bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictability of real temporal networks
Authors: Tang Disheng , Du Wenbo , Shekhtman Louis , Wang Yijie , Havlin Shlomo , Cao Xianbin , Yan Gang
Published: February 2020

Links in most real networks often change over time. Such temporality of links encodes the ordering and causality of interactions between nodes and has a profound effect on network dynamics and function. Empirical evidence has shown that the temporal nature of links in many real-world networks is not random. Nonetheless, it is challenging to predict temporal link patterns while considering the entanglement between topological and temporal link patterns. Here, we propose an entropy-rate-based framework, based on combined topological–temporal regularities, for quantifying the predictability of any temporal network. We apply our framework on various model networks, demonstrating that it indeed captures the intrinsic topological–temporal regularities whereas previous methods considered only temporal aspects. We also apply our framework on 18 real networks of different types and determine their predictability. Interestingly, we find that, for most real temporal networks, despite the greater complexity of predictability brought by the increase in dimension, the combined topological–temporal predictability is higher than the temporal predictability. Our results demonstrate the necessity for incorporating both temporal and topological aspects of networks in order to improve predictions of dynamical processes.
Dual Burden of Smoked and Smokeless Tobacco Use in India, 2009–2017: A Repeated Cross-Sectional Analysis Based on Global Adult Tobacco Survey
Authors: Singh Prashant Kumar , Yadav Amit , Lal Pranay , Sinha Dhirendra N , Gupta Prakash C , Swasticharan Leimapokpam , Singh Shalini , Mehrotra Ravi
Published: February 2020

Introduction

The dual use of smoked and smokeless tobacco (SLT) poses a serious challenge to tobacco control efforts. This article examines the trends and patterns of this usage in India during the period 2009–2010 and 2016–2017.

Methods

Data from two rounds of nationally representative cross-sectional Global Adult Tobacco Survey (GATS) conducted in 2009–2010 and 2016–2017 have been used. Dual use was assessed based on current smokers and SLT users in both rounds.

Results

Findings reveal that dual use in India has dropped from 5.3% during 2009–2010 to 3.4% during 2016–2017, a decline of nearly 10 million dual users. However, some states have added nearly 4.6 million new dual users during this period. While dual use continues to remain high in rural areas, there has been a manifold increase in urban areas. Findings revealed that intention to quit tobacco was lower among dual tobacco users as compared to single users with considerable difference between urban and rural areas.

Conclusion

Easy availability and affordability of SLT products compared to smoking products and restrictions on smoking in public places may have pushed current smokers and dual users to take to or intensify their SLT consumption. Measures relating to awareness, pricing, taxation, and enforcement of tobacco control laws should focus on all forms of tobacco, especially targeting high dual burden in rural and urban settings.

Implications

Dual form of tobacco users represent 12% of all tobacco users in the country. The study reveals that intention to quit tobacco among dual users is significantly lower than that among single tobacco product users. This requires improving public awareness about the morbidity and mortality that arises from the use of all forms of tobacco products. Efforts to restrict the availability of tobacco products should focus on licensing the sale of all tobacco products. Reduction in dual tobacco use will not only result in multiplied health benefits but also help in achieving the Non-Communicable Diseases targets under the United Nations Sustainable Development Goals.
Applying focused ethnographic methods: examining implications of intracultural diversity for nutrition interventions
Authors: Pelto Gretel H
Published: February 2020

This paper examines the implications of intracultural difference for the design and implementation of nutrition interventions. It raises the question of whether small-sample, mixed-method implementation research, using a focused ethnographic approach, has sufficient power to detect meaningful differences in cultural beliefs, values, perceptions, and attitudes that are important for the design and implementation of nutrition interventions. It first presents the theoretical framework that was used to guide the research, followed by a description of the methodology of the Focused Ethnographic Study for Infant and Young Child Feeding. It then uses the findings from recent research in Ghana to address the central question. The findings document strong elements of shared cultural consensus, but intracultural differences of importance, in relation to the planning and content of behavior change communication.
New constraints on the mass bias of galaxy clusters from the power spectra of the thermal Sunyaev–Zeldovich effect and cosmic shear
Authors: Makiya Ryu , Hikage Chiaki , Komatsu Eiichiro
Published: February 2020

The thermal Sunyaev–Zeldovich (tSZ) power spectrum is a powerful probe of the present-day amplitude of matter density fluctuations, and has been measured up to $\ell \approx 10^3$ from the Planck data. The largest systematic uncertainty in the interpretation of this data is the so-called “mass bias” parameter B, which relates the true halo mass to the mass proxy used by the Planck team as $M\,_{\rm 500c}^{\rm Planck}=M\,_{\rm 500c}^{\rm true}/B$. Since the power spectrum of the cosmic weak lensing shear is also sensitive to the amplitude of matter density fluctuations via $S_8\equiv \sigma _8 \Omega _{\rm m}^{\alpha }$ with $\alpha \sim 0.5$, we can break the degeneracy between the mass bias and the cosmological parameters by combining the tSZ and cosmic shear power spectra. In this paper, we perform a joint likelihood analysis of the tSZ power spectrum from Planck and the cosmic shear power spectrum from Subaru Hyper Suprime-Cam. Our analysis does not use the primordial cosmic microwave background (CMB) information. We obtain a new constraint on the mass bias as $B = 1.37 ^{+0.15}_{-0.23}$ or $(1-b) = B^{-1}=0.73^{+0.08}_{-0.13}$ ($68\%$ confidence limit), for $\sigma _8 < 0.9$. This value of B is lower than that needed to reconcile the tSZ data with the primordial CMB and CMB lensing data, i.e., $B = 1.64 \pm 0.19$, but is consistent with the mass bias expected from hydrodynamical simulations, $B = 1.28 \pm 0.20$. Thus our results indicate that the mass bias is consistent with the non-thermal pressure support from mass accretion of galaxy clusters via the cosmic structure formation, and that the cosmologies inferred from the tSZ and the cosmic shear are consistent with each other.
Beta-lactam allergy in the paediatric population
Authors: Wong Tiffany , Atkinson Adelle , t’Jong Geert , Rieder Michael J , Chan Edmond S , Abrams Elissa M
Published: February 2020

Beta-lactam allergy is commonly diagnosed in paediatric patients, but over 90% of individuals reporting this allergy are able to tolerate the medications prescribed after evaluation by an allergist. Beta-lactam allergy labels are associated with negative clinical and administrative outcomes, including use of less desirable alternative antibiotics, longer hospitalizations, increasing antibiotic-resistant infections, and greater medical costs. Also, children with true IgE-mediated allergy to penicillin medications are often advised to avoid all beta-lactam antibiotics, including cephalosporins, which is likely unnecessary in greater than 97% of those reporting penicillin allergies. Most patients can be safely treated with penicillin or amoxicillin if they do not have a history compatible with IgE-mediated or systemic, delayed reactions such as Stevens-Johnson syndrome (SJS), serum sickness-like reactions, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, or acute generalized exanthematous pustulosis (AGEP). Guidance is provided on how to stratify risk of beta-lactam allergy, and on test dosing and monitoring in the outpatient setting for patients deemed low risk. Guidance for patients at higher risk of beta-lactam allergy includes criteria for appropriate referral to allergists and the use of alternative antimicrobials, such as cephalosporins, while awaiting specialist assessment.
L’allergie aux bêta-lactamines dans la population pédiatrique
Authors: Wong Tiffany , Atkinson Adelle , t’Jong Geert , Rieder Michael J , Chan Edmond S , Abrams Elissa M
Published: February 2020

L’allergie aux bêta-lactamines est souvent diagnostiquée chez les patients pédiatriques, mais plus de 90 % de ceux qui déclarent en être victimes peuvent tolérer les médicaments prescrits après avoir été évalués par un allergologue. Une « étiquette » d’allergie aux bêta-lactamines est liée à des résultats cliniques et administratifs négatifs, y compris l’utilisation d’autres antibiotiques moins indiqués, des hospitalisations plus longues, une augmentation des infections antibiorésistantes et des coûts médicaux plus élevés. De plus, pour les enfants ayant une véritable allergie à médiation IgE aux pénicillines, on conseille souvent d’éviter toutes les bêta-lactamines, y compris les céphalosporines, ce qui n’est probablement pas nécessaire chez plus de 97 % de ceux qui déclarent être allergiques à la pénicilline. La plupart des patients peuvent recevoir un traitement à la pénicilline ou à l’amoxicilline en toute sécurité s’ils n’ont pas d’antécédents compatibles avec des réactions à médiation IgE ni avec des réactions systémiques tardives comme le syndrome de Stevens-Johnson, une réaction de type maladie sérique, le syndrome d’éruption médicamenteuse avec éosinophilie et manifestations systémiques ou la pustulose exanthématique aiguë généralisée. Des directives sont proposées pour stratifier le risque d’allergie aux bêta-lactamines ainsi que pour administrer des doses tests aux patients considérés comme à faible risque et les surveiller en milieu ambulatoire. Les directives sur les patients à plus haut risque d’allergie aux bêta-lactamines comprennent les critères pour les diriger vers des allergologues et l’utilisation d’autres antimicrobiens tels que les céphalosporines, en attendant l’évaluation par un spécialiste.
Circulating Adipokines in Predicting the Transition from Acute to Persistent Low Back Pain
Authors: Klyne David M , Hodges Paul W
Published: February 2020

Objectives

Cytokines such as tumor necrosis factor (TNF) contribute to the transition from acute to persistent pain. Despite increasing incidence of obesity and its linkage with chronic pain and inflammation, cytokines predominantly produced by adipose tissue (adipokines) have received little attention. Here we aimed to explore the longitudinal trajectory of adipokines from the onset of acute low back pain (LBP) and identify combinations of adipokines and/or other features that predict outcome.

Methods

Individuals with acute LBP (less than two weeks after onset) who had either recovered (no pain, N = 15) or remained unrecovered (no reduction/increase in pain, N = 13) at six months and 15 controls were retrospectively selected from a larger prospective cohort. Participants provided blood for the measurement of TNF, interleukin-6 (IL-6), resistin, visfatin, adiponectin, leptin, and C-reactive protein (CRP), and completed questionnaires related to pain/disability, depression, and sleep at baseline. LBP participants repeated measurements at six months.

Results

Compared with controls, acute LBP individuals had higher TNF and CRP but lower adiponectin. In LBP, unrecovered individuals had higher TNF at both time points, but lower CRP at baseline and leptin at six months. Although combined low CRP, high TNF, and depressive symptoms at baseline predicted poor recovery, the primary adipokines leptin, resistin, visfatin, and adiponectin did not.

Conclusions

Primary adipokines did not add to the prediction of poor LBP outcome that has been identified for the combination of low CRP, high TNF, and depressive symptoms in acute LBP. Whether adipokines play a role in LBP persistence in overweight/obese individuals requires investigation.
Regional variations in adverse event reporting rates and ACR responses in placebo/standard-of-care arms of rheumatoid arthritis trials
Authors: Keebler Daniel , Teng Edmond , Chia Jenny , Galanter Joshua , Peake Jodie , Tuckwell Katie
Published: February 2020

Objective

Clinical trials are increasingly globalized, and adverse event (AE) rates and treatment responses may differ by geographical region. This study assessed regional differences in AE reporting rates and ACR response rates (ACR20/50) in patients with RA who received placebo/standard-of-care treatment in clinical trials.

Methods

Patients from the placebo arms of 7 RA trials in the TransCelerate Biopharma Inc database were grouped into 5 geographical regions (Asia, Latin America, Russian Federation and Eastern Europe [RFEE], USA, and Western Europe). Differences in demographics, AE reporting rates and ACR response were evaluated using descriptive statistics and omnibus tests for significance; pairwise comparisons were made between regions, with false discovery rate correction for multiple comparisons.

Results

Among 970 patients included, week 12 AE rates were significantly lower in the RFEE than in Asia, Latin America and the USA (22% vs 51%, 49% and 53%, respectively; P < 0.05 after false discovery rate correction). Similar differences in AE rates across geographical regions were seen at week 52. Among 747 patients with ACR data, the lowest response rates were observed in the USA (ACR20, 22%) and RFEE (ACR50, 3%); the highest response rates were seen in Western Europe (ACR20, 43%) and Latin America (ACR50, 15%). Only the differences in ACR50 response between the RFEE and Latin America remained significant after false discovery rate correction.

Conclusion

These placebo/standard-of-care arm data revealed significant regional differences in AE reporting rates and ACR50 response rates. Regional distribution of patients should be considered when conducting RA clinical trials, particularly during recruitment.
Experiences and opinions of Danish livestock drivers transporting sows regarding fitness for transport and management choices relevant for animal welfare
Authors: Thodberg Karen , Gould Louisa M , Støier Susanne , Anneberg Inger , Thomsen Peter T , Herskin Mette S
Published: February 2020

Including Denmark, modern pig production typically involves annual culling rates close to 50%. One important professional group in this process are livestock drivers transporting the animals to slaughter. By use of oral interviews, we aimed to describe experiences and opinions of Danish livestock drivers transporting sows, regarding fitness for transport and management choices relevant for animal welfare. All livestock drivers (N = 30) associated with a large slaughterhouse in Denmark accepting sows were approached in person, after having unloaded sows, and asked questions by an interviewer. A total of 22 livestock drivers (73%) answered all questions, constituting of a heterogeneous group of men of varying age, level of experience, time since they achieved the legally required certificate of competence, and daily involvement in sow transportation. Among livestock drivers included in the present study, doubt about fitness for transport was not uncommon, and specific reasons underlying their doubt were listed. All respondents reported to have experienced having to reject loading a cull sow who had been selected for slaughter by a herd manager, and approximately 40% did this several times a year. In contrast, almost 50% had never experienced having a sow rejected by the veterinarian at the slaughterhouse due to lack of fitness for transport. When asked about their management of sows during transportation, the majority (71%) reported using special condition transport (use of extra bedding and partitions to separate individual sows from rest of the load) less than once per month. All respondents considered hot days a problem for welfare of sows and the majority reported to adjust air intake of trucks daily or several times per week. In addition, approximately half of the respondents mentioned stationary periods (e.g., mandatory driver rests) as a challenge to sow welfare, to a degree where they had violated regulation on mandatory driver rests for the sake of welfare of the sows. The present study is among the few to focus on livestock drivers transporting sows, including questions about management choices and the animals’ fitness for transport. The findings may form basis for future development of educational programs for drivers as well as for the formulation of hypotheses for future studies in this area, characterized by complicated underlying legislation and challenges to animal welfare.
Severe asthma: what is new in the new millennium
Authors: Ntontsi Polyxeni , Samitas Konstantinos , Zervas Eleftherion , Gaga Mina
Published: February 2020

Purpose of review

Severe asthma remains a debilitating disease and a challenge for the clinicians. Novel therapies have been introduced and have greatly improved asthma control and more are under development or in clinical studies. These include anti-IL5/IL5R, anti-IL4/IL4R, anti IL13, anti- thymic stromal lymphopoietin (TSLP) and more, and severe asthma is currently managed in personalized medicine approach. However, there is still an unmet need to discover new, clinically available biomarkers and targeted therapies for a large group of severe asthma patients, particularly those with T2-low asthma. In this review, we briefly present the phenotypes and endotypes of severe asthma, the omics technologies in asthma as well as current and future treatments for both T2-high and T2-low asthma.

Recent findings

In this review, we are going to present the effectiveness and safety of anti-IL5 therapies, the clinical trials for dupilumab and tezepelumab and the most significant molecules and biological agents used in trials as possible treatments forT2-low asthma.

Novel anti-IL5 agents have changed the management of T2-high asthma resulting in improved disease control, QoL and lung function and importantly, fewer exacerbations. Nevertheless, there is still the need to find new treatments, particularly for T2-low asthma, which remains a challenge.
Host–microbiome intestinal interactions during early life: considerations for atopy and asthma development
Authors: Pettersen Veronika Kuchařová , Arrieta Marie-Claire
Published: February 2020

Purpose of review

The body's largest microbial community, the gut microbiome, is in contact with mucosal surfaces populated with epithelial, immune, endocrine and nerve cells, all of which sense and respond to microbial signals. These mutual interactions have led to a functional coevolution between the microbes and human physiology. Examples of coadaptation are anaerobesBifidobacteriaandBacteroides, which have adjusted their metabolism to dietary components of human milk, and infant immune development, which has evolved to become reliant on the presence of beneficial microbes. Current research suggests that specific composition of the early-life gut microbiome aligns with the maturation of host immunity. Disruptions of natural microbial succession patterns during gut colonization are a consistent feature of immune-mediated diseases, including atopy and asthma.

Recent findings

Here, we catalog recent birth cohorts documenting associations between immune dysregulation and microbial alterations, and summarize the evidence supporting the role of the gut microbiome as an etiological determinant of immune-mediated allergic diseases.

Ecological concepts that describe microbial dynamics in the context of the host environment, and a portray of immune and neuroendocrine signaling induced by host–microbiome interactions, have become indispensable in describing the molecular role of early-life microbiome in atopy and asthma susceptibility.
Publication Productivity and Academic Rank in Medicine: A Systematic Review and Meta-Analysis
Authors: Zaorsky Nicholas G. , O’Brien Emily , Mardini Jennifer , Lehrer Eric J. , Holliday Emma , Weisman Carol S.
Published: February 2020

Purpose

Academic medical faculty members are assessed on their research productivity for hiring, promotion, grant, and award decisions. The current work systematically reviews, synthesizes, and analyzes the available literature on publication productivity by academic rank across medical specialties.

Method

The authors searched PubMed for medical literature, including observational studies, published in English from 2005 to 2018, using the term “h-index,” on July 1, 2018. Studies had to report on h-indices for faculty in academic medicine and, if available, other publication metrics, including number of citations, number of publications, and m-indices, stratified by academic rank. The DerSimonian and Laird method was used to perform meta-analyses for the primary (h-index) and secondary (m-index) outcome measures.

Results

The systematic review included 21 studies. The meta-analysis included 19 studies and data on 14,567 academic physicians. Both h- and m-indices increased with academic rank. The weighted random effects summary effect sizes for mean h-indices were 5.22 (95% confidence interval [CI]: 4.21–6.23, n = 6,609) for assistant professors, 11.22 (95% CI: 9.65–12.78, n = 3,508) for associate professors, 20.77 (95% CI: 17.94–23.60, n = 3,626) for full professors, and 22.08 (95% CI: 17.73–26.44, n = 816) for department chairs. Mean m-indices were 0.53 (95% CI: 0.40–0.65, n = 1,653) for assistant professors, 0.72 (95% CI: 0.58–0.85, n = 883) for associate professors, 0.99 (95% CI: 0.75–1.22, n = 854) for full professors, and 1.16 (95% CI: 0.81–1.51, n = 195) for department chairs.

Conclusions

Both h- and m-indices increase with successive academic rank. There are unique distributions of these metrics among medical specialties. The h- and m-indices should be used in conjunction with other measures of academic success to evaluate faculty members for hiring, promotion, grant, and award decisions.
ICU management based on big data
Authors: Falini Stefano , Angelotti Giovanni , Cecconi Maurizio
Published: February 2020

Purpose of review

The availability of large datasets and computational power has prompted a revolution in Intensive Care. Data represent a great opportunity for clinical practice, benchmarking, and research. Machine learning algorithms can help predict events in a way the human brain can simply not process. This possibility comes with benefits and risks for the clinician, as finding associations does not mean proving causality.

Recent findings

Current applications of Data Science still focus on data documentation and visualization, and on basic rules to identify critical lab values. Recently, algorithms have been put in place for prediction of outcomes such as length of stay, mortality, and development of complications. These results have begun being implemented for more efficient allocation of resources and in benchmarking processes, to allow identification of successful practices and margins for improvement. In parallel, machine learning models are increasingly being applied in research to expand medical knowledge.

Data have always been part of the work of intensivists, but the current availability has not been completely exploited. The intensive care community has to embrace and guide the data science revolution in order to decline it in favor of patients’ care.
Mortality Among People With Opioid Use Disorder: A Systematic Review and Meta-analysis
Authors: Bahji Anees , Cheng Breagh , Gray Samantha , Stuart Heather
Published: February 2020

Background and Aims:

Opioids are among the most commonly used class of illicit drugs. We aimed to produce pooled estimates of mortality risks among people with opioid use disorder (OUD), with a focus upon all-cause mortality, and also overdose-specific causes of death.

Design:

Systematic review and meta-analysis of cohorts of people with OUD involving illicit opioids with data on all-cause or overdose-specific mortality.

Setting and Participants:

Of 4247 papers, 92 were eligible, reporting on 101 cohorts that measured all-cause mortality and opioid-overdose mortality. Cohorts (n = 101–229,274) were in North America, Australia, several Eastern and Western European countries, and Asia.

Measurement:

Titles/abstracts and full texts were independently screened by 2 reviewers, with discrepancies resolved via a third reviewer. We extracted data on crude mortality rates (CMRs) per 1000 person-years (PY); we imputed CMRs where possible if not reported by study authors. We also calculated mortality relative risks. Data were pooled using random-effects models; potential reasons for heterogeneity were explored using subgroup analyses and meta-regressions.

Findings:

The overall all-cause CMR was 18.7 per 1000 PY (95% confidence interval [CI] 17.1–20.3). The overall overdose-specific CMR was 7.0 per 1000 PY (95% CI 6.1–8.0). All-cause and overdose-specific mortality were substantially higher in low/middle-income countries, among those with HIV, and among people who use injection drugs.

Conclusions:

Individuals with OUD carry a high risk of all-cause and overdose-specific mortality. Potentially modifiable risk factors, such as HIV and injection drug use, were predictive of mortality risk and are amenable to global efforts aiming to improve access to OUD treatment and targeted harm reduction efforts.
HIV Treatment Initiation and Retention Among Individuals Initiated on Injectable Opioid Agonist Therapy for Severe Opioid Use Disorder: A Case Series
Authors: Giang Valerie , Brar Rupinder , Sutherland Christy , Nolan Seonaid
Published: February 2020

Objectives:

Injectable opioid agonist therapy (iOAT) has previously been demonstrated to be an effective treatment option for individuals with a severe opioid use disorder (OUD) who have been unsuccessful on first line therapy (eg, buprenorphine/naloxone or methadone). Many individuals with severe OUD may also have HIV infection. Despite this, no literature currently exists examining the relationship between antiretroviral therapy (ART) initiation and adherence following iOAT initiation in the outpatient setting.

Methods:

Retrospective case series (n = 3) of HIV-infected individuals with a severe OUD who were refractory to oral opioid agonist treatment and were started on iOAT in a community setting in Vancouver, Canada. Outcomes of interest included: (1) iOAT induction and maintenance dosing schedules; (2) ART adherence demonstrated by change in HIV viral load.

Results:

All 3 patients initiated and successfully reached iOAT maintenance doses with significant reduction in illicit opioid use. Stable iOAT was associated with increased ART initiation and adherence, and decreased HIV viral loads. Conversely, poor retention or discontinuation of iOAT was associated with reduced adherence to ART and in 1 patient, increased HIV viral loads.

Conclusions:

The individual cases presented suggest that among individuals with severe OUD and HIV infection, iOAT may improve HIV treatment uptake and retention in care.
Where is the Science? A Critical Interrogation of How Sex and Gender are Used to Inform Low-Risk Alcohol Use Guidelines
Authors: Lowik A.J. , Hoong Peter , Knight Rod
Published: February 2020

Across the globe, many countries publish low-risk alcohol guidelines which outline the recommended best practices for drinking limits to reduce the health risks and harms associated with excessive alcohol use. Frequently, low-risk drinking guidelines include different recommendations for cisgender men and women. As researchers working in the area of trans-inclusive substance use treatment and care, we are interested in the rationale for how gender-based low-risk drinking guidelines are determined, including the role of evidence and science. We argue that low-risk drinking guidelines based on sex and/or gender are highly insufficient and not engaging with a robust evidence base, and we further argue that it is important that we attend to these concepts correctly as we develop clinical and public health guidelines, which will undeniably have an impact on the individuals and societies who rely on them.
The Use of the Methadone/Metabolite Ratio (MMR) to Identify an Individual Metabolic Phenotype and Assess Risks of Poor Response and Adverse Effects: Towards Scientific Methadone Dosing
Authors: McCarthy John J. , Graas Joseph , Leamon Martin H. , Ward Coburn , Vasti Ernest J. , Fassbender Catherine
Published: February 2020

Objectives:

Significant genetic variability of metabolism confounds reliable clinical use of methadone because physicians have no way of identifying individual patient metabolism. The methadone/metabolite ratio (MMR), the numerical ratio of serum methadone to its inactive metabolite ethylidine-dimethyl-diphenypyrrolidine (EDDP), represents the net expression of the genes controlling metabolism. The MMR has been adapted to four established pharmacogenetic metabolic categories: ultra-rapid (URM), extensive (EM, normal), intermediate (IM), and ultra-slow (USM).

Methods:

This study reports on the analysis of 1700 paired peak and trough serum samples for methadone and EDDP. The MMR data were stratified by metabolic category. The reliability of these categories and the relationship of the MMR to 2 other laboratory assessments, a peak/trough ratio (PTR) and a methadone half-life, was tested. Additionally, peak and trough serum levels were analyzed by MMR category.

Results:

Each category of MMR identified significantly different mean serum levels (peak and trough), peak/trough ratios, and half-lives. When serum levels were analyzed, evidence of subtherapeutic serum levels were found, predominantly in the URM and EM categories. Seventeen percent of peak serum levels were greater than 1000 ng (a level indicating potential toxicity) with a range up to 2384 ng, predominantly in the IM and USM categories.

Conclusions:

The MMR measures an individual's phenotype for methadone metabolism. The data suggested underdosing in the URM category, as well as evidence of excessive dosing in IM and USM categories. The MMR provides a guide to safe and effective dosing, an alternative to the pharmacokinetically ‘blind’ dosing algorithms currently in use.
The Clinical Significance of Food Addiction
Authors: Wenzel Kevin R. , Weinstock Jeremiah , McGrath Andrew B.
Published: February 2020

Objectives:

The construct of food addiction has received increased attention and has been proposed as a mental disorder. There is some evidence that supports the inclusion of food addiction in the psychiatric nosology; however, the construct has not been sufficiently validated for inclusion. This study used the addiction syndrome model as a guiding theoretical framework to understand food addiction. The addiction syndrome model emphasizes the shared antecedents and consequences of addictions even though specific manifestations may differ.

Methods:

Participants were adult community members with food addiction (n = 26) or healthy controls (n = 26) as classified by the Yale Food Addiction Scale. Participants completed a battery of self-report questionnaires assessing cognitive, emotional, and behavioral domains often associated with addiction.

Results:

Results revealed that individuals with food addiction demonstrated significantly higher scores than healthy controls on depressive symptoms, emotion dysregulation, emotional eating, demand characteristics, motives, impulsivity, and family history of mental health problems and addiction, providing support for the clinical significance of food addiction.

Conclusions:

Overall, this study replicates and extends previous findings, particularly in regard to behavioral economics and demand for food, providing further support for the consideration of food addiction in the psychiatric nosology.
Aldosterone Synthase in Peripheral Sensory Neurons Contributes to Mechanical Hypersensitivity during Local Inflammation in Rats
Authors: Mohamed Doaa M. , Shaqura Mohammed , Li Xiongjuan , Shakibaei Mehdi , Beyer Antje , Treskatsch Sascha , Schäfer Michael , Mousa Shaaban A.
Published: February 2020

Background

Recent emerging evidence suggests that extra-adrenal synthesis of aldosterone occurs (e.g., within the failing heart and in certain brain areas). In this study, the authors investigated evidence for a local endogenous aldosterone production through its key processing enzyme aldosterone synthase within peripheral nociceptive neurons.

Methods

In male Wistar rats (n = 5 to 8 per group) with Freund’s complete adjuvant hind paw inflammation, the authors examined aldosterone, aldosterone synthase, and mineralocorticoid receptor expression in peripheral sensory neurons using quantitative reverse transcriptase–polymerase chain reaction, Western blot, immunohistochemistry, and immunoprecipitation. Moreover, the authors explored the nociceptive behavioral changes after selective mineralocorticoid receptor antagonist, canrenoate-K, or specific aldosterone synthase inhibitor application.

Results

In rats with Freund’s complete adjuvant–induced hind paw inflammation subcutaneous and intrathecal application of mineralocorticoid receptor antagonist, canrenoate-K, rapidly and dose-dependently attenuated nociceptive behavior (94 and 48% reduction in mean paw pressure thresholds, respectively), suggesting a tonic activation of neuronal mineralocorticoid receptors by an endogenous ligand. Indeed, aldosterone immunoreactivity was abundant in peptidergic nociceptive neurons of dorsal root ganglia and colocalized predominantly with its processing enzyme aldosterone synthase and mineralocorticoid receptors. Moreover, aldosterone and its synthesizing enzyme were significantly upregulated in peripheral sensory neurons under inflammatory conditions. The membrane mineralocorticoid receptor consistently coimmunoprecipitated with endogenous aldosterone, confirming a functional link between mineralocorticoid receptors and its endogenous ligand. Importantly, inhibition of endogenous aldosterone production in peripheral sensory neurons by a specific aldosterone synthase inhibitor attenuated nociceptive behavior after hind paw inflammation (a 32% reduction in paw pressure thresholds; inflammation, 47 ± 2 [mean ± SD] vs. inflammation + aldosterone synthase inhibitor, 62 ± 2).

Conclusions

Local production of aldosterone by its processing enzyme aldosterone synthase within peripheral sensory neurons contributes to ongoing mechanical hypersensitivity during local inflammation via intrinsic activation of neuronal mineralocorticoid receptors.

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Comparison of Neonatal and Adult Fibrin Clot Properties between Porcine and Human Plasma
Authors: Nellenbach Kimberly A. , Nandi Seema , Kyu Alexander , Sivadanam Supriya , Guzzetta Nina A. , Brown Ashley C.
Published: February 2020

Background

Recent studies suggest that adult-specific treatment options for fibrinogen replacement during bleeding may be less effective in neonates. This is likely due to structural and functional differences found in the fibrin network between adults and neonates. In this investigation, the authors performed a comparative laboratory-based study between immature and adult human and porcine plasma samples in order to determine if piglets are an appropriate animal model of neonatal coagulopathy.

Methods

Adult and neonatal human and porcine plasma samples were collected from the Children’s Hospital of Atlanta and North Carolina State University College of Veterinary Medicine, respectively. Clots were formed for analysis and fibrinogen concentration was quantified. Structure was examined through confocal microscopy and cryogenic scanning electron microscopy. Function was assessed through atomic force microscopy nanoindentation and clotting and fibrinolysis assays. Lastly, novel hemostatic therapies were applied to neonatal porcine samples to simulate treatment.

Results

All sample groups had similar plasma fibrinogen concentrations. Neonatal porcine and human plasma clots were less branched with lower fiber densities than the dense and highly branched networks seen in adult human and porcine clots. Neonatal porcine and human clots had faster degradation rates and lower clot stiffness values than adult clots (stiffness [mmHg] mean ± SD: neonatal human, 12.15 ± 1.35 mmHg vs. adult human, 32.25 ± 7.13 mmHg; P = 0.016; neonatal pig, 10.5 ± 8.25 mmHg vs. adult pigs, 32.55 ± 7.20 mmHg; P = 0.015). The addition of hemostatic therapies to neonatal porcine samples enhanced clot formation.

Conclusions

The authors identified similar age-related patterns in structure, mechanical, and degradation properties between adults and neonates in porcine and human samples. These findings suggest that piglets are an appropriate preclinical model of neonatal coagulopathy. The authors also show the feasibility of in vitro model application through analysis of novel hemostatic therapies as applied to dilute neonatal porcine plasma.

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Abnormal Uterine Bleeding in the Adolescent
Authors: Hernandez Angela , Dietrich Jennifer E.
Published: February 2020

Abnormal uterine bleeding is a common problem in adolescents. The differential diagnosis varies from pregnancy and infection to anovulation and coagulopathy. Careful history and examination can help elucidate the best next steps for workup and management. Heavy menstrual bleeding is particularly worrisome in this group not only when it occurs at menarche, but also anytime afterward when bleeding lasts longer than 7 days, blood loss is greater than 80 mL per cycle, or other warning signs that indicate a history of heavy bleeding such as anemia. Once conditions of pregnancy, infection, structural abnormalities, and hormonal causes have been ruled out, first-line treatment is medical management with hormonal therapy or nonhormonal options. Invasive measures are a last resort in this patient population, because maintenance of fertility is of critical importance.
Prevalence of a Good Perinatal Outcome With Cryopreserved Compared With Fresh Donor Oocytes
Authors: Eaton Jennifer L. , Truong Tracy , Li Yi-Ju , Polotsky Alex J.
Published: February 2020

OBJECTIVE:

To compare the odds of a good perinatal outcome between cryopreserved and fresh donor oocytes.

METHODS:

We used the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System to conduct a retrospective cohort study of women undergoing donor oocyte in vitro fertilization (IVF) from 2012 to 2015. Cycles using cryopreserved embryos, a gestational carrier, or preimplantation genetic testing were excluded. The primary outcome was a good perinatal outcome, defined as a singleton live birth at 37 weeks of gestation or more with birth weight at or within 2,500 g and 4,000 g. Secondary outcomes included live birth, multiple birth, and prematurity. Generalized estimating equation models were used to test the effect of oocyte type on the primary outcome while accounting for covariates and the correlation induced by repeated cycles within a patient.

RESULTS:

Of the 36,925 cycles included in the analysis, 8,381 (22.7%) used cryopreserved and 28,544 (77.3%) used fresh oocytes. The odds of a good perinatal outcome were marginally but significantly lower with cryopreserved than with fresh oocytes before and after covariate adjustment (22.0% vs 24.1%, unadjusted odds ratio [OR] 0.90, 95% CI 0.85–0.96, adjusted OR 0.88, 95% CI 0.81–0.95). Compared with fresh oocytes, cryopreserved oocytes were associated with lower rates of live birth (39.6% vs 47.7%, OR 0.75, 95% CI 0.72–0.79), multiple birth (22.3% vs 31.2%, OR 0.63, 95% CI 0.58–0.69), and prematurity (27.6% vs 30.6%, OR 0.86, 95% CI 0.79–0.94).

CONCLUSION:

This retrospective national study demonstrated that the use of cryopreserved compared with fresh donor oocytes in IVF cycles is associated with marginally lower odds of a good perinatal outcome.
Association Between Time of Day and the Decision for an Intrapartum Cesarean Delivery
Authors: Son Moeun , Lai Yinglei , Bailit Jennifer , Reddy Uma M. , Wapner Ronald J. , Varner Michael W. , Thorp John M. , Caritis Steve N. , Prasad Mona , Tita Alan T.N. , Saade George , Sorokin Yoram , Rouse Dwight J. , Blackwell Sean C. , Tolosa Jorge E. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network
Published: February 2020

OBJECTIVE:

To examine whether the decision and indications for performing intrapartum cesarean delivery vary by time of day.

METHODS:

We conducted a secondary analysis of a multicenter observational cohort of 115,502 deliveries (2008–2011), including nulliparous women with term, singleton, nonanomalous live gestations in vertex presentation who were attempting labor. Those who attempted home birth, or underwent cesarean delivery scheduled or decided less than 30 minutes after admission were excluded. Time of day was defined as cesarean delivery decision time among those who delivered by cesarean and delivery time among those who delivered vaginally, categorized by each hour of a 24-hour day. Primary outcomes were decision to perform cesarean delivery and the indications for cesarean delivery (labor dystocia, nonreassuring fetal status, or other indications). Secondary outcomes included whether a dystocia indication adhered to standards promoted to reduce cesarean delivery rates. Bivariate analyses were performed using χ2 and Kruskal-Wallis tests for categorical and continuous outcomes, respectively, and generalized additive models with smoothing splines explored nonlinear associations without adjustment for other factors.

RESULTS:

Seven thousand nine hundred fifty-six (22.1%) of 36,014 eligible women underwent cesarean delivery. Decision for cesarean delivery (P<.001) decreased from midnight (21.2%) to morning, reaching a nadir at 10:00 (17.9%) and subsequently rising to peak at 21:00 (26.2%). The frequency of cesarean delivery for dystocia also was significantly associated with time of day (P<.001) in a pattern mirroring overall cesarean delivery. Among cesarean deliveries for dystocia (n=5,274), decision for cesarean delivery at less than 5 cm dilation (P<.001), median duration from 5 cm dilation to cesarean delivery decision (P=.003), and median duration from complete dilation to cesarean delivery decision (P=.014) all significantly differed with time of day. The frequency of nonreassuring fetal status and “other” indications were not significantly associated with time of day (P>.05).

CONCLUSION:

Among nulliparous women who were attempting labor at term, the decision to perform cesarean delivery, particularly for dystocia, varied with time of day. Some of these differences correlate with labor management differences, given the changing frequency of latent phase cesarean delivery and median time in active phase.
Association of Oxytocin Rest During Labor Induction of Nulliparous Women With Mode of Delivery
Authors: McAdow Molly , Xu Xiao , Lipkind Heather , Reddy Uma M. , Illuzzi Jessica L.
Published: February 2020

OBJECTIVE:

To evaluate the association between temporary cessation in oxytocin infusion (oxytocin rest) and mode of delivery in women undergoing induction of labor with a protracted latent phase.

METHODS:

We conducted a retrospective cohort analysis of nulliparous women with term, vertex, singleton gestations who were undergoing induction of labor with continuous oxytocin infusion at a large academic medical center. Episodes of oxytocin rest were identified among patients who were exposed to 8 hours of continuous oxytocin yet remained in latent labor (ie, protracted latent labor). Multivariable logistic regression analysis was performed to estimate the association between duration of oxytocin rest and mode of delivery while adjusting for duration of latent phase, maternal age, gestational age, body mass index, and indications for induction and oxytocin cessation. Maternal and neonatal morbidities were also compared among patients with different durations of oxytocin rest.

RESULTS:

From January 2012 to December 2016, 1,193 patients met eligibility criteria. Among these patients, 267 patients (22.4%) underwent an oxytocin rest that lasted at least 1 hour. After adjusting for potential confounders, the odds ratios of cesarean delivery for patients with oxytocin rest compared with those with no oxytocin rest were as follows: 1.12 (95% CI 0.79–1.58) for less than 1 hour, 0.78 (95% CI 0.48–1.27) for 1–2 hours, 0.60 (95% CI 0.35–1.04) for 2–8 hours, and 0.43 (95% CI 0.24–0.79) for 8 hours or more. We did not detect an association between oxytocin rest of more than 8 hours and a composite of maternal or neonatal morbidities.

CONCLUSION:

An oxytocin rest of at least 8 hours is a clinical tool that may reduce the risk of cesarean delivery among women with protracted latent labor without significantly increasing maternal or neonatal morbidity.
Sensation of Pain Using Buffered Lidocaine for Infiltration Before Vulvar Biopsy
Authors: Villavicencio Jennifer C. , Kulkarni Amita , Luis Christine , Mendez Heidy , Raker Christina , Cronin Beth , Robison Katina
Published: February 2020

OBJECTIVE:

To evaluate the effects of buffered lidocaine on pain scores during vulvar biopsy.

METHODS:

We conducted a double-blind, randomized controlled trial, using prefilled, sequentially numbered, randomized syringes to infiltrate either 3 mL of buffered or nonbuffered lidocaine before vulvar biopsy. The primary outcome was a pain score marked on a 100-mm visual analog scale during infiltration. Secondary outcomes included pain scores after the procedure and change from baseline to infiltration. Participants were recruited to detect a clinically meaningful 15-mm difference in pain scores between groups. Sample size was calculated based on the null hypothesis that the mean pain score would be the same in women treated with buffered lidocaine as in those treated with nonbuffered placebo based on prior studies. Categorical data were compared by Fisher exact test, and continuous data were compared between groups by t-test or Wilcoxon rank sum test.

RESULTS:

From July 2015 to April 2018, 129 participants were randomized to one of two groups: nonbuffered lidocaine or buffered lidocaine. One hundred twenty-five were analyzed (nonbuffered n=62, buffered n=63). Four patients were excluded. The majority of participants were non-Hispanic white women with a mean age of 59 years. There was no difference in the primary outcome of pain during infiltration with a mean pain score of 35.8 mm in the buffered lidocaine group compared with 42.2 in the nonbuffered lidocaine group (mean difference −6.4; 95% CI −18.4 to 5.6; P=.3 by Wilcoxon rank sum test). There was also no difference in secondary outcomes of pain over the entire procedure (mean difference −0.3, 95% CI −9.7 to 9.2; P=.7) or change in pain from baseline to infiltration (mean difference −6.9, 95% CI −18.4 to 4.7; P=.2).

CONCLUSION:

There was no difference in pain scores during vulvar biopsy infiltration between the buffered and nonbuffered lidocaine groups.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02698527.