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.).

Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease.

BACKGROUND: Renin-angiotensin system (RAS) inhibitors - including angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) - slow the progression of mild or moderate chronic kidney disease. However, the results of some studies have suggested that the discontinuation of RAS inhibitors in patients with advanced chronic kidney disease may increase the estimated glomerular filtration rate (eGFR) or slow its decline. METHODS: In this multicenter, open-label trial, we randomly assigned patients with advanced and progressive chronic kidney disease (eGFR, <30 ml per minute per 1.73 m2 of body-surface area) either to discontinue or to continue therapy with RAS inhibitors. The primary outcome was the eGFR at 3 years; eGFR values that were obtained after the initiation of renal-replacement therapy were excluded. Secondary outcomes included the development of end-stage kidney disease (ESKD); a composite of a decrease of more than 50% in the eGFR or the initiation of renal-replacement therapy, including ESKD; hospitalization; blood pressure; exercise capacity; and quality of life. Prespecified subgroups were defined according to age, eGFR, type of diabetes, mean arterial pressure, and proteinuria. RESULTS: At 3 years, among the 411 patients who were enrolled, the least-squares mean (±SE) eGFR was 12.6±0.7 ml per minute per 1.73 m2 in the discontinuation group and 13.3±0.6 ml per minute per 1.73 m2 in the continuation group (difference, -0.7; 95% confidence interval [CI], -2.5 to 1.0; P = 0.42), with a negative value favoring the outcome in the continuation group. No heterogeneity in outcome according to the prespecified subgroups was observed. ESKD or the initiation of renal-replacement therapy occurred in 128 patients (62%) in the discontinuation group and in 115 patients (56%) in the continuation group (hazard ratio, 1.28; 95% CI, 0.99 to 1.65). Adverse events were similar in the discontinuation group and continuation group with respect to cardiovascular events (108 vs. 88) and deaths (20 vs. 22). CONCLUSIONS: Among patients with advanced and progressive chronic kidney disease, the discontinuation of RAS inhibitors was not associated with a significant between-group difference in the long-term rate of decrease in the eGFR. (Funded by the National Institute for Health Research and the Medical Research Council; STOP ACEi EudraCT number, 2013-003798-82; ISRCTN number, 62869767.).

Evaluation of the stopping angiotensin converting enzyme inhibitor compared to angiotensin receptor blocker (STOP ACEi trial) in advanced and progressive chronic kidney disease.

In the STOP-ACEi trial, the outcome was similar whether or not renin-angiotensin system inhibitors (RASi) were discontinued. We now investigate whether the effect of withdrawing angiotensin converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARBs) differed. In this open label trial patients with estimated glomerular filtration rates (eGFR) under 30ml/min per 1.73 m2 and progressive chronic kidney disease (CKD) were randomized to stop or continue RASi. The primary outcome was eGFR at three years. The composite of kidney failure, over 50% fall in eGFR, or kidney replacement therapy (KRT) was also assessed. Of patients randomized, 99 stopped and 123 patients continued ACEi while 104 stopped and 77 continued ARB at baseline. At three years, the eGFR was similar whether or not patients were withdrawn from ACEi or from ARB. Kidney failure or initiation of KRT occurred in 65% of those stopping and 54% continuing ACEi (hazard ratio if stopped, 1.52; 95% Confidence Interval, 1.07 to 2.16) and in 60% on an ARB regardless of randomized group (hazard ratio if stopped, 1.23; 0.83 to 1.81). Kidney failure/Initiation of KRT with over 50% decline in eGFR occurred in 71% of those stopping and 59% continuing ACEi (relative risk if stopped, 1.19; 95% CI, 1.00 to 1.41) and in 65% stopping and 69% continuing ARB (relative risk if stopped, 0.96; 0.79 to 1.16). Thus, neither discontinuing ACEi nor ARB slowed the rate of decline in eGFR. Although discontinuation of ACEi appeared to have more unfavorable effects on kidney outcomes than stopping ARB, the trial was neither designed nor powered to show differences between agents.

Spinal Anesthesia or General Anesthesia for Hip Surgery in Older Adults.

BACKGROUND: The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied. METHODS: We conducted a pragmatic, randomized superiority trial to evaluate spinal anesthesia as compared with general anesthesia in previously ambulatory patients 50 years of age or older who were undergoing surgery for hip fracture at 46 U.S. and Canadian hospitals. Patients were randomly assigned in a 1:1 ratio to receive spinal or general anesthesia. The primary outcome was a composite of death or an inability to walk approximately 10 ft (3 m) independently or with a walker or cane at 60 days after randomization. Secondary outcomes included death within 60 days, delirium, time to discharge, and ambulation at 60 days. RESULTS: A total of 1600 patients were enrolled; 795 were assigned to receive spinal anesthesia and 805 to receive general anesthesia. The mean age was 78 years, and 67.0% of the patients were women. A total of 666 patients (83.8%) assigned to spinal anesthesia and 769 patients (95.5%) assigned to general anesthesia received their assigned anesthesia. Among patients in the modified intention-to-treat population for whom data were available, the composite primary outcome occurred in 132 of 712 patients (18.5%) in the spinal anesthesia group and 132 of 733 (18.0%) in the general anesthesia group (relative risk, 1.03; 95% confidence interval [CI], 0.84 to 1.27; P = 0.83). An inability to walk independently at 60 days was reported in 104 of 684 patients (15.2%) and 101 of 702 patients (14.4%), respectively (relative risk, 1.06; 95% CI, 0.82 to 1.36), and death within 60 days occurred in 30 of 768 (3.9%) and 32 of 784 (4.1%), respectively (relative risk, 0.97; 95% CI, 0.59 to 1.57). Delirium occurred in 130 of 633 patients (20.5%) in the spinal anesthesia group and in 124 of 629 (19.7%) in the general anesthesia group (relative risk, 1.04; 95% CI, 0.84 to 1.30). CONCLUSIONS: Spinal anesthesia for hip-fracture surgery in older adults was not superior to general anesthesia with respect to survival and recovery of ambulation at 60 days. The incidence of postoperative delirium was similar with the two types of anesthesia. (Funded by the Patient-Centered Outcomes Research Institute; REGAIN ClinicalTrials.gov number, NCT02507505.).

Long-term Outcomes with Spinal versus General Anesthesia for Hip Fracture Surgery: A Randomized Trial.

BACKGROUND: The effects of spinal versus general anesthesia on long-term outcomes have not been well studied. This study tested the hypothesis that spinal anesthesia is associated with better long-term survival and functional recovery than general anesthesia. METHODS: A prespecified analysis was conducted of long-term outcomes of a completed randomized superiority trial that compared spinal anesthesia versus general anesthesia for hip fracture repair. Participants included previously ambulatory patients 50 yr of age or older at 46 U.S. and Canadian hospitals. Patients were randomized 1:1 to spinal or general anesthesia, stratified by sex, fracture type, and study site. Outcome assessors and investigators involved in the data analysis were masked to the treatment arm. Outcomes included survival at up to 365 days after randomization (primary); recovery of ambulation among 365-day survivors; and composite endpoints for death or new inability to ambulate and death or new nursing home residence at 365 days. Patients were included in the analysis as randomized. RESULTS: A total of 1,600 patients were enrolled between February 12, 2016, and February 18, 2021; 795 were assigned to spinal anesthesia, and 805 were assigned to general anesthesia. Among 1,599 patients who underwent surgery, vital status information at or beyond the final study interview (conducted at approximately 365 days after randomization) was available for 1,427 (89.2%). Survival did not differ by treatment arm; at 365 days after randomization, there were 98 deaths in patients assigned to spinal anesthesia versus 92 deaths in patients assigned to general anesthesia (hazard ratio, 1.08; 95% CI, 0.81 to 1.44, P = 0.59). Recovery of ambulation among patients who survived a year did not differ by type of anesthesia (adjusted odds ratio for spinal vs. general, 0.87; 95% CI, 0.67 to 1.14; P = 0.31). Other outcomes did not differ by treatment arm. CONCLUSIONS: Long-term outcomes were similar with spinal versus general anesthesia.

Design and deployment of the STEEER-AF trial to evaluate and improve guideline adherence: A cluster-randomised trial by the European Society of Cardiology and European Heart Rhythm Association.

AIMS: To describe the rationale, design, delivery and baseline characteristics of STEEER-AF (Stroke prevention and rhythm control Treatment: Evaluation of an Educational programme of the European Society of Cardiology [ESC] in a cluster-Randomised trial in patients with Atrial Fibrillation). METHODS & RESULTS: STEEER-AF is a pragmatic trial designed to objectively and robustly determine whether guidelines are adhered to in routine practice, and evaluate a targeted educational programme for healthcare professionals. Seventy centres were randomised in 6 countries (France, Germany, Italy, Poland, Spain and United Kingdom; 2022-2023). STEEER-AF centres recruited 1732 patients with a diagnosis of atrial fibrillation (AF), with mean age 68.9 years (SD 11.7), CHA2DS2-VASc score 3.2 (SD 1.8) and 647 (37%) women. 843 patients (49%) were in AF and 760 (44%) in sinus rhythm at enrolment. Oral anticoagulant therapy was prescribed in 1,543 patients (89%), with the majority receiving direct oral anticoagulants (1,378; 89%). Previous cardioversion, antiarrhythmic drug therapy or ablation was recorded in 836 patients (48.3%). 551 patients (31.8%) were currently receiving an antiarrhythmic drug, and 446 (25.8%) were scheduled to receive a future cardioversion or ablation. The educational programme engaged 195 healthcare professionals across centres randomised to the intervention group, consisting of bespoke interactive online learning and reinforcement activities, supported by national expert trainers. CONCLUSION: The STEEER-AF trial was successfully deployed across six European countries to investigate guideline adherence in real-world practice, and evaluate if a structured educational programme for healthcare professionals can improve patient-level care. REGISTRATION: Clinicaltrials.gov NCT04396418.

Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis.

BACKGROUND: More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD). RESULTS: Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.).

Outcomes with spinal versus general anesthesia for patients with and without preoperative cognitive impairment: Secondary analysis of a randomized clinical trial.

INTRODUCTION: The effect of spinal versus general anesthesia on the risk of postoperative delirium or other outcomes for patients with or without cognitive impairment (including dementia) is unknown. METHODS: Post hoc secondary analysis of a multicenter pragmatic trial comparing spinal versus general anesthesia for adults aged 50 years or older undergoing hip fracture surgery. RESULTS: Among patients randomized to spinal versus general anesthesia, new or worsened delirium occurred in 100/295 (33.9%) versus 107/283 (37.8%; odds ratio [OR] 0.85; 95% confidence interval [CI] 0.60 to 1.19) among persons with cognitive impairment and 70/432 (16.2%) versus 71/445 (16.0%) among persons without cognitive impairment (OR 1.02; 95% CI 0.71 to 1.47, p = 0.46 for interaction). Delirium severity, in-hospital complications, and 60-day functional recovery did not differ by anesthesia type in patients with or without cognitive impairment. DISCUSSION: Anesthesia type is not associated with differences in delirium and functional outcomes among persons with or without cognitive impairment.

Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial.

Importance: There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure. Objective: To compare low-dose digoxin with bisoprolol (a ß-blocker). Design, Setting, and Participants: Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019. Interventions: Digoxin (n = 80; dose range, 62.5-250 µg/d; mean dose, 161 µg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d). Main Outcomes and Measures: The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting. Results: Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, -1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, -2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P < .001). At 12 months, 8 of 20 outcomes were significantly different (all favoring digoxin), with a median NT-proBNP level of 960 pg/mL (interquartile range, 626 to 1531 pg/mL) in the digoxin group vs 1250 pg/mL (interquartile range, 847 to 1890 pg/mL) in the bisoprolol group (ratio of geometric means, 0.77 [95% CI, 0.64 to 0.92]; P = .005). Adverse events were less common with digoxin; 20 patients (25%) in the digoxin group had at least 1 AE vs 51 patients (64%) in the bisoprolol group (P < .001). There were 29 treatment-related AEs and 16 serious AEs in the digoxin group vs 142 and 37, respectively, in the bisoprolol group. Conclusions and Relevance: Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points. Trial Registration: ClinicalTrials.gov Identifier: NCT02391337 and clinicaltrialsregister.eu Identifier: 2015-005043-13.

Computer-Aided Detection of Incidental Lumbar Spine Fractures from Routine Dual-Energy X-Ray Absorptiometry (DEXA) Studies Using a Support Vector Machine (SVM) Classifier.

To assess whether application of a support vector machine learning algorithm to ancillary data obtained from posterior-anterior dual-energy X-ray absorptiometry (DEXA) studies could identify patients with lumbar spine (L1-L4) vertebral body fractures without additional DEXA imaging or radiation. Three hundred seven patients (199 without any fractures of the spine, and 108 patients with at least one fracture of the L1, L2, L3, or L4 vertebral bodies) who had DEXA studies were evaluated. Ancillary data from DEXA output was analyzed. The dataset was split into training (80%) and test (20%) datasets. Support vector machines (SVMs) with 10-fold cross-validation and different kernels were used to identify the best kernel based on the greatest area under the curve (AUC) and the best training vectors in the training dataset. The SVM with the best kernel was then applied to the test dataset to assess the accuracy of the SVM. Receiver operating characteristic (ROC) curves of the SVMs using different kernels in the test dataset were compared using DeLong's test. The SVM classifier with the linear kernel had the greatest AUC in the training dataset (AUC = 0.9258). The AUC of the SVM classifier with the linear kernel in the test dataset was 0.8963. The SVM classifier with the linear kernel had an overall average accuracy of 91.8% in the test dataset. The sensitivity, specificity, positive predictive value, and negative predictive of the SVM classifier with the linear kernel to detect lumbar spine fractures were 81.8%, 97.4%, 94.7%, and 90.5%, respectively. The SVM classifier with the linear kernel ROC curve had a significantly better AUC than the SVM classifier with the cubic polynomial kernel (P = 0.034) for discriminating between patients with lumbar spine fractures and control patients, but not significantly different from the SVM classifier with a radial basis function (RBF) kernel (P = 0.317) or the SVM classifier with a sigmoid kernel (P = 0.729). All fractures identified by the SVM classifiers were not prospectively identified by the radiologist. SVM analysis of ancillary data obtained from routine DEXA studies can identify lumbar spine fractures without the use of vertebral fracture assessment (VFA) DEXA imaging or radiation, and identify fractures missed by radiologists.

Unhelmeted Motorcycle Riders Have Increased Injury Burden: A Need to Revisit Universal Helmet Laws.

BACKGROUND: The aim of this study was to compare hospital outcomes for patients in a motorcycle collision with and without helmet use. The study was conducted as a retrospective analysis of the National Trauma Data Bank's 2013 data set, which included reported data from 100 hospitals across the United States. METHODS: Inclusion criterion for this study is a motorcycle crash involving a driver or passenger. The total number of patients in motorcycle crashes as reported by the National Trauma Data Bank in 2013 was 10,345. Helmet use, hospital stay, ICU and ventilation days, mortality, Glasgow Coma Score, Injury Severity Score, patient payer mix, and complication data were obtained. RESULTS: Patients were divided into two groups: those wearing a helmet (n = 6250) and those without (n = 4095). Patients not wearing a helmet had an increased risk of admission to the ICU (OR = 1.36, P < 0.001, CI 1.25-1.48), requiring ventilation support (OR = 1.55, P < 0.001, CI 1.39-1.72), presenting with a Glasgow Coma Score of eight or below (OR = 2.15, P < 0.001), and in-patient mortality (OR = 2.00, P < 0.001, CI 1.58-2.54). Unhelmeted patients were more likely to have government insurance or be uninsured than those patients wearing a helmet (P < 0.001). CONCLUSIONS: It is not well understood why many states are repealing or have repealed universal helmet laws. Lack of helmet use increases the severity of injury in traumatized patients leading to a substantial financial impact on health care costs. Our analysis suggests the need to revisit the issue regarding laws that require protective headwear while riding motorcycles because of the individual and societal impact. LEVEL OF EVIDENCE: III.

The Saline Load Test is Effective at Diagnosing Traumatic Arthrotomies of the Shoulder.

The purpose of this study is to evaluate the fluid volume required for a saline load test to detect intra-articular involvement of the glenohumeral joint after penetrating trauma. A human cadaver study was conducted with 22 thawed, fresh-frozen forequarter amputations. A standard posterior shoulder portal was made with an 11-blade scalpel. A 19-gauge needle was inserted into the anterior portal site, and intra-articular position of both the blade and needle was confirmed with fluoroscopy. The blade was removed and normal saline was injected through the needle until extravasation of fluid was observed through the posterior portal. Injection volume required for extravasation was recorded. A logarithmic distribution of the volumes was then calculated in order to obtain estimated sensitivity ranges. Using a logarithmic distribution, 90%, 95% and 99% of simulated glenohumeral arthrotomies could be detected using injections of: 62 ml [41-96], 81 ml [50-133] and 136 ml [72-252], respectively. (Journal of Surgical Orthopaedic Advances 28(4):268-271, 2019).

The microbiota of traumatic, open fracture wounds is associated with mechanism of injury.

Open fractures are characterized by disruption of the skin and soft tissue, which allows for microbial contamination and colonization. Preventing infection-related complications of open fractures and other acute wounds remains an evolving challenge due to an incomplete understanding of how microbial colonization and contamination influence healing and outcomes. Culture-independent molecular methods are now widely used to study human-associated microbial communities without introducing culture biases. Using such approaches, the objectives of this study were to (1) define the long-term temporal microbial community dynamics of open fracture wounds and (2) examine microbial community dynamics with respect to clinical and demographic factors. Fifty-two subjects with traumatic open fracture wounds (32 blunt and 20 penetrating injuries) were enrolled prospectively and sampled longitudinally from presentation to the emergency department (ED) and at each subsequent inpatient or outpatient encounter. Specimens were collected from both the wound center and adjacent skin. Culture-independent sequencing of the 16S ribosomal RNA gene was employed to identify and characterize microbiota. Upon presentation to the ED and time points immediately following, sample collection site (wound or adjacent skin) was the most defining feature discriminating microbial profiles. Microbial composition of adjacent skin and wound center converged over time. Mechanism of injury most strongly defined the microbiota after initial convergence. Further analysis controlling for race, gender, and age revealed that mechanism of injury remained a significant discriminating feature throughout the continuum of care. We conclude that the microbial communities associated with open fracture wounds are dynamic in nature until eventual convergence with the adjacent skin community during healing, with mechanism of injury as an important feature affecting both diversity and composition of the microbiota. A more complete understanding of the factors influencing microbial contamination and/or colonization in open fractures is a critical foundation for identifying markers indicative of outcome and deciphering their respective contributions to healing and/or complication.

A randomized, multicenter, open-label, blinded end point trial comparing the effects of spironolactone to chlorthalidone on left ventricular mass in patients with early-stage chronic kidney disease: Rationale and design of the SPIRO-CKD trial.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased left ventricular (LV) mass and arterial stiffness. In a previous trial, spironolactone improved these end points compared with placebo in subjects with early-stage CKD, but it is not known whether these effects were specific to the drug or secondary to blood pressure lowering. AIM: The aim was to investigate the hypothesis that spironolactone is superior to chlorthalidone in the reduction of LV mass while exerting similar effects on blood pressure. DESIGN: This is a multicenter, prospective, randomized, open-label, blinded end point clinical trial initially designed to compare the effects of 40weeks of treatment with spironolactone 25mg once daily to chlorthalidone 25mg once daily on the co-primary end points of change in pulse wave velocity and change in LV mass in 350 patients with stages 2 and 3 CKD on established treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Because of slow recruitment rates, it became apparent that it would not be possible to recruit this sample size within the funded time period. The study design was therefore changed to one with a single primary end point of LV mass requiring 150 patients. Recruitment was completed on 31 December 2016, at which time 154 patients had been recruited. Investigations included cardiac magnetic resonance imaging, applanation tonometry, 24-hour ambulatory blood pressure monitoring, and laboratory tests. Subjects are assessed before and after 40weeks of randomly allocated drug therapy and at 46weeks after discontinuation of the study drug.

Transfusion Thresholds for Major Orthopedic Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: More than a million surgeries are performed annually in the United States for hip or knee arthroplasty or hip fracture stabilization. One-fifth of these patients have blood transfusions during their hospital stay. Increases in transfusion rates have caused concern about increased adverse events from unnecessary transfusions. METHODS: We systematically reviewed randomized trials examining the effect of restrictive vs liberal transfusion thresholds on patients having major orthopedic surgery. Study results were meta-analyzed with a random-effects model and heterogeneity was tested with the I2 statistic. Study risk of bias was assessed using a modified Jadad scale and evidence strength was measured using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system. RESULTS: A total of 504 published articles were screened, and 15 met inclusion criteria. The articles described 9 randomized trials, most comparing transfusion thresholds of 8 vs 10 g/dL hemoglobin. All involved hip or knee arthroplasty and/or hip fracture patients. Moderate-strength evidence suggested a reduction in need for transfusion (relative risk, 0.53; 95% confidence interval [CI], 0.39-0.71; I2 = 95%) and mean number of units transfused (-0.95 units, 95% CI, -1.48 to -0.41, I2 = 98%). There was a possible reduction in overall infections with more restrictive transfusion thresholds, although the result was not statistically significant (relative risk, 0.71; 95% CI, 0.47-1.06; I2 = 54%). Moderate-strength evidence suggested no differences in other clinical outcomes between the groups. Limitations included incomplete blinding, inconsistency, and imprecision. CONCLUSION: Moderate-strength evidence suggests that restrictive transfusion practices reduce utilization of transfusions and may decrease infections without increasing adverse outcomes in major orthopedic surgery.

Arthroscopic lysis of adhesions improves knee range of motion after fixation of intra-articular fractures about the knee.

BACKGROUND: Post-traumatic stiffness after open reduction and internal fixation of fractures about the knee can have dramatic effects on function. Traditionally, open quadricepsplasty has been the treatment of choice, but is associated with significant morbidity. PURPOSE: The purpose of this study is to examine the immediate and sustainable range of motion (ROM) changes after surgical arthroscopic lysis of knee adhesions (SALKA) for post-traumatic knee stiffness after open reduction internal fixation (ORIF). METHODS: We retrospectively reviewed a consecutive series of patients at a single institution who underwent SALKA for knee stiffness after intra-articular fractures about the knee treated with ORIF from 2009 to 2015. Pre-operative and immediate post-operative total ROM was assessed while patients were sedated during the SALKA procedure. Total ROM was assessed in the office pre-operatively and compared to the latest post-operative follow-up visit. Immediate post-operative ROM was also compared to the latest post-operative follow-up visit. Two-tailed paired Student's t test was calculated for analysis. RESULTS: Of the 14 patients included in the study, 10 (71 %) had tibial plateau ORIF, 3 (21 %) had patella ORIF, and 1 (8 %) had intra-articular distal femur ORIF. The mean time between ORIF and SALKA was 244 days. The mean follow-up time after SALKA was 135 days. Under sedation during SALKA, the mean total ROM increased from 72° to 127° immediately post-operatively (p < 0.01). The mean pre-operative in-office total ROM was 73° and increased to 104° at the latest follow-up visit (p < 0.01). The mean immediate post-operative ROM was 127° and decreased to 104° at the latest follow-up visit (p = 0.01). CONCLUSION: Lysis of adhesions utilizing SALKA after ORIF about the knee improves knee ROM immediately post-operatively and in the short-term follow-up. However, there is a decrease in the gains in the range of motion over time. Patients should be counseled as such. Lysis of adhesions utilizing arthroscopic techniques may provide a favorable alternative to open quadricepsplasty.

Teriparatide as a systemic treatment for lower extremity nonunion fractures: a case series.

OBJECTIVE: To investigate the effect of teriparatide (parathyroid hormone [1-34]) on the healing of long bone nonunion fractures. METHODS: We performed a retrospective chart review of patients with fracture nonunion, aged 10 to 99 years who were treated with teriparatide at the Children's Hospital of Philadelphia or the Hospital of the University of Pennsylvania between November 2002 and January 2013. The primary endpoints were radiographic evidence of callus formation and fracture union, ability to bear weight without affected limb limp, and normal range of motion and strength. RESULTS: Six patients aged 19 to 64 years with tibial or femoral fractures that had not healed for 3 to 36 months were treated with teriparatide 20 µg/day. Accelerated healing of fracture nonunion was confirmed in 5 of 6 patients with time to complete union of 3 to 9 months. The shortest time to recovery was observed in younger patients without comorbidities. Treatment was well tolerated. CONCLUSION: Teriparatide is a promising treatment for nonunion fractures, but its response depends on associated comorbidities. The potential benefit of teriparatide as an adjunct to treat nonunion justifies randomized placebo-controlled trials to determine its efficacy and safety in broader populations.

A cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): findings in the elderly versus all patients.

BACKGROUND: Patient age is one of many potential risk factors for fracture nonunion. Our hypothesis is that older patients (≥ 60) with fracture risk factors treated with low-intensity pulsed ultrasound (LIPUS) have similar heal rate (HR) to the population as a whole. We evaluate the impact of age in conjunction with other risk factors on HR in LIPUS-treated patients with fresh fracture (≤ 90 days old). METHODS: The Exogen Bone Healing System is a LIPUS device approved in 1994 to accelerate healing of fresh fracture. After approval, the FDA required a Post-Market Registry to assess performance. Patient data collected from October 1994 until October 1998 were individually reviewed and validated by a registered nurse. Four distinct data elements were required to report a patient: date fracture occurred; date treatment began; date treatment ended; and a dichotomous outcome of healed v. failed, by clinical and radiological criteria. Data were used to calculate two derived variables; days to treatment (DTT) and days on treatment (DOT). Every validated fresh fracture patient with DTT, DOT, and outcome is reported. RESULTS: The validated registry had 5,765 patients with fresh fracture; 73% (N = 4,190) are reported, while 13% of patients were lost to follow-up, 11% withdrew or were non-compliant, and 3% died or are missing outcome. Among treatment-compliant patients, HR was 96.2%. Logistic estimates of the odds ratio for healing are equivalent for patients age 30 to 79 years and all age cohorts had a HR > 94%. Open fracture, current smoking, diabetes, vascular insufficiency, osteoporosis, cancer, rheumatoid arthritis, and prescription NSAIDs all reduced HR, but older patients (≥ 60) had similar HRs to the population as a whole. DTT was significantly shorter for patients who healed (p < 0.0001). CONCLUSIONS: Comorbid conditions in conjunction with aging can reduce fracture HR. Patients with fracture who used LIPUS had a 96% HR, whereas the expected HR averages 93%. Time to treatment was significantly shorter among patients who healed (p < 0.0001), suggesting that it is beneficial to begin LIPUS treatment early. Older patients (≥ 60) with fracture risk factors treated with LIPUS exhibit similar heal rates to the population as a whole.

Bundled Payment in Total Joint Care: Survey of AAHKS Membership Attitudes and Experience with Alternative Payment Models.

The goal of alternative payment models (APMs), particularly bundling of payments in total joint arthroplasty (TJA), is to incentivize physicians, hospitals, and payers to deliver quality care at lower cost. To study the effect of APMs on the field of adult reconstruction, we conducted a survey of AAHKS members using an electronic questionnaire format. Of the respondents, 61% are planning to or participate in an APM. 45% of respondents feel that a bundled payment system will be the most effective model to improve quality and to reduce costs. Common concerns were disincentives to operate on high-risk patients (94%) and uncertainty about revenue sharing (79%). While many members feel that APMs may improve value in TJA, surgeons continue to have reservations about implementation.