bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Risk of Mortality Associated With Opioid Use in Patients With Acute Heart Failure: Systematic Review and Meta-analysis
Authors: Gao Daniel , David Cláudio , Rosa Mário M. , Costa João , Pinto Fausto J. , Caldeira Daniel 
Published: November 2020

Aims:
The impact of opioids in acute heart failure (AHF) is unclear. This systematic review with meta-analysis aimed to evaluate the mortality risk associated with opioid use in AHF.

Methods and Results:
An electronic search was performed in MEDLINE, CENTRAL, Web of Science Core Collection, and SCIELO (December 2019) for randomized controlled trials and observational studies evaluating the impact of opioids in in-hospital and 30-day mortality in patients with AHF. Data were screened, extracted, and appraised by 2 independent reviewers. A random-effects meta-analysis to estimate the pooled odds ratios (OR) with 95% confidence intervals (CI) was performed and heterogeneity was evaluated using the I2 statistics. Six observational retrospective studies with 151,735 participants were included. Pooled results showed a statistical significant association between morphine and in-hospital mortality (OR 1.78; 95% CI 1.01–3.13; I2 = 92%; 6 studies) and 30-day mortality (OR 1.56; 95% CI 1.14–2.15; I2 = 0; 2 studies). Both outcomes were rated as having a serious risk of bias and had a very low Grading of Recommendation, Assessment, Development, and Evaluation evidence.

Conclusions:
Opioids seem to be associated with an increased risk of short-term mortality in AHF patients; however, the confidence in the estimated effect is very low, which highlights the need of further research to evaluate this question.
Rapid Simultaneous Determination of 14 Antidepressants and 13 Antipsychotics in Human Plasma by Using High-Performance Liquid Chromatography–Tandem Mass Spectrometry With Dynamic Multiple Reaction Monitoring and Its Application to Therapeutic Drug Monitoring
Authors: Lyu Haiyan , Chen Binbin , Xu Xiangzhen , Zhu Chunyan , Ma Chunling , Du Yu , Liu Farong , Wu Caisheng 
Published: November 2020

Background:
A comprehensive, stable, and efficient high-performance liquid chromatography–tandem mass spectrometry method was developed for rapidly analyzing 14 antidepressants and 13 antipsychotics in human plasma for routine clinical therapeutic drug monitoring.

Methods:
Simple protein precipitation was used for the pretreatment of plasma samples; dynamic multiple reaction monitoring was used to avoid the loss of sensitivity caused by numerous ion transitions. In all, 80 ion transitions of 40 compounds were quantitatively determined in 6 minutes.

Results:
The limit of detection for the 27 analytes was in the range of 0.1–30 ng/mL, and all calibration lines prepared using blank plasma were linear with a correlation coefficient of r2 ≥ 0.99. The method was accurate and precise with acceptable intraday and interday precisions (coefficients of variation, ≤20% for a lower limit of quantification and ≤15% for other quality control samples) and an accuracy of 85.51%–114.77%. This analysis method has been completely validated and successfully used in routine clinical therapeutic drug monitoring for more than 9963 samples [including 488 samples having drug concentrations above the laboratory alert level (supra–alert-level samples)] at Xiamen Xianyue Hospital.

Conclusions:
This dynamic method is comprehensive (includes most antidepressants and antipsychotics listed in China), reliable (stably used for almost 2 years), and efficient (convenient sample processing and short run time) and provides a large amount of meaningful data for optimized pharmacotherapy. Our experimental data from the plasma concentrations of supra–alert-level samples could serve as a reference for the interpretation of the pharmacokinetics of patients with a high risk of toxicity or loss of tolerability.
Physician Perspective and Challenges Ordering/Interpreting Laboratory Tests Related to the Opioid Crisis in America
Authors: Zhu Xiaoying , Bratanow Nancy C. 
Published: November 2020

Abstract:
The opioid crisis is a profound public health crisis in the United States. It has significantly increased morbidity and mortality in our nation. There are many contributing factors to the opioid crisis, including a strong national and international interest to treat pain as effectively as possible. To combat this crisis, numerous strategies have been implemented over the past few years at the legislative, health system, and patient levels. As a result of these efforts, for the first time since 1999, drug overdose deaths in the United States decreased from 2017 to 2018, when deaths involving all opioids, prescription opioids, and heroin decreased by 2%, 13.5%, and 4.1%, respectively. To continue to curb the opioid crisis, it is imperative to optimize pain control through multidisciplinary and multimodal approaches and to adhere to opioid prescribing guidelines from regulatory and professional organizations to minimize risks for opioid misuse and abuse. Urine drug testing is an important means to assist with opioid monitoring and safe opioid prescribing. There are challenges when ordering urine drug tests, collecting specimens, and interpreting test results. Inaccurate interpretations of laboratory results can have significantly negative impacts on patients care and life. There is a critical need for prescriber education by laboratory experts in the use of drug testing and interpretation of results. To interpret test results correctly and make safe prescribing decisions, it is very important for prescribers/providers to consult clinical toxicologists, laboratory directors, and reporting staff. This interaction is vital and provides excellence of care for patients. This review aims to provide information concerning the opioid crisis in the United States and summarizes the challenges ordering and interpreting opioid-related laboratory testing as well as pertinent guidelines and recommendations.
Evolving Role of Pharmacogenetic Biomarkers to Predict Drug-Induced Hematological Disorders
Authors: Pattanaik Smita , Jain Arihant , Ahluwalia Jasmina 
Published: November 2020

Abstract:
Drug-induced hematological disorders constitute up to 30% of all blood dyscrasias seen in the clinic. Hematologic toxicity from drugs may range from life-threatening marrow aplasia, agranulocytosis, hemolysis, thrombosis to mild leukopenia, and thrombocytopenia. Pathophysiologic mechanisms underlying these disorders vary from an extension of the pharmacological effect of the drug to idiosyncratic and immune-mediated reactions. Predicting these reactions is often difficult, and this makes clinical decision–making challenging. Evidence supporting the role of pharmacogenomics in the management of these disorders in clinical practice is rapidly evolving. Despite the Clinical Pharmacology Implementation Consortium and Pharmacogenomics Knowledge Base recommendations, few tests have been incorporated into routine practice. This review aims to provide a comprehensive summary of the various drugs which are implicated for the hematological adverse events, their underlying mechanisms, and the current evidence and practical recommendations to incorporate pharmacogenomic testing in clinical care for predicting these disorders.
Relationship of Prolactin Concentrations to Steady-State Plasma Concentrations of Aripiprazole in Patients With Schizophrenia
Authors: Tasaki Minami , Yasui-Furukori Norio , Kubo Kazuyoshi , Yokoyama Saaya , Shinozaki Masataka , Sugawara Norio , Inoue Yoshimasa , Shimoda Kazutaka 
Published: November 2020

Background:
Aripiprazole is regarded as the first-line antipsychotic medication. Long-term aripiprazole therapy can cause hypoprolactinemia, which may result from its activity as a dopamine agonist. However, there is little information on hypoprolactinemia and steady-state aripiprazole concentrations.

Methods:
The subjects included 66 male and 177 female patients diagnosed with schizophrenia who were treated with aripiprazole. The plasma concentrations of aripiprazole and dehydroaripiprazole and the plasma concentration of prolactin were measured using high-performance liquid chromatography and enzyme immunoassay, respectively. A prolactin concentration of <5 ng/mL was defined as hypoprolactinemia.

Results:
Fifty-two of the 66 male patients (79%) and 58 of the 177 female patients (33%) had hypoprolactinemia. There were significant inverse correlations between plasma prolactin levels and plasma concentrations of aripiprazole (rs = −0.447, P < 0.001) and the active moiety (aripiprazole plus dehydroaripiprazole) (rs = −0.429, P < 0.001) in men. In women, significant inverse correlations were also found between plasma prolactin levels and plasma concentrations of aripiprazole (rs = −0.273, P < 0.01) and the active moiety (rs = −0.275, P < 0.01).

Conclusions:
These findings suggest that lower prolactin levels are, to some extent, associated with higher plasma drug concentrations in male and female patients with schizophrenia treated with aripiprazole.
Physical activity and menopausal symptoms in women who have received menopause-inducing cancer treatments: results from the Women's Wellness After Cancer Program
Authors: Bailey Tom G. , Mielke Gregore I. , Skinner Tina S. , Anderson Debra , Porter-Steele Janine , Balaam Sarah , Young Leonie , McCarthy Alexandra L. 
Published: November 2020

Abstract

Objective:
This randomized controlled trial tested a digitally-delivered whole-of-lifestyle program for women previously treated for cancer. We investigated (1) associations between self-reported physical activity (PA) and menopausal symptoms and (2) if the intervention was associated with beneficial changes in PA and menopausal symptoms.

Methods:
Women were randomized to intervention (n = 142) or control (n = 138). The intervention targeted lifestyle behavior including PA. Self-reported PA (International Physical Activity Questionnaire – Short Form) and menopausal symptom (Green Climacteric Scale, GCS) data were collected at baseline, with measures repeated at 12 weeks (end of intervention) and 24 weeks (to assess sustainability). Generalized estimating equation models explored associations between PA and GCS scores. Mixed-effects generalized equation models analyzed changes within and between groups in PA and GCS scores.

Results:
Total GCS scores were 1.83 (95% CI: 0.11-3.55) and 2.72 (95% CI: 1.12-4.33) points lower in women with medium and high levels of PA, respectively, than in women with low levels of PA. Total average GCS scores were 1.02 (0.21-2.26) and 1.61 (0.34-2.87) points lower in those undertaking moderate or vigorous intensity PA, respectively. Time spent walking, and performing moderate and vigorous PA were not different between intervention and control. The average GCS decrease of 0.66 points (95% CI: 0.03-1.29; p time = 0.03) over 24 weeks was not different between groups.

Conclusion:
This exploratory study established a stepwise association between moderate and vigorous PA and a lower total menopausal symptom score. The intervention did not appear to increase self-reported PA in women treated for early stage breast, reproductive, and blood cancers.
The ewe as an animal model of vaginal atrophy and vaginal Er:YAG laser application
Authors: Hympanova Lucie , Rynkevic Rita , Mori Da Cunha Marina G. M. C. , Diedrich Chantal M. , Blacher Silvia , De Landsheere Laurent , Mackova Katerina , Krofta Ladislav , Roovers Jan-Paul , Deprest Jan 
Published: November 2020

Abstract

Objective:
In sheep of reproductive age, we aimed to document decrease in epithelial thickness, glycogen amount, and other vaginal changes after castration and the effect of Er:YAG laser as used clinically.

Methods:
On day 0, 16 sheep underwent ovariectomy. They were randomized to sham or three vaginal Er:YAG laser applications at monthly intervals. Primary outcome was vaginal epithelial thickness (d60, d71, d73, d77, and d160). Secondary outcomes included indicators of atrophy (vaginal health index = VHI), pH, cytology, morphology at the above time points, microcirculation focal depth (FD; d70 and d160), and at sacrifice (d160) vaginal dimensions and active and passive biomechanical testing.

Results:
Menopausal changes between 60 and 160 days after ovariectomy included a progressive decrease in epithelial thickness, in VHI, FD, glycogen, elastin content and vasculature, and an increase in pH and collagen content. In lasered animals, the first day a few white macroscopic foci were visible and an increase in pH was measured. Both disappeared within 3 days. Seven days after laser the epithelial thickness increased. At sacrifice (d160), there were no differences between sham and laser group in vaginal dimensions, morphometry, mitotic and apoptotic activity, active contractility, vaginal compliance, except for a lower blood vessel density in the lamina propria of the midvagina in the laser group.

Conclusions:
In reproductive sheep, ovariectomy induces vaginal atrophy evidenced in different outcome measurements. Vaginal Er:YAG laser induced visual impact, a short-term increase in epithelial thickness yet no long-term changes compared to sham therapy in menopausal controls.

Video Summary:
http://links.lww.com/MENO/A672.
Relationship between number of menopausal symptoms and work performance in Japanese working women
Authors: Hashimoto Keiko , Yoshida Mikako , Nakamura Yasuka , Takeishi Yoko , Yoshizawa Toyoko 
Published: November 2020

Abstract

Objective:
The presence of various menopausal symptoms could decrease work performance because symptom management strategies differ, and it is difficult to control all symptoms at work. The aim of this study was to examine the relationship between the number of menopausal symptoms experienced and work performance in working women.

Methods:
An online cross-sectional study was conducted with 599 working Japanese women aged 45 to 65 years. To represent work performance, absolute presenteeism was measured using the Japanese version of the World Health Organization and Work Performance Questionnaire short form, and menopausal symptoms were measured using the Greene Climacteric Scale. The total number of subscales on which a participant scored more than one point represented the number of menopausal symptoms.

Results:
Participants’ mean age was 54.2 years, and 60.6% were postmenopausal. Their mean Greene Climacteric Scale score and mean absolute presenteeism score were 10.5 ± 10.6 and 61.7 ± 17.9, respectively. The proportions of participants who provided care for a family member, who had chronic disease, and who undertook regular exercise were significantly different among the four groups. After adjusting for other factors, absolute presenteeism was negatively correlated with the number of menopausal symptoms experienced (β = −0.13, P < 0.001).

Conclusions:
Higher numbers of menopausal symptoms were correlated with lower work performance. The maintenance of health and the provision of appropriate working environments would help working women and improve work performance by reducing menopausal symptoms.
Menopause, the gut microbiome, and weight gain: correlation or causation?
Authors: Becker Sarah L. , Manson JoAnn E. 
Published: November 2020

Abstract
The gut microbiome is a key regulator of metabolism and influences the metabolism of estrogens, however, the microbiome's role in the changes in body composition and metabolic risk factors experienced by menopausal women remains largely unexplored. Menopause has been shown to alter the gut microbiome, and rodent studies suggest that microbiome changes postovariectomy are associated with increased adiposity, decreased metabolic rate, and insulin resistance, changes attenuated by estrogen administration. Given these data, a deeper understanding of the gut microbiome's relationship to menopause-induced changes in body composition and metabolism is warranted and may offer opportunity for novel therapeutic interventions.
The microbiome is central to both systemic and estrogen metabolism, and is altered by the menopausal transition, suggesting an important role of the microbiome in the increased metabolic risk faced by menopausal women. Although additional research is needed to establish a causal link, the interrelationship between menopause and the gut microbiome may represent a new frontier to address menopause-related metabolic risk.
Internal Radiation Dose Evaluation for an Unruptured Post Release Tristructural Isotropic Fuel Particle for Advanced and Micro-reactor Applications
Authors: Condon Caitlin A. , Ivanusa Pavlo , Bunn Amoret L. , Jensen Philip J. 
Published: November 2020

Abstract
There are unique benefits from advanced/micro-reactor designs and fuel types that offer safety features in the case of an accident that may reduce environmental consequences compared to conventional reactors and fuels. Tristructural isotropic (TRISO) fuel particles are a robust advanced nuclear fuel type that leads to the unique question of how unruptured, activated TRISO particles will interact with humans. TRISO particles are 900 μm in size, and that particle size restricts internal dose assessment to the ingestion pathway. Activity of the TRISO particle was established by High Temperature Engineering Test Reactor simulations. The TRISO particle encapsulation was assumed to be perfect; exploration of internal dose contribution from radionuclides released from encapsulation was not included. The TRISO particle was assumed to be mixed actively within each alimentary tract compartment such that homogenous distribution could be assumed according to the International Commission on Radiological Protection publication 133. The dose assessment results indicate that the rectosigmoid colon had the highest internal organ dose for both reference male (2.1 Sv) and female (2.3 Sv). The internal dose from ingestion of the scenario-specific TRISO particle was 0.25 Sv for the reference male and 0.29 Sv for the reference female, which exceeds the annual occupational effective dose limit of 0.05 Sv in the Code of Federal Regulations, 10 CFR Part 20 Subpart C. Similarly, the annual occupational limit of 0.5 Sv to any one organ would be exceeded for the left colon, right colon, and rectosigmoid colon for both the reference male and female.
The Neutrophil to Lymphocyte Ratio as a Triage Tool in Criticality Accidents
Authors: Goans Ronald E. , Iddins Carol J. 
Published: November 2020

Abstract
During triage of possibly irradiated individuals after a criticality accident or nuclear weapon event, it is necessary to decide whether a patient has experienced a clinically significant dose (> 2 Gy) that would require referral for additional evaluation and medical treatment. This is a binary decision: yes or no. The neutrophil-to-lymphocyte ratio (NLR) is an appropriate decision parameter, is simple to obtain in field operations, and is recognized in clinical medicine as an independent marker of systemic inflammation. NLR is evaluated for usefulness in triage using data from the Radiation Accident Registry at the Radiation Emergency Assistance Center/Training Site (REAC/TS). A criticality accident data set has been prepared using historic complete blood counts from 12 criticality events with 33 patients. In addition, a cohort of 125 normal controls has been assembled for comparison with the radiation accident data. In the control set, NLR is found to be 2.1 ± 0.06 (mean ± SEM) and distributed consistent with a Gaussian distribution. A patient from the 1958 Y-12 criticality accident is presented as an example of the time dependence of NLR after an event. In this case, NLR is statistically elevated above controls from <4 h until ~20 d post-event, and for times >20 d post-event, NLR is less than the control value, returning to baseline > ~40 d. The latter result has been confirmed using late hematological data taken from patients at Hiroshima and Nagasaki, and this appears to be a general finding. Since triage is a binary decision, analyzing NLR with receiver operating characteristic (ROC) statistics is appropriate. Maximizing the Youden J statistic (sensitivity + specificity −1) determines an appropriate decision point. For this data set, the decision point for NLR is found to be 3.33, with area under the curve (AUC) 0.865, sensitivity 0.67, specificity 0.97, positive predictive value (PPV) 0.85, and negative predictive value (NPV) 0.92. Therefore, when a known criticality accident or nuclear weapon event has occurred and if the patient’s NLR is greater than 3.33 early post-event, then that person should be referred for further health physics and medical evaluation.
Intake Ratio of 131I to 137CS Derived from Thyroid and Whole-body Doses to Residents of Iwaki City in Japan's Fukushima Prefecture
Authors: Kim Eunjoo , Yajima Kazuaki , Igarashi Yu , Tani Kotaro , Hashimoto Shozo , Nakano Takashi , Akashi Makoto , Kurihara Osamu 
Published: November 2020

Abstract
It is very important to determine the precise internal thyroid doses of Fukushima residents involved in the 2011 Fukushima nuclear disaster, particularly for small children. This has been challenging due to the lack of direct human measurements to identify 131I, the biggest contributor to the thyroid doses. We previously used a dataset of late whole-body counter (WBC) measurements targeting 134Cs and 137Cs for the thyroid dose estimation in comparison with the intake ratios of 131I to 137Cs (or 134Cs) derived from thyroid and whole-body doses individually obtained from different subject groups, assuming simultaneous acute intake via inhalation. Herein, we applied the same method to the doses of residents in Iwaki city (located south of the Fukushima Daiichi Nuclear Power Plant) with a relatively high activity ratio (131I/137Cs) for the ground deposition density. Our analyses revealed that the intake ratio (131I/137Cs) for the Iwaki residents was 4.2–4.3, which is relatively consistent with the values obtained in other studies (average 3.0–5.0). No regional difference in the intake ratios from other areas was observed, but further studies are required to determine the accurate intake ratio in the early phase of the accident, in particular focusing on the reasonable interpretation of results of the late WBC measurements to evaluate the actual Cs intake.