Impact of a Transitional Pain Service on postoperative opioid trajectories: a retrospective cohort study.

INTRODUCTION: It has been well described that a small but significant proportion of patients continue to use opioids months after surgical discharge. We sought to evaluate postdischarge opioid use of patients who were seen by a Transitional Pain Service compared with controls. METHODS: We conducted a retrospective cohort study using administrative data of individuals who underwent surgery in Ontario, Canada from 2014 to 2018. Matched cohort pairs were created by matching Transitional Pain Service patients to patients of other academic hospitals in Ontario who were not enrolled in a Transitional Pain Service. Segmented regression was performed to assess changes in monthly mean daily opioid dosage. RESULTS: A total of 209 Transitional Pain Service patients were matched to 209 patients who underwent surgery at other academic centers. Over the 12 months after surgery, the mean daily dose decreased by an estimated 3.53 morphine milligram equivalents (95% CI 2.67 to 4.39, p<0.001) per month for the Transitional Pain Service group, compared with a decline of only 1.05 morphine milligram equivalents (95% CI 0.43 to 1.66, p<0.001) for the controls. The difference-in-difference change in opioid use for the Transitional Pain Service group versus the control group was -2.48 morphine milligram equivalents per month (95% CI -3.54 to -1.43, p=0.003). DISCUSSION: Patients enrolled in the Transitional Pain Service were able to achieve opioid dose reduction faster than in the control cohorts. The difficulty in finding an appropriate control group for this retrospective study highlights the need for future randomized controlled trials to determine efficacy.

Open-source pipeline for automatic segmentation and microstructural analysis of murine knee subchondral bone.

µCT images are commonly analysed to assess changes in bone density and microstructure in preclinical murine models. Several platforms provide automated analysis of bone microstructural parameters from volumetric regions of interest (ROI). However, segmentation of the regions of subchondral bone to create the volumetric ROIs remains a manual and time-consuming task. This study aimed to develop an automated end-to-end pipeline, combining segmentation and microstructural analysis, to evaluate subchondral bone in the mouse proximal knee. METHODS: A segmented dataset of µCT scans from 62 knees (healthy and arthritic) from 10-week male C57BL/6 mice was used to train a U-Net type architecture to automate segmentation of the subchondral trabecular bone. These segmentations were used in tandem with the original scans as input for microstructural analysis along with thresholded trabecular bone. Manually and U-Net segmented ROIs were fed into two available pipelines for microstructural analysis: the ITKBoneMorphometry library and CTan (SKYSCAN). Outcome parameters were compared between pipelines, including: bone volume (BV), total volume (TV), BV/TV, trabecular number (TbN), trabecular thickness (TbTh), trabecular separation (TbSp), and bone surface density (BSBV). RESULTS: There was good agreement for all bone measures comparing the manual and U-Net pipelines utilizing ITK (R = 0.88-0.98) and CTAn (R = 0.91-0.98). ITK and CTAn showed good agreement for BV, TV, BV/TV, TbTh and BSBV (R = 0.9-0.98). However, limited agreement was seen between TbN (R = 0.73) and TbSb (R = 0.59) due to methodological differences in how spacing is evaluated. Microstructural parameters generated from manual and automatic segmentations showed high correlation across all measures. Using the CTAn pipeline yielded strong R2 values (0.83-0.96) and very strong agreement based on ICC (0.90-0.98). The ITK pipeline yielded similarly high R2 values (0.91-0.96, except for TbN (0.77)), and ICC values (0.88-0.98). The automated segmentations yield lower average values for BV, TV and BV/TV (ranging from 14 % to 6.3 %), but differences were not found to be influenced by the mean ROI values. CONCLUSIONS: This integrated pipeline seamlessly automated both segmentation and quantification of the proximal tibia subchondral bone microstructure. This automated pipeline allows the analysis of large volumes of data, and its open-source nature may enable the standardization of microstructural analysis of trabecular bone across different research groups.

Cannabis use among pregnant women under different legalization frameworks in the United States.

Background: Cannabis use in pregnancy is associated with adverse neonatal outcomes, yet its use among pregnant women in the United States has increased significantly.Objectives: This cross-sectional study explored how cannabis use in pregnant women varied between different cannabis legalization frameworks, that is, permitted use of cannabidiol (CBD)-only, medical cannabis, and adult-use cannabis.Methods: Behavioral Risk Factor Surveillance System data from 2017 to 2020 was utilized with respondents classified by their state's policies into CBD-only, medical, and adult-use groups. Outcome measures included prevalence of use and usage characteristics (frequency, method of intake, and reason for use) among pregnant women. Logistic regression models were estimated to evaluate the association between legal status and prevalence of use.Results: The unweighted dataset included 1,992 pregnant women. Recent cannabis use was reported by (weighted proportions): 2.4% (95%CI: 0-4.4) of respondents in the CBD-only group, 7.1% (95%CI: 4.0-10.1) in the medical group and 6.9% (95%CI: 3.0-10.9) in the adult-use group. Compared to the CBD-only group, respondents in the medical and adult-use groups were 4.5-fold (adjusted; 95%CI: 1.4-14.7; p = .01) and 4.7-fold (adjusted; 95%CI: 1.3-16.2; p = .02) more likely to use cannabis. Across all groups, smoking was the most common method of intake and over 49% of users reported using partially or entirely for adult-use purposes.Conclusions: The increased use with legalization motivates further research on the impacts of cannabis as a therapeutic agent during pregnancy and supports the need for increased screening and patient counseling regarding the potential effects of cannabis use on fetal development.

Can CD200R1 Agonists Slow the Progression of Osteoarthritis Secondary to Injury?

Post-traumatic knee osteoarthritis is characterized by cartilage degeneration, subchondral bone remodeling, osteophyte formation, and synovial changes. Therapeutic targeting of inflammatory activity in the knee immediately post injury may alter the course of osteoarthritis development. This study aimed to determine whether CD200R1 agonists, namely the protein therapeutic CD200Fc or the synthetic DNA aptamer CCS13, both known to act as anti-inflammatory agents, are able to delay the pathogenesis of injury-associated knee osteoarthritis in a murine model. Ten week old male C57BL/6 mice were randomized and surgical destabilization of the medial meniscus (DMM) to induce knee arthritis or sham surgery as a control were performed. CCS13 was evaluated as a therapeutic treatment along with CD200Fc and a phosphate-buffered saline vehicle control. Oligonucleotides were injected intra-articularly beginning one week after surgery, with a total of six injections administered prior to sacrifice at 12 weeks post-surgery. Histopathological assessment was used as the primary outcome measure to assess cartilage and synovial changes, while µCT imaging was used to compare the changes to the subchondral bone between untreated and treated arthritic groups. We did not find any attenuation of cartilage degeneration or synovitis in DMM mice with CD200Fc or CCS13 at 12 weeks post-surgery, nor stereological differences in the properties of subchondral bone. The use of CD200R1 agonists to blunt the inflammatory response in the knee are insufficient to prevent disease progression in the mouse DMM model of OA without anatomical restoration of the normal joint biomechanics.

The relationship between cannabis use and legalization frameworks: A cross-sectional analysis using a nationally representative survey.

State policies related to cannabis have rapidly evolved but the impact of current legislative frameworks on usage is not well characterized. This study explored cannabis use patterns under different legalization statuses in the United States. The dataset included individuals from the Behavioral Risk Factor Surveillance System survey in 2017 and 2018. Respondents were categorized into limited medical use, full medical use, or full legalization groups based on their state's cannabis policies. The primary outcome was cannabis use in the past 30 days. Among users, we characterized frequency, method, and reason for use. Logistic regression models were estimated to assess associations between legal status and these outcome measures. The study sample included 168,299 respondents. The unweighted proportion of respondents reporting cannabis use were: 4.96% in states with limited medical use, 6.50% in states with full medical use, and 12.33% in states with full legalization. Adjusted odds of use were greater for the full medical use group (1.13, 95%CI:1.02-1.25) and the full legalization group (2.53, 95%CI:2.28-2.82) compared to the limited medical use group. Users were more likely to use non-smoking methods in the full legalization group compared to the limited medical use group (1.77, 95%CI:1.41-2.22). A greater proportion of users in the full legalization group reported medical usage than in the other two groups. Policymakers should consider these findings in order to allow for use while safeguarding public health.

Recent cannabis use and nightly sleep duration in adults: a population analysis of the NHANES from 2005 to 2018.

BACKGROUND: While popularly consumed for its perceived benefits as a sleeping aid, the impact of cannabis on sleep-wake regulation in clinical studies is inconclusive. The purpose of this study was to determine the relationship between cannabis use and nightly sleep duration in a nationally representative dataset. METHODS: A cross-sectional analysis of adults was undertaken using the National Health and Nutrition Examination Survey data from 2005 to 2018. Respondents were dichotomized as recent users or non-users if they had used or not used cannabis in the past 30 days, respectively. The primary outcome was nightly sleep duration, categorized as short (<6 hours), optimal (6-9 hours), and long (>9 hours). Multinomial logistic regression was used to adjust for sociodemographic and health-related covariates, and survey sample weights were used in modeling. RESULTS: From a sample representing approximately 146 million adults in the USA, 14.5% reported recent cannabis use. In an adjusted analysis, recent users were more likely than non-users to report both short sleep (OR 1.34, 95% CI 1.12 to 1.59, p<0.001) and long sleep (OR 1.56, 95% CI 1.25 to 1.96, p<0.001). Heavy users (≥20 of the past 30 days) were even more likely to be at the extremes of nightly sleep duration. DISCUSSION: Recent cannabis use was associated with the extremes of nightly sleep duration in a nationally representative sample of adults, with suggestions of a dose-response relationship. Our findings highlight the need to further characterize the sleep health of regular cannabis users in the population.

Does Coronavirus Disease 2019 (COVID-19) Affect Perioperative Morbidity and Mortality for Patients Requiring Emergency Instrumented Spinal Surgery? A Single-Center Cohort Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic sent shockwaves through health services worldwide. Resources were reallocated. Patients with COVID-19 still required instrumented spinal surgery for emergencies. Clinical outcomes for these patients are not known. The objective of this study was to evaluate the effects of COVID-19 on perioperative morbidity and mortality for patients undergoing emergency instrumented spinal surgery and to determine risk factors for increased morbidity/mortality. METHODS: This retrospective cohort study included 11 patients who were negative for COVID-19 and 8 patients who were positive for COVID-19 who underwent emergency instrumented spinal surgery in 1 hospital in the United Kingdom during the pandemic peak. Data collection was performed through case note review. Patients in both treatment groups were comparable for age, sex, body mass index (BMI), comorbidities, surgical indication, and preoperative neurologic status. Predefined perioperative outcomes were recorded within a 30-day postoperative period. Univariable analysis was used to identify risk factors for increased morbidity. RESULTS: There were no mortalities in either treatment group. Four patients positive for COVID-19 (50%) developed a complication compared with 6 (55%) in the COVID-19-negative group (P > 0.05). The commonest complication in both groups was respiratory infection. Three patients positive for COVID-19 (37.5%) required intensive care unit admission, compared with 4 (36%) in the COVID-19-negative group (P > 0.05). The average time between surgery and discharge was 19 and 10 days in COVID-19-positive and -negative groups, respectively (P = 0.02). In the COVID-19 positive group, smoking, abnormal BMI, preoperative oxygen requirement, presence of fever, and oxygen saturations <95% correlated with increased risk of complications. CONCLUSIONS: Emergency instrumented spinal surgery in patients positive for COVID-19 was associated with increased length of hospital stay. There was no difference in occurrence of complications or intensive care unit admission. Risk factors for increased morbidity in patients with COVID-19 included smoking, abnormal BMI, preoperative oxygen requirement, fever and saturations <95%.

Lithium for Fracture Treatment (LiFT): a double-blind randomised control trial protocol.

INTRODUCTION: Fracture healing can fail in up to 10% of cases despite appropriate treatment. While lithium has been the standard treatment for bipolar disorder, it may also have a significant impact to increase bone healing in patients with long bone fractures. To translate this knowledge into clinical practice, a randomised clinical trial (RCT) is proposed. METHODS AND ANALYSIS: A multicentre double blind, placebo-controlled RCT is proposed to evaluate the efficacy of lithium to increase the rate and predictability of long bone fracture healing in healthy adults compared to lactose placebo treatment. 160 healthy individuals from 18 to 55 years of age presenting with shaft fractures of the femur, tibia/fibula, humerus or clavicle will be eligible. Fractures will be randomised to placebo (lactose) or treatment (300 mg lithium carbonate) group within 2 weeks of the injury. The primary outcome measure will be radiographic union defined as visible callus bridging on three of the four cortices at the fracture site using a validated radiographic union score. Secondary outcome measures will include functional assessment and pain scoring. ETHICS AND DISSEMINATION: Participant confidentiality will be maintained with publication of results. Research Ethics Board Approval: Sunnybrook Research Institute (REB # 356-2016). Health Canada Approval (HC6-24-C201560). Results of the main trial and secondary endpoints will be submitted for publication in a peer-reviewed journal and presented at conferences. TRIAL REGISTRATION NUMBER: NCT02999022.

Perceptions of using lithium in fracture management: a survey of orthopaedic surgeons, fracture patients and the general public.

BACKGROUND: Lithium, an established psychiatric medication, has recently been shown to enhance new bone formation in preclinical fracture models. Current research is focused on evaluating the efficacy of low-dose, short-term lithium treatment to improve long bone fracture healing through a Phase II randomized clinical trial (LiFT NCT02999022). In working towards future applications of lithium for fracture management, this study aimed to understand the current perceptions of lithium as a psychiatric drug and the potential barriers to its orthopaedic adoption. METHODS: Three questionnaires, evaluating knowledge about lithium and willingness to embrace its use in fracture healing were disseminated among the general population, fracture patients eligible for the LiFT (Lithium for Fracture Treatment) trial and orthopaedic surgeons across Canada. RESULTS: Of the 768 public respondents, 84% were willing to take a medication that would aid fracture healing but only 62.6% if the medication was lithium. Willingness dropped to 44.6% among the 168 respondents who knew about the psychiatric use of lithium. Lack of sufficient knowledge (n = 50) and concerns about side effects including effects on the brain (n = 74) were the main reasons cited by those who were unwilling to use lithium. Of the 29 fracture patients, only 20 patients had previously heard of lithium. Of these, 40% were willing to take lithium for fracture healing with an additional 10% if the dose was low or if the intake duration was short. Only 50% knew that lithium has side effects. Of the 43 orthopaedic surgeons, 38 surgeons knew about clinical use of lithium. Of these, 68% knew that lithium has side effects and 29% knew that it interacts with other drugs. While most agreed that new strategies are needed to improve fracture management, only 68% were willing to prescribe lithium for fractures with an additional 16% if there is scientific evidence and/or a standard dosing protocol. CONCLUSIONS: This study identified a lack of knowledge about uses and side effects of lithium among all three cohorts. A robust educational framework for orthopaedic surgeons, their patients and the members of their clinical care teams will be essential to widespread repurposing of lithium for fracture care.

A Hemodynamic Safety Checklist Can Improve Blood Pressure Monitoring in Patients with Acute Spinal Cord Injury.

OBJECTIVE: The American Association and Congress of Neurological Surgeons recommended mean arterial blood pressure (MAP) in patients with acute spinal cord injury (SCI) should be 85-90 mm Hg for the first 7 days. We evaluated whether hemodynamic management differed between a primary-receiving and tertiary hospital in the first 24 hours for patients with acute SCI and assessed whether use of a checklist could improve hemodynamic management. METHODS: Observational review was performed of 79 patients with acute SCI before and after introduction of a blood pressure monitoring checklist and staff educational program designed to improve tertiary center management. Hemodynamic management in the primary-receiving hospital was compared with the tertiary center before and after checklist introduction. RESULTS: At the primary-receiving center, mean number of documented MAP readings/hour was 2.2 and 3 before and after checklist introduction. The proportion having >50% of MAP recordings <80 mm Hg was 26% and 22%. The proportion having >50% of MAP recordings <70 mm Hg was 8.5% and 7%. At the tertiary center, mean number of MAP readings/hour was 1.3 and 2.7 before and after checklist introduction (P = 0.02). The proportion having >50% of MAP recordings <80 mm Hg decreased from 36.5% to 16% after checklist introduction (P = 0.05). The proportion having >50% of MAP recordings <70 mm Hg decreased from 9% to 5.5% (P = 0.6). Polytrauma, inotrope use, and head injury significantly correlated with low MAP recordings (P < 0.05). Polytrauma was an independent risk predictor for low MAP recordings (P < 0.05). CONCLUSIONS: Achieving MAP targets for patients with acute SCI is challenging. Checklist use and staff education were associated with improved hemodynamic management. Presence of polytrauma identified patients at particular risk.

The impact of surgical manipulation on lower lateral cartilage stiffness.

BACKGROUND: Cephalic trimming of the alar (or lower lateral) cartilage may cause weakening leading to external nasal valve collapse. Numerous methods have been proposed to combat this weakening in order to maintain lateral crural stiffness. The purpose of this study was to quantify the effect of mucosal stripping, cephalic trimming, cephalic turn-in flap, and lateral crural strut grafting on lateral crural stiffness. METHODS: In situ cyclic compressive loading was performed on eight lateral crura in 4 fresh frozen cadaveric specimens. Testing was performed on the unaltered degloved cartilage (intact) and following each of the following interventions: mucosal stripping, cephalic turn-in flap, cephalic trimming, and lateral crural strut grafting. Linear regression of the generated force-displacement curves was used to calculate stiffness. Each intervention was compared to the intact cartilage. RESULTS: Alar cartilage of all of the specimens demonstrated a linear response to compressive loading. Intact cartilage had a mean stiffness of 3.53 N/mm. Mucosal stripping and cephalic turn-in flaps yielded similar stiffness values to intact cartilage. Cephalic trimming reduced stiffness in all cases by a mean of 1.09 N/mm (p = 0.003). Lateral crural strut grafting significantly increased stiffness by a mean of 3.67 N/mm (p = 0.0001). CONCLUSIONS: Cephalic trimming leads to decreased lateral crural stiffness in cadaveric specimens. Cephalic turn-in flaps restore pre-trimmed stiffness, and lateral crural strut grafting increases overall stiffness of the cartilage. These findings should be considered in patients undergoing rhinoplasty, particularly if there are concerns regarding potential external valve collapse.

Results of Early and Late Surgical Decompression and Stabilization for Acute Traumatic Cervical Spinal Cord Injury in Patients with Concomitant Chest Injuries.

BACKGROUND: The benefits of early surgical decompression and stabilisation (within 24 hours of injury) for patients with acute traumatic spinal cord injury (SCI) is unclear. The study objective was to investigate the effects of early (<24 hours of injury) versus late (>24 hours of injury) decompressive and stabilisation surgery for traumatic cervical SCI in patients with concomitant chest injuries. METHODS: This was a retrospective study including adults aged 16 years or over with traumatic cervical SCI, Glasgow Coma Scale score >13, and concomitant chest injuries (e.g. hemopneumothoraces, flail chest and pulmonary contusions) necessitating intensive care unit (ICU) admission. Forty patients who met the inclusion criteria and underwent decompressive surgery within 24 hours were compared with 55 patients who underwent decompressive surgery after 24 hours. Primary outcomes were ordinal change in the ASIA Impairment Scale (AIS) at 6 months and duration of ICU stay. Secondary outcomes included complications occurring within 30 days. RESULTS: In the early surgery group, 21 patients (52.5%) showed no improvement in ASIA grade, 13 (32.5%) had a 1-grade improvement, and 6 (15%) had a 2-grade improvement. The median length of ICU stay was 14 days (range, 2-68). 42.5% of patients developed a complication and 45% required a tracheostomy. In the late surgery group, AIS grade improvement was as follows: 32 (58%) no improvement, 19 (34.5%) had a 1 grade improvement, 3 (5.5%) had a 2 grade improvement and 1 (2%) had a 3 grade improvement. Mean ICU stay was 23 days (4-68). 53% of patients developed a complication and 55% required a tracheostomy. There was one mortality in the late surgery group. CONCLUSIONS: For patients with acute traumatic cervical SCI and concomitant chest trauma, early surgical decompression and stabilisation was associated with reduced ICU stay and a lower complication rate. Neurological recovery was more likely in younger patients and those with an incomplete SCI.

Design of experiments confirms optimization of lithium administration parameters for enhanced fracture healing.

Fracture healing is a lengthy process which fails in 5-10% of cases. Lithium, a low-cost therapeutic used in psychiatric medicine, up-regulates the canonical Wingless pathway crucial for osteoblastic mineralization in fracture healing. A design-of-experiments (DOE) methodology was used to optimize lithium administration parameters (dose, onset time and treatment duration) to enhance healing in a rat femoral fracture model. In the previously completed first stage (screening), onset time was found to significantly impact healing, with later (day 7 vs. day 3 post-fracture) treatment yielding improved maximum yield torque. The greatest strength was found in healing femurs treated at day 7 post fracture, with a low lithium dose (20 mg/kg) for 2 weeks duration. This paper describes the findings of the second (optimization) and third (verification) stages of the DOE investigation. Closed traumatic diaphyseal femur fractures were induced in 3-month old rats. Healing was evaluated on day 28 post fracture by CT-based morphometry and torsional loading. In optimization, later onset times of day 10 and 14 did not perform as well as day 7 onset. As such, efficacy of the best regimen (20 mg/kg dose given at day 7 onset for 2 weeks duration) was reassessed in a distinct cohort of animals to complete the DOE verification. A significant 44% higher maximum yield torque (primary outcome) was seen with optimized lithium treatment vs. controls, which paralleled the 46% improvement seen in the screening stage. Successful completion of this robustly designed preclinical DOE study delineates the optimal lithium regimen for enhancing preclinical long-bone fracture healing.

Low-dose lithium regimen enhances endochondral fracture healing in osteoporotic rodent bone.

Osteoporotic bone fractures are highly prevalent and involve lengthy recovery. Lithium, commonly used in psychiatric medicine, inhibits glycogen synthase kinase-3ß in the Wnt/ß-catenin pathway, leading to up-regulation of osteogenesis. Our recent preclinical work demonstrated that a 20 mg/kg lithium dose administered beginning 7 days post-fracture for 14 days optimally improved femoral fracture healing in healthy rats at 4 weeks post fracture (46% higher torsional strength). In this study, lithium treatment was evaluated for healing of osteoporotic bone fractures. Six-month-old ovariectomized rats were subjected to closed, load-drop induced femoral diaphyseal fracture. Two regimens involving treatment initiation on day 7 and day 10, respectively, 20 mg/kg/day oral dose and 14 days duration were evaluated. Femurs of lithium- vs. saline- treated rats were analyzed at 4 weeks (for day 7 onset regimen) or 6 weeks (for day 10 onset regimen) post-fracture by stereology and torsional mechanical testing. Initiation on day 10 led to a significant 50% higher maximum yield torque (primary outcome measure) at 6 weeks (309 vs. 206 N-mm, p = 0.005; n = 7, 7). Initiation on day 7 suggested a trend toward a more modest improvement in maximum yield torque (13%) evaluated at 4 weeks post-fracture (234 vs. 206 N-mm, p = 0.10; n = 10, 13). Qualitatively, lithium-treated femurs demonstrated better periosteal and mineralized callus bridging in the day 10 initiation group. Lithium is a widely-available, orally administered, low-cost drug, which represents a feasible pharmacological intervention for both healthy and osteoporotic fracture healing. This study provides important guidelines for future clinical evaluation of lithium in osteoporotic fracture patients. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1783-1789, 2018.