Utilization of the Psoriasis Epidemiology Screening Tool (PEST): A Risk Stratification Strategy for Early Referral of Psoriatic Arthritis Patients to Minimize Irreversible Erosive Joint Damage.

Psoriatic arthritis (PsA) can affect a diverse range of anatomical sites and its heterogeneous presentation contributes to misdiagnosis and delayed treatment with conventional and biologic disease-modifying antirheumatic drugs (DMARDs). Up to 15% of psoriasis (PsO) patients affected by PsA remain undiagnosed. Early detection and referral to a rheumatologist are crucial to optimize care and minimize irreversible erosive joint damage. To improve the rheumatology referral process, the authors propose a risk stratification tool to identify and triage patients with possible psoriatic arthritis. With the aim of ultimately assisting in early treatment initiation, this risk stratification algorithm can be used in both dermatology and primary care clinics. It is based on the Psoriasis Epidemiology Screening Tool (PEST) combined with the ClASsification criteria for Psoriatic Arthritis (CASPAR). This article intends to provide a rationale for further prospective studies whose objective would be to validate this screening algorithm.

Preexisting autoimmune disease and immune-related adverse events associated with anti-PD-1 cancer immunotherapy: a national case series from the Canadian Research Group of Rheumatology in Immuno-Oncology.

BACKGROUND: Limited data are available on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with preexisting autoimmune diseases (PAD). METHODS: Retrospective study of patients with PAD referred for rheumatologic evaluation prior to starting or during immunotherapy between January 2013 and July 2019 from 10 academic sites across Canada. Data were extracted by chart review using a standardized form. RESULTS: Twenty-seven patients with PAD on ICI therapy were identified. The most common PADs were rheumatoid arthritis (30%), psoriasis/psoriatic arthritis (30%), inflammatory bowel disease (IBD, 15%) and axial spondyloarthritis (11%), and the most frequently observed cancers were lung cancer and melanoma. All patients received anti-PD-1 therapies, and 2 received additional sequential anti-CTLA-4 therapy. PAD exacerbations occurred in 52% over a median (IQR) follow-up of 11.0 (6.0-17.5) months, with 14% being severe, 57% requiring corticosteroids, 50% requiring immunosuppression and 14% requiring ICI discontinuation. Flares were generally more frequent and severe in patients who previously required more intensive immunosuppression (i.e., biologics). Flares occurred despite background immunosuppression at the time of ICI initiation. In patients with preexisting psoriasis, IBD and axial spondyloarthritis, rheumatic immune-related adverse events (irAEs), mostly polyarthritis and tenosynovitis, were frequently observed. Tumor progression was not associated with exposure to immunosuppressive drugs before or after ICI initiation and was numerically less frequent in patients with irAEs. CONCLUSION: PAD exacerbations in the context of ICI treatment are common, although generally mild, and occur despite background immunosuppression. Exacerbations are more frequent and severe in patients on more intensive immunosuppressive therapies pre-immunotherapy.

Vaccinium angustifolium (lowbush blueberry) leaf extract increases extravillous trophoblast cell migration and invasion in vitro.

Perturbations to extravillous trophoblast (EVT) cell migration and invasion are associated with the development of placenta-mediated diseases. Phytochemicals found in the lowbush blueberry plant (Vaccinium angustifolium) have been shown to influence cell migration and invasion in models of tumorigenesis and noncancerous, healthy cells, however never in EVT cells. We hypothesized that the phenolic compounds present in V. angustifolium leaf extract promote trophoblast migration and invasion. Using the HTR-8/SVneo human EVT cell line and Boyden chamber assays, the influence of V. angustifolium leaf extract (0 to 2 × 104  ng/ml) on trophoblast cell migration (n = 4) and invasion (n = 4) was determined. Cellular proliferation and viability were assessed using immunoreactivity to Ki67 (n = 3) and trypan blue exclusion assays (n = 3), respectively. At 20 ng/ml, V. angustifolium leaf extract increased HTR-8/SVneo cell migration and invasion (p < .01) and did not affect cell proliferation or viability. Chlorogenic acid was identified as a major phenolic compound of the leaf extract and the most active compound. Evidence from Western blot analysis (n = 3) suggests that the effects of the leaf extract and chlorogenic acid on trophoblast migration and invasion are mediated through an adenosine monophosphate-activated protein (AMP) kinase-dependent mechanism. Further investigations examining the potential therapeutic applications of this natural health product extract and its major chemical compounds in the context of placenta-mediated diseases are warranted.

Classification of Suicide Attempt Risk Using Environmental and Lifestyle Factors in 3 Large Youth Cohorts.

Importance: Suicide is the third-leading cause of death among US adolescents. Environmental and lifestyle factors influence suicidal behavior and can inform risk classification, yet quantifying and incorporating them in risk assessment presents a significant challenge for reproducibility and clinical translation. Objective: To quantify the aggregate contribution of environmental and lifestyle factors to youth suicide attempt risk classification. Design, Setting, and Participants: This was a cohort study in 3 youth samples: 2 national longitudinal cohorts from the US and the UK and 1 clinical cohort from a tertiary pediatric US hospital. An exposome-wide association study (ExWAS) approach was used to identify risk and protective factors and compute aggregate exposomic scores. Logistic regression models were applied to test associations and model fit of exposomic scores with suicide attempts in independent data. Youth from the Adolescent Brain Cognitive Development (ABCD) study, the UK Millennium Cohort Study (MCS), and the Children's Hospital of Philadelphia emergency department (CHOP-ED) were included in the study. Exposures: A single-weighted exposomic score that sums significant risk and protective environmental/lifestyle factors. Main Outcome and Measure: Self-reported suicide attempt. Results: A total of 40 364 youth were included in this analysis: 11 564 from the ABCD study (3 waves of assessment; mean [SD] age, 12.0 [0.7] years; 6034 male [52.2%]; 344 attempted suicide [3.0%]; 1154 environmental/lifestyle factors were included in the ABCD study), 9000 from the MCS cohort (mean [SD] age, 17.2 [0.3] years; 4593 female [51.0%]; 661 attempted suicide [7.3%]; 2864 environmental/lifestyle factors were included in the MCS cohort), and 19 800 from the CHOP-ED cohort (mean [SD] age, 15.3 [1.5] years; 12 937 female [65.3%]; 2051 attempted suicide [10.4%]; 36 environmental/lifestyle factors were included in the CHOP-ED cohort). In the ABCD discovery subsample, ExWAS identified 99 risk and protective exposures significantly associated with suicide attempt. A single weighted exposomic score that sums significant risk and protective exposures was associated with suicide attempt in an independent ABCD testing subsample (odds ratio [OR], 2.2; 95% CI, 2.0-2.6; P < .001) and explained 17.6% of the variance (based on regression pseudo-R2) in suicide attempt over and above that explained by age, sex, race, and ethnicity (2.8%) and by family history of suicide (6.3%). Findings were consistent in the MCS and CHOP-ED cohorts (explaining 22.6% and 19.3% of the variance in suicide attempt, respectively) despite clinical, demographic, and exposure differences. In all cohorts, compared with youth at the median quintile of the exposomic score, youth at the top fifth quintile were substantially more likely to have made a suicide attempt (OR, 4.3; 95% CI, 2.6-7.2 in the ABCD study; OR, 3.8; 95% CI, 2.7-5.3 in the MCS cohort; OR, 5.8; 95% CI, 4.7-7.1 in the CHOP-ED cohort). Conclusions and Relevance: Results suggest that exposomic scores of suicide attempt provided a generalizable method for risk classification that can be applied in diverse samples from clinical or population settings.

Receptivity of Young Adult Hookah Users to Health Warning Labels.

OBJECTIVES: We examined the receptivity of non-college young adult hookah users to health warning labels. METHODS: We conducted in-person qualitative interviews with 23 hookah users, aged 18-29 in Austin, Texas, who were not currently enrolled in college/university. Data were transcribed, coded, and thematically analyzed using NVivo Pro, version 11. RESULTS: Gaps in knowledge were evident regarding the level of chemical exposure, cancer risks, and negative health consequences of hookah use. Respondents preferred warning labels that factually listed health consequences rather than labels that used "sensationalistic" wording (eg, "kills") or technical terms. Participants thought placement of hookah warning labels would be most effective on product packaging or on the door of establishments selling hookah. Respondents thought most of the warning labels would be effective in deterring hookah use; however, the majority stated they would likely continue to use hookah over the next year. CONCLUSIONS: Non-college-attending young adult hookah users preferred hookah health warning labels that are simple, factual, informative, and non-sensationalistic. These results may inform regulations regarding the packaging of tobacco products, specifically in the design and placement of warning labels, which may result in better user message receptivity.

Hookah Use and Perceptions among Young Adult Hookah Users.

BACKGROUND: Despite declining cigarette use, hookah use has increased substantially among youth and young adults. This is alarming, as hookah can lead to the same health risks as cigarettes and expose users to a high amount of smoke, nicotine, and toxicants. Determining patterns of hookah use and perceptions in young adults is important in prevention efforts. METHODS: Structured in-person interviews were conducted for this qualitative study in June 2016. Twenty-three hookah users between the ages of 18 and 29 years living in Austin, TX who were not currently enrolled in a college or university completed the interview. NVivo 11 Pro was utilized to code transcribed transcripts for common themes among participants. RESULTS: When trying hookah for the first time, all participants had used flavored tobacco, with fruit flavors being most popular at initiation and for current use. Many participants initiated hookah use under the age of 18 years old. While only one participant initiated hookah use alone, one-third of participants had smoked hookah alone, not in the company of others. The majority of participants owned or previously owned their own hookah device. Common motivational factors for hookah use involved being social, taste, and the calming/relaxation effect. Participants perceived hookah use to be both harmful and addictive; however, many participants were unsure if hookah was more harmful to health than cigarettes. CONCLUSION: Young adults who are not currently enrolled in college may have similar hookah use behaviors and risk perceptions as do college students, yet non-college students in this sample are using hookah alone and report owning a hookah device. This study supports the need for research on the effect of policy changes on hookah use, receptivity to warning labels, and programs to correct misperceptions.

Social Norms, Perceptions and Dual/Poly Tobacco Use among Texas Youth.

OBJECTIVES: We assessed risk perceptions and social norms about tobacco use across adolescent non-users of tobacco, single- product users, and dual/poly-product users. METHODS: Use behaviors specific to e-cigarettes, cigarettes, hookah, cigars, and smokeless tobacco were assessed among 6th, 8th and 10th grade students (sample [n] = 3907 from a population of [N] = 461,069 students). Multivariate regression was used to examine differences in these factors across use categories, adjusted for demographic factors. RESULTS: Results highlight differences between non-users and single- or dual/poly-product users for most tobacco products. Dual/poly-product users differed from single-product users most notably in their higher perceived use of tobacco products by close friends and dating partners, and a higher proportion of single-product users reported most products were not harmful and not addictive compared to non-users. Few differences were seen between dual/poly-product users and single-product users in their perceptions of harm and addictiveness. CONCLUSIONS: Findings demonstrate the importance of proximal social influences (ie, close friends and dating partners) for adolescent dual/poly-tobacco product users. Understanding similarities and differences in risk factors between these adolescent groups can guide effective public health prevention and treatment programs.

The effects of dietary polyphenols on reproductive health and early development.

BACKGROUND: Emerging evidence from clinical and epidemiological studies suggests that dietary polyphenols play an important role in the prevention of chronic diseases, including cancer, cardiovascular disease, diabetes and neurodegenerative disorders. Although these beneficial health claims are supported by experimental data for many subpopulation groups, some studies purport that excessive polyphenol consumption may have negative health effects in other subpopulations. The ever-growing interest and public awareness surrounding the potential benefits of natural health products and polyphenols, in addition to their widespread availability and accessibility through nutritional supplements and fortified foods, has led to increased consumption throughout gestation. Therefore, understanding the implications of polyphenol intake on obstetrical health outcomes is of utmost importance with respect to safe consumption during pregnancy. METHODS: Using relevant keywords, a literature search was performed to gather information regarding polyphenol pharmacology and the molecular mechanisms by which polyphenols exert their biological effects. The primary focus of this paper is to understand the relevance of these findings in the context of reproductive physiology and medicine. RESULTS: Evidence from both in vitro experiments and in vivo studies using animals and humans demonstrates that polyphenols regulate key targets related to oxidative stress, inflammation and advanced glycation end products. Although the majority of these studies have been conducted in the context of chronic diseases, such as cancer and diabetes, several of the key targets influenced by polyphenols are also related to a variety of obstetrical complications, including pre-eclampsia, intrauterine growth restriction and preterm birth. Polyphenols have also been shown to influence fertility and sexual development, fetal health and the bioavailability of nutrients. CONCLUSIONS: Further research leading to a thorough understanding of the physiological roles and potential clinical value that polyphenol consumption may play in pregnancy is urgently needed to help inform patient safety.

Assessment of hazard risk associated with the intravenous use of viral vectors in rodents.

Viral vectors are emerging as potent basic research tools and gene therapy vehicles in many laboratory animal models. However, little information is available on the potential shedding of these vectors and the consequent exposure risk to investigators and animal care staff from animals over time. This study provides empirical information to Institutional Biosafety Committees and animal care programs, to enhance their ability to perform risk management of laboratory animals treated with viral vectors. Control experiments evaluated the limit of detection of third-generation lentivirus, recombinant adeno-associated virus, and E1-deleted adenovirus tested directly from stocks and after application onto cage plastic or bedding. After inoculation of ICR or NOD-SCID mice, we quantified the recovery of viral vector genomes directly from blood, urine, and fecal samples and assessed the persistence of infectious vector at the site of injection and from soiled bedding at different time points after inoculation. No differences were seen between ICR and NOD-SCID mice. We saw no evidence of vector amplification after in vivo inoculation. The most environmentally persistent vector was recombinant adeno-associated virus, which has no known pathogenicity in humans. In light of these data, we conclude that commonly used replication-deficient viral vectors pose minimal exposure risk by 72 h after inoculation. Prudent precautions at Animal Biosafety Level 2 are warranted during initial administration, but Level 1 safety measures may be sufficient after cage changing and biosafety evaluation.