Optimal delivery of endothelial progenitor cells in a rat model of critical-size bone defects.

Nonunion and segmental bone defects are complex issues in orthopedic trauma. The use of endothelial progenitor cells (EPCs), as part of a cell-based therapy for bone healing is a promising approach. In preclinical studies, culture medium (CM) is commonly used to deliver EPCs to the defect site, which has the potential for immunogenicity in humans. The goal of this study was to find an effective and clinically translatable delivery medium for EPCs. Accordingly, this study compared EPCs delivered in CM, phosphate-buffered saline (PBS), platelet-poor plasma (PPP), and platelet-rich plasma (PRP) in a rat model of femoral critical-size defects. Fischer 344 rats (n = 35) were divided into six groups: EPC+CM, EPC+PBS, EPC+PPP, EPC+PRP, PPP alone, and PRP alone. A 5 mm mid-diaphyseal defect was created in the right femur and stabilized with a miniplate. The defect was filled with a gelatin scaffold impregnated with the corresponding treatment. Radiographic, microcomputed tomography and biomechanical analyses were performed. Overall, regardless of the delivery medium, groups that received EPCs had higher radiographic scores and union rates, higher bone volume, and superior biomechanical properties compared to groups treated with PPP or PRP alone. There were no significant differences in any outcomes between EPC subgroups or between PPP and PRP alone. These results suggest that EPCs are effective in treating segmental defects in a rat model of critical-size defects regardless of the delivery medium used. Consequently, PBS could be the optimal medium for delivering EPCs, given its low cost, ease of preparation, accessibility, noninvasiveness, and nonimmunogenic properties.

Association of age, sex and race with prescription of anti-osteoporosis medications following low-energy hip fracture in a retrospective registry cohort.

BACKGROUND: Initiation of anti-osteoporosis medications after hip fracture lowers the risk of subsequent fragility fractures. Historical biases of targeting secondary fracture prevention towards certain groups may result in treatment disparities. We examined associations of patient age, sex and race with anti-osteoporosis medication prescription following hip fracture. METHODS: A cohort of patients with a hip fracture between 2016-2018 was assembled from the American College of Surgeons National Surgical Quality Improvement Program registry. Patients on anti-osteoporosis medications prior to admission were excluded. Multivariable logistic regression was used to determine adjusted associations between patient age, sex and race and their interactions with prescription of anti-osteoporosis medications within 30 days of surgery. RESULTS: In total, 12,249 patients with a hip fracture were identified with a median age of 82 years (IQR: 73-87), and 67% were female (n = 8,218). Thirty days postoperatively, 26% (n = 3146) of patients had been prescribed anti-osteoporosis medication. A significant interaction between age and sex with medication prescription was observed (p = 0.04). Male patients in their 50s (OR:0.75, 95%CI:0.60-0.92), 60s (OR:0.81, 95%CI:0.70-0.94) and 70s (OR:0.89, 95%CI:0.81-0.97) were less likely to be prescribed anti-osteoporosis medication compared to female patients of the same age. Patients who belonged to minority racial groups were not less likely to receive anti-osteoporosis medications than patients of white race. INTERPRETATION: Only 26% of patients were prescribed anti-osteoporosis medications following hip fracture, despite consensus guidelines urging early initiation of secondary prevention treatments. Given that prescription varied by age and sex, strategies to prevent disparities in secondary fracture prevention are warranted.

The induced membrane technique: Optimization of bone grafting in a rat model of segmental bone defect.

INTRODUCTION: The induced membrane technique (IMT) is a two-stage surgical procedure used to treat fracture nonunion and bone defects. Although there is an increasing number of animal studies investigating the IMT, few have examined the outcomes of bone healing after a second stage grafting procedure. This study aimed at comparing two bone grafting procedures, as part of the IMT, in order to establish a rat model providing consistent healing outcomes. METHODS: In male Fischer 344 rats, we created a 5 mm defect in the right femur, stabilized the bone with a plate and screws, and inserted a polymethylmethacrylate spacer into the defect. Four weeks later, the spacer was removed. Bone graft was harvested from a donor rat and placed into the defect, followed by membrane and wound closure. Experiments were conducted in two groups. In group 1 (n = 11), the bone graft contained a variable amount of cortical and cancellous bone, the time from donor euthanasia to grafting was up to 240 min, and one donor rat provided graft for 5-6 recipients. In group 2 (n = 12), we reduced the contribution of cortical bone to the graft, included bone marrow, and kept donor euthanasia to grafting time under 150 min. One donor was used per 3-4 recipients. The volume of graft per recipient and all other elements of the protocol were the same across groups. Bone healing at 12 weeks post grafting was compared radiographically by two orthopaedic surgeons in a blinded fashion, based on union status and a modified Lane & Sandhu score. RESULTS: Healing rates improved from 36.4% in Group 1 to 91.6% in Group 2. There was a significant relationship between the methods and resulting union status (p = 0.004). The odds of achieving full union were significantly higher in group 2 compared to group 1 (odds ratio=19.25, 95% confidence interval [1.77-209.55]; p = 0.009). The average radiographic score was also significantly higher in group 2 (p = 0.005). CONCLUSION: The revised bone grafting method significantly improved the healing outcomes and contributed to establishing a consistent rat model of the IMT. This model can benefit preclinical investigations by allowing for reliable and clinically-relevant comparisons.

Systemically impaired fracture healing in small animal research: A review of fracture repair models.

Fracture healing is a complex process requiring mechanical stability, an osteoconductive matrix, and osteoinductive and osteogenic biology. This intricate process is easily disrupted by various patient factors such as chronic disease and lifestyle. As the medical complexity and age of patients with fractures continue to increase, the importance of developing relevant experimental models is becoming paramount in preclinical research. The objective of this review is to describe the most common small animal models of systemically impaired fracture healing used in the orthopedic literature including osteoporosis, diabetes mellitus, smoking, alcohol use, obesity, and ageing. This review will provide orthopedic researchers with a summary of current models of systemically impaired fracture healing used in small animals and present an overview of the methods of induction for each condition.

Anemia at Presentation Predicts Acute Mortality and Need for Readmission Following Geriatric Hip Fracture.

There is a paucity of research regarding the relationship between anemia and postoperative morbidity and mortality among geriatric patients presenting with hip fracture. The objective of this study was to determine the effect of anemia at presentation on 30-day morbidity and mortality among geriatric patients with hip fracture. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for all hip fracture patients ≥60 years old from 2011 to 2016. Included were all emergency unilateral, nonpathological hip fractures (femoral neck, intertrochanteric, or subtrochanteric) treated with arthroplasty, intramedullary nailing, or open reduction and internal fixation. Anemia was classified as a hematocrit (HCT) level of <0.41 and <0.36 for male and female patients, respectively. Age, body mass index (BMI), race, comorbidities, smoking status, American Society of Anesthesiologists (ASA) class, baseline functional status, time to surgery, operative time, anesthesia type, need for transfusion, fixation method, length of stay (LOS), and discharge destination were collected. Our primary outcome of interest was 30-day postoperative mortality, with all-cause readmission and any postoperative ischemic events (cerebrovascular accident [CVA] and myocardial infarction [MI]) analyzed as secondary outcomes. A multivariable regression analysis was performed and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated while controlling for confounding variables. RESULTS: Of 34,805 patients identified, 22,469 (65%) were anemic at presentation (63% female; mean age, 80 ± 8 years), while 12,336 (35%) were non-anemic (85% female; mean age, 79 ± 8 years). Anemia at presentation was independently associated with higher odds of mortality (OR,1.3 [95% CI, 1.1 to 1.5]) and readmission (OR, 1.2 [95% CI, 1.1 to 1.3]), while no relationship was observed for MI (OR, 1.1 [95% CI, 0.9 to 1.4]) or CVA (OR, 0.8 [95% CI, 0.6 to 1.1]). CONCLUSIONS: Our findings suggest that anemia at presentation is associated with greater 30-day postoperative morbidity and mortality in geriatric hip fracture patients. Additional research should focus on elucidating this modifiable risk factor and advancing the preoperative optimization of hip fracture patients. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Nonpharmacological management of neonatal abstinence syndrome: a review of the literature.

BACKGROUND: Infants with neonatal abstinence syndrome (NAS) experience withdrawal that occurs as a result of termination of placental opioid supply following delivery. Common symptoms include restlessness, tremors, agitation and gastrointestinal disturbances. Severe NAS is often treated using opioids and/or sedatives. Although commonly employed effectively in neonatal care, there is a lack of published information regarding nonpharmacological management of the NAS infant. OBJECTIVE: The purpose of this review was to summarize the current literature on nonpharmacological management of NAS. METHODS: A literature search of Medline and EMBASE was performed for articles published between 2000 and June 2107. RESULTS: Nonpharmacological management encompasses "environmental control", "feeding methods", "social integration", "soothing techniques" and "therapeutic modalities". Several interventions, including: breastfeeding, swaddling, rooming-in, environmental control and skin to skin contact have proven to be effective in managing NAS and should be incorporated into standard of care for this population (Level I-III Evidence). These interventions can be effective when offered in combination with pharmacological therapy, or as stand-alone therapy for less severe cases of NAS (Finnegan score <8). CONCLUSIONS: Given the increasing body of evidence on its efficacy and ease of implementation, nonpharmacological treatment should universally be incorporated into standard of care for NAS.

Maternal opioid use disorder and neonatal abstinence syndrome in northwest Ontario: a 7-year retrospective analysis.

INTRODUCTION: Opioid use in pregnancy is increasing globally. In northwest Ontario, rates of neonatal abstinence syndrome (NAS) are alarmingly high. We sought to document the increasing rates of opioid exposure during pregnancy and associated cases of NAS over a 7-year period in northwest Ontario. METHODS: We conducted a retrospective chart review at the Sioux Lookout Meno Ya Win Health Centre catchment area (population 29 000) maternity program in northwest Ontario of mother-infant dyads of live births from Jan. 1, 2009, to Dec. 31, 2015. The Integrated Pregnancy Program provides maternal, neonatal and addiction care for obstetrical patients at the health centre. We collected data on prenatal opioid exposure due to illicit and opioid agonist therapy (OAT) from patient/prescription histories and urine toxicology reports. Rates of NAS (diagnosed as a Finnegan score > 7) were recorded retrospectively from neonatal hospital charts. RESULTS: There were 2743 live births during the study period. Opioid exposure occurred in 672 pregnancies (335 OAT, 337 illicit). The incidence of prenatal opioid exposure increased significantly between 2009 and 2012 (11.1% to 28.5%, p < 0.001) but remained relatively constant at around 30% thereafter. Despite this, absolute rates of NAS remained relatively stable, with an average of 22.2 cases per 1000 live births over the study period. In comparison, the North West Local Health Integration Network (LHIN) experienced an average of 52.8 cases of NAS per 1000 live births in 2009-2012. The incidence of NAS in our centre decreased significantly over the study period (17.6% of opioid-exposed pregnancies in 2009 v. 4.0% in 2015, p = 0.001). There was a gradual transition toward a preponderance of OAT- versus illicit-exposed pregnancies, increasing from 0% in 2009 to 76.9% in 2015 (p < 0.001). CONCLUSION: Despite our continually increasing rates of opioid exposure in pregnancy, rates of NAS decreased annually and were substantially lower than those of our regional LHIN. In contrast to 2009, most opioid exposure in our region is now iatrogenic as a result of OAT. These improvements may be attributable in part to the rural community-based prenatal and addictions services developed in our catchment area.

INTRODUCTION: La consommation d'opioïdes pendant la grossesse est à la hausse dans le monde entier. Dans le nord-ouest de l'Ontario, le taux de syndrome de sevrage néonatal est alarmant. Nous avons tenté de documenter les taux croissants d'exposition aux opioïdes pendant la grossesse et les cas associés de syndrome de sevrage néonatal sur une période de sept ans dans le nord-ouest de l'Ontario. METHODS: Nous avons mené une étude rétrospective des dossiers des patientes du programme obstétrical de la région desservie par le Centre de santé Meno Ya Win de Sioux Lookout (population de 29 000), dans le nord-ouest de l'Ontario, et des naissances vivantes de la dyade mère­nourrisson pour la période du 1er janvier 2009 au 31 décembre 2015. Des soins maternels, néonataux et de traitement de la toxicomanie sont offerts aux patientes en obstétrique du Centre de santé dans le cadre d'un programme de soins intégrés pendant la grossesse. Nous avons obtenu des données sur l'exposition prénatale aux opioïdes due à la consommation d'opioïdes illégaux et aux traitements par agonistes opioïdes dans les antécédents des patientes, l'historique des médicaments prescrits et les rapports de toxicologie des dépistages urinaires. Le taux de syndrome de sevrage néonatal (diagnostiqué selon un score de Finnegan > 7) a été obtenu et consigné de manière rétrospective à partir des dossiers néonataux d'hôpitaux. RESULTS: Il y a eu 2743 naissances vivantes pendant la période de l'étude et 672 grossesses exposées aux opioïdes (335 aux traitements par agonistes opioïdes, 337 aux opioïdes illégaux). L'incidence de l'exposition prénatale aux opioïdes a augmenté de façon importante entre 2009 et 2012 (11,1 % à 28,5 %, p < 0,001), mais est ensuite demeurée relativement constante à environ 30 % par la suite. Malgré cela, le taux absolu de syndrome de sevrage néonatal est demeuré relativement stable, soit une moyenne de 22,2 cas par 1000 naissances vivantes pendant la période de l'étude. Par comparaison, le Réseau local d'intégration des services de santé (RLISS) du Nord-Ouest a enregistré une moyenne de 52,8 cas de syndrome de sevrage néonatal par 1000 naissances vivantes entre 2009 et 2012. L'incidence du syndrome de sevrage néonatal dans notre centre a diminué considérablement au cours de la période de l'étude (17,6 % de grossesses exposées aux opioïdes en 2009 contre 4 % en 2015, p = 0,001). Nous avons observé une transition graduelle vers la prépondérance des grossesses exposées aux traitements par agonistes opioïdes par rapport aux grossesses exposées aux opioïdes illégaux. Leur taux est passé de 0 % en 2009 à 76,9 % en 2015 (p < 0,001). CONCLUSION: Malgré la croissance continue de l'exposition aux opioïdes pendant la grossesse, notre taux de syndrome de sevrage néonatal a diminué annuellement et était nettement inférieur au taux du RLISS de la région. Par comparaison à 2009, la plupart des cas d'exposition aux opioïdes dans notre région sont maintenant d'origine iatrogène et liés aux traitements par agonistes opioïdes. Ces améliorations pourraient s'expliquer en partie par la création de services communautaires de soins prénataux et de traitement de la toxicomanie en régions rurales dans notre circonscription hospitalière.

Infraspinatus Isolation During External Rotation Exercise at Varying Degrees of Abduction.

CONTEXT: External rotation (ER) strengthening exercises are a common component of shoulder injury prevention and rehabilitation programs. They are primarily intended to target the infraspinatus muscle, based on its role in glenohumeral stabilization and inferior humeral glide. ER also recruits the posterior deltoid, which can be undesirable due to its role in subacromial space narrowing. OBJECTIVE: To determine the angle of humeral abduction that maximizes the infraspinatus to posterior deltoid activation ratio (INFRA/PD) during ER. DESIGN: Within-subjects repeated-measures controlled lab trial. PARTICIPANTS: A total of 10 healthy participants (5 males, 5 females) aged 21 (0.67) years participated in the study. INTERVENTION: 7 consecutive repetitions of ER at 7 different abduction angles ranging from 0° to 90°, with resistance normalized to 3% body mass. MAIN OUTCOME MEASURES: Surface electromyography was performed on the infraspinatus, middle deltoid, and posterior deltoid. Surface electromyography data were processed to determine absolute muscle activation as well as INFRA/PD at each abduction angle. Group means were compared between abduction angles using 1-way analysis of variance. RESULTS: Abduction significantly reduced overall infraspinatus activity but increased posterior deltoid activity (P < .01). Average and peak INFRA/PD decreased as the angle of abduction increased (P < .001 and P < .01, respectively). CONCLUSION: Our findings suggest that ER should be performed in 0° of abduction to maximize infraspinatus isolation. Slight abduction, such as placing a towel under the humerus, as recommended by some clinicians, may improve patient comfort, but did not increase infraspinatus isolation in this study.

First Nations hepatitis C virus infections: Six-year retrospective study of on-reserve rates of newly reported infections in northwestern Ontario.

OBJECTIVE: To document rates of newly reported hepatitis C virus (HCV) cases from 2010 to 2015 in remote First Nations communities. DESIGN: Retrospective analysis of aggregate data of newly reported HCV antibody-positive (Ab+) cases. SETTING: Northwestern Ontario. PARTICIPANTS: A total of 31 First Nations communities (an on-reserve population of 20 901) supported in health care by the Sioux Lookout First Nations Health Authority. MAIN OUTCOME MEASURES: The aggregate characteristic data included year of notification, age range, and sex for a 6-year period (2010 to 2015). RESULTS: There were 267 HCV Ab+ cases in the 6-year study period. The incidence in 2015 was 324.2 per 100 000 population. This is 11 times the rate for all of Ontario. The most common associated risk factor was sharing of intravenous drug use equipment. Women made up 52% of patients with newly reported HCV Ab+ cases. More than 45% of cases were in patients between 20 and 29 years of age. CONCLUSION: This high burden of newly reported HCV Ab+ cases in geographically remote First Nations communities is concerning, and prevention and treatment resources are needed. This burden of disease might pose more urgent health and social challenges than can be generalized from the experience of the rest of Canada.

Maternal-Fetal Monitoring of Opioid-Exposed Pregnancies: Analysis of a Pilot Community-Based Protocol and Review of the Literature.

OBJECTIVES: To describe/analyse a novel, community-based prenatal monitoring protocol for opioid-exposed pregnancies developed by our centre in 2014 to optimize prenatal care for this population. A literature review of published monitoring protocols for this population is also presented. METHODS: Retrospective comparison of pre-protocol (n = 215) and post-protocol (n = 251) cohorts. Medline and Embase were searched between 2000-2016 using MeSH terms: [fetal monitoring OR prenatal care] AND [opioid-related disorders OR substance-related disorders] in Medline and [fetal monitoring OR prenatal care] AND [opiate addiction OR substance abuse] in Embase, producing 518 results. Thirteen studies included protocols for monitoring opioid-exposed pregnancies. No comprehensive monitoring protocols with high-quality supporting evidence were found. RESULTS: We evaluated 466 opioid-exposed pregnancies, 215 before and 251 after introduction of the protocol. Since implementation, there was a significant increase in the number of opioid-exposed patients who have underwent urine drug screening (72.6% to 89.2%, P < 0.0001); a significant reduction in the number of urine drug screenings positive for illicit opioids (50.2% to 29.1%, P < 0.0001); and a significant increase in the number of patients who discontinued illicit opioid use by the time of delivery (24.7% to 39.4%, P < 0.01). There was no difference in the CS rate (27.4% vs. 26.3%, P > 0.05). There were no observed differences in the rate of preterm birth, birth weight <2500 g, or Apgar score <7 (P > 0.05). CONCLUSIONS: Care of women with increased opioid use during pregnancy is an important but under-studied health issue. A novel protocol for focused antenatal care provision for women with opioid-exposed pregnancies improves standard of care and maternal/fetal outcomes.