COVID-19 induces a hyperactive phenotype in circulating platelets.

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected over 30 million globally to date. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Therefore, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and nonsevere COVID-19. An assessment of clinical blood parameters in patients with severe COVID-19 disease (requiring intensive care), patients with nonsevere disease (not requiring intensive care), general medical in-patients without COVID-19, and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. We demonstrated that routine clinical blood parameters including increased mean platelet volume (MPV) and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit (ICU) admission. Strikingly, agonist-induced ADP release was 30- to 90-fold higher in COVID-19 patients compared with hospitalised controls and circulating levels of platelet factor 4 (PF4), soluble P-selectin (sP-selectin), and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that distinct differences exist in routine full blood count and other clinical laboratory parameters between patients with severe and nonsevere COVID-19. Moreover, we have determined all COVID-19 patients possess hyperactive circulating platelets. These data suggest abnormal platelet reactivity may contribute to hypercoagulability in COVID-19 and confirms the role that platelets/clotting has in determining the severity of the disease and the complexity of the recovery path.

Utilization and outcomes of V-AV ECMO: A systematic review and meta-analysis.

BACKGROUND: Veno-arterial-venous extracorporeal membrane oxygenation (V-AV ECMO) is a less commonly used configuration of ECMO. We sought to understand the indications, utilization patterns, and outcomes of V-AV ECMO by quantitatively pooling the existing evidence from the literature. METHODS: Electronic search was performed to identify all relevant studies reporting V-AV ECMO usage. Five studies comprising 77 patients were selected and cohort-level data were extracted for further analysis. RESULTS: Mean patient age was 61 (95% CI: 55.2, 66.5) years and 30% (23/77) were female. The majority of cases [91% (70/77)] were transitioned to V-AV ECMO from another pre-existing ECMO configuration: V-A ECMO in 55% (42/77) vs. V-V ECMO in 36% (28/77), p = 0.04. Only 9% (7/77) of cases were directly placed on V-AV ECMO. The mean duration of hospital stay was 42.3 (95% CI: 10.5, 74.2) days, while ICU mortality was 46% (29, 64). Transition to durable left ventricular assist device was performed in 3% (2/64) of patients, while 3% (2/64) underwent heart transplantation. V-AV ECMO was successfully weaned to explantation in 33% (21/64) of patients. CONCLUSION: V-AV ECMO is a viable option for optimizing cardiopulmonary support in selected patients. Survival to weaning or bridging therapy appears comparable to more common ECMO configurations.

Comparison of endoscopic vs microscopic ossiculoplasty: a study of 157 consecutive cases.

PURPOSE: The relatively new technique of trans-canal endoscopic ear surgery (TEES) when compared to microsurgery for ossiculoplasty has advantages of better visualization and no external incision but also has the disadvantage of being a one-handed procedure. Our study aimed to compare audiometric outcomes following ossiculoplasty performed via TESS with results of microsurgery. MATERIALS AND METHODS: Data from a prospective audit of 157 consecutive patients who underwent ossiculoplasty by a single otologist from 2009 to 2018 was analyzed. TEES was introduced in the department in 2014; therefore, all patients before this period underwent microsurgery. Patients were classified by surgical approach, TEES, or microsurgery. Audiological outcomes were recorded at 3 and 12 months postoperatively and compared to pre-operative levels. Other variables included were the condition of stapes and reconstruction material used. RESULTS: Of the 157 cases, 50 were TEES and 107 were microsurgery (81 microscope only and 27 combined with endoscope). There was statistically significant improvement (p < 0.001) in AC (43.4 dB pre-operatively, 36.2 dB postoperatively), BC (20.3 dB pre-operatively, 17.6 dB postoperatively), and ABG (21.8 dB pre-operatively, 16.7 dB postoperatively) in the total cohort. Both groups achieved an ABG better than 20 dB; 72% in TEES, 73% in the microscopic group, and there was no significant difference. There was no change in hearing at 12 months when compared to 3 months. No statistically significant difference was noted based on stapes condition, type of material used for ossiculoplasty, or tympanic membrane graft. CONCLUSION: TEES is safe and as effective as microsurgery in ossiculoplasty with possibly much less pain and morbidity.

Intravenous ibuprofen for acute treatment of migraine: A double-blind, randomized, placebo-controlled pilot study.

OBJECTIVE: To evaluate the efficacy and safety of intravenous (IV) Ibuprofen for acute treatment of migraine. BACKGROUND: IV nonsteroidal anti-inflammatory drugs (NSAIDs) are an alternative to oral NSAIDs, especially in patients with severe migraine who have emesis or gastroparesis. To date, only three IV NSAIDs (ketorolac, ibuprofen, and meloxicam) are available in the United States for use in moderate and severe pain, but no placebo-controlled trial is available for migraine. We performed a single-center, double-blind, randomized, placebo-controlled pilot study to evaluate the efficacy and safety of IV ibuprofen as an acute treatment of migraine (NCT01230411). METHODS: Individuals with episodic migraine were screened at the Jefferson Headache Center. Qualified subjects were treated for migraine attacks within 2-72 h following the headache onset with either 800 mg of IV ibuprofen or placebo in 250 ml saline bolus. Migraine pain intensity (4-point Likert scale) and associated symptoms were assessed at predetermined time points (0.25, 0.5, 1, 1.5, 2, 4, 8, 24 h). The primary endpoint was pain relief at 2 h after infusion. Important secondary endpoints included pain freedom at 2 h, sustained relief over 24 h, use of rescue therapy, and absence of associated symptoms. Adverse events (AEs) were also collected. RESULTS: Seventy-four participants were enrolled between 2011 and 2017. Forty-four subjects (female 33/44; 75.0%) with mean (SD) age 41.0 (11.2)   11.2 years came for the treatment. All treated subjects (n = 44) were included in the analysis. Among them, 23 were randomized to receive IV ibuprofen. Both groups were demographically similar except for longer migraine duration (i.e., years lived with disease) in the active treatment than in the placebo group. At 2 h posttreatment, pain relief was found in 74% (17/23) and 48% (10/21) after IV ibuprofen and placebo, respectively (odds ratio [OR] 3.12, 95% CI: 0.88-11.0; p = 0.078). Other secondary endpoints at 2 and 24 h were not significant. The longitudinal repeated-measures analysis within 2 h on ibuprofen treatment showed significant pain relief (OR 2.47, 95% CI 1.08-5.7; p = 0.033) and absence of associated symptoms: photophobia (OR 4.0, 95% CI 1.57-10.3; p = 0.004), phonophobia (OR 3.12, 95% CI 1.16-8.4; p = 0.025), and osmophobia (OR 3.45, 95% CI 1.01-11.8; p = 0.048). AEs were observed in seven subjects in both groups, with arm pain being the most common. No serious AE was reported. CONCLUSION: This study did not meet the primary endpoint but showed pain relief and elimination of several associated symptoms within 2 h on repeated-measures analysis. Although limited by small sample size and high placebo response, our results indicate that IV ibuprofen may be a safe and effective option for acute treatment of migraine, but more extensive studies are necessary.

Prospective Evaluation of Surgical and Anesthetic Technique of Carpal Tunnel Release in an Orthopedic Practice.

PURPOSE: The goal of this study was to determine whether the type of anesthesia (monitored anesthesia care [MAC] vs wide-awake local anesthesia no tourniquet technique [WALANT]) or the surgical technique (mini-open vs endoscopic) would affect patient satisfaction with postoperative pain control, postoperative pain, or opioid use after carpal tunnel release (CTR). The hypothesis was that endoscopic and open CTR surgery would have the same patient satisfaction with postoperative pain control, postoperative pain, and opioid use, but WALANT surgery would have higher patient satisfaction with postoperative pain control, postoperative pain, and opioid use than MAC. METHODS: This prospective study examined all patients undergoing carpal tunnel surgery by 4 hand surgeons at our institution. Two surgeons perform primarily 1-incision endoscopic CTR and the other 2 perform mini-open CTR. Two surgeons perform all procedures under WALANT; the other 2 employ MAC with a local anesthetic. Postsurgical questionnaires were completed at the 2-week postoperative visit. Patients reported remaining pills, average pain, highest pain, lowest pain, and overall satisfaction with postoperative pain control. RESULTS: A total of 93 patients underwent CTR by the 4 participating hand surgeons. Of these, 43 underwent open CTR and 50 underwent endoscopic CTR. Sixty-two were performed under MAC and 31 with WALANT. With regard to anesthesia type, overall there was 5.5 mean morphine equivalents (MME) less prescribed and an average of 3.6 MME more remaining on the first postoperative visit with WALANT compared with MAC. Patient satisfaction with postoperative pain control was an average score of 7.9 for MAC and 7.4 for WALANT. With regard to surgical technique, overall, there was 15.2 MME less prescribed and an average of 1.03 MME more remaining on the first postoperative visit with endoscopic CTR compared with open CTR. Patient satisfaction with postoperative pain control between endoscopic and open release demonstrated an average score of 7.1 and 8.0, respectively. CONCLUSIONS: This study demonstrates minimal differences in opioid pain medication use, patient satisfaction with postoperative pain control, and pain scores in a comparison of surgical technique as well as anesthesia type. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

The Association of Opioid Utilization and Patient Satisfaction Following Outpatient Orthopaedic Surgery: More May Not Be Better.

Postoperative analgesia remains an important area of research in orthopaedics. There remains a lack of information on the complex interplay between opioid utilization postoperatively, pain and patient satisfaction. This study aims to describe the relationship between opioid utilization, postoperative pain, and patient satisfaction following outpatient orthopaedic surgery in a multispecialty orthopaedic practice. As a part of an ongoing quality control project at our institution patients were instructed to monitor utilization of postoperative opioids. The results of a convenience sample of 139 patients representing a 53% response rate among eligible patients that completed the survey following outpatient orthopaedic surgery are reported. Among patients undergoing outpatient orthopaedic surgery, there was no clinically significant association between opioid utilization and patient satisfaction. This association appeared largely independent of the patient's actual pain. While lower pain scores were associated with increasing patient satisfaction, this appeared to be independent of opioid utilization. (Journal of Surgical Orthopaedic Advances 29(2):88-93, 2020).

Comparing Fourth Generation Statistical Iterative Reconstruction Technique to Standard Filtered Back Projection in Pediatric Head Computed Tomography Examinations.

OBJECTIVE: Although advanced statistical iterative reconstruction (IR) techniques are valued in pediatric computed tomography (CT) imaging, there is little published data on how these techniques affect image quality and radiation dose in the pediatric population. This is particularly true in the context of pediatric head CT examinations. This study analyzed the differences in image quality and several standard metrics of radiation dose on multidetector pediatric head CT examinations performed using standard filtered back projection (FBP) with reconstructions using iDose, a fourth-generation statistical iterative reconstruction technique. MATERIALS AND METHODS: Using a retrospective review of 282 pediatric head CT examinations, we compared how iDose fared against FBP for effects on several standard metrics of radiation dose and qualitative and quantitative assessment of image quality. RESULTS: Our assessment revealed that examinations obtained using low-dose protocols reconstructed using iDose, when compared with standard-dose examinations reconstructed using FBP, resulted in significant radiation dose reduction while performing equally or better in quantitative image quality parameters. For most qualitative image quality parameters, the iDose group demonstrated equal performance to standard filtered back technique with a few notable exceptions. In the parameter of image sharpness in the 1.5 to 7 year olds, iDose fared better than FBP. However, FBP outperformed iDose in the qualitative parameters of decreased image graininess/noise in patients older than 13 years, improved image sharpness in patients aged between 7 and 13 years, and improved visibility of small parts for those aged 7 to 13 years. CONCLUSIONS: We conclude that iDose is effective at allowing significant radiation dose reduction while maintaining or, rarely, even improving quantitative image quality compared with FBP in the setting of pediatric head CT examinations. However, for certain qualitative image quality parameters in older-aged children, the use of iDose resulted in a poorer performance compared with FBP.

Gender differences in substance use and psychiatric distress among medical students: A comprehensive statewide evaluation.

BACKGROUND: Medical student wellness has emerged as an important issue in medical education. The purpose of the present study was to obtain a comprehensive assessment of substance use, psychological distress, and help-seeking among male and female medical students in order to identify targets for continued intervention efforts. METHODS: Medical students from all 9 medical schools in the state of Florida were invited via e-mail and/or announcements to complete an anonymous online questionnaire assessing their well-being. Of 5053 matriculating medical students, 1137 (57.1% female) responded to the questionnaire. Descriptive statistics, t tests, and chi-square analyses were computed using SPSS 20. RESULTS: Over 70% of students acknowledged binge drinking, with men reporting higher frequency than women (χ2 = 13.90, P = .003), and 22.7% (n = 201) reported marijuana use during medical school, with higher rates (χ2 = 9.50, P = .02) among men (27.0%, n = 99) than women (18.9%, n = 93). A significant minority of students reported nonmedical use of prescription stimulants and prescription opioids. In addition, 3.3% of male students (n = 12) compared with 0.6% of female students (n = 3) reported problematic drug use. Further, almost 2/3 of respondents reported decreased psychological health since beginning medical school, with women noting greater reductions (χ2 = 12.39, P = .05) and higher levels of stress (χ2 = 16.30, P = .003). Over 10% of students (n = 102) endorsed "thoughts of committing suicide" during medical school, and 70.1% felt they would benefit from mental healthcare (79.3% of women vs. 59.6% of men; χ2 = 41.94, P < .001), although only 39.8% accessed help. CONCLUSIONS: Despite efforts to address medical student wellness, students continue to report concerning levels of psychological distress, suicidal ideation, and substance use. More work is needed to effectively address medical student mental health and well-being.

Hospital variation in cesarean delivery rates: contribution of individual and hospital factors in Florida.

BACKGROUND: Primary cesarean deliveries are a major contributor to the large increase in cesarean delivery rates in the United States over the past 2 decades and are an essential focus for the reduction of related morbidity and costs. Studies have shown that primary cesarean delivery rates among low-risk women in the United States vary 3-fold across hospitals and are not explained by differences in patient case-mix. However, the extent to which maternal vs hospital characteristics contribute to this variation remains poorly understood because previous studies were limited in scope and did not assess the influence of factors such as maternal ethnicity subgroups or prepregnancy obesity. OBJECTIVE: We assessed the contribution of individual- and hospital-level risk factors to the hospital variation in primary cesarean delivery rates among low-risk women in Florida. STUDY DESIGN: Our population-based retrospective cohort study used Florida's linked birth certificate and hospital discharge records for the period of 2004-2011. The study population was comprised of 412,192 nulliparous, singleton, vertex, live births with labor at 37-40 weeks gestation in 122 nonmilitary delivery hospitals. Data were analyzed with logistic mixed-effects regression with cesarean delivery as the outcome. This approach provided adjusted risk estimates at an individual and hospital level and the estimated percent of hospital variation statewide that was explained by these factors. RESULTS: The primary cesarean delivery rate in the study population was 23.9%, with hospital-specific estimates that ranged from 12.8-47.3%. Leading risk factors for cesarean delivery were maternal age ≥35 years (adjusted relative risk, 2.22), prepregnancy obesity (body mass index, ≥30 kg/m(2); adjusted relative risk, 1.73), medical risk conditions (adjusted relative risk, 1.72), labor induction (adjusted relative risk, 1.52), and delivery in hospitals located in Miami-Dade County (adjusted relative risk, 1.73). Hospital geographic location was a significant effect modifier for prepregnancy obesity, medical conditions, and labor induction (P < .05), with a tendency towards lower adjusted relative risks for these factors in Miami-Dade County relative to other Florida regions. Conversely, Miami-Dade County had an increased prevalence of higher-risk ethnic subgroups, such as Cuban or Puerto Rican mothers, and also substantially higher adjusted relative risks that were associated with practice-related factors, such as delivery during weekday hours. Whereas hospital geographic location contributed to 39.6% of the observed variation statewide, the estimated contribution of maternal ethnicity ranged from 1.6-15.7% among Florida regions. CONCLUSIONS: Hospital geographic location contributes to hospital variation in primary cesarean delivery rates among low-risk women in Florida. In contrast to previous studies, our findings suggest that individual level risk factors such as maternal ethnicity also contribute to some of this variation, with differing extent by region. These individual factors likely interact with practice factors and add to the variation. This study was limited by not including maternal Bishop score before induction or obstetrics provider in the analysis. These were not available on the dataset but likely contribute to the variation. Our findings suggest potential issues to consider in quality improvement efforts, such as the need for future qualitative research that focuses on mothers in higher-risk ethnic subgroups and providers in high-rate hospitals, particularly those in Miami-Dade County. These studies may help to identify potential cultural differences in maternal beliefs and expectations for delivery and maternal reasons for differences in obstetrics practices.

The Obstetric Hemorrhage Initiative (OHI) in Florida: The Role of Intervention Characteristics in Influencing Implementation Experiences among Multidisciplinary Hospital Staff.

Objectives Obstetric hemorrhage is one of the leading causes of maternal mortality. The Florida Perinatal Quality Collaborative coordinates a state-wide Obstetric Hemorrhage Initiative (OHI) to assist hospitals in implementing best practices related to this preventable condition. This study examined intervention characteristics that influenced the OHI implementation experiences among Florida hospitals. Methods Purposive sampling was employed to recruit diverse hospitals and multidisciplinary staff members. A semi-structured interview guide was developed based on the following constructs from the intervention characteristics domain of the Consolidated Framework for Implementation Research: evidence strength; complexity; adaptability; and packaging. Interviews were audio-recorded, transcribed and analyzed using Atlas.ti. Results Participants (n = 50) across 12 hospitals agreed that OHI is evidence-based and supported by various information sources (scientific literature, experience, and other epidemiologic or quality improvement data). Participants believed the OHI was 'average' in complexity, with variation depending on participant's role and intervention component. Participants discussed how the OHI is flexible and can be easily adapted and integrated into different hospital settings, policies and resources. The packaging was also found to be valuable in providing materials and supports (e.g., toolkit; webinars; forms; technical assistance) that assisted implementation across activities. Conclusions for Practice Participants reflected positively with regards to the evidence strength, adaptability, and packaging of the OHI. However, the complexity of the initiative adversely affected implementation experiences and required additional efforts to maximize the initiative effectiveness. Findings will inform future efforts to facilitate implementation experiences of evidence-based practices for hemorrhage prevention, ultimately decreasing maternal morbidity and mortality.

Pediatric schwannomatosis, a rare but distinct form of neurofibromatosis.

Schwannomatosis is the third major form of neurofibromatosis, distinct from neurofibromatosis type 2 (NF2) and type 1 (NF1). This condition is rare with a variable phenotypic presentation and complex molecular and genetic findings. In this case, a previously healthy teenager was found to have multiple spinal lesions and an enhancing right parotid mass on MRI. On extensive further work-up, this patient met the existing clinical criteria for schwannomatosis. This case report aims to review the clinical features and current diagnostic criteria for schwannomatosis and compare it to NF1 and NF2. Special emphasis will be placed on imaging features that should prompt the radiologist to suggest this rare diagnosis.

Infant and maternal characteristics in neonatal abstinence syndrome--selected hospitals in Florida, 2010-2011.

Neonatal abstinence syndrome (NAS) is a constellation of physiologic and neurobehavioral signs exhibited by newborns exposed to addictive prescription or illicit drugs taken by a mother during pregnancy. The number of hospital discharges of newborns diagnosed with NAS has increased more than 10-fold (from 0.4 to 4.4 discharges per 1,000 live births) in Florida since 1995, far exceeding the three-fold increase observed nationally. In February 2014, the Florida Department of Health requested the assistance of CDC to 1) assess the accuracy and validity of using Florida's hospital inpatient discharge data, linked to birth and infant death certificates, as a means of NAS surveillance and 2) describe the characteristics of infants with NAS and their mothers. This report focuses only on objective two, describing maternal and infant characteristics in the 242 confirmed NAS cases identified in three Florida hospitals during a 2-year period (2010-2011). Infants with NAS experienced serious medical complications, with 97.1% being admitted to an intensive care unit, and had prolonged hospital stays, with a mean duration of 26.1 days. The findings of this investigation underscore the important public health problem of NAS and add to current knowledge on the characteristics of these mothers and infants. Effective June 2014, NAS is now a mandatory reportable condition in Florida. Interventions are also needed to 1) increase the number and use of community resources available to drug-abusing and drug-dependent women of reproductive age, 2) improve drug addiction counseling and rehabilitation referral and documentation policies, and 3) link women to these resources before or earlier in pregnancy.

Serological Surveillance of Wild Waterfowl in Northern Australia for Avian Influenza Virus Shows Variations in Prevalence and a Cyclical Periodicity of Infection.

The virological surveillance of 3582 wild waterfowl in northern Australia from 2004 to 2009 for avian influenza virus (AIV) found an apparent prevalence (AP) of 1% (31 of 2989 cloacal swabs; 95% CI: 0.71%-1.47%) using a Taqman Type A real-time reverse transcription polymerase chain reaction test and no viral isolations from 593 swabs tested by the embryonating chicken egg culture method. From serological testing using a nucleoprotein competitive enzyme-linked immunosorbent assay for AIV antibody, 1131 of 3645 sera had ≥ 40% inhibition, indicating an apparent seroprevalence of 31% (95% CI: 29.5%-32.6%). This value suggests that the low AP from virological testing does not reflect the dynamics of AIV infection in these populations. Spatiotemporal and species variations in seroprevalence were found at wetland sampling sites, with consistently higher values at Kununurra in Western Australia (AP  =  39%, 95% CI: 36.9%-41.4%) compared to other locations. At Kununurra, seroprevalence values had a two-year cyclical periodicity and suggest this location is a hotspot of AIV activity. From hemagglutination inhibition (HI) testing using multiple subtype antigens, the highest AP of HI reactions were to H6 and H5 subtypes. The phenomenon of cyclic periodicity in NP seroprevalence at Kununurra is hypothesized as being related to the prevalent H6 subtype that may have either become predominant or cycled back into a mostly AIV naïve flock. The inclusion of serological testing provided insight into the dynamics of AIV infection in wild birds such as species risk profiles and spatiotemporal patterns, important epidemiological information for a risk-based approach to surveillance.

Advanced urothelial carcinoma: next-generation sequencing reveals diverse genomic alterations and targets of therapy.

Although urothelial carcinoma (UC) of the urinary bladder generally portends a favorable prognosis, metastatic tumors often follow an aggressive clinical course. DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded (FFPE) sections from 35 stage IV UCs that had relapsed and progressed after primary surgery and conventional chemotherapy. Next-generation sequencing (NGS) was performed on hybridization-captured, adaptor ligation-based libraries for 3320 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer to at an average sequencing depth of 1164 × and evaluated for all classes of genomic alterations (GAs). Actionable GAs were defined as those impacting the selection of targeted anticancer therapies on the market or in registered clinical trials. A total of 139 GAs were identified, with an average of 4.0 GAs per tumor (range 0-10), of which 78 (56%) were considered actionable, with an average of 2.2 per tumor (range 0-7). Twenty-nine (83%) cases harbored at least one actionable GA including: PIK3CA (9 cases; 26%); CDKN2A/B (8 cases; 23%); CCND1 (5 cases; 14%); FGFR1 (5 cases; 14%); CCND3 (4 cases; 11%); FGFR3 (4 cases; 11%); MCL1 (4 cases; 11%); MDM2 (4 cases; 11%); EGFR (2 cases, 6%); ERBB2 (HER2/neu) (2 cases, 6%); NF1 (2 cases, 6%) and TSC1 (2 cases, 6%). Notable additional alterations included TP53 (19 cases, 54%) and RB1 (6 cases; 17%). Genes involved in chromatin modification were altered by nonsense mutation, splice site mutation or frameshift indel in a mutually exclusive manner in nearly half of all cases including KDM6A (10 cases; 29%) and ARID1A (7 cases; 20%). Comprehensive NGS of 35 UCs of the bladder revealed a diverse spectrum of actionable GAs in 83% of cases, which has the potential to inform treatment decisions for patients with relapsed and metastatic disease.

Surveillance of Charadriiformes in northern Australia shows species variations in exposure to avian influenza virus and suggests negligible virus prevalence.

The virologic surveillance of 4248 Charadriiformes since 1992 primarily from coastal northwest Australia did not detect any evidence of avian influenza virus (AIV) excretion (test prevalence = 0%; 95% confidence interval [CI]: 0%-0.09%). Past exposure to AIV was evident from serologic testing using nucleoprotein (NP) competitive-ELISA (c-ELISA) with an overall seroprevalence of 8.8% (95% CI: 8%-9.7%). The c-ELISA seroprevalence of family Scolopacidae and genus Numenius was significantly higher when compared with other families and genera, respectively. Exposure risk profiles, based on c-ELISA seroprevalence, were compiled for 40 species with the following species having significantly higher values when compared with the combined value of all other species: eastern curlew (Numenius madagascariensis), whimbrel (Numenius phaeopus), ruddy turnstone (Arenaria interpres), grey plover (Pluvialis squatarola), little curlew (Numenius minutus), red knot (Calidris canutus), sharp-tailed sandpiper (Calidris acuminata), and red-necked stint (Calidris ruficollis). From hemagglutination inhibition (HI) testing, the more prevalent HI reactions were against H2, H5, H6, and H9 subtypes, with no reactions against subtypes H11, H14, H15, and H16. Serologic testing using c-ELISA provided species risk profiles for optimizing a surveillance strategy for AIV in diverse populations of wild birds. The paucity of knowledge about the role of waders in the ecology of AIV and the overall very low to negligible virus prevalence reported globally, and in this study, suggests that waders are spillover hosts in shared ecosystems with a lesser role than previously considered.

Evaluation of avian influenza serologic and virologic diagnostic methods in wild Anseriformes and Charadriiformes.

Evaluation of avian influenza virus (AIV) diagnostic methods, including a nucleoprotein (NP) competitive enzyme-linked immunosorbent assay (c-ELISA), hemagglutination inhibition (HI) test, type A real-time reverse transcription polymerase chain reaction (RRT-PCR), and embryonating chicken egg (ECE) virus isolation (VI), suggested validity of these tests in wild birds comparable to that reported in poultry. This was determined by analyzing the results from experimental inoculation of three species of wild birds with a low-pathogenicity AIV and from field surveillance data. The NP c-ELISA in a high-AIV prevalence setting had 100% diagnostic sensitivity (Se; 95% confidence interval [CI]: 81.5%-100%) and 91% diagnostic specificity (Sp; 95% CI: 70.8%-98.9%) in negative controls compared with the RRT-PCR. In low-AIV prevalence flocks using a > 60% inhibition positivity threshold, relative to the HI test, c-ELISA performed with 90.5% Se (95% CI: 86.2%-93.8%) and 41.2% Sp (95% CI: 38.1%-44.5%). Assessment of HI suggests a titer > or = 8 is a positive test result in wild-bird sera, and using this titer had 83.3% Se (95% CI: 58.6%-96.4%) in experimentally infected birds. The RRT-PCR diagnostic performance compared with VI in cloacal swabs varied over 2-6 days postinoculation, having high Se (83.3%-100%) and Sp (94.1%-100%) with substantial agreement (kappa = 0.8). The cycle thresholds (C(t)) for the RRT-PCR of C(t) < 37 for positivity and C(t) = 37-40 as indeterminate were found to be valid for the species included in this study. In view of the interpretative diagnostic difficulties in heterogeneous populations of wild birds, this evaluation in three species of wild birds and in surveillance data should provide greater confidence in the application of these methods routinely used in poultry.

Maternal and hospital characteristics of non-medically indicated deliveries prior to 39 weeks.

Non-medically indicated (NMI) deliveries prior to 39 weeks increase the risk of neonatal mortality, excess morbidity, and health care costs. The study's purpose was to identify maternal and hospital characteristics associated with NMI deliveries prior to 39 weeks. The study included 207,775 births to women without a previous cesarean and 38,316 births to women with a previous cesarean, using data from Florida's 2006-2007 linked birth certificate and inpatient record file. Adjusted risk ratios (ARR) and 95 % confidence intervals (CI) for characteristics were calculated using generalized estimating equation for multinomial logistic regression. Among women without a previous cesarean, NMI deliveries occurred in 18,368 births (8.8 %). Non-medically indicated inductions were more likely in women who were non-Hispanic white (ARR: 1.41, 95 % CI 1.31-1.52), privately-insured (ARR: 1.42, 95 % CI 1.26-1.59), and delivered in hospitals with <500 births per year. Non-medically indicated primary cesareans were more likely in women who were older than 35 years (ARR: 2.96, 95 % CI 2.51-3.50), non-Hispanic white (ARR: 1.44, 95 % CI 1.30-1.59), and privately-insured (ARR: 1.43, 95 % CI 1.17-1.73). Non-medically indicated primary cesareans were also more likely to occur in hospitals with <30 % nurse-midwife births, <500 births per year, and in large metro areas. Among women with previous cesarean, NMI repeat cesareans occurred in 16,746 births (43.7 %). Only weak risk factors were identified for NMI repeat cesareans. The risk factors identified varied by NMI outcome. This information can be used to inform educational campaigns and identify hospitals that may benefit from quality improvement efforts.

Evaluation of a cadaveric wrist motion simulator using marker-based X-ray reconstruction of moving morphology.

Surgical intervention is a common option for the treatment of wrist joint arthritis and traumatic wrist injury. Whether this surgery is arthrodesis or a motion preserving procedure such as arthroplasty, wrist joint biomechanics are inevitably altered. To evaluate effects of surgery on parameters such as range of motion, efficiency and carpal kinematics, repeatable and controlled motion of cadaveric specimens is required. This study describes the development of a device that enables cadaveric wrist motion to be simulated before and after motion preserving surgery in a highly controlled manner. The simulator achieves joint motion through the application of predetermined displacements to the five major tendons of the wrist, and records tendon forces. A pilot experiment using six wrists aimed to evaluate its accuracy and reproducibility. Biplanar X-ray videoradiography (BPVR) and X-Ray Reconstruction of Moving Morphology (XROMM) were used to measure overall wrist angles before and after total wrist arthroplasty. The simulator was able to produce flexion, extension, radioulnar deviation, dart thrower's motion and circumduction within previously reported functional ranges of motion. Pre- and post-surgical wrist angles did not significantly differ. Intra-specimen motion trials were repeatable; root mean square errors between individual trials and average wrist angle and tendon force profiles were below 1° and 2 N respectively. Inter-specimen variation was higher, likely due to anatomical variation and lack of wrist position feedback. In conclusion, combining repeatable intra-specimen cadaveric motion simulation with BPVR and XROMM can be used to determine potential effects of motion preserving surgeries on wrist range of motion and biomechanics.

Procrustes is a machine-learning approach that removes cross-platform batch effects from clinical RNA sequencing data.

With the increased use of gene expression profiling for personalized oncology, optimized RNA sequencing (RNA-seq) protocols and algorithms are necessary to provide comparable expression measurements between exome capture (EC)-based and poly-A RNA-seq. Here, we developed and optimized an EC-based protocol for processing formalin-fixed, paraffin-embedded samples and a machine-learning algorithm, Procrustes, to overcome batch effects across RNA-seq data obtained using different sample preparation protocols like EC-based or poly-A RNA-seq protocols. Applying Procrustes to samples processed using EC and poly-A RNA-seq protocols showed the expression of 61% of genes (N = 20,062) to correlate across both protocols (concordance correlation coefficient > 0.8, versus 26% before transformation by Procrustes), including 84% of cancer-specific and cancer microenvironment-related genes (versus 36% before applying Procrustes; N = 1,438). Benchmarking analyses also showed Procrustes to outperform other batch correction methods. Finally, we showed that Procrustes can project RNA-seq data for a single sample to a larger cohort of RNA-seq data. Future application of Procrustes will enable direct gene expression analysis for single tumor samples to support gene expression-based treatment decisions.