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Simple scaling laws control the genetic architectures of human complex traits

Simons, Yuval B; Mostafavi, Hakhamanesh; Smith, Courtney J; Pritchard, Jonathan K; Sella, Guy
ORIGINAL:0016889
ISSN: 2692-8205
CID: 5495012

Provider discussion of genetic counseling among high-risk Spanish-preferring Latina breast cancer survivors

Conley, Claire C; Rivera Rivera, Jessica N; Castro-Figueroa, Eida M; Moreno, Laura; Dutil, Julie; García, Jennifer D; Ricker, Charité; Quinn, Gwendolyn P; Soliman, Hatem; Vadaparampil, Susan T
Among high-risk breast cancer (BC) survivors, genetic counseling (GC) and genetic testing (GT) may inform cascade testing and risk management. Compared to non-Hispanic White BC survivors, Spanish-preferring Latina BC survivors are less likely to report discussing GC with a healthcare provider. However, few studies have examined Latinas' experiences with GC/GT, particularly outside of the mainland USA. This study aimed to compare frequency of provider discussion of GC between Spanish-preferring Latina BC survivors living in Florida (FL) and Puerto Rico (PR). We conducted secondary data analysis of baseline assessments from a randomized pilot of an educational intervention for Spanish-preferring Latina BC survivors. Participants (N = 52) were GC/GT-naive, but met clinical criteria for GC/GT referral. Participants self-reported sociodemographic, clinical, and cultural variables, including previous provider discussion of GC. Descriptive statistics characterized frequency of GC discussion. Logistic regression examined the relationships between sociodemographic, clinical, and cultural characteristics and GC discussion. Only 31% of participants reported previous GC discussion. More participants from PR reported having GC discussions (43% vs. 21% in the mainland USA). In multivariable analyses, greater likelihood of GC discussion was associated with PR (vs. mainland USA) residence (odds ratio [OR] = 6.00, p = .03), older age at baseline (OR = 1.19, p = .04), and younger age at BC diagnosis (OR = 0.80, p = .03). Few high-risk Spanish-preferring Latina BC survivors in the mainland USA and PR had discussed GC with their providers. These results highlight a gap in the implementation of evidence-based genetics guidelines. Provider-directed interventions may be needed to increase uptake of GC/GT among Latina BC survivors.
PMCID:9540969
PMID: 36205471
ISSN: 1613-9860
CID: 5351722

Warning Signs of Acute Infectious Disease-Related Illness in Persons Living With Dementia: Perspectives of Primary Care Providers, Adult Day Service Center Staff, and Family Care Partners

Omeally-Soto, Shanique; Zhong, Jie; Boafo, Jonelle; Wu, Bei; Brody, Abraham A; Riffin, Catherine; Sadarangani, Tina R
In the current study, we conducted one-on-one interviews with primary care providers (PCPs) and family care partners (FCPs) and held focus groups with interdisciplinary adult day service center (ADSC) staff to understand the perspectives of care providers across community settings regarding early warning signs of acute illnesses in persons living with dementia (PLWD). We used content analysis to analyze qualitative data. Warning signs of acute illnesses in PLWD fell into one of five categories, including new onset changes in (a) physical functions, (b) moods or behaviors (psychological), (c) social interactions, (d) speech, or (e) appearance. FCPs (n = 11) focused on physical changes, whereas ADSC staff (n = 33) emphasized changes in speech and social interactions in addition to the other categories. Although ADSC staff and PCPs (n = 22) focused on changes in functions and moods, each group described these changes differently. ADSC staff possess rich information that can be used to identify acute changes in PLWD and describe a broader range of warning signs compared to PCPs and FCPs. FCPs may benefit from further training in distinguishing between normal disease progression and acute illness. Future research should focus on the implementation of standardized tools across community-based care providers to simplify the identification and reporting of early warning signs in PLWD. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.].
PMID: 36198122
ISSN: 0279-3695
CID: 5388092

Diabetes Duration and Subclinical Myocardial Injury: The Atherosclerosis Risk in Communities Study (ARIC)

Hamo, Carine E; Echouffo-Tcheugui, Justin B; Zhang, Sui; Florido, Roberta; Pankow, James S; Michos, Erin D; Goldberg, Ronald; Nambi, Vijay; Gerstenblith, Gary; Post, Wendy S; Blumenthal, Roger S; Ballantyne, Christie; Selvin, Elizabeth; Coresh, Josef; Ndumele, Chiadi E
BACKGROUND:Diabetes exerts adverse effects on the heart, and a longer diabetes duration is associated with greater heart failure risk. We studied diabetes duration and subclinical myocardial injury, as reflected by high-sensitivity cardiac troponin (hs-cTnT). METHODS:We analyzed 9052 participants without heart failure or coronary heart disease (mean age 63 years, 58% female, 21% Black, 15% with diabetes) at The Atherosclerosis Risk in Communities Study (ARIC) Visit 4 (1996 to 1998). Diabetes duration was calculated based on diabetes status at Visits 1 (1987 to 1989) through 4, or using self-reported age of diabetes diagnosis prior to Visit 1. We used multinomial logistic regression to determine the association of diabetes duration with increased (≥14 ng/L) or detectable (≥6 ng/L) Visit 4 hs-cTnT, relative to undetectable hs-cTnT, adjusted for demographics and cardiovascular risk factors. RESULTS:The prevalence of increased Visit 4 hs-cTnT was higher in persons with longer diabetes duration, from 12% for those with diabetes 0 to <5 years up to 31% among those with diabetes for ≥15 years (P for trend <0.0001). New onset diabetes at Visit 4 was associated with 1.92× higher relative risk (95% CI, 1.27-2.91) of increased hs-cTnT than no diabetes. Longer diabetes duration was associated with greater myocardial injury, with duration ≥15 years associated with 9.29× higher risk (95% CI, 5.65-15.29) for increased hs-cTnT and 2.07× (95% CI, 1.24-3.16) for detectable hs-cTnT, compared to no diabetes. CONCLUSIONS:Longer diabetes duration is strongly associated with subclinical myocardial injury. Interventional studies are needed to assess whether the prevention and delay of diabetes onset can mitigate early myocardial damage.
PMID: 35904048
ISSN: 1530-8561
CID: 5586742

ASO Author Reflections: Same but Different: Implications of Surgical Delays for Breast Cancer Patients Treated in NYC Public Hospitals During the COVID-19 Pandemic

Escobar, Natalie; Joseph, Kathie-Ann
PMCID:9533985
PMID: 36197559
ISSN: 1534-4681
CID: 5351582

MRI Evaluation of Uterine Masses for Risk of Leiomyosarcoma: A Consensus Statement

Hindman, Nicole; Kang, Stella; Fournier, Laure; Lakhman, Yulia; Nougaret, Stephanie; Reinhold, Caroline; Sadowski, Elizabeth; Huang, Jian Qun; Ascher, Susan
Laparoscopic myomectomy, a common gynecologic operation in premenopausal women, has become heavily regulated since 2014 following the dissemination of unsuspected uterine leiomyosarcoma (LMS) throughout the pelvis of a physician treated for symptomatic leiomyoma. Research since that time suggests a higher prevalence than previously suspected of uterine LMS in resected masses presumed to represent leiomyoma, as high as one in 770 women (0.13%). Though rare, the dissemination of an aggressive malignant neoplasm due to noncontained electromechanical morcellation in laparoscopic myomectomy is a devastating outcome. Gynecologic surgeons' desire for an evidence-based, noninvasive evaluation for LMS is driven by a clear need to avoid such harms while maintaining the availability of minimally invasive surgery for symptomatic leiomyoma. Laparoscopic gynecologists could rely upon the distinction of higher-risk uterine masses preoperatively to plan oncologic surgery (ie, potential hysterectomy) for patients with elevated risk for LMS and, conversely, to safely offer women with no or minimal indicators of elevated risk the fertility-preserving laparoscopic myomectomy. MRI evaluation for LMS may potentially serve this purpose in symptomatic women with leiomyomas. This evidence review and consensus statement defines imaging and disease-related terms to allow more uniform and reliable interpretation and identifies the highest priorities for future research on LMS evaluation.
PMID: 36194109
ISSN: 1527-1315
CID: 5361682

Why are Black individuals disproportionately burdened with uterine fibroids and how are we examining this disparity? A systematic review

Charifson, Mia A.; Vieira, Dorice; Shaw, Jacquelyn; Kehoe, Siobhan; Quinn, Gwendolyn P.
Objective: To systematically review and summarize the literaure on nongenetic risk factors that may contribute to the racial disparity in uterine fibroids (UF) that disproportionality impacts Black individuals at 2-3 times the rate of White individuals and how the racial disparity has been studied to date. Evidence Review: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol checklist guided the systematic review process. From January 1 to June 1, 2021, relevant articles were retrieved from PubMed, EMBASE, Web of Science, and Cochrane Library. Multiple investigators screened, assessed, extracted, and critically appraised the data. Results: A total of 44 articles examined the relationship among UFs, race/ethnicity, and nongenetic risk factors, including cardiometabolic features, comorbidities, diet, chemical exposures, vitamin D levels, reproductive characteristics and socioeconomic factors, and life experiences. Most studies reported on the same 3 cohort study populations, and there was inconsistent statistical reporting of the race/ethnicity, risk factors, and UF relationship. Conclusion: Many potential risk factors related to the racial disparity in UF have been studied thus far. There is still little conclusive evidence regarding which risk factors are the greatest contributors to racial disparities in UF. Promising areas of research deserve greater attention and a greater diversity of study populations and analytical methods.
SCOPUS:85139058840
ISSN: 2666-5719
CID: 5349272

Predicting a Positive Antibody Response After 2 SARS-CoV-2 mRNA Vaccines in Transplant Recipients: A Machine Learning Approach With External Validation

Alejo, Jennifer L; Mitchell, Jonathan; Chiang, Teresa P-Y; Chang, Amy; Abedon, Aura T; Werbel, William A; Boyarsky, Brian J; Zeiser, Laura B; Avery, Robin K; Tobian, Aaron A R; Levan, Macey L; Warren, Daniel S; Massie, Allan B; Moore, Linda W; Guha, Ashrith; Huang, Howard J; Knight, Richard J; Gaber, Ahmed Osama; Ghobrial, Rafik Mark; Garonzik-Wang, Jacqueline M; Segev, Dorry L; Bae, Sunjae
BACKGROUND:Solid organ transplant recipients (SOTRs) are less likely to mount an antibody response to SARS-CoV-2 mRNA vaccines. Understanding risk factors for impaired vaccine response can guide strategies for antibody testing and additional vaccine dose recommendations. METHODS:Using a nationwide observational cohort of 1031 SOTRs, we created a machine learning model to explore, identify, rank, and quantify the association of 19 clinical factors with antibody responses to 2 doses of SARS-CoV-2 mRNA vaccines. External validation of the model was performed using a cohort of 512 SOTRs at Houston Methodist Hospital. RESULTS:Mycophenolate mofetil use, a shorter time since transplant, and older age were the strongest predictors of a negative antibody response, collectively contributing to 76% of the model's prediction performance. Other clinical factors, including transplanted organ, vaccine type (mRNA-1273 versus BNT162b2), sex, race, and other immunosuppressants, showed comparatively weaker associations with an antibody response. This model showed moderate prediction performance, with an area under the receiver operating characteristic curve of 0.79 in our cohort and 0.67 in the external validation cohort. An online calculator based on our prediction model is available at http://transplantmodels.com/covidvaccine/. CONCLUSIONS:Our machine learning model helps understand which transplant patients need closer follow-up and additional doses of vaccine to achieve protective immunity. The online calculator based on this model can be incorporated into transplant providers' practice to facilitate patient-centric, precision risk stratification and inform vaccination strategies among SOTRs.
PMID: 35859275
ISSN: 1534-6080
CID: 5279212

Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial

Bogenschutz, Michael P; Ross, Stephen; Bhatt, Snehal; Baron, Tara; Forcehimes, Alyssa A; Laska, Eugene; Mennenga, Sarah E; O'Donnell, Kelley; Owens, Lindsey T; Podrebarac, Samantha; Rotrosen, John; Tonigan, J Scott; Worth, Lindsay
Importance/UNASSIGNED:Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown. Objective/UNASSIGNED:To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy. Design, Setting, and Participants/UNASSIGNED:In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD. Interventions/UNASSIGNED:Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy. Main Outcomes and Measures/UNASSIGNED:The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance. Results/UNASSIGNED:A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 5 (5.3%) were Black, 16 (16.8%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin. Conclusions and Relevance/UNASSIGNED:Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT02061293.
PMID: 36001306
ISSN: 2168-6238
CID: 5331632

Varicocele Treatment and Serum Testosterone

Bernstein, Ari P.; Najari, Bobby B.
Varicoceles are an abnormal dilation of the pampiniform plexus within the spermatic cord that can impair spermatogenesis and testosterone production in the testes through a variety of theorized mechanisms. Nearly 15% of the male population is affected by varicocele, though most men are entirely asymptomatic. Among men presenting with infertility, the incidence of varicocele has been observed to be as high as 35-40%. Varicoceles are the most commonly identified abnormalities in men presenting with infertility, and, when associated with abnormal semen parameters, present the urologist with an opportunity for intervention. Serum testosterone levels have been demonstrated to be lower on average among patients with varicoceles and data have suggested that varicocelectomy improves mean serum testosterone levels postrepair. Nonetheless, there are no current guideline indications for varicocelectomy for men with symptomatic hypogonadism, and it is not yet known whether the reported improvement in serum testosterone with surgical intervention is clinically meaningful. In this review, we discuss the most up-to-date literature on the mechanisms by which varicoceles are purported to impair both spermatogenesis and testosterone production as well as the effect of varicocelectomy on serum testosterone levels.
SCOPUS:85142376962
ISSN: 2689-4653
CID: 5370842