Vitamin D in pregnancy: Where we are and where we should go.

Vitamin D deficiency has been widely reported among pregnant women and infants around the world. Women with low sun exposure, high BMI, low vitamin D intakes and socioeconomic disadvantage with poor quality diets are at greatest risk of vitamin D deficiency, leading to very low serum concentrations of 25-hydroxyvitamin D (25(OH)D) in their offspring and an increased risk of nutritional rickets. Many observational studies, supported by compelling in vitro and in vivo data, have generated evidence suggesting that low vitamin D status in pregnancy may also contribute to the risk of adverse perinatal outcomes including hypertensive disorders (e.g., preeclampsia), fetal growth restriction, and preterm birth. However, the few large randomized controlled trials (RCTs) conducted to date have generated conflicting evidence for a role of vitamin D supplementation in improving perinatal outcomes. Vitamin D supplementation policies during pregnancy and implementation of policies vary within and between jurisdictions. Regulatory authorities have cited insufficient evidence to establish pregnancy-specific targets for serum 25(OH)D concentrations or prenatal vitamin D intake that effectively reduce the risks of adverse perinatal and infant outcomes. This paper arises from a Debate on Vitamin D Requirements during Pregnancy, held at the 22nd Vitamin D Workshop, 2019. From varied perspectives, our objectives were to evaluate the evidence for: vitamin D metabolism in pregnancy and the prevalence of gestational vitamin D deficiency worldwide; the translation of laboratory research findings to clinical studies on the role of vitamin D in perinatal health; the challenges of designing and conducting clinical trials to establish prenatal vitamin D requirements; and results to date of major large RCTs of prenatal vitamin D supplementation. Lastly, we explored potential next steps towards generating robust clinical data in this field to address both public health protection and patient care.

Comparison of routine field epidemiology and whole genome sequencing to identify tuberculosis transmission in a remote setting.

Yukon Territory (YT) is a remote region in northern Canada with ongoing spread of tuberculosis (TB). To explore the utility of whole genome sequencing (WGS) for TB surveillance and monitoring in a setting with detailed contact tracing and interview data, we used a mixed-methods approach. Our analysis included all culture-confirmed cases in YT (2005-2014) and incorporated data from 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping, WGS and contact tracing. We compared field-based (contact investigation (CI) data + MIRU-VNTR) and genomic-based (WGS + MIRU-VNTR + basic case data) investigations to identify the most likely source of each person's TB and assessed the knowledge, attitudes and practices of programme personnel around genotyping and genomics using online, multiple-choice surveys (n = 4) and an in-person group interview (n = 5). Field- and genomics-based approaches agreed for 26 of 32 (81%) cases on likely location of TB acquisition. There was less agreement in the identification of specific source cases (13/22 or 59% of cases). Single-locus MIRU-VNTR variants and limited genetic diversity complicated the analysis. Qualitative data indicated that participants viewed genomic epidemiology as a useful tool to streamline investigations, particularly in differentiating latent TB reactivation from the recent transmission. Based on this, genomic data could be used to enhance CIs, focus resources, target interventions and aid in TB programme evaluation.

Whole genome sequencing for improved understanding of Mycobacterium tuberculosis transmission in a remote circumpolar region.

Few studies have used genomic epidemiology to understand tuberculosis (TB) transmission in rural and remote settings - regions often unique in history, geography and demographics. To improve our understanding of TB transmission dynamics in Yukon Territory (YT), a circumpolar Canadian territory, we conducted a retrospective analysis in which we combined epidemiological data collected through routine contact investigations with clinical and laboratory results. Mycobacterium tuberculosis isolates from all culture-confirmed TB cases in YT (2005-2014) were genotyped using 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) and compared to each other and to those from the neighbouring province of British Columbia (BC). Whole genome sequencing (WGS) of genotypically clustered isolates revealed three sustained transmission networks within YT, two of which also involved BC isolates. While each network had distinct characteristics, all had at least one individual acting as the probable source of three or more culture-positive cases. Overall, WGS revealed that TB transmission dynamics in YT are distinct from patterns of spread in other, more remote Northern Canadian regions, and that the combination of WGS and epidemiological data can provide actionable information to local public health teams.

Do pediatricians routinely perform genitourinary examinations during well-child visits? A review from a large tertiary pediatric hospital.

BACKGROUND: The male genital examination is a common source of discomfort for the patient and medical provider. Performance of male genital examination is imperative; however, as many treatable diagnoses can be made. Undescended testicles (UDTs), hernias, testicular tumors, and urethral abnormalities are all potentially concerning findings which can be discovered on routine examination. OBJECTIVE: The objectives of this study are to determine the rate at which general pediatricians perform routine genitourinary (GU) examinations in the pediatric population and to determine the rate at which UDT are diagnosed or documented in the patient's history. The authors hypothesize the rate of pediatric GU examination during routine well-child visits to be in line with the previously reported rates in the adult literature. STUDY DESIGN: Nine hundred ninety-six consecutive male well-child visits conducted by general pediatricians at the study institution were reviewed. These visits were evaluated for documentation of a detailed GU examination as well as the presence of UDT from these examinations. In addition, past medical and surgical histories were reviewed to determine if a diagnosis of UDT was noted. RESULTS: Pediatricians at the study institution documented GU examinations 99.1% of the time during male well-child visits. Only 1.1% of the cohort had a documentation of UDT at any time point. Of the 11 patients with UDT, 6 boys (54.5%) had spontaneous descent with no referral to urology, whereas 5 (45.5%) required orchidopexy. DISCUSSION: Prior reports suggest 70-75% of routine office visits include a genital examination. None of these reports reviewed the pediatric population, thus making this review novel in this respect. In addition, the results are vastly different from these prior studies as the authors demonstrated over 99% of male well-child examinations included documentation of a thorough genital examination. A limitation of the study is its retrospective nature, which creates a lack of standardization across the data set. In addition, without being physically present in the examination room, one cannot discern whether an examination is simply being documented without actual performance because of the template format of the electronic medical record (EMR). Furthermore, the study was not designed to best evaluate the true rate of UDTs; therefore, the reported rate of 1.1% cannot be accurately associated with a particular age at diagnosis. CONCLUSIONS: Pediatricians do, in fact, document GU examinations on a routine basis. This finding cannot be taken with complete certainty as verification of actual examination performance is impractical. While the data demonstrated a lower than expected rate of UDT, depending upon age at diagnosis, this could indicate that although examinations are being documented, their accuracy may be diminished because of various factors at play in the healthcare system as a whole, including improper exam performance and EMR templates. Follow-up studies are required to verify these potentially changing rates of UDT and to determine if there is discordance between documentation and performance of GU examinations.

Outcome of fetuses with lower urinary tract obstruction and normal amniotic fluid volume in second trimester of pregnancy.

OBJECTIVE: Congenital lower urinary tract obstruction (LUTO) is a rare condition with high perinatal mortality and morbidity when associated with severe oligohydramnios or anhydramnios in the second trimester of pregnancy. Severe pulmonary hypoplasia and end-stage renal disease are the underlying causes of poor neonatal outcome in these cases. However, little is known about the subset of fetal LUTO that is associated with a normal volume of amniotic fluid at midgestation. The objective of the current study was to describe the natural history, underlying causes, survival and postnatal renal function outcomes in pregnancies with fetal LUTO and normal amniotic fluid volume during the second trimester of pregnancy. METHODS: This was a retrospective study of all pregnancies with fetal LUTO and normal amniotic fluid volume in the second trimester that received prenatal and postnatal care at our quaternary care institution between 2013 and 2017. Data on demographic characteristics, fetal interventions, perinatal survival, need for neonatal respiratory support, postnatal renal function and need for dialysis at the age of 1 and 24 months were analyzed. RESULTS: Of the 18 fetuses that met the study criteria, 17 (94.4%) survived the perinatal period. Eleven (61.1%) pregnancies developed oligohydramnios in the third trimester, six of which were eligible for and underwent fetal intervention with vesicoamniotic shunt placement, which was performed successfully in all six cases. Two (11.1%) neonates required respiratory support owing to pulmonary hypoplasia. At the age of 2 years, 14 children had follow-up information available, two (14.3%) of whom had normal renal function, eight (57.1%) had developed some degree of chronic kidney disease (Stage 1-4) and four (28.6%) had developed end-stage renal disease (ESRD), including two who had already manifested ESRD in the neonatal period. CONCLUSIONS: Most fetuses diagnosed prenatally with LUTO that is associated with a normal volume of amniotic fluid at midgestation will have a favorable outcome in terms of perinatal survival and few will need long-term respiratory support. However, these children are still at increased risk for chronic renal disease, ESRD and need for renal replacement therapy. Larger multicenter studies are needed to characterize the prenatal factors associated with postnatal renal function, and to investigate the role of fetal intervention in the group of fetuses that present with late-onset oligohydramnios and evidence of preserved fetal renal function. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Behavior of major and trace elements in a transient surface water/groundwater system following removal of a long-term wastewater treatment facility source.

In many aquatic environments, municipal wastewater treatment facility (WWTF) effluent discharges influence local hydrologic and chemical connectivity between the surface-water and adjacent alluvial shallow-groundwater systems. Fourmile Creek located in Polk County, Iowa received effluent from the Ankeny WWTF for nearly forty years before it was shut down in November 2013. The decommissioning of the municipal WWTF provided a unique opportunity to characterize the recovery from impacts of treated wastewater discharge on water quality at the surface-water/groundwater interface in a shallow, unconfined alluvial aquifer. Dissolved major element and trace element concentrations in Fourmile Creek surface water, hyporheic-zone water, and shallow, unconfined groundwater were monitored upstream and downstream from the WWTF discharge before and after the shutdown. Multivariate statistical techniques including principal component analysis (PCA) and agglomerative hierarchical clustering (AHC) were used to differentiate source-water contributions, characterize elemental components, and describe surface-water/groundwater interaction dynamics. During the post-closure assessment, there was subsurface attenuation of wastewater constituents including Al, B, Cu, Gd, K, Mo, Na, P, Pb, Sb, and Zn. During the same time, groundwater concentrations increased for As, Ba, Ca, Fe, Mg, Mn, SiO2, Sr, and U and represented a profile characteristic of the shallow alluvial aquifer. Hydrologic conditions transitioned from predominantly wastewater infiltration and hyporheic exchange before the WWTF shutdown, to predominantly discharge of native groundwater. Precipitation-driven streamflow events created fluctuations in the groundwater water-table elevations, resulting in variable contact between the saturated and unsaturated zones within the unconfined, alluvial aquifer and intermittent exposure to constituents stored in the sediments. The inorganic fingerprint of municipal wastewater was flushed relatively quickly (≤19 weeks) from the hyporheic zone indicating that processes like diffusion or sorption/desorption that might extend recovery may not be important for many trace elements in this system.

Bedside tests for predicting difficult airways: an abridged Cochrane diagnostic test accuracy systematic review.

Although bedside screening tests are routinely used to identify people at high risk of having a difficult airway, their clinical utility is unclear. We estimated the diagnostic accuracy of commonly used bedside examination tests for assessing the airway in adult patients without apparent anatomical abnormalities scheduled to undergo general anaesthesia. We searched for studies that reported our pre-specified bedside index screening tests against a reference standard, published in any language, from date of inception to 16 December 2016, in seven bibliographic databases. We included 133 studies (127 cohort type and 6 case-control) involving 844,206 participants. Overall, their methodological quality (according to QUADAS-2, a standard tool for assessing quality of diagnostic accuracy studies) was moderate to high. Our pre-specified tests were: the Mallampati test (6 studies); modified Mallampati test (105 studies); Wilson risk score (6 studies); thyromental distance (52 studies); sternomental distance (18 studies); mouth opening test (34 studies); and the upper lip bite test (30 studies). Difficult facemask ventilation, difficult laryngoscopy, difficult intubation and failed intubation were the reference standards in seven, 92, 50 and two studies, respectively. Across all reference standards, we found all index tests had relatively low sensitivities, with high variability, but specificities were consistently and markedly higher than sensitivities. For difficult laryngoscopy, the sensitivity and specificity (95%CI) of the upper lip bite test were 0.67 (0.45-0.83) and 0.92 (0.86-0.95), respectively; upper lip bite test sensitivity (95%CI) was significantly higher than that for the mouth opening test (0.22, 0.13-0.33; p < 0.001). For difficult tracheal intubation, the modified Mallampati test had a significantly higher sensitivity (95%CI) at 0.51 (0.40-0.61) compared with mouth opening (0.27, 0.16-0.41; p < 0.001) and thyromental distance (0.24, 0.12-0.43; p < 0.001). Although the upper lip bite test showed the most favourable diagnostic test accuracy properties, none of the common bedside screening tests is well suited for detecting unanticipated difficult airways, as many of them are missed.

The changing gender landscape of pediatric urology fellowship: results from a survey of fellows and recent graduates.

INTRODUCTION: Women are entering the subspecialty of pediatric urology at an accelerated rate. Gender differences affecting fellowship and job selection have been identified in other fields of medicine. OBJECTIVE: The objective of this study was to understand gender differences in pediatric urology fellowship and job selection and how they may affect the workforce. STUDY DESIGN: A 47-question electronic survey consisting of questions regarding demographics, residency training, and factors influencing fellowship and job selection was distributed to current fellows and recent graduates in pediatric urology in May 2017. RESULTS: A total of 111 recent and current fellows were contacted, and 72% completed the survey (55% female [F] and 45% male [M]; 61% current fellows and 39% recent fellows). Respondents rated factors important in choosing pediatric urology on a scale of 1-5 (1, not important and 5, extremely important), and the top three for both genders were 1-working with children, 2-influential mentors, and 3-bread and butter cases such as inguinal orchiopexy. During residency, 93% of respondents reported having influential mentors in pediatric urology. However, mentorship was more important in fellowship choice for males than females (3.6 F, 4.1 M; P-value = 0.048), and 45% reported having only male mentors. Rating factors important in job choice on a scale of 1-5, respondents reported the top factors as 1-rapport with partners/mentorship (4.5), 2-geography/family preferences (4.3), and 3-participation in mentoring/teaching (3.8). Although most job selection criteria were rated similarly between genders, females rated call schedule higher than males (3.5 F, 2.9 M, P-value = 0.009). Although most females and males (79% of F, 78% of M, P-value = 0.868) sought primarily academic positions, a smaller proportion of females accepted academic positions (52% of F, 72% of M, P-value 0.26), and females reported lower satisfaction regarding the availability of jobs on a scale of 1-5 (1, very dissatisfied and 5, very satisfied; 3.1 F, 3.7 M; P-value = 0.034), particularly in academic positions (3.1 F, 3.7 M; P-value = 0.06). This difference was more pronounced in current fellows than recent graduates and may represent a worsening trend. CONCLUSION: Although significant gender differences in fellowship and job selection may exist in other fields, we found that women and men choose pediatric urology fellowships and jobs using similar criteria, which include work-life balance. Gender differences exist in the influence of mentors, indicating a need for more female mentors. While men and women sought similar types of jobs, women were less satisfied with the availability of jobs, particularly academic jobs, than men, which warrants further investigation.

Birth prevalence of hypospadias and hypospadias risk factors in newborn males in the United States from 1997 to 2012.

BACKGROUND: Hypospadias is a common genitourinary malformation and there are conflicting data on whether its prevalence is increasing. Previous studies have described associations with risk factors including small for gestational age (SGA), multiple gestation birth, environmental influences, and maternal factors. OBJECTIVE: The objective of this study was to examine birth prevalence of hypospadias and hypospadias risk factors in a large national dataset and to evaluate for changes from 1997 to 2012. We hypothesized that any increase in the birth prevalence of hypospadias would be associated with an increase in risk factors such as SGA, prematurity, or multiple gestation birth. STUDY DESIGN: The Kids' Inpatient Database was used to generate national estimates for prevalence of males born with hypospadias, SGA, prematurity, or to a multiple gestation and then prevalences were evaluated for association with time. Multivariable logistic regression was used to evaluate whether birth prevalence of hypospadias was associated with increasing year, SGA, prematurity, and multiple gestation birth. RESULTS: The estimated birth prevalence of hypospadias increased from 6.1 per 1000 births (95% confidence interval [CI] 5.9 to 6.3) to 6.8 per 1000 births (95% CI 6.7 to 7.0), an 11.5% increase from 1997-2012 (P = 0.014). Among male births, the prevalence of SGA increased 74%, multiple gestation increased 25%, and prematurity increased 20% (P < 0.001 for all) (Summary Figure). A risk factor was seen in around 20% of males born with hypospadias. Hypospadias birth prevalence also increased in males without risk factors but was not statistically significant (9.1% increase, P = 0.5). On multivariable logistic regression, being born SGA (odds ratio [OR] = 3.3), to a multiple gestation (OR = 1.1), or premature (OR 1.9) were associated with increased odds of hypospadias (P < 0.01 for all), whereas increasing year was not (P = 0.3). CONCLUSIONS: The estimated birth prevalence of hypospadias in the United States increased from 6.1 to 6.8 per 1000 births from 1997 to 2012. Known hypospadias risk factors of SGA birth, multiple gestation birth, and premature birth also increased over this time to a higher degree. About 20% of males born with hypospadias had one of these risk factors. The birth prevalence of hypospadias in males without any studied risk factors also increased, but this was not statistically significant. More studies are needed to evaluate whether this increase in hypospadias prevalence is due to increases in known hypospadias risk factors, new environmental exposures, improved diagnosis at birth, some combination, or unrelated causes.

Long-Term Training-Induced Gains of an Auditory Skill in School-Age Children As Compared With Adults.

The few studies that compared auditory skill learning between children and adults found variable results, with only some children reaching adult-like thresholds following training. The present study aimed to assess auditory skill learning in children as compared with adults during single- and multisession training. It was of interest to ascertain whether children who do not reach adult-like performance following a single training session simply require additional training, or whether different mechanisms underlying skill learning need to reach maturity in order to become adult-like performers. Forty children (7-9 years) and 45 young adults (18-35 years) trained in a single session. Of them, 20 children and 24 adults continued training for eight additional sessions. Each session included six frequency discrimination thresholds at 1000 Hz using adaptive forced-choice procedure. Retention of the learning-gains was tested 6 to 8 months posttraining. Results showed that (a) over half of the children presented similar performance and time course of learning as the adults. These children had better nonverbal reasoning and working memory abilities than their non-adult-like peers. (b) The best predicting factor for the outcomes of multisession training was a child's performance following one training session. (c) Performance gains were retained for all children with the non-adult-like children further improving, 6 to 8 months posttraining. Results suggest that mature auditory skill learning can emerge before puberty, provided that task-related cognitive mechanisms and task-specific sensory processing are already mature. Short-term training is sufficient, however, to reflect the maturity of these mechanisms, allowing the prediction of the efficiency of a prolonged training for a given child.

Comparing treatment modalities for transplant kidney vesicoureteral reflux in the pediatric population.

INTRODUCTION: Non-refluxing ureteral reimplantation is favored in pediatric renal transplantation to prevent complications, such as vesicoureteral reflux (VUR) in the transplant ureter. VUR resulting in febrile urinary tract infections remains a problem in this population, leading to repeated hospitalizations and increased morbidity. Revision of the vesicoureteral anastomosis can be a surgical challenge due to scar tissue and tenuous vascularity of the transplant ureter. Therefore, alternative options such as endoscopic injection of Deflux at the neo-orifice and surveillance with prophylactic antibiotics have emerged as potential treatment modalities for transplant ureter VUR. OBJECTIVE: The authors reviewed their experience of the management of VUR in the transplant ureter, comparing outcomes of various modalities. STUDY DESIGN: With Institutional Review Board approval, a retrospective chart review of all renal transplant patients from January 2002 to January 2017 was conducted. All patients with VUR on voiding cystourethrogram (VCUG) after surgery were identified. Indications for end-stage renal disease, urologic comorbidities, pretransplant VCUG, and operative details were recorded. After transplantation, febrile urinary tract infections, ultrasound findings, and any further interventions-surveillance, subureteral endoscopic injection of Deflux, or ureteral reimplantation-were documented along with their outcomes. RESULTS: Overall, VUR was identified in 35/285 (12.3%) transplant patients after a non-refluxing ureteroneocystostomy. VUR was managed with surveillance in 17/35 (49%), intravesical Deflux injection in 11/35 (31%), and immediate redo ureteral reimplantation in 7/35 (20%). Ten out of 11 patients undergoing Deflux injection had a postoperative VCUG. All patients developed VUR recurrence; the majority showed immediate failure and only 1/10 showed late recurrence. Of the immediate failures, 3/9 patients were maintained on prophylactic antibiotics, and 6/9 patients underwent ureteral reimplantation. In these six patients undergoing reimplantation after failed Deflux, 3/6 (50%) patients required additional surgeries: One patient developed recurrence of reflux and two patients developed ureterovesical junction obstruction. In contrast, no complications were seen in patients undergoing primary ureteral reimplantation. DISCUSSION: The study is limited by low numbers and a retrospective design. However, the results of this study differ significantly from the published Deflux series showing a success rate of more than 50% in the treatment of transplant kidney VUR. In fact, post-Deflux redo ureteral reimplantation was associated with an increased risk of postoperative complication. CONCLUSION: The use of Deflux in the post-transplant setting has poor results. In the study series, 11/11 patients demonstrated clinical and radiographic failure. Therefore, as an institution the authors do not recommend Deflux as first-line treatment of VUR in the transplant patient.

A 6-month open-label extension study of the safety and efficacy of subcutaneous belimumab in patients with systemic lupus erythematosus.

Objective To evaluate the safety, tolerability and efficacy of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE) beyond 1 year. Methods This was a 24-week, open-label extension following a 52-week, double-blind, placebo-controlled trial of belimumab SC. Patients who completed the double-blind phase were eligible to enter the open-label phase. All patients received weekly belimumab 200 mg SC plus standard SLE therapy. Outcome measures included safety and efficacy (SLE Response Index (SRI) and SLE Flare Index (SFI) rates), and changes in biomarker and B cell levels. Results Of 677 patients who completed the 52-week, double-blind phase, 662 entered the open-label phase; 206 had previously received placebo and 456 had previously received belimumab. Despite differences in total belimumab exposure (24 weeks in the placebo-to-belimumab group versus 76 weeks in the belimumab group), the proportions of patients experiencing more than one adverse event (AE) or a serious AE in the open-label phase were similar between groups (placebo-to-belimumab: 51.5 and 6.8%; belimumab: 48.2 and 5.5%, respectively). Most AEs were mild/moderate in severity. Efficacy was maintained through the extension phase. An SRI response was achieved by 16.1% of patients in the placebo-to-belimumab group and 76.3% patients in the belimumab group. Furthermore, 1.0% of patients in the placebo-to-belimumab group and 2.6% of patients in the belimumab group experienced a severe SFI flare. Conclusion Belimumab SC was well tolerated and efficacy was maintained during the extension phase of this study. The safety profile of belimumab SC is consistent with that of previous experience with belimumab. Trial registration ClinicalTrials.gov identifier: NCT01484496.

Efficacy and Safety of Subcutaneous Belimumab in Anti-Double-Stranded DNA-Positive, Hypocomplementemic Patients With Systemic Lupus Erythematosus.

OBJECTIVE: To investigate the efficacy and safety of belimumab, a human immunoglobulin monoclonal antibody against B lymphocyte stimulator, in a subset of patients with systemic lupus erythematosus (SLE) who were hypocomplementemic (C3 <90 mg/dl and/or C4 <10 mg/dl) and anti-double-stranded DNA (anti-dsDNA) positive (≥30 IU/ml) at baseline. METHODS: In this phase III, double-blind, placebo-controlled study (BEL112341; ClinicalTrials.gov identifier: NCT01484496), patients with moderate to severe SLE (Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index [SELENA-SLEDAI] score ≥8) were randomized (2:1) to receive weekly subcutaneous (SC) belimumab 200 mg or placebo, plus standard SLE therapy, for 52 weeks. The primary end point was SLE Responder Index 4 (SRI-4) response rate at week 52. Secondary end points were time to severe flare and reduction in corticosteroid dose (weeks 40-52). Safety was assessed throughout. RESULTS: Of the 836 patients in the intent-to-treat (ITT) population, 356 were hypocomplementemic and anti-dsDNA positive at baseline (108 in the placebo group and 248 in the SC belimumab 200 mg group). Compared with placebo, the belimumab group contained more SRI-4 responders (47.2% versus 64.6%; P = 0.0014), had a lower incidence of severe flare according to the SELENA-SLEDAI flare index (31.5% versus 14.1%), and had a greater percentage of patients who reduced corticosteroid dosage by ≥25% to ≤7.5 mg/day during weeks 40-52 (11.4% versus 20.7%; P = 0.0844). Adverse events (AEs) were similar between treatment groups. CONCLUSION: Our findings indicate that in hypocomplementemic, anti-dsDNA-positive SLE patients, weekly SC belimumab 200 mg significantly improves SRI-4 response, decreases severe flare incidence, and reduces corticosteroid use versus placebo; a trend toward greater benefit compared with the overall ITT population was observed. AEs were consistent with the known safety profile of belimumab.

Project HELP: a study protocol to pilot test a shared decision-making tool about treatment options for patients with hepatitis C and chronic kidney disease.

BACKGROUND: Recent advances in treatment have given patients with chronic kidney disease (CKD) access to safer and more effective medications to treat comorbid hepatitis C virus (HCV) infection. Given the variety and complexity of treatment options that depend on patients' clinical characteristics and personal preferences, education and decision support are needed to prepare patients better to discuss treatment options with their clinicians. METHODS: Drawing on International Patient Decision Aids Standards guidelines, literature reviews, and guidance from a diverse expert advisory group of nephrologists, hepatologists, and patients, we will develop and test a HCV and CKD decision support tool. Named Project HELP (Helping Empower Liver and kidney Patients), this tool will support patients with HCV and CKD during decisions about whether, when, and how to treat each illness. The tool will (1) explain information using plain language and graphics; (2) provide a step-by-step process for thinking about treating HCV and CKD; (3) tailor relevant information to each user by asking about the individual's stage of CKD, stage of fibrosis, prior treatment, and comorbidities; (4) assess user knowledge and values for treatment choices; and (5) help individuals use and consider information appropriate to their values and needs to discuss with a clinician. A pilot study including 70 individuals will evaluate the tool's efficacy, usability, and likelihood of using it in clinical practice. Eligibility criteria will include individuals who understand and read English, who are at least 18 years old, have a diagnosis of HCV (any genotype) and CKD (any stage), and are considering treatment options. DISCUSSION: This study can identify particular characteristics of individuals or groups that might experience challenges initiating treatment for HCV in the CKD population. This tool could provide a resource to facilitate patient-clinician discussions regarding HCV and CKD treatment options.

Diphyllobothriidea in the north area of the Andean Patagonia: Epidemiology in urban dogs, morphometrical and molecular identification, with comments on wild carnivores.

Diphyllobothriidea are the principal agents of Diphyllobothriosis, a widespread food-borne cestodosis. Accurate identification of the species in samples is therefore crucial for diagnosis and epidemiology in wild and domestic animals, and also humans. We aim to identify at specific level the causative agent, and provide an observational, descriptive, and transversal study of the epidemiology of this zoonosis in urban dogs. Also data on wild carnivores from Northwestern Patagonia are presented. Dog feces were collected in thirteen neighborhoods of varying socioeconomic status, and stools were analyzed by two concentration methods. Adult worms were collected and identified by molecular methods. The population of free-roaming dogs in each neighborhood was estimated, and surveys were conducted at all veterinary clinics registered in the Veterinary Medical College of Bariloche city. A total of 36 wild carnivores road killed or found dead in three National Parks were analyzed. Molecular and morphometric analyses of proglottids and eggs from dogs indicate they are infected with D. latum. Twenty out of 118 dog feces were positive for Diphyllobothrium, from 9 out of 13 neighborhoods, with infection values between 10% and 66%. Percentage of infection was correlated positively with the number of free roaming dogs per block, and with Unsatisfied Basic Needs (UBN %), but not with distance to nearest water body. Infection by D. latum in dogs is widely distributed throughout the city. Not all local veterinarians know the occurrence of Diphyllobothriosis in the dogs of the city, and it is evident that this zoonosis is underdiagnosed in relation to the percentage of infection found in this study. None of the analyzed wild carnivores were positive for Diphyllobothrium.

Electronic Stopping of Slow Protons in Oxides: Scaling Properties.

Electronic stopping of slow protons in ZnO, VO_{2} (metal and semiconductor phases), HfO_{2}, and Ta_{2}O_{5} was investigated experimentally. As a comparison of the resulting stopping cross sections (SCS) to data for Al_{2}O_{3} and SiO_{2} reveals, electronic stopping of slow protons does not correlate with electronic properties of the specific material such as band gap energies. Instead, the oxygen 2p states are decisive, as corroborated by density functional theory calculations of the electronic densities of states. Hence, at low ion velocities the SCS of an oxide primarily scales with its oxygen density.

Increase in electron scattering length in PEDOT:PSS by a triflic acid post-processing.

ABSTRACT: A stringent limitation in many optoelectronic devices, such as solar cells and light emitting diodes, is the intrinsic need for a transparent electrode. Uniting relevant aspects, indium tin oxide (ITO) is often the material of choice, however, alternatives are sought and being in particular found in conductive polymers. In this work, we present a novel doping strategy to arrive at highly conducting polymeric material based on poly-3,4-ethylenedioxythiophene (PEDOT). Based on commercial high conductivity PEDOT:PSS (Clevios PH 1000), and a post processing with aqueous triflic acid delivers a material that is both transparent and of low resistivity (5.23 × 10-4 Ω cm). Furthermore, this material retains its conductive character over a large temperature range, indicating metallic behaviour. This is further supported by positive magnetoconductance effects at low temperatures (1.8-10 K) and extended mean free paths of the conduction electrons are observed-evidencing for a metallic state in this polymer.

A randomized, open-label study to investigate the effect of belimumab on pneumococcal vaccination in patients with active, autoantibody-positive systemic lupus erythematosus.

Objective Intravenous belimumab 10 mg/kg is approved as an add-on therapy in patients with active, autoantibody-positive systemic lupus erythematosus. This study aimed to assess the impact of belimumab on immune response to pneumococcal vaccination in patients with systemic lupus erythematosus. Methods This was a Phase 4, open-label study (GSK BEL115470; NCT01597492) conducted in the United States. Patients were randomized (7:9) to receive a 23-valent pneumococcal vaccination four weeks prior to (pre-belimumab cohort) or 24 weeks after (belimumab-concurrent cohort) commencing four-weekly belimumab 10 mg/kg intravenous treatment plus standard systemic lupus erythematosus therapy. Analyses of vaccine titers were performed on the as-treated population (received ≥1 dose of belimumab). The primary endpoint was the proportion of patients with positive antibody responses (≥2-fold increase from pre-vaccination levels, or post-vaccination level ≥ 0.6 µg/mL if pre-vaccination levels were unquantifiable) to ≥1 of 23 pneumococcal vaccine serotypes, four weeks post vaccination. Other endpoints included the proportion of patients with positive antibody responses to ≥2 to ≥10, and ≥11-23 (post hoc analysis) of serotypes. Safety was assessed by monitoring adverse events. Results Seventy-nine patients received pneumococcal vaccination (pre-belimumab cohort, n = 34; belimumab-concurrent cohort, n = 45). The majority (87.3% [69/79]) completed the study; 10 (12.7%) withdrew (patient request, n = 3; adverse event, n = 3; lost to follow-up, n = 2; other, n = 2). At Week 4 post-vaccination, 97.0% (32/33) and 97.6% (40/41) of patients (pre-belimumab and concurrent belimumab cohorts, respectively) had a positive response to ≥1 of 23 pneumococcal serotypes. Over 85% of patients in both cohorts responded to ≥10 of serotypes, approximately 80% responded to ≥12 serotypes, and approximately two-thirds responded to ≥16 serotypes. Little difference was observed between cohorts across a broad response, up to 23 serotypes. Eight (23.5%) patients experienced an adverse event considered by the investigator to be treatment-related in the pre-belimumab cohort and four (8.9%) in the belimumab-concurrent cohort; seven patients experienced non-fatal serious adverse events (pre-belimumab cohort, 11.8% [ n = 4]; concurrent-belimumab cohort, 6.7% [ n = 3]), and no deaths were reported. Conclusion The proportion of patients generating a response to ≥1 pneumococcal serotype did not differ between the pre-belimumab and belimumab-concurrent cohorts; the proportions were also comparable across a broader response (from ≥2 serotypes to 23 serotypes).

Electronic Stopping of Slow Protons in Transition and Rare Earth Metals: Breakdown of the Free Electron Gas Concept.

The electronic stopping cross sections (SCS) of Ta and Gd for slow protons have been investigated experimentally. The data are compared to the results for Pt and Au to learn how electronic stopping in transition and rare earth metals correlates with features of the electronic band structures. The extraordinarily high SCS observed for protons in Ta and Gd cannot be understood in terms of a free electron gas model, but are related to the high densities of both occupied and unoccupied electronic states in these metals.