Assessing the Change in Operative Treatment Rates for Acute Midshaft Clavicle Fractures: Incorporation of Evidence-Based Surgery Results in Orthopaedic Practice.

In 2007, a randomized controlled trial (RCT) by the Canadian Orthopaedic Trauma Society (COTS) demonstrated better functional outcomes and a lower proportion of patients who developed malunion or nonunion following operative, compared with nonoperative, treatment of midshaft clavicle fractures. The primary aim of the present study was to compare the proportion of midshaft clavicle fractures treated operatively prior to and following the publication of the COTS RCT. An additional exploratory aim was to assess whether the proportion of midshaft clavicle fractures that were treated with surgery for malunion or nonunion decreased. Methods: This retrospective cohort analysis used population-level administrative health data on the residents of British Columbia, Canada. Cases were identified by International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes and procedure fee codes. Adult patients (≥18 years) with closed middle-third clavicle fractures between 1997 and 2018 were included. Multivariable logistic regression modeling compared the proportion of clavicle fractures treated operatively before and after January 1, 2007, controlling for patient factors. The Pearson chi-square test compared the proportion of fractures treated operatively for malunion or nonunion in the cohorts. Results: A total of 52,916 patients were included (mean age, 47.5 years; 65.6% male). More clavicle fractures were treated operatively from 2007 onward: 6.9% compared with 2.2% prior to 2007 (odds ratio [OR] = 3.35, 95% confidence interval [CI] = 3.03 to 3.70, p < 0.001). Male sex, moderate-to-high income, and younger age were associated with a greater proportion of operative fixation. The rate of surgery for clavicle malunion or nonunion also increased over this time period (to 4.1% from 3.4%, OR = 1.26, 95% CI = 1.15 to 1.38, p < 0.001). Conclusions: We found a significant change in surgeon practice regarding operative management of clavicle fractures following the publication of a Level-I RCT. With limited high-quality trials comparing operative and nonoperative management, it is important that clinicians, health-care institutions, and health-authority administrations determine what steps can be taken to increase responsiveness to new clinical studies and evidence-based guidelines. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Use of intraoperative impression smear cytology to guide successful treatment of a large renal cyst in a dog: a case report.

A 13-yr-old Shih tzu was referred for surgical management of right-sided cranial abdominal mass, which corresponded to large, cavitated renal mass on ultrasonography, and was suspected to represent neoplasia. Intraoperative impression smear cytology (ISC) of the renal mass wall was consistent with benign renal cyst (RC), without evidence of neoplasia or infection. Deroofing and omentalisation were performed and histopathology was consistent with benign RC. Chronic kidney disease was diagnosed 4 mon postoperatively, however, the dog was asymptomatic, without cyst reoccurrence. Intraoperative ISC is an expedient and inexpensive diagnostic technique that can guide most appropriate treatment in dogs with large RCs.

Responsiveness of the PROMIS physical function measure in orthopaedic trauma patients.

OBJECTIVES: To compare the responsiveness of the Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) to the 36-Item Short Form Survey Physical Component Score (SF36-PCS) in orthopaedic trauma patients from pre-injury to one year recovery. DESIGN AND SETTING: Prospective cohort study at a Level 1 trauma centre. PARTICIPANTS: Patients over the age of 18 with orthopaedic trauma injuries to the pelvis, lower extremity or upper extremity between 2017 and 2018. MAIN OUTCOMES MEASUREMENTS: The PROMIS-PF and SF36-PCS assessments were conducted at baseline, 3 months, 6 months and 12 months. Responsiveness of each measure was assessed between time points by calculating the standardized response mean (SRM), the proportions of patients exceeding minimal clinically important difference (MCID), and the floor and ceiling effects. RESULTS: Sixty-eight patients with completed assessments at every timepoint were included: mean age 44.7 years, 39 were male and mean Injury Severity Score (ISS) was 7.4 (range: 4-16). Mean time of completion for the SF-36 at all the time points was 5.6 min vs 1.7 min for the PROMIS-PF (p<0.01). The SRM was comparable between measures at all the time points. Although a greater proportion of patients achieved MCID for SF36-PCS between all the time points, this only approached statistical significance between the 6- and 12-month assessments (47.1% vs 33.8%; p = 0.15). There was a significant ceiling effect demonstrated with the PROMIS-PF at baseline and 12-month assessments, with 34 (50.0%) patients and 7 (10.3%) patients achieving the maximum scores at each time point, respectively. DISCUSSION AND CONCLUSIONS: PROMIS-PF has a more favourable responder burden based on lower time to completion and comparable responsiveness to the SF-36 PCS. However, there are limitations in responsiveness with the PROMIS-PF in patients who are higher functioning as demonstrated by the ceiling effects in patients at baseline pre-injury and at 12 months post-injury timepoints.

Unreamed Intramedullary Nailing Versus External Fixation for the Treatment of Open Tibial Shaft Fractures in Uganda: A Randomized Clinical Trial.

OBJECTIVE: To compare unreamed intramedullary nailing versus external fixation for the treatment of Gustilo-Anderson type II and IIIA open tibial fractures admitted to a hospital in rural Uganda. DESIGN: Randomized clinical trial. SETTING: Regional referral hospital in Uganda. PATIENTS: Fifty-five skeletally mature patients with a Gustilo-Anderson type II or IIIA open tibia shaft fracture treated within 24 hours of injury between May 2016 and December 2019. INTERVENTION: Unreamed intramedullary nailing (n = 31) versus external fixation (n = 24). MAIN OUTCOME MEASUREMENTS: The primary outcome was function within 12 months of injury, measured using the Function IndeX for Trauma (FIX-IT) score. Secondary outcomes included health-related quality of life (HRQoL) using the 3-level version of the 5-dimension EuroQol instrument (EQ-5D-3L), radiographic healing using the Radiographic Union Scale for Tibia (RUST) fractures score, and clinical complications. RESULTS: Treatment with an intramedullary nail resulted in a 1.0-point higher [95% credible intervals (CrI), 0.1 to 1.9] FIX-IT score compared with external fixation. Results were similar for the secondary patient-reported outcomes, EQ-5D-3L and the visual analog scale component of the EuroQol instrument (EQ-VAS). RUST scores were not different between groups at any time point. Treatment with an intramedullary nail was associated with a 22.1% (95% CrI, -42.6% to 1.7%) lower rate of malunion and a 20.8% (95% CrI, -44.0% to 2.9%) lower rate of superficial infection. CONCLUSION: In rural Uganda, treatment of open tibial shaft fractures with an unreamed intramedullary nail results in marginal clinically important improvements in functional outcomes, although there is likely an important reduction in malunion and superficial infection. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Quantifying Urinary and Sexual Dysfunction After Pelvic Fracture.

OBJECTIVES: To quantify the severity of urinary and sexual dysfunction and to evaluate the relationship between urinary and sexual dysfunction, injury, and treatment factors in patients with pelvic fracture. DESIGN: Prospective cohort study. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: One hundred thirteen patients with surgically treated pelvic fracture (65.5% OTA/AO 61B fractures; 7 open fractures; 74 men). INTERVENTIONS: Surgical pelvic stabilization. MAIN OUTCOME MEASURES: The 36-Item Short Form Health Survey and International Consultation Incontinence Questionnaire responses were collected at baseline, 6 months, and 1, 2, and 5 years. Patients were scored on symptoms of voiding and incontinence, and filling (for women), to derive urinary function. Sexual function was scored as a single domain. Both genders reported urinary and sexual bothersome symptoms. Regression analysis was used to isolate the importance of predictive factors on urinary and sexual function, urinary and sexual bother, and their impact on quality of life. RESULTS: Patients with pelvic fracture have significant urinary and sexual dysfunction, which is sustained or worsens over time. Male urinary function was predicted by Injury Severity Score (P = 0.03) and 61C fracture (odds ratio: 3.23, P = 0.04). Female urinary function was predicted by urinary tract injury at admission (odds ratio: 7.57, P = 0.03). Neurologic injury and anterior fixation were identified as significant predictors for male sexual function and sexual bother, whereas urological injuries were important in predicting female urinary and sexual bother (P < 0.01). Sexual function (P = 0.02) and sexual bother (P < 0.001) were important predictors of overall mental well-being in men. CONCLUSIONS: Urinary and sexual dysfunction are prevalent and sustained in men and women and do not follow the prolonged slow recovery trajectory seen in physical function. Male urinary and sexual dysfunction was closely tied to neurologic injury, whereas female urinary and sexual dysfunction was predicted by the presence of a urinary tract injury. Urinary and sexual dysfunction were important to overall mental well-being in men. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Long-Term Trajectory of Recovery Following Pilon Fracture Fixation.

OBJECTIVES: To describe the trajectory of recovery following fixation of pilon fractures from baseline to 5-year follow-up. DESIGN: Prospective cohort study. SETTING: Level-1 trauma center. PATIENTS/PARTICIPANTS: Patients with pilon fractures (OTA/AO 43.C) treated with open reduction and internal fixation. INTERVENTION: None. MAIN OUTCOMES MEASURES: Patient-reported outcome measures were measured at baseline, 6 months, 1 year, and 5 years using the Short-Form 36 Health Survey (SF-36) Physical Component Score and Mental Component Score, Short Musculoskeletal Functional Assessment, and the Foot and Ankle Outcome Score. RESULTS: One hundred two patients were enrolled: mean age was 42.6 years; 69% were males; 88% had an injury severity score of 9; 74 patients (73%) completed 1-year follow-up; 40 patients (39%) completed 5-year follow-up. Trajectory of recovery of physical function showed a significant decline between baseline and 6 months, with significant improvement between 6 months and 1 year and then ongoing but slower improvement between 1 year and 5 years. Sixty-four patients returned to baseline SF-36 Physical Component Score at 5 years. Pain was a persistent issue and remained significantly worse at 5 years when compared with baseline. Psychological well-being (SF-36 Mental Component Score) did not significantly change from baseline at 5 years. CONCLUSION: Functional recovery following open reduction and internal fixation for pilon fractures was characterized by an initial decrease in function from baseline, followed by an increase between 6 months and 1 year, and then slower but continued increases from 1 year to 5 years. Function did not return to baseline levels, pain was a persistent issue, and mental well-being showed no change from baseline at 5 years. This information may be useful when counselling patients. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Comparing the responsiveness of a generic and a musculoskeletal specific functional outcome measure in orthopaedic patients with operative fixation of pelvic ring, acetabulum, or tibia fractures: a comparison between single injury and multiply injured patients.

OBJECTIVES: This study compares the responsiveness, or the ability to detect clinical change in a disease, between the generic Short Form-36 (SF-36) and musculoskeletal specific Short Musculoskeletal Functional Assessment (SMFA) patient-reported outcome measures (PROMs) in the orthopaedic trauma population. Stratified analysis was performed to compare whether responsiveness differs between patients with single or multiple orthopaedic injuries. DESIGN: Prospective case series. SETTING: Level 1 Trauma Center. PATIENTS: A total of 659 patients with orthopaedic trauma injuries to the pelvis, acetabulum, or tibia were included for analysis. There were 485 patients with a single isolated injury and 174 patients with multiple orthopaedic injuries. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: Responsiveness was calculated through the standard response mean (SRM), the proportion meeting a minimal clinically important difference, and floor and ceiling effects. RESULTS: Between baseline and 6 months the magnitude of the SRM for SF-36 was consistently greater than that of SMFA in patients with single (P < .01) and multiple injuries (P < .01). Between 6 and 12 months, there were no differences in SRM across all cohorts. The proportion of patients who achieved minimal clinically important difference was consistently higher when assessed with SF-36 compared with SMFA between baseline and 6 months (81.8% vs 68.1%, P < .0001) and between 6 and 12 months (63.3% vs 55.4%, P = .01).A ceiling effect was only observed at baseline for the SMFA with 16.6% of patients achieving the maximal level of functioning detectable. No floor effects were seen in either PROM. CONCLUSION: This study demonstrates that SF-36 has superior responsiveness versus SMFA in both polytrauma and isolated injury patients and supports the collection of SF-36 as the primary PROM in prospective orthopaedic trauma studies irrespective of whether the patient has an isolated injury or multiple injuries.

Which general functional outcome measure does a better job of capturing change in clinical status in pelvic and acetabular fracture patients? An analysis of responsiveness over the first year of recovery.

OBJECTIVE: To compare the responsiveness of the Short Form-36 (SF-36) physical component score (PCS) to the Short Musculoskeletal Function Assessment (SMFA) dysfunction index (DI) in pelvic and acetabular fracture patients over multiple time points in the first year of recovery. DESIGN: Prospective cohort study. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Four hundred seventy-three patients with surgically treated pelvic and acetabular fractures (Orthopaedic Trauma Association B or C-type pelvic ring disruption or acetabular fracture) were enrolled into the center's prospective orthopaedic trauma database between January 2005 and February 2015. Functional outcome data were collected at baseline, 6 months, and 12 months. MAIN OUTCOME MEASUREMENTS: Evaluation was performed using the SF-36 Survey and Short Musculoskeletal Function Assessment. Responsiveness was assessed by calculating the standard response mean (SRM), the minimal clinically important difference (MCID), and floor and ceiling effects. RESULTS: Three hundred five patients had complete data for both outcome scores. SF-36 PCS and SMFA DI scores showed strong correlation for all time intervals (r = -0.55 at baseline, r = -0.78 at 6 months, and r = -0.85 at 12 months). The SRM of the SF-36 PCS was greater in magnitude than the SRM of SMFA DI at all time points; this was statistically significant between baseline and 6 months (P < .001), but not between 6 and 12 months (P = .29). Similarly, the proportion of patients achieving MCID in SF-36 PCS was significantly greater than the proportion achieving MCID in SMFA DI between baseline and 6 months (84.6% vs 69.8%, P < .001), and between 6 and 12 months (48.5% vs 35.7%, P = .01). There were no ceiling or floor effects found for SF-36 PCS at any time intervals. However, 16.1% of patients achieved the highest level of functioning detectable by the SMFA DI at baseline, along with smaller ceiling effects at 6 months (1.3%) and 12 months (3.3%). CONCLUSIONS: SF-36 PCS is a more responsive measure of functional outcome than the SFMA DI over the first year of recovery in patients who sustain a pelvic ring disruption or acetabular fracture. This superiority was found in using the SRM, proportion of patients meeting MCID, and ceiling effects. Furthermore, the SF-36 PCS correlated with the more disease-specific SMFA DI. LEVEL OF EVIDENCE: Prognostic Level II.

A head-to-head Caco-2 assay comparison of the mechanisms of action of the intestinal permeation enhancers: SNAC and sodium caprate (C10).

Salcaprozate sodium (SNAC) and sodium caprate (C10) are the two leading intestinal permeation enhancers (PEs) in oral peptide formulations in clinical trials. There is debate over their mechanism of action on intestinal epithelia. The aims were: (i) to compare their effects on the barrier function by measuring transepithelial electrical resistance (TEER), permeability of FITC-4000 (FD4) across Caco-2 monolayers, and on immunohistochemistry of tight junction (TJ)-associated proteins; and (ii) to compare cellular parameters using conventional end-point cytotoxicity assays and quantitative high content analysis (HCA) of multiple sub-lethal parameters in Caco-2 cells. C10 (8.5 mM) reversibly reduced TEER and increased FD4 permeability across monolayers, whereas SNAC had no effects on either parameter except at cytotoxic concentrations. C10 exposure induced reorganization of three TJ proteins, whereas SNAC only affected claudin-5 localization. High concentrations of C10 and SNAC were required to cause end-point toxicology changes in vitro. SNAC was less potent than C10 at inducing lysosomal and nuclear changes and plasma membrane perturbation. In parallel, HCA revealed that both agents displayed detergent-like features that reflect initial membrane fluidization followed by changes in intracellular parameters. In conclusion, FD4 permeability increases in monolayers in response to C10 were in the range of concentrations that altered end-point cytotoxicity and HCA parameters. For SNAC, while HCA parameters were also altered in a similar overall pattern as C10, they did not lead to increased paracellular flux. These assays show that both agents are primarily surfactants, but C10 has additional TJ-opening effects. While these in vitro assays illucidate their epithelial mechanism of action, clinical experience suggests that they over-estimate their toxicology in the dynamic intestinal environment.

Measuring Outcomes Over Time in Distal Radius Fractures: A Comparison of Generic, Upper Extremity-Specific and Wrist-Specific Outcome Measures.

Purpose: This study compared the responsiveness of a generic (Short Form-36 [SF-36]), an upper extremity-specific (Disabilities of the Arm, Shoulder, and Hand [DASH]) and a wrist-specific (Patient-Rated Wrist Evaluation [PRWE]) outcome score when evaluating distal radius fractures over time. Methods: We observed 235 patients who met the inclusion criteria of an isolated distal radius fracture treated surgically or nonsurgically and greater than age 50 years for 12 months in this prospective study. Standardized assessments were performed at baseline and at 6 and 12 months. Exclusion criteria included subjects with concomitant injuries in the ipsilateral limb and follow-up of less than 1 year. Responsiveness was evaluated through the standardized response mean and the proportion who met a minimal clinically important difference. Floor and ceiling effects were also calculated. Results: The standardized response mean was significantly greatest for the DASH between baseline and 6 months (P < .001), and the PRWE between both baseline and 6 months (P < .01) and 6 and 12 months (P < .01) compared with the SF-36. The proportion of patients who met a minimal clinically important difference between baseline and 6 months was greater in the PRWE, but it did not meet statistical significance (P = .12). The PRWE demonstrated a high ceiling effect at baseline (76.6%) but less so at 12 months (16.9%). The DASH demonstrated similar ceiling effects at baseline (62.9%) and 12 months (18.6%). The SF-36 had no ceiling effect. Conclusions: In the first 6 months, both the DASH and PRWE have greater responsiveness in assessing change over the SF-36 in distal radius fractures. From 6 to 12 months, the wrist-specific PRWE has greater responsiveness over both the DASH and SF-36. This supports the use of the anatomy- and injury-specific outcome measures over the generic outcome measure in detecting change over a patient's early recovery. However, as the time from injury increases, the absence of a ceiling effect from the generic outcome measure may become more useful. Clinical relevance: This study demonstrates the responsiveness of the DASH, PRWE, and SF36 in assessing distal radius fractures treated in patients greater than age 50 in the first year. In establishing the most responsive measure, respondent burden can be decreased in future research.

The Feasibility of a Randomized Controlled Trial for Open Tibial Fractures at a Regional Hospital in Uganda.

BACKGROUND: The inclusion of low and middle-income country (LMIC) hospitals in multicenter orthopaedic trials expands the pool of eligible patients and improves the external validity of the evidence. Furthermore, promoting studies in LMIC hospitals defines the optimal treatments for low-resource settings, the conditions under which the majority of musculoskeletal injuries are treated. The objective of this study was to determine the feasibility of a randomized controlled trial comparing external fixation with intramedullary (IM) nailing in patients with an isolated open tibial fracture who presented to a regional hospital in Uganda. METHODS: From July 2016 to July 2017, skeletally mature patients who presented to a Ugandan regional hospital with an isolated Gustilo-Anderson type-II or IIIA open fracture of the tibial shaft were eligible for inclusion. The primary feasibility outcomes were the enrollment rate, the recruitment rate, and the 3 and 12-month follow-up rates. The secondary outcomes included a comparison of 3 and 12-month follow-up rates between the treatment arms and a qualitative assessment of barriers to enrollment, timely treatment, and missed follow-up. RESULTS: During the 12-month enrollment period, 37.5% (30 of 80) of eligible patients were successfully enrolled and operatively treated on the basis of their random allocation, with an enrollment rate of 2.5 patients per month. Of the 30 enrolled patients, 53% completed their 3-month follow-up appointment, and 40% completed their 1-year follow-up appointment. Rates of 1-year follow-up were significantly higher for patients receiving IM nails than for those receiving external fixation (absolute difference, 52%; 95% confidence interval [CI], 21 to 83, p < 0.01). The main reasons that patients declined to participate in the trial were preferences for treatment by traditional bonesetters and prehospital delays that were related to a disorganized referral system. Barriers to follow-up included prohibitive transportation costs and community pressure to turn to traditional forms of treatment. CONCLUSIONS: A regional hospital in Uganda can successfully enroll, randomize, and operatively treat multiple patients with an open tibial fracture each month. Patient follow-up presents substantial concerns over trial feasibility in this setting. Cultural pressure to utilize traditional treatments remains a particularly common barrier to study-participant enrollment and retention.

Failure Patterns of Femoral Neck Fracture Fixation in Young Patients.

The primary purpose of this study was to describe the failure patterns of femoral neck fracture fixation in young patients. The secondary purpose was to determine if pattern of failure varies by type of implant. Adult patients (age range, 18-55 years) who experienced a "fixation failure" following internal fixation of a femoral neck fracture were identified from 5 level 1 trauma centers. Failure was defined by screw cutout, implant breakage, varus collapse (<120° neck-shaft angle), or severe fracture shortening (≥1 cm). When multiple complications were identified, mechanical failures were preferentially noted for the analysis. Failure patterns were compared between patients who received multiple cancellous screws and patients who received a sliding hip screw plus a derotation screw. Severe fracture shortening was the most common complication identified (61%). No differences in the incidence of severe shortening (P=.750) or implant breakage (P=1.000) were detected between the fixation groups. However, among the failures with a sliding hip screw plus a derotation screw construct, a greater portion were related to screw cutout (38% for a sliding hip screw plus a derotation screw vs 7% for screws, P=.019). Failures with multiple screws were associated with varus collapse (25% for screws vs 0% for a sliding hip screw plus a derotation screw, P=.037). Severe shortening was the most common fixation failure. Sliding hip screw plus derotation screw implants were associated with screw cutout. Multiple cancellous screw implants failed by varus collapse. Selecting a surgical implant based on its likely failure pattern may allow surgeons to minimize the severity of failure or the need for secondary conversion to hip arthroplasty. [Orthopedics. 2019; 42(4):e376-e380.].

High rate of reoperation and conversion to total hip arthroplasty after internal fixation of young femoral neck fractures: a population-based study of 796 patients.

Background and purpose - Most often, the goal of non-geriatric femoral neck fracture surgery is to preserve the native hip joint. However, reoperations for painful implants, osteonecrosis, and nonunion are common. We determined the reoperation rate and time-to-reoperation following internal fixation of these fractures in a large population cohort. Patients and methods - This retrospective cohort study included patients between the ages of 18 and 50 years old who underwent internal fixation for a femoral neck fracture during 1997-2013. Patients were followed until December 2013. Primary outcomes were reoperation rate and time-to-reoperation. Time-to-event analysis was performed to estimate the rate of any reoperation and for THA specifically, while testing the dependency of time-to-reoperation on secondary variables. Results - 796 young femoral neck fracture patients were treated with internal fixation during the study period (median age 43 years, 39% women). Median follow-up was 8 years (IQR 4-13). One-third underwent at least 1 reoperation at a median 16 months after the index surgery (IQR 8-31). Half of reoperations were for implant removal, followed by conversion to total hip arthroplasty. 14% of the cohort were converted to THA. The median time to conversion was 2 years (IQR 1-4). Neither female sex nor older age had a statistically significant effect on time-to-reoperation or time-to-THA conversion. Interpretation - Following internal fixation of young femoral neck fracture, 1 in 3 patients required a reoperation, and 1 in 7 were converted to THA. These data should be considered by patients and surgeons during treatment decision-making.

Predicting completion of follow-up in prospective orthopaedic trauma research.

OBJECTIVE: Orthopaedic trauma studies that collect long-term outcomes are expensive and maintaining high rates of follow-up can be challenging. Knowing what factors influence completion of follow-up could allow interventions to improve this. We aimed to assess which factors influence completion of follow-up in the 12 months following surgery in prospective orthopaedic trauma research. DESIGN: Prospective Cohort Study. SETTING: Level 1 Trauma Center, Vancouver, Canada. PARTICIPANTS: Eight hundred seventy patients recruited to 4 prospective studies investigating the outcomes of operatively treated lower extremity fractures. MAIN OUTCOME MEASUREMENTS: Completion of follow-up defined as completion of all outcome measures at all time points up to 12 months following injury. RESULTS: Univariate analysis and subsequent analysis by building a reductive multivariate regression model allowed for estimation of the influence of factors in completion of follow-up.Eight hundred seventy patients with complete data had previously been recruited and were included in the analysis. Seven hundred seven patients (81.2%) completed follow-up to 12 months. Factors associated with completion of follow up included higher physical component score of SF-36 at baseline, not being on social assistance at the time of injury, being married and having a higher level of educational attainment. CONCLUSIONS: Our study has demonstrated several important factors identifiable at baseline which are associated with a failure to complete follow-up. Although these factors are not modifiable themselves, we advocate that researchers designing studies should plan for additional follow-up resources and interventions for at risk patients. LEVEL OF EVIDENCE: Level IV.

Comparison of Generic, Musculoskeletal-Specific, and Foot and Ankle-Specific Outcome Measures Over Time in Tibial Plafond Fractures.

BACKGROUND: This study performed a psychometric analysis assessing and comparing the responsiveness of the relevant components of a generic (Short Form-36 [SF36]), a musculoskeletal-specific (Short Musculoskeletal Functional Assessment [SMFA]), and a foot and ankle-specific (Foot and Ankle Outcome Score [FAOS]) outcome score when evaluating surgically treated tibial plafond fractures over time. METHODS: Fifty-one patients were followed for 12 months after their tibial plafond fracture. Responsiveness, or the ability to detect clinical change in a disease, was evaluated through the standardized response mean (SRM), the proportion meeting a minimal clinically important difference (MCID), and floor and ceiling effects. RESULTS: The SRM of the SF36-Physical Component Summary (PCS) was significantly greater than the SMFA-dysfunction index (DI) (P < .01) and FAOS-Activities of Daily Living (ADL) (P = .01) between baseline and 6 months, whereas the SRMs of only SF36-PCS and FAOS-ADL differed (P = .01) between 6 and 12 months. The proportion of patients achieving an MCID for SF36-PCS was higher than FAOS-ADL (P = .03) between baseline and 6 months and higher than SMFA-DI (P = .04) between 6 and 12 months. The FAOS-ADL showed substantial ceiling effects at baseline (88.2%) but much less at 6 months (5.9%) and 12 months (9.8%). Smaller ceiling effects were observed for the SMFA-DI (11.8%) at baseline, whereas none were observed for the SF36-PCS. CONCLUSIONS: This study found that the SF36-PCS had greater responsiveness in assessing tibial plafond fractures compared to the SMFA-DI and FAOS-ADL, particularly in the first 6 months after surgery. In addition, limitations were revealed in the SMFA-DI and FAOS-ADL. This study illustrates the necessary diligence required for selection of outcome measures, as musculoskeletal and anatomy specific scores are not necessarily superior. LEVEL OF EVIDENCE: Level II, prospective cohort study.

The Socioeconomic Implications of Isolated Tibial and Femoral Fractures from Road Traffic Injuries in Uganda.

BACKGROUND: The purpose of this study was to determine the socioeconomic implications of isolated tibial and femoral fractures caused by road traffic injuries in Uganda. METHODS: This prospective longitudinal study included adult patients who were admitted to Uganda's national referral hospital with an isolated tibial or femoral fracture. The primary outcome was the time to recovery following injury. We assessed recovery using 4 domains: income, employment status, health-related quality of life (HRQoL) recovery, and school attendance of the patients' dependents. RESULTS: The majority of the study participants (83%) were employed, and they were the main income earner for their household (74.0%) at the time of injury, earning a mean annual income of 2,375 U.S. dollars (USD). All of the patients had been admitted with the intention of surgical treatment; however, because of resource constraints, only 56% received operative treatment. By 2 years postinjury, only 63% of the participants had returned to work, and 34% had returned to their previous income level. Overall, the mean monthly income was 62% less than preinjury earnings, and participants had accumulated 1,069 USD in debt since the injury; 41% of the participants had regained HRQoL scores near their baseline, and 62% of school-aged dependents, enrolled at the time of injury, were in school at 2 years postinjury. CONCLUSIONS: At 2 years postinjury, only 12% of our cohort of Ugandan patients who had sustained an isolated tibial or femoral fracture from a road traffic injury had recovered both economically and physically. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Methotrexate induced mitochondrial injury and cytochrome c release in rat liver hepatocytes.

Methotrexate (MTX) is a folic acid antagonist that is widely used to treat a variety of diseases. One of the most serious side effects of MTX therapy is hepatotoxicity. The potential molecular cytotoxic mechanisms of MTX toward isolated rat hepatocytes were investigated using Accelerated Cytotoxicity Mechanism Screening (ACMS) techniques. A concentration and time dependent increase in cytotoxicity and reactive oxygen species (ROS) formation and a decrease in mitochondrial membrane potential (MMP) were observed with MTX. Furthermore, a significant increase in MTX (300 µM)-induced cytotoxicity and ROS formation were observed when glutathione (GSH)-depleted hepatocytes were used whereas addition of N-acetylcysteine (a GSH precursor) decreased cytotoxicity. Catalase inactivation also increased MTX-induced cytotoxicity, while the direct addition of catalase to the hepatocytes decreased cytotoxicity. MTX treatment in isolated rat mitochondria caused swelling and significantly decreased adenosine triphosphate (ATP) and GSH content, and cytochrome c release. Potent antioxidants such as mesna, resveratrol and Trolox decreased MTX-induced cytotoxicity and ROS formation and increased MMP. This study suggests that MTX-induced cytotoxicity caused by ROS formation and GSH oxidation leads to oxidative stress and mitochondrial injury in rat hepatocytes.

Digital blinding of radiographs to mask allocation in a randomized control trial.

AIM: To demonstrate the effectiveness of a digital radiographic altering technique in concealing treatment allocation to blind outcome assessment of distal femur fracture fixation. METHODS: Digital postoperative anteroposterior and lateral radiographs from a sample of 33 randomly-selected patients with extra-articular distal femur fractures treated by surgical fixation at a Level 1 trauma center were included. Using commercially available digital altering software, we devised a technique to blind the radiographs by overlaying black boxes over the implant hardware while preserving an exposed fracture site for assessment of fracture healing. Three fellowship-trained surgeons evaluated a set of blinded radiographs twice and a control set of unblinded radiographs once. Each set of radiographs were reviewed independently and in a randomly-assigned order. The degrees of agreement and disagreement among evaluators in identifying implant type while reviewing both blinded and unblinded radiographs were assessed using the Bang Blinding Index and James Blinding Index. The degree of agreement in fracture union was assessed using kappa statistics. RESULTS: The assessment of blinded radiographs with both the Bang Blinding Index (BBI) and James Blinding Index (JBI) demonstrated a low degree of evaluator success at identifying implant type (Mean BBI, far cortical locking: -0.03, SD: 0.04; Mean BBI, standard screw: 0, SD: 0; JBI: 0.98, SD: 0), suggesting near perfect blinding. The assessment of unblinded radiographs with both blinding indices demonstrated a high degree of evaluator success at identifying implant type (Mean BBI, far cortical locking: 0.89, SD: 0.19; Mean BBI, standard screw: 0.87, SD: 0.04; JBI: 0.26, SD: 0.12), as expected. There was moderate agreement with regard to assessment of fracture union among the evaluators in both the blinded (Kappa: 0.38, 95%CI: 0.25-0.52) and unblinded (Kappa: 0.35, 95%CI: 0.25-0.45) arms of the study. There was no statistically significant difference in fracture union agreement between the blinded and unblinded groups. CONCLUSION: The digital blinding technique successfully masked the surgeons to the type of implant used for surgical treatment of distal femur fractures but did not interfere with the surgeons' ability to reliably evaluate radiographic healing at the fracture site.

Marked paraneoplastic basophilia accompanying eosinophilia in a cat with alimentary T-cell lymphoma.

CASE SUMMARY: A 5-year-old male neutered domestic shorthair cat was referred with a history of persistent pyrexia, pica, soft faeces, inappetence, intermittent vomiting, mild-to-moderate granulocytosis and mild hypercalcaemia. No significant improvement was noted after antibiotic and corticosteroid treatment, except that the hypercalcaemia resolved. Physical examination, including thoracic auscultation, and abdominal and peripheral lymph node palpation, were unremarkable. On admission, haematology revealed moderate leukocytosis (36.8 × 109/l) with moderate-to-marked eosinophilia (21.3 × 109/l) and marked basophilia (4.04 × 109/l), the latter identified microscopically. Lymphocytes were markedly decreased (0.37 × 109/l). Blood smear examination revealed 58% eosinophils, 28% neutrophils, 11% basophils, 2% monocytes, 1% lymphocytes and marked, diffuse platelet clumping. Biochemistry abnormalities indicated mild pancreatitis, dehydration and anorexia with mildly increased pancreatic lipase, mild hypernatraemia (157 mmol/l), a moderate decrease in urea (3.1 mmol/l) and a slight decrease in phosphate (1.32 mmol/l). Ultrasound and radiographic imaging revealed enlargement of the mesenteric lymph nodes. Fine-needle aspiration, a Tru-cut biopsy and immunohistochemistry were performed. Cytological examination revealed ~65-75% lymphocytes (~80% were larger than a neutrophil), ~25-35% eosinophils and occasional basophils. Lymphocytes had single, small (<1/3 red blood cells), prominent nucleoli and increased pale, mildly vacuolated cytoplasm. On histopathology, cells were monomorphic, large, with prominent nucleoli, and mild, multifocal, staining for T-cell marker CD3. Smaller cells were strongly CD3-positive. Cells were negative for B-cell marker CD45R. RELEVANCE AND NOVEL INFORMATION: This is the most severe case of paraneoplastic basophilia reported with feline alimentary T-cell lymphoma with accompanying eosinophilia and lymph node infiltration. Feline basophil prevalence is reported for the first time.

When Surgical Resources are Severely Constrained, Who Receives Care? Determinants of Access to Orthopaedic Trauma Surgery in Uganda.

BACKGROUND: In low- and middle-income countries, the volume of traumatic injuries requiring orthopaedic intervention routinely exceeds the capacity of available surgical resources. The objective of this study was to identify predictors of surgical care for lower extremity fracture patients at a high-demand, resource-limited public hospital in Uganda. METHODS: Skeletally mature patients admitted with the intention of definitive surgical treatment of an isolated tibia or femur fractures to the national referral hospital in Uganda were recruited to participate in this study. Demographic, socioeconomic, and clinical data were collected through participant interviews at the time of injury and 6 months post-injury. Social capital (use of social networks to gain access to surgery), financial leveraging, and ethnicity were also included as variables in this analysis. A probit estimation model was used to identify independent and interactive predictors of surgical treatment. RESULTS: Of the 64 patients included in the final analysis, the majority of participants were male (83%), with a mean age of 40.6, and were injured in a motor vehicle accident (77%). Due to resource constraints, only 58% of participants received surgical care. The use of social capital and femur fractures were identified as significant predictors of receiving surgical treatment, with social capital emerging as the strongest predictor of access to surgery (p < 0.05). CONCLUSION: Limited infrastructure, trained personnel, and surgical supplies rations access to surgical care. In this environment, participants with advantageous social connections were able to self-advocate for surgery where demand for these services greatly exceeded available resources.