bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clozapine-Associated Pulmonary Embolism: A High-Mortality, Dose-Independent and Early-Onset Adverse Effect
Authors: Sarvaiya Nilofar , Lapitskaya Yevgeniya , Dima Lorena , Manu Peter 
Published: July 2018

Background:
Recent epidemiological studies have identified an excess of pulmonary embolism (PE) cases in patients treated with antipsychotic drugs. The findings are particularly relevant for patients treated with clozapine, which has many potentially life-threatening adverse drug effects. Among these adverse drug effects are myocarditis and agranulocytosis that have early onset and are dose independent, but also seizures and myocardial repolarization delay, which are dose dependent and may occur at any time. Together with death rates, these variables have important implications for clinical practice.

Areas of Uncertainty:
Study Question: What are the time of onset, dose relationship, and mortality of clozapine-associated PE?

Data sources:
The published case reports of clozapine-associated PE were identified in a MEDLINE search. Cases occurring within 6 months of starting clozapine were considered to have early onset. Dosages of clozapine at the time of PE were defined as low (200 mg/d or less) or high (300 mg/d or greater). Patient outcome was divided into survival of the PE event and death.

Results:
The search identified 23 cases of clozapine-associated PE. The PE had early onset (6.4 ± 7.0 weeks) in 20 patients (87%, 95% confidence interval 67.9%–95.5%). PE occurred in 9 patients treated with low doses (152.8 ± 50.7 mg/d) and in 11 patients on high doses (372.7 ± 127.2 mg/d) of clozapine. Six patients (26.1%, 95% confidence interval 12.6%–46.5%) died.

Conclusions:
A systematic review of the published case reports of clozapine-associated PE indicates that this adverse effect is highly lethal, has early onset and is dose independent. The findings should prompt careful monitoring and consideration of prophylactic treatment for venous thromboembolism for 6 months after starting treatment with clozapine.
Genetic Diversity of Norovirus Infections, Coinfections, and Undernutrition in Children From Brazilian Semiarid Region
Authors: Gondim Rafhaella D.G. , Pankov Rafaela C. , Prata Mara M.G. , Medeiros Pedro H.Q.S. , Veras Herlice N. , Santos Ana K.S. , Magalhães Lyvia M.C. , Havt Alexandre , Fumian Tulio M. , Miagostovich Marize P. , Leite José P.G. , Lima Aldo A.M. 
Published: July 2018

ABSTRACTBackground and Objective:Norovirus (NoV) infections are known to have high‐morbidity and mortality rates and are a major health problem globally. The impact of NoV on child development is, however, poorly understood. We evaluated the distribution of NoV genotypes in children from a low‐income Brazilian semiarid region, in relation with their clinical symptoms, nutritional status, and co‐pathogens.Methods:The test population included children aged 2 to 36 months from 6 cities of the Brazilian semiarid region. Fecal samples were collected from each child, along with the information regarding their socioeconomic/clinical conditions using a standardized questionnaire. Detection and quantification of NoV were performed by reverse‐transcription quantitative polymerase chain reaction, followed by molecular and phylogenetic analyses.Results:The NoV detection rate was 45.2%. Presence of NoV was associated with lower z scores for weight‐for‐age (P = 0.03), weight‐for‐height (P = 0.03), and body mass index‐for‐age (P = 0.03). NoV infection was associated with more frequent respiratory illnesses (P < 0.01). GII.P7 (polymerase) and GII.3 (capsid) were the most frequent NoV genotypes. Analysis of the open reading frame (ORF)1‐2 junction identified recombinant NoV strains in 80% of the sequenced samples. Enteroaggregative Escherichia coli coinfection was the major predictor for diarrhea in NoV‐positive samples (P < 0.02). Moreover, Shigella spp was also associated with NoV‐positive diagnosis (P = 0.02).Conclusions:This study highlights the genetic variability of NoV and, associated co‐infections and undernutrition in infants from low‐income Brazilian semiarid region.
Switching From Originator to Biosimilar Infliximab in Paediatric Inflammatory Bowel Disease Is Feasible and Uneventful
Authors: Gervais Lisa , McLean Luke L. , Wilson Michelle L. , Cameron Carol , Curtis Lee , Garrick Vikki , Armstrong Kat , Tayler Rachel , Henderson Paul , Hansen Richard , Chalmers Iain , Wilson David C. , Russell Richard K. 
Published: July 2018

ABSTRACTThe safety, clinical efficacy, and cost‐effectiveness of biosimilar infliximab in adult inflammatory bowel disease (IBD) have now been extensively shown. Limited data have been collected in the paediatric setting. We report nationwide, prospective, clinical safety and effectiveness data for patients from all 3 Scottish paediatric inflammatory bowel disease networks switching from originator to biosimilar infliximab. Prospective clinical data were collected for 33 patients. Information was collected from electronic patient records, laboratory reports, and patient case notes. There were no clinically significant changes to disease activity, biomarkers, antidrug antibodies, or trough drug levels (P> 0.1) within a 12‐month follow‐up period; in addition, there were no significant adverse events reported. No infusion reactions were seen in the 264 infusions delivered. Switching from originator infliximab to the biosimilar (CT‐P13) appears to be associated with neither an increase in infusion reactions nor significant loss of effectiveness in the short term.
Survey of Obstetrician-gynecologists in the United States About Trichomoniasis, 2016
Authors: Liu Eugene W. , Workowski Kimberly A. , Taouk Laura H. , Schulkin Jay , Secor William E. , Jones Jeffrey L. 
Published: July 2018

Purpose
Trichomoniasis is the most prevalent nonviral sexually transmitted infection (STI) in the United States. It can present with vaginitis in women and urethritis in men, but is most often asymptomatic or occurs with minimal symptoms. It is associated with other STIs, adverse pregnancy outcomes and pelvic inflammatory disease. For these reasons, health care provider awareness of trichomoniasis is of public health importance.

Methods
To assess practitioner knowledge, attitudes, and practices concerning trichomoniasis management, the American College of Obstetricians and Gynecologists conducted an online survey in 2016 of its members, and we analyzed results from 230 respondents.

Results
We note discrepancies between practice and recommendations among surveyed providers: a minority of respondents routinely screen human immunodeficiency virus (HIV)-positive patients for trichomoniasis (10.7%, “most of the time”; 95% confidence interval [CI], 6.7–15.8; 33.0%, “always”; 95% CI, 26.5%–40.0%), treat trichomoniasis in HIV-positive patients with the recommended dose of metronidazole 500 mg twice a day for 7 days (25.8%; 95% CI, 20.0%–32.3%), or retest patients diagnosed with trichomoniasis 3 months after treatment (9.6%; 95% CI, 6.1%–14.3%). Only 29.0% (95% CI, 23.0%–35.5%) retreat with metronidazole 500 mg twice a day for 7 days in patients who have failed prior treatment.

Conclusions
Screening for and treatment of trichomoniasis in HIV-positive patients, and retesting and retreatment for trichomoniasis in the general population appear to be suboptimal. Continuing education for providers is needed for this common but “neglected” STI.
Antiretroviral Drug Use and HIV Drug Resistance Among Young Women in Rural South Africa: HPTN 068
Authors: Zhang Yinfeng , Sivay Mariya V. , Hudelson Sarah E. , Clarke William , Breaud Autumn , Wang Jing , Piwowar-Manning Estelle , Agyei Yaw , Fogel Jessica M. , Hamilton Erica L. , Selin Amanda , MacPhail Catherine , Kahn Kathleen , Gómez-Olivé Francesc Xavier , Hughes James P. , Pettifor Audrey , Eshleman Susan H. 
Published: July 2018

Background:
Antiretroviral (ARV) drugs are used for HIV treatment and prevention. We analyzed ARV drug use and HIV drug resistance in a cohort of young women in rural South Africa enrolled in the HIV Prevention Trials Network (HPTN) 068 study, which evaluated the use of a cash transfer conditional on school attendance to reduce HIV incidence.

Methods:
ARV drug testing was performed using plasma samples from 2526 young women. This included 2526 enrollment samples (80 HIV-infected and 2446 HIV-uninfected) and 162 seroconversion samples (first HIV-positive study visit). Testing was performed using a qualitative assay that detects 20 ARV drugs from 5 drug classes. HIV drug resistance testing was performed with the ViroSeq HIV-1 Genotyping System for samples that had HIV viral loads ≥400 copies per milliliter.

Results:
At enrollment, ARV drugs were detected in 10 (12.5%) of 80 HIV-infected young women. None of 2446 HIV-uninfected young women had ARV drugs detected at enrollment. ARV drugs were also detected in 16 (9.9%) of 162 seroconverters. At enrollment, 9 (13.4%) of 67 young women with genotyping results had HIV drug resistance; resistance was also detected in 9 (6.9%) of 131 seroconverters with genotyping results.

Conclusions:
Most of the HIV-infected young women in this cohort from rural South Africa were not taking ARV drugs, suggesting they were unaware of their HIV status or were not in care. HIV drug resistance was detected in young women with both prevalent and new HIV infection.
Impact of Protease Inhibitors on HIV-Associated Kaposi Sarcoma Incidence: A Systematic Review
Authors: Chang Elaine , Mapakshi Srikar R. , Mbang Pamela , El-Mallawany Nader Kim , Kramer Jennifer R. , White Donna L. , Chiao Elizabeth Y. 
Published: July 2018

Background:
Protease inhibitors (PIs) may inhibit Kaposi sarcoma (KS) carcinogenesis. However, PI-based antiretroviral therapy (ART) is rarely a first-line choice in people living with HIV (PLWH) because of cost and toxicities. This is the first systematic review to assess KS incidence stratified by ART type.

Methods:
We searched PubMed to identify original, full research reports of KS incidence in ART-treated adult PLWH, stratified by ART class, published between 1996 and 2017. For overlapping cohorts, we included only the most recent study and supplemented data with earlier relevant analyses. We described study design, sociodemographic characteristics, statistical adjustment factors, and KS incidence.

Results:
We identified 3 unique retrospective cohort studies, and supplemented one of the studies with results from 6 previous subgroup reports, which included 242,309 PLWH and 3570 incident KS cases. Overall, KS crude incidence decreased by a factor of 10 between untreated and ART-treated PLWH; CD4-adjusted KS incidence decreased by ∼50%, with either non-nucleoside reverse transcriptase inhibitor– or PI-based ART. A single study measured a cumulative dose-/time-dependent effect of ART, which reported a relative risk reduction in only the cohort receiving boosted PI-based ART. Other studies defined ART categories by first-line therapy only.

Conclusions:
The risk of incident KS was significantly reduced, regardless of ART class even after adjusting for CD4 count. The quality of evidence (ie, most studies categorizing users by first-line ART) does not permit KS risk reduction comparisons across ART types. Given the limited number and retrospective nature of these studies, prospective data are indicated.
Risk of infectious complications in pelvic fracture urethral injury patients managed with internal fixation and suprapubic catheter placement
Authors: Johnsen Niels V. , Vanni Alex J. , Voelzke Bryan B. 
Published: July 2018

BACKGROUND
There exists significant controversy regarding the use of suprapubic tubes (SPT) in pelvic fracture urethral injury (PFUI) patients undergoing internal fixation (IF) as to the potential risk of infection. Using the National Trauma Data Bank, we sought to examine if placement of SPT in patients with traumatic urethral injuries undergoing IF of pelvic fractures increases the risks of infectious complications during the index hospitalization.

PATIENTS AND METHODS
Using International Classification of Disease, version 9 and Abbreviated Injury Scale codes, patients with PFUI were identified in the National Trauma Data Bank between 2002 and 2014. International Classification of Disease, version 9 codes were used to identify patients who underwent IF of pelvic fractures, as well as those who underwent SPT placement. Covariates analyzed included age, Injury Severity Score (ISS), diabetes, hypertension, coronary artery disease, obesity, smoking status, associated colorectal injuries, and pelvic angioembolization. Demographics, management and infectious complications were compared between IF patients who did or did not undergo SPT placement using χ2 and t tests. Poisson regression analysis was performed to identify independent predictors of infectious complications.

RESULTS
Six hundred ninety-six PFUI patients were identified. Two hundred four (29.3%) patients underwent IF during the index hospitalization, of which 35 underwent concomitant SPT placement during that same admission. There was no difference in likelihood of undergoing IF in patients with or without SPT (p = 0.36). Multivariate analysis revealed that only ISS (Relative risk [RR], 4.00; 95% confidence interval, 1.25–12.77) and smoking status (RR, 2.45; 95% confidence interval, 1.11–5.43) were significant predictors of infectious complications, while SPT placement was not.

CONCLUSION
Among patients with PFUI undergoing IF, SPT placement does not appear to increase the risk for acute infectious complications during the index hospitalization, while higher ISS and smoking are significantly associated. Further longitudinal studies are required to provide definitive recommendations regarding the long-term safety of SPT placement in this patient population.

LEVEL OF EVIDENCE
Prognostic, level IV.
Implementation is not enough: Graduated drivers licensing benefits from a comprehensive enforcement, education, and awareness campaigns
Authors: Bonne Stephanie , Suber Iesha , Anderson Arnold , Livingston David H. 
Published: July 2018

BACKGROUND
Graduated drivers license (GDLs) are required in most states. Graduated drivers licenses are intermediate licenses requiring a supervisory period prior to full licensure. Surveys suggests poor acceptance of GDL restrictions high variability in GDL compliance. New Jersey initiated GDLs in 2002 and introduced a comprehensive public health campaign in 2010. This study analyzed the effect of GDL and the campaign on teen driver–related fatalities and hypothesized that implementation alone was insufficient to decrease deaths.

METHODS
Data were analyzed from 1998 to 2016 from New Jersey’s Fatal Accident Investigation Unit. In 2005, collaboration with state police added total crash fatalities and teen passenger deaths to the data set. Patterns in data before and after GDL implementation in 2002 and a comprehensive campaign in 2010 were evaluated to determine effects in New Jersey. Paired t tests, analysis of variance, and regression analyses were performed, with p value less than 0.05 considered significant.

RESULTS
Little effect was seen after initiation of GDL, with no change in number of dead teen drivers (44 vs. 49, p > 0.05) or fatal accidents (117 vs.115, p > 0.05) in the 4 years before and after implementation. However, after the comprehensive campaign, decreases are seen in dead teenaged drivers (42 vs. 22, p < 0.005) and total fatal accidents involving teens (107 vs. 61, p < 0.005). Comparing 4 years before and 6 years after the campaign demonstrates decreases in total crash fatalities involving teen drivers (112 vs. 66, p < 0.05) and in the number of dead teenaged passengers in a vehicle operated by another teen (19 vs. 11 p < 0.05).

CONCLUSIONS
Implementation of GDLs alone may not be an effective strategy in decreasing the number of teen fatalities. A multipronged approach combining comprehensive, public-health based campaign with targeted enforcement is necessary to decrease the number of teen driver–related deaths. Additional studies are needed to assess the relationship between decreased death and compliance with GDLs.

LEVEL OF EVIDENCE
Retrospective comparative study, level III.
Multimodal Approach to Decision to Treat Critically Ill Patients With Periodic or Rhythmic Patterns Using an Ictal–Interictal Continuum Spectral Severity Score
Authors: Kapinos Gregory , Trinka Eugen , Kaplan Peter W. 
Published: July 2018

Summary:
We propose a comprehensive review of the subject of epileptiform and potentially harmful EEG patterns that lie on the interictal continuum (IIC) to help with therapeutic decision-making and target future research. This approach to “electro-physiological SE” encompasses five dimensions of the IIC: it characterizes a periodic or rhythmic pattern, not only regarding its ictal morphology and potential harm with secondary neuronal injury, but also addresses the “metabolic footprint,” clinical repercussion, and epileptogenic potential. Recent studies have attempted to determine and qualify the ictal nature and the epileptogenic potential (i.e., risk of subsequent acute seizures) of particular IIC patterns and their intrinsic EEG characteristics. Others have correlated non-convulsive seizures with cognitive outcomes beyond mortality; non-convulsive seizures and sporadic, periodic, or rhythmic discharges to encephalopathy severity; and the spectrum of periodic or rhythmic patterns to measurable secondary brain injury. Equivocal periodic or rhythmic patterns on the IIC are frequently encountered in critical care neurology where clinicians often incorporate advanced neuroimaging, metabolic neuromonitoring, and anti-seizure drug short trials, in an effort to gauge these patterns. We propose portraying the IIC with a multiaxial graph to disambiguate each of these risks. Quantification along each axis may help calibrate therapeutic urgency. An adaptable scoring system assesses which quasi-ictal EEG patterns in this spectrum might reach the tipping point toward anti-seizure drug escalation, in neurocritically ill patients.
A wavelet neural control scheme for a quadrotor unmanned aerial vehicle
Authors: Jurado F. , Lopez S. 
Published: July 2018

Wavelets are designed to have compact support in both time and frequency, giving them the ability to represent a signal in the two-dimensional time–frequency plane. The Gaussian, the Mexican hat and the Morlet wavelets are crude wavelets that can be used only in continuous decomposition. The Morlet wavelet is complex-valued and suitable for feature extraction using the continuous wavelet transform. Continuous wavelets are favoured when high temporal and spectral resolution is required at all scales. In this paper, considering the properties from the Morlet wavelet and based on the structure of a recurrent high-order neural network model, a novel wavelet neural network structure, here called a recurrent Morlet wavelet neural network, is proposed in order to achieve a better identification of the behaviour of dynamic systems. The effectiveness of our proposal is explored through the design of a decentralized neural backstepping control scheme for a quadrotor unmanned aerial vehicle. The performance of the overall neural identification and control scheme is verified via simulation and real-time results.
This article is part of the theme issue ‘Redundancy rules: the continuous wavelet transform comes of age’.
Tissue-specific degradation of essential centrosome components reveals distinct microtubule populations at microtubule organizing centers
Authors: Sallee Maria D. , Zonka Jennifer C. , Skokan Taylor D. , Raftrey Brian C. , Feldman Jessica L. 
Published: July 2018

AbstractNon-centrosomal microtubule organizing centers (ncMTOCs) are found in most differentiated cells, but how these structures regulate microtubule organization and dynamics is largely unknown. We optimized a tissue-specific degradation system to test the role of the essential centrosomal microtubule nucleators γ-tubulin ring complex (γ-TURC) and AIR-1/Aurora A at the apical ncMTOC, where they both localize inC. elegansembryonic intestinal epithelial cells. As at the centrosome, the core γ-TURC component GIP-1/GCP3 is required to recruit other γ-TuRC components to the apical ncMTOC including MZT-1/MZT1, characterized here for the first time in animal development. In contrast, AIR-1 and MZT-1 were specifically required to recruit γ-TuRC to the centrosome, but not to centrioles or to the apical ncMTOC. Surprisingly, microtubules remain robustly organized at the apical ncMTOC upon γ-TuRC and AIR-1 co-depletion, and upon depletion of other known microtubule regulators including TPXL-1/TPX2, ZYG-9/chTOG, PTRN-1/CAMSAP, and NOCA-1/Ninein. However, loss of GIP-1 removed a subset of dynamic EBP-2/EB1-marked microtubules, and the remaining dynamic microtubules grew faster. Together, these results suggest that different MTOCs use discrete proteins for their function, and that the apical ncMTOC is composed of distinct populations of γ-TuRC-dependent and independent microtubules that compete for a limited pool of resources.
Simple and rapid separation of diverse neoagaro-oligosaccharides
Authors: Lin Fudi , Huang Yayan , Zhang Na , Ye Jing , Xiao Meitian 
Published: July 2018

AbstractA rapid and simple method for obtaining pure and well-defined oligosaccharides was established by hydrolyzing agar with β-agarase fromVibrio natriegens. The conditions for enzymolysis were optimized as follows: temperature of 45 °C, pH of 8.5, substrate concentration of 0.3%, enzyme amount of 100 U/g and enzymolysis time of 20 h. Neoagaro-oligosaccharides with different degree of polymerizations were gained by hydrolyzing agar with β-agarase at different enzymolysis time. After removing pigment by activated carbon and salts by dialyzing, the enzyme hydrolysis solution was separated with Bio-Gel P2 column chromatography. Neoagaro-oligosaccharides with different degree of polymerizations were acquired. By comparing with standard substances, along with further confirmation by FTIR, MS and NMR, structures of the purified neoagaro-oligosaccharides were identified as neoagarobiose, neoagaroteraose, neoagarohexaose, neoagarooctaose, neoagarodecaose and neoagarododecaose with purities more than 97.0%, respectively. The present study established a method for rapid preparation of various monomers of neoagaro-oligosaccharides that may be of great significance for further study of bioactivities.