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.).

Epithelial and stromal circadian clocks are inversely regulated by their mechano-matrix environment.

The circadian clock is an autonomous molecular feedback loop inside almost every cell in the body. We have shown that the mammary epithelial circadian clock is regulated by the cellular microenvironment. Moreover, a stiff extracellular matrix dampens the oscillations of the epithelial molecular clock. Here, we extend this analysis to other tissues and cell types, and identify an inverse relationship between circadian clocks in epithelia and fibroblasts. Epithelial cells from mammary gland, lung and skin have significantly stronger oscillations of clock genes in soft 3D microenvironments, compared to stiff 2D environments. Fibroblasts isolated from the same tissues show the opposite response, exhibiting stronger oscillations and more prolonged rhythmicity in stiff microenvironments. RNA analysis identified that a subset of mammary epithelial clock genes, and their regulators, are upregulated in 3D microenvironments in soft compared to stiff gels. Furthermore, the same genes are inversely regulated in fibroblasts isolated from the same tissues. Thus, our data reveal for the first time an intrinsic difference in the regulation of circadian genes in epithelia and fibroblasts.

MRI-guided definition of cerebrospinal fluid distribution around cranial and sacral nerves: implications for brain tumors and craniospinal irradiation.

Background: The SIOPE-Brain Tumor Group recently published a guideline on craniospinal target volume delineation for highly conformal radiotherapy. In order to spare critical structures like e.g., the lens or cochlea, highly conformal techniques can underdose the cerebrospinal fluid (CSF) in the dural reflections around cranial and sacral nerves. The purpose of this study is to generate evidence for CSF extension within the dural sheaths of the cranial and sacral nerves in order to improve accuracy in target volume delineation.Material and methods: Ten healthy volunteers, age 21 till 41 years, underwent an MRI-scan of the skull-base and sacral plexus. To evaluate CSF extension, cT2-weighted images with fat suppression, low signal to noise ratio and little to no motion-related artifacts were used. Two observers measured the extension of CSF from the inner table of the skull for the cranial nerves, and outside the spinal canal for the sacral nerves.Results: CSF extension (mean distance [95% CI]) was visible within the dural sheaths surrounding the majority of the cranial nerves: optic nerve (40 mm [38-42]), trigeminal nerve (16 mm [15-19]), facial-vestibulocochlear nerve (11 mm [11-12]), glossopharyngeal-vagus-accessory nerve (7 mm [7-9]) and hypoglossal nerve (8 mm [7-9]). No CSF was observed outside the spinal canal at sacral level. No significant difference between both observers was measured.Conclusion: This study generates evidence for significant CSF extension outside the inner table of the skull. Despite the vicinity of the lens and cochlea, we therefore recommend the inclusion of both optic nerves and internal auditory canals in the clinical target volume for craniospinal irradiation when using highly conformal delivery techniques.

Cervical Cerclage versus Vaginal Progesterone for Management of Short Cervix in Low-Risk Women.

OBJECTIVE: To evaluate the risk of preterm birth in low-risk women with cervical length (CL) ≤25 mm on transvaginal ultrasound (TVUS) managed with vaginal progesterone (VagP) therapy versus cerclage. STUDY DESIGN: This is a retrospective cohort of women with no prior history of preterm birth or cervical insufficiency and CL ≤ 25 mm on TVUS, managed with either VagP therapy alone or cerclage (with or without VagP). The primary outcome was rate of preterm delivery < 37 weeks gestational age (GA). Secondary outcomes included delivery at ≤ 32 or ≤ 28 weeks GA, premature preterm rupture of membranes, pregnancy latency, GA at delivery, and composite neonatal outcome. RESULTS: Women undergoing cerclage placement (n = 31) were older and had an earlier GA at the time of diagnosis of short cervix compared with women receiving VagP (n = 62). Delivery at < 37 weeks occurred in 21/62 (33.9%) in the VagP group and 14/31 (45.2%) in the cerclage group (adjusted odds ratio: 1.72, 95% confidence interval: 0.52, 5.66). There were no differences in secondary outcomes. CONCLUSION: Cerclage compared with VagP therapy did not decrease risk of preterm birth in women with CL ≤ 25 mm. Further research is needed to determine optimal management in such women given a residual 40% risk of preterm birth despite optimal therapy.

Neonatal Outcomes Associated with Noncephalic Presentation at Delivery in Preterm Birth.

OBJECTIVE: The objective of this study is to evaluate the effect of noncephalic presentation on neonatal outcomes in preterm delivery. STUDY DESIGN: In this study a secondary analysis of the BEAM trial was performed. It included women with singleton, liveborn, and nonanomalous fetuses. Neonatal outcomes were compared in noncephalic versus cephalic presentation. Adjusted odds ratios and 95% confidence intervals were calculated for each outcome with logistic regression while controlling for possible confounders. A stratified analysis by mode of delivery was also performed in this study. RESULTS: A total of 458 noncephalic deliveries were compared with 1,485 cephalic deliveries. In multivariate analysis, noncephalic presentation was associated with increased risk of death in the neonatal intensive care unit (NICU) or death at <15 months corrected gestational age (cGA), and a decreased risk of IVH. The risk of death persisted in stratified analysis, with increased risk of death at <15 months cGA in noncephalic neonates born via cesarean delivery. In the vaginal delivery group, there was an increased risk of death at <15 months cGA and NICU death. CONCLUSION: After controlling for possible confounders, neonates who are noncephalic at delivery have higher risk for death <15 months cGA and death in the NICU while their risk of IVH is reduced. The risk of death persisted in stratified analyses by mode of delivery.

Optimal Admission Cervical Dilation in Spontaneously Laboring Women.

OBJECTIVE: To estimate the impact of admission cervical dilation on the risk of cesarean in spontaneously laboring women at term. STUDY DESIGN: Secondary analysis of a prospective cohort study of women admitted in term labor with a singleton gestation. Women with rupture of membranes before admission, induction of labor, or prelabor cesarean were excluded. The association between cesarean and cervical dilation at admission was estimated, and results were stratified by parity. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated, using cervical dilation ≥ 6 cm as the reference group. Cesarean for arrest was secondarily explored. RESULTS: A total of 2,033 spontaneously laboring women met inclusion criteria. Women admitted at <6 cm dilation had an increased risk of cesarean compared with those admitted at ≥6 cm (13.2 vs. 3.5%; RR 3.73; 95% CI 1.94-7.17). The increased risk was noted in nulliparous (16.8 vs. 7.1%; RR 2.35; 95% CI 0.90-6.13) and multiparous (11.0 vs. 2.5%; RR 4.36; 95% CI 1.80-10.52) women, but was statistically significant only in multiparous women. CONCLUSIONS: Decreasing cervical dilation at admission, particularly <6 cm, is a modifiable risk factor for cesarean, especially in multiparous women. This should be considered in the decision-making process about timing of admission in term labor.

Discussion: 'Sleep-disordered breathing and adverse pregnancy outcomes' by Pamidi et al.

In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research.

SHEA/IDSA/APIC Practice Recommendation: Strategies to prevent healthcare-associated infections through hand hygiene: 2022 Update.

The purpose of this document is to highlight practical recommendations to assist acute-care hospitals in prioritization and implementation of strategies to prevent healthcare-associated infections through hand hygiene. This document updates the Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals through Hand Hygiene, published in 2014. This expert guidance document is sponsored by the Society for Healthcare Epidemiology (SHEA). It is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America, the Association for Professionals in Infection Control and Epidemiology, the American Hospital Association, and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise.

Clinical Issues-April 2022.

Perioperative care of the patient with alpha-gal syndrome Key words: alpha-gal syndrome (AGS), red meat allergy, allergic reaction, mammalian-derived ingredients, gelatin. Overnight storage of sterile supplies Key words: sterile supplies, event-related sterility, terminal cleaning, damp dusting, instrument table. Unsterile medication cartridges Key words: dental cartridge, local anesthesia, lidocaine, alcohol, sterile field. Personnel traffic into the OR Key words: OR traffic, door openings, airflow, environmental contamination, automatic doors.

Clinical Issues-November 2022.

Reuse of single-use bronchoscopes Key words: single use, bronchoscope, contamination, time limit, instructions for use (IFU). Endoscope processing room workflow Key words: one-room design, decontamination sink, droplets, clean storage, transport. Simethicone use during endoscopy Key words: adenosine triphosphate (ATP) testing, defoaming agent, water bottle, borescope inspection, residue. Implementing borescope inspection of flexible endoscopes Key words: visual inspection, cleaning verification, high-risk endoscopes, competency verification, prepurchase evaluation.

Clinical Issues-September 2021.

Interviewing the patient about cannabis use Key words: cannabis, marijuana, tetrahydrocannabinol (THC), cannabidiol (CBD), patient interview. AORN guidance for non-OR settings Key words: cardiac catheterization laboratory, endoscopy suite, interventional radiology suite, practice setting, invasive procedure. Using personal continuous positive airway pressure devices in the perioperative setting Key words: continuous positive airway pressure (CPAP), obstructive sleep apnea (OSA), home equipment, biomedical engineering, electrical devices. Screening for cognitive impairment in the older adult patient Key words: older adult patient, dementia, delirium, cognitive impairment screening tool, prehabilitation.

Clinical Issues-February 2021.

Moving the surgical lights over a sterile field Key words: surgical lights, light handles, sterile field contamination, surgical site infection (SSI). Transport stretchers in the OR Key words: transport stretcher, bed linens, cross-contamination, sterile field, infectious disease. Using positive-pressure ORs for patients who require airborne precautions Key words: airborne precautions, positive-pressure airflow, positive-pressure OR, anteroom. Discontinuing the use of intraoperative bacitracin irrigation Key words: bacitracin for injection, antibiotic irrigation, antimicrobial irrigation, surgical site infection (SSI).

Vaginal Mycoplasmataceae colonization and association with immune mediators in pregnancy.

OBJECTIVE: To determine the prevalence of Mycoplasmataceae species in pregnant women and evaluate their association with immune system mediators. METHODS: Women were prospectively enrolled between 16-22 weeks' gestation. Vaginal swabs were self-collected and analyzed with PCR for Mycoplasma hominis (MH) and Mycoplasma genitalium (MG) as well as Ureaplasma urealyticum (UU) and Ureaplasma parvum (UP) (collectively, Myc). Immune mediators were measured via Luminex multiplex assay. Women with vaginal Mycoplasmataceae were compared to women without Myc, and women with Mycoplasma species (MH or MG) were compared to women without MH or MG. Linear regression models were used to investigate the relationship of the presence of Mycoplasmataceae on log-transformed immune mediators while controlling for confounders using propensity scores. RESULTS: One-hundred-twenty women were enrolled and had complete lab data available. Colonization was 20.8, 2.5, 10.0, and 48.3% for MH, MG, UU, and UP, respectively. Women with any Mycoplasmataceae were more likely to be younger, of the Black race, and have public insurance. There were no significant differences in immune mediators between women with vaginal Mycoplasmataceae versus those without. After controlling for confounders, women with MH and/or MG had significantly elevated levels of IL-1ß compared to women without MH or MG (estimate = 1.12; 95% CI = 0.33, 1.93). There were no other significant differences in immune mediators in women with MH and/or MG compared to those without. CONCLUSIONS: Colonization rates were highest for UP and lowest for MG. Higher IL-1ß levels were seen in the presence of MH and/or MG, indicating that these less frequently encountered organisms may incite a stronger host response. There were no other significant differences in immune mediator levels.

Influence of eye movement on lens dose and optic nerve target coverage during craniospinal irradiation.

PURPOSE: Optic nerves are part of the craniospinal irradiation (CSI) target volume. Modern radiotherapy techniques achieve highly conformal target doses while avoiding organs-at-risk such as the lens. The magnitude of eye movement and its influence on CSI target- and avoidance volumes are unclear. We aimed to evaluate the movement-range of lenses and optic nerves and its influence on dose distribution of several planning techniques. METHODS: Ten volunteers underwent MRI scans in various gaze directions (neutral, left, right, cranial, caudal). Lenses, orbital optic nerves, optic discs and CSI target volumes were delineated. 36-Gy cranial irradiation plans were constructed on synthetic CT images in neutral gaze, with Volumetric Modulated Arc Therapy, pencil-beam scanning proton therapy, and 3D-conventional photons. Movement-amplitudes of lenses and optic discs were analyzed, and influence of gaze direction on lens and orbital optic nerve dose distribution. RESULTS: Mean eye structures' shift from neutral position was greatest in caudal gaze; -5.8±1.2 mm (±SD) for lenses and 7.0±2.0 mm for optic discs. In 3D-conventional plans, caudal gaze decreased Mean Lens Dose (MLD). In VMAT and proton plans, eye movements mainly increased MLD and diminished D98 orbital optic nerve (D98OON) coverage; mean MLD increased up to 5.5 Gy [total ΔMLD range -8.1 to 10.0 Gy], and mean D98OON decreased up to 3.3 Gy [total ΔD98OON range -13.6 to 1.2 Gy]. VMAT plans optimized for optic disc Internal Target Volume and lens Planning organ-at-Risk Volume resulted in higher MLD over gaze directions. D98OON became ≥95% of prescribed dose over 95/100 evaluated gaze directions, while all-gaze bilateral D98OON significantly changed in 1 of 10 volunteers. CONCLUSION: With modern CSI techniques, eye movements result in higher lens doses and a mean detriment for orbital optic nerve dose coverage of <10% of prescribed dose.

Clinical Issues-September 2020.

THIS MONTH: Surgical counts during a partial cystectomy Key words: partial cystectomy, retained surgical item (RSI), counts, bladder, guidewire. Preparing the OR for patients who require both airborne and contact precautions Key words: airborne precautions, contact precautions, contamination, Coronavirus Disease 2019 (COVID-19), negative pressure. Preoperative transport of patients who require both airborne and contact precautions Key words: preoperative patient transport, hand hygiene, personal protective equipment (PPE), N95 respirator, Coronavirus Disease 2019 (COVID-19). Postoperative transport of patients who require both airborne and contact precautions Key words: postoperative patient transport, hand hygiene, personal protective equipment (PPE), N95 respirator, Coronavirus Disease 2019 (COVID-19).

Clinical Issues-October 2020.

Bundling cords during laparoscopic procedures Key words: antenna coupling, laparoscopy, monopolar active electrode, burns, thermal injury. Cleaning dirty instruments in scrub sinks Key words: instrument cleaning, instrument decontamination, scrub sinks, manual cleaning, mechanical cleaning. Using cotton balls in neurosurgery Key words: gossypiboma, foreign body granuloma, cotton ball, neurosurgery, retained surgical item (RSI). Surgical hand rub allergies Key words: hand allergy, dermatitis, eczema, hand rub, product trial.

Cluster identification, selection, and description in cluster randomized crossover trials: the PREP-IT trials.

BACKGROUND: In cluster randomized crossover (CRXO) trials, groups of participants (i.e., clusters) are randomly allocated to receive a sequence of interventions over time (i.e., cluster periods). CRXO trials are becoming more comment when they are feasible, as they require fewer clusters than parallel group cluster randomized trials. However, CRXO trials have not been frequently used in orthopedic fracture trials and represent a novel methodological application within the field. To disseminate the early knowledge gained from our experience initiating two cluster randomized crossover trials, we describe our process for the identification and selection of the orthopedic practices (i.e., clusters) participating in the PREP-IT program and present data to describe their key characteristics. METHODS: The PREP-IT program comprises two ongoing pragmatic cluster randomized crossover trials (Aqueous-PREP and PREPARE) which compare the effect of iodophor versus chlorhexidine solutions on surgical site infection and unplanned fracture-related reoperations in patients undergoing operative fracture management. We describe the process we used to identify and select orthopedic practices (clusters) for the PREP-IT trials, along with their characteristics. RESULTS: We identified 58 potential orthopedic practices for inclusion in the PREP-IT trials. After screening each practice for eligibility, we selected 30 practices for participation and randomized each to a sequence of interventions (15 for Aqueous-PREP and 20 for PREPARE). The majority of orthopedic practices included in the Aqueous-PREP and PREPARE trials were situated in level I trauma centers (100% and 87%, respectively). Orthopedic practices in the Aqueous-PREP trial operatively treated a median of 149 open fracture patients per year, included a median of 11 orthopedic surgeons, and had access to a median of 5 infection preventionists. Orthopedic practices in the PREPARE trial treated a median of 142 open fracture and 1090 closed fracture patients per year, included a median of 7.5 orthopedic surgeons, and had access to a median of 6 infection preventionists. CONCLUSIONS: The PREP-IT trials provide an example of how to follow the reporting standards for cluster randomized crossover trials by providing a clear definition of the cluster unit, a thorough description of the cluster identification and selection process, and sufficient description of key cluster characteristics. TRIAL REGISTRATION: Both trials are registered at ClinicalTrials.gov (A-PREP: NCT03385304 December 28, 2017, and PREPARE: NCT03523962 May 14, 2018).

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials.

An amendment to this paper has been published and can be accessed via the original article.

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.