (-0.01; P = .018), and larger QT graft width (-0.049; P = .053)., Conclusion: Factors influencing knee extensor LSI after ACLR with QT autograft in this study population spanned patient and surgical factors, including female sex, older age at the time of surgery, and wider graft harvest. Surgeons should consider the association between these factors and lower postoperative knee extensor LSI to optimize patient outcomes., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding. J.J.G. has received grant support from Arthrex; education payments from Smith & Nephew, Mid-Atlantic Surgical Systems, and Great Lakes Orthopedics. V.M. has received consulting fees from Smith & Nephew. B.P.L. has received education payments from Mid-Atlantic Surgical Systems. J.D.H. has received grant support from Arthrex, education payments from Mid-Atlantic Surgical Systems and Smith & Nephew, and hospitality payments from SI-BONE. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval for this study was obtained from the University of Pittsburgh (reference No. 19030196)., (© The Author(s) 2024.)

Despite growing acceptability of health-related social needs (HRSN) screening and increasing policy incentives for adoption, clinical implementation of HRSN screening remains low. HRSN screening has been particularly difficult for Community Health Centers (CHCs), which have limited resources to implement and sustain new workflows. While CHCs provide care to patients with disproportionately high levels of unmet social needs, identifying HRSN screening implementation strategies that take CHC-specific contexts into account remains elusive. This study uses the Practical Robust Implementation and Sustainability Model (PRISM) to design an implementation strategy accounting for the unique context of CHCs. We used Rapid Ethnographic Assessment observations and stakeholder focus groups to identify current workflow barriers and facilitators to HRSN screening, and to develop implementation strategies that include multi-level contexts and perspectives. We identified eight themes contributing to low screening implementation: perceived stigma around screening; need for community-based solutions; re-confirming organizational priorities and values; Electronic Medical Record (EMR) limitations; multi-tasking pressures limiting implementation; staff turnover; limited knowledge of regulatory requirements; and community resource availability for referral. Based on the themes, we identified implementation strategies including non-EMR data collection; integration into the workflow for multiple staff members; creation of new training and educational modules; and identification of peer champions for retraining in real time. Administrative requirements are necessary but not sufficient for implementation of HRSN screening in CHCs. Resource-constrained settings benefit from context-specific stakeholder engagement to improve implementation success. The use of PRISM ensured contextual factors were central to the implementation strategy design., (Published by Oxford University Press on behalf of the Society of Behavioral Medicine 2023.)

Introduction: Declarative memories are initially dependent on the hippocampus and become stabilized through the neural reorganization of connections between the medial temporal lobe and neocortex. The exact time-course of these neural changes is not well established, although time-dependent changes in retrieval-related brain function can be detected across relatively short time periods in humans (e.g., hours to months)., Methods: In a study involving older adults with normal cognition (N = 24), we investigated changes in brain activity and functional connectivity associated with the long-term memory consolidation of verbal material over one month. Participants studied fact-like, three-word sentences at 1-month, 1-week, 1-day, and 1-hour intervals before a recognition memory test inside an MRI scanner. Old/new recognition with confidence ratings and response times were recorded. We examined whole-brain changes in retrieval-related brain activity, as well as functional connectivity of the hippocampus and ventromedial prefrontal cortex (vmPFC), as memories aged from 1 hour to 1 month. Secondary analyses minimized the effect of confounding factors affected by memory age (i.e., changes in confidence and response time or re-encoding of targets)., Results: Memory accuracy, confidence ratings, and response times changed with memory age. A memory age network was identified where retrieval-related brain activity in cortical regions increased or decreased as a function of memory age. Hippocampal brain activity in an anatomical region of interest decreased with memory age. Importantly, these changes in retrieval-related activity were not confounded with changes in activity related to concomitant changes in behavior or encoding. Exploratory analyses of vmPFC functional connectivity as a function of memory age revealed increased connectivity with the posterior parietal cortex, as well as with the vmPFC itself. In contrast, hippocampal functional connectivity with the vmPFC and orbitofrontal cortex decreased with memory age., Discussion: The observed changes in retrieval-related brain activity and functional connectivity align with the predictions of standard systems consolidation theory. These results suggest that processes consistent with long-term memory consolidation can be identified over short time periods using fMRI, particularly for verbal material., Competing Interests: The 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., (Copyright © 2024 Tallman, Luo and Smith.)

Objective: To compare postoperative isometric quadriceps strength indices (QI%) and hamstring strength limb symmetry indices (HI%) between partial thickness quadriceps tendon (pQT), full thickness quadriceps tendon (fQT), and bone-patellar-tendon bone (BPTB) autograft anterior cruciate ligament reconstruction (ACLR)., Methods: Patients with primary ACLR with pQT, fQT, or BPTB autograft with the documentation of quantitative postoperative strength assessments between 2016 and 2021 were included. Isometric Biodex data, including QI% and HI% (calculated as the percentage of involved to uninvolved limb strength) were collected between 5 and 8 months and between 9 and 15 months postoperatively., Results: In total, 124 and 51 patients had 5-8- and 9-15-month follow-up strength data, respectively. No significant difference was detected between groups for sex. However, patients undergoing fQT were found to be older than those undergoing BPTB (24.6±7 vs 20.2±5; ​p = 0.01). There were no significant differences in the number of concomitant meniscus repairs between the groups (pQT vs. fQT vs. BPTB). No significant differences were detected in median (min-max) QI% between pQT, fQT, and BPTB 5-8 months [87 ​% (44%-130 ​%), 84 ​% (44%-110 ​%), 82 ​% (37%-110 ​%) or 9-15 months [89 ​% (50%-110 ​%), 89 ​% (67%-110 ​%), and 90 ​% (74%-140 ​%)] postoperatively. Similarly, no differences were detected in median HI% between the groups 5-8 months or 9-15 months postoperatively., Conclusion: The study was unable to detect differences in the recovery of quadriceps strength between patients undergoing ACLR with pQT, fQT, and BPTB autografts at 5-8 months and 9-15-months postoperatively., Level of Evidence: III., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Primary care physicians (PCPs) often face a complex intersection of patient expectations, evidence, and policy that influences their care recommendations for acute low back pain (aLBP). The purpose of this study was to elucidate patterns of PCP orders for patients with aLBP, identify the most common patterns, and describe patient clinical and demographic characteristics associated with patterns of aLBP care., Methods: This prospective cohort study included 9574 aLBP patients presenting to 1 of 77 primary care practices in 4 geographic locations in the United States. We performed a cluster analysis of PCP orders extracted from electronic health records within the first 21 days of an initial visit for aLBP., Results: 1401 (15%) patients did not receive a PCP order related to back pain within the first 21 days of their initial visit. These patients predominantly had aLBP without leg pain, less back-related disability, and were at low-risk for persistent disability. Of the remaining 8146 patients, we found 4 distinct order patterns: combined nonpharmacologic and first-line medication (44%); second-line medication (39%); imaging (10%); and specialty referral (7%). Among all patients, 29% received solely 1 order from their PCP. PCPs more often combined different guideline concordant and discordant orders. Patients with higher self-reported disability and psychological distress were more likely to receive guideline discordant care., Conclusion: Guideline discordant orders such as steroids and NSAIDS are often combined with guideline recommended orders such as physical therapy. Further defining patient, clinician, and health care setting characteristics associated with discordant care would inform targeted efforts for deimplementation initiatives., Competing Interests: Conflict of interest: The authors have no conflicts of interest to declare., (© Copyright by the American Board of Family Medicine.)

Immunofluorescent microscopy enables the examination of cellular expression and localization of proteins. Cellular localization can often impact protein function, as certain molecular interactions occur in specific cellular compartments. Here we describe in detail the processes necessary for identifying phosphatases in the cell through immunofluorescent microscopy. Identification of phosphatase expression and localization could lead to the discovery of protein function in disease states along with potential substrates and binding partners., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Physical activity (PA) may help maintain brain structure and function in aging. Since the intensity of PA needed to effect cognition and cerebrovascular health remains unknown, we examined associations between PA and cognition, regional white matter hyperintensities (WMH), and regional cerebral blood flow (CBF) in older adults., Method: Forty-three older adults without cognitive impairment underwent magnetic resonance imaging (MRI) and comprehensive neuropsychological assessment. Waist-worn accelerometers objectively measured PA for approximately one week., Results: Higher time spent in moderate to vigorous PA (MVPA) was uniquely associated with better memory and executive functioning after adjusting for all light PA. Higher MVPA was also uniquely associated with lower frontal WMH volume although the finding was no longer significant after additionally adjusting for age and accelerometer wear time. MVPA was not associated with CBF. Higher time spent in all light PA was uniquely associated with higher CBF but not with cognitive performance or WMH volume., Conclusions: Engaging in PA may be beneficial for cerebrovascular health, and MVPA in particular may help preserve memory and executive function in otherwise cognitively healthy older adults. There may be differential effects of engaging in lighter PA and MVPA on MRI markers of cerebrovascular health although this needs to be confirmed in future studies with larger samples. Future randomized controlled trials that increase PA are needed to elucidate cause-effect associations between PA and cerebrovascular health.

Background: While there is extensive literature on the use of allograft versus autograft in anterior cruciate ligament (ACL) reconstruction, there is limited clinical evidence to guide the surgeon in choice of allograft tissue type., Purpose: To assess the revision rate after primary ACL reconstruction with allograft and to compare revision rates based on allograft tissue type and characteristics., Study Design: Cohort study; Level of evidence, 3., Methods: Patients who underwent primary allograft ACL reconstructions at a single academic institution between 2015 and 2019 and who had minimum 2-year follow-up were included. Exclusion criteria were missing surgical or allograft tissue type data. Demographics, operative details, and subsequent surgical procedures were collected. Allograft details included graft tissue type (Achilles, bone-patellar tendon-bone [BTB], tibialis anterior or posterior, semitendinosus, unspecified soft tissue), allograft category (all-soft tissue vs bone block), donor age, irradiation duration and intensity, and chemical cleansing process. Revision rates were calculated and compared by allograft characteristics., Results: Included were 418 patients (age, 39 ± 12 years; body mass index, 30 ± 9 kg/m 2 ). The revision rate was 3% (11/418) at a mean follow-up of 4.9 ± 1.4 years. There were no differences in revision rate according to allograft tissue type across Achilles tendon (3%; 3/95), BTB (5%; 3/58), tibialis anterior or posterior (3%; 5/162), semitendinosus (0%; 0/46), or unspecified soft tissue (0%; 0/57) ( P = .35). There was no difference in revision rate between all-soft tissue versus bone block allograft (6/283 [2%] vs 5/135 [4%], respectively; P = .34). Of the 51% of grafts with irradiation data, all grafts were irradiated, with levels varying from 1.5 to 2.7 Mrad and 82% of grafts having levels of <2.0 Mrad. There was no difference in revision rate between the low-dose and medium-to high-dose irradiation cohorts (4% vs 6%, respectively; P = .64)., Conclusion: Similarly low (0%-6%) revision rates after primary ACL reconstruction were seen regardless of allograft tissue type, bone block versus all-soft tissue allograft, and sterilization technique in 418 patients with mean age of 39 years. Surgeons may consider appropriately processed allograft tissue with or without bone block when indicating ACL reconstruction in older patients., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: I.D.E. has received grant support from Arthrex and education payments from Mid-Atlantic Surgical Systems and Smith & Nephew. A.J.C. has received grant support from Arthrex and education payments from Smith & Nephew, Mid-Atlantic Surgical Systems, Arthrex, and Supreme Orthopedic Systems. J.D.H. has received grant support from Arthrex; education payments from Mid-Atlantic Surgical Systems, Smith & Nephew, and Medical Device Business Services; and hospitality payments from SI-BONE. B.P.L. has received education payments from Mid-Atlantic Surgical Systems. V.M. has received consulting and nonconsulting fees from Smith & Nephew. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval for this study was obtained from the University of Pittsburgh (No. 19030196)., (© The Author(s) 2023.)

Background: Mild traumatic brain injury (mTBI) affects ~18,000 military personnel each year, and although most will recover in 3-4 weeks, many experience persisting symptoms and impairment lasting months or longer. Current standard of care for U.S. military personnel with complex mTBI involves initial (<48 h) prescribed rest, followed by behavioral (e.g., physical activity, sleep regulation, stress reduction, hydration, nutrition), and symptom-guided management. There is growing agreement that mTBI involves different clinical profiles or subtypes that require a comprehensive multidomain evaluation and adjudication process, as well as a targeted approach to treatment. However, there is a lack of research examining the effectiveness of this approach to assessing and treating mTBI. This multisite randomized controlled trial (RCT) will determine the effectiveness of a targeted multidomain (T-MD) intervention (anxiety/mood, cognitive, migraine, ocular, vestibular; and sleep, autonomic) compared to usual care (behavioral management) in military-aged civilians with complex mTBI., Methods: This study employs a single-blinded, two-group repeated measures design. The RCT will enroll up to 250 military-aged civilians (18-49 yrs) with a diagnosed complex mTBI within 8 days to 6 months of injury from two concussion specialty clinics. The two study arms are a T-MD intervention and a usual care, behavioral management control group. All participants will complete a comprehensive, multidomain clinical evaluation at their first clinical visit. Information gathered from this evaluation will be used to adjudicate mTBI clinical profiles. Participants will then be randomized to either the 4-week T-MD or control arm. The T-MD group will receive targeted interventions that correspond to the patient's clinical profile (s) and the control group will receive behavioral management strategies. Primary outcomes for this study are changes from enrollment to post-intervention on the Neurobehavioral Symptom Inventory (NSI), Patient Global Impression of Change (PGIC), and functional near-infrared spectroscopy (fNIRS). Time to return to activity (RTA), and healthcare utilization costs will also be assessed., Discussion: Study findings may inform a more effective approach to treat complex mTBI in military personnel and civilians, reduce morbidity, and accelerate safe return-to-duty/activity., Ethics and Dissemination: The study is approved by the University of Pittsburgh Institutional Review board and registered at clinicaltrials.gov. Dissemination plans include peer-reviewed publications and presentations at professional meetings., Clinical Trial Registration: www.clinicaltrials.gov, identifier: NCT04549532., Competing Interests: AK and MC receive funding for research through the University of Pittsburgh from the National Football League and royalties from APA Books. MC was a co-developer and shareholder for ImPACT applications (ended December 2019). 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., (Copyright © 2023 Elbin, Trbovich, Womble, Mucha, Fedor, Stephenson, Holland, Dollar, Sparto, Durfee, Patterson, Smith, Huppert, Okonkwo, Collins and Kontos.)

Purpose: To determine whether surgeon volume affects revision rate following primary anterior cruciate ligament reconstruction (ACLR) with allograft and to determine whether surgeon volume impacts allograft tissue type used., Methods: All patients aged 14 years or older who underwent primary allograft ACLR at a large hospital system between January 2015 to December 2019 with minimum 2-year follow-up were included. Patients with double-bundle ACLR, multiligament reconstruction, and absent allograft type data were excluded. Surgeon volume was categorized as 35 or more ACLR/year for high-volume surgeons and less than 35 ACLR/year for low-volume surgeons. Revision was defined as subsequent ipsilateral ACLR. Patient characteristics, operative details, allograft type, and revision ACLR rates were retrospectively collected. Revision rate and allograft type were analyzed based on surgeon volume., Results: A total of 457 primary allograft ACLR cases (mean age: 38.8 ± 12.3 years) were included. Low-volume surgeons experienced greater revision rates (10% vs 5%, P  = .04) and used allograft in a younger population (37.6 vs 40.0 years old, P  = .03) than high-volume surgeons. Subgroup analysis of the total cohort identified a significantly increased failure rate in patients <25 years old compared with ≥25 years old (30% vs 4%, P < .001). Allograft type selection varied significantly between surgeon volume groups, with low-volume surgeons using more bone-patellar tendon-bone ( P < .001) and less semitendinosus allograft ( P  = .01) than high-volume surgeons. No differences in revision rate were observed based on allograft type ( P  = .71)., Conclusions: There was a greater revision rate following primary allograft ACLR among low-volume surgeons compared with high-volume surgeons. Low-volume surgeons also used allograft in a younger population than did high-volume surgeons., Level of Evidence: Level III, retrospective comparative prognostic trial., (© 2023 The Authors.)

Objective: We assessed whether race or ethnicity was associated with the incidence of high-impact chronic low back pain (cLBP) among adults consulting a primary care provider for acute low back pain (aLBP)., Methods: In this secondary analysis of a prospective cohort study, patients with aLBP were identified through screening at seventy-seven primary care practices from four geographic regions. Incidence of high-impact cLBP was defined as the subset of patients with cLBP and at least moderate disability on Oswestry Disability Index [ODI >30]) at 6 months. General linear mixed models provided adjusted estimates of association between race/ethnicity and high-impact cLBP., Results: We identified 9,088 patients with aLBP (81.3% White; 14.3% Black; 4.4% Hispanic). Black/Hispanic patients compared to White patients, were younger and more likely to be female, obese, have Medicaid insurance, worse disability on ODI, and were at higher risk of persistent disability on STarT Back Tool (all P < .0001). At 6 months, more Black and Hispanic patients reported high-impact cLBP (30% and 25%, respectively) compared to White patients (15%, P < .0001, n = 5,035). After adjusting for measured differences in socioeconomic and back-related risk factors, compared to White patients, the increased odds of high-impact cLBP remained statistically significant for Black but not Hispanic patients (adjusted odds ration [aOR] = 1.40, 95% confidence interval [CI]: 1.05-1.87 and aOR = 1.25, 95%CI: 0.83-1.90, respectively)., Conclusions: We observed an increased incidence of high-impact cLBP among Black and Hispanic patients compared to White patients. This disparity was partly explained by racial/ethnic differences in socioeconomic and back-related risk factors. Interventions that target these factors to reduce pain-related disparities should be evaluated., Clinicaltrials.gov Identifier: NCT02647658., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although the infection rates for bone-patellar tendon-bone autograft (BTB), hamstring tendon autograft (HT), and allograft have been reported previously, there are limited data available for a large cohort of individuals undergoing anterior cruciate ligament (ACL) reconstruction (ACLR) using quadriceps tendon autograft (QT)., Purpose: The aims of this study are (1) to compare rates of septic arthritis after primary and revision ACLR with QT, BTB, HT, and allograft and (2) to evaluate the association between an infection after ACLR and potential risk factors in a large single-system analysis., Study Design: Cohort study; Level of evidence, 3., Methods: All ACLR cases performed by 10 high-volume sports medicine fellowship-trained ACL surgeons between January 2000 and January 2022 were retrospectively analyzed. Minimum follow-up was 90 days after ACLR, and all multiligament reconstructions were excluded. Demographic information, surgical variables, infection characteristics, and rate of ACL graft retention were collected for all included patients. Independent samples t test, chi-square test, or Fisher exact tests with adjusted Benjamini-Hochberg post hoc procedure were used for group comparisons., Results: In total, 6652 patients were included in this study. The most commonly used graft was allograft (n = 2491; 37.4%), followed by HT (n = 1743; 26.2%), BTB (n = 1478; 22.2%), and QT (n = 940; 14.1%). The overall postoperative rate of septic arthritis was 0.34% (n = 23). Septic arthritis rates based on graft type were 0.74% (n = 13) for HT, 0.24% (n = 6) for allograft, 0.20% (n = 3) for BTB, and 0.10% (n = 1) for QT. While a statistically significant difference with regard to graft type ( P = .01) was observed, no significant relationships were found between postoperative septic arthritis and age, sex, revision ACLR, ACLR surgical technique, and accompanying intra-articular procedures for all septic arthritis patients ( P > .05). The average time from the onset of the symptoms of infection to surgical irrigation and debridement (I&D) was 2 days (minimum, 0; maximum, 6). ACL grafts were retained during I&D procedures in all patients with postoperative septic arthritis., Conclusion: The postoperative rate of septic arthritis was 0.1% after use of the QT autograft. While graft choice may affect rates of septic arthritis after ACLR, patient characteristics, ACLR technique, revision ACLR, and accompanying intra-articular procedures during ACLR were not associated with postoperative septic arthritis with the numbers available for analysis.

Phosphatase of Regenerating Liver-3 (PRL-3) is associated with cancer progression and metastasis. The mechanisms that drive PRL-3's oncogenic functions are not well understood, partly due to a lack of research tools available to study this protein. We have begun to address these issues by developing alpaca-derived single domain antibodies, or nanobodies, targeting PRL-3 with a KD of 30-300 nM and no activity towards highly homologous family members PRL-1 and PRL-2. We found that longer and charged N-terminal tags on PRL-3, such as GFP and FLAG, changed PRL-3 localization compared to untagged protein, indicating that the nanobodies may provide new insights into PRL-3 trafficking and function. The nanobodies perform equally, if not better, than commercially available antibodies in immunofluorescence and immunoprecipitation. Finally, hydrogen-deuterium exchange mass spectrometry (HDX-MS) showed that the nanobodies bind partially within the PRL-3 active site and can interfere with PRL-3 phosphatase activity. Co-immunoprecipitation with a known PRL-3 active site binding partner, the CBS domain of metal transporter CNNM3, showed that the nanobodies reduced the amount of PRL-3:CBS inter-action. The potential of blocking this interaction is highly relevant in cancer, as multiple research groups have shown that PRL-3 binding to CNNM proteins is sufficient to promote metastatic growth in mouse models. The anti-PRL-3 nanobodies represent an important expansion of the research tools available to study PRL-3 function and can be used to define the role of PRL-3 in cancer progression., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Smith 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.)

Following cervical spine fusion there is a reduction in maximum range of motion (ROM) but how this impacts activity of daily living (ADLs) and quality of life is unknown. This study's purpose is to quantify maximum and functional cervical spine ROM in patients with multi-level cervical fusion (>3 levels) compared to controls during ADLs and to correlate functional range of motion with scores from patient reported outcomes measures (PROs) including the Comparative Pain Scale (CPS), Fear Avoidance Belief Questionnaire (FABQ), and Neck Disability Index (NDI). An inertial measurement unit (IMU) system quantified ROM during ADLs in the extension/flexion, lateral bending, and axial rotation directions of motion. The reliability of this system was compared to standard optical motion tracking. Fourteen participants (8 females, age = 60.0 years (18.7) (median, (interquartile range)) with a history of multi-level cervical fusion (years post-op 0.9 (0.7)) were compared to 16 controls (13 females, age = 52.1 years (15.8)). PROs were collected for each participant. Fusion participants had significantly decreased maximum ROM in all directions of motion. Fusion participants had decreased ROM for some ADLs (backing up a car, using a phone, donning socks, negotiating stairs). CPS, FABQ, and NDI scores were significantly increased in fusion participants. Reductions in two activities (backing up a car, stair negotiation) correlated with a combination of increased PRO scores. Cervical fusion decreases maximum ROM and is correlated with increased PROs in some ADLs, however there is minimal impact on functional ROM. Investigation into velocity and acceleration may yield categorization of pathologic movement., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Abstract: Treatment effect modifiers identify patient characteristics associated with treatment responses. The purpose of this secondary analysis was to identify potential treatment effect modifiers for disability from the TARGET trial that compared usual care (control) with usual care + psychologically informed physical therapy (PIPT). The sample consisted of a STarT Back tool identified high-risk patients with acute low back pain that completed Oswestry Disability Index (ODI) data at index visit and 6 months later (n = 1250). Candidate treatment effect modifiers were identified a priori and informed by the literature. Linear mixed models tested for treatment effect modification through tests of statistical interaction. All statistical interactions ( P ≤ 0.20) were stratified by modifier to inspect for specific effects ( P ≤ 0.05). Smoking was identified as a potential effect modifier (treatment * smoking interaction, P = 0.08). In participants who were smokers, the effect of PIPT was (ODI = 5.5; 95% CI: 0.6-10.4; P = 0.03) compared with usual care. In participants who were nonsmokers, the effect of PIPT was (ODI = 1.5; 95% CI: -1.4 to 4.4; P = 0.31) compared with usual care. Pain medication was also identified as a potential effect modifier (treatment × pain medication interaction, P = 0.10). In participants prescribed ≥3 pain medications, the effect of PIPT was (ODI = 7.1; 95% CI: -0.1 to 14.2; P = 0.05) compared with usual care. The PIPT effect for participants prescribed no pain medication was (ODI = 3.5; 95% CI: -0.4 to 7.4; P = 0.08) and for participants prescribed 1 to 2 pain medications was (ODI = 0.6; 95% CI: -2.5 to 3.7; P = 0.70) when compared with usual care. These findings may be used for generating hypotheses and planning future clinical trials investigating the effectiveness of tailored application of PIPT., (Copyright © 2022 International Association for the Study of Pain.)

Background: Revision total hip arthroplasty (THA) for adverse local tissue reactions (ALTRs) secondary to head-neck taper corrosion is associated with a high complication rate. Diagnosis of ALTR is based on risk stratification using the patient's history and examination, implant risk, serum metal ion levels, and imaging. The purpose of this study was to determine if stratification using similar risk factors is predictive of outcomes following revision THA for metal-on-polyethylene (MoP) ALTR., Methods: We performed a retrospective review on 141 patients revised for ALTR due to head-neck taper corrosion. Pain outcomes following surgery were analyzed using a generalized linear mixed model. Complications were defined as instability/dislocation, infection, fracture, nerve palsy, leg-length discrepancy, or reoperation., Results: The overall complication rate was 17.7%. The odds of having pain decreased by 44% after revision surgery (Odds Ratio = 0.56, 95% Confidence Interval: 0.324 to 0.952). There was no significant difference in instability/dislocation based on either increased or decreased head-neck offset (P = .67) or magnetic resonance imaging findings of abductor loss, effusion size, and degree of ALTR (P = .73). Increased serum cobalt (P = .31) and chromium (P = .08) levels did not predict complications; however, a decreased cobalt-chromium ratio was associated with postoperative complications (2.8 versus 3.5; P = .002)., Conclusion: These findings are the first to suggest that patients who have ALTR after MoP THA undergoing revision surgery demonstrated major pain relief. Increasing femoral head offset did not change rates of instability/dislocation. In clinical scenarios where preoperative cobalt-chromium femoral head offsets were greater than available ceramic head offsets, a mandatory decrease in femoral head offset did not increase rates of instability/dislocation., (Copyright © 2022. Published by Elsevier Inc.)

Competing Interests: All authors have no conflicts of interest to declare.

Novel tests of semantic memory (SM)-for example, memory for news events (NE; news facts) or famous personalities-are useful for estimating the severity of retrograde amnesia. Individuals with mild cognitive impairment exhibit relatively intact SM/language on traditional neuropsychological tests but exhibit consistent impairment on novel tests of SM, suggesting novel SM tests are dissimilar from traditional SM tests. To identify the relationship between NE memory and traditional cognitive measures, older adults ( N = 51) completed a traditional neuropsychological battery and the Retrograde Memory News Events Test (RM-NET; a new test that robustly measures NE memory across the adult life span with high temporal resolution), and the relationship between performance on these tests was examined. Total RM-NET scores were more closely aligned with episodic memory scores than SM scores. The strength of the association between NE scores and episodic memory scores decreased as the age of NE memory increased. Tests of news events appear to reflect performance on traditional tests of episodic memory rather than SM, especially when recent news events are tested., (© 2022 Cawley-Bennett et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: Pregabalin (PGB) is an effective adjunctive treatment for focal epilepsy and acts by binding to the alpha2-delta subunit of voltage-gated calcium channels to reduce excitatory neurotransmitter release. Limited data exist on its use in the neurocritical care setting, including cyclic seizures-a pattern of recurrent seizures occurring at nearly regular intervals. Although the mechanism underpinning cyclic seizures remains elusive, spreading excitation linked to spreading depolarizations may play a role in seizure recurrence and periodicity. PGB has been shown to increase spreading depolarization threshold; hence, we hypothesized that the magnitude of antiseizure effect from PGB is more pronounced in patients with cyclic versus noncyclic seizures in a critically ill cohort with recurrent seizures., Methods: We conducted a retrospective case series of adults admitted to two academic neurointensive care units between January 2017 and March 2019 who received PGB for treatment of seizures. Data collected included demographics, etiology of brain injury, antiseizure medications, and outcome. Continuous electroencephalogram recordings 48 hours before and after PGB administration were reviewed by electroencephalographers blinded to the administration of antiseizure medications to obtain granular data on electrographic seizure burden. Cyclic seizures were determined quantitatively (i.e., < 50% variation of interseizure intervals for at least 50% of consecutive seizures). Coprimary outcomes were decrease in hourly seizure burden in minutes and decrease in seizure frequency in the 48 hours after PGB initiation. We used nonparametric tests for comparison of seizure frequency and burden and segmented linear regression to assess PGB effect., Results: We included 16 patients; the median age was 69 years, 11 (68.7%) were women, three (18.8%) had undergone a neurosurgical procedure, and five (31%) had underlying epilepsy. All seizures had focal onset; ten patients (62.5%) had cyclic seizures. The median hourly seizure burden over the 48 hours prior to PGB initiation was 1.87 min/hour (interquartile range 1.49-8.53), and the median seizure frequency was 1.96 seizures/hour (interquartile range 1.06-3.41). In the 48 hours following PGB (median daily dose 300 mg, range 75-300 mg), the median number of seizures per hour was reduced by 0.80 seizures/hour (95% confidence interval 0.19-1.40), whereas the median hourly seizure burden decreased by 1.71 min/hour (95% confidence interval 0.38-3.04). When we compared patients with cyclic versus noncyclic seizures, there was a relative decrease in hourly seizure frequency (- 86.7% versus - 2%, p = 0.04) and hourly seizure burden (- 89% versus - 7.8%, p = 0.03) at 48 hours., Conclusions: PGB was associated with a relative reduction in seizure burden in neurocritically ill patients with recurrent seizures, especially those with cyclic seizures, and may be considered in the therapeutic arsenal for refractory seizures. Whether this effect is mediated via modulation of spreading depolarization requires further study., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

The cotton osteotomy or the medial cuneiform opening wedge osteotomy has been a common adjunct procedure in flatfoot reconstruction to correct for forefoot varus or a dorsiflexed first ray. The main goal of the study is to retrospectively review outcomes specifically in the short-intermediate term for the cotton osteotomy. The medical records of a single foot and ankle surgeon (PRB) were reviewed for patients who met inclusion and exclusion criteria. The study period was from January 2006 to October 2018. The analysis was performed using information obtained from chart-review to examine union and complication rates, as well as changes in the cuneiform articular angle based on graft size and type. A total of 71 feet in 61 patients underwent cotton osteotomies for flatfoot reconstruction. Overall complication rate was 5.6% (4/71) with 2 nonunions (2/47) in those that had radiographic follow-up of greater than 9 months. Change in cuneiform articular angle (CAA) showed 0.91° of correction per 1-millimeter increase in graft wedge size from preoperative to 3 weeks. Change for anterior-posterior medial cuneiform bisection dorsal length (AP length) was 0.70 mm per 1 mm of graft used from preoperative to 3 weeks. 6 weeks to 10 weeks showed statistically significant changes in the CAA (p = .01) and the AP length (p = .002). The cotton osteotomy showed statistically significant radiographic loss of correction between the 6- and 10-week time points when patients were allowed to begin weightbearing. Metal grafts may provide maintenance of correction which warrants future studies on their efficacy., (Copyright © 2021 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Episodic memory impairment and hippocampal pathology are hallmark features of both temporal lobe epilepsy (TLE) and amnestic mild cognitive impairment (aMCI). Pattern separation (PS), which enables the distinction between similar but unique experiences, is thought to contribute to successful encoding and retrieval of episodic memories. Impaired PS has been proposed as a potential mechanism underling episodic memory impairment in aMCI, but this association is less established in TLE. In this study, we examined behavioral PS in patients with TLE and explored whether profiles of performance in TLE are similar to aMCI., Method: Patients with TLE, aMCI, and age-matched, healthy controls (HCs) completed a modified recognition task that relies on PS for the discrimination of highly similar lure items, the Mnemonic Similarity Task (MST) . Group differences were evaluated and relationships between clinical characteristics, California Verbal Learning Test-Second Edition scores, and MST performance were tested in the TLE group., Results: Patients with TLE and aMCI demonstrated poorer PS performance relative to the HCs, but performance did not differ between the two patient groups. Neither the side of seizure focus nor having hippocampal sclerosis affected performance in TLE. However, TLE patients with clinically defined memory impairment showed the poorest performance., Conclusion: Memory performance on a task that relies on PS was disrupted to a similar extent in TLE and aMCI. The MST could provide a clinically useful tool for measuring hippocampus-dependent memory impairments in TLE and other neurological disorders associated with hippocampal damage.

Background: Periprosthetic joint infection (PJI) mortality rate is approximately 20%. The etiology for high mortality remains unknown. The objective of this study was to determine whether mortality was associated with preoperative morbidity (frailty), sequalae of treatment, or the PJI disease process itself., Methods: A multicenter observational study was completed comparing 184 patients treated with septic revision total knee arthroplasty (TKA) to a control group of 38 patients treated with aseptic revision TKA. Primary outcomes included time and the cause of death. Secondary outcomes included preoperative comorbidities and Charlson Comorbidity Index (CCMI) measured preoperatively and at various postoperative timepoints., Results: The septic revision TKA cohort experienced earlier mortality compared to the aseptic cohort, with a higher mortality rate at 90 days, 1, 2, and 3 years after index revision surgery (P = .01). There was no significant difference for any single cause of death (P > .05 for each). The mean preoperative CCMI was higher (P = .005) in the septic revision TKA cohort. Both septic and aseptic cohorts experienced a significant increase in CCMI from the preoperative to 3 years postoperative (P < .0001 and P = .002) and time of death (P < .0001 both) timepoints. The septic revision TKA cohort had a higher CCMI 3 years postoperatively (P = .001) and at time of death (P = .046), but not one year postoperatively (P = .119)., Conclusion: Compared to mortality from aseptic revision surgery, septic revision TKA is associated with earlier mortality, but there is no single specific etiology. As quantified by changes in CCMI, PJI mortality was associated with both frailty and the PJI disease process, but not treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Several novel ideas and suggestions were made in response to our discussion paper (Tallman et al., this issue). Careful consideration of the content and context of memory while accounting for the neuroanatomy and functional specialization of the hippocampus may reveal more consistent patterns in fMRI studies of memory consolidation. Below we address these ideas as well as issues that arise when interpreting the fMRI signal in memory consolidation studies. In addition, we describe new analyses suggested by the commentators that clarify our findings with respect to current theories.

Theories of memory consolidation suggest the role of brain regions and connectivity between brain regions change as memories age. Human lesion studies indicate memories become hippocampus-independent over years, whereas animal studies suggest this process occurs across relatively short intervals, from days to weeks. Human neuroimaging studies suggest that changes in hippocampal and cortical activity and connectivity can be detected over these short intervals, but many of these studies examined only two time periods. We examined memory and fMRI activity for photos of indoor and outdoor scenes across four time periods to examine these neural changes more carefully. Participants (N = 21) studied scenes 1 hour, 1 day, 1 week, or 1 month before scanning. During scanning, participants viewed scenes, made old/new recognition memory judgments, and gave confidence ratings. Memory accuracy, confidence ratings, and response times changed with memory age. Brain activity in a widespread cortical network either increased or decreased with memory age, whereas hippocampal activity was not related to memory age. These findings were almost identical when effects of behavioral changes across time periods were minimized. Functional connectivity of the ventromedial prefrontal cortex with the posterior parietal cortex increased with memory age. By contrast, functional connectivity of the hippocampus with the parahippocampal cortex and fusiform gyrus decreased with memory age. In sum, we detected changes in cortical activity and changes in hippocampal and cortical connectivity with memory age across short intervals. These findings provide support for the predictions of systems consolidation and suggest that these changes begin soon after memories are formed.

Background: Adverse local tissue reaction (ALTR) is a recognized complication of total hip arthroplasty (THA) with metal-on-polyethylene (MoP) bearing surface implants. Specific models of THA implants have been identified as having a higher incidence of ALTR. The purpose of this study is to determine if serum metal levels, patient symptoms, implant factors, and imaging findings can be predictive of ALTR within this high-risk population., Methods: We retrospectively reviewed an observational cohort of 474 patients who underwent MoP THA and were at increased risk of having ALTR. Patients were stratified based on the presence or absence of ALTR. Patient symptoms, serum metal ions, implant head offset, and imaging findings were compared., Results: Patients with ALTR were more likely to be symptomatic (52.9% vs 9.9%, P < .0001). The presence of ALTR was associated with significantly higher serum cobalt and chromium levels (6.2 ppb vs 3.6 ppb, P  < .0001; 2.3 ppb vs 1.2 ppb, P < .0001). Head offsets greater than 4 mm were associated with a higher prevalence of ALTR (53% vs 38%, P  = .05). On metal artifact reduction sequence magnetic resonance imaging, patients with ALTR had larger effusions (4.7 cm vs 2.1 cm, P < .001) and a higher incidence of trochanteric bursitis (47% vs 16%, P < .001)., Conclusions: In high-risk MoP implants, serum cobalt and chromium levels are elevated, even in patients without ALTR. A larger femoral head offset is a risk factor for the development of ALTR. Our study suggests that patients presenting with painful THA and elevated metal ions require risk stratification based on patient symptoms, metal artifact reduction sequence magnetic resonance imaging findings, and implant factors., (© 2021 The American Association of Hip and Knee Surgeons. Published by Elsevier Inc.)

Purpose: The purpose of this study was to review post-operative complications after surgical intervention of MLKIs within the first 6 months to be better able to counsel patients before surgical intervention., Methods: All patients who underwent surgical reconstruction for a MLKI at one institution from 2009 to 2018 were included in this study. A retrospective review was performed of all patients and post-operative complications were recorded, including motion loss (which included > 10 degree flexion loss or > 3 degree extension loss), hematoma formation, infection, iatrogenic vascular or nerve injury, deep vein thrombosis (DVT), pulmonary embolism (PE), skin lesions, symptomatic hardware, recurrent ligamentous laxity, and need for additional surgery. Knee ligament injuries were classified based on the Schenck Knee Dislocation (KD) Classification., Results: A total of 136 patients were included in this study, 83 with KD I injuries, 40 with KD III injuries, 9 with KD IV injuries, and 4 with KD V injuries. Of these total patients, 48 (35.5%) sustained a post-operative complication: 11 out of 133 (8.3%) from 0 to 1 week, 46 out of 132 (34.8%) from 1 week to 1 month, 28 out of 124 (22.6%) from 1 to 3 months, and 26 out of 121 (21.5%) from 3 to 6 months. Out of the total complications, 99 (78.5%) occurred at 1 week-3 months post-operation. Patients who had an external fixator placed at initial injury were more likely to sustain a post-operative complication. The most common complication was motion loss in 39 (28.6%) patients. There was a significant difference in mean number of complications between the KD I and KD III groups, as well as the KD III and KD IV-V groups. There was no significant difference in the overall prevalence of post-operative complications or occurrence of motion loss with KD grade., Conclusion: The main finding of this study was 48 (35.5%) patients sustained a complication after surgical treatment of MLKIs, with 99 (78.5% of all complications) complications occurring at 1 week-3 months post-operation. Patients who had an external fixator placed at initial injury were more likely to sustain a post-operative complication. The most common post-operative complication was motion loss in 39 (28.6%) patients. The KD grade was not associated with post-operative development of motion loss, but KD III had a significantly greater mean number of complications than KD I or KD IV-V grades., Level of Evidence: IV., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Over 34 000 patients are diagnosed yearly with multiple myeloma (MM), which remains a fatal malignancy. Expression of the phosphatase PRL-3 is associated with poor prognosis in MM patients, and Vandsemb et al. have demonstrated that PRL-3 contributes to enhanced MM cell fitness through activation of a glycolysis-associated feedback loop. PRL-3 resulted in increased expression of signal transducer and activator of transcription 1 (STAT1) and 2 (STAT2) and increased glycolysis. Increased glucose metabolism in turn activated STAT1/2 and interferon 1-related genes. This discovery advances the MM field by providing a new potential treatment avenue. Comment on: https://doi.org/10.1111/febs.16058., (© 2021 Federation of European Biochemical Societies.)

Background: Professional burnout represents a significant threat to the American healthcare system. Organizational and individual factors may increase healthcare providers' susceptibility or resistance to burnout. We hypothesized that during the COVID-19 pandemic, 1) higher levels of perceived organizational support (POS) are associated with lower risk for burnout and anxiety, and 2) anxiety mediates the association between POS and burnout., Methods: In this longitudinal prospective study, we surveyed healthcare providers employed full-time at a large, multihospital healthcare system monthly over 6 months (April to November 2020). Participants were randomized using a 1:1 allocation stratified by provider type, gender, and academic hospital status to receive one of two versions of the survey instrument formulated with different ordering of the measures to minimize response bias due to context effects. The exposure of interest was POS measured using the validated 8-item Survey of POS (SPOS) scale. Primary outcomes of interest were anxiety and risk for burnout as measured by the validated 10-item Burnout scale from the Professional Quality (Pro-QOL) instrument and 4-item Emotional Distress-Anxiety short form of the Patient Reported Outcome Measurement Information System (PROMIS) scale, respectively. Linear mixed models evaluated the associations between POS and both burnout and anxiety. A mediation analysis evaluated whether anxiety mediated the POS-burnout association., Results: Of the 538 participants recruited, 402 (75%) were included in the primary analysis. 55% of participants were physicians, 73% 25-44 years of age, 73% female, 83% White, and 44% had ≥1 dependent. Higher POS was significantly associated with a lower risk for burnout (-0.23; 95% CI -0.26, -0.21; p<0.001) and lower degree of anxiety (-0.07; 95% CI -0.09, -0.06; p = 0.010). Anxiety mediated the associated between POS and burnout (direct effect -0.17; 95% CI -0.21, -0.13; p<0.001; total effect -0.23; 95% CI -0.28, -0.19; p<0.001)., Conclusion: During a health crisis, increasing the organizational support perceived by healthcare employees may reduce the risk for burnout through a reduction in anxiety. Improving the relationship between healthcare organizations and the individuals they employ may reduce detrimental effects of psychological distress among healthcare providers and ultimately improve patient care., Competing Interests: No author have competing interests.

Background: Diagnosis of adverse local tissue reaction (ALTR) in metal-on-polyethylene (MoP) total hip arthroplasty (THA) secondary to head-neck taper corrosion is challenging. The purpose of this study is to compare differences between asymptomatic and symptomatic ALTR in an observational cohort, including presentation, metal ion differences, and metal artifact reduction sequence (MARS) magnetic resonance imaging (MRI) findings., Methods: We performed a retrospective review of an observational cohort of 492 MoP THA patients at increased risk of developing ALTR. Ninety-four patients underwent revision arthroplasty for ALTR. Patients were stratified into symptomatic and asymptomatic ALTR groups. Presentation, metal ion levels, and imaging findings were compared., Results: For patients with confirmed ALTR, 41% were asymptomatic. There was a statistically significant difference in the serum chromium levels between symptomatic and asymptomatic ALTR patients (2.2 μg/L vs 3.1 μg/L, P = .05). There was no statistically significant difference between the serum cobalt levels or MRI findings in these 2 groups. We observed that extracapsular disease associated with ALTR could be misinterpreted as trochanteric bursitis., Conclusion: Almost half of the MoP THA ALTR cases identified were asymptomatic. Cobalt levels could not differentiate between symptomatic and asymptomatic pseudotumor formation. Symptomatic and asymptomatic MoP ALTRs have similar MARS MRI characteristics. Our findings suggest that it is essential to risk stratify patients who could potentially have ALTR based on implant type, symptoms, ion levels, and MARS MRI., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In vitro biomechanical studies of the osteoligamentous spine are widely used to characterize normal biomechanics, identify injury mechanisms, and assess the effects of degeneration and surgical instrumentation on spine mechanics. The objective of this study was to determine how well four standards in vitro loading paradigms replicate in vivo kinematics with regards to the instantaneous center of rotation and arthrokinematics in relation to disc deformation. In vivo data were previously collected from 20 asymptomatic participants (45.5 ± 5.8 years) who performed full range of motion neck flexion-extension (FE) within a biplane x-ray system. Intervertebral kinematics were determined with sub-millimeter precision using a validated model-based tracking process. Ten cadaveric spines (51.8 ± 7.3 years) were tested in FE within a robotic testing system. Each specimen was tested under four loading conditions: pure moment, axial loading, follower loading, and combined loading. The in vivo and in vitro bone motion data were directly compared. The average in vitro instant center of rotation was significantly more anterior in all four loading paradigms for all levels. In general, the anterior and posterior disc heights were larger in the in vitro models than in vivo. However, after adjusting for gender, the observed differences in disc height were not statistically significant. This data suggests that in vitro biomechanical testing alone may fail to replicate in vivo conditions, with significant implications for novel motion preservation devices such as cervical disc arthroplasty implants., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, small molecule inhibitors of PRL-3 are lacking. Here, we screened 1443 FDA-approved drugs for their ability to inhibit the activity of the PRL phosphatase family. We identified five specific inhibitors for PRL-3 as well as one selective inhibitor of PRL-2. Additionally, we found nine drugs that broadly and significantly suppressed PRL activity. Two of these broad-spectrum PRL inhibitors, Salirasib and Candesartan, blocked PRL-3-induced migration in human embryonic kidney cells with no impact on cell viability. Both drugs prevented migration of human colorectal cancer cells in a PRL-3 dependent manner and were selective towards PRLs over other phosphatases. In silico modeling revealed that Salirasib binds a putative allosteric site near the WPD loop of PRL-3, while Candesartan binds a potentially novel targetable site adjacent to the CX 5 R motif. Inhibitor binding at either of these sites is predicted to trap PRL-3 in a closed conformation, preventing substrate binding and inhibiting function.

Introduction: Bone is the most common distant site of breast cancer metastasis. Skeletal lesions can cause significant morbidity due to pain, pathologic fracture, and electrolyte abnormalities. Current treatment for patients with bone metastases (BoM) from breast cancer is highly personalized and often involves a multidisciplinary approach with chemotherapy, hormone therapy, bone-targeted antiresorptive agents, radiation therapy, and surgery. We have retrospectively collected clinical data from a series of patients with bone metastases to evaluate the clinical characteristics, prognostic factors, and survival patterns of patients with breast cancer BoM receiving standard multimodal therapy., Methods: A consecutive series of 167 patients with breast cancer BoM treated at a single institution between August 2013 and March 2020 were identified. Clinical information was obtained from the medical record and survival analyses were performed to evaluate patient outcomes and identify prognostic factors., Results: Thirty-seven patients (22%) presented with de novo BoM - bone metastases at the time of breast cancer diagnosis - and were 2.6 times more likely to die within the study period than those with asynchronous BoM (HR = 2.62, p = <0.0001). Patients who received bone-targeted medical therapy were 61% less likely to die after BoM diagnosis than those who did not (HR = 0.39, p = 0.001). Operative stabilization of BoM was more frequently employed in patients with lytic (p = 0.02) or mixed (p = 0.02) tumors than it was for those with blastic lesions. Patients treated with surgery had a lower overall bone metastasis survival than those treated without (p < 0.03)., Discussion: These findings reflect the current patterns in metastatic breast cancer treatment and associated outcomes. In a series of 167 consecutive patients, we demonstrate the natural history of breast cancer with BoM being treated with modern multimodal therapy. Understanding these treatment patterns and prognostic factors enhances the provider's ability to counsel patients and direct appropriate treatments., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Lucas reports other from Amgen, other from Bayer/Loxo, outside the submitted work. Dr. Puhalla reports personal fees from Abbvie, personal fees from Medimmune, personal fees from Puma, personal fees from Pfizer, grants and personal fees from Astra Zeneca, personal fees from Esai, personal fees from Nanostring, grants and non-financial support from Abbvie, grants from Pfizer, grants from Lilly, grants from Novartis, grants from Incyte, grants from Covance-Bayer, grants from Astra-zeneca, grants from Genentech, grants from Medivation, outside the submitted work. All other authors certify that he or she has no commercial associations that might pose a conflict of interest to this submitted article., (© 2021 The Authors.)

Background: Health care providers are unprepared to meet the health needs of patients who have disabilities. Disability training is needed, yet there is little agreement about what should be taught., Objective: Establish a national consensus on what healthcare providers across disciplines need to know to provide quality care to patients with all types of disabilities (e.g., mobility, sensory, developmental, mental health)., Methods: People with disabilities, disability advocates, family members of people with disabilities, disability and health professionals, and inter-disciplinary health educators systematically evaluated and provided feedback on a draft set of disability competencies. Based on this feedback, competencies were iteratively refined., Results: After two waves of feedback, six competencies, 49 sub-competencies, and 10 principles and values emerged that addressed topics such as respect, person-centered care, and awareness of physical, attitudinal, and communication health care barriers. An overwhelming majority (89%) agreed or strongly agreed that the disability competencies reflected the core understandings needed to provide quality care for patients with disabilities, were relevant across disability types (85%), and across health care disciplines (96%). Averaging evaluative feedback across competencies, participants reported that the competencies were important (98%) and clear (96%)., Conclusions: This consensus on what to teach is an important milestone in preparing a disability competent health care workforce. Future directions for research, training, and policy are discussed. When disability is included in health care education, the health care workforce will be prepared to deliver accessible, patient-centered, quality health care to patients with disabilities., Competing Interests: Declaration of competing interest The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention or the Department of Health and Human Services., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Physicians report discomfort when interacting with patients with disabilities, which can negatively impact the quality of healthcare they provide., Objective/hypothesis: An intervention structured around a formative clinical encounter was assessed for its effectiveness in changing comfort towards treating patients with disabilities. It was predicted that this encounter would have a positive short- and long-term impact on medical students., Method: During the 2017-2018 academic year, 169 third-year medical students conducted a patient encounter with a person who had a disability. Students met individually with the "patient" and completed a brief social and medical history as if they were meeting a new patient to establish care. A measure of perceived comfort caring for patients with disabilities was administered to students before and after the encounter. One year after the patient encounter, 59 students were surveyed about their satisfaction and the impact of the patient encounter., Results: The impact of encountering people with disabilities in a clinical setting was positive, with statistically significant improvements across all items on the measure of perceived comfort. Students were highly satisfied with the experience and anticipated feeling more confident, more comfortable, less awkward, and more skilled and efficacious when encountering a person with a disability in their future practice. A thematic analysis of the one year follow-up data suggest that students valued the encounter and desired more content on disability throughout their education., Conclusions: Medical education should include dedicated exposure to persons with disabilities and a simulated patient experience allowing for a safe environment to gain skills and confidence., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: As virtual reality (VR) technologies become increasingly accessible and affordable, clinicians are eager to try VR therapy as a novel means to manage behavioral and psychological symptoms of dementia, which are exacerbated during acute care hospitalization, with the goal of reducing the use of antipsychotics, sedatives, and physical restraints associated with negative adverse effects, increased length of stay, and caregiver burden. To date, no evaluations of immersive VR therapy have been reported for patients with dementia in acute care hospitals., Objective: This study aimed to determine the feasibility (acceptance, comfort, and safety) of using immersive VR therapy for people living with dementia (mild, moderate, and advanced) during acute care hospitalization and explore its potential to manage behavioral and psychological symptoms of dementia., Methods: A prospective, longitudinal pilot study was conducted at a community teaching hospital in Toronto. The study was nonrandomized and unblinded. A total of 10 patients aged >65 years (mean 86.5, SD 5.7) diagnosed with dementia participated in one or more research coordinator-facilitated sessions of viewing immersive 360° VR footage of nature scenes displayed on a Samsung Gear VR head-mounted display. This mixed-methods study included review of patient charts, standardized observations during the intervention, and pre- and postintervention semistructured interviews about the VR experience., Results: All recruited participants (N=10) completed the study. Of the 10 participants, 7 (70%) displayed enjoyment or relaxation during the VR session, which averaged 6 minutes per view, and 1 (10%) experienced dizziness. No interference between the VR equipment and hearing aids or medical devices was reported., Conclusions: It is feasible to expose older people with dementia of various degrees admitted to an acute care hospital to immersive VR therapy. VR therapy was found to be acceptable to and comfortable by most participants. This pilot study provides the basis for conducting the first randomized controlled trial to evaluate the impact of VR therapy on managing behavioral and psychological symptoms of dementia in acute care hospitals., (©Lora Appel, Erika Kisonas, Eva Appel, Jennifer Klein, Deanna Bartlett, Jarred Rosenberg, Christopher NC Smith. Originally published in JMIR Formative Research (http://formative.jmir.org), 03.02.2021.)

Importance: Acute low back pain (LBP) is highly prevalent, with a presumed favorable prognosis; however, once chronic, LBP becomes a disabling and expensive condition. Acute to chronic LBP transition rates vary widely owing to absence of standardized operational definitions, and it is unknown whether a standardized prognostic tool (ie, Subgroups for Targeted Treatment Back tool [SBT]) can estimate this transition or whether early non-guideline concordant treatment is associated with the transition to chronic LBP., Objective: To assess the associations between the transition from acute to chronic LBP with SBT risk strata; demographic, clinical, and practice characteristics; and guideline nonconcordant processes of care., Design, Setting, and Participants: This inception cohort study was conducted alongside a multisite, pragmatic cluster randomized trial. Adult patients with acute LBP stratified by SBT risk were enrolled in 77 primary care practices in 4 regions across the United States between May 2016 and June 2018 and followed up for 6 months, with final follow-up completed by March 2019. Data analysis was conducted from January to March 2020., Exposures: SBT risk strata and early LBP guideline nonconcordant processes of care (eg, receipt of opioids, imaging, and subspecialty referral)., Main Outcomes and Measures: Transition from acute to chronic LBP at 6 months using the National Institutes of Health Task Force on Research Standards consensus definition of chronic LBP. Patient demographic characteristics, clinical factors, and LBP process of care were obtained via electronic medical records., Results: Overall, 5233 patients with acute LBP (3029 [58%] women; 4353 [83%] White individuals; mean [SD] age 50.6 [16.9] years; 1788 [34%] low risk; 2152 [41%] medium risk; and 1293 [25%] high risk) were included. Overall transition rate to chronic LBP at six months was 32% (1666 patients). In a multivariable model, SBT risk stratum was positively associated with transition to chronic LBP (eg, high-risk vs low-risk groups: adjusted odds ratio [aOR], 2.45; 95% CI, 2.00-2.98; P < .001). Patient and clinical characteristics associated with transition to chronic LBP included obesity (aOR, 1.52; 95% CI, 1.28-1.80; P < .001); smoking (aOR, 1.56; 95% CI, 1.29-1.89; P < .001); severe and very severe baseline disability (aOR, 1.82; 95% CI, 1.48-2.24; P < .001 and aOR, 2.08; 95% CI, 1.60-2.68; P < .001, respectively) and diagnosed depression/anxiety (aOR, 1.66; 95% CI, 1.28-2.15; P < .001). After controlling for all other variables, patients exposed to 1, 2, or 3 nonconcordant processes of care within the first 21 days were 1.39 (95% CI, 1.21-2.32), 1.88 (95% CI, 1.53-2.32), and 2.16 (95% CI, 1.10-4.25) times more likely to develop chronic LBP compared with those with no exposure (P < .001)., Conclusions and Relevance: In this cohort study, the transition rate to chronic LBP was substantial and increased correspondingly with SBT stratum and early exposure to guideline nonconcordant care.

Rehabilitation has been shown to improve functional outcomes following total knee replacement (TKR). However, its delivery and associated costs are highly variable. The authors have developed and previously validated the accuracy of a remote (wearable) rehabilitation monitoring platform ( interACTION ). The present study's objective was to assess the feasibility of utilizing interACTION for the remote management of rehabilitation after TKR and to determine a preliminary estimate of the effects of the interACTION system on the value of rehabilitation. Specifically, we tested post-operative outpatient rehabilitation supplemented with interACTION (n = 13) by comparing it to a standard post-operative outpatient rehabilitation program (n = 12) using a randomized design. Attrition rates were relatively low and not significantly different between groups, indicating that participants found both interventions acceptable. A small (not statistically significant) decrease in the number of physical therapy visits was observed in the interACTION Group, therefore no significant difference in total cost could be observed. All patients and physical therapists in the interACTION Group indicated that they would use the system again in the future. Therefore, the next steps are to address the concerns identified in this pilot study and to expand the platform to include behavioral change strategies prior to conducting a full-scale randomized controlled trial. Trial registration: ClinicalTrials.gov NCT02646761 " interACTION : A Portable Joint Function Monitoring and Training System for Remote Rehabilitation Following TKA" 6 January 2016.

Objectives: To assess the construct validity and responsiveness of the floor sitting-rising test (SRT) in individuals with total knee arthroplasty (TKA)., Design: Cohort study with 6-month follow-up. Secondary analysis using data from a randomized controlled trial., Setting: An outpatient rehabilitation research center., Participants: Participants (N=240) enrolled in the parent study who had unilateral primary TKA., Intervention: Participants in the parent study underwent 12 weeks of exercise programs., Main Outcome Measures: Validity analysis correlated baseline data of participants who completed the SRT and measures of knee motion, muscle strength, performance-based tests, and patient-reported outcomes of physical and psychosocial function. Responsiveness analysis used the 3- and 6-month follow-up data. Effect sizes were calculated using changes from baseline. Areas under the receiving operating characteristics curve were calculated using a global rating of change as the external anchor., Results: Of the 240 participants (148 women; age, 70±7y), 180 (75%) were able to perform the SRT at baseline. Performers scored significantly better in all physical function tests (P<.0001) than nonperformers. SRT scores generally converged with measures of knee impairment and performance-based tests (associations ranged from small [r=0.15; P=.0516] to moderate [r=0.52; P<.0001]). SRT scores associated with self-efficacy for function (r=0.34; P<.0001) and fear of falls (r=-0.25; P=.001). At 3 (n=174) and 6 months (n=160), SRT effect sizes were 0.38 (95% confidence interval, 0.25-0.52) and 0.42 (95% confidence interval, 0.25-0.60), and areas under the curve were 0.59 (95% confidence interval, 0.49-0.69) and 0.62 (95% confidence interval, 0.52-0.73), respectively., Conclusions: The results add evidence to the validity of the SRT in patients after TKA. The strength of the associations suggests that the SRT measures a physical function construct not captured by the other tests. The magnitude of indices of responsiveness for the SRT were similar to other performance-based tests, indicating comparable responsiveness to more widespread tests of functional performance., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The pivot-shift test has become more consistent and reliable and is a meaningful outcome measurement after anterior cruciate ligament reconstruction (ACLR)., Purpose/hypothesis: The purpose of this investigation was to assess patient-reported outcomes (PROs) and the quantitative pivot shift (QPS) preoperatively, at time zero immediately after anatomic ACLR, and after 24 months as well as the relationship between PROs and the QPS. It was hypothesized that anatomic ACLR would restore rotatory stability measured by the pivot-shift test and that QPS measurements would be positively correlated with PROs., Study Design: Cohort study; Level of evidence, 2., Methods: The ACL-injured and contralateral uninjured knees from 89 of 107 (83.2%) enrolled patients at 4 international centers were evaluated using a standardized pivot-shift test. Tibial acceleration was assessed with an inertial sensor, and lateral compartment translation was measured using an image analysis system preoperatively, at time zero immediately postoperatively, and at follow-up after 2 years. PROs were assessed at 12 and 24 months postoperatively with the International Knee Documentation Committee (IKDC) subjective knee form, Cincinnati Knee Rating System (CKRS), Marx activity rating scale, and activity of daily living score (ADLS)., Results: The mean patient age at surgery was 27 years (range, 15-45 years). A positive pivot shift preoperatively (side-to-side difference in tibial acceleration, 2.6 ± 4.0 m/s 2 ; side-to-side difference in anterior tibial translation, 2.0 ± 2.0 mm) was reduced at time zero postoperatively (side-to-side difference in tibial acceleration, -0.5 ± 1.3 m/s 2 ; side-to-side difference in anterior tibial translation, -0.1 ± 1.0 mm). All PROs improved from preoperatively to final follow-up at 24 months: from 56.5 to 85.5 points for the IKDC ( P = .0001), from 28.8 to 32.4 points for the CKRS ( P = .04), from 11.2 to 7.9 points for the Marx ( P < .0001), and from 75.7 to 91.6 points for the ADLS ( P < .0001). Neither preoperative nor time zero postoperative rotatory laxity assessed by the pivot-shift test correlated with PROs at 24-month follow-up. A graft retear was observed in 4 patients (4.5%) within 2 years of follow-up., Conclusion: Anatomic ACLR resulted in significantly improved and acceptable PROs at 2-year follow-up and a low failure rate. Anatomic ACLR restored QPS measurements of anterior tibial translation and tibial acceleration to those of the contralateral knee immediately after surgery while still under anesthesia, but there was no correlation between the QPS preoperatively or at time zero after ACLR and PROs at 2-year follow-up., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was funded by an International Society for Arthoscopy, Knee Surgery and Orthopedic Sports Medicine/Orthopedic Research and Eduction Foundation research grant (No. 708661). J.J.I., Y.H., and V.M. are codevelopers of the image analysis system used in this study; at the moment, the system is not on the market and not producing revenue. R.K. has received grants from Smith & Nephew, Zimmer Biomet, Stryker, and Johnson & Johnson; consulting fees from Medacta, Arthrex, Japan Tissue Engineering, and Hirosaki Life Science Innovation; and speaking fees from Arthrex, Smith & Nephew, Zimmer Biomet, Johnson & Johnson, and Japan Tissue Engineering. V.M. has received consulting fees and speaking fees from Smith & Nephew. A.S. has received grant support from Arthrex and Stryker; educational support from Arthrex, Mid-Atlantic Surgical Systems, and Smith & Nephew; and hospitality payments from Stryker. J.M.B. has received grant support from Arthrex and educational support from Arthrex, Smith & Nephew, and Mid-Atlantic Surgical Systems. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2020.)

Background: People with disabilities disproportionately use tobacco and suffer associated negative health consequences. Research is needed to explore tobacco cessation programming for people with disabilities to counter these health disparities., Objective: We evaluated the impact of Living Independent From Tobacco on tobacco use, knowledge and attitudes about tobacco use, coping skills, and perceived health status among people with disabilities. We also assessed participants' subjective impressions at post-test., Methods: Living Independent From Tobacco was evaluated via train the trainer model at three Midwestern sites serving people with disabilities. Outcomes were assessed at four time points: pre- and post-test (n = 30), and again at 1-month (n = 26) and 6-months (n = 13)., Results: Long-term tobacco users with disabilities significantly reduced tobacco use from pre-test to post-test (p = 0.003), and, compared to baseline, this reduction continued to be significant 1-month after the intervention (p = 0.02). From pre-test to post-test, perceived health status significantly improved (p = 0.0001). No significant changes were observed across time points for knowledge and attitudes about tobacco use nor for coping skills. Qualitative data revealed the importance of coping skills to mitigate the negative effects of nicotine withdrawal. Peer accountability was also noted as an important source of motivation for tobacco cessation., Conclusions: Data from the present study provide evidence for the short-term effectiveness of Living Independent From Tobacco to reduce tobacco use and improve health status among people with disabilities. Qualitative data revealed the importance of coping skills and peer accountability to support tobacco cessation. Implications for tobacco cessation programming for people with disabilities are discussed., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

People with disabilities have more health complications and higher healthcare utilization related to tobacco use than people without disabilities. Yet, they are less likely to use tobacco cessation resources. Important to meaningful and lasting health behavior change are relationships developed in the home, workplace, and community. Some people with disabilities rely on paid and unpaid caregivers. Just like people with disabilities, paid caregivers are more likely to use tobacco, creating a unique opportunity to target smoking cessation to people with disabilities and their caregivers. Living Independent From Tobacco (LIFT), an evidence-based tobacco cessation intervention, was implemented with dyads of people with disabilities (n = 5) and their caregivers (n = 7). Qualitative analyses revealed that participants valued the dyadic approach and the opportunity to learn coping skills to help with smoking cessation. Lessons for offering inclusive health promotion interventions to people with disabilities and their caregivers are discussed., (©AAIDD.)