Pilot study of micromotion nailing for mechanical stimulation of tibial fracture healing

Aims The study objective was to prospectively assess clinical outcomes for a pilot cohort of tibial shaft fractures treated with a new tibial nailing system that produces controlled axial interfragmentary micromotion. The hypothesis was that axial micromotion enhances fracture healing compared to static interlocking. Methods Patients were treated in a single level I trauma centre over a 2.5-year period. Group allocation was not randomized; both the micromotion nail and standard-of-care static locking nails (control group) were commercially available and selected at the discretion of the treating surgeons. Injury risk levels were quantified using the Nonunion Risk Determination (NURD) score. Radiological healing was assessed until 24 weeks or clinical union. Low-dose CT scans were acquired at 12 weeks and virtual mechanical testing was performed to objectively assess structural bone healing. Results A total of 37 micromotion patients and 46 control patients were evaluated. There were no significant differences between groups in terms of age, sex, the proportion of open fractures, or NURD score. There were no nonunions (0%) in the micromotion group versus five (11%) in the control group. The proportion of fractures united was significantly higher in the micromotion group compared to control at 12 weeks (54% vs 30% united; p = 0.043), 18 weeks (81% vs 59%; p = 0.034), and 24 weeks (97% vs 74%; p = 0.005). Structural bone healing scores as assessed by CT scans tended to be higher with micromotion compared to control and this difference reached significance in patients who had biological comorbidities such as smoking. Conclusion In this pilot study, micromotion fixation was associated with improved healing compared to standard tibial nailing. Further prospective clinical studies will be needed to assess the strength and generalizability of any potential benefits of micromotion fixation. Cite this article: Bone Jt Open 2021;2(10):825–833.

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Ketamine as an Analgesic Adjuvant in Adult Trauma Intensive Care Unit Patients With Rib Fracture

Annals of Pharmacotherapy ◽

10.1177/1060028018768451 ◽

2018 ◽

Vol 52 (9) ◽

pp. 849-854 ◽

Cited By ~ 11

Author(s):

Mary K. Walters ◽

Joseph Farhat ◽

James Bischoff ◽

Mary Foss ◽

Cory Evans

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Length Of Stay ◽

Group Versus ◽

Standard Of Care ◽

Pain Scale ◽

Rib Fracture ◽

Hospital Length Of Stay ◽

Control Group ◽

Opioid Use

Background: Rib fracture associated pain is difficult to control. There are no published studies that use ketamine as a therapeutic modality to reduce the amount of opioid to control rib fracture pain. Objective: To examine the analgesic effects of adjuvant ketamine on pain scale scores in trauma intensive care unit (ICU) rib fracture. Methods: This retrospective, case-control cohort chart review evaluated ICU adult patients with a diagnosis of ≥1 rib fracture and an Injury Severity Score >15 during 2016. Patients received standard-of-care pain management with the physician’s choice analgesics with or without ketamine as a continuous, fixed, intravenous infusion at 0.1 mg/kg/h. Results: A total of 15 ketamine treatment patients were matched with 15 control standard-of-care patients. Efficacy was measured via Numeric Pain Scale (NPS)/Behavioral Pain Scale (BPS) scores, opioid use, and ICU and hospital length of stay. Safety of ketamine was measured by changes in vital signs, adverse effects, and mortality. Average NPS/BPS, severest NPS/BPS, and opioid use were lower in the ketamine group than in controls (NPS: 4.1 vs 5.8, P < 0.001; severest NPS: 7.0 vs 8.9, P = 0.004; opioid use: 2.5 vs 3.5 mg morphine equivalents/h/d, P = 0.015). No difference was found between the cohort’s length of stay or mortality. Average diastolic blood pressure was higher in the treatment group versus the control group (75.3 vs 64.6 mm Hg, P = 0.014). Conclusion: Low-dose ketamine appears to be a safe and effective adjuvant option to reduce pain and decrease opioid use in rib fracture.

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Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow–Derived Mesenchymal Stem Cells

The American Journal of Sports Medicine ◽

10.1177/0363546519862284 ◽

2019 ◽

Vol 47 (11) ◽

pp. 2729-2736

Author(s):

Jun Lu ◽

Connie S. Chamberlain ◽

Ming-liang Ji ◽

Erin E. Saether ◽

Ellen M. Leiferman ◽

...

Keyword(s):

Bone Marrow ◽

Bone Healing ◽

Macrophage Polarization ◽

Group Versus ◽

Autologous Bone Marrow ◽

Bone Tunnel ◽

Control Group ◽

M2 Macrophage ◽

Bone Interface ◽

Autologous Bone

Background: Despite widespread acceptance of fresh autologous bone marrow (BM) for use in clinical practice, limited information exists to analyze if tendon-to-bone healing could be accelerated with local use of fresh autologous BM. Purpose: To investigate the effect of fresh autologous BM on tendon-to-bone healing with a novel rat model. Study Design: Controlled laboratory study. Methods: An extra-articular bone tunnel was created and filled with an autologous tendon graft in skeletally mature Sprague-Dawley rats (N = 60). They were then randomly divided into 3 groups: BM group (injection of fresh autologous BM into the tendon-bone interface, n = 20), BM-derived mesenchymal stem cell (BMSC) group (injection of allogenic cultured BMSCs, n = 20), and the control group (tendon-bone interface without injection of BM or BMSCs, n = 20). Biomechanical, histological, and immunohistochemical analyses were performed at 2 and 6 weeks after surgery. Results: The BM group showed a relatively well-organized and dense connective tissue interface with better orientation of collagen fibers as compared with the BMSC group. At 2 weeks, the tendon-bone interface tissue thickness of the BMSC group was 140 ± 25 μm (mean ± SEM), which was significantly greater than the BM group (58 ± 15 μm). The BM group showed fewer M1 macrophages at the tendon-bone interface at 2 and 6 weeks ( P < .001). In contrast, there were more M2 macrophages at the interface in the BM group 2 and 6 weeks postoperatively when compared with controls and the BMSC group ( P < .001). Biomechanical tests revealed significantly higher stiffness in the BM group versus the control and BMSC groups at 2 and 6 weeks after surgery ( P < .05). Load to failure showed similar trends to stiffness. Conclusion: These findings indicate that local delivery of fresh autologous BM enhances tendon-to-bone healing better than the alternative treatments in this study. This effect may be partially due to the observed modulation of inflammatory processes, especially in M2 macrophage polarization. Clinical Relevance: Fresh autologous BM could be a treatment option for this disorder.

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116 An Experimental Study to Assess the Professional and Social Consequences of Tardive Dyskinesia

CNS Spectrums ◽

10.1017/s1092852920000346 ◽

2020 ◽

Vol 25 (2) ◽

pp. 275-276 ◽

Cited By ~ 1

Author(s):

Rajeev Ayyagari ◽

Debbie Goldschmidt ◽

Fan Mu ◽

Stanley N. Caroff ◽

Benjamin Carroll

Keyword(s):

Tardive Dyskinesia ◽

Involuntary Movement ◽

Population Sample ◽

Group Versus ◽

Test Group ◽

Categorical Variables ◽

Control Group ◽

Study Objective ◽

Social Lives ◽

The Impact

Abstract:Study Objective:Evaluate the impact of orofacial tardive dyskinesia (TD) symptoms on the professional and social lives of patients with TD.Background:TD, a movement disorder affecting the face and extremities, may arise in patients taking antipsychotics. The impact of social stigma on the professional and social lives of patients with orofacial manifestations of TD has not been thoroughly examined.Methods:This study is an experimental, randomized digital survey of a general population sample. Three component surveys were developed, corresponding to employment, dating, and friendship domains. For each domain, participants were randomized 1:1 into either a test group (who viewed a video of a scripted interview with a standardized patient actor depicting TD movements) or a control group (who viewed the same actors but without TD movements), and asked about their impressions of the video subject. Actor simulations were validated by physicians familiar with TD and rehearsed to simulate a total Abnormal Involuntary Movement Scale score between 6 and 10. Statistical comparison was made using Wilcoxon sign-rank or chi-squared tests for continuous and categorical variables, respectively.Results:A total of 800 respondents completed each survey. In all domains, respondents had more-negative perceptions of actors portraying TD movements than of the same actors without movements. Regarding employment, 34.8% fewer respondents in the test group versus the control group agreed that the actor would be suitable for client-facing jobs (P<0.001). Regarding dating, the proportions of respondents who agreed that they would like to continue talking to the actor and who would be interested in meeting them for coffee/drink were 25.0% and 27.2% lower, respectively, in the test group than in the control group (P<0.001). Regarding friendship, the proportions of respondents who rated the actor as interesting and who would be interested in friendship with them were 18.8% and 16.5% lower, respectively, in the test group than in the control group (P<0.001).Conclusions:Actors simulating orofacial TD movements were perceived to be statistically significantly less likely to move forward in a job interview, be considered as a potential romantic partner, or be a new friend. This is the first study to quantify the stigma faced by people with TD in a variety of professional and social situations.Funding Acknowledgements:This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

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Virtual Structural Analysis of Tibial Fracture Healing from Low-Dose Clinical CT Scans

10.31224/osf.io/7c8kz ◽

2018 ◽

Author(s):

Peter Schwarzenberg ◽

Hannah L. Dailey

Keyword(s):

Structural Analysis ◽

Fracture Healing ◽

Bone Healing ◽

Structural Integrity ◽

Torsional Rigidity ◽

Torsion Test ◽

Ct Scans ◽

Orthopaedic Trauma ◽

Element Analysis ◽

Trauma Research

Quantitative assessment of bone fracture healing remains a significant challenge in orthopaedic trauma research. Accordingly, we developed a new technique for assessing bone healing using virtual mechano-structural analysis of computed tomography (CT) scans. CT scans from 19 fractured human tibiae at 12 weeks after surgery were segmented and prepared for finite element analysis (FEA). Boundary conditions were applied to the models to simulate a torsion test that is commonly used to access the structural integrity of long bones in animal models of fracture healing. The output of each model was the virtual torsional rigidity (VTR) of the healing zone, normalized to the torsional rigidity of each patient’s virtually reconstructed tibia. This provided a structural measure to track the percentage of healing each patient had undergone. Callus morphometric measurements were also collected from the CT scans. Results showed that at 12 weeks post-op, more than 75% of patients achieved a normalized VTR (torsional rigidity relative to uninjured bone) of 85% or above. The predicted intact torsional rigidities compared well with published cadaveric data. Across all patients, callus volume and density were weakly and non-significantly correlated with normalized VTR and time to clinical union. Conversely, normalized VTR was significantly correlated with time to union (R2 = 0.383, p = 0.005). This suggests that fracture scoring methods based on the visual appearance of callus may not accurately predict mechanical integrity. The image-based structural analysis presented here may be a useful technique for assessment of bone healing in orthopaedic trauma research.

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Activity Aprons for Inpatients Requiring Individual Nursing Assignment Care: A Prospective Randomized Controlled Pilot Study

The Neurohospitalist ◽

10.1177/1941874418773945 ◽

2018 ◽

Vol 8 (4) ◽

pp. 183-187

Author(s):

Michael W. Ruff ◽

Anthony Fine ◽

Jay Mandrekar ◽

Cindy Sweeney ◽

Lyell K. Jones ◽

...

Keyword(s):

Pilot Study ◽

Standard Care ◽

Hospital Setting ◽

Length Of Hospital Stay ◽

Standard Of Care ◽

Control Group ◽

Inpatient Setting ◽

Term Care ◽

Randomized Controlled ◽

Restraint Use

Background: Activity aprons are commercially available products used to occupy patients with dementia at home or in long-term care facilities. We hypothesized that inpatient use of activity aprons could potentially reduce or eliminate behaviors that result in self-harm, increased nursing supervision, and restraint use in an inpatient hospital setting. Methods: A single-center prospective randomized controlled pilot study was performed from July 2015 to November 2016 comparing activity apron plus standard care versus standard care alone. Consecutively enrolled patients were randomized by stratified randomization using age (cutoff: 80 years) and preexisting diagnosis of dementia or cognitive impairment. Primary outcomes were safety and feasibility of apron use. Secondary outcomes included duration of hospitalization postrandomization and individual nursing assignment (IA), time in restraints, nonphysical restraints use, falls, apron-related complications, dismissal destination, and 30-day hospital readmission. Results: Thirty patients were enrolled, with 13 randomized to apron and 17 randomized to the control group. There was no statistically significant reduction in mean length of hospital stay (15.8 vs 21.5 day; P = .40), duration of IA compared to non-apron control group (6.4 vs 9.1, respectively; P = .39), or antipsychotic medication use (61.5% vs 70.6% in control group; P = .60). No complications secondary to apron use were seen. Conclusions: Activity aprons are a safe addition to the standard of care when managing encephalopathic patients in the inpatient setting. These aprons may have a role as part of a comprehensive complement of interventions to address delirium and encephalopathy in hospitalized patients.

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Alternative Schedule of Filgrastim after Autologous Transplantation: Less Dosing, Same Efficacy

Blood ◽

10.1182/blood.v112.11.4334.4334 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4334-4334

Author(s):

Aida B. Sousa ◽

Fatima Costa ◽

Gilda Ferreira

Keyword(s):

Pilot Study ◽

Median Time ◽

Autologous Transplantation ◽

Standard Of Care ◽

Control Group ◽

Study Group ◽

Current Standard ◽

Transfusion Requirements ◽

Clinical Instability ◽

Grade 3

Abstract Administration of colony-stimulating factors (CSF) after autologous peripheral-blood progenitor cell transplantation is the current standard of care, and G-CSF is usually given from day +5 or +7 until engraftment. Recent preliminary data in a non-transplant setting suggest that 2 doses of G-CSF may be equivalent to the standard schedule. In this pilot study, we evaluated the safety and efficacy of giving only 2 doses of filgrastim post-transplant (days +7 and +9) in non-myeloma pts; exclusion criteria were re-transplants and clinical instability at day +7. From July 07 to June 08, 19 consecutive pts were included (16 lymphomas, 3 acute leukaemias) and their outcome was compared to a historical control group of 42 similar pts transplanted from Jan 06 to Jun 07, who received filgrastim from d+7 until 1000 neutrophils/ul (4–18 days, median 9). There were no significant differences in primary endpoints: median time to neutrophil engraftment (500/ul reached on day +12 vs +11) rate of documented infections (with bacteremia in 23% of transplants in the study group vs 36% in the control group) and median length of hospitalisation (both 22 days). Median duration of intravenous antibiotics (11 vs 12 days) median time to platelet engraftment (20,000/ul reached on day +13 vs +14) incidence of grade 3/4 mucositis and transfusion requirements were also similar. There were no deaths at day +30 in the study group. In 2 of the 19 pts a secondary prescription of filgrastim was made (for 2 and 4 days). In this pilot study, reducing filgrastim administration to 2 doses seems possible without undue risks. If confirmed in a randomized trial, these findings could have a significant impact on the cost of transplantation.

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Pilot study of Stem Cell Therapy in Heart Failure Patients

University Heart Journal ◽

10.3329/uhj.v16i2.49647 ◽

2020 ◽

Vol 16 (2) ◽

pp. 52-58

Author(s):

M Mustafa Zaman ◽

Md Fakhrul Islam Khaled ◽

Bishnu Pada Dey ◽

Masuda Begum ◽

Sayed Mainuddin Ahmed ◽

...

Keyword(s):

Heart Failure ◽

Stem Cell ◽

Pilot Study ◽

Cell Therapy ◽

Standard Of Care ◽

Control Group ◽

Borg Scale ◽

Absolute Change ◽

The Absolute

Introduction: Chronic heart failure with reduced ejection fraction is a major complication of diseases involving myocardium. Despite numerous pharmacological interventions and invasive therapeutic techniques, therapeutic options for end stage heart failure remain limited to left ventricular assist device & organ transplantation. Regenerative medicine may bring hope here. Method: This pilot study was carried out at the Department of cardiology in collaboration with department of haematology, Bangabandhu Sheikh Mujib Medical University, Dhaka, from October 2017 to March 2018. Considering inclusion & exclusion crieteria ten (10) patients were taken in stem cell group and ten (10) patients in control group. Patients in the control arm received standard of care in accordance with practice guidelines for heart failure management (GDMT). Patients in the cell therapy arm received, in addition to standard of care, bone marrow–derived cardiopoietic stem cells (G-CSF) meeting quality release criteria. Baseline clinical and echocardiographic data were obtained and recorded in pre-formed data sheet. Close liaison was maintained with all patients and followed up after 30 days & after 3 months and for any complication. The absolute change in 6 MWD from baseline to 30 days, 3 months & 6 months improved significantly in the both groups. But significant improvement was found at 6 months follow up of 6MWD between the two groups (300±28 vs 375±25, p= 0.04). Baseline BORG scale was similar in the control group and the SCT group (8.1±0.56 and 8.3±0.67 respectively, P= 0.45). The absolute change in BORG scale from baseline to 30 days, 3 months & 6 months improved significantly in the both groups. But improvement was not statistically significant in between the two groups (p= 0.32, 0.45, 0.23 respectively). Echocardiographic observation also revealed a similar baseline LVIDd, LVEF level in the control group and the SCT group which was not statistically significant (p = 0.45, 0.52 respectively). Gradual improvement in LVIDd were found at 30 days, 3 months, 6 months follow up observation but statistically significant absolute change was found only at 6 months follow up in between groups (62.4±1.8 vs 56±2.4, p=0.03). Baseline LVEF were less than 30% in both control & SCT group (29.5±0.8% & 28.7±1.3% respectively). The echocardiographic evaluation also revealed a significant increase in LVEF at 6 months (34% ±1.6 and 40% ± 2.5%, p = 0.04) of follow-up in between group but not at 30 days & 3 months follow up. University Heart Journal Vol. 16, No. 2, Jul 2020; 52-58

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Proxalutamide (GT0918) Reduces the Rate of Hospitalization and Death in COVID-19 Male Patients: A Randomized Double-Blinded Placebo-Controlled Trial.

10.21203/rs.3.rs-135303/v1 ◽

2020 ◽

Author(s):

Flavio Adsuara Cadegiani ◽

John McCoy ◽

Carlos Gustavo Wambier ◽

Maja Kovacevic ◽

Jerry Shapiro ◽

...

Keyword(s):

Controlled Trial ◽

Cohort Analysis ◽

Group Versus ◽

Standard Of Care ◽

Time Frame ◽

Ordinal Scale ◽

Control Group ◽

Androgen Treatment ◽

Reductase Inhibitors ◽

Double Blinded

Abstract Importance: Previously, we have reported a retrospective cohort analysis demonstrating the protective effect of anti-androgens (5-alpha-reductase inhibitors) in COVID-19. Objective: To determine if the anti-androgen proxalutimide is an effective treatment for men with ambulatory mild COVID-19 disease.Design: A double-blinded, randomized, prospective, investigational study of proxalutamide for the treatment men with ambulatory mild COVID-19 disease.Setting: Outpatient centers (Brasilia, Brazil) from July 15 to December 1, 2020. Participants: Men with ambulatory mild COVID-19 disease (WHO ordinal scale ≤3).Interventions: Proxalutimide 200mg/day, or standard of care for 30 days or until full COVID-19 remission. Main Outcome and Measures: Percentage of subjects hospitalized due to COVID-19 [Time Frame: 30 days].Results: A total of 214 men were included and completed the trial; 114 men were randomized to the proxalutamide group, and 100 men were randomized to the control group. A statistically significant reduction in the percentage of subjects hospitalized due to COVID-19 was observed in men taking proxalutamide (0%) compared to the standard of care (27%), (p<0.001). The percentage of men requiring mechanical ventilation was reduced in the proxalutamide group (0%) compared to control (9%), (p<0.001). Zero fatalities occurred in the proxalutamide group, versus 2 in the control group.Conclusions and Relevance: Men with ambulatory mild COVID-19 disease (WHO ordinal scale ≤3) receiving anti-androgen treatment with proxalutamide, had significantly reduced rate of hospitalization compared to men not receiving anti-androgen treatment. Trial Registration: NCT04446429

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Flunixin Meglumine Enhanced Bone Fracture Healing in Rabbits Associated with Activation of Early Collagen Deposition and Enhancement of Vascular Endothelial Growth Factor Expression

Animals ◽

10.3390/ani11102834 ◽

2021 ◽

Vol 11 (10) ◽

pp. 2834

Author(s):

Mohamed Elgendy ◽

Gamal Elsayad ◽

Magdi Seleim ◽

Walied Abdo ◽

Roua S. Baty ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Fracture Healing ◽

Bone Healing ◽

Callus Formation ◽

Control Group ◽

Vascular Endothelial ◽

Collagen Deposition ◽

Flunixin Meglumine ◽

Endothelial Growth Factor

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used postoperative analgesics, antipyretics, and anti-inflammatories, and they help prevent blood clotting. However, most NSAIDs delay bone healing. This study was aimed to investigate bone healing in a rabbit animal model by assessing the ability of flunixin meglumine (FM) and ketoprofen to induce fracture healing by examining histology, radiological changes, and vascular endothelial growth factor (VEGF) immunostaining during bone healing. For this purpose, 24 New Zealand rabbits were assigned to three groups: the control group, the FM group, and the ketoprofen group. Our results revealed that there were no intraoperative complications, and all surviving rabbits achieved full-weight bearing. Significant periosteal reaction and callus formation were confirmed at 2 postoperative weeks. Interestingly, FM enhanced callus formation, bone union, and remodeling in the FM group compared to the control and ketoprofen groups. FM enhanced bone healing through early collagen deposition and marked angiogenesis process activation by increasing the expression of VEGF. Our findings demonstrated, for the first time, the potential imperative action of FM in the bone healing process rather than other NSAIDs in animals.

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Visual Schedule System in Dental Care for Patients with Autism: A Pilot Study

Journal of Clinical Pediatric Dentistry ◽

10.17796/1053-4628-40.5.393 ◽

2016 ◽

Vol 40 (5) ◽

pp. 393-399 ◽

Cited By ~ 5

Author(s):

Janet WT Mah ◽

Phoebe Tsang

Keyword(s):

Pilot Study ◽

Test Group ◽

Standard Of Care ◽

Children With Autism ◽

Control Group ◽

Schedule System ◽

Visual Schedule ◽

Dental Appointment ◽

Picture Communication ◽

Dental Appointments

Objectives: A pilot study to test whether a visual schedule system using picture communication symbols can help children with autism have successful routine dental cleaning visits. Study Design: 14 boys with autism between three- to eight-years-old presented to the dental clinic for four weekly consecutive dental appointments. Patients were randomly assigned to either the control group who received the tell-show-do method (i.e., standard of care), or the test group who received the tell-show-do method plus the visual schedule system. Results: Patients in the test group completed an average of 1.38 more steps, at 35.52 seconds per step faster, and with 18.7% lower levels of behavioral distress than those in the control group. Conclusion: The use of a visual schedule system, along with repeated weekly visits, showed some promise in helping children with autism successfully complete more steps, progress at a quicker rate, and exhibit lower levels of behavioral distress within a dental appointment, compared to a traditional tell-show-do approach.

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