Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease.

The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus. Vaccinated dams challenged with a heterologous ZIKV strain at embryo day 6 (E6) and evaluated at E13 showed markedly diminished levels of viral RNA in maternal, placental, and fetal tissues, which resulted in protection against placental damage and fetal demise. As modified mRNA and live-attenuated vaccine platforms can restrict in utero transmission of ZIKV in mice, their further development in humans to prevent congenital ZIKV syndrome is warranted.

Development of the Enthusiastic Substance Use Attitudes Scale: Preliminary Evidence of a Novel Maintenance Factor.

Background: Expectancies, motives, and attitudes toward substances are cognitive factors that partially account for substance use; however, existing measures tend to have monotonous phrasing, diverging from the enthusiastic attitude toward the perceived benefits of substance use exhibited by those who use substances regularly in informal settings. Objective: I aimed to characterize a new cognitive maintenance factor that precedes substance use by creating a brief, multidimensional measure to capture this tone nuance, which I called the Enthusiastic Substance Use Attitudes Scale (ESUAS). Method: Undergraduate students (n = 198) between ages 18 and 62 (M = 19.15, SD = 3.65; 66.2% women; 71.71% White) completed the study for course credit. Results: I used exploratory and confirmatory factor analyses to reduce a 90-item item pool based on a comprehensive qualitative thematic analysis of social media, traditional media, and the scientific literature to an 18-item hierarchical bifactor model. This model contained nine specific factors, which are (1) sociability, (2) enjoyment, (3) physical health, (4) mental health, (5) relaxation, (6) personal growth, (7) performance enhancement, (8) boredom, and (9) life processing; two general factors, which are (1) substance-induced emotion regulation and (2) substance-based assistance; and a higher-order single factor above the nine specific factors - resulting in twelve highly internally consistent, empirically supported scales. Further, the ESUAS demonstrated excellent structural, convergent, divergent, incremental, and diagnostic validity. The degree of enthusiasm towards substance use positively related to substance use disorder symptomology, polysubstance use, neuroticism, and difficulty with regulating emotions while negatively relating to one's psychological quality of life and agreeableness. Conclusion: The ESUAS may be an effective tool for professionals to characterize these enthusiastic attitudes further and measure a more ecologically valid view of the perceived benefits of substance use among those who use substances, thereby developing a more compassionate, non-stigmatizing understanding within the general public, advancing medicinal uses of illicit substances, and improving conceptualizations and treatments.

Gluteus Maximus Transfer for Irreparable Hip Abductor Deficiency: A Systematic Review and Meta-Analysis.

BACKGROUND: Gluteus maximus tendon transfer has recently been described as a treatment option for irreparable abductor tendon tears. The purpose of this study was to systematically review outcomes following gluteus maximus tendon transfer for hip abductor deficiency. METHODS: The published literature was queried for outcomes following gluteus maximus transfer in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Outcomes of interest included preoperative and postoperative functional scores, resolution of pain and gait abnormalities, postoperative rehabilitation protocols, surgical complications, reoperation rates, and postoperative magnetic resonance imaging. In total, 10 studies with a total of 125 patients (76% women) with a mean age of 67 years (range, 30 to 87) were identified for inclusion. RESULTS: Modified Harris Hip Score (+30.1 ± 6.6 [95% confidence interval: +15.5 to +46.5]) and Visual Analog Scale for pain (-4.1 ± 1.1 [95% confidence interval: -7.1 to -1.0]) were improved following gluteus maximus transfer, compared to preoperative levels. No significant improvement was noted in abduction strength and 33% of patients demonstrated a residual Trendelenburg gait postoperatively. The overall complication rate was 5.6% (7 of 125), with a reoperation rate of 1.6% (2 of 125). CONCLUSIONS: Gluteus maximus tendon transfer for abductor insufficiency has demonstrated reliable outcomes at 3 years, with improvement in hip function and pain. However, patients demonstrate modest improvements in abduction strength, and a significant subset will continue to demonstrate a Trendelenburg gait postoperatively.

Researcher degrees of freedom in statistical software contribute to unreliable results: A comparison of nonparametric analyses conducted in SPSS, SAS, Stata, and R.

Researcher degrees of freedom can affect the results of hypothesis tests and consequently, the conclusions drawn from the data. Previous research has documented variability in accuracy, speed, and documentation of output across various statistical software packages. In the current investigation, we conducted Pearson's chi-square test of independence, Spearman's rank-ordered correlation, Kruskal-Wallis one-way analysis of variance, Wilcoxon Mann-Whitney U rank-sum tests, and Wilcoxon signed-rank tests, along with estimates of skewness and kurtosis, on large, medium, and small samples of real and simulated data in SPSS, SAS, Stata, and R and compared the results with those obtained through hand calculation using the raw computational formulas. Multiple inconsistencies were found in the results produced between statistical packages due to algorithmic variation, computational error, and statistical output. The most notable inconsistencies were due to algorithmic variations in the computation of Pearson's chi-square test conducted on 2 × 2 tables, where differences in p-values reported by different software packages ranged from .005 to .162, largely as a function of sample size. We discuss how such inconsistencies may influence the conclusions drawn from the results of statistical analyses depending on the statistical software used, and we urge researchers to analyze their data across multiple packages to check for inconsistencies and report details regarding the statistical procedure used for data analysis.

Assessing the potential chronic, sublethal and lethal ecotoxicity of land-applying biosolids on Folsomia candida and Lumbricus terrestris.

The ecotoxicity of biosolids has been studied extensively using single-compound toxicity testing and 'spiking' studies; however, little knowledge exists on the ecotoxicity of biosolids as they are land-applied in the Canadian context. The purpose of this study is to elucidate the chronic, sub-lethal (i.e., behavioural), and lethal impacts of land- applying biosolids on the environmentally relevant Folsomia candida (springtails) and Lumbricus terrestris (earthworms) and concomitantly ascertain whether the use of biosolids for nutrient amendment is a sustainable practice. This study is part of a larger multi-compartment programme which includes terrestrial plants and aquatic arthropods. After a review of existing government protocols and research, the current study suggests new environmentally relevant bioassays as to elucidate the true nature of the potential ecotoxicity of land-applying biosolids, within a laboratory context. Specifically, protocols were developed (e.g., shoebox bioassays for L. terrestris sub-lethal testing) or modified (e.g., using Evans' boxes (Evans 1947) for chronic and sub-lethal testing on L. terrestris). Subsequently, two biosolids were tested on springtails and earthworms using avoidance and reproductive bioassay endpoints, at application rates that represent standard (8 tonnes ha-1) and worst-case scenarios (22 tonnes ha-1). Results indicated no effect of biosolids at the environmentally relevant concentration; the worst-case scenario exhibited a positive significantly significant relationship (indicating preference for treatment conditions). We suggest that further assessment of the potential ecotoxicological impact of biosolids employ (i) environmentally relevant organisms, (ii) appropriate bioassays including the use of whole-organism endpoints, and (iii) multi-kingdom testing (e.g., Kingdom Plantae, Animalia) to comprehensively elucidate answers. Lastly, in situ (field assays) are strongly encouraged for future studies.

The Nonoperative Instability Severity Index Score: Is It Predictive in a Larger Shoulder Instability Population at Long-Term Follow-Up?

PURPOSE: To evaluate the effect of the Nonoperative Instability Severity Index Score (NISIS) criteria on an established US-geographic population-based cohort of patients with anterior shoulder instability. METHODS: An established geographically based medical record system was used to identify patients <40 years of age with anterior shoulder instability between 1994 and 2016. Medical records were reviewed to obtain patient demographics and instability characteristics. Patient-specific risk factors were individually incorporated into the 10-point NISIS criteria: age (>15 years), bone loss, type of instability (dislocation vs subluxation), type of sport (collision vs noncollision), male sex, and dominant arm involvement. High risk was considered a score of ≥7 points and low risk as <7 points. Failure was defined as either progression to surgery or recurrent instability diagnosed by a consulting physician at any point after initial consultation. RESULTS: The study population consisted of 405 patients with a mean follow-up time of 9.6 ± 5.9 years. Failure was defined as recurrent instability or progression to surgery, and the overall failure rate was 52.8% (214/405). The rate of recurrent instability after initial consultation was 34.6% (140/405), and the rate of conversion to surgery was 37.8% (153/405). A total of 264 (65.2%) patients were considered low risk (NISIS < 7), and 141 (34.8%) patients were considered high risk (NISIS ≥ 7). Patients in the high-risk group were more likely to fail nonoperative management than those in the low-risk group (60.3% vs 48.9%; P = .028). CONCLUSIONS: The NISIS has been proposed as a potentially useful tool in clinical decision-making regarding the appropriate use of nonoperative treatment in scholastic athletes. When applied to an established US-geographic population-based cohort consisting of competitive and recreational athletes under the age of 40 with longer-term follow-up, the NISIS high-risk cutoff was able to predict overall failure with 60.3% accuracy. LEVEL OF EVIDENCE: III, retrospective observation trial.

The Feasibility of Utilizing Malunion Criteria to Limit Radiographs After Spica Casting for Pediatric Femur Fractures.

BACKGROUND: There are no existing guidelines regarding the timing or frequency of postoperative radiographs following spica casting for pediatric femur fractures. The purpose of this study was to evaluate established femoral malunion criteria as a potential screening tool to limit postoperative radiographs by identifying patients at risk for unacceptable alignment in the early treatment period. METHODS: A retrospective chart review was conducted for pediatric femoral shaft fractures presenting to a tertiary pediatric referral hospital from 2012 to 2017. Pediatric femur malunion criteria were applied to radiographs at initial presentation, first follow-up visit, and final follow-up visit. The primary outcome was a change in management based on radiographic findings in the early postoperative period. Secondary outcomes included radiographic measures, number of follow-up visits, and complications. RESULTS: Of 449 consecutive pediatric femur fractures treated at our center, 149 patients aged 1 to 4 years (mean age: 2.5±1.6 y) met inclusion criteria. At initial presentation, 36.9% (55/149) of patients met malunion criteria. Only 4.0% (6/149) of patients had a change in management following initial closed reduction and spica cast application due to radiographic findings at subsequent follow-up. Of these patients, 67% (4/6) were identified on preoperative imaging, and 83.3% (5/6) were identified by their first clinic appointment. Four of the 149 patients were converted to definitive surgical fixation, and 2 patients required cast wedging due to either unacceptable fracture shortening or coronal/sagittal angulation. CONCLUSIONS: Routine early postoperative radiographs may not be necessary for all pediatric femur fractures managed with closed reduction and spica casting. The value of this study is that it is the first to demonstrate the feasibility of limiting postoperative radiographs using a preoperative screening tool. However, the established femoral malunion criteria utilized in this study were limited in their predictive value, and further work is necessary to improve the sensitivity and specificity before widespread clinical application. LEVEL OF EVIDENCE: Level IV.

Limited Flavivirus Cross-Reactive Antibody Responses Elicited by a Zika Virus Deoxyribonucleic Acid Vaccine Candidate in Humans.

Zika virus (ZIKV) deoxyribonucleic acid vaccine VRC5283 encoding viral structural genes has been shown to be immunogenic in humans. Recognizing that antigenically related flaviviruses cocirculate in regions with ZIKV activity, we explored the degree of antibody cross-reactivity elicited by this vaccine candidate using genetically diverse flaviviruses. The antibody response of vaccinated individuals with no evidence of prior flavivirus infection or vaccine experience had a limited capacity to bind heterologous viruses. In contrast, vaccine-elicited antibodies from individuals with prior flavivirus experience had a greater capacity to bind, but not neutralize, distantly related flaviviruses. These findings suggest that prior flavivirus exposure shapes the humoral immune response to vaccination.

The explanatory ability of COVID-19 life changes on quality of life: A comparison of those who have had and not had COVID-19.

The COVID-19 pandemic has undoubtedly negatively affected individuals' quality of life through multiple means such as social isolation, exacerbated mental health conditions, and financial instability. Multiple studies have demonstrated that one of the negative correlates of quality of life is the perceived danger of COVID-19 (i.e., fear of and anxiety about COVID-19). The current study addresses limitations in the literature by testing how life changes from COVID-19 explain the direct effect of the perceived danger of COVID-19 on quality of life using a United States sample between those who have had COVID-19 compared to those who have not had COVID-19. Undergraduate students (n = 196) from a Midwestern University in the United States participated in this study for course credit (White: n = 109; 55.61%; Male: n = 94; 48.0%). Participants completed this study online and at home where they responded to a demographic form and several measures of the effects of COVID-19 and quality of life. The results suggest that COVID-19 life changes fully explain the negative relationship between the perceived danger of COVID-19 and quality of life, but only in those who have had COVID-19. In the group that has never had COVID-19, the only significant relationship was the positive relationship between the perceived danger of COVID-19 on COVID-19 life changes. The results suggest that researchers may consider steering research away from the perceived danger of COVID-19 and onto remedying life changes from COVID-19 to improve individuals' quality of life. I further discuss the theoretical findings, implications, limitations, and future directions.

Society for Cardiovascular Magnetic Resonance 2019 Case of the Week series.

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). The SCMR web site ( https://www.scmr.org ) hosts a case series designed to present case reports demonstrating the unique attributes of CMR in the diagnosis or management of cardiovascular disease. Each clinical presentation is followed by a brief discussion of the disease and unique role of CMR in disease diagnosis or management guidance. By nature, some of these are somewhat esoteric, but all are instructive. In this publication, we provide a digital archive of the 2019 Case of the Week series as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.

The key components of a successful model of midwifery-led continuity of carer, without continuity at birth: findings from a qualitative implementation evaluation.

BACKGROUND: Recent UK maternity policy changes recommend that a named midwife supports women throughout their pregnancy, birth and postnatal care. Whilst many studies report high levels of satisfaction amongst women receiving, and midwives providing, this level of continuity of carer, there are concerns some midwives may experience burnout and stress. In this study, we present a qualitative evaluation of the implementation of a midwife-led continuity of carer model that excluded continuity of carer at the birth. METHODS: Underpinned by the Conceptual Model for Implementation Fidelity, our evaluation explored the implementation, fidelity, reach and satisfaction of the continuity of carer model. Semi-structured interviews were undertaken with midwives (n = 7) and women (n = 15) from continuity of carer team. To enable comparisons between care approaches, midwives (n = 7) and women (n = 10) from standard approach teams were also interviewed. Interviews were recorded, transcribed and analysed using thematic analysis. RESULTS: For continuity of carer team midwives, manageable caseloads, extended appointment times, increased team stability, and flexible working patterns facilitated both care provided and midwives' job satisfaction. Both continuity of carer and standard approach midwives reported challenges in providing postnatal continuity given the unpredictable timing of labour and birth. Time constraints, inadequate staffing and lack of administrative support were reported as additional barriers to implementing continuity of carer within standard approach teams. Women reported continuity was integral to building trust with midwives, encouraged them to disclose mental health issues and increased their confidence in making birth choices. CONCLUSIONS: Our evaluation highlighted the successful implementation of a continuity of carer model for ante and postnatal care. Despite exclusion of the birth element in the model, both women and midwives expressed high levels of satisfaction in comparison to women and midwives within the standard approach. Implementation successes were largely due to structural and resource factors, particularly the combination of additional time and smaller caseloads of women. However, these resources are not widely available within the resources of maternity unit budgets. Future research should further explore whether a continuity of carer model focusing on antenatal and postnatal care delivery is a feasible and sustainable model of care for all women.

Post-arthroscopic Subchondral Insufficiency Fractures of the Knee Yield High Rate of Conversion to Arthroplasty.

PURPOSE: To evaluate both the potential causes and resultant outcomes in patients in whom subchondral insufficiency fracture of the knee (SIFK) develops after arthroscopy. METHODS: We performed a retrospective review of all patients with a magnetic resonance imaging diagnosis of SIFK after arthroscopic meniscectomy and chondroplasty over a 12-year period. RESULTS: A total of 28 patients were included, with a mean age of 61 years and mean follow-up period of 5.7 years. SIFK showed a predilection for the medial compartment (n = 25, 89%), specifically the medial femoral condyle (n = 21, 75%). In 7 patients (25%), SIFK developed in both the femoral condyle and tibial plateau in the ipsilateral compartment. Fifteen patients (54%) went on to conversion to arthroplasty at a mean of 0.72 years. The rate of survival free of conversion to arthroplasty was 57%, 45%, and 40% at 1 year, 2 years, and 5 years, respectively. Furthermore, 63% of patients with a meniscal tear and SIFK in the same compartment went on to arthroplasty (P = .04). There was an increased risk of conversion to arthroplasty if SIFK was present in both the femur and tibia in the same compartment (P = .04). A higher Kellgren-Lawrence grade at the time of the SIFK diagnosis increased the likelihood of eventual arthroplasty (P = .03). The presence of SIFK in both the femur and tibia in the ipsilateral compartment, an increased Kellgren-Lawrence grade, and a meniscal tear or prior meniscectomy in the same compartment as SIFK were associated with an increased risk of eventual arthroplasty. CONCLUSIONS: Post-arthroscopic SIFK most commonly occurs in the medial compartment, particularly in patients who underwent a prior meniscectomy. The presence of meniscal root and radial tears in these patients is notable (75%). Ultimately, there is a high rate of progression of arthrosis (33%) and eventual conversion to arthroplasty. LEVEL OF EVIDENCE: Level IV, case series.

Machine learning can reliably identify patients at risk of overnight hospital admission following anterior cruciate ligament reconstruction.

PURPOSE: Overnight admission following anterior cruciate ligament reconstruction has implications on clinical outcomes as well as cost benefit, yet there are few validated risk calculators for reliable identification of appropriate candidates. The purpose of this study is to develop and validate a machine learning algorithm that can effectively identify patients requiring admission following elective anterior cruciate ligament (ACL) reconstruction. METHODS: A retrospective review of a national surgical outcomes database was performed to identify patients who underwent elective ACL reconstruction from 2006 to 2018. Patients admitted overnight postoperatively were identified as those with length of stay of 1 or more days. Models were generated using random forest (RF), extreme gradient boosting (XGBoost), linear discriminant classifier (LDA), and adaptive boosting algorithms (AdaBoost), and an additional model was produced as a weighted ensemble of the four final algorithms. RESULTS: Overall, of the 4,709 patients included, 531 patients (11.3%) required at least one overnight stay following ACL reconstruction. The factors determined most important for identification of candidates for inpatient admission were operative time, anesthesia type, age, gender, and BMI. Smoking history, history of COPD, and history of coagulopathy were identified as less important variables. The following factors supported overnight admission: operative time > 200 min, age < 35.8 or > 53.5 years, male gender, BMI < 25 or > 31.2 kg/m2, positive smoking history, history of COPD and the presence of preoperative coagulopathy. The ensemble model achieved the best performance based on discrimination assessed via internal validation (AUC = 0.76), calibration, and decision curve analysis. The model was integrated into a web-based open-access application able to provide both predictions and explanations. CONCLUSION: Modifiable risk factors identified by the model such as increased BMI, operative time, anesthesia type, and comorbidities can help clinicians optimize preoperative status to prevent costs associated with unnecessary admissions. If externally validated in independent populations, this algorithm could use these inputs to guide preoperative screening and risk stratification to identify patients requiring overnight admission for observation following ACL reconstruction. LEVEL OF EVIDENCE: IV.

Arthritic progression secondary to meniscus root tear treated with knee arthroplasty demonstrates similar outcomes to primary osteoarthritis: a matched case-control comparison.

PURPOSE: There is limited data comparing the outcomes of knee arthroplasty for arthritis secondary to meniscus root tear versus primary osteoarthritis. The aim of this 2:1 matched case control series was to compare outcomes in patients who underwent arthroplasty for arthritis following a meniscus root tear (root tear cohort-"RTC") with a control group of patients with primary osteoarthritis (primary osteoarthritis-"controls"). The authors hypothesized that the meniscus root tear patients would have similar clinical outcomes, return to activity, complication and reoperation rates as their matched controls. METHODS: A consecutive series of patients who had a clinically and radiographically confirmed meniscus root tear between 2002 and 2017 at a mean 4.8 year follow-up that developed secondary arthritis were matched 2:1 by laterality, surgery, age at surgery, date of surgery, sex, and surgeon to a control group of patients with primary osteoarthritis, without a root tear, who underwent arthroplasty. No patients were lost to follow-up. Patient demographics, Kellgren-Lawrence grades at the time of surgery, pre- and post-operative Knee Society Score pain and function scores, Tegner score, complications, and survival free of reoperation were analyzed between groups. RESULTS: A total of 225 subjects were identified, including 75 root tear cohort patients (13 UKA, 62 TKA) and 150 control patients. The root tear cohort had significantly lower Kellgren-Lawrence grades than the control group at the time of arthroplasty (p ≤ 0.001), but similar baseline pre-operative Knee Society Score pain, Knee Society Score function, and Tegner activity scale score. Post-operatively, Knee Society Score pain scores were comparable, and root tear cohort Knee Society Score function scores statistically significantly improved (p ≤ 0.007). Complication rates and survival free of reoperation at final follow-up were not statistically significantly different between groups. CONCLUSION: Patients treated with arthroplasty for secondary arthritis after a meniscus root tear demonstrated less severe radiographic arthritis, but similar pre-operative pain levels compared to matched controls with primary osteoarthritis. The root tear cohort patients demonstrated improved outcomes with respect to function, and similar outcomes with respect to pain, activity level, complication rates, and reoperation rates. The authors conclude that arthroplasty can be a reliable option for selected patients with an irreparable root tear and ongoing pain and dysfunction refractory to non-operative management, even in the setting of less advanced osteoarthritis on X-ray. LEVEL OF EVIDENCE: III.

The Impact of Cast Immobilization on Return to Daycare.

BACKGROUND: Children who are prohibited from returning to daycare (RTD) after treatment with cast immobilization place an increased burden on parents and caregivers. The purpose of this study was to assess the impact of cast immobilization on RTD. Specifically, we sought to determine the prevalence of RTD after orthopaedic immobilization based on daycare facility policy. METHODS: This was a survey study of randomly selected daycare facilities servicing a total of 6662 children within 10 miles of a major metropolitan city center. The 40-question survey included information on daycare policies and experience caring for children treated with orthopaedic immobilization. The survey also included questions about daycare type, enrollment, and geographic location. Photographs of the types of immobilization were embedded in the survey to facilitate understanding. Daycare facilities were randomly selected based on a power analysis to estimate a 50% prevalence of RTD after spica casting within 10% margin of error. RESULTS: Seventy-three daycare facilities completed the survey study. The average child-staff ratio was 5:1 and most daycare facilities (78%) did not have a nurse on staff. Predetermined policies regarding RTD after injury were available at 81% of daycares. Twenty-eight (38.5%) facilities had encountered a child with a cast in the previous year. The rate of RTD for children with upper limb injuries was 90.5% compared with 79% for lower limb injuries (P=0.003). Spica casts showed the lowest RTD rate: single leg (22.5%), 1 and a half leg (18%), and 2 leg (16%) (P<0.0001). Experienced daycare facilities (>5 y) had a higher RTD rate compared with less experienced facilities (P=0.026). CONCLUSIONS: The ability to RTD is dependent on immobilization type. Children with long leg and spica casts are disproportionately restricted when compared with other cast types. At minimum, surgeons should consider the socioeconomic implications of orthopaedic immobilization. There is also a need for orthopaedic involvement in policy formation at the local level to provide standardized guidelines for re-entry into childcare facilities following orthopaedic immobilization. LEVEL OF EVIDENCE: Level IV.

Intraoperative Burden of Flexible Intramedullary Nailing and Spica Casting for Femur Fractures in Young Children.

BACKGROUND: Spica casting (Spica) remains the widely accepted treatment of closed femoral shaft fractures in young children aged 6 months to 5 years. In some centers, there has been a recent trend towards surgical fixation of these fractures with flexible intramedullary nails (FINs). Despite numerous studies evaluating both Spica and FIN treatment of femoral shaft fractures, there remains a paucity of data regarding patient burden during the intraoperative period. The purpose of this study was to compare the intraoperative burden, defined as anesthetic exposure, fluoroscopic duration, and radiation load, between Spica and FIN treatment of femoral shaft fractures in young children. METHODS: A retrospective chart review was conducted for pediatric femoral shaft fractures presenting to a tertiary pediatric referral hospital from 2012 to 2017. Comparison groups included pediatric femur fractures treated with Spica and those treated with FIN. Outcomes included anesthetic exposure, fluoroscopy duration, and radiation exposure. In addition, length of stay, clinic visits, and complications were recorded. RESULTS: Of 449 consecutive pediatric femur fractures treated at our center, 143 patients ages 2 to 6 years (mean age 3.8±1.4 y) met inclusion criteria. The Spica group contained 91 patients; FIN contained 52 patients. Mean anesthetic exposure was less for Spica compared with FIN [45.1 min, 95% confidence interval (CI): 38.0-52.3 vs. 90.7 min, 95% CI: 80.5-100.8 min; P<0.001]. On average, Spica procedures required less fluoroscopy time compared with FIN (15.4 s, 95% CI: 4.8-26.0 vs. 131.6 s, 95% CI: 117.6-145.6 s; P<0.001). Mean radiation load was less for Spica compared with FIN (1.6 mGy, 95% CI: 0.6-2.6 vs. 6.9 mGy, 95% CI: 5.7-8.1 mGy; P<0.001). There was no difference in length of hospital stay (P=0.831), follow-up visits (P=0.248), or complication rate (P=0.645) between Spica and FIN groups. The most common complication was skin irritation for Spica (18.7%) and symptomatic hardware for FIN (17.3%). CONCLUSIONS: The findings of this study suggest that pediatric patients with femoral shaft fractures experience an increased intraoperative burden when treated with FIN compared with Spica. Treatment with FIN was associated with increased exposure to anesthesia, fluoroscopic duration, and radiation load despite similar complication rates when compared with Spica. LEVEL OF EVIDENCE: Level III.

Surgical Outcomes of Obese Patients With Adolescent Idiopathic Scoliosis From Endemic Areas of Obesity in the United States.

BACKGROUND: Obesity rates continue to rise among children and adolescents across the globe. A multicenter research consortium composed of institutions in the Southern US, located in states endemic for childhood obesity, was formed to evaluate the effect of obesity on pediatric musculoskeletal disorders. This study evaluates the effect of body mass index (BMI) percentile and socioeconomic status (SES) on surgical site infections (SSIs) and perioperative complications in patients with adolescent idiopathic scoliosis (AIS) treated with posterior spinal fusion (PSF). METHODS: Eleven centers in the Southern US retrospectively reviewed postoperative AIS patients after PSF between 2011 and 2017. Each center contributed data to a centralized database from patients in the following BMI-for-age groups: normal weight (NW, 5th to <85th percentile), overweight (OW, 85th to <95th percentile), and obese (OB, ≥95th percentile). The primary outcome variable was the occurrence of an SSI. SES was measured by the Area Deprivation Index (ADI), with higher scores indicating a lower SES. RESULTS: Seven hundred fifty-one patients were included in this study (256 NW, 235 OW, and 260 OB). OB and OW patients presented with significantly higher ADIs indicating a lower SES (P<0.001). In addition, SSI rates were significantly different between BMI groups (0.8% NW, 4.3% OW, and 5.4% OB, P=0.012). Further analysis showed that superficial and not deep SSIs were significantly different between BMI groups. These differences in SSI rates persisted even while controlling for ADI. Wound dehiscence and readmission rates were significantly different between groups (P=0.004 and 0.03, respectively), with OB patients demonstrating the highest rates. EBL and cell saver return were significantly higher in overweight patients (P=0.007 and 0.002, respectively). CONCLUSION: OB and OW AIS patients have significantly greater superficial SSI rates than NW patients, even after controlling for SES. LEVEL OF EVIDENCE: Level III.

Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials.

BACKGROUND: The Zika virus epidemic and associated congenital infections have prompted rapid vaccine development. We assessed two new DNA vaccines expressing premembrane and envelope Zika virus structural proteins. METHODS: We did two phase 1, randomised, open-label trials involving healthy adult volunteers. The VRC 319 trial, done in three centres, assessed plasmid VRC5288 (Zika virus and Japanese encephalitis virus chimera), and the VRC 320, done in one centre, assessed plasmid VRC5283 (wild-type Zika virus). Eligible participants were aged 18-35 years in VRC19 and 18-50 years in VRC 320. Participants were randomly assigned 1:1 by a computer-generated randomisation schedule prepared by the study statistician. All participants received intramuscular injection of 4 mg vaccine. In VRC 319 participants were assigned to receive vaccinations via needle and syringe at 0 and 8 weeks, 0 and 12 weeks, 0, 4, and 8 weeks, or 0, 4, and 20 weeks. In VRC 320 participants were assigned to receive vaccinations at 0, 4, and 8 weeks via single-dose needle and syringe injection in one deltoid or split-dose needle and syringe or needle-free injection with the Stratis device (Pharmajet, Golden, CO, USA) in each deltoid. Both trials followed up volunteers for 24 months for the primary endpoint of safety, assessed as local and systemic reactogenicity in the 7 days after each vaccination and all adverse events in the 28 days after each vaccination. The secondary endpoint in both trials was immunogenicity 4 weeks after last vaccination. These trials are registered with ClinicalTrials.gov, numbers NCT02840487 and NCT02996461. FINDINGS: VRC 319 enrolled 80 participants (20 in each group), and VRC 320 enrolled 45 participants (15 in each group). One participant in VRC 319 and two in VRC 320 withdrew after one dose of vaccine, but were included in the safety analyses. Both vaccines were safe and well tolerated. All local and systemic symptoms were mild to moderate. In both studies, pain and tenderness at the injection site was the most frequent local symptoms (37 [46%] of 80 participants in VRC 319 and 36 [80%] of 45 in VRC 320) and malaise and headache were the most frequent systemic symptoms (22 [27%] and 18 [22%], respectively, in VRC 319 and 17 [38%] and 15 [33%], respectively, in VRC 320). For VRC5283, 14 of 14 (100%) participants who received split-dose vaccinations by needle-free injection had detectable positive antibody responses, and the geometric mean titre of 304 was the highest across all groups in both trials. INTERPRETATION: VRC5283 was well tolerated and has advanced to phase 2 efficacy testing. FUNDING: Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Use of progression criteria to support monitoring and commissioning decision making of public health services: lessons from Better Start Bradford.

BACKGROUND: Commissioning and monitoring of community-based interventions is a challenge due to the complex nature of the environment and the lack of any explicit cut-offs to guide decision making. At what point, for example, is participant enrolment to interventions, course completion or satisfaction deemed to be acceptable or sufficient for continued funding? We aimed to identify and quantify key progression criteria for fourteen early years interventions by (1) agreeing the top three criteria for monitoring of successful implementation and progress; and (2) agreeing boundaries to categorise interventions as 'meeting anticipated target' (green); 'falling short of targets' (amber) and 'targets not being met' (red). METHODS: We ran three workshops in partnership with the UK's Big Lottery Fund commissioned programme 'Better Start Bradford' (implementing more than 20 interventions to improve the health, wellbeing and development of children aged 0-3) to support decision making by agreeing progression criteria for the interventions being delivered. Workshops included 72 participants, representing a range of professional groups including intervention delivery teams, commissioners, intervention-monitoring teams, academics and community representatives. After discussion and activities, final decisions were submitted using electronic voting devices. All participants were invited to reconsider their responses via a post-workshop questionnaire. RESULTS: Three key progression criteria were assigned to each of the 14 interventions. Overall, criteria that participants most commonly voted for were recruitment, implementation and reach, but these differed according to each intervention. Cut-off values used to indicate when an intervention moved to 'red' varied by criteria; the lowest being for recruitment, where participants agreed that meeting less than 65% of the targeted recruitment would be deemed as 'red' (falling short of target). CONCLUSIONS: Our methodology for monitoring the progression of interventions has resulted in a clear pathway which will support commissioners and intervention teams in local decision making within the Better Start Bradford programme and beyond. This work can support others wishing to implement a formal system for monitoring the progression of public health interventions.

Association of food security status with overweight and dietary intake: exploration of White British and Pakistani-origin families in the Born in Bradford cohort.

BACKGROUND: Food insecurity has been associated with dietary intake and weight status in UK adults and children although results have been mixed and ethnicity has not been explored. We aimed to compare prevalence and trajectories of weight and dietary intakes among food secure and insecure White British and Pakistani-origin families. METHODS: At 12 months postpartum, mothers in the Born in Bradford cohort completed a questionnaire on food security status and a food frequency questionnaire (FFQ) assessing their child's intake in the previous month; at 18 months postpartum, mothers completed a short-form FFQ assessing dietary intake in the previous 12 months. Weights and heights of mothers and infants were assessed at 12-, 24-, and 36-months postpartum, with an additional measurement of children taken at 4-5 years. Associations between food security status and dietary intakes were assessed using Wilcoxon-Mann-Whitney for continuous variables and χ2 or Fisher's exact tests for categorical variables. Quantile and logistic regression were used to determine dietary intakes adjusting for mother's age. Linear mixed effects models were used to assess longitudinal changes in body mass index (BMI) in mothers and BMI z-scores in children. RESULTS: At 12 months postpartum, White British mothers reported more food insecurity than Pakistani-origin mothers (11% vs 7%; p < 0.01) and more food insecure mothers were overweight. Between 12 and 36 months postpartum, BMI increased more among food insecure Pakistani-origin mothers (ß = 0.77 units, [95% Confidence Interval [CI]: 0.40, 1.10]) than food secure (ß = 0.44 units, 95% CI: 0.33, 0.55). This was also found in Pakistani-origin children (BMI z-score: food insecure ß = 0.40 units, 95% CI: 0.22, 0.59; food secure ß = 0.25 units, 95% CI: 0.20, 0.29). No significant increases in BMI were observed for food secure or insecure White British mothers while BMI z-score increased by 0.17 (95% CI: 0.13, 0.21) for food secure White British children. Food insecure mothers and children had dietary intakes of poorer quality, with fewer vegetables and higher consumption of sugar-sweetened drinks. CONCLUSIONS: Food security status is associated with body weight and dietary intakes differentially by ethnicity. These are important considerations for developing targeted interventions.