bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Adipokines in Predicting the Transition from Acute to Persistent Low Back Pain
Authors: Klyne David M , Hodges Paul W 
Published: February 2020

Abstract

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

Abstract

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 &lt; 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

AbstractIncluding 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.

Summary
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 reviewThe 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 findingsHere, 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.SummaryEcological 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

PurposeAcademic 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.MethodThe 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.ResultsThe 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.ConclusionsBoth 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.

Summary
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.
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

Abstract

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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