Factors contributing to delays in initiation of front-line cervical cancer therapy: disparities in a diverse south Florida population.

OBJECTIVE: Delay in initiating cervical cancer treatment may impact outcomes. In a cohort of patients initially treated by surgery, chemoradiation, chemotherapy, or in a clinical trial, we aim to define factors contributing to prolonged time to treatment initiation. METHODS: Data from patients initiating treatment for cervical cancer at a single institution was abstracted. Time to treatment initiation was defined as the interval from the date of cancer diagnosis to the date of treatment initiation. Poisson regression model was used for analysis. RESULTS: Of 274 patients studied, the median time to treatment initiation was 60 days (range 0-551). The median times to initiate surgery (54 days, range 3-96) and chemoradiation (58 days, range 4-187) were not significantly different (relative risk (RR) 1.01, 95% CI 0.98 to 1.04, p=0.54). The shortest median initiation time was for chemotherapy (47 days; RR 1.13, 95% CI 1.08 to 1.19, p<0.0001) and the longest was for clinical trial (62 days; RR 1.18, 95% CI 1.12 to 1.24, p<0.0001). Charity care (RR 1.09, 95% CI 1.05 to 1.14, p<0.0001), Medicare or Medicaid (RR 1.10, 95% CI 1.06 to 1.14, p<0.0001), and self-pay (RR 1.38, 95% CI 1.32 to 1.45, p<0.0001) delayed treatment initiation more than private insurance. Hispanic White women (RR 0.69, 95% CI 0.66 to 0.73, p<0.0001) had a shorter treatment initiation time compared with non-Hispanic White patients, while Afro-Caribbean/Afro-Latina women (RR 0.86, 95% CI 0.81 to 0.90, p<0.0001) and African-American patients (RR 1.13, 95% CI 1.07 to 1.19, p<0.0001) had longer initiation times. Spanish speaking patients did not have a prolonged treatment initiation (RR 0.68, 95% CI 0.66 to 0.71, p<0.0001), though Haitian-Creole speaking patients did (RR 1.07, 95% CI 1.01 to 1.13, p<0.002). Diagnosis at an outside institution delayed treatment initiation time (RR 1.24, 95% CI 1.18 to 1.30, p<0.0001) compared with diagnosis at the cancer center. CONCLUSION: Factors associated with prolonged time to treatment initiation include treatment modality, insurance status, language spoken, and institution of diagnosis. By closely examining each of these factors, barriers to treatment can be identified and modified to shorten treatment initiation time.

Greek Validation of the Factor Structure and Longitudinal Measurement Invariance of the Strengths and Difficulties Questionnaire-Self Report (SDQ-SR): Exploratory Structural Equation Modelling.

The study examined the factor structure and longitudinal measurement invariance over three time points (1-year apart) of the Strengths and Difficulties Questionnaire-Self Report (SDQ-SR) for ratings provided by adolescents in Greece. It used exploratory structural equation modelling (ESEM) to achieve these two goals. At time point one, a total of 968 adolescents (males = 508, and females = 460) between 12 and 17.9 years completed the SDQ-SR. In relation to factor structure, ESEM tested the fit of one- to five-factor models. The findings were interpreted as indicating most support for the ESEM model with three factors (the factors being dysregulation, peer problems, and prosocial behaviour). This model showed support for configural invariance and full metric invariance across the three time points. Except for two thresholds, all other thresholds were also invariant across the three time points. Thus, there was good support for longitudinal measurement invariance. The implications of the findings for use of the SDQ-SR are discussed.

The Moore Criteria: Applicability in a diverse, non-trial, recurrent cervical cancer population.

OBJECTIVE: The Moore Criteria is a prognostic index for recurrent or metastatic cervical cancer based on five factors. The criteria were developed retrospectively and validated prospectively in clinical trial populations receiving systemic chemotherapy (C). Our objective was to evaluate the prognostic value of the Moore Criteria in a largely minority, non-trial population at first recurrence. METHODS: Patients treated for recurrent cervical cancer diagnosed between 2012 and 2017 were analyzed retrospectively. Progression free survival (PFS) was defined from the date of recurrence to date of second recurrence. Overall survival (OS) was defined from the date of recurrence to date of death. RESULTS: Of 274 patients identified, 78 were treated in the second line. 48 (61.5%) were Hispanic, 22 (28.2%) were black, and 7 (9%) were white non-Hispanic. By Moore criteria, 9 patients (11.5%) were classified as low-risk, 48 (61.5%) as moderate risk, and 21 (26.9%) as high-risk. 53 patients (67.9%) received C, and 25 (32.1%) received other treatment modalities without C. The high-risk category carried a significantly higher hazard ratio for both PFS (5.24, p < .001) and OS (3.15, p = .002) compared with the low- and intermediate-risk combined group. The low- and intermediate-risk groups demonstrated 78.9% response rate, compared with 33.3% in the high-risk category (p = .001). Black race did not affect survival or response rate. CONCLUSION: The Moore Criteria carries prognostic value across a diverse recurrent cervical cancer population outside of the clinical trial setting. Our data suggest that in a non-trial population, black race is not predictive of worse OS or PFS.

mRNA expression in low grade serous ovarian cancer: Results of a nanoString assay in a diverse population.

OBJECTIVE: Mutations in the MAP kinase pathway (KRAS, NRAS, BRAF) are common in low grade serous ovarian carcinoma (LGSOC). The effect of these and other mutations on RNA transcription in this disease is poorly understood. Our objective was to describe patterns of somatic mutations and gene transcription in a racially diverse population with LGSOC. METHODS: Utilizing an institutional tumor registry, patients with LGSOC were identified and charts were reviewed. RNA was extracted from available tumor tissue. Commercial tumor profiling results were analyzed with PanCancer pathway nanoString mRNA expression data. Along with nanoString n-Solver software, Chi-squared, Fishers Exact, and Cox proportional hazards models were used for statistical analysis, with significance set at p < 0.05. RESULTS: 39 patients were identified-20% Black, 43% Hispanic, and 36% non-Hispanic White. 18 patients had commercial somatic DNA test results, and 23 had available tumor tissue for RNA extraction and nanoString analysis. The most common somatic alterations identified was KRAS (11 patients, 61%), followed by ERCC1 and TUBB3 (9 each, 50%). KRAS mutations were less common in smokers (14.3% vs 90.9%, p = 0.002). RNA expression analysis demonstrated a greater than two-fold decrease in expression of HRAS in tumors from older patients (p = 0.04), and a greater than two-fold decrease in the expression of HRAS in recurrent tumors (p = 0.007). No significant differences were seen in somatic testing results, RNA expression analysis, or progression free survival between different racial and ethnic cohorts. CONCLUSIONS: Somatic deficiencies in ERCC1, TUBB3, and KRAS are common in LGSOC in a population of minority patients. HRAS demonstrates decreased expression in tumors from older patients and recurrent tumors.

United States Pharmacopeia Safety Review of Willow Bark.

Willow bark (Salix spp.) is an ingredient in some dietary supplements. No serious adverse effects were reported from trials of willow bark extracts delivering 120 - 240 mg salicin (the purported active constituent) daily for up to 8 weeks. All studies involved adults only; none involved special subpopulations such as pregnant or breastfeeding women, or children. The most common adverse effects associated with willow bark are gastrointestinal; a few allergic reactions were also reported. Some publications advise caution when taking willow bark. There is a risk of increased bleeding in vulnerable individuals, salicylates cross the placenta and are eliminated slowly in newborns, some persons are sensitive or allergic to aspirin, and children are at risk of Reye syndrome. Concurrent use with other salicylate-containing medicines increases these risks. Metabolism of 240 mg salicin from willow bark could yield 113 mg of salicylic acid, yet dietary supplement products are not required to be labeled with warnings. In contrast, over-the-counter low-dose aspirin (81 mg strength), which delivers 62 mg salicylic acid, is required by law to include cautions, warnings, and contraindications related to its use in pregnant and nursing women, children, and other vulnerable subpopulations, e.g., those using anticoagulants. In the interest of protecting public health, the United States Pharmacopeia has included a cautionary labeling statement in the United States Pharmacopeia Salix Species monograph as follows: "Dosage forms prepared with this article should bear the following statement: 'Not for use in children, women who are pregnant or nursing, or by persons with known sensitivity to aspirin.'".

Improved diagnostic clarity in shrimp allergic non-dust-mite sensitized patients.

BACKGROUND: Allergen specific immunoglobulin E (sIgE) levels predictive of shrimp allergy have not been identified, but these may be helpful in identifying patients at risk for shrimp-induced allergic reactions. OBJECTIVE: This study sought to identify component resolved diagnostic tests useful for diagnosis of shrimp allergy in patients with or without house-dust mite (HDM) sensitization to the major allergen cysteine protease (Der p 1). METHODS: Patients with positive skin-prick test (SPT) results and/or sIgE values were recruited. Shrimp allergy was classified by oral food challenge (OFC) or by a clear history of anaphylaxis after shrimp ingestion. Patients with shrimp allergy and patients who were tolerant were further classified based on HDM sensitivity (Der p 1 > 0.35 kUA/L). Testing for sIgE to total shrimp, and shrimp and HDM components was performed. The Fisher exact test, Wilcoxon sum rank test, and receiver operating characteristics analyses were used to compare sIgE levels in patients with allergy and patients who were tolerant. RESULTS: Of 79 patients recruited, 12 patients with shrimp allergy (7 with positive OFC results and 5 with a history of anaphylaxis) and 18 patients who were shrimp tolerant were enrolled. Of the patients not HDM sensitized, sIgE levels to shrimp (10.5 kUA/L, p = 0.012) and Der p 10 (4.09 kUA/L, p = 0.035) were higher in patients with shrimp allergy. Shrimp sIgE of ≥3.55 kUA/L had 100% diagnostic sensitivity and 85.7% specificity (receiver operating characteristic 0.94 [0.81, 1.0] 95% CI) and Der p 10 sIgE levels of ≥3.98 kUA/L had a diagnostic sensitivity of 80% and specificity of 100% (receiver operating characteristic 0.86 [0.57, 1.0] 95% CI) for prediction of clinical reactivity. CONCLUSION: HDM sensitization influences shrimp and HDM component sIgE levels and, consequently, their diagnostic accuracy in shrimp allergy. In our series, in the patients who were non-HDM sensitized, a shrimp sIgE level of >3.55 kUA/L showed 100% sensitivity and, Der p 10 sIgE of >3.98 kUA/L showed 100% specificity for the diagnosis of shrimp allergy. These levels may not be applicable to every patient and, therefore, may not obviate the need for OFC.

Assessing Natural Product-Drug Interactions: An End-to-End Safety Framework.

The use of natural products (NPs), including herbal medicines and other dietary supplements, by North Americans continues to increase across all age groups. This population has access to conventional medications, with significant polypharmacy observed in older adults. Thus, the safety of the interactions between multi-ingredient NPs and drugs is a topic of paramount importance. Considerations such as history of safe use, literature data from animal toxicity and human clinical studies, and NP constituent characterization would provide guidance on whether to assess NP-drug interactions experimentally. The literature is replete with reports of various NP extracts and constituents as potent inhibitors of drug metabolizing enzymes, and transporters. However, without standard methods for NP characterization or in vitro testing, extrapolating these reports to clinically-relevant NP-drug interactions is difficult. This lack of a clear definition of risk precludes clinicians and consumers from making informed decisions about the safety of taking NPs with conventional medications. A framework is needed that describes an integrated robust approach for assessing NP-drug interactions; and, translation of the data into formulation alterations, dose adjustment, labelling, and/or post-marketing surveillance strategies. A session was held at the 41st Annual Summer Meeting of the Toxicology Forum in Colorado Springs, CO, to highlight the challenges and critical components that should be included in a framework approach.

Perceived Health in Patients with Primary Immune Deficiency.

PURPOSE: Perceived health (PH) is a subjective measure of global health of individuals. While many studies have evaluated outcomes in patients with primary immune deficiency (PID), published literature evaluating PH among patients with PID is sparse. We evaluated the results of the largest self-reported survey of patients with PID to determine the factors that may contribute to differences in PH. METHODS: Data from a National Survey of Patients with Primary Immune Deficiency Diseases conducted by the Immune Deficiency Foundation was studied. Multivariate logistic regression was employed for data analysis. RESULTS: Thirty percent of the patients perceived their health status as excellent or very good (EVG), 31 % as good (G), and 39 % as fair, poor or very poor (P). Older patients were less likely to have EVG-PH compared to G-PH. Ones with college degrees were more likely to have P-PH compared to G-PH, and less likely to have EVG-PH. Patients who were acutely ill and hospitalized in the past 12 months, ones with limited activity, and chronic diseases, were more likely to have P-PH compared to G-PH. Patients with "on demand" access to specialty care and ones on regular IVIG had higher OR of having EVG-PH as opposed to G-PH. Patients cared for mostly by an immunologist were less likely to have P-PH compared to G-PH. CONCLUSIONS: Our results emphasize the importance of PH in clinical practice. We suggest that recognizing the factors that drive PH in patients with PID is important for the development of disease prevention and health promotion programs, and delivery of appropriate health and social services to individuals with PID.

Ultrasound Fusion: Applications in Musculoskeletal Imaging.

Ultrasound fusion is an established technique that pairs real time B-scan ultrasound (US) with other forms of cross-sectional imaging, including computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). Each of these imaging modalities has distinct advantages. CT provides superior anatomic resolution, with improved imaging of bone and calcified structures; MRI has superior contrast resolution; and PET provides physiologic information, identifying processes that are metabolically active (i.e., tumor, inflammatory conditions). However, these modalities are static. A key highlight of ultrasound is its capability of dynamic, real-time scanning. The ability to pair CT, MRI or PET with ultrasound can have significant advantages, both in diagnostic evaluation and when performing difficult or challenging image-guided interventions. Percutaneous interventions using ultrasound fusion have been described in the abdominal imaging literature; however, there have been very few musculoskeletal applications detailed in the literature. The purpose of this article is to review the basic concepts of real-time ultrasound fusion, and to detail, through the use of multiple case examples, its potential use as a safe and effective method for performing image-guided musculoskeletal interventions.

Case report: Artemis deficiency and 3M syndrome-coexistence of two distinct genetic disorders.

The presence of two different genetic conditions in the same individual is possible, especially in populations with consanguinity. In this case report, we present the coexistence of Artemis deficiency (OMIM 602450) and Three M (3M) syndrome (OMIM 273750). A 10-months-old male patient with neuromotor developmental delay was evaluated for immunodeficiency due to recurrent respiratory infections diarrhea and oral moniliasis from the age of 1.5 months. He had facial dysmorphism with rotated ears, flat nose and hypertelorism. Neurological examination revealed generalized hypotonia and mental motor delay. Immunological screening of the patient demonstrated mild lymphopenia, hypogammaglobulinemia, reduced number of CD3+ T cells (980 cells/mm3) and CD19+ B cells (35 cells/mm3). He was diagnosed with leaky T-B-NK+ SCID. Exome sequence analysis showed the presence of a homozygous pathogenic DCLRE1C variant [c.194C > T; p.T65I (NM_001033855)] and a homozygous pathogenic variant in OBSL1, a gene associated with 3M syndrome [c.3922C > T; p.R1308X (NM_001173431)]. Our proband died of sepsis and multiple organ failure. This case illustrates that different clinical findings in patients might not be explained with a single genetic defect, and consanguinity increases the change for coexistence of autosomal recessive diseases. Clinicians should consider exome sequencing to identify disease-causing mutations in patients with heterogeneity of clinical findings.

Inflammation and Invasion in Oral Squamous Cell Carcinoma Cells Exposed to Electronic Cigarette Vapor Extract.

Electronic cigarettes (eCig) represent a new avenue of tobacco exposure that involves heating oil-based liquids and the delivery of aerosolized flavors with or without nicotine, yet little is known about their overall health impact. The oral cavity is an anatomic gateway for exposure that can be compromised by activating myriad of signaling networks. Oral squamous cell carcinoma (OSSC) is a common malignancy affecting 30,000 people in the United States each year. Our objective was to determine the impact of eCig and nicotine on gingival OSSC invasion and their secretion of pro-inflammatory molecules. Gingiva-derived Ca9-22 cells and tongue-derived Cal27 cells were exposed to eCig vapor extract (EVE) generated from Red Hot or Green Apple (Apple) flavored eCig solution +/- nicotine for 6 hours. Isolation of protein lysates and collection conditioned media was done after treatment. Real-time cellular invasion was assessed using a RTCA DP instrument. Protein expression was determined using western blot. Compared to controls, we observed: elevated NF-kB, TNF-α, ERK, JNK, MMP-13 and cell invasion by Ca9-22 treated with Apple EVE; increased TNF-α and JNK by Ca9-22 treated with Red Hot EVE; and increased TNF-α and JNK by Cal27 cells treated with both Apple and Red Hot EVE. We conclude that eCig flavoring and nicotine orchestrated differential cell invasion and inflammatory effects. This study provides an important initial step in dissecting mechanisms of cancerous invasion and molecular avenues employed by OSCC.

Impact of changes in tissue optical properties on near-infrared diffuse correlation spectroscopy measures of skeletal muscle blood flow.

Near-infrared diffuse correlation spectroscopy (DCS) is increasingly used to study relative changes in skeletal muscle blood flow. However, most diffuse correlation spectrometers assume that tissue optical properties-such as absorption (µa) and reduced scattering (µ's) coefficients-remain constant during physiological provocations, which is untrue for skeletal muscle. Here, we interrogate how changes in tissue µa and µ's affect DCS calculations of blood flow index (BFI). We recalculated BFI using raw autocorrelation curves and µa/µ's values recorded during a reactive hyperemia protocol in 16 healthy young individuals. First, we show that incorrectly assuming baseline µa and µ's substantially affects peak BFI and BFI slope when expressed in absolute terms (cm2/s, P < 0.01), but these differences are abolished when expressed in relative terms (% baseline). Next, to evaluate the impact of physiologic changes in µa and µ's, we compared peak BFI and BFI slope when µa and µ's were held constant throughout the reactive hyperemia protocol versus integrated from a 3-s rolling average. Regardless of approach, group means for peak BFI and BFI slope did not differ. Group means for peak BFI and BFI slope were also similar following ad absurdum analyses, where we simulated supraphysiologic changes in µa/µ's. In both cases, however, we identified individual cases where peak BFI and BFI slope were indeed affected, with this result being driven by relative changes in µa over µ's. Overall, these results provide support for past reports in which µa/µ's were held constant but also advocate for real-time incorporation of µa and µ's moving forward.NEW & NOTEWORTHY We investigated how changes in tissue optical properties affect near-infrared diffuse correlation spectroscopy (NIR-DCS)-derived indices of skeletal muscle blood flow (BFI) during physiological provocation. Although accounting for changes in tissue optical properties has little impact on BFI on a group level, individual BFI calculations are indeed impacted by changes in tissue optical properties. NIR-DCS calculations of BFI should therefore account for real-time, physiologically induced changes in tissue optical properties whenever possible.

Multi-Criteria Decision Analysis Model for Assessing the Risk from Multi-Ingredient Dietary Supplements (MIDS).

Military personnel use dietary supplements (DS) for performance enhancement, bodybuilding, weight loss, and to maintain health. Adverse events, including cardiovascular (CV) effects, have been reported in military personnel taking supplements. Previous research determined that ingestion of multi-ingredient dietary supplements (MIDS), can lead to signals of safety concerns. Therefore, to assess the safety of MIDS, the Department of Defense via a contractor explored the development of a model-based risk assessment tool. We present a strategy and preliminary novel multi-criteria decision analysis (MCDA)-based tool for assessing the risk of adverse CV effects from MIDS. The tool integrates toxicology and other relevant data available on MIDS; likelihood of exposure, and biologic plausibility that could contribute to specific aspects of risk.Inputs for the model are values of four measures assigned based on the available evidence supplemented with the opinion of experts in toxicology, modeling, risk assessment etc. Measures were weighted based on the experts' assessment of measures' relative importance. Finally, all data for the four measures were integrated to provide a risk potential of 0 (low risk) to 100 (high risk) that defines the relative risk of a MIDS to cause adverse reactions.We conclude that the best available evidence must be supplemented with the opinion of experts in medicine, toxicology and pharmacology. Model-based approaches are useful to inform risk assessment in the absence of data. This MCDA model provides a foundation for refinement and validation of accuracy of the model predictions as new evidence becomes available.

Assessment of herbal medicinal products: challenges, and opportunities to increase the knowledge base for safety assessment.

Although herbal medicinal products (HMP) have been perceived by the public as relatively low risk, there has been more recognition of the potential risks associated with this type of product as the use of HMPs increases. Potential harm can occur via inherent toxicity of herbs, as well as from contamination, adulteration, plant misidentification, and interactions with other herbal products or pharmaceutical drugs. Regulatory safety assessment for HMPs relies on both the assessment of cases of adverse reactions and the review of published toxicity information. However, the conduct of such an integrated investigation has many challenges in terms of the quantity and quality of information. Adverse reactions are under-reported, product quality may be less than ideal, herbs have a complex composition and there is lack of information on the toxicity of medicinal herbs or their constituents. Nevertheless, opportunities exist to capitalise on newer information to increase the current body of scientific evidence. Novel sources of information are reviewed, such as the use of poison control data to augment adverse reaction information from national pharmacovigilance databases, and the use of more recent toxicological assessment techniques such as predictive toxicology and omics. The integration of all available information can reduce the uncertainty in decision making with respect to herbal medicinal products. The example of Aristolochia and aristolochic acids is used to highlight the challenges related to safety assessment, and the opportunities that exist to more accurately elucidate the toxicity of herbal medicines.

Co-actors Exhibit Similarity in Their Structure of Behavioural Variation That Remains Stable Across Range of Naturalistic Activities.

Human behaviour, along with any natural/biological behaviour, has varying degrees of intrinsic 'noise' or variability. Many studies have shown that the structure or patterning of this variability is sensitive to changes in task and constraint. Furthermore, two or more humans interacting together often begin to exhibit similar structures of behavioural variability (i.e., the patterning of their behavioural fluctuations becomes aligned or matched) independent of any moment-to-moment synchronization (termed complexity matching). However, much of the previous work has focused on a subset of simple or contrived behaviours within the context of highly controlled laboratory tasks. In the current study, individuals and pairs performed five self-paced (unsupervised), semi-structured activities around a university campus. Empatica E4 wristbands and iPhones were used to record the participants' behavioural activity via accelerometers and GPS. The results revealed that the structure of variability in naturalistic human behaviour co-varies with the task-goal constraints, and that the patterning of the behavioural fluctuations exhibited by co-acting individuals does become aligned during the performance of everyday activities. The results also revealed that the degree of complexity matching that occurred between pairs remained invariant across activity type, indicating that this measure could be employed as a robust, task-independent index of interpersonal behaviour.

Race and Ethnicity Influence Survival Outcomes in Women of Caribbean Nativity With Epithelial Ovarian Cancer.

Background: Caribbean immigrants represent one of the largest groups of minorities in the United States (US), yet are understudied. Racial and ethnic disparities among women with ovarian cancer have been reported, but not in immigrant populations. Our objective was to evaluate differences in the clinicopathologic features and survival outcomes of Caribbean-born (CB) immigrants with ovarian cancer, with special focus on the influence of race and ethnicity on these measures. Methods: A review of the institutional cancer registry was performed to identify women with known nativity treated for epithelial ovarian cancer between 2005 and 2017. Sociodemographic, clinical, and outcomes data were collected. Analyses were done using chi-square, Cox proportional hazards models, and the Kaplan-Meier method, with significance set at p < 0.05. Results: 529 women were included in the analysis, 248 CB and 281 US-born (USB). CB women were more likely to have residual disease after debulking surgery (31.2 vs. 16.8%, p = 0.009) and be treated at a public facility (62.5 vs. 33.5%, p < 0.001). Black CB women less frequently received chemotherapy compared to White CB women (55.2 vs. 82.2%, p = 0.001). Among all CB women, Hispanic ethnicity was independently associated with improved survival when adjusting for other factors (HR 0.61 [95% CI 0.39-0.95], p = 0.03). White Hispanic CB women had a median overall survival (OS) of 59 months while Black, non-Hispanic CB women had a median OS of 24 months (log-rank p = 0.04). Conclusion: Among Caribbean-born women with ovarian cancer, Hispanic ethnicity is significantly associated with improved survival outcomes, regardless of race.

Personality method validation in common marmosets (Callithrix jacchus): Getting the best of both worlds.

Animal personality, consistent interindividual differences in behavior through time, has been intensively studied across animal taxa and particularly in nonhuman primates. Two different methods have been used to study personality: questionnaires filled out by trusted raters, following the research tradition in human personality psychology, and behavioral observations or testing, based on the behavioral ecology research tradition. Systematic research of cross-method validity has, however, brought equivocal results. Here we report a systematic method comparison with strict validation criteria in common marmosets (Callithrix jacchus). We compared questionnaire data, observational behavioral data, and experimentally assessed behavioral data independently collected in two different research laboratories and across two years. Notably, we constructed a priori predictions on the degree and direction of correlations between the questionnaire-derived constructs and behaviorally derived constructs/variables. Convergent validity of the constructs/variables was present but was not found in both laboratories for any of the constructs. Discriminant validity was found to some degree for all constructs in both laboratories, with important exceptions. It seems that marmoset personality structure obtained with descriptor ratings does not consistently capture the predicted behavioral variables. Our finding that these two methods do not quite reach common ground thus urges caution in the choice of the suitable methods to study personality in nonhuman primates. We discuss the directions to which animal personality research should go so that it can get the "best of both worlds." (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Effects of initiating physician-performed germline testing in safety net clinic patients with epithelial overian cancer.

Germline genetic mutations occur in approximately 25% of women with epithelial ovarian cancers (EOC). We sought to determine whether newly initiated in-office oncologist-led germline testing improved time to testing and dissemination of results compared with historical controls. Patients with epithelial ovarian cancer seen between 4/1/2018 and 12/31/2019 were identified. Patients treated before genetic testing kits were made available in the gynecologic oncology clinics were compared to those treated after. Categorical variables were compared using Chi Squared and Fisher's Exact test. Cox proportional hazards model was used to compare elapsed time from testing to results. 73 patients were identified, and 502 clinic visits were analyzed. 56 (76.7%) patients were White Hispanic, 15 (20.5%) were Black, and 2 (2.7%) were White non-Hispanic. 55 (75.7%) underwent germline testing. Median time to genetic testing in the intervention group was shorter than in the control group (5, vs 24.3 weeks, 95% CI = 0-10.8 vs 14.9-33.7, p < 0.001). Among the 51 patients with genetic tests completed; results were recorded in a clinic note at 14 weeks (95% CI = 0-28.1) from first visit in the intervention group compared with 47 weeks (95% CI = 30.7-63.3) in the control group (p < 0.001). The majority of patients tested had county charity care insurance or were uninsured. Genetic testing in a safety net gynecologic oncology clinic is feasible. By initiating in-office testing, time to testing and receipt of results were meaningfully shortened. This allowed for timely identification of patients who would most benefit from PARP inhibitor maintenance therapy.

United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts.

As part of the United States Pharmacopeia's ongoing review of dietary supplement safety data, a new comprehensive systematic review on green tea extracts (GTE) has been completed. GTEs may contain hepatotoxic solvent residues, pesticide residues, pyrrolizidine alkaloids and elemental impurities, but no evidence of their involvement in GTE-induced liver injury was found during this review. GTE catechin profiles vary significantly with manufacturing processes. Animal and human data indicate that repeated oral administration of bolus doses of GTE during fasting significantly increases bioavailability of catechins, specifically EGCG, possibly involving saturation of first-pass elimination mechanisms. Toxicological studies show a hepatocellular pattern of liver injury. Published adverse event case reports associate hepatotoxicity with EGCG intake amounts from 140 mg to ∼1000 mg/day and substantial inter-individual variability in susceptibility, possibly due to genetic factors. Based on these findings, USP included a cautionary labeling requirement in its Powdered Decaffeinated Green Tea Extract monograph that reads as follows: "Do not take on an empty stomach. Take with food. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes)."

Safety Surveillance of Dietary Supplements: Importance, Challenges, and New Horizons.

Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other possible drug-related problems.1 While current models of pharmacovigilance, with their tools and methodologies, were developed for prescription drugs, safety surveillance is just as important for over-the-counter health products such as dietary supplements. The practice of pharmacovigilance is challenging in itself; however, there are unique challenges associated with dietary supplements.2.