A New Computed Tomography-Based Measure that Provides Insight Into Hip Stability in Patients With Posterior Wall Acetabular Fractures.

OBJECTIVES: To describe the technique and results of a new sagittal plane computed tomography (CT)-based angular measure for predicting stability after posterior wall acetabular fractures (PWF). DESIGN: Retrospective review. SETTING: Academic Level II trauma center. PATIENT SELECTION CRITERIA: Fifty-eight consecutive patients with PWF (AO/OTA class 62A.1), 98% were high-energy injuries. INTERVENTION: A new sagittal CT measure of PWF based on the angle subtending the joint center, cranial and caudal fracture exits. OUTCOME MEASURES AND COMPARISONS: Hip incongruity or dislocation demonstrated using gold standard test, examination under anesthesia (EUA), or instability on static images. Prediction of hip instability using a sagittal CT angular measure based on cranial and caudal fracture exits was compared with previous axial CT measures suggestive of increased risk for instability including posterior wall size >50%, and those with cranial exit within 5.0 mm of the acetabular dome. RESULTS: There were 32 operative and 26 nonoperatively treated fractures. Thirty fractures were determined to be unstable, and 28 were stable after EUA. Measurements of >70 degrees using the sagittal CT angular measure predicted instability in 28 of 28 patients, and ≤70 degrees predicted stability in 30 of 30 patients (sensitivity 100% and specificity 100%). Prevalence of EUA confirmed instability for subgroups with PWF based on prior axial CT measures were as follows: ≥50% wall involvement (11/16; sensitivity 67% and specificity 60%; 95% CI, 45%-89%/45%-75%), fracture within 5.0 mm of dome (5/18; sensitivity 86% and specificity 73%; 95% CI, 71%-100%/59%-87%), fracture within 5.0 mm of dome and ≥50% involvement (1/9; sensitivity 89% and specificity 56%; 95% CI, 69%-100%/24%-88%). CONCLUSIONS: In a sample of 58 mostly high energy posterior wall fractures all having had an EUA, a new sagittal angular CT measurement of ≤70 degrees predicted hip stability and >70 degrees predicted instability with 100% sensitivity and specificity. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Infection Rates and Surgical Procedures Associated With Isolated Open Talar Neck and Body Fractures.

BACKGROUND: Open fractures of the talar body and neck are uncommon. Previous reports of associated deep infection rates and resulting surgical requirements vary widely. The primary objective of this study is to report the incidence of deep infections for isolated open talar body and neck fractures, and secondarily the incidence and number of total surgeries performed (TSP), secondary salvage procedures (SSPs), and nonsalvage procedures (NSPs). METHODS: Retrospective case-control study of 32 consecutive isolated open talus fracture patients (22 neck, 10 body) were followed for an average of 39.2 months. RESULTS: Five (15.6%) fractures developed deep infections. Fifty percent of open body fractures became infected compared with 0% of neck fractures (P < .001). There was no difference between infected group (IG) and uninfected fracture group (UG) with respect to age, sex, body mass index, tobacco, diabetes, vascular disease, open fracture type, wound location, hours to irrigation and debridement, or definitive treatment. The majority (92.6%) of UG fractures used a dual incision with open wound extension. There were more single extensile approaches in the IG group (P = .04). The IG required 5.8 TSP per patient compared with 2.1 in the UG (P = .004). All (100%) of the IG required an SSP compared with 29.6% of the UG (P = .006). All (100%) of the IG required an NSP compared to 40.7% of the UG (P = .043). In the IG, 2.8 NSPs per patient were required after definitive surgery compared with 1.18 in the UG (P = .003). Of those followed 1 year, the incidence of SSP remained higher in the IG (P = .016). CONCLUSION: The incidence of deep infection following isolated open talar fractures is high and occurs disproportionally in body fractures. Infected fractures required nearly 6 surgeries, and all required SSP. LEVEL OF EVIDENCE: Level IV, prognostic.

Skin Antisepsis before Surgical Fixation of Extremity Fractures.

BACKGROUND: Studies evaluating surgical-site infection have had conflicting results with respect to the use of alcohol solutions containing iodine povacrylex or chlorhexidine gluconate as skin antisepsis before surgery to repair a fractured limb (i.e., an extremity fracture). METHODS: In a cluster-randomized, crossover trial at 25 hospitals in the United States and Canada, we randomly assigned hospitals to use a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol (iodine group) or 2% chlorhexidine gluconate in 70% isopropyl alcohol (chlorhexidine group) as preoperative antisepsis for surgical procedures to repair extremity fractures. Every 2 months, the hospitals alternated interventions. Separate populations of patients with either open or closed fractures were enrolled and included in the analysis. The primary outcome was surgical-site infection, which included superficial incisional infection within 30 days or deep incisional or organ-space infection within 90 days. The secondary outcome was unplanned reoperation for fracture-healing complications. RESULTS: A total of 6785 patients with a closed fracture and 1700 patients with an open fracture were included in the trial. In the closed-fracture population, surgical-site infection occurred in 77 patients (2.4%) in the iodine group and in 108 patients (3.3%) in the chlorhexidine group (odds ratio, 0.74; 95% confidence interval [CI], 0.55 to 1.00; P = 0.049). In the open-fracture population, surgical-site infection occurred in 54 patients (6.5%) in the iodine group and in 60 patients (7.3%) in the chlorhexidine group (odd ratio, 0.86; 95% CI, 0.58 to 1.27; P = 0.45). The frequencies of unplanned reoperation, 1-year outcomes, and serious adverse events were similar in the two groups. CONCLUSIONS: Among patients with closed extremity fractures, skin antisepsis with iodine povacrylex in alcohol resulted in fewer surgical-site infections than antisepsis with chlorhexidine gluconate in alcohol. In patients with open fractures, the results were similar in the two groups. (Funded by the Patient-Centered Outcomes Research Institute and the Canadian Institutes of Health Research; PREPARE ClinicalTrials.gov number, NCT03523962.).

Technical Factors Contributing to Nonunion in Supracondylar Distal Femur Fractures Treated With Lateral Locked Plating: A Risk-Stratified Analysis.

OBJECTIVE: To identify technical factors associated with nonunion after operative treatment with lateral locked plating. DESIGN: Retrospective cohort study. SETTING: Ten Level I trauma centers. PATIENT SELECTION CRITERIA: Adult patients with supracondylar distal femur fractures (OTA/AO type 33A or C) treated with lateral locked plating from 2010 through 2019. OUTCOME MEASURES AND COMPARISONS: Surgery for nonunion stratified by risk for nonunion. RESULTS: The cohort included 615 patients with supracondylar distal femur fractures. The median patient age was 61 years old (interquartile range: 46 -72years) and 375 (61%) were female. Observed were nonunion rates of 2% in a low risk of nonunion group (n = 129), 4% in a medium-risk group (n = 333), and 14% in a high-risk group (n = 153). Varus malreduction with an anatomic lateral distal femoral angle greater than 84 degrees, was associated with double the odds of nonunion compared to those without such varus [odds ratio, 2.1; 95% confidence interval (CI), 1.1-4.2; P = 0.03]. Malreduction by medial translation of the articular block increased the odds of nonunion, with 30% increased odds per 4 mm of medial translation (95% CI, 1.0-1.6; P = 0.03). Working length increased the odds of nonunion in the medium risk group, with an 18% increase in nonunion per 10-mm increase in working length (95% CI, 1.0-1.4; P = 0.01). Increased proximal screw density was protective against nonunion (odds ratio, 0.71; 95% CI, 0.53-0.92; P = 0.02) but yielded lower mRUST scores with each 0.1 increase in screw density associated with a 0.4-point lower mRUST (95% CI, -0.55 to -0.15; P < 0.001). Lateral plate length and type of plate material were not associated with nonunion. ( P > 0.05). CONCLUSIONS: Malreduction is a surgeon-controlled variable associated with nonunion after lateral locked plating of supracondylar distal femur fractures. Longer working lengths were associated with nonunion, suggesting that bridge plating may be less likely to succeed for longer fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Patient preferences for physical therapy programs after a lower extremity fracture: a discrete choice experiment.

OBJECTIVE: To quantify patients' preferences for physical therapy programmes after a lower extremity fracture and determine patient factors associated with preference variation. DESIGN: Discrete choice experiment. SETTING: Level I trauma centre. PARTICIPANTS: One hundred fifty-one adult (≥18 years old) patients with lower extremity fractures treated operatively. INTERVENTION: Patients were given hypothetical scenarios and asked to select their preferred therapy course when comparing cost, mobility, long-term pain, session duration, and treatment setting. MAIN OUTCOME MEASURES: A multinomial logit model was used to determine the relative importance and willingness to pay for each attribute. RESULTS: Mobility was of greatest relative importance (45%, 95% CI: 40% to 49%), more than cost (23%, 95% CI: 19% to 27%), long-term pain (19%, 95% CI: 16% to 23%), therapy session duration (12%, 95% CI: 9% to 5%) or setting (1%, 95% CI: 0.2% to 2%). Patients were willing to pay US$142 more per session to return to their preinjury mobility level (95% CI: US$103 to US$182). Willingness to pay for improved mobility was higher for women, patients aged 70 years and older, those with bachelor's degrees or higher and those living in less-deprived areas. Patients were willing to pay US$72 (95% CI: US$50 to US$93) more per session to reduce pain from severe to mild. Patients were indifferent between formal and independent home therapy (willingness to pay: -US$12, 95% CI: -US$33 to US$9). CONCLUSIONS: Patients with lower extremity fractures highly value recovering mobility and are willing to pay more for postoperative physical therapy programmes that facilitate returning to their pre-injury mobility level. These patient preferences might be useful when prescribing and designing new techniques for postoperative therapy.

A deep surgical site infection risk score for patients with open tibial shaft fractures treated with intramedullary nail.

OBJECTIVES: To identify deep infection risk factors in patients with open tibial shaft fractures and to develop a scoring algorithm to predict the baseline deep infection risk in this patient population. METHODS: A retrospective cohort study conducted at a single academic trauma center identified patients with open tibial shaft fractures treated with intramedullary nail fixation from December 2006 to October 2020. The primary outcome was a deep surgical site infection requiring surgical debridement. The outcome was identified by Current Procedural Terminology codes and confirmed with a medical chart review documenting evidence of a tibial draining wound or sinus tract. RESULTS: Deep surgical site infection occurred in 13% of patients (97/769). Factors that predicted deep surgical site infection were identified. Gustilo-Anderson type IIIB or IIIC was the strongest predictor with a 12-fold increase in the odds of deep infection (OR 11.8, p < 0.001). Additional factors included age >40 years (OR 1.7, p = 0.03), American Society of Anesthesiologists score ≥3 (OR 1.9, p < 0.01), Gustilo-Anderson type IIIA vs. type I or II (OR 2.8, p = 0.004), and gunshot wounds (OR 2.9, p = 0.02). The risk scoring model predicted patients who would develop an infection with an acceptable level of accuracy (AUC 0.79). The risk score categorized patients from a low probability of deep infection 2%-6% with <10 points to high risk (58%-69%) with >40 points. CONCLUSIONS: This risk score model predicts deep postoperative infection in patients with open tibial shaft fractures treated with intramedullary nails. The ability to accurately estimate deep infection risk at the time of presentation might aid patient expectation management and allow clinicians to focus infection prevention strategies on the high-risk subset of this population.

Effect of Vitamin D3 Supplementation on Acute Fracture Healing: A Phase II Screening Randomized Double-Blind Controlled Trial.

Nearly half of adult fracture patients are vitamin D deficient (serum 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Many surgeons advocate prescribing vitamin D supplements to improve fracture healing outcomes; however, data supporting the effectiveness of vitamin D3 supplements to improve acute fracture healing are lacking. We tested the effectiveness of vitamin D3 supplementation for improving tibia and femur fracture healing. We conducted a single-center, double-blinded phase II screening randomized controlled trial with a 12-month follow-up. Patients aged 18-50 years receiving an intramedullary nail for a tibia or femoral shaft fracture were randomized 1:1:1:1 to receive (i) 150,000 IU loading dose vitamin D3 at injury and 6 weeks (n = 27); (ii) 4000 IU vitamin D3 daily (n = 24); (iii) 600 IU vitamin D3 daily (n = 24); or (iv) placebo (n = 27). Primary outcomes were clinical fracture healing (Function IndeX for Trauma [FIX-IT]) and radiographic fracture healing (Radiographic Union Score for Tibial fractures [RUST]) at 3 months. One hundred two patients with a mean age of 29 years (standard deviation 8) were randomized. The majority were male (69%), and 56% were vitamin D3 deficient at baseline. Ninety-nine patients completed the 3-month follow-up. In our prespecified comparisons, no clinically important or statistically significant differences were detected in RUST or FIX-IT scores between groups when measured at 3 months and over 12 months. However, in a post hoc comparison, high doses of vitamin D3 were associated with improved clinical fracture healing relative to placebo at 3 months (mean difference [MD] 0.90, 80% confidence interval [CI], 0.08 to 1.79; p = 0.16) and within 12 months (MD 0.89, 80% CI, 0.05 to 1.74; p = 0.18). The study was designed to identify potential evidence to support the effectiveness of vitamin D3 supplementation in improving acute fracture healing. Vitamin D3 supplementation, particularly high doses, might modestly improve acute tibia or femoral shaft fracture healing in healthy adults, but confirmatory studies are required. The Vita-Shock trial was awarded the Orthopaedic Trauma Association's (OTA) Bovill Award in 2020. This award is presented annually to the authors of the most outstanding OTA Annual Meeting scientific paper. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Does iliosacral screw removal reduce postoperative pain in unstable pelvic fracture patients? A matched prospective cohort study.

BACKGROUND: To compare pain and function in patients with unstable posterior pelvic fractures stabilized with posterior fixation who undergo iliosacral screw removal versus those who retain their iliosacral screws. METHODS: A prospective observational cohort study identified 59 patients who reported pain at least 4 months after iliosacral screw fixation of an unstable posterior pelvic ring fracture from 2015-2019. The primary intervention was iliosacral screw removal versus a matched iliosacral screw retention control group. Patient-reported pain was measured with the 10-point Brief Pain Inventory, and patient-reported function was measured with the Majeed Pelvic Outcome Score. Both measured within 6 months of the intervention. RESULTS: Before iliosacral screw removal, the mean pain was 4.7 (SD, 3.0) compared with 4.7 (SD, 3.0) in the matched control group. Following iliosacral screw removal, the average pain in the screw removal group was 3.7 (SD, 2.7) and 3.3 (SD, 2.5) in the matched control group. We found no evidence that iliosacral screw removal reduced pain in this population (mean difference, 0.2 points; 95% CI, -1.0 to 1.5; p = 0.71). In addition, the improvement in function after iliosacral screw removal was not statistically indistinguishable from zero (mean difference, 3.1 points; 95% CI, -4.6 to 10.9; p = 0.42). CONCLUSIONS: The results suggest that iliosacral screw removal offers no significant pelvic pain or function benefit when compared with a matched control group. Surgeons should consider these data when managing patients with pelvic pain who are candidates for iliosacral screw removal.

The impact of COVID-19 restrictions on participant enrollment in the PREPARE trial.

Background: At the initiation of the COVID-19 pandemic, restrictions forced researchers to decide whether to continue their ongoing clinical trials. The PREPARE (Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities) trial is a pragmatic cluster-randomized crossover trial in patients with open and closed fractures. PREPARE was enrolling over 200 participants per month at the initiation of the pandemic. We aim to describe how the COVID-19 research restrictions affected participant enrollment. Methods: The PREPARE protocol permitted telephone consent, however, sites were obtaining consent in-person. To continue enrollment after the initiation of the restrictions participating sites obtained ethics approval for telephone consent scripts and the waiver of a signature on the consent form. We recorded the number of sites that switched to telephone consent, paused enrollment, and the length of the pause. We used t-tests to compare the differences in monthly enrollment between July 2019 and November 2020. Results: All 19 sites quickly implement telephone consent. Fourteen out of nineteen (73.6%) sites paused enrollment due to COVID-19 restrictions. The median length of enrollment pause was 46.5 days (range, 7-121 days; interquartile range, 61 days). The months immediately following the implementation of restrictions had significantly lower enrollment. Conclusion: A pragmatic design allowed sites to quickly adapt their procedures for obtaining informed consent via telephone and allowed for minimal interruptions to enrollment during the pandemic.

Prospective Characterization of Pain and Function in Patients With Unstable Pelvic Fractures Treated With Posterior Screw Fixation.

OBJECTIVES: Describe patient-reported pain and function within 24 months of a pelvic fracture treated with posterior screw fixation and identify factors associated with increased pain. DESIGN: Prospective case series. SETTING: Academic trauma center. PATIENTS/INTERVENTION: Eighty-eight patients with adult pelvic fracture treated with sacroiliac or transiliac screws. MAIN OUTCOME MEASURES: Average pain measured with the Brief Pain Inventory (BPI); function measured with the Majeed Pelvic Outcome Score from 6 to 24 months postinjury. RESULTS: The mean pain from 6 to 24 months postinjury was 2.22 on the 10-point BPI scale (95% CI, 0.64-3.81). Sixty-nine patients (78.4%) reported mild to no pain at 6 months; 12 (13.6%) patients had severe pain. Two years after injury, 71 patients (80.6%) exhibited mild to no pain. Within 24 months of injury, the mean pelvic function was 71 on the 100-point Majeed scale (95% CI, 60-82). Half of the sample (n = 44) had good to excellent pelvis function by 6 months postinjury; 55 patients (62.5%) attained this level of function by 24 months. A history of chronic pain (1.31; 95% CI, 0.26-2.37; P = 0.02), initial fracture displacement (≥5 mm) (0.99; 95% CI, 0.23-1.69; P = 0.01), and socioeconomic deprivation (0.28; 95% CI, 0.11-0.44; P < 0.01) were significantly associated with increased pain. CONCLUSION: Our findings suggest that most patients with unstable pelvic ring fractures treated with posterior screw fixation achieve minimal to no pelvis pain and good to excellent pelvic function 6-24 months after injury. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

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

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

Patient Satisfaction After Discharge Is Discordant With Reported Inpatient Experience.

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

Pragmatic randomized trial evaluating pre-operative aqueous antiseptic skin solution in open fractures (Aqueous-PREP): the feasibility of a cluster randomized crossover study.

BACKGROUND: Preoperative antiseptic skin solutions are used prior to most surgical procedures; however, there is no definitive research comparing infection-related outcomes following use of the various solutions available to orthopedic trauma surgeons. The objective of this pilot study was to test the feasibility of a cluster randomized crossover trial that assesses the comparative effectiveness of a 10% povidone-iodine solution versus a 4% chlorhexidine gluconate solution for the management of open fractures. METHODS: Two orthopedic trauma centers participated in this pilot study. Each of these clinical sites was randomized to a starting solution (povidone-iodine solution or chlorhexidine gluconate) then subsequently crossed over to the other treatment after 2 months. During the 4-month enrollment phase, we assessed compliance, enrollment rates, participant follow-up, and accurate documentation of the primary clinical outcome. Feasibility outcomes included (1) the implementation of the interventions during a run-in period; (2) enrollment of participants during two 2-month enrollment phases; (3) application of the trial interventions as per the cluster randomization crossover scheme; (4) participant follow-up; and (5) accurate documentation of the primary outcome (surgical site infection). Feasibility outcomes were summarized using descriptive statistics reported as means (standard deviation) or medians (first quartile, third quartile) for continuous variables depending on their distribution and counts (percentage) for categorical variables. Corresponding 95% confidence intervals (CIs) were also reported. RESULTS: All five of the criteria for feasibility were met. During the run-in phase, all 18 of the eligible patients identified at the two clinical sites received the correct cluster-assigned treatment. A total of 135 patients were enrolled across both sites during the 4-month recruitment phase, which equates to 92% (95% CI 85.9 to 96.4%) of eligible patients being enrolled. Compliance with the assigned treatment in the pilot study was 98% (95% CI 93.5 to 99.8%). Ninety-eight percent (95% CI 93.5 to 99.8%) of participants completed the 90-day post-surgery follow-up and the primary outcome (SSI) was accurately documented for 100% (95% CI 96.6 to 100.0%) of the participants. CONCLUSIONS: These results confirm the feasibility of a definitive study comparing antiseptic solutions using a cluster randomized crossover trial design. Building upon the infrastructure established during the pilot phase, a definitive study has been successfully initiated. TRIAL REGISTRATION: ClincialTrials.gov , number NCT03385304 . Registered December 28, 2017.

Patients' preferences for occupational therapy after upper extremity fractures: a discrete choice experiment.

OBJECTIVE: Occupational therapy is often prescribed after the acute treatment of upper extremity fractures. However, high out-of-pocket expenses and logistical constraints can reduce access to formal therapy services. We aimed to quantify preferences of patients with upper extremity fracture for attending occupational therapy, when considering possible differences in clinical outcomes. DESIGN: Discrete choice experiment. SETTING: Level 1 trauma centre in Baltimore, Maryland, USA. PARTICIPANTS: 134 adult patients with upper extremity fractures. PRIMARY OUTCOME MEASURES: The scenarios were described with five attributes: cost, duration of therapy session, location of therapy, final range of motion and pain. We report the relative importance of each attribute as a proportion of total importance, and the willingness to pay for benefits of the therapy services. RESULTS: Of the 134 study participants, the mean age was 47 years and 53% were men. Cost (32%) and range of motion (29%) were the attributes of greatest relative importance. Pain (17%), duration of therapy (13%) and location of therapy (8%) were of lesser importance. Patients were willing to pay $85 more per therapy session for a 40% improvement in their range of motion. Patients were willing to pay $43 more per therapy session to improve from severe pain to mild pain. Patients were indifferent to whether the therapy treatment was home-based or in a clinical environment. CONCLUSIONS: When deciding on an upper extremity fracture therapy programme, out-of-pocket costs are a paramount consideration of patients. Improvements in range of motion are of greater importance than residual pain, the duration of therapy sessions and the location of service provision. Patients with upper extremity fracture should be prescribed occupational therapy services that align with these patients' preferences.

Effectiveness of Iodophor vs Chlorhexidine Solutions for Surgical Site Infections and Unplanned Reoperations for Patients Who Underwent Fracture Repair: The PREP-IT Master Protocol.

Importance: The risk of developing a surgical site infection after extremity fracture repair is nearly 5 times greater than in most elective orthopedic surgical procedures. For all surgical procedures, it is standard practice to prepare the operative site with an antiseptic solution; however, there is limited evidence to guide the choice of solution used for orthopedic fracture repair. Objective: To compare the effectiveness of iodophor vs chlorhexidine solutions to reduce surgical site infections and unplanned fracture-related reoperations for patients who underwent fracture repair. Design, Setting, and Participants: The PREP-IT (Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma) master protocol will be followed to conduct 2 multicenter pragmatic cluster randomized crossover trials, Aqueous-PREP (Pragmatic Randomized Trial Evaluating Pre-Operative Aqueous Antiseptic Skin Solution in Open Fractures) and PREPARE (Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities). The Aqueous-PREP trial will compare 4% aqueous chlorhexidine vs 10% povidone-iodine for patients with open extremity fractures. The PREPARE trial will compare 2% chlorhexidine in 70% isopropyl alcohol vs 0.7% iodine povacrylex in 74% isopropyl alcohol for patients with open extremity fractures and patients with closed lower extremity or pelvic fractures. Both trials will share key aspects of study design and trial infrastructure. The studies will follow a pragmatic cluster randomized crossover design with alternating treatment periods of approximately 2 months. The primary outcome will be surgical site infection and the secondary outcome will be unplanned fracture-related reoperations within 12 months. The Aqueous-PREP trial will enroll a minimum of 1540 patients with open extremity fractures from at least 12 hospitals; PREPARE will enroll a minimum of 1540 patients with open extremity fractures and 6280 patients with closed lower extremity and pelvic fractures from at least 18 hospitals. The primary analyses will adhere to the intention-to-treat principle and account for potential between-cluster and between-period variability. The patient-centered design, implementation, and dissemination of results are guided by a multidisciplinary team that includes 3 patients and other relevant stakeholders. Discussion: The PREP-IT master protocol increases efficiency through shared trial infrastructure and study design components. Because prophylactic skin antisepsis is used prior to all surgical procedures and the application, cost, and availability of all study solutions are similar, the results of the PREP-IT trials are poised to inform clinical guidelines and bring about an immediate change in clinical practice. Trial Registration: ClinicalTrials.gov Identifiers: NCT03385304 and NCT03523962.

Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study

Background: Approximately one-third of people with schizophrenia have elevated levels of anti-gliadin antibodies of the immunoglobulin G type (AGA IgG) ­ a higher rate than seen in healthy controls. We performed the first double-blind clinical trial of gluten-free versus gluten-containing diets in a subset of patients with schizophrenia who were positive for AGA IgG. Methods: In this pilot feasibility study, 16 participants with schizophrenia or schizoaffective disorder who had elevated AGA IgG (≥ 20 U) but were negative for celiac disease were admitted to an inpatient unit for a 5-week trial. All participants received standardized gluten-free meals and were randomized in a double-blind fashion to receive a shake containing 10 g of gluten flour or 10 g of rice flour each day. Participants were rated for psychiatric, cognitive and gastrointestinal symptoms at baseline and endpoint. Results: Of the 16 participants, 14 completed the 5-week trial (2 discontinued early for administrative reasons). Compared with participants on the gluten-containing diet, participants on the gluten-free diet showed improvement on the Clinical Global Impressions scale (Cohen d = ­0.75) and in negative symptoms (Cohen d = ­0.53). We noted no improvement in positive or global cognitive symptoms, but did observe an improvement in attention favouring the gluten-free diet (Cohen d = 0.60). Robust improvements in gastrointestinal adverse effects occurred in the gluten-free group relative to the glutencontaining group. Adverse effects were similar between groups. Limitations: This study was limited by its small sample size; larger studies are needed. Conclusion: This feasibility study suggests that removal of gluten from the diet is associated with improvement in psychiatric and gastrointestinal symptoms in people with schizophrenia or schizoaffective disorder.

Gut permeability and mimicry of the Glutamate Ionotropic Receptor NMDA type Subunit Associated with protein 1 (GRINA) as potential mechanisms related to a subgroup of people with schizophrenia with elevated antigliadin antibodies (AGA IgG).

About one third of people with schizophrenia have elevated IgG antibodies to gliadin (AGA IgG) and increased inflammation. Understanding the mechanism by which this immune response occurs is critical to the development of personalized treatments. We examined gut permeability and mimicry to the glutamate receptor as possible mechanisms related to high gliadin antibodies (AGA IgG) seen in some people with schizophrenia. The Glutamate Ionotropic Receptor NMDA type Subunit Associated with protein 1 (GRINA) has a similar protein structure to gliadin representing a potential target for cross reactivity or mimicry. In a population of schizophrenia subjects (N = 160) and healthy controls (N = 80) we analyzed serum samples for both GRINA and Anti-Saccharomyces Cerevisiae antibodies (ASCA), related to gut permeability. Schizophrenia patients compared to controls had a higher prevalence of positivity to ASCA IgA (p = 0.004) and IgG (p < 0.001). Multinomial logistic regression showed an association between AGA IgG and ASCA IgG in schizophrenia (p = 0.05 for the estimated regression coefficient) but not in healthy controls (p = 0.13). GRINA IgG was higher in schizophrenia patients than in healthy controls (0.43 ±â€¯0.30 vs. 0.22 ±â€¯0.24, p < 0.001). Logistic regressions showed an association between AGA IgG and GRINA IgG in schizophrenia (p = 0.016 for the estimated regression coefficient) but not for the controls (p = 0.471). Thus, we propose that mimicry through the presence of cross-reactivity between gliadin and GRINA might disrupt the functions of the glutamate system and relate to illness pathophysiology in those with schizophrenia and elevated AGA IgG.

Relationship of Interferon-γ to Cognitive Function in Midlife Women with Schizophrenia.

Recent literature suggests that schizophrenia is linked to an abnormal response of the immune system. Interferon-γ is a cytokine that acts as a mediator between immune stimulation and the kynurenine pathway and may be related to cognitive abilities. The objectives of the present study are to determine if serum cytokines are correlated with cognitive function differently in patients with schizophrenia compared to controls. Fourteen midlife (30-70 year-old) females with DSM-IV diagnosis of schizophrenia or schizoaffective disorder and 13 midlife control females were analyzed. Cytokines were collected from serum blood draws and analyzed at the Cytokine Core Lab at the University of Maryland, Baltimore. The RBANS, HVLT-R, and UPSA were performed to measure cognition and social performance. The results demonstrate a non-significant difference between interferon-γ levels in women with schizophrenia compared to controls, but this cytokine appears to correlate to cognitive abilities differently in these groups. There were several significant negative correlations between interferon-γ and cognition in midlife patients with schizophrenia, but only one in the midlife control group. The negative correlations between interferon-γ and cognition in patients with schizophrenia suggest the hypothesis that inflammation and the kynurenine pathway have important roles in this disorder.