bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human papillomavirus vaccination in immigrants and descendants of immigrants in Denmark
Authors: Hertzum-Larsen Rasmus , Thomsen Louise T. , Frederiksen Kirsten , Kjær Susanne K. 
Published: August 2019

Objective
In Denmark, human papillomavirus (HPV) vaccination has been offered at age of 12 to girls born in 1996 and later. In this cohort study, we examined routine HPV vaccination uptake in immigrants and descendants from different countries and regions compared with native Danes, including the influence of socioeconomic characteristics and potential changes in uptake by birth cohort.

Methods
In nationwide registers, we identified all girls born in 1996–2003 (n = 260 251) and obtained information on country of origin, HPV vaccinations and parents’ income and employment. Vaccination was defined as receiving ≥1 dose within 2 years after eligibility for routine vaccination. Odds ratios (ORs) were estimated by logistic regression separately for birth cohorts 1996–2000 and 2001–2003.

Results
Uptake in immigrants and descendants varied by country and region of origin. Overall, immigrants had lower uptake than native Danes, in birth cohorts 1996–2000 [79% vs. 93%, OR = 0.31; 95% confidence interval (CI), 0.29–0.34] and 2001–2003 (63% vs. 73%, OR = 0.60; 95% CI, 0.54–0.66). Descendants had lower uptake than native Danes in cohorts 1996–2000 (89% vs. 93%, OR = 0.65; 95% CI, 0.60–0.68), but higher uptake in cohorts 2001–2003 (76% vs. 73%, OR = 1.15; 95% CI, 1.08–1.21). Most associations were attenuated, but not entirely explained, when adjusting for socioeconomic characteristics.

Conclusion
HPV vaccination uptake varied by country and region. Most immigrants had lower uptake than native Danes, and in most groups, this was not fully explained by socioeconomic differences. Patterns in descendants were mixed. Interventions to increase uptake should be tailored to specific groups of immigrants/descendants.
Sevoflurane Preconditioning Prevents Septic Myocardial Dysfunction in Lipopolysaccharide-Challenged Mice
Authors: Li Jianling , Liu Panhong , Li Hongmei , Wang Yanping , Chen Yifei , Qi Renbin , Li Yalan 
Published: August 2019

Abstract:
Myocardial dysfunction accompanied by severe sepsis could significantly increase the mortality rate of septic patients. This study investigated the effects and the potential mechanisms of sevoflurane preconditioning on septic myocardial dysfunction, which was induced by lipopolysaccharide (LPS; from Escherichia coli O55:B5; 18 mg/kg) in mice. Results indicated that 1 hour after the administration, LPS induced a significant increase in cell-surface Toll-like receptor 4 (TLR4), cytoplasmic IKKα protein expression, and nuclear translocation of nuclear factor kappa-B (NF-κB) protein (P < 0.05), which was attenuated by preconditioning with sevoflurane. Two hours after the administration, inhalation of sevoflurane significantly reduced the serum levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-10 (P < 0.05). Twelve hours after administration, LPS caused pathological damage to the heart and elevated the serum levels of lactate dehydrogenase (LDH) and creatine kinase-MB (P < 0.05). Echocardiography indicated that sevoflurane preconditioning significantly improved systolic and diastolic function. The inhalation of sevoflurane inhibited increases in myeloperoxidase (MPO), macrophage inflammatory protein-2 (MIP-2), TNF-α, and IL-1β levels (P < 0.05) induced by endotoxemia, whereas IL-6 release was facilitated. Sevoflurane attenuated the myocardial levels of nitric oxide (P < 0.05) without an apparent influence on malondialdehyde (MDA) or superoxide dismutase (P > 0.05). In conclusion, our study indicates that exposure to 2% sevoflurane before LPS challenge is protective against myocardial dysfunction. Sevoflurane preconditioning may attenuate neutrophil infiltration and the release of inflammatory mediators during endotoxemia.
Exploration of Physiological and Pathophysiological Implications of miRNA-143 and miRNA-145 in Cerebral Arteries
Authors: Christensen Simon Topp , Johansson Sara Ellinor , Warfvinge Karin , Braun Thomas , Boettger Thomas , Edvinsson Lars , Haanes Kristian Agmund 
Published: August 2019

Abstract:
Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke with a high short-term mortality rate which leads to cognitive impairments that reduce the quality of life of the majority of patients. The miRNA-143/145 cluster is highly expressed in vascular smooth muscle cells (VSMC) and has been shown to be necessary for differentiation and function, as well as an important determinant for phenotypic modulation/switching of VSMCs in response to vascular injury. We aimed to determine whether miRNA-143 and miRNA-145 are important regulators of phenotypical changes of VSMCs in relation to SAH, as well as establishing their physiological role in the cerebral vasculature. We applied quantitative PCR to study ischemia-induced alterations in the expression of miRNA-143 and miRNA-145, for rat cerebral vasculature, in an ex vivo organ culture model and an in vivo SAH model. To determine the physiological importance, we did myograph studies on basilar and femoral arteries from miRNA-143/145 knockout mice. miRNA-143 and miRNA-145 are not upregulated in the vasculature following our SAH model, despite the upregulation of miR-145 in the organ culture model. Regarding physiological function, miRNA-143 and miRNA-145 are very important for general contractility in cerebral vessels in response to depolarization, angiotensin II, and endothelin-1. Applying an anti-miRNA targeting approach in SAH does not seem to be a feasible approach because miRNA-143 and miRNA-145 are not upregulated following SAH. The knockout mouse data suggest that targeting miRNA-143 and miRNA-145 would lead to a general reduced contractility of the cerebral vasculature and unwanted dedifferentiation of VSMCs.
Generation and Validation of a Limited Sampling Strategy to Monitor Mycophenolic Acid Exposure in Children With Nephrotic Syndrome
Authors: Benz Marcus R. , Ehren Rasmus , Kleinert Daniela , Müller Carsten , Gellermann Jutta , Fehrenbach Henry , Schmidt Heinrich , Weber Lutz T. 
Published: August 2019

Background:
Mycophenolate mofetil (MMF) plays an increasingly important role in the treatment of children with nephrotic syndrome, especially in steroid sparing protocols. Recent publications show the relationship of exposure to its active moiety mycophenolic acid (MPA) and clinical efficacy. Performance of full-time pharmacokinetic (PK) profiles, however, is inconvenient and laborious. Established limited sampling strategies (LSS) to estimate the area under the concentration (AUC) versus time curve of MPA (MPA-AUC) in pediatric renal transplant recipients cannot be easily transferred to children suffering from nephrotic syndrome, mainly because of the lack of concomitant immunosuppressive therapy. We therefore aimed for the generation and validation of a LSS to estimate MPA exposure to facilitate therapeutic drug monitoring in children with nephrotic syndrome.

Methods:
We performed 27 complete PK profiles in 23 children in remission [mean age (±SD):12.3 ± 4.26 years] to generate and validate an LSS. Sampling time points were before administration (C0) and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours after the administration of MMF. MPA was measured by enzyme multiplied immunoassay technique. There was no concomitant treatment with calcineurin inhibitors.

Results:
Mean daily dose of MMF was 927 ± 209 mg/m2 of body surface area resulting in a mean MPA-AUC0-12 value of 59.2 ± 29.3 mg × h/L and a predose level of 3.03 ± 2.24 mg/L. Between-patient variability of dose-normalized MPA-AUC0-12 was high (coefficient of variation: 45.5%). Correlation of predose levels with the corresponding MPA-AUC0-12 was moderate (r
2 = 0.59) in a subgroup of 18 patients (20 PK profiles, generation group). An algorithm based on 3 PK sampling time points during the first 2 hours after MMF dosing (estimated AUC0-12 = 8.7 + 4.63 × C0 + 1.90 × C1 + 1.52 × C2) was able to predict MPA-AUC with a low percentage prediction error (3.88%) and a good correlation of determination (r
2 = 0.90). Validation of this algorithm in a randomized separate group of 6 patients (7 PK profiles, validation group) resulted in comparably good correlation (r
2 = 0.95) and low percentage prediction error (5.57%).

Conclusions:
An abbreviated profile within the first 2 hours after MMF dosing gives a good estimate of MPA exposure in children with nephrotic syndrome and hence has the potential to optimize MMF therapy.
Pharmacodynamic Monitoring of Mycophenolic Acid Therapy: Improved Liquid Chromatography–Tandem Mass Spectrometry Method for Measuring Inosin-5′-Monophosphate Dehydrogenase Activity
Authors: Weißbarth Gero , Wiesen Martin H. J. , Fietz Cornelia , Streichert Thomas , Ehren Rasmus , Weber Lutz T. , Müller Carsten 
Published: August 2019

Background:
Mycophenolic acid (MPA), a powerful inhibitor of lymphocyte proliferation, is widely used in transplantation medicine and as a glucocorticoid-sparing agent in rheumatic and inflammatory diseases. As inosine-5′-monophosphate dehydrogenase (IMPDH), the target enzyme of MPA, shows high interindividual variability in its basal activity, the assessment of IMPDH activity in addition to pharmacokinetic monitoring has emerged as a strategy to individualize MPA pharmacotherapy.

Methods:
A liquid chromatography–tandem mass spectrometry method was developed to measure IMPDH activity in peripheral blood mononuclear cells from lithium-heparinized blood. Stable isotope-labeled analogs of analytes were used as internal standards for the quantitative analyses of xanthosine-5′-monophosphate (XMP) and adenosine-5′-monophosphate (AMP). IMPDH activity was expressed as enzymatic production of XMP per time normalized to the AMP concentration. Validation and evaluation of the new method were performed by using blood samples from healthy volunteers (n = 10).

Results:
Linearity was demonstrated over the concentration ranges of 0.25–80 μM for XMP and 4–80 µM for AMP (R2 > 0.99). Between-day and within-day assay precisions and accuracies were within the acceptance criterion of ±15%. Matrix effects were fully compensated by the coelution of internal standards. Specific and linear XMP production (R2 > 0.99) and the inhibition of IMPDH activity by MPA at clinically relevant doses were demonstrated.

Conclusions:
In this study, a liquid chromatography–tandem mass spectrometry method to measure IMPDH activity was established and fully evaluated for matrix and ion suppression effects. The method enabled precise quantification of IMPDH activity for the improvement of pharmacokinetic/pharmacodynamic therapeutic drug monitoring approaches to optimize immunosuppressive treatment with MPA.
Population Pharmacokinetics of Ganciclovir in Critically Ill Patients
Authors: Krens Stefanie D. , Hodiamont Caspar J. , Juffermans Nicole P. , Mathôt Ron A.A. , van Hest Reinier M. 
Published: August 2019

Background:
The pharmacokinetic (PK) data of ganciclovir (GCV), a first-line antiviral treatment for cytomegalovirus infections, in critically ill patients are limited. This study aimed at characterizing GCV population PK and interindividual variability (IIV) in intensive care unit (ICU) patients. Secondary objectives were to identify patient characteristics responsible for IIV and simulate GCV exposure for different dosing regimens.

Method:
In this retrospective observational study, clinical data and serum GCV levels were collected from ICU patients on intravenous GCV. PK modeling, covariate analyses, and explorative Monte Carlo dosing simulations (MCS) were performed using nonlinear mixed-effects modeling. Bootstrap and visual predictive checks were used to determine model adequacy.

Results:
In total, 128 GCV measurements were obtained from 34 patients. GCV PK conformed to a 1-compartment model with first-order elimination. After multivariate analyses, only the estimated glomerular filtration rate calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (P < 0.001) was included as a covariate. In the final model, the estimated clearance (CL) and volume of distribution (V1) were 2.3 L/h and 42 L, respectively, for a patient with the median CKD-EPI of the population (65 mL/min per 1.73 m2). The association between CKD-EPI and CL decreased the residual variability from 0.56 to 0.43 and V1-IIV from 114% to 80%, whereas CL-IIV changed from 43% to 47%. MCS revealed that a substantial number of patients may not achieve the GCV PK/pharmacodynamic target trough level (>1.5 mg/L) when administering the label-recommended dose reductions for patients with CKD-EPI <50 mL/min.

Conclusions:
A large IIV was observed in GCV PK among ICU patients. CKD-EPI could partially explain the IIV, although a large part of the variability remains unclear. MCS suggested that recommended dose reductions for CKD-EPI <50 mL/min may lead to subtherapeutic plasma GCV levels in these patients.
Excretion of Antipsychotics Into the Amniotic Fluid, Umbilical Cord Blood, and Breast Milk: A Systematic Critical Review and Combined Analysis
Authors: Schoretsanitis Georgios , Westin Andreas A. , Deligiannidis Kristina M. , Spigset Olav , Paulzen Michael 
Published: August 2019

Background:
Antipsychotics are being increasingly prescribed during pregnancy and in the postpartum period. However, knowledge regarding the ability of antipsychotics to enter the fetal, newborn, and infant circulation presents inconsistencies. Evidence for penetration ratios in an array of matrices will contribute to further studies examining the mechanistic pathway from antipsychotic use to adverse events.

Methods:
A systematic literature search of PubMed and EMBASE was performed to identify studies assessing the concentrations of antipsychotics in maternal blood (serum or plasma), amniotic fluid, umbilical cord blood, and/or breast milk. The penetration ratios were estimated by dividing the antipsychotic concentrations in the target matrix (ie, amniotic fluid, umbilical cord blood or breast milk) by the maternal concentration. Data are provided in means with ranges or SD depending on data availability.

Results:
Forty-nine eligible studies were identified. For amniotic fluid, the penetration ratios were estimated for quetiapine, clozapine, and flupentixol, with quetiapine displaying the highest ratio (mean 0.59, range 0.09–1.70 versus 0.56, range 0.31–0.82 for clozapine and 0.24, range 0.23–0.24 for flupentixol). For umbilical cord blood, olanzapine had the highest ratio (mean 0.71 ± 0.42) followed by haloperidol (mean 0.66 ± 0.40) and paliperidone (mean 0.53, range 0.50–0.58). In case of breast milk, the highest ratio was observed for amisulpride (mean 14.42, range 11.86–19.50) followed by clozapine (mean 3.19, range 2.79–4.32) and haloperidol (mean 3.11, range 0.59–6.67).

Conclusions:
The ability of antipsychotics to enter the fetal, newborn, and infant circulation varies considerably among antipsychotics. Given sampling constraints of other matrices, measuring antipsychotic concentrations in maternal blood may represent the least expensive, most readily available, and reliable estimate of fetal/infant exposure.
Monitoring Prenatal Exposure to Buprenorphine and Methadone
Authors: Di Trana Annagiulia , La Maida Nunzia , Tittarelli Roberta , Huestis Marilyn A. , Pichini Simona , Busardò Francesco P. , Carlier Jeremy 
Published: August 2019

Purpose:
Buprenorphine and methadone are international gold standards for managing opioid use disorders. Although they are efficacious in treating opioid dependence, buprenorphine and methadone present risks, especially during pregnancy, causing neonatal abstinence syndrome and adverse obstetrical outcomes. Buprenorphine and methadone are also abused during pregnancy, and identifying their use is important to limit unprescribed prenatal exposure. Previous studies have suggested that concentrations of buprenorphine, but not methadone markers in unconventional matrices may predict child outcomes, although currently only limited data exist. We reviewed the literature on concentrations of buprenorphine, methadone, and their metabolites in unconventional matrices to improve data interpretation.

Methods:
A literature search was conducted using scientific databases (PubMed, Scopus, Web of Science, and reports from international institutions) to review published articles on buprenorphine and methadone monitoring during pregnancy.

Results:
Buprenorphine and methadone and their metabolites were quantified in the meconium, umbilical cord, placenta, and maternal and neonatal hair. Methadone concentrations in the meconium and hair were typically higher than those in other matrices, although the concentrations in the placenta and umbilical cord were more suitable for predicting neonatal outcomes. Buprenorphine concentrations were lower and required sensitive instrumentation, as measuring buprenorphine glucuronidated metabolites is critical to predict neonatal outcomes.

Conclusions:
Unconventional matrices are good alternatives to conventional ones for monitoring drug exposure during pregnancy. However, data are currently scarce on buprenorphine and methadone during pregnancy to accurately interpret their concentrations. Clinical studies should be conducted with larger cohorts, considering confounding factors such as illicit drug co-exposure.
Current Situation of the Metabolomics Techniques Used for the Metabolism Studies of New Psychoactive Substances
Authors: Manier Sascha K. , Meyer Markus R. 
Published: August 2019

Purpose:
The purpose of this short overview is to summarize and discuss the English-written and PubMed-listed review articles and original studies published between January 2015 and April 2019 on the use of metabolomics techniques for investigating the metabolism of new psychoactive substances (NPS). First, a brief introduction is given on the metabolism of NPS and metabolomics techniques in general. Afterward, the selected original studies are summarized and discussed. Finally, a section dedicated to the studies on NPS beyond metabolism using metabolomics techniques is provided. Thereafter, both sections are concluded and perspectives are given.

Methods:
PubMed was searched for English-written literature published between January 1, 2015 and April 1, 2019.

Results:
The present short overview found that the current use of metabolomics techniques in investigating the metabolism of NPS is rather limited, but these techniques can support and facilitate traditional metabolism studies.

Conclusions:
Thus, there may be a certain potential for using metabolomics techniques in the field of NPS research, but a great challenge remains to thoroughly adopt the existing metabolomics methods.
DIAGNOSTIC CHALLENGES IN NECROTIC UVEAL MELANOMA
Authors: Peddada Krishi , Dalvin Lauren A. , Mashayekhi Arman , Shields Carol L. 
Published: August 2019

Purpose:
To describe a case of ciliochoroidal melanoma with massive spontaneous hemorrhagic retinal and choroidal detachment that presented a diagnostic challenge because of poor fundus visualization and atypical imaging features.

Methods:
Case report.

Results:
A 71-year-old white man on apixaban for atrial fibrillation presented with sudden onset of pain and vision loss in the left eye. The patient was found to have total hemorrhagic retinal detachment and was referred for our opinion. On examination, visual acuity was 20/25 in the right eye and light perception in the left eye. Intraocular pressures were 10 mmHg in the right eye and 21 mmHg in the left eye. The unaffected right eye demonstrated only macular retinal pigment epithelial alterations. Evaluation of the left eye revealed dilated episcleral sentinel vessels superonasally, shallow anterior chamber, and total hemorrhagic retinal and choroidal detachment to the back of the crystalline lens. There was no view of the choroid. Transillumination demonstrated diffuse blockage of light from blood and no specific shadow. B-scan ultrasonography revealed total retinal and choroidal detachment with dense echoes of blood under the retina and in the suprachoroidal space with elevation of 12 mm and no definite mass or spontaneous vascular pulsations. Magnetic resonance imaging revealed diffuse high signals within the globe on T1-weighted images with no specific mass. On gadolinium enhancement, a localized enhancing area temporally of 12-mm thickness and a localized nonenhanced area nasally of 11-mm thickness was noted. Both areas showed low signal on T2-weighted images. Despite atypical features, suspicion for underlying ciliochoroidal melanoma and poor visual prognosis lead to enucleation. Histopathology confirmed an extensively necrotic, mushroom-shaped ciliochoroidal melanoma with total hemorrhagic retinal and choroidal detachment.

Conclusion:
Diagnosis of necrotic posterior uveal melanoma can be challenging, because these tumors can be camouflaged by overlying hemorrhagic retinal and choroidal detachment and can present with atypical features on ultrasonography and magnetic resonance imaging. Patients with spontaneous hemorrhagic retinal and choroidal detachment should be evaluated for possible underlying malignancy.
PARACENTRAL ACUTE MIDDLE MACULOPATHY FOLLOWING ORAL INTAKE OF SUMATRIPTAN
Authors: Zonnevylle Kirsten E. , Jacob Julie , Luyten Steven , Stanescu-Segall Dinu 
Published: August 2019

Purpose:
The purpose of this report was to describe a case with paracentral acute middle maculopathy after oral intake of sumatriptan.

Methods:
Case presentation.

Results:
One patient showed typical findings on fundoscopic examination and optical coherence tomography consistent with paracentral acute middle maculopathy following oral intake of sumatriptan.

Conclusion:
Sumatriptan may be a trigger for paracentral acute middle maculopathy.
Promoting treatment for hepatitis C in people who inject drugs: A review of the barriers and opportunities
Authors: Pedlar Annie , Sandhu Prabjot (Jodie) 
Published: August 2019

ABSTRACT

Background:
People who inject drugs (PWIDs) comprise a significant amount of the population who are also positive for hepatitis C virus (HCV) around the world. Even though there is evidence that patients who currently inject drugs do not display altered treatment adherence or medication effectiveness, health care providers are still hesitant to treat this patient population based on perceived threats and barriers.

Objectives:
This literature review informs of the perceived barriers associated with PWID in receiving HCV treatment and supports recommendations to address these barriers.

Data sources:
For this review, eight scholarly articles rated levels I A through II B using John Hopkins Evidence-Based Practicing ratings consisting of randomized controlled trials, systematic reviews, and meta-analyses were selected. Both qualitative and quantitative data contributed to identifying perceived barriers and suggested course of action that should be taken to increase HCV treatment uptake among PWID.

Conclusions:
The three main perceived barriers are evidence of barriers to treatment in the PWID populations and include increased risk of reinfection, low adherence to treatment, and decreased response to treatment. Removal of these barriers by increasing education about HCV disease and treatment options to both patients and health care workers and changing current policy in health care settings to provide enhanced access to HCV treatment for PWID can promote an opportunity for successful treatment of these patients.

Implications for practice:
There is a significant need for HCV treatment among PWID. Opportunities for successful treatment exist and should be adopted.