bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple drug intolerance syndrome and multiple drug allergy syndrome: Epidemiology and associations with anxiety and depression
Authors: Blumenthal K. G. , Li Y. , Acker W. W. , Chang Y. , Banerji A. , Ghaznavi S. , Camargo C. A. , Zhou L. 
Published: March 2018

AbstractBackgroundThe epidemiology of multiple drug intolerance syndrome (MDIS) and multiple drug allergy syndrome (MDAS) is poorly characterized. We used electronic health record (EHR) data to describe prevalences of MDIS and MDAS and to examine associations with anxiety and depression.MethodsPatients with ≥3 outpatient encounters at Partners HealthCare System from 2008 to 2015 were included. Patients with MDIS had intolerances to ≥3 drug classes, and patients with MDAS had hypersensitivities to ≥2 drug classes. Psychiatric conditions and comorbidities were defined from the EHR and used in multivariable logistic regression models to assess the relation between anxiety/depression and MDIS/MDAS.ResultsOf 746 888 patients, 47 634 (6.4%) had MDIS and 8615 (1.2%) had MDAS; 3171 (0.4%) had both. Anxiety (adjusted odds ratio [aOR] 1.72 [1.65, 1.80]), depression (aOR 1.46 [1.41, 1.52]), and both anxiety and depression (aOR 1.97 [1.86, 2.08]) were associated with increased odds of MDIS. Depression was associated with increased odds of MDAS (aOR 1.41 [1.28, 1.56]), but there were no clear associations with anxiety (aOR 1.13 [0.99, 1.30]) nor both depression and anxiety (aOR 1.13 [0.92, 1.38]).ConclusionWhile 6% of patients had MDIS, only 1% had MDAS. MDIS was associated with both anxiety and depression; patients with both anxiety and depression had an almost twofold increased odds of MDIS. MDAS was associated with a 40% increased odds of depression, but there was no significant association with anxiety. Psychological assessments may be useful in the evaluation and treatment of patients with MDIS and MDAS; physiologic causes for MDAS warrant further investigation.
Advancing the Science of Self‐Management in Adults With Long‐Term Left Ventricular Assist Devices
Authors: Casida Jesus , Aikens James , Pagani Francis , Ewald Gregory , Craddock Heidi , Pavol Marykay , Schroeder Sarah , Yang James 
Published: March 2018

AbstractThis study tested the applicability of the individual and family self‐management theory (IFSMT) to self‐management (SM) in patients with left ventricular assist devices (LVADs). From an existing data set, we extracted the following variables that correspond to IFSMT's conceptual dimensions: anxiety, depression, and cognition (context dimension); self‐efficacy (SM process dimension); adherence and quality of life (QOL; outcome dimensions). Descriptive statistics and partial least squares path modeling procedures were used for data analyses. A total of 100 patients (mean age 52 ± 13.4 years) with continuous flow LVAD designs comprised the present study. Most patients were White (78%), married (69%), college‐educated (72%), and on disability (53%). Their mean anxiety and depression scores were slightly above normal, while their cognitive function scores were slightly lower than normal. LVAD care self‐efficacy, adherence, and QOL were within normal ranges. Factor loadings ranged from 0.50 to 1.0, and there were significant forward path relationships among the context, process, and outcome dimensions (β ranges from 0.02 to 0.60, all P values < 0.05). In conclusion, the IFSMT provides a good fit for SM in LVAD. Further research is needed to clarify how best to improve LVAD SM practice and treatment outcomes.
Ocular microcirculation measurement with laser speckle flowgraphy and optical coherence tomography angiography in glaucoma
Authors: Kiyota Naoki , Kunikata Hiroshi , Shiga Yukihiro , Omodaka Kazuko , Nakazawa Toru 
Published: March 2018

AbstractPurposeTo compare glaucoma severity with ocular microcirculation, measured with either laser speckle flowgraphy (LSFG) or optical coherence tomography angiography (OCTA).MethodsWe retrospectively studied 82 eyes of 82 open‐angle glaucoma (OAG) patients who underwent same‐day LSFG and OCTA examinations, with 20 eyes of 20 healthy subjects as controls. In OCTA images, vessel density (VD) (%) was calculated in concentric regions (regions 1, 2 and 3: R1, R2 and R3, respectively) defined by 1.6‐, 3.2‐ and 3.6‐mm‐diameter circles around the optic nerve head (ONH). In R3, the large vessels were automatically masked to calculate pure capillary density (auto R3 VD). LSFG‐measured mean blur rate (MBR) was examined in the overall ONH (MA), vessel‐area ONH (MV) and tissue‐area ONH (MT).ResultsAuto R3 VD had high reproducibility (coefficient of variation: 1.65–3.88%) and accurately reflected manual R3 VD [mean bias: −0.0087% (auto R3 VD – manual R3 VD)]. MA and MT decreased significantly with OAG severity, especially in the early OAG stages (control vs. mild: p = 0.003 and p < 0.001, respectively). R1 VD did not change with severity. R2 and auto R3 VD decreased significantly with OAG severity, especially in the severe stages (R2, mild vs. severe: p = 0.008; auto R3 VD, mild vs. severe: p < 0.001, moderate vs. severe: p = 0.028).ConclusionOptical coherence tomography angiography‐derived auto R3 VD is novel, reproducible and accurately reflects manual measurements. It is useful for differentiating moderate and advanced glaucoma, while LSFG‐derived MT is useful for identifying early glaucoma.
Comparability of subjective and objective measurements of nuclear density in cataract patients
Authors: Makhotkina Natalia Y. , Berendschot Tos T. J. M. , van den Biggelaar Frank J. H. M. , Weik Alexander R. H. , Nuijts Rudy M. M. A. 
Published: March 2018

AbstractPurposeTo evaluate the relationship between subjective and objective measurements of lens density and the energy of phacoemulsification.SettingUniversity Eye Clinic, Maastricht University Medical Centre, Maastricht, the Netherlands.DesignCross‐sectional study.MethodsThe study population included 69 patients. Nuclear opalescence (NO) was graded with the Lens Opacities Classification System III (LOCS III). Thereafter, lens density was measured objectively with Scheimpflug imaging, anterior segment optical coherent tomography and spectral fundus reflectometry (SFR). Cumulative dissipative energy (CDE) and total ultrasound time (US t.t.) of the phacoemulsification were noted. The relationship between the different measurement techniques and energy of phacoemulsification was assessed using Spearman's correlation coefficients.ResultsWe found moderate to strong correlations between LOCS III and objective measurements of the lens density (rho's from 0.53 to 0.78, p < 0.05) and a moderate correlation between three objective measurement techniques (rho's between 0.29 and 0.57, p < 0.05). There was a moderate correlation between CDE, US t.t. and lens density measurements (rho's from 0.29 to 0.55, p < 0.05), and the highest correlation was found between CDE and NO scores. Exclusion of patients with advanced cortical and posterior subcapsular opacities improved the correlation between SFR and lens density measurements but not the correlation with the energy of phacoemulsification.ConclusionLens Opacities Classification System III has shown the highest correlation with phacoemulsification energy and may be a preferred technique for prediction of use of phacoemulsification energy. Advanced cortical and posterior opacities may interfere with the quality of objective measurements but do not affect the correlation between lens density measurements and phacoemulsification energy.
Optic disc–fovea distance and myopia progression in school children: the Beijing Children Eye Study
Authors: Guo Yin , Liu Li Juan , Tang Ping , Feng Yi , Wu Min , Lv Yan Yun , Xu Liang , Jonas Jost B. 
Published: March 2018

AbstractPurposeTo assess changes in the optic disc–fovea distance (DFD) with progressing myopia in school children.MethodsThe school‐based, prospective, longitudinal study included grade‐1 children in 2011 who were yearly re‐examined until 2016. We measured DFD, optic disc diameters and width of parapapillary gamma zone (parapapillary region without Bruch's membrane (BM)) on fundus photographs.ResultsOf 382 grade‐1 children examined in 2011, 294 (77.0%) children (mean age in 2011: 6.4 ± 0.5 years) returned to be examined in 2016. In relative terms, the increase in DFD (1.15 ± 0.33 mm) was more due to an increase in gamma zone width (+300% or 0.29 ± 0.30 mm) than an increase in macular BM length (+18% or 0.74 ± 0.21 mm). In multivariate regression analysis, longer increase in DFD was correlated (regression coefficient r2 = 0.79) with longer axial elongation during the study period (p < 0.001; standardized regression coefficient β: 0.61; non‐standardized regression coefficient B: 0.30; 95% confidence interval (CI): 0.26, 0.33), larger increase in gamma zone width (p < 0.001; β: 0.35; B: 0.40; 95%CI: 0.32, 0.48) and longer axial length in 2011 (p = 0.01; β:0.07; B:0.03; 95%CI:0.01, 0.06). Larger increase in gamma zone width was associated (r2 = 0.73) with larger increase in DFD (p < 0.001; β: 0.51; B: 0.46; 95%CI: 0.39, 0.53), larger increase in the vertical‐to‐horizontal disc diameter ratio (p < 0.001; β: 0.43; B:1.21; 95%CI: 1.00, 1.42) and longer vertical disc diameter (p < 0.001; β: 0.15; B:0.24; 95%CI: 0.14, 0.34).ConclusionIn adolescent school children, axial elongation‐associated increase in DFD was mainly due to an enlargement (+300%) of parapapillary gamma zone, while macular BM length increased to minor degree (+18%). Gamma zone enlargement was correlated with axial elongation‐associated vertical optic disc rotation, potentially due to an increased backward pull of the optic nerve on the temporal optic disc border.
Underlying maternal and pregnancy‐related conditions account for a substantial proportion of neonatal morbidity in late preterm infants
Authors: Bonnevier Anna , Brodszki Jana , Björklund Lars J. , Källén Karin 
Published: March 2018

AbstractAimWe studied the impact of maternal and pregnancy‐related conditions and the effect of gestational age itself, on the health of infants born late preterm.MethodsSingletons born in gestational weeks 34 + 0 to 41 + 6 in 1995–2013 in the southern region of Sweden were identified from a perinatal register. We found 14 030 infants born late preterm and 294 814 born at term. A hierarchical system was developed to examine the impact of pregnancy complications. The outcomes studied were as follows: neonatal death, central nervous system (CNS) or respiratory disease, infection, neonatal admission and respiratory support. Odds ratios (OR) and 95% confidence intervals (95% CI) were obtained using logistic regression analyses.ResultsLate preterm infants were at increased risk for all outcomes compared to term infants, with adjusted ORs from 13.1 (95% CI: 12.7–13.6) for neonatal admission to 2.3 (95% CI: 1.8–2.9) for infections. Late preterm birth after preterm prelabour rupture of membranes was associated with an overall lower risk compared to late preterm births due to other causes. Exposure to antepartum haemorrhage or maternal diabetes increased the risk for CNS and respiratory morbidity.ConclusionMorbidity decreased in late preterm infants with increasing gestational age. Underlying conditions accounted for a substantial part of the morbidity.
A pharmacological rationale for improved everolimus dosing in oncology and transplant patients
Authors: ter Heine R. , van Erp N. P. , Guchelaar H. J. , de Fijter J. W. , Reinders M. E. J. , van Herpen C. M. , Burger D. M. , Moes D. J. A. R. 
Published: March 2018

AimsEverolimus is a drug from the class of mammalian target of rapamycin inhibitors used for both immunosuppressant and oncological indications. We postulate that there is room for improvement of dosing, as the optimal immunosuppressive dose in calcineurin‐free regimens is unknown and since the once daily dosing regimen for oncological indications is often associated with treatment‐limiting toxicity.MethodsWe developed a mechanistic population pharmacokinetic model for everolimus in cancer and transplant patients and explored alternative dosing regimens.ResultsWe found that formulation did not influence bioavailability and that use of >20 mg prednisolone daily increased everolimus clearance. In transplant patients, the approved dose of 0.75–1 mg twice daily (BID) results in subtherapeutic trough levels (<6 μg l–1) and that a higher starting dose of 2.25–3 mg BID is required.ConclusionFor oncological indications, our results encourage the investigation of dosing everolimus 3.75 mg BID in terms of superiority in safety and noninferiority in efficacy.
Vitamin D Analogues Tacalcitol and Calcipotriol Inhibit Proliferation and Migration of T98G Human Glioblastoma Cells
Authors: Emanuelsson Ida , Wikvall Kjell , Friman Tomas , Norlin Maria 
Published: March 2018

AbstractThe active form of vitamin D (1α,25‐dihydroxyvitamin D) acts as a steroid hormone and binds to the vitamin D receptor. This receptor is expressed in most cell types including cells in the central nervous system (CNS). Vitamin D has several functions in the body including effects on brain development, neuroprotection and immunological regulation. It has been shown that vitamin D has antiproliferative activities in different cancer cell lines. Tacalcitol and calcipotriol are synthetic analogues of 1α,25‐dihydroxyvitamin D with reduced effect on calcium metabolism. The aim of this study was to analyse the effects of tacalcitol and calcipotriol on cell viability, proliferation and migration in the human glioblastoma cell line T98G. Glioblastoma is the most lethal type of primary tumours in the CNS. Both analogues decreased cell viability and/or growth, dose‐dependently, in concentrations between 1 nM and 10 μM. Manual counting indicated suppressive effects by the vitamin D analogues on proliferation. Treatment with tacalcitol strongly suppressed thymidine incorporation, indicating that the vitamin D analogues mainly inhibit proliferation. Also, effects on cell migration were measured with wound‐healing assay. Both calcipotriol and tacalcitol reduced the migration rate of T98G cells compared to vehicle‐treated cells. However, they had no effect on caspase‐3 and ‐7 activities, suggesting that their mechanism of action does not involve induction of apoptosis. The current results indicate that the vitamin D analogues tacalcitol and calcipotriol strongly reduce proliferation and migration of human glioblastoma T98G cells, suggesting a potential role for this type of compounds in treatment of brain cancer.
A 28‐day Sub‐acute Genotoxic and Behavioural Assessment of Garcinielliptone FC
Authors: Coelho Vanessa R. , Prado Lismare S. , Rossato Raíssa R. , Ferraz Alexandre B. F. , Vieira Caroline G. , de Souza Luana P. , Pfluger Pricila , Regner Gabriela G. , Valle Marina T. C. , Leal Mirna B. , Dallegrave Eliane , Corrêa Dione S. , Picada Jaqueline N. , Pereira Patrícia 
Published: March 2018

AbstractGarcinielliptone FC (GFC) is a polyisoprenylated benzophenone isolated from Platonia insignis Mart (Clusiaceae) with promising anticonvulsant properties. However, its safe use and other effects on the central nervous system require assessment. This study assessed the toxicological effects of GFC using the comet assay and the micronucleus test in mice treated for 28 days. A behavioural model was employed to detect possible injuries on the central nervous system. Mice treated with GFC (2, 10 and 20 mg/kg; i.p.) daily for 28 days were submitted to rotarod test, open‐field test and tail suspension test (TST). After the behaviour tasks, biological samples were assessed to evaluate genotoxic and mutagenic effects using the comet assay and the micronucleus test. Garcinielliptone FC did not impair the performance of the animals in the rotarod and open‐field tests, with no antidepressant‐like effect in TST. No genotoxic effects in blood and cerebral cortex were observable in the comet assay; however, there was a significant increase in index and frequency of damage in liver after treatment with GFC 20 mg/kg. Garcinielliptone FC did not increase micronucleus frequency in bone marrow. At the tested doses, GFC was not toxic to the CNS and did not induce genotoxic damage to blood or bone narrow cells. DNA damage to liver tissue was caused only by the highest dose, although no mutagenic potential was observed.
HLA‐A*02:07 Allele Associates with Clarithromycin‐Induced Cutaneous Adverse Drug Reactions in Chinese Patients
Authors: Chen Sheng‐An , Zhang Li‐Rong , Yang Fan‐Ping , Yang Lin‐Lin , Yang Ying , Chen Zi‐Hua , Jiang Meng‐Lin , Xiong Hao , Zhu Hui‐Zhong , Qi Zheng , Xing Qing‐He , Luo Xiao‐Qun 
Published: March 2018

AbstractGenetic risk factors could cause cutaneous adverse drug reactions (cADRs) in patients after treatment with clarithromycin. This study explored the association of HLA class I genes with clarithromycin‐cADRs in Han Chinese patients. A total of 12 clarithromycin‐cADR patients and 34 clarithromycin‐tolerant controls were recruited for the high‐resolution genotyping of HLA class I genes (HLA‐A, HLA‐B and HLA‐C). The population controls consisted of 283 Han Chinese retrieved from the MHC database for validated comparison. A molecular docking analysis of HLA‐A*02:07 protein and clarithromycin was conducted using glide module with Schrödinger Suite. Among all tested HLA alleles, the carrier frequencies of HLA‐A*02:07 (58% versus 5.9%, OR = 22.40, 95% CI = 3.58–139.98, p = 8.20 × 10E‐5, pc = 1.1 × 10E‐3) and HLA‐B*46:01 (50% versus 5.9%, OR = 16.00, 95% CI = 2.59–98.99, p = 0.002, pc = 0.03) were significantly higher in clarithromycin‐cADRs than in clarithromycin‐tolerant controls. However, when compared to population controls, only HLA‐A*02:07, and not HLA‐B*46:01, reached statistical significance (58% versus 15.5%, OR = 7.61, 95% CI = 2.31–25.04, p = 1.2 × 10E‐4, pc = 1.7 × 10E‐3). Furthermore, molecular docking data revealed that clarithromycin could bind to and interact with HLA‐A*02:07 in two possible binding situations. These data suggest that HLA‐A*02:07 might be a genetic risk factor for developing clarithromycin‐cADRs in Han Chinese and serve as a useful biomarker for personalized medicine to prevent clarithromycin‐cADRs.
Preventing family transmission of anxiety: Feasibility RCT of a brief intervention for parents
Authors: Cartwright‐Hatton Sam , Ewing Donna , Dash Suzanne , Hughes Zoe , Thompson Ellen J. , Hazell Cassie M. , Field Andy P. , Startup Helen 
Published: March 2018

ObjectivesChildren of anxious parents are at high risk of anxiety disorders themselves. The evidence suggests that this is due to environmental rather than genetic factors. However, we currently do little to reduce this risk of transmission. There is evidence that supporting parenting in those with mental health difficulties can ameliorate this risk. Therefore, the objective of this study was to test the feasibility of a new one‐session, group‐based, preventive parenting intervention for parents with anxiety disorders.DesignFeasibility Randomized Controlled Trial.MethodsA total of 100 parents with anxiety disorders, recruited from adult mental health services in England (and child aged 3–9 years), were randomized to receive the new intervention (a 1‐day, group workshop), or to treatment as usual. Children's anxiety disorder and anxiety symptoms were assessed to 12 months by outcome assessors who were blind to group allocation. Exploratory analyses were conducted on an intention to treat basis, as far as possible.ResultsA total of 51 participants were randomized to the intervention condition and 49 to the control condition (82% and 80% followed to 12 months, respectively). The attendance rate was 59%, and the intervention was highly acceptable to parents who received it. The RCT was feasible, and 12‐month follow‐up attrition rates were low. Children whose parents were in the control condition were 16.5% more likely to have an anxiety disorder at follow‐up than those in the intervention group. No adverse events were reported.ConclusionsAn inexpensive, light‐touch, psycho‐educational intervention may be useful in breaking the intergenerational cycle of transmission of anxiety disorders. A substantive trial is warranted.Practitioner points

Anxiety disorders run in families, but we currently do little to help anxious parents to raise confident children. A brief group workshop was highly acceptable to such parents and was very inexpensive to run.

Children of parents who took part in the brief intervention were 16.5% less likely to have an anxiety disorder, 1 year later, than children whose parents were in the control group.

This was a feasibility study, and while it showed that both the intervention and the research were feasible, the study needs replicating with a much larger sample.

Many parents faced barriers to attending the workshop, and future efforts should focus on widening accessibility.

We were unable to obtain sufficient self‐report data from children, so the outcomes are based on parent report only.
Human hepatocytes and cytochrome P450‐selective inhibitors predict variability in human drug exposure more accurately than human recombinant P450s
Authors: Lindmark Bo , Lundahl Anna , Kanebratt Kajsa P , Andersson Tommy B , Isin Emre M 
Published: March 2018

Background and PurposeDrugs metabolically eliminated by several enzymes are less vulnerable to variable compound exposure in patients due to drug–drug interactions (DDI) or if a polymorphic enzyme is involved in their elimination. Therefore, it is vital in drug discovery to accurately and efficiently estimate and optimize the metabolic elimination profile.Experimental ApproachCYP3A and/or CYP2D6 substrates with well described variability in vivo in humans due to CYP3A DDI and CYP2D6 polymorphism were selected for assessment of fraction metabolized by each enzyme (fmCYP) in two in vitro systems: (i) human recombinant P450s (hrP450s) and (ii) human hepatocytes combined with selective P450 inhibitors. Increases in compound exposure in poor versus extensive CYP2D6 metabolizers and by the strong CYP3A inhibitor ketoconazole were mathematically modelled and predicted changes in exposure were compared with in vivo data.Key ResultsPredicted changes in exposure were within twofold of reported in vivo values using fmCYP estimated in human hepatocytes and there was a strong linear correlation between predicted and observed changes in exposure (r2 = 0.83 for CYP3A, r2 = 0.82 for CYP2D6). Predictions using fmCYP in hrP450s were not as accurate (r2 = 0.55 for CYP3A, r2 = 0.20 for CYP2D6).Conclusions and ImplicationsThe results suggest that variability in human drug exposure due to DDI and enzyme polymorphism can be accurately predicted using fmCYP from human hepatocytes and CYP‐selective inhibitors. This approach can be efficiently applied in drug discovery to aid optimization of candidate drugs with a favourable metabolic elimination profile and limited variability in patients.