Quitline usage does not improve rates of smoking cessation in orthopaedic trauma patients unless combined with nicotine replacement therapy.

PURPOSE: The negative effects of smoking following traumatic orthopaedic injury can lead to serious complications and decreased quality of life. The widely available quitline could be easily implemented in the orthopaedic postoperative period to improve outcome, but the effectiveness of this intervention in this population is unknown. The goal of this study was to determine if active referral to a quitline would improve rates of smoking cessation in this population. METHODS: This is a secondary analysis of a randomized control trial assessing the effectiveness of an inpatient intervention with varying intensities to promote smoking cessation. Participants were actively referred to the quitline as part of their intervention. Participants were surveyed at 6 weeks, 3 months and 6 months following their injury for 7-day abstinence, chemically confirmed with exhaled carbon monoxide monitoring. RESULTS: Smoking quitline use alone does not independently improve 7-day abstinence. Quitline and nicotine use are synergistic (OR, 5.6 vs. 2.3 at 3 months in patients who used nicotine patch and quitline vs. patch; OR, 7.8 vs. 2.1 at 3 months in patients who used any NRT and quitline vs. NRT alone). CONCLUSIONS: NRT use improves smoking cessation rates in orthopaedic trauma patients. Although smoking quitline use might not independently improve cessation rates in orthopaedic trauma patients postoperatively, concomitant use of NRT with quitline improves quit rates over NRT alone. Patients referred to quitline should be encouraged to use NRT.

Differential efficacy of two small molecule PHLPP inhibitors to promote nucleus Pulposus cell health.

Background: Intervertebral disc (IVD) degeneration is associated with chronic back pain. We previously demonstrated that the phosphatase pleckstrin homology domain and leucine-rich repeat protein phosphatase (PHLPP) 1 was positively correlated with IVD degeneration and its deficiency decelerated IVD degeneration in both mouse IVDs and human nucleus pulposus (NP) cells. Small molecule PHLPP inhibitors may offer a translatable method to alleviate IVD degeneration. In this study, we tested the effectiveness of the two PHLPP inhibitors NSC117079 and NSC45586 in promoting a healthy NP phenotype. Methods: Tail IVDs of 5-month-old wildtype mice were collected and treated with NSC117079 or NSC45586 under low serum conditions ex vivo. Hematoxylin & eosin staining was performed to examine IVD structure and NP cell morphology. The expression of KRT19 was analyzed through immunohistochemistry. Cell apoptosis was assessed by TUNEL assay. Human NP cells were obtained from patients with IVD degeneration. The gene expression of KRT19, ACAN, SOX9, and MMP13 was analyzed via real time qPCR, and AKT phosphorylation and the protein expression of FOXO1 was analyzed via immunoblot. Results: In a mouse IVD organ culture model, NSC45586, but not NSC117079, preserved vacuolated notochordal cell morphology and KRT19 expression while suppressing cell apoptosis, counteracting the degenerative changes induced by serum deprivation, especially in males. Likewise, in degenerated human NP cells, NSC45586 increased cell viability and the expression of KRT19, ACAN, and SOX9 and reducing the expression of MMP13, while NSC117079 treatment only increased KRT19 expression. Mechanistically, NSC45586 treatment increased FOXO1 protein expression in NP cells, and inhibiting FOXO1 offset NSC45586-induced regenerative potential, especially in males. Conclusions: Our study indicates that NSC45586 was effective in promoting NP cell health, especially in males, suggesting that PHLPP plays a key role in NP cell homeostasis and that NSC45586 might be a potential drug candidate in treating IVD degeneration.

Community of trauma care partnering with stakeholders to improve injury outcomes: focus group analysis.

Introduction: Engaging trauma survivors/caregivers results in research findings that are more relevant to patients' needs and priorities. Although their perspectives increase research significance, there is a lack of understanding about how best to incorporate their insights. We aimed to capture stakeholder perspectives to ensure research is meaningful, respectful, and relevant to the injured patient and their caregivers. Methods: A multiphase, inductive exploratory qualitative study was performed, the first phase of which is described here. Virtual focus groups to elicit stakeholder perspectives and preferences were conducted across 19 trauma centers in the USA during 2022. Discussion topics were chosen to identify patients' motivation to join research studies, preferences regarding consent, suggestions for increasing diversity and access, and feelings regarding outcomes, efficacy, and exception from informed consent. The focus groups were audio recorded, transcribed, coded, and analyzed to identify the range of perspectives expressed and any common themes that emerged. Results: Ten 90-minute focus groups included patients/caregiver (n=21/1) and researchers (n=14). Data analysis identified common themes emerging across groups. The importance of trust and preexisting relationships with the clinical care team were the most common themes across all groups. Conclusion: Our findings reveal common themes in preferences, motivations, and best practices to increase patient/caregiver participation in trauma research. The project's next phases are distribution of a vignette-based survey to establish broad stakeholder consensus; education and dissemination activities to share strategies that increase research engagement and relevance for patients; and the formation of a panel of patients to support future research endeavors. Level of evidence: Level IV.

PHLPP1 deficiency protects against age-related intervertebral disc degeneration.

Background: Intervertebral disc (IVD) degeneration is strongly associated with low back pain and is highly prevalent in the elderly population. Hallmarks of IVD degeneration include cell loss and extracellular matrix degradation. The PH domain leucine-rich-repeats protein phosphatase (PHLPP1) is highly expressed in diseased cartilaginous tissues where it is linked to extracellular matrix degradation. This study explored the ability of PHLPP1 deficiency to protect against age-related spontaneous IVD degeneration. Methods: Lumbar IVDs of global Phlpp1 knockout (KO) and wildtype (WT) mice were collected at 5 months (young) and 20 months (aged). Picrosirius red-alcian blue staining (PR-AB) was performed to examine IVD structure and histological score. The expression of aggrecan, ADAMTS5, KRT19, FOXO1 and FOXO3 was analyzed through immunohistochemistry. Cell apoptosis was assessed by TUNEL assay. Human nucleus pulposus (NP) samples were obtained from patients diagnosed with IVD degeneration. PHLPP1 knockdown in human degenerated NP cells was conducted using small interfering RNA (siRNA) transfection. The expression of PHLPP1 regulated downstream targets was analyzed via immunoblot and real time quantitative PCR. Results: Histological analysis showed that Phlpp1 KO decreased the prevalence and severity of age-related IVD degeneration. The deficiency of PHLPP1 promoted the increased expression of NP phenotypic marker KRT19, aggrecan and FOXO1, and decreased levels of ADMATS5 and cell apoptosis in the NP of aged mice. In degenerated human NP cells, PHLPP1 knockdown induced FOXO1 protein levels while FOXO1 inhibition offset the beneficial effects of PHLPP1 knockdown on KRT19 gene and protein expression. Conclusions: Our findings indicate that Phlpp1 deficiency protected against NP phenotypic changes, extracellular matrix degradation, and cell apoptosis in the process of IVD degeneration, probably through FOXO1 activation, making PHLPP1 a promising therapeutic target for treating IVD degeneration.

Can You Believe Your Patients If They Say They Have Quit Smoking?

OBJECTIVES: To determine the reliability of self-reported smoking status in the orthopaedic trauma population and determine if certain patient factors might predispose inaccurate self-reported smoking cessation. DESIGN: Prospective. SETTING: Level I trauma center. PATIENTS: Two hundred forty-seven orthopaedic trauma patients were included in the study. INTERVENTION: In-office measurement of exhaled carbon monoxide (CO). MAIN OUTCOME MEASUREMENTS: Self-reported smoking cessation with exhaled CO measurements. RESULTS: A total of 906 self-reported surveys were completed over 4 follow-up visits. Of the responses indicating smoking cessation (n = 174), 12.6% [95% confidence interval (CI), 0.081-0.185] reported smoking cessation with positive CO readings, suggesting inaccurate self-reporting of smoking status. Over 20% of those patients inaccurately reporting abstinence did so more than once. The odds of inaccurate self-reporting was 3 times higher in patients with no insurance or government insurance [odds ratio (OR), 3.5; 95% CI, 1.1-11.0; P = 0.043] and in the unemployed (OR, 3.3; 95% CI, 0.97-8.57; P = 0.049). CONCLUSIONS: Self-reported smoking status in the orthopaedic population is fairly reliable, with 13% of patient's inaccurately self-reporting smoking cessation despite knowing their smoking status was being measured. Clinicians should be aware of the potential for inaccuracy in self-reported smoking cessation, particularly in patients with the identified socioeconomic factors. Point-of-care testing before elective trauma procedures to confirm smoking status might have a role if the procedure outcome is highly dependent on smoking status. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Prospective Randomized Trial on Smoking Cessation in Orthopaedic Trauma Patients: Results From the Let's STOP (Smoking in Trauma Orthopaedic Patients) Now Trial.

OBJECTIVES: Determine if extended inpatient counseling increases smoking cessation. DESIGN: Prospective randomized trial. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: Current smokers with an operative fracture. INTERVENTION: Randomly assigned to control (no counseling), brief counseling (inpatient counseling), or extended counseling (brief counseling plus follow-up counseling) groups in a 1:3:3 ratio. MAIN OUTCOME MEASUREMENTS: Smoking cessation confirmed by exhaled carbon monoxide at 3 and 6 months. Secondary outcomes are proportion accepting services from a nationally based quitline. RESULTS: Overall, 266 patients participated, with 40, 111, and 115 patients in the control and 2 treatment groups, respectively. At 3 months, 17% of control patients versus 11% in the brief counseling and 10% in the extended counseling groups quit smoking, respectively (P = 0.45, 0.37). At 6 months, 15% of control, and 10% and 5% of the respective counseling groups quit (P = 0.45, 0.10). Extended counseling patients were 3 times more likely to accept referral to a quitline [odds ratio (OR), 3.1; 95% confidence interval (CI), 1.4-6.9], and brief counseling patients were more than 2 times as likely to accept referral (OR, 2.3; 95% CI, 1.0-5.1) than the control group. Extended counseling (OR, 8.2; 95% CI, 1.0-68.5) and brief counseling (OR, 5.3; 95% CI, 0.6-44.9) patients were more likely to use quitline services than the control group. CONCLUSION: Increasing levels of inpatient counseling can improve successful referral to a smoking quitline, but it does not seem to influence quit rates among orthopaedic trauma patients. Extended counseling does not appear to provide substantial benefit over brief counseling. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Patient Satisfaction After Discharge Is Discordant With Reported Inpatient Experience.

Patient satisfaction measures are commonly used to evaluate clinical performance. However, research on the correlation between patient satisfaction scores and actual patient experience is limited. This study aimed to determine the concordance between patient satisfaction reported as an inpatient and patient satisfaction reported after discharge. The study enrolled 231 adult orthopedic patients at least 48 hours after admission to an academic hospital. Study participants rated their overall inpatient experience on a scale of 0 to 10, followed by open-ended questions on their hospital experience. Participants were then randomized to a second survey by either phone or mail at 4 to 6 weeks after discharge. Statistical and qualitative techniques were used to assess concordance in satisfaction scores and the agreement and association between patient experiences and patient satisfaction scores. The median overall patient satisfaction scores were 9.5 as inpatients (interquartile range [IQR], 8-10) and 10 at follow-up (IQR, 8-10), with a poor concordance between the inpatient and follow-up satisfaction scores (ρc=0.28). This study raises concerns regarding the validity of patient satisfaction measures to accurately quantify inpatient experience and the limitations related to its modes of administration. The authors observed poor agreement between the reported experience as an inpatient and the recollection of the inpatient experience after discharge. [Orthopedics. 2021;44(3):e427-e433.].

Implementing stakeholder engagement to explore alternative models of consent: An example from the PREP-IT trials.

INTRODUCTION: Cluster randomized crossover trials are often faced with a dilemma when selecting an optimal model of consent, as the traditional model of obtaining informed consent from participant's before initiating any trial related activities may not be suitable. We describe our experience of engaging patient advisors to identify an optimal model of consent for the PREP-IT trials. This paper also examines surrogate measures of success for the selected model of consent. METHODS: The PREP-IT program consists of two multi-center cluster randomized crossover trials that engaged patient advisors to determine an optimal model of consent. Patient advisors and stakeholders met regularly and reached consensus on decisions related to the trial design including the model for consent. Patient advisors provided valuable insight on how key decisions on trial design and conduct would be received by participants and the impact these decisions will have. RESULTS: Patient advisors, together with stakeholders, reviewed the pros and cons and the requirements for the traditional model of consent, deferred consent, and waiver of consent. Collectively, they agreed upon a deferred consent model, in which patients may be approached for consent after their fracture surgery and prior to data collection. The consent rate in PREP-IT is 80.7%, and 0.67% of participants have withdrawn consent for participation. DISCUSSION: Involvement of patient advisors in the development of an optimal model of consent has been successful. Engagement of patient advisors is recommended for other large trials where the traditional model of consent may not be optimal.

Valuing the Recovery Priorities of Orthopaedic Trauma Patients After Injury: Evidence From a Discrete Choice Experiment Within 6 Weeks of Injury.

OBJECTIVES: To determine the recovery priorities of extremity fracture patients during the subacute phase and the patient factors associated with variation in recovery priorities. DESIGN: Discrete choice experiment. SETTING: Academic trauma center. PATIENTS: One hundred ninety-eight patients with a fracture to the appendicular skeleton. Patients with severe traumatic brain injuries, spinal cord injuries, and non-English-speaking patients were excluded. MAIN OUTCOME MEASUREMENT: The relative importance of clinical recovery, work-related recovery, and obtaining disability benefits after injury. RESULTS: In the subacute period, clinical recovery was the main priority for fracture patients (mean: 62%, SD: 5.3). Work-related recovery (mean: 27%, SD: 3.9) and the receipt of other disability benefits (mean: 11%, SD: 6.4) were each of significantly less importance. Heterogeneity was observed across these estimates based on the physical demands of preinjury employment, preinjury physical health, preinjury work status, health insurance type, and the severity of the fracture. CONCLUSION: Clinical recovery was of paramount importance for fracture patients during the subacute recovery phase. However, patients also valued resuming work and access to disability benefits. Understanding a patient's recovery priorities early in the clinical care pathway will enable the development of multidisciplinary care plans that are responsive to these priorities and, hence, deliver value-based health care. LEVEL OF EVIDENCE: Level V. See Instructions for Authors for a complete description of levels of evidence.

Cytotoxicity effects of different surfactant molecules conjugated to carbon nanotubes on human astrocytoma cells.

Phase contrast and epifluorescence microscopy were utilized to monitor morphological changes in human astrocytoma cells during a time-course exposure to single-walled carbon nanotube (SWCNT) conjugates with different surfactants and to investigate sub-cellular distribution of the nanotube conjugates, respectively. Experimental results demonstrate that cytotoxicity of the nanotube/surfactant conjugates is related to the toxicity of surfactant molecules attached on the nanotube surfaces. Both sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) are toxic to cells. Exposure to CNT/SDS conjugates (0.5 mg/mL) for less than 5 min caused changes in cell morphology resulting in a distinctly spherical shape compared to untreated cells. In contrast, sodium cholate (SC) and CNT/SC did not affect cell morphology, proliferation, or growth. These data indicate that SC is an environmentally friendly surfactant for the purification and dispersion of SWCNTs. Epifluorescence microscopy analysis of CNT/DNA conjugates revealed distribution in the cytoplasm of cells and did not show adverse effects on cell morphology, proliferation, or viability during a 72-h incubation. These observations suggest that the SWCNTs could be used as non-viral vectors for diagnostic and therapeutic molecules across the blood-brain barrier to the brain and the central nervous system.

Cytotoxicity of single-walled carbon nanotubes suspended in various surfactants.

The cytotoxicity of single-walled carbon nanotubes (SWCNTs) suspended in various surfactants was investigated by phase contrast light microscopy characterization in combination with an absorbance spectroscopy cytotoxicity analysis. Our data indicate that individual SWCNTs suspended in the surfactants, sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS), were toxic to 1321N1 human astrocytoma cells due to the toxicity of SDS and SDBS on the nanotube surfaces. This toxicity was observed when cells were exposed to an SDS or SDBS solution having a concentration as low as 0.05 mg ml(-1) for 30 min. The proliferation and viability of the cells were not affected by SWCNTs alone or by conjugates of SWCNTs with various concentrations of sodium cholate (SC) or single-stranded DNA. The cells proliferated similarly to untreated cells when surrounded by SWCNTs as they grow, which indicated that the nanotubes did not affect cells adversely. The cytotoxicity of the nanotube-surfactant conjugates was controlled in these experiments by the toxicity of the surfactants. Consequently, when evaluating a surfactant to be used for the dispersion of nanoscale materials in applications such as nanoscale electronics or non-viral biomolecular transporters, the cytotoxicity needs to be evaluated. The methodology proposed in this study can be used to investigate the cytotoxicity of other nanoscale materials suspended in a variety of surfactants.